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Cli 



Fourth Edition 



mica 




Surgery; in 

Genera ' 



Edited by 

R.M. Kirk 
WJ. Ribbans 






Clinical 
Surgery in 
General 

RCS Course Manua 



Commissioning Editor: Laurence Hunter 
Project Development Manager: Janice Urquhart 
Project Manager: Frances Affleck 
Designer: Erik Bigland 
Illustration Manager: Bruce Hogarth 
Illustrator: Ethan Danielson 





Clinical 
Surgery in 

General 



RCS Course Manua 



Edited by 

R. M. KirkMSFRcs 

Honorary Consultant Surgeon, The Royal Free Hospital, London, UK 

W. J. Ribbans frcs frcs Ed onh 

Consultant Orthopaedic Surgeon, Northampton General Hospital, 
Northampton, UK 



FOURTH EDITION 



s» 



CHURCHILL 

LIVINGSTONE 



EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 
2004 



CHURCHILL LIVINGSTONE 

An imprint of Elsevier Science Limited 

© Royal College of Surgeons 1993 
© Royal College of Surgeons 1996 
© Royal College of Surgeons 1999 
© R. M. Kirk, W. J. Ribbans 2004 All rights reserved. 

The right of R. M. Kirk and W. J. Ribbans to be identified as 
authors of this work has been asserted by them in 
accordance with the Copyright, Designs and Patents Act 
1988 

No part of this publication may be reproduced, stored in a 
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Note 

Medical knowledge is constantly changing. Standard safety 
precautions must be followed, but as new research and 
clinical experience broaden our knowledge, changes in 
treatment and drug therapy may become necessary or 
appropriate. Readers are advised to check the most current 
product information provided by the manufacturer of each 
drug to be administered to verify the recommended dose, 
the method and duration of administration, and 
contraindications. It is the responsibility of the practitioner, 
relying on experience and knowledge of the patient, to 
determine dosages and the best treatment for each 
individual patient. Neither the Publisher nor the editors 
and contributors assumes any liability for any injury 
and /or damage to persons or property arising from this 
publication. 
The Publisher 



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ELSEVIER 

SCIENCE 



First edition 1993 
Second edition 1996 
Third edition 1999 
Fourth edition 2004 

ISBN 443 07262 

British Library Cataloguing in Publication Data 

A catalogue record for this book is available from the 
British Library 

Library of Congress Cataloging in Publication Data 

A catalog record for this book is available from the Library 
of Congress 



Printed in China 



The 

publisher's 

policy is to use 

paper manufactured 

from sustainable forests 




Preface 



What is the book about? Basic science texts deal with 
anatomy, physiology and pathology. Clinical textbooks 
deal in a systematic manner with guidance on managing 
individual patients. We have attempted to create a bridge 
between the basic sciences and their incorporation into 
clinical practice. In the past general surgery dominated 
teaching and postgraduate surgical examinations, but 
many of the included subjects have successively been 
separated into specialities. In order to offer the best 
management to our patients, we may need to know about 
specialities outside of surgery, such as imaging tech- 
niques, radiotherapy, cancer chemotherapy, and terminal 
care. We have tried to identify and demonstrate some of 
those subjects. 

The chapters fall into three types. Some are intended to 
be revelatory; not intended to cover the subject in detail 
but offering a simply presented, comprehensible account, 
which can be expanded by further reading, for example, 
Pathogenesis of cancer. Some are for reference, because 
apart from the principles, the specific details cannot be 
retained in full and need to be looked up, for example 
Fluid, electrolyte and acid/base balance. The third type are 
intended to emphasize that becoming a surgeon is 
more than acquiring facts; even more important is the 
acquisition of professional attitudes of common sense, 
competence, commitment, and compassion. Books cannot 
transmit attitude, they can merely set out for young 
surgeons the high personal and professional standards 
that are crucial, for example in Good surgical practice. 

Experts often find it difficult to write 'down' for 
trainees, and especially for those whose first language is 
not English and those taught medicine in languages other 
than English. Teachers often feel, quite reasonably, that 
aspiring experts should learn the basic specialist terms, 
but too often the trainees learn the words without fully 
understanding their clear meaning. Consequently, the 
contributors have been exhorted to use simple, direct 
language, define complex terms and acronyms, and, 
when in doubt, to prefer comprehensibility over compre- 
hensiveness. Most have been very tolerant. 



A minority of readers studied Latin or Greek at school 
and even those who have done so, do not always recognize 
the words when they encounter them in medical texts. One 
of us, deprived of such an education, vividly remembers 
encountering the word 'parotid' in a dictionary; it was a 
revelation to discover that the parotid gland is simply the 
'beside the ear gland' (G para = beside + otis = ear). In con- 
sequence of this the contributors have been encouraged to 
define interesting or difficult terms. Although it is often 
frowned upon, the eponymous (G epi = upon + onyma = a 
name; a distinguishing name) titles of diseases, instru- 
ments, clinical features, incisions and manoeuvres honour 
those who described or recognized them. They could be 
inserted as footnotes, or in a glossary at the end of the 
book. They do not get overlooked within the text and they 
offer struggling readers moments of relaxation. 

Surgery was traditionally taught within the master/ 
apprentice relationship. The master is often not con- 
sciously aware of the tacit skills he or she has acquired and 
passes on to the apprentice by example, rather than by 
explicit teaching. The trainee is similarly unaware of assim- 
ilating it. The transfer of this unrecognized wisdom is often 
disparaged as mere skill but is described and extolled by 
Michael Polanyi in his book Personal knowledge? Words 
alone and this book alone, cannot contain the whole of 
knowledge. In the present day obsession with objectivity, 
information that defies statistical analysis is often ignored, 
when in reality it is only our ignorance of it that prevents 
us from utilizing it. The really important truths defy objec- 
tive description. Bernard Levin 2 stated, 'Most things that 
are fundamentally important are not susceptible to logical 
analysis. I would go so far as to state that that is how we 
know they are fundamentally important.' Because of the 
need for trainees to rotate through the sub-specialities, 
long-term master/ apprentice relationships are truncated. 
As a trainee, assimilate as much as possible by reading but 



Michael Polanyi. Personal knowledge, Routledge & Keegan 

Paul, London, 1958 

2 Times, London, 13 th February 1989 



V 



I 



PREFACE 



be receptive to the lessons you can acquire through your 
contact with experienced senior colleagues. In the longer 
term, when you become a senior/ be receptive to the fresh 
lessons to be learned from your juniors. 



Apology 

There is no epicene (G epi - upon + koinos - common; 
common to both genders) word for he and she/ him and 



her, his and hers. Most of the older textbooks recognized 
only male surgeons but this must no longer be so. 
However/ there are times when specifying both sexes 
several times in a sentence becomes tedious; repeated 
cutting from singular to plural is clumsy. Some sexually 
attributable words have acquired special meanings, such 
as Master with the connotation of teacher or leader; 
Mistress has a quite different connotation! 



2003 



R. M. K. 
W.J.R 





Acknowledgements 



We are grateful for the expert and experienced advice of 
Laurence Hunter r the pleasure of working once again 
with Janice Urquhart and with a newly encountered and 
expert copy editor, Rosaline Crum. The contributors have 
generously agreed to forego any payment in order that 
the royalties can be donated to the Royal College of 
Surgeons of England towards funding the very successful 
Research Fellowships. 



Professor Marc Winslet, Head of the Academic De- 
partment of Surgery at the Royal Free Hospital/ has not 
only contributed to the book, but he has also generously 
allowed the organization and editing of the book to be 
centred within the Department. 



VI 




Contributors 



Tushar Agarwal MB BS MRCS(Ed) 

Specialist Registrar Academic Surgical Unit, St Mary's 

Hospital, London, UK 

Peter L. Amlot MB BS FRCP 

Senior Lecturer, Department of Immunology, Royal Free 

and University College Medical School, London, UK 

J. L. Atkins MSc FRCS 

Registrar in Plastic Surgery, Royal Free Hospital, 

London, UK 

Wynne Aveling MA MB BChir FRCA 

Consultant Anaesthetist, University College London 

Hospitals, London, UK 

Daryll M. Baker PhD FRCS(Gen) 

Consultant Vascular Surgeon, Royal Free Hospital, 

London, UK 

Tom Bates MB BS MRCS LRCP FRCS 

Consultant Surgeon in General Surgery, The William 

Harvey Hospital, Ashford, Kent, UK 

T. J. Beale FRCS(Eng) FRCR 

Consultant Radiologist, Central Middlesex Hospital, 

London, UK 

Satyajit Bhattacharya MS MPhil FRCS 

Consultant Surgeon, Hepatic and Pancreatic Surgery 

Unit, The Royal London Hospital, London, UK 

Colin Bicknell BM MRCS 

Research Fellow, Regional Vascular Unit, St Mary's 

Hospital, London, UK 

Laura J. Buist MD FRCS 

Consultant Transplant Surgeon, Queen Elizabeth 

Hospital, Birmingham, UK 



Peter E. M. Butler FRCSI FRCS FRCS(Plast) 
Consultant Plastic Surgeon, Royal Free Hospital, 
London, UK 

N. J. W. Cheshire MD FRCS FRCS(gen) 

Consultant Vascular Surgeon, Regional Vascular Unit, 

St Mary's Hospital, London, UK 

John P. S. Cochrane MS FRCS 

Consultant Surgeon, Whittington Hospital, London, UK 

Richard E. C. Collins FRCS(Eng) FRCS(Ed) 
Chairman Intercollegiate Board in General Surgery 
1998-2001; Consultant General and Endocrine Surgeon, 
Kent and Canterbury Hospital, Canterbury, UK 

Carmel Coulter FRCR FRCP 

Consultant Clinical Oncologist, St Mary's Hospital, 

London, UK 

K. Cox MB MS MA FRCS FRACS FACS 

Emeritus Professor of Surgery, University of New South 
Wales, New South Wales, Australia; Formerly Director 
of the World Health Organization Regional Training 
Centre for Health Development 

M. K. H. Crumplin MB FRCS 

Honorary Consultant Surgeon, Maelor Hospital, North 

East Wales Trust, UK 

Professor Sir Ara Darzi KBE 

Professor of Surgery and Head of Department of 
Surgical Oncology and Technology, Imperial College of 
Science, Technology and Medicine, St Mary's Hospital, 
London, UK 

Andrew Davenport MA MD FRCP 
Director, International Society of Hemodialysis; 
Consultant Renal Physician and Honorary Senior 
Lecturer, Royal Free Hospital, London, UK 



VII 



1 



CONTRIBUTORS 



Brian Davidson MB ChB MD FRCS 

Professor of Surgery, Royal Free and University College 

School of Medicine, London, UK 

J. L> Dawson (deceased) 

Ahmet Dogan MD PhD MRCPath 
Senior Lecturer and Consultant, Department of 
Histopathology, Royal Free and University College 
Medical School, UCL Hospitals, London, UK 

Glenn Douglas BA(Hons) IPFA MIHSM 

Chief Executive, Ashford and St Peter's Hospitals NHS 

Trust, Eastbourne, UK 

Len Doyal BA MSc 

Professor of Medical Ethics, Barts and the London 
School of Medicine, Queen Mary, University of London, 
London, UK 

Peter A. Driscoll BSc MD FRCS FFAEM 

Consultant in Emergency Medicine, Hope Hospital, 

Salford, UK 

Roshan Fernando MB ChB FRCA 

Consultant Anaesthetist and Honorary Senior Lecturer, 
Department of Anaesthesia, Royal Free Hospital, 
London, UK 

F. Kate Gould MB BS FRCPath 

Consultant Microbiologist, Freeman Hospital, 

Newcastle upon Tyne, UK 

Stuart W. T. Gould FRCS 

Senior Lecturer in Surgery, Imperial College of Science, 

Technology and Medicine, London, UK 

Clair S. Gricks BSc PhD 

Post Doctoral Research Fellow, Dana Farber Cancer 

Institute, Harvard Medical School, Boston, USA 

Pierre J. Guillou BSc MD FRCS FRCPS(Glas) FMedSci 
Professor of Surgery, St James's University Hospital, 
School of Medicine, Leeds, UK 

Amy Guppy MRCP BSc 

Specialist Registrar, Mount Vernon Cancer Centre, 

Northwood, Middlesex, UK 



Chris G. Hargreaves BSc MRCP FRCA 

Consultant in Intensive Care Medicine and Anaesthesia, 

Whittington Hospital, London, UK 

John A. Henry FRCP FFAEM 

Honorary Consultant, Head of Academic Department of 
Accident and Emergency Medicine, Imperial College 
Faculty of Medicine, St Mary's Hospital, London, UK 

Barrie HiggS MB BS MSc FRCA 

Consultant and Honorary Senior Lecturer, Departments 
of Anaesthesia and Physiology, Royal Free Hospital and 
Royal Free and University College School of Medicine, 
London, UK 

Daniel Hochhauser MRCP DPhil 

Kathleen Ferrier Reader in Medical Oncology, Royal 

Free and University College Medical School, London, 

UK 

R. W. Hoile MS FRCS(Eng) 

Consultant General Surgeon, Medway Maritime 
Hospital, Gillingham, Kent, UK; Principal Surgical 
Coordinator of National Confidential Enquiry into 
Perioperative Deaths (NCEPOD) 

Robert A. Huddart MA MB BS MRCP FRCR PhD 
Senior Lecturer and Honorary Consultant, Institute of 
Cancer Research and Royal Marsden Hospital, Surrey, 
UK 

Iain A. Hunter BMedSci BM BS FRCS(Eng) 

Clinical Research Fellow, St James's University Hospital, 

School of Medicine, Leeds, UK 

Donald J. Jeffries BSc MB BS FRCP FRCPath 
Professor of Virology and Head of Department of 
Medical Microbiology, St Bartholomew's and the Royal 
London School of Medicine and Dentistry, London, UK 

Jennifer Jones BSc MB BS FRCP FRCA 

Consultant Anaesthetist, St Mary's Hospital, London, 

UK 

R. M. Jones MD FRCA 

Professor of Anaesthetics, St Mary's Hospital, London, 

UK 



Mark A. Hamilton BSc MB BS MRCP 

Research Fellow, Centre for Anaesthesia, Middlesex 

Hospital, London, UK 



R. M. Kirk MS FRCS 

Honorary Consultant Surgeon, The Royal Free Hospital, 

London, UK 



VIII 



CONTRIBUTORS 






Anna C. Kurowska BSc BA FRCP 

Consultant in Palliative Medicine, Whittington Hospital 

and Edenhall Marie Curie Centre, London, UK 

Sunil R. Lakhani BSc MB BS MD FRCPath 
Professor of Breast Cancer Pathology, The Breakthrough 
Toby Robins Breast Cancer Research Centre, Institute of 
Cancer Research and The Royal Marsden Hospital, 
London, UK 

David Leaper MD ChM FRCS FRCSEd FRCSGlas FACS 
Professor of Surgery, University Hospital of North Tees, 
Stockton-on-Tees, UK 

Richard C. Leonard BA MRCP FRCA FANZCA FFICANZCA 
Consultant Intensivist, St Mary's Hospital, London, UK 

Liang Low FRCSI 

Specialist Registrar in Surgery, University Hospital of 

North Tees, Stockton-on-Tees, UK 

Valentine M. Macaulay MD PhD MRCP 
Cancer Research UK Senior Clinical Research Fellow and 
Honorary Consultant in Medical Oncology, Molecular 
Oncology Laboratories, Weatherall Institute of Molecular 
Medicine and Oxford Radcliff Trust, Oxford, UK 

John W. McClenahan MA MS DiplIndMgt PhD FOR 
Fellow in Leadership Development, King's Fund, 
London, UK 

Paul McMaster MA MB ChM FRCS 

Professor of Hepatobiliary Surgery and Transplantation, 
Queen Elizabeth Hospital, University of Birmingham, 
Birmingham, UK 

Caroline A. Marshall MB BS MRCP FRCA 
Consultant Anaesthetist, Southampton University 
Hospitals Trust, Southampton, UK 

Atul B. Mehta MA MB BChir MD FRCP FRCPath 

Consultant Haematologist, Royal Free Hospital, 
London, UK 



Katherine E. Orr MB ChB FRCPath 

Consultant Microbiologist and Honorary Senior 

Lecturer, Freeman Hospital, Newcastle upon Tyne, UK 

Jason Payne-James LLM FRCS (Ed & Eng) DFM 
Honorary Senior Research Fellow, Central Middlesex 
Hospital, London; Director, Forensic Healthcare 
Services, London 

Anthony L. G. Peel MA MChir FRCS 
Consultant Surgeon, North Tees Hospital, Stockton-on- 
Tees, UK 

Michael W. Piatt MB BS FRCA 
Consultant and Honorary Senior Lecturer in 
Anaesthetics and Pain Management, St Mary's Hospital 
NHS Trust, London, UK 

William J. Ribbans FRCS FRCSEdOrth 

Consultant Surgeon, Northampton General Hospital, 

Northampton, UK 

Jonathan Robin MRCP 

Lecturer in Clinical Pharmacology and Intensive Care 

Medicine, University College London, London, UK 

Gordon J. S. Rustin MD MSc FRCP 

Director of Medical Oncology, Mount Vernon Cancer 

Centre, Northwood, Middlesex, UK 

Michael Saleh MB ChB MSc Bioeng FRCSEd FRCSEng 

Professor of Orthopaedic and Traumatic Surgery, 
University of Sheffield; Honorary Consultant, Northern 
General Hospital, Sheffield; Honorary Consultant, 
Sheffield Children's Hospital, Sheffield, UK 

Hank J. Schneider FRCS 

Consultant General and Paediatric Surgeon, The James 

Paget Hospital, Great Yarmouth, UK 

J. A. R. Smith PhD FRCS(Ed) FRCS(Eng) 
Consultant Surgeon, Northern General Hospital, 
Sheffield, UK 



Richard W. Morris BSc MSc PhD 

Senior Lecturer in Medical Statistics, Department of 
Primary Care and Population Sciences, Royal Free and 
University College London, London, UK 

Paul D. Nathan PhD MRCP 

Specialist Registrar Medical Oncology, Department of 

Oncology, Royal Free Hospital, London, UK 



Martin Smith MB ChB FRCSEd (A&E) FFAEM 
Specialist Registrar in Emergency Medicine, Hope 
Hospital, Salford UK 

Vinnie Sodhi MB BS BSc FRCA 
Portex Research Fellow in Obstetric Anaesthesia, 
Department of Anaesthesia, Royal Free Hospital, 
London, UK 



IX 



1 



CONTRIBUTORS 



Jeremy J. T. Tate MS FRCS 

Consultant Surgeon, Royal United Hospital, Bath, UK 

Clare P. E Taylor MB BS PhD MRCP MRCPath 
Consultant in Haematology and Transfusion Medicine, 
Royal Free Hospital and National Blood Service, 
London, UK 

Adrian Tookman MB BS FRCP 

Medical Director, Edenhall Marie Curie Centre, London; 
Consultant in Palliative Medicine, Royal Free Hospital, 
London, UK 

Robin Touquet RD FRCS FFAEM 

Consultant in Accident and Emergency Medicine, 

St Mary's Hospital, London, UK 

Ines Ushiro-Lumb MB BS MSc MRCPath 

Consultant Virologist, Department of Virology, Barts 

and The London NHS Trust, London, UK 



Patricia A. Ward MB BS MRCP FRCSEd(A&E) FFAEM 
Director of Resuscitation, Accident and Emergency 
Department, St Mary's Hospital, London, UK 

Denis Wilkins MB ChB MD FRCS ILT 
Consultant General and Vascular Surgeon, Derriford 
Hospital, Plymouth; Chairman, Court of Examiners, 
Royal College of Surgeons of England; Chairman of the 
Specialist Advisory Committee in Training in General 
Surgery for Great Britain and Ireland 

M. C. Winslet MS FRCS 

Professor of Surgery and Head of Department, 
University Department of Surgery, Royal Free Hospital, 
London, UK 

Gillian M. H. Wray MB BS FRCA 

Consultant in Anaesthesia and Intensive Care Medicine, 

St Bartholomew's Hospital, London, UK 




Contents 



SECTION 1 

EMERGENCY 



SECTION 2 

PATIENT ASSESSMENT 



1. Resuscitation 3 

R. Touquet, P. A. Ward, M. W. Piatt J- A Henry 

2. Trauma 18 

M. Smith, P. A Driscoll 



3. Clinical diagnosis 49 

R. M. Kirk 

4. Investigations 53 

N. J. W. Cheshire, C Bicknell 

5. Imaging techniques 59 

S. W. T. Gould, T. Agarwal, T. J. Beafe 

6. Influence of co-existing disease 64 
R. M. Jones, C. A. Marshall 

7. Immunity in surgery 82 

P. L Amlot, C S. G ricks 

8. Haematological assessment and blood 
component therapy 90 

C P. F. Taylor, A. B. Mehta 

9. Fluid, electrolyte and acid-base balance 107 

W. Ave ling, M. A. Hamilton 

10. Nutritional support 125 

J. Payne James 

11. Clinical pharmacology 131 

J. Robin 

12. Evidence-based practice 138 

J. W. McLenahan 



13. Decision making 144 

R. M. Kirk, K. Cox 




CONTENTS 



SECTION 3 

PREPARATIONS FOR SURGERY 



SECTION 4 

OPERATION 



14. Consent for surgical treatment 155 

L Doyal 

15. Preoperative preparation for surgery 165 

S. Bhattacharya, G. M. H. Wray 

16. Preoperative assessment and anaesthesia 172 

M. W. Piatt 

17. Operating theatres and special equipment 183 

M. K. H. Crump! in 

18. Adjuncts to surgery 199 

A. L. G. Peel 

19. Prevention of infection in surgical practice 206 

K. E. Orr, F. K. Gould 

20. The risks to surgeons of nosocomial virus 
transmission 215 

D. J. Jeffries, I. Ushiro-Lumb 



21. Good surgical practice 225 

R. M. Kirk, J. Dawson 

22. Surgical access: incisions, and the management 
of wounds 230 

D. J. Lea per, L Low 

23. Minimal access surgery 237 

A. Darzi 

24. Principles of skin cover 241 

P. E. M. Butler, J. L. Atkins 

25. Transplantation 249 

P. McMaster, L. J. Buist 



SECTION 5 

MALIGNANT DISEASE 

26. Pathogenesis of cancer 259 

P. D. Nathan, D. Hochhauser 



27. Principles of surgery for malignant disease 265 

P. J. Guiflou, I. A. Hunter 

28. Principles of radiotherapy 271 

R. A. Huddart 

29. Cancer chemotherapy 284 

V. M. Macaulay, C Coulter 

30. Tumour markers 302 

G. J. S. Rust in, A. E. Guppy 



XII 



CONTENTS 



. 



SECTION 6 

POSTOPERATIVE 



SECTION 8 

GENERAL CONSIDERATIONS 



31. The body's response to surgery 313 

J. P. S. Cochrane, C G. Hargreaves 

32. Wound healing 322 

S. R. La khan i, A. Dogan 

33. Responses of connective tissue and bone 331 

W. J. Ribbans, M. Safeh 

34. Postoperative care 349 

J. J, T. Tate 

35. Management of postoperative pain 357 
V, Sodhi, R. Fernando 



SECTION 7 

COMPLICATIONS 

36. Complications: prevention and management 

373 

J. A. R. Smith 

37. Intensive care 388 

J. Jones, R. C Leonard 

38. Dialysis 398 
A. Davenport 

39. Chronic illness, rehabilitation and terminal care 
402 

A. C Kurowska, A. Tookman 



40. Genetic aspects of surgery 417 

M. C Winslet 

41. Screening for surgical disease 423 

T. Bates 

42. Audit 428 

B. Davidson, H. J. Schneider 

43. Clinical governance 437 
B. Higgs 

44. Economic aspects of surgery 442 

R. W. Hoile, G. Douglas 

45. Statistical concepts: a tool for evidence-based 
practice 445 

/?. W. Morris 

46. Critical reading of the literature 454 

R. M. Kirk 

47. Communication skills 458 

R. M. Kirk, V. M. Macaulay 

48. The surgical logbook 463 

D. M. Baker 

49. The MRCS examination 466 

D. Wilkins 

50. The intercollegiate examinations in surgery 

472 

R. E. C Collins 

Index 475 



XHI 



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This page intentionally left blank 




Resuscitation 

/?. Touquet, P A Ward, M. W. Piatt J- A. Henry 




Objectives 

• Recognize the variety of presentations to 
an accident and emergency (A & E) 
department; these are often 
multidisciplinary, complex, and neither 
solely medical nor solely surgical. 

• Understand the rationale for prioritizing 
resuscitation sequences and basing 
decisions on the patient's responses to 
interventions. 

• Follow protocols to avoid errors of omission. 

• Understand arterial blood gases, both in 
terms of acid-base balance and gas 
exchange. 

• Understand the difference between 
oxygen tension (Pao 2 , partial pressure) and 
oxygen saturation (Sao 2 ). 

• Recognize that the doctor in A & E may be 
the last generalist to manage the patient 
before admission under a specialist team. 

'Scientia vincit timorem' 
(Knowledge conquers fear) 



INTRODUCTION 

Collapse (Latin col = together + lapsare = to slip; extreme 
prostration, depression and circulatory failure) or coma 
(Greek koma = deep sleep; unrousable loss of conscious- 
ness) are features of diverse life-threatening conditions 
depressing or injuring the central nervous system. The cause 
is often unknown when the patient arrives in the resuscita- 
tion room. Furthermore, there may be more than one 
cause, for example a hypoglycaemic patient may fall and 
sustain a head injury. 

When a patient with an altered level of consciousness 
arrives in the accident and emergency department, apply 
the resuscitation sequence described in the American 
College of Surgeons' Advanced Trauma Life Support 



Course, whether the cause appears medical or surgical. 
The initial sequence is the primary survey (ABCDE, see 
below), a systematic assessment that can be performed 
while undertaking any resuscitative procedures. Institute 
ongoing monitoring of vital signs while observing their 
response to any procedure undertaken, such as immedi- 
ately infusing 2 litres of crystalloid into an adult with 
hypovolaemic shock. 

When the patient is stable, with clinically acceptable 
vital signs, carry out the secondary survey, a thorough 
examination from head to toe to avoid missing any patho- 
logical condition. You are often the last doctor to carry out 
a complete examination. If the patient needs to be trans- 
ferred immediately to the operating theatre, the second- 
ary survey must be carried out later, on the ward, by 
members of the admitting team. 

PART 1: PRIMARY SURVEY WITH 
INITIAL RESUSCITATION 

Greet and talk reassuringly to a conscious patient. Do not 
treat the patient as an inanimate object. Take notice of the 
history from the ambulance crew. Involve them in the 
initial resuscitation and have them immediately available 
to give any further details of the history. Ensure that the 
ambulance transfer form is signed by a member of the 
accident and emergency department staff. 

The standard sequence of the initial primary survey is: 

Airway, with cervical spine control 
Breathing 
Circulation 

Disability - a brief neurological assessment 
Exposure - undress the patient completely, but briefly, to 
avoid hypothermia. 



■■■> 



Key points 



Apply an appropriately sized cervical collar to 
steady the head. In-line cervical spine 




EMERGENCY 



immobilization prevents iatrogenic (Greek iatros 
= physician + gennaein = produce) spinal cord 
damage in those with unsuspected neck injury. 
• Be particularly careful if you pass an 
orotracheal tube. 

Airway 

Assess 

Talk to the patient; look for signs of confusion or agitation 
which may indicate cerebral hypoxia. Listen for stridor or 
gurgling sounds from a compromised airway Detect 
expired warm air with your hand in a patient who is 
breathing. Check if chest movements are adequate and 
equal. 

If the patient has inhaled smoke, look for carbon 
deposits in the mouth or nostrils, which raise the possi- 
bility of upper airway burns and associated carbon 
monoxide poisoning. If so, call an anaesthetist to pass an 
endotracheal tube. 

Manage 

Keep the airway open and clear it. Remove any foreign 
bodies, such as sweets; suck out vomit. Lift the chin for- 
wards to bring the tongue off the back of the naso- 
pharynx. If the gag reflex is diminished, insert an oral 
(Guedel) airway; if this is not tolerated, but obstruction is 
still present, consider gently inserting a well-lubricated 
nasopharyngeal airway. Do not insert a nasopharyngeal 
airway if basal skull fracture is a possibility. Once the 
airway is secured, deliver 10-15 1 min -1 oxygen through a 
face mask with a reservoir device, which provides about 
85% inspired oxygen. 

None of these basic airway manoeuvres protects the 
lungs from aspiration of gastric contents or blood. If the 
patient has an absent gag reflex, insert a cuffed tracheal 
tube by the oral or nasal route to facilitate efficient venti- 
lation and protect the lungs. 

If you cannot provide an airway in any other way, 
urgently carry out a needle cricothyroidotomy followed, 
if necessary, by a surgical cricothyroidotomy. 

Breathing 

Assess 

Assess any cyanosis. If the neck veins are engorged, con- 
sider the possibility of a tension pneumothorax, cardiac 
tamponade, air embolus, pulmonary embolus or myo- 
cardial contusion. Check the position of the trachea; if it is 
deviated to one side, has it been pushed over by a tension 
pneumothorax on the opposite side? Count the respir- 
atory rate (normally 12-20 per minute) and expose, inspect 



and palpate the anterior chest wall. Assess breath sounds 
or their absence by auscultation. A severe asthmatic may 
present with collapse and have a silent chest because with 
extreme airway narrowing no air can move in or out of 
the lungs. If three or more consecutive ribs are fractured 
in two or more places, with a segment of paradoxical 
chest wall motion, this is a flail chest. The underlying pul- 
monary contusion may cause acute respiratory failure. If 
there is any doubt about the adequacy of the patient's 
airway or breathing, urgently obtain expert help from 
physicians and anaesthetists. 

Manage 

Prevent hypoventilation, hypercapnia (Greek kapnos - 
smoke, vapour - carbon dioxide) and cerebral vasodi- 
latation. They produce increased intracerebral pressure 
which is extremely dangerous in traumatized patients, 
especially if they have suffered a head injury. Both adults 
and children have a normal tidal volume of 7 ml kg -1 . A 
patient with rapid, shallow breathing and signs of fatigue 
and distress is unable to sustain a normal tidal volume. 
Hypercapnia is likely, with a resultant increase in cerebral 
perfusion and oedema. Institute assisted respiration, 
initially by bag-valve-mask positive pressure ventilation. 
An arterial blood sample demonstrates a high arterial 
carbon dioxide tension (PaC0 2 ) level if breathing is inad- 
equate. If possible, ventilate and oxygenate the hypoxic or 
apnoeic patient for at least 3 min before attempting intu- 
bation. Do not prolong any attempt for more than 30 s 
before returning to bag-valve-mask ventilation. An 
apnoeic patient needs urgent ventilatory support. 

With assisted ventilation, aim to keep the arterial blood 
oxygen above 10 kPa (80 rnmHg) and the carbon dioxide 
below 55 kPa (40 rnmHg), but above 4 kPa (30 mmHg) to 
prevent brain ischaemia. In a patient with head injury and 
decreased consciousness, a reduction of the Paco2 to just 
above 4 kPa (30 rnmHg) reduces cerebral oedema and intra- 
cerebral acidosis. 




Key points 

• Assume that a spontaneously breathing patient 
who is agitated, aggressive or with a 
depressed level of consciousness, is hypoxic. 

• Remember, though, that restlessness is also 
caused by, for example, a full bladder or a tight 
plaster of Paris splint. 

Urgently take arterial blood samples from all collapsed 
patients who are not likely to recover immediately, for 
measurement of oxygen, carbon dioxide and acid-base 



RESUSCITATION 




1 



^^^^^^d^^u 



balance. Aspirate arterial blood from the radial artery or, 
failing this, from the femoral artery, into a heparinized 
syringe (a 2 ml syringe whose dead space has been filled 
with heparin 1000 units ml -1 ). 

Maintain arterial oxygen tension (Fao 2 ) above 10 kPa 
(80 mmHg), with added inspired oxygen, to preserve 
tissue viability. The exception is the patient with chronic 
obstructive airways disease (COAD), who depends on 
hypoxic drive rather than Paco 2 to breathe and will tend 
to hypoventilate when given added oxygen of more than 
35%. Diagnose this from the arterial blood gas, which 
shows a high Paco 2 with a normal pH. Give all collapsed 
patients high-flow oxygen initially, as patients whose res- 
piration is dependent on hypoxic drive are uncommonly 
encountered in A & E. 

You may need to administer oxygen to produce a 
higher than normal Pao 2 . In, for example, carbon monox- 
ide poisoning, elevated pulmonary vascular resistance, 
sickle cell crisis and anaerobic infections the treatment is 
to produce an elevated Pao 2 . 

Circulation 

Assess 

Assess the patient for shock. 




Early signs of shock 

• Anxiety, tachycardia of 100-120 min -1 , 
tachypnoea of 20-30 min \ skin mottling, 
capillary refill time of more than 2 s r and 
postural hypotension. 

Initially assume hypovolaemia from occult bleeding if 
there is postural hypotension with a fall of systolic blood 
pressure of 20 mmHg, a fall of diastolic blood pressure 
of 10 mmHg and a rise of pulse of 20 beats per minute 
(20:10:20 rule). Supine systolic blood pressure does not 
drop until an adult has lost around 1500-2000 ml of 
blood, or 30-40% of the blood volume of 70 ml kg -1 body- 
weight; by this time the patient is ashen in colour because 
of blood-drained extremities. 

The level of consciousness is also decreased because of 
inadequate cerebral circulation, particularly if blood loss 
was rapid. As a guide, a palpable carotid pulse indicates 
a svstemic blood pressure of at least 60 mmHg. 




Key point 

If the carotid pulse is absent, initiate 
immediate basic cardiopulmonary resuscitation 
(CPR, see below). 



Manage 

Control haemorrhage from any external bleeding 
points by direct pressure, with limb elevation where 
appropriate. 

1 . Intravenous access. The Parisian scientist Jean Poiseuille 
(1797-1869) calculated that the rate of flow of fluid 
through a pipe is proportional to the fourth power of the 
radius, and inversely proportional to the length. In a 
severely traumatized or hypovolaemic patient, never fail 
to insert two short, wide-bore cannulae of 14 gauge or 
larger, sited in peripheral veins, whether introduced per- 
cutaneously or by surgical cutdown. 

2. Venous cutdown. Acquire skill in this safe, simple and 
quick technique for intravenous access. Prefer the saphe- 
nous vein anterior to the medial malleolus or the basilic 
vein in the elbow crease. Make a transverse, 2 cm incision 
anterior to the medial malleolus or to the medial epi- 
condyle of the humerus. Delineate, by blunt dissection, 
the long saphenous or basilic vein. Ligate the vein distally 
with 2/0 black silk. Control the vein proximally with a 
similar loose ligature. Make a transverse incision across 
one-third of the circumference of the vein to enable the 
insertion of a 14- to 12-gauge cannula. Secure the cannula 
in place by tightening the proximal suture. This technique 
is applicable for collapsed infants. 

3. Intraosseous infusion is an even simpler technique for 
children under 7 years. In order to avoid the potential risk 
of osteomyelitis, thoroughly clean the area around the 
site of insertion, two fingers 7 breadth distal to the tibial 
tuberosity, on the anteromedial tibial surface. Insert a spe- 
cially designed intraosseous trocar and cannula through 
the cortex of the bone into the marrow cavity. You may 
slowly infuse crystalloid and colloid solutions into the 
marrow (20 ml kg -1 initially for the collapsed child), 
together with drugs used in resuscitation, with the excep- 
tion of sodium bicarbonate and bretylium. The circulation 
time from here to the heart is only 20 s. 

4. Central venous cannulation, even in experienced 
hands, may be dangerous for the trauma patient, who is 
often restless. Such patients may not survive an iatrogenic 
pneumothorax or a cervical spinal cord injury caused by 
turning in the presence of an unsuspected neck injury; as 
the above routes of access avoid the possibility of these 
complications, they are to be preferred. Central venous 
pressure monitoring is useful in the stabilized patient, but 
these lines are not for resuscitation other than in patients 
with cardiac arrest, when drugs should be administered 
centrally. Carry out central vein cannulation after clean- 
ing the area with antiseptic surgical solution. 

a. Unless the patient has a head injury, apply a 20° 
head-down tilt to fill the vein and reduce the risk of air 
embolus. The easiest route for an anaesthetist is via the 
right internal jugular vein, which provides the most direct 




EMERGENCY 



access to the right atrium. Turn the patient's head towards 
the opposite side and you can feel the vein as the softest 
part of the neck, usually lateral to the carotid artery in a 
line from the mastoid process to the suprasternal notch. 
The easiest route for you, or an accident and emergency 
clinician, is probably through the right subclavian vein. 
Pull the right arm caudaUy, to place the vein in the most 
convenient relation to the clavicle for cannulation. Unless 
there is a possibility of spinal injury, to improve access 
place a sandbag beneath the upper thoracic spine so that 
the shoulders lie more posteriorly. 

b. For jugular vein cannulation, introduce the needle 
through the skin at approximately the midpoint of a line 
running from the mastoid process to the suprasternal 
notch, aiming laterally at 30° to the skin, towards the right 
big toe or right nipple, or towards the previously pal- 
pated jugular vein. For subclavian vein access, introduce 
the needle through the skin 2 cm inferior to the junction 
of the lateral and middle thirds of the clavicle. Advance 
the needle, aspirating continuously and snugging the 
inferior bony surface of the clavicle, aiming at the supe- 
rior aspect of the right sternoclavicular joint for not more 
than 6 cm. 

c. Aspirate until blood freely appears; ensure the bevel 
of the needle is now directed caudally; remove the 
syringe and immediately insert the Seldinger wire, flexi- 
ble end first, through the needle. Remove the needle; rail- 
road the plastic cannula over the Seldinger wire, then 
remove the wire. Check that the cannula is in the central 
vein by briefly allowing retrograde blood flow into the 
attached intravenous giving set. 

d. Aftercare: secure the line with a suture through the 
skin and dress the wound with a sterile dressing. Return 
the patient to the horizontal position and obtain a chest 
X-ray to check the position of the central venous cannula 
and to exclude a pneumothorax. 



5. Correct hypovolemia by rapid intravenous infusion 
of warmed crystalloid or colloid solutions followed by 
blood. Rapid loss of more than 40% of a patient's blood 
volume produces pulseless electrical activity, leading to 
circulatory standstill unless you carry out immediate 
resuscitation. You cannot measure the blood volume or 
blood loss in the resuscitation room. Therefore monitor 
the vital signs (delineated in Part 2), especially in 
response to treatment such as fluid replacement, adjust- 
ing your treatment accordingly 

6. If the carotid pulse is impalpable, the heart has 
become an ineffective pump and irreversible brain 
damage results unless you take immediate action to 
correct the specific causes of electromechanical dissoci- 
ation, such as massive blood loss, tension pneumothorax 
or cardiac tamponade. If there is no improvement or if 
these conditions are not present, commence cardiac 
massage for cardiac arrest (Fig. 1.1). Check the heart's 
electrical rhythm on the monitor. Place the leads in the 
correct positions as quickly as possible. If no rhythm is 
visible, turn up the gain knob on the monitor and check 
for a rhythm in two different ECG leads. Alternatively, 
monitor through the paddles of a defibrillator, one placed 
just to the left of the expected position of the apex beat 
and one inferior to the right clavicle. 

7. External chest compression. If you cannot feel the 
carotid pulse after you have controlled ventilation, place 
one hand over the other on the sternum, the lower border 
of the hands being two fingers breadth above the 
xiphisternal-sternal junction. If the hands are lower you 
risk damaging the liver. Keep your arms straight, with the 
shoulders in a direct line over the hands so that you do 
not tire. Depress the sternum smoothly for 4-5 cm, at a 
rate of 100 per minute, with a ratio of two ventilations to 
fifteen compressions. 




Key point 

• The absence of a pneumothorax on this film 
does not exclude the possibility of one 
developing subsequently, possibly under 
tension. 

If direct venous access is not obtained during CPR, for 
immediate drug therapy to the heart muscle give 
drugs via a peripheral venous line, infusing 5% dex- 
trose solution after injecting each drug, to flush it into 
the central circulation. You may give certain drugs, 
such as adrenaline (epinephrine), atropine, lidocaine 
(lignocaine) and naloxone via the tracheal tube route, 
in double the intravenous dosage. 




Key point 

• Do not interrupt cardiac massage for 
ventilations. 

Keep the compression rate regular. In this way the pres- 
sure is increased generally in the chest both during com- 
pression and by ventilation. In addition, the expanding 
lungs drive the diaphragm down, leading to compression 
of the vena cava, further facilitating the driving of blood 
up the carotid arteries; this is the thoracic pump effect. 
Feel for the carotid or femoral pulse every 2 min. 

8. Diagnose the correct cardiac rhythm quickly. The 
rhythm is ventricular fibrillation in 70% of patients with 
non-traumatic cardiac arrest and the chance of successful 



RESUSCITATION 




1 



Cardiac Arrest 



IZ 



Precordial thump 
if appropriate 



v 



BLS algorithm 
if appropriate 



2 



Attach 
defib-monitor 



C 



VF/VT 




Defibrillate x 3 
as necessary 




<=> 



] 



1 




During CPR 

Correct reversible causes 

If not already: 

* Check electrodes, paddle 
position and contact 

4 Attempt' verify: 
airway & O^ 
intravenous access 

• Give epinephrine every 3 min 

Consider; 

amiodarone, atropine/ pacing 

buffers 




Non-VF/VT 



) 





CPR 1 min 

* 1 min if immediately 
after defibrillation 



Potential reversible causes: 

Hypoxia 

Hypovolemia 

Hypo/hyperkalaemia and metabolic disorders 

Hypothermia 

Tension pneumothorax 

Tamponade 

Toxic/therapeutic disorders 

Thrombo-embolic and mechanical obstruction 



^^N^^^^^^^^^^^^^^^^^M 



Fig. 1.1 Adult advanced life support. The Resuscitation Council (UK). Reproduced with permission. 



resuscitation is directly proportional to the speed of 
applying a DC shock in the correct manner and sequence 
(Fig. 1.1). There must be no delay following arrest, and 
this is why ambulance crews are being trained to use, and 
are issued with, defibrillators. 



9. Internal cardiac massage. External chest compression 
does not effectively resuscitate an empty heart that is in 
cardiac arrest from hypovolaemic shock; however inter- 
nal cardiac massage is indicated in the A & E department 
for direct penetrating trauma only. It is not for blunt 



1 1 



EMERGENCY 



trauma, when the patient, at the very least, just has a 
palpable pulse on arrival. When there is no appropriate 
response to prompt rapid transfusion, consider internal 
cardiac massage for penetrating trauma. This is the only 
indication for an emergency thoracotomy for internal 
cardiac massage by trained personnel in the A & E depart- 
ment. If you have had appropriate training, it is both 
safe and haemodynamically superior to external cardiac 
massage, although the latter can be initiated without 
delay and performed by non-surgeons. Open-chest cardio- 
pulmonary resuscitation (CPR) enables you to feel and 
see the heart, and direct electric defibrillation. 

1 0. Create a left-sided thoracotomy through the fourth or 
fifth intercostal space once the patient is receiving intermit- 
tent positive pressure ventilation through a tracheal tube. 
Immediately compress the heart using your left hand, 
without at first opening the pericardial sac, by placing your 
thumb over the left ventricle posteriorly and fingers anteri- 
orly in front of the heart. Compress the heart at the rate of 
100 times per minute, adjusting the force and rate to the 
filling of the heart. Open the pericardium, avoiding the 
phrenic and vagus nerves. You may inject adrenaline 
(epinephrine), atropine and lidocaine (lignocaine), but 
not sodium bicarbonate, directly into the left ventricle, 
avoiding the coronary arteries. For internal defibrillation use 
internal 6 cm paddle electrodes with saline-soaked gauze 
pads and insulated handles. Place one paddle posteriorly 
over the left ventricle and one over the anterior surface of the 
heart (10-20 J). 

11. Drugs. In a patient with cardiac arrest, if possible 
give drugs such as adrenaline (epinephrine) centrally, and 
for this reason become proficient in at least one method 
of central venous cannula tion. Use the approach with 
which you are most familiar. The infraclavicular approach 
is often the most convenient and practicable means of 



access. 



Disability 

This term signifies a brief neurological assessment you 
must carry out at this stage of the initial examination. The 
mnemonic used in the Advanced Trauma Life Support 
Course is useful: 

A = Alert 

V = responds to Verbal stimuli 
P ~ responds to Painful stimuli 
U = Unresponsive 

Now assess the presence or absence of orientation in time 
(does the patient know the day and month?), space 
(knows where he or she is?) and person (knows who he 
or she is?). These perceptions are usually lost in this 
sequence with lessening of consciousness. Alternatively 
use the Glasgow coma scale at the outset. 



Record the pupil size and response to light (Table 1.1). 
Bilateral small pupils denote opiate poisoning unless dis- 
proved by failure of naloxone to reverse the constriction. 
If necessary, give up to 2 mg of naloxone (i.e. five vials of 
0.4 mg). If there is a response, you may need to give more, 
because naloxone has a short half-life. You may give it via 
an endotracheal tube if you do not have intravenous 
access. The other common cause of bilateral small pupils 
is a pontine haemorrhage, for which there is no specific 
treatment. 

Expose 

In a severely traumatized patient always carry out a 
complete examination of the entire skin surface. Remove 
every article of clothing. Carefully protect the spine. 
Complete examination demands log-rolling by a mini- 
mum of four trained people so that you can examine the 
back. Perform this early if there is a specific indication, 
such as injury to the posterior chest wall, or at the latest 
at the end of the secondary survey. Protect all patients, 
particularly children, from hypothermia. 

Consider inserting a nasogastric tube or, if you suspect 
a cribriform plate fracture, an orogastric tube. Insert a 
urinary catheter after inspecting the perineum for bruis- 
ing and bleeding, and carrying out a rectal examination 
in an injured patient (see Ch. 2). 



PART 2: MONITORING 







Key point 

Throughout the initial assessment, resuscitate, 
monitor and react to changing clinical and vital 
measurements (see also Ch. 9). 

Pulse. Remember that in an elderly or even a middle- 
aged person a rate of more than 140 beats per minute 
is very unlikely to be sinus tachycardia as this is too fast 
for someone of that age. Atrial flutter runs at around 
300 beats per minute, and therefore if there is 2-1 atrio- 
ventricular block the ventricular rate is 150 beats per 
minute. The rate of supraventricular tachycardia is 
usually 160-220 beats per minute. 
Respiratory rate is important. Do not forget it. The 
normal range is 12-20 breaths per minute. It rises early 
with blood loss or hypoxia, and, as well as being a very 
useful indication of the patient's clinical state, it is one 
of the physiological parameters that is mandatory for 
the calculation of the revised trauma score. 
Blood pressure drops in hypovolaemia when the blood 
loss is greater than 30-40% of the total blood volume - 



8 



RESUSCITATION 




1 



— a «M ^w s ^gM*ii ^ i tt^ atfc « a a feaaa^ :i ^i 



Table 1.1 Pupil size and response to light in comatose patients 



Dilated 



One pupil 



Both pupils 



Atropine in eye 

3rd nerve lesion normal consensual light 

reflex, e.g. posterior communicating 

artery aneurysm 

Enlarging mass lesion above the tentorium, 

causing a pressure cone 



Optk nerve lesion: 

Old; pale disc and afferent pupil 

New: afferent pupil with normal disc, loss of direct 

light reflex, loss of consensual reflex in other 

eye - both constrict with light in other eye 



Cerebral anoxia 

Very poor outlook if increasing supratentorial 
pressure - if dilated pupils preceded by unilateral 
dilatation or if due to diffuse cerebral damage 

Overdose: e.g. amphetamines {including MDMA 

"Ecstasy") 

carbon monoxide 

phenothiazines 

cocaine 

glutethimide 

antidepressants 
Hypothermia 



Constricted 



Pilocarpine in eye 
Horner's, e.g. brachial plexus lesion 
Acute stroke uncommonly (brainstem 
occlusion or carotid artery ischaemia: small 
pupil opposite side to weakness) 



Pilocarpine in both eyes (glaucoma treatment) 
Opiates, organophosphate insecticides and 
trichloroethanol (chloral) 

Pontine haemorrhage or ischaemia (brisk tendon 
reflexes, and raised temperature; poor 
prognostic sign) 

Alcohol poisoning (dilatation shaking) 
(Macewan's pupil)) 



If pupils normal in size, and reacting to light, consider metabolic, systemic non-cerebral causes 
(N,B. Normal pupiis do not exclude a drug overdose) 



about 2000 ml in an adult. Fit young adults, and 
especially children, maintain their blood pressure 
resiliency, but then it falls precipitously when com- 
pensatory mechanisms are overwhelmed. 
Pulse pressure is the difference between systolic and 
diastolic pressures. Diastolic pressure rises initially fol- 
lowing haemorrhage / because of vasoconstriction from 
circulating catecholamines. Systolic pressure stays con- 
stant, therefore the pulse pressure decreases. This is fol- 
lowed by a greater decrease in the pulse pressure as the 
systolic blood pressure falls once 30% of the patient's 
blood volume has been lost. 

Capillary refill time is the period it takes for blood to 
return to a compressed nailbed on release of pressure. 
It may be lengthened by hypothermia, peripheral 
microvascular disease and collagen diseases, in addi- 
tion to hypovolemia. The normal value is 2 s, but this 
increases early in shock, following a 15% loss of blood 
volume. 

Temperature fall indicates the degree of blood loss in a 
hypovolemic patient, quite apart from primary 
hypothermia. Restore blood volume adequately 



because simple warming of a hypovolaemic patient 
produces vasodilatation with resulting further fall in 
blood pressure. A patient with primary hypothermia is 
usually also hypovolaemic, so rapid rewarming results 
in a drop in blood pressure unless blood volume is 
replaced. Ensure your resuscitation room has a 
warming device, ideally as part of a rapid transfuser, so 
that intravenous fluid at 37-38°C can be immediately 
infused to the hypovolaemic or hypothermic patient. 

• Urinary output. The minimum normal obligatory 
output is 30 ml h _1 . In a child it is easily remembered as 
1 ml kg" 1 h" 1 . Suspect renal pathology if you find more 
than a trace of +protein on stick testing. 

• Central venous pressure (CVP) is measured in centime- 
tres of water by positioning the manometer on a stand 
such that the zero point is level with the patient's right 
atrium. The normal pressure is around 5 cmH 2 from 
the angle of Louis, with the patient at 45° to the 
horizontal. 

The CVP is a measure of the filling pressure (preload) to 
the right atrium. It reflects the volume of blood in the 




EMERGENCY 



**pUitUferilMHAillrtMUb 



central veins relative to the venous tone. It is not a 
measure of left heart function, until right ventricular func- 
tion is compromised as a result of poor left heart function. 
It may be low if the patient is hypovolaemic, and rises to 
normal with correction. If it rises slowly with a fluid chal- 
lenge, this usually indicates hypovolaemia. Particularly in 
the young, peripheral vasoconstriction to conserve central 
blood volume occurs in the presence of hypovolaemic 
shock, maintaining central venous pressure to a limited 
degree. It is raised if the circulating volume is too large, 
as might happen with renal failure or with overtransfu- 
sion. Overtransfusion not only precipitates heart failure, 
due to dilatation of the heart, but in a patient with a head 
injury the resultant rise in intracranial pressure may cause 
irreversible damage to the already bruised brain. 
Therefore assiduously monitor the CVP in these circum- 
stances. 

The CVP also rises with malfunctioning of the right 
side of the heart. It cannot then be used as an indicator of 
systemic circulatory filling, except as a measure of chang- 
ing cardiac function. It may be raised for mechanical 
reasons, such as tension pneumothorax or cardiac tam- 
ponade. It is also raised in the presence of pulmonary 
embolism, or when the heart is failing for lack of muscu- 
lar power due to contusion or infarction. 

Arterial blood gases 

pH (normal range 7.35-7.45) 

Does the patient have an acidosis, alkalosis or neither 
(Table 1.2)? The lower the pH, the more acidic is the blood 
sample, the opposite being the case for alkalosis. Acid (as 
hydrogen ions) is produced continually from metaboliz- 
ing cells, mostly as carbon dioxide. More is generated by 
lactic acid production during conditions of hypoxia, for 
example in shock, or in cardiac or respiratory arrest. 
Inadequate tissue perfusion results in acid buildup. Most 
acid-base abnormalities result from an imbalance 
between production and removal of H + ions (Table 1.3). 



Hydrogen is adsorbed by buffers, the largest being pro- 
teins, both intra- and extracellularly. In the extracellular 
fluid, the largest buffer is haemoglobin. However, bicar- 
bonate is a highly dynamic buffer, enabling an exchange 
to occur between hydrogen and carbon dioxide. This 
enables hydrogen to be excreted rapidly via the lungs as 
carbon dioxide: 

H + + HCOi ±? H 2 C0 3 ±? C0 2 + H 2 

Hydrogen ions are also excreted via the kidneys, but over 
hours or days, leaving respiratory compensation to be the 
most rapid method the body has for correction. 

The complex proteins of the body are optimally con- 
formed at ideal pH. When the pH of tissues changes, it 
induces conformational changes in proteins, affecting 
their function, especially enzymes and cell membrane 
channels. This is why it is crucial to maintain normal pH. 
Carbon dioxide is the largest generator of H + ions, ten 
times more than the production of lactic or other 
metabolic acids (Table 1.3). 

Pco 2 (normal range 35-45 mmHg, 4.5-5.5 kPa) 

• Pco 2 is high: suggests a respiratory acidosis (if pH is 
low); or a compensated metabolic alkalosis (see below). 

• Pco 2 is low: suggests a respiratory alkalosis (if pH is 
high); or a compensated metabolic acidosis (see below). 

The partial pressure of carbon dioxide is related to the 
degree of lung ventilation. Hyperventilation reduces 
Pco 2 and vice versa. If the patient is not breathing ade- 
quately, carbon dioxide is not adequately excreted and 
hydrogen ions build up, leading to acidosis caused by 
inadequate ventilation, that is, a respiratory acidosis. pH 
falls, indicating acidosis. Anxious patients and those in 
early hypovolaemic shock have a tachypnoea, resulting in 
overexcretion of carbon dioxide, with loss of hydrogen 
and a resulting respiratory alkalosis. 

When the patient is ventilated mechanically or manu- 
ally, an end-tidal carbon dioxide measuring device gives 



r" 



Table 1.2 Reading of arterial blood gases for acid-base balance 



Acidosis or alkalosis? 
Respiratory component? 



Metabolic component? 




pH 7.35-7.45 

If Pco 2 < 4.5 kPa, suggests respiratory alkalosis (pH > 7.45) r or attempted 
compensation of a metabolic acidosis (pH < 7.35 and BE < -3) 
If Pco ? > 5.5 kPa r suggests respiratory acidosis (pH < 7.35), or attempted 
compensation of a metabolic alkalosis (pH > 7 45 and BE > + 3) 

Base excess (BE) >s always affected by metabolic acid-base changes: 
Metabolic acidosis causes BE < -3 
Metabolic alkalosis causes BE > +3 



10 



RESUSCITATION 




1 



Table 1.3 Production a 


rtd elimination of hydrogen ions 


J 


Clas: 




Daily production 


Source Excreted in Metabolic 


Normal organ of 






(mol) 


breath removal 


elimination 








possible 




1 


CO 2 


15 


Tissue respiration + 


Lungs 


11 


Organic acids and 
urea synthesis 










Lactic 


1.2 


Muscle, brain - + 
erythrocytes, skin, etc. 


Liver (50%), 

kidneys, heart 

Many tissues (not fiver) 




Hydroxy butyric and 


0.6* 


Liver - + 






aceto acetic 










Fatty free acids 


0.7 


Adipose tissue - + 


Most tissues 




(FFA) 










H + generated during 


1.1 f 


Liver — + 


Most tissues (see te*t) r 




urea synthesis 






small fraction in urine 


111 


Fixed acids' 










Sulphuric 






Dietary sulphur-containing *i 










► 


0.1 


amino acids 




Urinary excretion 




Phosphoric 






Organic phosphate 


h 


(partly) 








metabolism J 


i 


The 


daily production rates for the organic acids are calculated from results obtained in a resting 70 kg man after an overnight 


fast, 


and are proportioned 


up to 2A h values. 






* Because of ingestion of food during daytime 


and consequent suppression of FFA and ketone body production, the values for 


these acids may be conside 


rable overestimates 


, 




'On 


100 g protein diet. 









a good correlation of arterial carbon dioxide, unless there 
is significant lung disease. End-tidal carbon dioxide 
partial pressure reflects that in the pulmonary artery, and 
indicates correct siting of the tracheal tube. 

Base excess (or deficit) (normal range -3 to 
+3) 

• High negative value: (e.g. -10) always indicates a 
metabolic acidosis. pH tends to normalize because of 
hyperventilation to reduce PaC0 2/ producing a com- 
pensatory 'respiratory alkalosis'. 

• High positive value: (e.g. +10) always indicates a 
metabolic alkalosis. Similarly, hypoventilation to increase 
Paco 2 tends to compensate and normalizes the pH. 

A metabolic acidosis indicates an inability of the kidneys 
to shift an increased hydrogen load, as occurs in shock, 
diabetes or renal failure. 

Chronic respiratory acidosis with normal pH occurs in 
chronic lung disease associated with chronic hypercar- 
bia, causing the kidneys to retain bicarbonate ion. This 
produces an increase in plasma bicarbonate concentra- 
tion and a normalizing of blood pH, despite the hyper- 



carbia (metabolic compensation). These changes take 
several days to occur but will identify those patients 
who normally run high PaC0 2 levels, not just those with 
acute changes. Whenever there is an attempted com- 
pensation, the pH never quite reaches completely 
normal values, which is how you can tell if there has 
been compensation. 

Overenthusiastic treatment with sodium bicarbonate is 
hazardous (Table 1.4). Do not give bicarbonate during the 
first 15 min of a cardiac arrest in a previously healthy 
patient. The principal method of controlling acid-base 
status during a cardiorespiratory arrest is adequate ven- 
tilation to ensure carbon dioxide excretion. If the pH is 
below 7.1 at 15 min with a normal or low Pco 2 , give either 
50 ml of 8.4% sodium bicarbonate intravenously (1 ml = 
1 mmol) or calculate the amount of bicarbonate needed to 
correct the metabolic acidosis from the blood gas result. 
Multiply the base deficit by the estimated extracellular 
volume (divide the product of the patient's weight in kilo- 
grams and the base deficit by 3). Base deficit is defined as 
the millimoles of alkali required to restore the pH of 1 litre 
of the patient's blood to normal at Pco 2 = 5.33 kPa. In 
practice, do not normally give more than 1 mmol kg^ 1 
initially. Of paramount importance in the traumatized 



11 



1 1 



EMERGENCY 



Table 1-4 Hazards of bicarbonate therapy 



1, 

4, 



Inactivates simultaneously administered catecholamines 

Shifts the oxyhaemoglobin dissociation curve to the left, inhibiting the release of oxygen to the tissues 
Exacerbates central venous acidoses and may, by production of carbon dioxide, produce a paradoxical acidosis 
Induces Hypernatremia, hyperosmolarity and an extracellular alkalosis; the last causes an acute intracellular 
shift of potassium and a decreased plasma ionized calcium 



patient is restoration of blood volume and reperfusion of 
the tissues. 

A lowered pH is desirable, provided that it does not fall 
below 7.1. Correct it if it falls below this; further acidosis 
lowers the threshold of the heart to ventricular fibrillation 
and inhibits normal cell metabolism. 

Pao 2 and oxygen saturation 

The partial pressure of oxygen in the arterial blood (also 
called the oxygen tension) is that pressure which oxygen 
gas produces if it is in a gaseous phase - if the blood is in 
a glass vessel with a gaseous phase immediately above it. 
Gases move down pressure gradients, and so oxygen in 
the body always moves from an area of higher partial 
pressure to an area of lower pressure, for example, from 
lung alveoli to mixed venous blood in the pulmonary 
artery. The Pao 2 indicates the amount of oxygen reaching 
the arterial blood from the lungs, or shows if there is some 
dilution with venous blood by shunting. 

Oxygen saturation is the proportion of haemoglobin 
bound to oxygen, expressed as a percentage. Oxygen car- 
riage depends on haemoglobin, and haemoglobin-bound 
oxygen is the main supplier of the tissues. The amount of 
oxygen in solution in the blood is minute, becoming sig- 
nificant only at ambient pressures which are multiples of 
atmospheric pressure. This is demonstrated in the oxygen 
flux equation, which gives the amount of oxygen flowing 
to the tissues per minute: 

2 flux = CO [(Sao 2 x Hb x 1 .34) + f] 

where CO is the cardiac output, Sa0 2 is the arterial oxygen 
saturation, 1.34 is Hoeffner's constant (the amount of 
oxygen that is capable of combining with Hb) and F is 
the small amount of oxygen dissolved in the blood. The 
values are converted to give millilitres per minute: 
normal oxygen flux is 1000 ml min -1 . The minimum flux 
compatible with life is 400 ml min -1 . 

Oxygen saturation is now routinely measured non- 
invasively by shining several infrared wavelengths of 
light across a finger, earlobe or other piece of skin. A 
sensor detects those waves not absorbed by haemoglobin. 
Oxy haemoglobin and deoxyhaemoglobin have different 
infrared absorption spectra, so the machine can calculate 



the mean oxygen saturation of blood reaching the part 
with each pulse, compensating for tissue absorption by an 
algorithm. 

The relationship between Pao 2 and Sao 2 is shown in the 
oxygen dissociation curve (Fig. 1.2). Note how the curve 
becomes steep below 90% saturation - the situation for 
many patients with lung disease. 

This curve is calculated for HbA, with normal charac- 
teristics. Other haemoglobins produce curves in different 
positions. For example, sickle cell anaemia shows a 
marked shift to the right, and fetal haemoglobin is shifted 
to the left. 

Acidosis increases ease of unloading oxygen from the 
blood into tissues; this is the Bohr effect, described by the 
Danish physiologist Christian Bohr (1855-1911), of pH on 
the oxygen dissociation curve (Fig. 1.2). Increasing tem- 
perature and increasing partial pressure of carbon dioxide 
have the same effect, the latter not just because of an asso- 
ciated acidosis but also because carbon dioxide combines 
directly with haemoglobin to form carbamino com- 
pounds. Anaemia, heat, raised carbon dioxide, acidosis 
and increased 2,3-diphosphoglycerate (2,3-DPG) cause a 
rightward shift to the oxygen dissociation curve, the 
opposite effects producing a leftward shift. 




40 60 80 100 
Oxygen pressure mm Hg 



Fig. 1.2 Effect of pH on the oxyhaemoglobin 
dissociation curve of human blood at 38°C. 



12 



RESUSCITATION 




1 



Blood sugar (fasting blood glucose normal 
range 3.6-5.8 mm I" 1 ) 




Key point 

Order an immediate blood glucose estimation, 
using a reagent strip, on every patient who has 
an altered level of consciousness, otherwise 
you will miss hypoglycaemia. 



Follow this with a laboratory estimation. When giving 
glucose in A & E, be aware of the possibility of precipi- 
tating Wernicke's encephalopathy (confusion, ophthal- 
moplegia, nystagmus, ataxia and peripheral neuritis - 
described in 1881), and give B vitamins (Pabrinex) intra- 
venously at the same time if there is any evidence of 
alcohol misuse. 



PART 3: THE SECONDARY SURVEY: 
DETERMINING THE CAUSE OF THE 
PATIENT'S COLLAPSE 






After carrying out the initial assessment (primary survey) 
and resuscitation of a collapsed patient presenting to the 
A & E department with no history, a deceptively incom- 
plete history or, worse, an incorrect history, now proceed 
to make a full head-to-toe examination. This is the sec- 
ondary survey, during which you aim to gain a clearer 
picture of the cause of the patient's collapse. Ensure that 
there is no occult injury. Examine all the skin, including 
the mouth and throat, the external auditory meati and the 
perineum. Always consider all the forensic possibilities, 
noting needle marks, pressure blisters and the presence of 
any visible soft tissue injuries. Remember that bruising 
may appear at a distance from the site of injury. 

1. Follow a routine to ensure you do not omit any 
feature. Keep in mind the common causes of collapse 
(Tables 1.5, 1.6), especially if communication is difficult, 
because of language, because the patient is unconscious 
or cannot communicate, or when obvious initial clinical 
signs deflect you from finding the hidden life-threatening 
pathology. 

2. Strictly adhere to standard guidelines for protection 
of medical and nursing staff from contamination with 
body fluids: wear gloves, waterproof gowns and masks 
with visors. Take special care to avoid needlestick 
injuries. Ensure all staff are immunized against hepatitis 
B virus. 

3. Leave on the cervical collar in all trauma patients 
while they are in the resuscitation room. This is manda- 
tory for all patients who have evidence of trauma above 



the level of the clavicle and have any decrease in level of 
consciousness, whether it be from the trauma itself or 
from drugs, especially alcohol. 

4. Keep an open mind to all diagnostic possibilities 
while both collecting the clinical evidence and monitoring 
the response of the vital signs to treatment. Beware a 
patient found by the police, and smelling of alcohol, who 
develops an acute intracranial haematoma after a rela- 
tively trivial head injury Involve your anaesthetist early 
with preparation for the CT scan of brain and possibly 
cervical spine. Patients with a head injury who misuse 
alcohol may have a larger subdural space and prolonged 
clotting times. Patients taking aspirin or warfarin are also 
at risk. 

5. If the conscious level is reduced and the gag reflex is 
depressed, the patient cannot protect his or her own 
airway. Call for anaesthetic assistance immediately. 
Provided he or she is breathing spontaneously, place the 
patient in the recovery position on the side (ensure first 
there is no evidence whatever of a spinal injury). 
Otherwise immediate preparations must be made to intu- 
bate the trachea in order to protect the lungs. This also 
applies if the patient is to receive gastric lavage and 
cannot protect his or her own airway with complete cer- 
tainty. If gastric contents are aspirated into the lungs they 
must be promptly sucked out because they produce a 
chemical pneumonitis followed by bacterial pneumonia. 
The clinical picture may well develop into adult respir- 
atory distress syndrome (ARDS). 

6. Consider forensic possibilities (Latin forum = market 
place, where courts of law were held; the application of 
medical science to elucidating appropriate legal ques- 
tions). Look for needle marks, soft tissue injuries and 
bruising, which may appear at a distance from the site of 
injury. Remember the possibility of non-accidental injury 
in children and in the elderly. 

7. Rhabdomyolysis and myoglobinuria may develop in 
any comatose patient after prolonged tissue pressure and 
muscle ischaemia, which is then relieved. Local swelling 
of muscles may be evident and compartment syndromes 
can develop because of positional obstruction of the cir- 
culation. Muscle death starts after 4h of complete 
ischaemia. Look for the early symptoms and signs of pain 
and paraesthesiae in a pallid, cool, weak limb. Passively 
extend the fingers or flex the foot to test for a developing 
compartment syndrome (anterior tibial compartment 
syndrome is the commonest). Losses of distal pulses, 
numbness, paralysis and development of a flexion con- 
tracture are all late signs. With myoglobinuria ensure that 
the urinary output is maintained at over 100 ml h _1 in an 
adult, or 2 ml kg -1 h" 1 in a child. Alkalinization of the 
urine in an appropriate high dependency setting with 
adequate monitoring increases the excretion of myo- 
globin, and will help prevent renal failure. 



13 






EMERGENCY 



Table 1 .5 Synopsis of causes of collapse to be considered during secondary survey 



System 



Cardiac 



Vascular 



Diagnosis 



Respiratory Upper airway obstruction 



Ventilatory failure 



Failure of alveolar gas exchange 



Tension pneumothorax 



Ventricular fibrillation 

Asystole 

Pulseless electrical activity 

Cardiogenic shock or failure 



Hypovolemic shock 



Anaphylactic shock 

Dissecting thoracic aorta 

Leaking abdominal aortic 

aneurysm 
Septic Shock 

Neurogenic shock 



Gastrointestinal Haemorrhage 

Perforated peptic ulcer 
Pancreatitis 
Mesenteric embolism 



Gynaecological Ruptured ectopic pregnancy 



Obstetric 



Supine hypotension 

Edarnpsra 

Pulmonary embolism 
Amniotic fluid embolism 



Notes 



InhaJed foreign body (try Heimlich manoeuvre) 

Infection such as epiglottitis (occurs in aduits, although 

commoner in children) 

Call help urgently 

Trauma including respiratory burns 

Asthma 

Chest trauma such as sucking open wound 

Paralysis such as in Guillain-Barre syndrome 

Pneumonia 

Pulmonary contusions 

Cardiogenic pulmonary oedema 

Adult respiratory distress syndrome 

From trauma (including iatrogenic) 

Ruptured emphysematous bulla 



Follow Resuscitation Council (UK) guidelines for treatment 

of cardiac arrest 

Look for treatable cause; tension pneumothorax, cardiac 

tamponade, hypoxia or hypovolemia, drug overdose 

Acute myocardial infarct 

Arrhythmia 

Pulmonary embolism 

Cardiac contusions after blunt chest trauma 

Valve rupture 



Revealed or concealed haemorrhage 

Diarrhoea and vomiting 

Fistulae 

Heat exhaustion 

From stings and bites, drugs or iodine-containing contrast 

used for radiological investigation 

Usually in previously hypertensive patients, pain radiates 

to back 

Always check femoral pulses so that you consider aortic 

pathology (although pulses may not be lost) 

Initially massive peripheral vasodilatation: 'warm shock'. 

Temperature may be normal 

From loss of sympathetic vascular tone in cervical or high 

thoracic spinal cord injury 



Always check: serum amylase 
Abdominal signs may be absent initially 



Usually at 4-6 weeks gestation. Always think of diagnosis 
in collapsed young woman 



The gravid uterus obstructs venous return from the vena 
cava unless the pregnant woman is turned onto her left side 



14 



RESUSCITATION 




1 



Table 1.5 (cont'd) 



System 



Diagnosis 



Neurological Head injury 



Infection 



Cerebrovascular 



Epilepsy 

Poisoning 

Alcohol 



Haematological Sickle cell crisis 

Malaria 
Coagulopathy 



Metabolic 



Hypoglycaemia 
Hyperglycaemia 
Hyponatremia 
Hypocalcaemia 
Hepatic failure 



Renal failure 



Endocrine 



Hypothermia 



Addisonian crisis 



Myxoedema 



Notes 




Isolated head injuries do not cause shock in adults. Look for 

sites of blood loss elsewhere 

Meningitis in children (often meningococcal in UK), tetanus, 

botulism, pofiornyelitis, rabies 

intracranial embolism or haemorrhage 

Subarachnoid haemorrhage may present solely as a severe 

headache 

Including the postictal (following a seizure) state 

See Table 16 



May lead to respiratory failure 
Cerebral malaria causes coma 
Thrombocytopenia may present with bleeding 



Check blood glucose in every patient 
Coma may be first presentation of diabetes mellitus 
May be addisonian crisis 
May present with fits 

Precipitated by paracetamol overdose in previously fit 
people, and by intestinal haemorrhage, drugs, or high- 
protein diet in those with chronic liver disease 
Prerenal from dehydration 

Renal, e,g, from crush syndrome and myoglobinuria 
Post-renal from ureteric obstruction (dangerous 
hyperkalemia causes tall tented T waves and widening of 
the QRS complexes) 

Resuscitation may include passive or active core rewarming 
Sepsis and hypovolemia often coexist 



Give 200 mg hydrocortisone i.v. (hypotension, low serum 
sodium, raised serum potassium) 
Always consider in hypothermic patients 



Ta b I e 1 . 6 Co m mon d r ugs 


and poisons 




Drug 


Symptoms and signs 


Treatment 


Paracetamol 


Liver and renal failure, hypoglycaemia 


Charcoal 




May be asymptomatic initially 


Acetylcysteine 


Salicylates 


Tinnitus, abdominal pain 


Lavage and charcoal 




Vomiting, hypoglycaemia, hyperthermia, 


Rehydration 




sweating 


Urinary alkalinization 




Acid-base disturbances 


Haemodia lysis 


Tricyclic antidepressants 


Arrhythmias and hypotension 


Lavage and charcoal 




Dilated pupils, convulsions 


Cardiopulmonary support 




Coma 


Sodium bicarbonate 


Benzodiazepines 


Drowsiness or coma 


Respiratory support 




Respiratory depression 


(Flumazenil) 


Opioids (heroin) 


Pinpoint pupils 


Respiratory support 




Loss of consciousness 


Naloxone 




Respiratory depression 






Needle marks 





15 




EMERGENCY 



Table 1.6 (cont'd) 






Drug 


Symptoms and signs 


Treatment 


Phenothiazines 


Dyskinesia, torticollis 


Procyclidine 


Lidocaine (lignocaine) 


Tingling tongue 


Cardiopulmonary support 




Perioral paraesthesiae 


Diazepam for convulsions 




Convulsions 






Ventricular fibrillation 




Carbon monoxide 


Nausea and vomiting 
Headache, drowsiness 
Hallucinations, convulsions 


100% or hyperbaric oxygen 


Cyanide 


Headache, vomiting, weakness 


Amyl nitrite inhalation 




Tachypnoea, convulsions 


Dicobalt edetate i.v. if diagnosis certain 




Coma 




Iron 


Hypotension, vasodilatation 


Lavage 




Gastric haemorrhage 


Desferrioxamine 


Organophosphates 


Nausea, vomiting, diarrhoea 


Lavage 


(pesticides, nerve gases) 


Salivation, pulmonary oedema 


Atropine 




Pinpoint pupils, convulsions, coma 


Pyridostigmine 



8. Keep clear, precise medical records of any resuscita- 
tion sequence, remembering that, since 1 November 1991, 
patients or their relatives have had the legal right to see 
medical records. This record keeping is the responsibility 
of the senior doctor present. Take appropriate care with 
forensic evidence, especially from terrorist incidents — 
anything removed from victims must be removed by a 
named person and must also be handed to a named 
person who personally seals the item in a labelled bag. 




Key point 

• If there is any clinical deterioration return to 
the basic initial sequence of the primary survey 
and recheck AIRWAY, BREATHING, CIRCULATION 
yet again. 

9. Ensure all patients with a diminished level of con- 
sciousness are seen by an anaesthetist before they leave 
the A & E department. Patients must be in the best poss- 
ible clinically supported condition for transportation, 
whether their journey is to the CT scanner, to a ward or 
to another hospital. If necessary, ensure that the patient is 



ventilated, depending on the length of journey and the 
form of transport employed. Order an appropriate 
trained attendant, such as an anaesthetist. 

10. Do not allow the patient to leave the A & E depart- 
ment without stable vital signs, appropriate intravenous 
lines in place, and having been thoroughly examined, 
unless there is an acceptable reason. A patient may all too 
easily deteriorate clinically in the X-ray room or, even 
more dangerously by reasons of reduced space, in the CT 
scanner. There must at the very least be a doctor of regis- 
trar grade in command of the resuscitation team. 

11 . For an A & E department to receive patients who 
need immediate resuscitation from a 'blue-light' ambu- 
lance, the hospital must have a minimum of an anaes- 
thetic registrar, a medical registrar and a surgical registrar 
'living in' on site 24 hours a day Even if the patient does 
not survive, you will be able to tell the relatives truthfully 
that everything possible was done. 

12. Both medical audit and medicolegal considerations 
dictate the above minimal adequate standards of care. All 
doctors who are expected to resuscitate the collapsed 
patient as part of their work practice are expected to be 
trained in the above. This is your responsibility, but more 
especially that of the supervising consultant and above all 
of the employing authority. 



16 



RESUSCITATION 




1 



Summary 

• Do you understand the importance of 
following routines and protocols when 
examining and treating collapsed patients? 

• Can you perform a competent initial 
primary survey, and identify and perform 
appropriate resuscitation procedures? 

• Are you capable of setting up monitoring 
procedures, interpreting the findings and 
taking the correct actions? 

• Do you have a grasp of the basic sciences 
as regards normal and altered body 
functions? 

• Can you carry out a complete, thorough, 
secondary survey and interpret the 
features? 

• Are you aware of the forensic aspects of 
working in the accident and emergency 
department? 





Further reading 

Advanced Life Support Course Sub-Committee 2000 Advanced 

life support course provider manual 4th edn. Resuscitation 

Council UK 
Advanced Life Support Group 1997 Advanced paediatric life 

support, 2nd edn. BMJ Publishing Group, London 
Advanced Trauma Life Support Course Manual 1997 American 

College of Surgeons, Chicago IL 
Driscoll P, Gwinnutt C, Jimmerson CL, Good all O 1993 Trauma 

resuscitation. Macmillan, London 
Driscoll P, Brown T, Gwinnutt C, Wardle T 1997 A simple guide 

to blood gas analysis. BMJ Publishing Group, London 
Evans TR 1995 ABC of resuscitation. British Medical 

Association, London 
Henry J A 1997 Poisoning. In: Skinner D, Swain A, Peyton R, 

Robertson C (eds) Cambridge textbook of accident and 

emergency. Cambridge University Press, Cambridge 
Jones RM 1989 Drug therapy in cardiopulmonary resuscitation. 

In: Baskett PJF (ed.) Cardiopulmonary resuscitation. Elsevier, 

Amsterdam, pp 99-101 
Royal College of Physicians 1991 Some aspects of the medical 

management of casualties of the Gulf War. RCP, London 
Skinner D, Driscoll P, Earlam R 1996 ABC of major trauma. 

British Medical Journal, London 
Touquet R, Fothergill J, Henry JA, Harris NH (2000) Accident 

and emergency medicine. In: Powers MJ, Harris NH (eds) 

Medical negligence, 3rd edn. Butterworths, London 



APPENDIX: CHEMICAL WEAPONS 



Terrorist or military attacks with chemical weapons may 
result in pathology and panic. Here we describe the 
effects of nerve gas and mustard gas. 

Nerve gases such as sarin, tabun 

These are organophosphorus compounds that act by 
inhibiting the enzyme acetylcholinesterase and therefore 
preventing the breakdown of acetylcholine at motor end- 
plates. The symptoms and signs of poisoning are the same 
as for organophosphorus insecticide poisoning - over- 
activity of the parasympathetic system and paralysis of 
the muscles of respiration. 

Initially treat by reversing the effects of acetylcholine at 
muscarinic receptors, using atropine. Give 2 mg intra- 
venously every 10-15 min in severe poisoning. Support 
respiration, reactivate inhibited acetylcholinesterase with 
oximes (pralidoxime mesilate) and suppress convulsions 
with diazepam. Pretreatment with pyridostigmine 
(reversible inhibitor of acetylcholinesterase) protects a 
proportion of the total quantity of enzyme present against 
a subsequent attack by nerve gas. 

Mustard gas (sulphur mustard) 

Exposure to the liquid or vapour produces blistering of 
the skin and damage to the cornea and conjunctiva. 
Classically there is an asymptomatic latent period of up 
to 6 h before reddening of the skin develops, leading to 
blistering. Burns are initially superficial, and blister fluid 
does not contain free sulphur mustard. Early vigorous 
scrubbing of the skin with soap and water reduces the 
severity of the skin burns. 

Treat eye exposure with saline irrigations, mydriatics, 
Vaseline to prevent sticking of the eyelids, dark glasses 
and antibiotic drops. The damage usually resolves over a 
number of weeks. 

Inhalation produces damage to the upper respiratory 
tract, with sloughing of the epithelium of the airways and 
nasal passages. The most severely affected patients need 
assisted ventilation with oxygen. Absorption of sulphur 
mustard leads to depression of the bone marrow and a fall 
in the white count, with a maximum effect at about 2 
weeks post-exposure. 

In the First World War the death rate from mustard gas 
was 2% of those exposed, resulting from burns, respir- 
atory damage and bone marrow depression. 



17 




Trauma 



M. Smith, P. A Driscoll 




Objectives 

Describe the biomechanics of injury 

commonly seen in clinical practice. 

Revise those aspects of human anatomy 

important in trauma care. 

Discuss the normal and pathophysiological 

response to trauma. 

Quantify trauma severity by using the 

anatomical and physiological assessments. 



Trauma is a major cause of death in the UK. It is sur- 
passed only by ischaemic heart disease, respiratory 
disease and carcinoma. Irrespective of gender it is the 
leading cause of death in the first four decades. Trauma 
accounts for 8.3% of all potential years lost under age 75. 
In England and Wales, approximately 10 000 people die 
each year: just under half of these deaths result from road 
traffic accidents; a not dissimilar number occur in the 
home. 

There has been a gradual fall in the number of UK 
deaths and serious injuries following trauma. This is due 
to primary, secondary and tertiary injury prevention, 
illustrated for road traffic accidents (RTA) in Table 2.1. 
Between 1974 and 2000 the number of fatalities fell by 
49% to 3409, and the number of seriously injured by 56% 



to 41 564. In contrast, the number of minor injuries rose 
by around 35% to 320 283. 

It is estimated that for every trauma death 2-3 victims 
are disabled, a proportion of whom require continuing 
healthcare facilities for life. The cost to the NHS and social 
service budgets could exceed £1.2 billion (Department of 
Health 1998); the cost to the country's economy is con- 
siderably greater. 

Trimodal distribution of death following 
trauma 

Over a decade ago, Trunkey, an American pioneer in 
the study of trauma, showed that trauma deaths in 
San Francisco followed a trimodal distribution over time. 

1. The first peak occurs at, or shortly after, the injury; 
these patients die from major neurological or vascular 
injury, most being unsalvageable with current technology. 




Key point 



• Up to 40% of irrecoverable trauma deaths may 
be avoided by appropriate prevention 
programmes. 

2. The second peak occurs several hours after the 
injury. Patients commonly die from airway, breathing or 
circulatory problems and many are potentially treatable. 





Table 2.1 


Initiatives in reducing RTA trauma 




initiative 


Definition 


Examples 


Primary 


Prevents the RTA occurring 


Better roads, speed restrictions, better car brakes, drink 
driving legislation 


Secondary 


Reduces the effect of the collision 


Seat belts, air bags, pedestrian-friendly' cars 


Tertiary 


Improvements in medical care 


Speedy and effective resuscitation, 






integrated trauma care, early rehabilitation. 



18 



TRAUMA 



2 




This period is known as the 'golden hour', emphasizing 
the time following injury when it is critical to resuscitate 
and stabilize patients. 

3. The final peak occurs days or weeks following injury. 
These victims die from multisystem organ failure (MSOF) 
or sepsis syndrome. Suboptimal resuscitation in the 
immediate or early postinjury phase increases the inci- 
dence of mortality and morbidity during this phase. 

The relative sizes of these peaks are now known to vary 
depending on the country. In Scotland, the first peak 
accounts for 76% of all the trauma deaths, the second 7% 
and the third 17%. This contrasts with San Francisco's 
figures of 50%, 30% and 20%, respectively. Indeed, recent 
work questions the existence of the trimodal distribution 
of death in the UK, suggesting an early peak followed by 
an exponential decline in mortality over time. 



BIOMECHANICS OF INJURY 



BLUNT TRAUMA 

Over 90% of trauma in the UK is a result of a blunt mech- 
anism. The force is dissipated over a wide area, minimiz- 
ing the energy transfer at any one spot and so reducing 
tissue damage. In low energy impacts, the clinical conse- 
quences are dependent on the organs involved. In con- 
trast, when high energies are involved, considerable 
tissue disruption can be produced, irrespective of the 
underlying organs. There are three types of force: 

1. Shearing results from two forces acting in opposite 
directions. Skin lacerations and abrasions produced by 
shear tend to be irregular, have a higher risk of infection 
and are associated with more damage to the surrounding 
tissue and more excessive scarring than follows low energy 
penetrating trauma. Shearing forces have a maximal effect 
on abdominal viscera at the points where the organs are 
tethered. Common examples include the peritoneal attach- 
ments at the duodenojejunal flexure, spleen, ileocaecal 
junction and the vascular attachments of the liver. 

2. Tension occurs when a force acts on a tissue surface 
at an angle of less than 90 s , causing avulsions and flap for- 
mation. Both are associated with more tissue damage and 
necrosis than are found after a shearing force. 

3. Compression acts on a tissue surface at 90 s and can 
produce significant damage and necrosis of the underly- 
ing structures. The impact site usually shows contusion 
(Latin tundere - to bruise), haematoma if a significant 
number of blood vessels are damaged, and possibly a 
breach of the surface tissue. Additionally, compression 
forces may raise internal pressure sufficiently to rupture 
the outer layer of closed gas or liquid-filled organs such 
as the bowel. 



A combination of these forces frequently contributes to 
the pattern of injury seen in victims of blunt trauma. 
Typically, multiple injuries occur, one system usually being 
severely affected and one to two others damaged to a 
lesser degree. Overall, the UK incidence of life-threatening 
injuries in different systems is: head 50.2%, chest 21.8%, 
abdomen 23.9% and spine 8.55%. More than 69% of trauma 
victims also have orthopaedic injuries, but these are not 
usually life threatening. 

Determining how these various forces result in patient 
injury is complicated. Seek help from the members of the 
emergency services who have had the opportunity to 
inspect the scene. For example, a frontal impact with a 
'bull's-eye' pattern on the windscreen, a collapsed steer- 
ing column and indentations on the dashboard indicate 
that the driver of this vehicle may have sustained a 
number of injuries (Table 2.2). 

Following a frontal impact, the patient is at risk of sus- 
taining a flexion-distraction type injury to the lumbar 
vertebrae if only a lap seat belt has been worn. This can 
produce a Chance fracture (vertebral fracture caused by 
acute flexion, with horizontal splitting of the spinal pro- 
cesses and neural arch), in addition to some or all of the 
listed injuries. Motorcyclists, pedestrians and victims 
ejected from a car have a significant risk of multiple 
injuries, including head, spinal, wrist and lower limb 
damage. 

A completely different pattern oi injuries results from 
rapid deceleration following a fall from a height on to a 
solid surface, landing on the feet (Table 2.3). 

Knowing the mechanism of injury allows you to predict 
possible life-threatening secondary injuries that may not 
be immediately apparent (see Ch. 1). It also gives you a 
clue as to the degree of energy transfer and, consequently, 
the level of tissue damage. 



Table 2,2 Potential driver injuries from a frontal 
car impact 



Facial fractures 

Obstructed airway 

Cervkal injury 

Cardiac contusion 

Pneumothorax 

Flail chest/fractured ribs 

Liver and/or spienk injury 

Posterior dislocation of the hip 

Acetabular fracture 

Fractured femur 

Patella fracture 

Carpometacarpal injuries 

Tarsometatarsal injuries 



J 



19 



2 . 



EMERGENCY 



Table 2.3 Potential injuries when landing on the 
feet from a fall 



L 



Tarsometatarsal injuries 

Calcaneal compression fractures 

Ankle fracture 

Tibial plateau fractures 

Pelvic vertical shear fracture 

Vertebral wedge fracture 

Cervical injury 

Rupture of the thoracic aorta 

Tracheobronchial disruption 

Liver avulsion 




Key point 

Anticipate high energy transfer following road 
traffic accidents, falls from a height and crush 
injuries. 



PENETRATING TRAUMA 






£-:^&^& ; -^^^^;^^ 






Around 7% of the annual trauma deaths in the UK are a 
result of a penetrating mechanism. The clinical conse- 
quences of penetrating trauma are dependent on both 
energy transfer and anatomical factors. 

Energy transfer 

Energy transferred to tissues surrounding the track of a 
weapon or missile depend upon: 

• The kinetic energy of the weapon or missile (KE = mass / 
2 x velocity 2 ) 

• The mean presenting area of the weapon or missile 

• The tendency of the weapon or missile to deform and 
fragment 

• The density of the tissues 

• The mechanical characteristics of the tissues. 

It follows that if the missile has a high velocity such as a 
rifle bullet, then it carries considerable kinetic energy, 
even though its mass is small. Realize that the crucial 
speed is the impact velocity, the speed of the missile 
when it hits the patient, not its initial velocity as it leaves 
the barrel of the gun. In contrast, a knife has a much 
lower kinetic energy because it travels at a much slower 
speed. 

Neighbouring tissues may be injured as kinetic energy 
is transferred to them. If the missile impacts in the tissues 
and fails to exit, all the kinetic energy is transferred, pro- 
ducing the maximum possible damage. This is more 



likely if the missile tumbles or fragments within the 
tissues. High energy pushes away surrounding tissues 
from the missile track, creating a temporary cavity. 
Although this lasts but a few milliseconds, it can extend 
to 30-40 times the diameter of the missile, depending on 
the amount of energy transferred to the tissues and their 
elasticity. As the energy waves dissipate, the tissues 
rapidly retract to a permanent cavity created by the 
destruction of the tissues in the direct path of the missile. 
This has three consequences: 

1 . There is functional and mechanical disruption of the 
neighbouring tissues / related to energy transfer and the 
tissue characteristics. Solid organs, such as the liver and 
spleen sustain severe damage. Lungs and other low 
density organs such as muscle, skin and blood vessels 
may escape significant disruption because of their greater 
elastic properties. 

2. A core of any covering clothing is carried deeply into 
the wound by the missile. The higher the projectile vel- 
ocity, the finer the shearing of material and the wider its 
spread. Negative pressure at the exit wound sucks in 
further material, increasing the chance of wound 
contamination. 

3. If a missile traverses a narrow part of the body the 
exit wound is usually larger than the entry wound 
because the temporary cavitation effect extends along the 
wound track. The temporary cavitation effect finishes if 
the missile gives up kinetic energy to become a low 
energy missile before leaving the body. There are, 
however, no certainties about the size of the entry and exit 
wounds. 



Anatomical factors 

An incision with low energy penetrating trauma, such as 
a stab wound, produces a wound with minimum oedema 
and inflammation that heals quickly and with minimum 
scarring (see Ch. 31). Nevertheless it can still be fatal, for 
example from a stab wound to the heart. 



BURNS 












There are 16 000 NHS admissions with burns each year in 
the UK. 

Thermal burns are most common, caused by heat from 
flames, flashes, scalds and contact with hot surfaces. 
Children and the elderly are the most frequent victims, 
but scalds are also the most prevalent type of industrial 
burn. 

Electrical burns cause damage depending on voltage, 
duration, tissue resistance and the direction and path 
taken by the current (see Ch. 24). Although the entrance 



20 



TRAUMA 



r 2 



and exit wounds are treated as thermal wounds, they do 
not accurately indicate the extent of the burn. Electric 
current travels along the path of least resistance; skin is 
resistant and current travels preferentially along arteries, 
veins, nerves, bones and tendons, making assessment 
difficult. 



By\STINJURIES_^ 

When a bomb is detonated there is a sudden release of 
considerable energy. The instantaneous pressure rise in 
the surrounding air is the shock front or blast wave, 
which travels at supersonic speed through the surround- 
ing air in all directions. The pressure falls progressively 
as the wave front travels further from the epicentre. 
Behind the shock front comes the blast wind, which is 
movement of the air itself, rapidly spreading out from the 
epicentre, carrying fragments from the bomb or sur- 
rounding debris at high velocity, some of it producing 
'high energy transfer' wounds. 

Primary effect 

This is a result of the shock front, mainly affecting air- 
containing organs such as lung, bowel and ears. The band 
of pressure strikes the surface of the body, causing dis- 
tortion and damage depending on its magnitude and rate 
of onset. These waves produce most of the damage, at the 
air-tissue boundary, associated with 'blast' lung, gut and 
tympanic membrane (Table 2.4). If the pulmonary 
changes are extensive, a ventilation-perfusion (V/Q) 
mismatch develops and hypoxia results. High blast pres- 
sures may also lead to air emboli; if they obstruct the cere- 
bral or coronary arteries, they may cause sudden death. 



area for these fragments is much greater than that of the 
shock front. Furthermore, at distances outside this area, 
they can still produce considerable damage. The patient 
usually presents with multiple, extensive wounds of 
varying depth, which are grossly contaminated. As the 
distance from the epicentre increases, the wounds become 
more superficial. 

Tertiary effects 

These are the result of the dynamic force of the wind 
itself, which can be so great as to carry all or part 
of the patient along with it. This results in impact (decel- 
eration) injuries and, in extreme cases, amputations. 

Miscellaneous effects 

These encompass all other causes of injury, including 
falling masonry, fires, toxic chemicals, flash burns, 
together with acute and chronic psychological disturb- 
ances. In addition to the primary effects, blasts give rise 
to penetrating, blunt and burn trauma. 



MAIN ANATOMICAL SITES OF 
TRAUMA 



The damage sustained by the patient depends not only on 
the biomechanics of the trauma but also on the anatomi- 
cal site of injury. 

These are discussed in the order in which they are 
usually managed clinically. 




AIRWAY 



Secondary effects 

These are the result of the direct impact of fragments 
carried in the blast wind. In most explosions, the lethal 



Table 2,4 Primary effects of Wast on lungs, gut 
and ears 



Haemorrhage into alveolar spaces 
Damage to alveolar septae 
Stripping of bronchial epithelium 
Emphysematous blebs produced on the pleural 

surface 
Contusion of the gut wall 
Leakage of blood into the gut lumen 
Perforation 
Rupture or congestion of the tympanic membrane 



The important structures and surface landmarks of the 
upper airway are shown in Figure 2.1. 



THORAX 






Chest wall 



1. The upper two ribs are extensively protected by the 
scapula and overlying muscle, requiring considerable 
force to break them. Consequently if they do break there 
is a high risk of concomitant damage to vital structures 
such as the thoracic aorta, main bronchi, lungs and spinal 
cord. Therefore, closely assess these vital structures if you 
discover fractures of the first two ribs. Remember that the 
neck is mobile and the pleural cavity and lung apex 
project above the clavicle, so pneumothorax or lung 
injury may result from penetrating injuries to the lower 



21 



2 . 



EMERGENCY 



Soft 
palate 







Palatine 
tonsil 

Epiglottis 

Hyoid bone 
Epiglottic cartilage 
Thyroid cartilage 
Cricoid cartilage 



Pharyngeal recess 



Pharyngeal 

tonsil 

Auditory 
tube 

Palato- 
pharyngeal 
fold 

Pharyngeal 
part of 
dorsum of 
tongue 












Laryngeal 
ventricle 






i 



Fig. 2.1 The upper airway. 

neck. Similarly, the lower six ribs overlie the abdominal 
cavity when the diaphragm is elevated during expiration, 
so both the lung and the upper abdominal viscera may be 
injured. Trauma to the 'midzone' of the trunk may be 
associated with both abdominal and chest injuries. 




Key point 

Following stab wounds of the lower chest the 
incidence of abdominal visceral involvement is 
15%. Following penetrating injury to the lower 
chest from gunshots it rises to 46%. 



2. When two or more adjacent ribs are fractured in two 
or more places they form a flail segment - a flail (proba- 
bly from Latin flagellum), classically has a loose segment 
hinged on to the handle. The adjacent doubly fractured 
clavicle and first rib may also produce a flail segment. On 
inspiration/ when the chest wall rises, the partially 
detached segment is sucked in - this is paradoxical move- 
ment. This may not be visible in the early stages when 
spasm of the chest wall muscles splint the fractures but 
becomes apparent when the muscles tire. Flail segment 
can be life threatening in the presence of underlying 
pulmonary contusion, which increases the tendency to 
hypoxia as a result of the impaired ventilation. 

3. The neurovascular bundle lying in the subcostal 
groove may be torn when ribs are fractured. Multiple 



fractures or significant disruption may cause massive 
haemothorax. The internal mammary artery may be torn. 
Large lung lacerations may not stop bleeding when the 
lung has been re-expanded by insertion of a chest drain. 
4. A one-way valve may develop on the lung surface, 
allowing air to enter the pleural cavity during inspiration 
but blocking its escape during expiration. This produces 
a tension pneumothorax unless the intrapleural pressure 
is relieved. 

Mediastinum 

The trachea, oesophagus and major blood vessels lie 
close together, so penetrating injuries of the mediastinum 
may damage one or more structures. The surface land- 
marks of the mediastinum are medial to the nipple line 
anteriorly, or medial to the medial edges of the scapulae 
posteriorly. 



CIRCUS 

1. Tough, inelastic, fibrous pericardium encloses and 
protects the heart. Even in a healthy person, a small 
collection of blood within the pericardium creates tam- 
ponade (French tampion = a plug) occupying space, com- 
promising ventricular filling and hence cardiac output. 
Intrapericardial haemorrhage usually follows penetrating 
trauma of the heart 

2. Blunt trauma can cause cardiac contusion, possibly 
associated with an overlying sternal fracture. A combina- 
tion of vascular spasm, intimal tearing and neighbouring 
tissue oedema may lead to coronary artery occlusion. 
Myocardial damage may cause dysrhythmias, infarction 
and impaired cardiac performance (see below), with 
electrocardiographic (ECG) abnormalities. Severe blunt 
trauma with rupture of the chordae tendinae produces 
mitral or tricuspid valve incompetence. 

3. The distal arch of the aorta is anchored just inferior to 
the left subclavian artery. During a deceleration injury 
there is a risk that the mobile aortic arch will shear off the 
fixed descending aorta, disrupting it. The injury may occur 
in falls over 9 metres (30 feet) or vehicle crashes at over 
50 k.p.h. (30 m.p.h.). In 10% of cases the escaping blood is 
contained by the outer, adventitial layer of the aorta but 
eventually this is also breached, rapidly exsanguinating 
the patient in the absence of surgical intervention. 



SKULL 






1. The scalp consists of five layers: Skin, subcutaneous 
layer, Aponeurosis, Loose areolar tissue, Periosteum 
(SCALP). The vascular subcutaneous layer is divided by 



22 



TRAUMA 



2 



fibrous bands into loculi, while the areolar layer is loose, 
and this is where scalp haematomas collect. If the apo- 
neurosis is breached, the wound tends to evert. 

2. The interior of the neurocranium is divided into two 
levels by a fibrous structure called the tentorium (tent) 
cerebelli. The midbrain passes through the opening in the 
anterior aspect of this layer, partially covered on its 
anterolateral aspects by the corticospinal tract. The ocu- 
lomotor (Illrd) nerve leaves the anterior aspect of the mid- 
brain to run forward, lying between the free and attached 
edges of the tent. In the intact state, there is free com- 
munication above and below the tentorium as well as 
between the intracranial and spinal subarachnoid spaces. 

3. Following head trauma, the development of a mass 
lesion above the tent, as from haematoma or cerebral 
oedema, may produce a pressure gradient. If this is unre- 
lieved it can result in one or both medial surfaces of the 
temporal lobes herniating through the opening in the tent. 
In so doing, the brain tissue presses on, and damages, 
structures in this region, namely the oculomotor nerve 
and motor fibres in the corticospinal tract. This is tentorial 
herniation, resulting in an ipsilateral (same side) fixed 
dilated pupil and contralateral weakness in the limbs. If 
the pressure increases further, the medulla and cerebel- 
lum are forced downwards into the foramen magnum - 
coning. This is a preterminal condition resulting in com- 
pression of the vital centres and disturbance of cardio- 
vascular and respiratory function. 

4. The base of the neurocranium is irregular, with the 
sphenoid wings and petrous processes projecting from its 
surface. Acceleration and deceleration forces move the 
brain over the base of the skull so that it collides with 
these projections, which damage it. 

5. The internal surface of the neurocranium is lined 
with the thick, hard, fibrous dura mater (Latin = hard 
mother, a translation from the Arabic) (Fig. 2.2). Its blood 
vessels closely adhere to the bone surface, grooving it in 
places, so they can be torn when forces are applied to the 
overlying bone. A haematoma collects between the bone 
and dura - an extradural haematoma; 90% of these are 
associated with a fractured skull. The middle meningeal 
artery is most at risk and the commonest site is the thin 
temporoparietal area. 

6. The arachnoid (Greek arachne = spider; like a 
spider's web) mater is connected to the pia mater (Latin 
translation of Arabic umm raqiqah = thin mother), across 
the cerebrospinal fluid (CSF)-filled subarachnoid space, 
by thin fibrous strands. Running between these strands 
are bridging veins, carrying blood from the brain to the 
venous sinuses. With age the brain atrophies, increasing 
the subarachnoid and subdural spaces, stretching the 
bridging veins and making them more likely to tear fol- 
lowing a head injury The resulting blood collects in the 
subdural and subarachnoid spaces. 



Subarachnoid space 

Arachnoid mater 

Subdural space 

Endocranium 
and dura mater 



Pia mater 




Meningeal 
vein and 
artery 

inner 

table of $Z>\ 

skull 



Cerebral vein Cerebral 

artery 



Grey 
matter 



White 
matter 



Fig. 2.2 The meninges and their blood supply. 



MAXILLOFACIAL SKELETON 










Key point 



• The major acute problem associated with 
significant facial fractures is the potential for 
associated airway obstruction secondary to 
swelling, haemorrhage and structural damage. 

The maxillofacial skeleton consists of a complex series of 
mainly aerated bones which provide a firm but light 
foundation to the face (Fig. 2.3). The nasal, frontal and 
zygoma tic-maxillary buttresses provide vertical support, 
with lateral stability coming from the zygomatic- 
temporal buttresses. Several of these bones, especially 
those making up the bony orbits, are closely associated 
with nerves and blood vessels, which may therefore be 
damaged when these bones are broken. In addition, the 
associated bleeding and deformity can lead to obstruction 
of the patient's airway. 

Nasoethmoidal-orbital fractures 

These result from trauma to the bridge of the nose or 
medial orbital wall. In view of their location, they are asso- 
ciated with lacrimal duct (Latin lacrima, Greek dakre = tear) 
injury, dural rupture and traumatic telecanthus (Greek 
tele = far + kanthos - angle at junction of the eyelids); 
the medial canthus is tethered to the displaced medial 
orbital wall, drawing it down and widening the angle. 



23 



2 -" 



EMERGENCY 




Frontal bone 
Nasal bone 
Sphenoid bone 
Ethmoid bone 
Lacrimal bone 
Zygomatic bone 
Maxillary bone 

Mandible 






Fig. 2.3 The facial skeleton. 

Blow-out fractures 

These result from blunt injury to the eyeball, increasing 
intraorbital pressure, depressing and fracturing the thin 
floor of the orbit, often with associated fracture of the 
medial orbital wall. The infraorbital nerve is usually 
damaged, producing anaesthesia of the cheek, upper lip 
and upper gum and also diplopia (Greek diploos = double 
+ ops = eye; double vision), especially to upward gaze. 
This results from a combination of muscle haematoma, 
third nerve damage, entrapment of periorbital fat and, 
in a minority of cases, true entrapment of extraocular 
muscles. Subcutaneous emphysema (Greek em = in + 
physaein = to blow; to inflate) occurs if the fracture extends 
into a sinus or nasal antrum. 

Zygomatic complex fractures 

Two types can be caused by blunt trauma. Zygomatic arch 
fractures are produced by a direct blow and can give rise to 
limited mouth opening due to impingement of temporalis 
muscle. The more serious 'tripod 7 type of fracture involves 
the displacement of the whole zygoma. This bone can be 
compared to a four-legged stool, with the 'legs' being the 
floor and lateral wall of the orbit, the zygomatic arch and 
the lateral wall of the antrum. The 'seat' of the stool cannot 
be moved without displacement of at least two of the legs'. 
This is associated with lateral subconjunctival haemorrhage 
and infraorbital anaesthesia. In addition, the displacement 
leads to a downward angulation of the lateral canthus and 
either trismus or an open bite. 



Fractures of the middle third of the facial 
skeleton 

It takes approximately 100 times the force of gravity to 
break the middle third of the face. Consequently, patients 
with this condition have significant multisystem trauma 
in addition to the malocclusion, facial anaesthesia and 
visual symptoms described above. Traditionally, the 
fractures are classified using the system devised by the 
French paediatric orthopaedic surgeon, Rene Le Fort in 
1901 (Fig. 2.4). The grade of fracture is often asymmetri- 
cal, that is, different on two sides. The Le Fort I fracture 
runs in a transverse plane above the alveolar ridge to the 
pterygoid region. Le Fort II extends from the nasal bones 
into the medial orbital wall and crosses the infraorbital 
rim. Le Fort III detaches the middle third of the facial 
skeleton from the cranial base; it is therefore commonly 
associated with fractures of the base of the skull and 
bloody CSF rhinorrhoea and otorrhoea (Greek rhinos = 
nose, otos = ear + rhoia = a flow). A characteristic 'dish 
face' may be evident due to retropositioning (Greek 
retros - backward) of the midface along the base of the 
skull 

Mandibular fractures 

The mandible, like the pelvis, is a ring structure and 
therefore rarely fractured in isolation. Usually there are 
multiple fractures or an injury to the temporomandi- 
bular joint. Common fracture sites are the condylar 
process, through the posterior alveolar margin, and 




Fig. 2.4 Common sites of fracture of the midface. 



24 



TRAUMA 



2 




Fig. 2.5 Common sites of fracture of the mandible. 



through the alveolar margin anterior to the premolar 
teeth. In the majority of the latter cases the fracture is 
open as it extends between the teeth and communicates 
with the oral cavity (Fig. 2.5). It is common to find 
numbness of the lower lip on the affected side and 
malocclusion. 



ABDOMEN AND GENITOURINARY 
SYSTEM 



SSfH^SS^&^^i*W&*~ 



&*& ■>?-- ^-tV^if -F^^^^^^^i^r 



Peritoneal cavity 

This can be subdivided into intrathoracic and abdominal 
regions. Remember, however, that on expiration, the 
diaphragm rises anteriorly to the level of the fourth inter- 
costal space. As a result, several of the intraperitoneal 
organs, such as the liver, spleen and stomach, lie within 
the bony thorax and are therefore at risk if the patient 
suffers trauma to the lower chest. 

1. Diaphragmatic injury is uncommon and rarely 
occurs in isolation. It may result from both blunt and 
penetrating injury. The former tends to occur with greater 
force than the latter and commonly leads to larger tears 
in the diaphragm, through which abdominal contents 
may enter the thorax and compromise respiration. 
Injuries to the diaphragm may be so slight that the patient 
is asymptomatic and the damage may not be discovered 
until weeks, months or even years later. 

2. The liver and biliary tree are largely covered by the 
rib cage, affording some protection from injury. Although 
numerically less common than splenic injury, liver 
injuries account for more deaths as a result of unsus- 
pected intra-abdominal haemorrhage. Consider the 



possibility of underlying liver damage when assessing 
trauma victims. 

Because of their location, the gallbladder and extra- 
hepatic biliary tract are usually damaged in association 
with other viscera. Liver trauma is the most common 
coexisting pathology (50% of cases), but there is a signif- 
icant chance of pancreatic damage (17% of cases). 
Consequently, injury of the gallbladder and biliary tree 
are usually masked by the features resulting from damage 
to the surrounding viscera. This condition has an overall 
mortality of 16% due to coexisting organ injuries. Blunt 
trauma is the usual cause of gallbladder damage, and 
rupture is more likely when the gallbladder is distended, 
as between meals. 

3. The spleen is the most commonly injured solid organ 
in the abdomen following blunt trauma, and is therefore 
a frequent cause of shock in patients with abdominal 
injury. Any injury to the left lower chest or upper 
abdomen may cause splenic damage, ranging from small 
tears to complete shattering of the organ. 

4. Stomach injury is infrequent following blunt trauma 
but the stomach may be punctured by penetrating 
wounds; this usually presents as peritonitis. 

5. Small bowel damage may result from blunt or pen- 
etrating wounds, as well as blast injury. Blunt trauma and 
blast can cause bowel injury in one of three ways: (1) the 
force may squeeze the viscus between the anterior 
abdominal wall and vertebral column; (2) the bowel may 
rupture as a result of a sudden increase in pressure within 
the lumen, as when the abdomen is compressed (the 
closed-loop phenomenon); (3) the bowel may be rendered 
ischaemic by damage to the mesentery and its vessels. 
Mesenteric tears often result if the abdomen is subjected 
to deceleration or shearing forces; it is particularly 
common at points where the bowel crosses the interface 
between the intra- and retro peritoneum, including the 
duodenojejunal flexure and ileocaecal junction. Blast 
injuries can also lead to multiple intestinal perforations 
and areas of infarction. Bowel penetration injury usually 
produces small tears in the wall but may completely tran- 
sect it. Unlike injuries to the liver and spleen, trauma to 
the bowel is rarely immediately life threatening. As with 
the stomach, the major problem is peritonitis, which 
develops over several hours as a result of leakage of 
bowel contents into the peritoneum. 

Retroperitoneum 

1 . Injuries to the retroperitoneal organs are more diffi- 
cult to diagnose than are those in the peritoneal cavity 
because they are less accessible to physical examination 
and investigation. 

2. Pancreas and duodenum may be injured as a result 
of both blunt and penetrating trauma, the commonest 



25 



2 



EMERGENCY 



mechanism being that of the unrestrained car driver 
impacting with the steering wheel. 

3. Bowel. All of the caecum and ascending colon, as 
well as between one- and two-thirds of the circumference 
of the descending colon He within the retroperitoneal 
space. The remainder of the colon is located within the 
peritoneal cavity. Blunt or penetrating trauma can 
damage any part of the colon, allowing leakage of the 
bowel contents. However, in cases of retroperitoneal per- 
foration, the symptoms are usually ill-defined and slow to 
develop / leading to delayed diagnosis and increasing the 
risk of abscess formation. 

4. Vascular. The abdominal aorta is susceptible to 
damage as a result of penetrating injury. Severe trauma 
is almost invariably lethal, but lesser injuries manifest 
as hypotension and /or symptoms of ischaemia. If the 
haemorrhage is contained within the retroperitoneum, 
the hypotension may be transient, responding to fluid 
resuscitation. Later, a retroperitoneal haematoma may 
become visible as bruising in the flank or back, 
described by the Newcastle surgeon George Grey Turner 
in 1920, or around the umbilicus, described in 1919 
by Thomas Cullen, gynaecologist of Johns Hopkins 
Hospital in Baltimore. The inferior vena cava is suscep- 
tible to the same types of injury as the aorta, resulting in 
significant blood loss, although usually less than from 
an equivalent injury to the aorta. This is because the 
intravenous pressure is low and the external tissue pres- 
sure is relatively higher. However, if this pressure is lost, 
as occurs in the presence of a large wound, external pres- 
sure is diminished, so haemorrhage increases and may 
be life threatening. 

5. Renal system. The kidneys are well protected by soft 
tissue in front and bone and muscle behind. As a result, 
isolated injury to the kidneys is uncommon, barring 
sporting incidents. Significant renal damage following 
major penetrating or blunt trauma is usually associated 
with multiple organ injuries. Ureteric injury of either type 
is uncommon. Assiduously investigate macroscopic 
haematuria, or microscopic haematuria in the presence of 
shock. 

Pelvis 

1. Pelvic injuries mainly involve the bladder and 
posterior urethra. 

2. Urinary system. Although the bladder lies within the 
pelvis, when full it may extend as high as the umbilicus 
and be susceptible to injury to the lower abdomen. 
Compression of the abdomen increases intravesical pres- 
sure and may cause 'full-bladder blowout', although 
more commonly the bladder is punctured by bone 
fragments generated by fracture of the pelvis. Bladder 
rupture into the peritoneal cavity produces peritonitis. 



Extraperitoneal rupture is usually less dramatic but, if it 
remains undiagnosed, tissue necrosis follows. The short, 
female urethra is rarely injured. In males, posterior ure- 
thral injury usually occurs above the urogenital 
diaphragm (which contains the external sphincter ure- 
thrae) as a result of pelvic fracture and is therefore often 
associated with injuries to other body regions. Anterior 
urethral injury is generally the result of blunt trauma to 
the perineum, such as falling astride a beam, and is there- 
fore usually an isolated injury. If urethral rupture is com- 
plete, the patient is unable to pass urine. In contrast, a 
lesser injury, such as a submucosal haematoma, makes 
micturition slow, painful, but possible. 

3. The pelvis contains the rectum and the female repro- 
ductive organs. In addition to perforation from bony 
pelvic fragments following trauma, injuries to the rectum 
are similar to those described for the colon and bowel 
above. Uterine injuries are uncommon but can result 
from both blunt and penetrating trauma. The chance of 
damage from either mechanism is increased during 
pregnancy because of the greater uterine size. 



Abdominal wall 

1. In fit, athletic individuals this forms a firm muscular 
layer, offering considerable protection from blunt trauma. 
Protection is reduced in children and those with poorly 
developed muscles. The anterior abdominal muscles can 
rupture spontaneously, for example following vigorous 
exercise or coughing. The most common cause of tears is 
compression from a seat belt in a deceleration injury; if it 
produces an imprint of the overlying clothes and seat belt 
on the skin, there is a high probability of significant intra- 
abdominal injury. 

2. Although penetrating trauma can breach the ante- 
rior abdominal wall, it may not necessarily cause intra- 
abdominal injury. The degree of damage sustained 
depends on the nature of the weapon used: the wound 
may be either a stab wound or gunshot wound. 



Perineum 

Blunt or penetrating injury may injure the penis. 
Fractured penis infrequently results from forceful 
bending of the erect organ, rupturing one or both corpora 
cavernosa, causing a large subcutaneous haematoma and 
detumescence (Latin de = reversal + temure = to swell). 
The testes can be damaged by blunt or, more rarely, 
penetrating trauma. Rupture of the testis following the 
former is uncommon because of the scrotal position, 
cremasteric retraction and the frictionless surface of the 
tunica vaginalis. All these features allow the testis to 
evade the direct effects of blunt trauma. 



26 



TRAUMA 



r 2 



BONY PELVIS 

The bony pelvis is usually injured as a result of road 
traffic accidents (60-80%) or falls from a height (10%). 
These mechanisms give rise to anteroposterior compres- 
sion, lateral compression or vertical shear acting on the 
pelvis either singularly or in combination. They are all 
capable of producing pelvic instability and haemorrhage 
from the vascular and bony damage. Because of the 
nature of this high energy transfer, 98% of patients with 
major pelvic trauma have other injuries (Table 2.5). The 
mortality rate is therefore high, at 10%, but rises to 30% 
with an open fracture, and in this case mortality 
approaches 100% if the open fracture is missed. 

The bones of the pelvis can be separated only if the liga- 
ments uniting them are torn. When this occurs, structures 
running close to the ligaments, such as vessels and 
nerves, can be damaged. The resulting bleeding is usually 
venous and extraperitoneal, so it can be life threatening. 
However, a tamponading (plugging) effect can be 
achieved if fractures occur while the ligaments remain 
intact, in which case haemorrhage is less severe, and 
mortality lower. 



Table 2.5 Associations with pelvic 


fractures 






Major haemorrhage 


over 70% 


Musculoskeletal injury 


over 80% 


Intraabdominal injury 


18-35% 


Urologkal injury 


12-20% 


Lumbosacral plexus injury 


8-30% 



LIMBS 

Bone 

The size, shape and consistency of bone varies with age. 
Old bones require less force to break them than young 
ones because they are more brittle and often osteoporotic 
(Greek poros - passage; porous or rarefaction). In chil- 
dren, fractures may involve the physis (Greek = nature; 
growth plate), resulting in deformity if reduction is not 
accurate. 

Bone is a living tissue with a generous blood supply 
and can bleed profusely after injury. Furthermore, blood 
loss from adjacent vessels and oedema into the sur- 
rounding tissues can be severe enough to cause hypo- 
volemic shock. The approximate blood loss with some 
closed fractures is: pelvis 1.0-5.0 litres, femur 1.0-2.5 
litres, tibia 0.5-1.5 litres and humerus 0.5-1.5 litres. These 
volumes can be much higher if there is an open fracture 
(see below). 



Nerves 

These tend to lie within neurovascular fascial bundles 
close to the long bones in the limbs. This close proxim- 
ity is particularly noticeable around joints, making 
the nerves prone to damage following fractures and 
dislocations. 



Structure and function of a peripheral nerve 

The neuronal processes making up a nerve trunk are 
grouped into fascicles (Latin fascis - bundle). In the more 
proximal segments there is considerable crossing over 
and rearrangement between fascicles, but, more distally, 
below the elbow for example, the fascicular arrangement 
is constant, predictable and corresponds to the eventual 
motor and cutaneous branches. Some nerves, such as the 
ulnar, have small numbers of well-defined fascicles; 
others, such as the median nerve, have large numbers of 
smaller ones. 

You need to know the connective tissue framework of 
the nerve in order to understand nerve injuries. The out- 
ermost layer is the epineurium (Greek epi = upon + neuron 
= nerve), the chief characteristic of which is mechanical 
strength. It is usually in a state of longitudinal tension, 
which is why the ends of a cut nerve spring apart. Each 
fascicle is surrounded by perineurium (Greek peri = 
around); this functions as a blood-nerve barrier and 
determines the biochemical environment of the nerve 
tissue. The individual axons are invested in endoneurium 
(Greek endo - within), which forms conduits guiding each 
axon to the appropriate end organ. 

The nerve is nourished by an internal longitudinal 
plexus of vessels, fed at intervals by perforators from the 
adventitia. This plexus becomes occluded if the nerve is 
subjected to undue tension, otherwise it can support the 
nerve trunk even when it has been lifted from its bed over 
a distance. The cell body and axonal parts of the neuron 
communicate with each other chemically by means of the 
axoplasmic transport system. Under normal conditions 
this carries transmitter substances centrifugally (Latin 
centrum + fugare = to flee); during regeneration after 
injury, structural proteins are also carried. Signalling 
molecules from the end organs or from axons which are 
damaged are conveyed to the centrally sited cell body, 
thus transmitting peripheral influences proximally to the 
nucleus, which controls the repair. 

Vessels 

Following trauma, the intimal layer may be the only part 
of a limb artery damaged. This can be very difficult to 
detect clinically, initially because distal pulses and capil- 
lary refill are maintained. Subsequently, the intimal tear 



27 




EMERGENCY 



can become a focus for the formation of an intravascular 
thrombosis and can also give rise to distal embolization. 

More overt acute signs are seen only if a significant area 
of the lumen is occluded. When all the layers of the artery 
are transected transversely, the vessel goes into spasm 
from constriction of the muscle fibres in the media, limit- 
ing the degree of blood loss. Conversely, if there is a 
partial or longitudinal laceration, the muscle spasm tends 
to keep the hole in the artery open, and blood loss 
continues. 

Veins have less muscle in their walls but the venous 
pressure is lower than arterial pressure. However, many 
veins have external attachments, especially in the pelvis 
and intracranial sinuses, which hold them open. In addi- 
tion, many venous tears produce side holes rather than 
transections, prejudicing the sealing effects of annular 
contraction. Consequently, blood continues to leak from 
the lumen until direct pressure is applied. 

Limb compartments 

These are regions in the limbs where skeletal muscle is 
enclosed by relatively non-compliant fascia. Running 
through these areas are blood vessels and nerves, the 
function of which can be affected if intracompartmental 
pressure rises above capillary pressure. This is most com- 
monly seen in the four compartments around the tibia 
and fibula. Nevertheless, compartments also occur in the 
shoulder, forearm, hand, buttocks and thigh, and these 
can also give rise to the compartment syndrome (see 
below). 



SPINAL COLUMN 



y^S^^W^^fe^.^^ 



AW^ i &ViW: r ^T%&flfcy?4*.?&teS 



The stability of the vertebral column depends mainly on 
the integrity of a series of ligaments but the vertebral 
bodies and the intervertebral discs also contribute. These 
can be considered as three vertical columns. The anterior 
column comprises the anterior longitudinal ligament and 
the anterior half of both the vertebral body and inter- 
vertebral disc. The middle complex consists of the poste- 
rior longitudinal ligament and the posterior half of both 
the vertebral body and intervertebral disc. The posterior 
column comprises the remaining posterior ligament 
complex and the facet joints; it is structurally the most 
important column. If any two of these columns are dis- 
rupted, the vertebral column becomes unstable. 

The spinal cord runs down the spinal canal to the level 
of the second (adult) or third (baby) lumbar vertebra. The 
size of the space around the cord in the canal varies, 
depending on the relative diameters of the spinal cord 
and spinal canal. In the region of the thorax it is very 
small because the spinal cord is relatively wide. In 



contrast, there is a large potential space at the level of C2. 
Consequently, injuries in this area are not automatically 
fatal because there is a potential space behind the odon- 
toid process or dens (Latin - tooth). 




Key point 



• Steel's rule of three states that at the level of 
the first cervical vertebra one-third of the 
available space in the vertebral canal is 
occupied by the odontoid process and 
one-third by the spinal cord, leaving a free 
space of one-third. 

Free space in the spinal canal is an important safety factor 
in adaptation to injury; it can be reduced by spinal steno- 
sis or posterior osteophytes. 

Incidents leading to spinal injury are: 



• Road traffic accidents 


48% 


• Falls 


21% 


• Violent acts 


14% 


• Sport 


14% 


• Others 


3% 



1. Road traffic accidents can result from side, rear or 
front collision. Ejection from a car increases the chance of 
a spinal injury to approximately 1 in 14. Rear-end colli- 
sions can produce hyperextension of the neck followed by 
hyperflexion (the 'whiplash phenomenon'). Unprotected 
victims, such as pedestrians hit by cars or motorcyclists, 
have a higher chance of sustaining a spinal injury than 
those within a vehicle. 

2. Rugby football, especially following collapse of the 
scrum, is infamous for producing spinal trauma, but 
almost all sports have been implicated in spinal injury. 
Diving into shallow water, particularly by young males 
following alcohol imbibition, is a common cause of neck 
injuries during the spring and summer months. The 
victim usually misjudges the depth of the water or dives 
from too steep an angle, hitting his head on the underly- 
ing solid surface. Because of the mechanism of injury, 50% 
of patients with spinal trauma have other injuries, 7-20% 
have head injuries, 15-20% have chest injuries and 
around 2.5% have abdominal injuries. 

3. Injury may result from single or combined forces, 
including flexion, extension, rotation, lateral flexion, 
compression and distraction. In the adult, the vertebral 
column is more likely to be injured at C5/C6/C7 and 
T12/L1. The more mobile cervical and lumbar regions 
meet the relatively immobile thoracic segments, focusing 
stress and increasing the chance of fracture at these 
points. 



28 






TRAUMA 



2 



SKIN 

The principal soft tissue in the body is the skin. Ageing 
decreases the amount of collagen in both the skin and 
subcutaneous tissues, as well as weakening the elastic 
fibres. This process can be accelerated by the administra- 
tion of long-term steroids. These changes reduce the 
tensile strength of skin, allowing extensive lacerations to 
develop with minor trauma. 



THE BODY'S RESPONSE TO TRAUMA 

Injury initiates many well-developed physiological 
responses. Consequently, when you treat trauma victims 
you are presented with a complex combination of patho- 
physiological changes, some of which are a direct result 
of the injury and others the body's response to the initial 
insult. The underlying mechanisms controlling response 
are a mixture of cardiovascular, paracrine and endocrine 
reactions. Individual examples of the more important 
pathophysiological processes are listed in Table 2.6. 

METABOLIC RESPONSE TO INJURY 






Table 2.6 Pathophysiological effects contributing 
to the body's response to trauma 



Metabolic response to injury 

Shock and cardiovascular pathophysiology 

Systemic inflammatory response syndrome (SIRS) 

Coagulopathy 

Multiorgan failure {MQFJ 

Neu ^pathophysiology 

Spinal injuries 

Fractures 

Peripheral nerve injury 

Compartment syndrome 

Crush syndrome 

Fat emboli 

Wound healing 

Burns 



Three phases are recognized: the early, acute ebb phase, fol- 
lowed by the flow phase if resuscitation and homeostasis 



are successful, or by necrobiosis if treatment fails and death 
ensues (Fig. 2.6). Following very severe injuries, the ebb 
phase may be short and necrobiosis may already have 
started by the time the patient reaches the accident and 
emergency (A & E) department 

Ebb phase 

1. The body anticipates danger and prepares for fight 
or flight (the defence reaction). Superimposed on this is 



• Changes in homoeostatic 
reflex activity (thermoregulato- 
ry and cardiovascular) 

■ Compensation of fluid loss 

• Increase in plasma hormone 
levels (e.g. catecholamines) 

• Mobilization of energy reserves 

• Changes in fuel utilization 

• Initiation of acute phase 
plasma protein response 



■ Increase in metabolic rate 



Insulin resistance 

Increase in skeletal muscle breakdown 

— loss of lean body mass 

Increase in urinary nitrogen loss 



r 



APPRECIATION 
OF DANGER 



ACUTE (EBB) RESPONSE 
(12/24 HR) 



DELAYED (FLOW) RESPONSE 
(WEEKS) 



RECOVERY 



INJURY 



NECROBIOSIS — DEATH 



Fluid loss 
Tissue damage 



* Failure of tissue O2 delivery 

* Anaerobic metabolism 

* Organ failure 



Fig. 2.6 Defence reaction. 



29 




EMERGENCY 



the body's response to haemorrhage, tissue injury, pain 
and hypoxia 7 the response being related to the severity of 
the injury. The ebb phase is characterized by mobilization 
of energy reserves and changes in cardiovascular reflex 
activity. The latter corresponds to the clinical state 
commonly referred to as 'shock' (see below). Increased 
sympathetic nervous activity links these changes and is 
reflected by rises in plasma catecholamine (derived from 
catechu an extract of Indian plants), such as adrenaline 
(epinephrine) and noradrenaline (norepinephrine)/ with 
concentrations proportionate to the severity of the injury. 
Additionally there is a rapid secretion of hormones from 
the posterior and anterior pituitary gland as well as the 
adrenal medulla. 

2. Increased sympathetic activity stimulates the break- 
down of liver and muscle glycogen, leading to increased 
levels of plasma glucose. This hyperglycaemia is potenti- 
ated by reduced glucose utilization in skeletal muscle 
because high adrenaline (epinephrine) levels inhibit 
insulin secretion. A relative intracellular insulin resistance 
develops, the mechanism of which is unclear, although 
glucocorticoids maybe involved. 

3. The changes in carbohydrate metabolism in the ebb 
phase can be interpreted as defensive. In addition to pro- 
viding fuel for fight or flight, hyperglycaemia may also 
play a role in compensating for post-traumatic fluid loss, 
both by mobilizing water associated with glycogen and 
through its osmotic effects. The decrease in glucose clear- 
ance associated with the development of insulin resist- 
ance can be considered as a mechanism for preventing the 
wasteful use of the mobilized carbohydrate, which is an 
essential fuel for the brain and the wound, at a time when 
the supply of nutrients may be limited. 

4. Increased sympathetic activity also mobilizes fat 
from adipose tissue. Plasma concentrations of non- 
esterified fatty acids (NEFAs) and glycerol are raised fol- 
lowing accidental injury in humans, although the rela- 
tionship with injury severity is complex. Plasma NEFA is 
lower after severe injuries than after moderate ones, poss- 
ibly resulting from metabolic effects such as stimulation 
of re-esterification within adipose tissue by raised plasma 
lactate levels, or circulatory factors such as poor perfusion 
of adipose tissue. 

5. Increased plasma Cortisol, mediated by adrenocorti- 
cotrophic hormone (ACTH), occurs rapidly following all 
forms of injury, although the relationship with severity is 
again complex. Unexpectedly low Cortisol concentrations 
are found following severe injuries, which cannot be 
related to a failure of the ACTH response but are possibly 
caused by impaired adrenocortical blood flow in major 
trauma. 

6. In normal subjects the total consumption of oxygen 
per minute (Vo 2 ) is constant throughout a wide range of 
oxygen delivery (Do 2 X The normal Vo 2 for a resting male 



is 100-160 ml min -1 m~ 2 and the normal value of Do 2 in 
the same person is 500-720 ml min' 1 m" 2 ; therefore/ tissues 
are taking up only 20-25% of the oxygen brought to them. 
This is known as the oxygen extraction ratio (OER) and 
demonstrates that normally there is great potential for 
the tissues of the body to remove more oxygen from the 
circulating blood. 

7. Following trauma, both oxygen delivery and con- 
sumption can be affected. In simple haemorrhage, Vo 2 is 
maintained in the face of falling Do 2 by increasing the 
oxygen extraction ratio. When tissue injury occurs on the 
background of haemorrhage, despite the oxygen extraction 
ratio rising, oxygen consumption falls with oxygen deliv- 
ery. In other words, Vo 2 has become supply dependent. 

8. Nociceptive (Latin nocere — to hurt + recepere = to 
receive) stimulation also complicates the cardiovascular 
response to fluid loss. The heart rate response to simple 
haemorrhage is an initial tachycardia, mediated by the 
baroreflex (Greek baros — weight, pressure)/ followed, as 
the severity of haemorrhage increases, by a bradycardia 
(Greek bradys = slow) mediated by the 'depressor reflex'. 
The sensitivity of the baroreflex is reduced by injury, 
contrary to the increase seen following haemorrhage. 
Impairment of the baroreflex, which can persist for 
several weeks following modest injuries, means that 
vasopressors such as vasopressin (antidiuretic hormone, 
ADH) released acutely after injury are more effective in 
maintaining blood pressure than normally, when the 
baroreflex buffers their pressor effects. The bradycardia 
caused by the depressor reflex is also markedly 
attenuated by additional tissue injury. This complex 
interaction between the cardiovascular responses to 
haemorrhage and injury may be harmful. Maintenance of 
blood pressure following haemorrhage and injury can be 
achieved at the expense of intense vasoconstriction in 
peripheral vascular beds. Reduced gut blood flow is 
thought to be pivotal in the production of inflammatory 
cytokines such as interleukin 6 (IL-6) and tumour 
necrosis factor a (TNFa). Raised levels of these inflam- 
matory markers/ as well as abnormalities in IL-10, an 
anti-inflammatory cytokine, may lead to further tissue 
damage and increase the likelihood of developing 
multiple organ failure. 

9. There is clinical evidence for changes in the control 
of thermoregulation: severely injured patients do not 
shiver, despite having body temperatures below the 
normal threshold for the onset of shivering. The selection 
of the ambient temperature for thermal comfort is modi- 
fied. This may be centrally mediated, but cytokines are 
likely to be important. 

10. If tissue damage and fluid loss from the circulation 
are so severe that endogenous homoeostatic mechanisms 
are overwhelmed and resuscitation is inadequate, the 
necrobiotic phase begins. This is characterized by a 



30 



TRAUMA 




2 



progressive imbalance between oxygen demand and 
supply in the tissues, leading to a downward spiral of 
anaerobic metabolism, with irreversible tissue damage 
and death. 




Key point 

• If the ebb phase is successfully managed and 
oxygen delivery maintained, the flow phase 
ensues. 

Flow phase 

1 . The main features are increased metabolic rate and 
urinary nitrogen excretion associated with weight loss 
and muscle wasting, reaching a maximum at 7-10 days 
following uncomplicated injuries. This response pattern 
may last many weeks if sepsis and /or multiple organ 
failure supervene. The increased metabolic rate, which is 
proportional to the severity of injury, results from neural, 
hormonal and immunological factors. The wound acts 
as the "afferent arc', priming the inflammatory response, 
while systemically released stress hormones perpetuate 
the metabolic changes (efferent arc). The complex inter- 
action between the factors is still unclear. 

2. The wound, whether a fracture site or a burned 
surface, can be considered as an extra organ that is 
metabolically active and has a circulation that is not under 
neural control. It consumes large amounts of glucose, 
which is converted to lactate, which in turn is carried to the 
liver and reconverted to glucose. This is an energy- 
consuming process, reflected by an increase in hepatic 
oxygen consumption. Other factors possibly contributing to 
the hypermetabolism are: increases in cardiac output 
(needed to sustain a hyperdynamic circulation); the energy 
cost of the latent heat of evaporation of water from, for 
example, the surface of the burn; the energy costs of sub- 
strate cycling (metabolic processes which involve the 
expenditure of energy without any change in the amount of 
either substrate or product); and increased protein turnover. 

3. During the flow phase, the metabolic rate seldom 
exceeds 3000-4000 kcal per day, twice the normal resting 
metabolic expenditure, with the highest values following 
major burns. Energy expenditure is often lower than 
expected and may be close to, or even lower than, values 
predicted from standard tables. This is because the hyper- 
metabolic stimulus of injury or sepsis is superimposed on 
a background of inadequate calorie intake, immobility 
and loss of muscle mass, all of which tend to reduce 
metabolic rate. 

4. Hypermetabolism of the flow phase is fuelled by 
increases in the rates of turnover of both fat and glucose. 



Turnover of NEFAs is raised in relation to their plasma 
concentration, and the normal suppression of fat oxida- 
tion following the administration of exogenous glucose is 
not seen in these hypermetabolic patients. Both changes 
have been attributed to increased sympathetic activity, 
although plasma catecholamine concentrations are not 
always increased at this time. The rate of hepatic gluco- 
neogenesis is increased from a number of precursors, 
such as lactate and pyruvate from the wound and muscle, 
amino acids from muscle protein breakdown, and glyc- 
erol from fat mobilization. This increase in hepatic 
glucose production is not suppressed by infusing large 
quantities of glucose into burned or septic patients. The 
apparent resistance to the effects of insulin is mirrored by 
the failure of peripheral glucose utilization to rise to the 
extent predicted from the raised plasma glucose and 
insulin concentrations. This insulin resistance in, for 
example, uninjured skeletal muscle, seems to be an intra- 
cellular, postreceptor change. 

5. The balance between whole body protein synthesis 
and breakdown is obviously disturbed in the flow phase. 
The observed changes probably represent the interaction 
between the severity of injury and the nutritional state: 
increasing severity of injury causes increasing rates of 
both synthesis and breakdown, while undernutrition 
depresses synthesis. Thus, increasing nutritional intake 
should move a patient towards nitrogen balance but, 
despite technical advances for administering nutrients 
and modifications to the type and composition of feeding 
regimens, no amount of nitrogen is sufficient to produce 
a positive balance following severe injuries. Nevertheless, 
the use of anabolic agents, such as growth hormone or 
testosterone derivatives, and manipulations of ambient 
temperature may be advantageous as the patient moves 
from the catabolic flow phase into the anabolic convales- 
cent phase. 

6. A major site of net protein loss is skeletal muscle, 
both in the injured area and at a distance. For example, 
following moderate injury the patient can lose 2 kg of lean 
body mass, sufficient to compromise mobility, especially 
in the elderly whose reserves of muscle mass and strength 
are already reduced. Although the changes in skeletal 
muscle are very obvious, the liver is another tissue in 
which changes in protein synthesis are of particular inter- 
est after injury; it is the source of the acute-phase reactants 
such as C-reactive protein, fibrinogen and a r antitrypsin, 
the concentrations of which rise in response to infection, 
inflammation and trauma. 

7. These metabolic changes, not attributable to starva- 
tion or immobility, can be mimicked to some extent by the 
infusion of the counterregulatory hormones glucagon, 
adrenaline (epinephrine) and Cortisol. However, the 
plasma concentrations required to elicit relatively modest 
increases in nitrogen excretion, metabolic rate and induce 



31 



2 



EMERGENCY 



peripheral insulin resistance are much higher than those 
found in the flow phase, although they are similar to 
those noted in the ebb phase. 



SHOCK AND CARDIOVASCULAR 
PATHOPHYSIOLOGY 

Shock can be defined as inadequate organ perfusion and 
tissue oxygenation. Tissue oxidation depends on ade- 
quate pulmonary function with satisfactory gas exchange, 
together with an adequate quantity of functioning 
haemoglobin able to deliver and release oxygen to the 
tissues. 

When a sufficient cell mass has been damaged, shock 
becomes irreversible and the patient inevitably dies. 
Fortunately, the body has several compensatory mech- 
anisms which sustain adequate organ perfusion and 
lower the risk. 

Circulatory control 

Pressure receptors in the heart and baroreceptors in the 
carotid sinus and aortic arch trigger a reflex sympathetic 
response via control centres in the brainstem in response to 
hypovolaemia. The sympathetic discharge stimulates many 
tissues in the body, including the adrenal medulla, which 
releases increased amounts of systemic catecholamines, so 
enhancing the effects of direct sympathetic discharge, par- 
ticularly on the heart. This prevents or limits the fall in 
cardiac output by positive inotropic (Greek inos = muscle, 
fibre + tvepeein - to turn, influence) and chronotropic (Greek 
chronos = time + trepeein; influencing time or rate) effects on 
the heart and by increasing venous return as a result of 
venoconstriction. Furthermore, selective arteriolar and pre- 
capillary sphincter constriction supplying non-essential 
organs, such as skin and gut, maintains perfusion of vital 
organs, such as brain and heart. Selective perfusion lowers 
hydrostatic pressure in capillaries serving non-essential 
organs, also reducing diffusion of fluid across the capillary 
membrane into the interstitial space, thereby decreasing 
further loss of intravascular volume. Reduction in renal 
blood flow is detected by the juxtaglomerular apparatus in 
the kidney, which releases renin. This leads to the formation 
of angiotensin II and aldosterone; these, together with ADH 
released by the pituitary gland, increase renal reabsorption 
of sodium and water, reducing urine volume, and helping 
to maintain the circulating volume. Renin, angiotensin II 
and ADH can also produce generalized vasoconstriction, 
promoting increase in venous return. In addition, the body 
attempts to enhance the circulating volume by releasing 
osmotically active substances from the liver, which increase 
plasma osmotic pressure, drawing interstitial fluid into the 
intravascular space. 



Oxygen delivery 

Although sympathetically induced tachypnoea (Greek 
tachys = rapid + pnoia = breathing) occurs, it does not 
increase oxygen uptake because the blood haemoglobin 
traversing ventilated alveoli is already fully saturated. 



Causes of shock 

1. Reduced venous return following haemorrhage is 
the commonest cause of shock in traumatized patients. 
Bleeding may be occult, collecting in the large spaces of 
the thorax, abdomen and pelvis. As well as the potential 
spaces intrapleurally and within the retroperitoneum, 
blood may be lost into muscles and tissues around long- 
bone fractures; in addition, intravascular volume may be 
reduced as a result of leakage of plasma into the intersti- 
tial spaces. This can account for up to 25% of the volume 
of tissue swelling following blunt trauma. The rate of 
blood returning to the heart depends on the pressure 
gradient created by the high hydrostatic pressure in the 
peripheral veins and low hydrostatic pressure in the 
cardiac right atrium. Any reduction in this gradient, as 
from tension pneumothorax, cardiac tamponade or 
increasing right atrial pressure, reduces venous return to 
the heart. External compression on the thorax or abdomen 
can have a similar action in obstructing the venous return. 

2. Cardiogenic shock from ischaemic heart disease 
and cardiac contusions have negative inotropic effects. 
Nevertheless, it does not occur unless more than 40% of 
the left ventricular myocardium is dead or severely 
damaged. In cardiogenic shock the compensatory sym- 
pathetic and catecholamine responses only serve to 
increase the myocardial oxygen demand and further 
increase ischaemia. Certain dysrhythmias alone, from 
pre-existing cardiac ischaemia or following cardiac 
contusion, significantly reduce cardiac performance. Be 
aware that all antiarrhythmic agents may have negative 
inotropic effects, impeding the patient's physiological 
response to the injury. Cardiac tamponade not only preju- 
dices venous return but also restricts ventricular filling. 

3. Reduced arterial tone complicates spinal injury 
above T6 by impairing sympathetic nervous system 
outflow from the spinal cord below that level. 
Consequently, both the reflex tachycardia and vasocon- 
striction responses to hypovolaemia are restricted to a 
degree proportional to the level of sympathetic block. 
Generalized vasodilatation, bradycardia and loss of tem- 
perature control can follow high level spinal injuries, pro- 
ducing neurogenic shock; additional nervous damage may 
result from the reduced blood supply to the spinal 
column. Any associated haemorrhage from the injury 
aggravates this situation, further reducing spinal blood 
flow. In addition, these patients are very sensitive to any 



32 



TRAUMA 




2 



vagal stimulation. For example, pharyngeal suction can 
aggravate the bradycardia, leading to cardiac arrest. 

4, Septic shock results when circulating endotoxins, 
commonly from Gram-negative organisms/ produce 
vasodilatation and impair energy utilization at a cellular 
level. Hypoxia can devlop even with normal or high 
oxygen delivery rates, because the tissue oxygen demand 
is extremely high and there is impaired oxygen uptake by 
the cells. In addition, endotoxin makes the capillary walls 
leaky at the site of infection; this becomes more general- 
ized, allowing sodium and water to move from the inter- 
stitial to the intracellular space. This eventually leads to 
hypovolemia, making it indistinguishable from hypo- 
volemic shock. Further cellular damage by endotoxins 
causes the release of proteolytic enzymes, which paralyse 
precapillary sphincters, enhance capillary leakage and 
increase hypovolemia. The situation is aggravated by 
the endotoxin acting as a negative inotrope on the 
myocardium. It follows that in the late stage of sepsis 
there are several causes of the shock state. 



DISSEMINATED INTRAVASCULAR 

Trauma, massive blood transfusion, infection, hypother- 
mia, tissue injury and damage to the microvascular endo- 
thelium are all common causes of DIC. Procoagulant tissue 
factors such as IL-6 and TNFa are released, promoting 
inappropriate intravascular activation of the coagulation, 
fibrinolytic and complement systems. Both thrombin and 
plasmin are activated but out of balance; as a result, 
platelet-fibrin thrombi form in the microvasculature, while 
fibrin degradation products are raised in the plasma. 
Platelets are reduced in number and impaired in function; 
coagulation and fibrinolytic factors are also reduced and 
coagulation studies show prolongation of clotting time. 

Coagulopathy resulting in vascular occlusion can 
provoke end-organ ischaemia, infarction and failure. At 
the same time it can lead to haemorrhage and uncon- 
trolled bleeding at many sites, as in surgical wounds, the 
skin, the pulmonary system, the gastrointestinal tract and 
the cranium. Haemorrhagic complications usually domi- 
nate in acute DIC following trauma. 



MULTIPLE ORGAN FAILURE (MOF) 



■y?-&s&x¥r?*W 



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;.f.5^.^:.lS^^. j^j;^; ^■'^^■^W^^i^^^i^B^S-^^-^ \ 



This is defined as the presence of altered function in two 
or more organs in an acutely ill patient, such that inter- 
vention is required to maintain homeostasis (Greek 
homoios = like + stasis = standing; tendency to stable 
state). It represents the final common pathway of many 
disease processes, of which trauma is one. It is invariably 



preceded by a condition known as the systemic inflam- 
matory response syndrome (SIRS), characterized by two 
or more of the following: 

• Temperature >38° C or <36° C 

• Tachycardia >90 beats per minute 

• Respiratory rate >20 breaths per minute or PaC0 2 
<4.3 kPa 

• White blood count >12 x 10 9 l" 1 or < 4 x 10 9 l" 1 or >10% 
immature (band) forms. 




Key point 

Multiple organ failure is a deadly condition 
with a mortality rate of about 60%. 



1 . The pathophysiology behind MOF has yet to be fully 
elucidated. A 'one-hit model' accounts for early MOF as 
a result of massive trauma. The initial insult triggers a 
severe SIRS, leading to MOF. It was apparent that some 
traumatized patients who had sustained non-massive 
trauma developed delayed MOF. The 'two-hit model' was 
developed to explain the occurrence of MOF in such 
patients. In this model the initial injury primes the inflam- 
matory machinery to a subclinical level. This gives rise to 
the exaggerated response seen in MOF only if the patient 
is subjected to a 'second hit', such as hypoxia, hypoten- 
sion, infection, operation, anaesthesia or further trauma. 

2. Irrespective of the actual cause, it is probable that a 
stimulus such as injury or infection initiates the release of 
a number of mediators by macrophages, monocytes and 
endothelial cells. These include TNF, IL-1(3, IL-6 and IL-8. 
Following 'relook' laparotomies (reoperations to identify 
and correct any complications that have developed), 
raised levels of IL-6 were found; this suggests that 
cytokines may have a role in intensifying and perpetu- 
ating the inflammatory state following such a 'second hit'. 
These changes cause further white cell activation in addi- 
tion to adhesion of leucocytes to endothelial cells lining 
blood vessels. This occurs in virtually all organs of the 
body, but particularly the lungs, liver and intestine. The 
process leads to the migration of white cells into the inter- 
stitial space, the release of proteases and oxygen radicals 
and the activation of arachidonic acid. Such changes ex- 
acerbate existing capillary damage, leading to widespread 
leakage of fluid into the interstitial space. In addition, 
arachidonic acid activation gives rise to prostacyclin, 
thromboxane A 2 and leukotrienes. 

3. Tissue damage is simultaneously resulting from 
vasoconstriction and intravascular thrombosis in the 
microvascular circulation. In the lungs, this can give rise 
to right heart failure due to the increases in pulmonary 
vascular resistance and pulmonary artery pressure. 



33 



2 




EMERGENCY 



4. In managing these patients, recognize that the 
normal relationship between oxygen delivery to tissue 
(Do 2 ) and oxygen consumption (Vo 2 ) is altered. In MOF, 
partly because of the marked increase in Vo 2 , tissues 
become flow dependent, that is reliant upon Do 2 (see 
p. 30). Consequently, any hypovolemia, pulmonary 
disease or myocardial dysfunction jeopardizes the deliv- 
ery of oxygen even further, and so increases the degree of 
tissue hypoxia and organ dysfunction. 

Adult respiratory distress syndrome/acute 
lung injury 

Adult respiratory distress syndrome (ARDS) represents 
the severe form of acute lung injury (ALI). Although only 
approximately 2% of trauma patients develop ARDS, they 
then have a mortality rate of approximately 40-50%. 

ALI is a collective term for hypoxaemic respiratory 
failure, characterized by the American-European con- 
sensus as: 

• Bilateral pulmonary infiltrates visible on chest X-ray 

• Pulmonary capillary wedge pressure <18 mmHg 

• Pao 2 /fio 2 <300. 

In ARDS: 

• Pao 2 /Ho 2 <200 

Aetiology and pathogenesis 

1. Acute lung injury can be caused by local or systemic 
inflammation. In trauma patients it may result from direct 
lung injury or, when the injured tissue is more distant, by 
SIRS (see above). 

2. Direct causes include pulmonary contusion, aspir- 
ation of gastric contents, near drowning, inhalation of 
toxic fumes, thermal injury to the respiratory tract, 
bacterial or viral pneumonia, and radiation injury. 

3. Indirect causes include sepsis, massive haemorrhage, 
multiple transfusions, shock from any cause, DIC, massive 
burns, major and multiple trauma, pre-eclampsia, amni- 
otic fluid embolism, pancreatitis, head injuries and 
cardiopulmonary bypass. 

4. In addition, it has been suggested that any critical 
illness that leads to inadequate cellular oxygenation can 
precipitate the syndrome. 

5. Regardless of the cause, pathogenesis follows a 
common pathway (Fig. 2.7). Neutrophils adhere to the 
vascular endothelium, then migrate into the interstitium 
and alveolar airspaces. They release inflammatory medi- 
ators that attract and activate other inflammatory cells, 
stimulate the coagulation cascade and release oxygen free 
radicals, producing widespread endothelial damage. As a 
result of the increased capillary permeability, protein-rich 
fluid occupies the interstitium and alveolar airspaces; 



Direct lung 
injury 



Causative event 




Indirect lung 
injury 



i 



Neutrophils 
Platelets 
Macrophages 
{all activated) 



t 




l 



Widespread endothelial damage 



t 

Cell destruction and 
death 



i 



ARDS and multiple organ failure 



Fig. 2.7 A simplified flow chart illustrating the 
development of ARDS. 



this, coupled with the deactivation of surfactant, causes 
stiff lungs with decreased compliance. The protein-rich 
fluid, coupled with increased lung lymph flow, thickens 
the alveolar capillary membrane, impairing oxygen dif- 
fusion. In the later stages of the disease, fibrosis may 
develop. 



NEUROLOGICAL PATHOPHYSIOLOGY 



"^S^-^W+S-^-' 



Head injuries are common. In the UK head-injured 
patients account for 7-10% of all emergency department 
attendances, of whom 1 in 7 are admitted. Most serious 
head injuries result from road accidents, falls and 
assaults. Over 5000 people die from traumatic brain 
injury in England and Wales every year. It is estimated 
that a further 1500 patients survive to endure significant 
lifelong morbidity. Remember that victims have a mean 



34 



TRAUMA 



2 



age of 30, so there is a major impact on society. The 
combination of head injury and extracranial injury is 
particularly dangerous, as the presence of hypoxia and 
hypotension is associated with a 75% increase in mortal- 
ity from severe head injury. This is partly the result of 
impaired autoregulatory capacity of the injured brain, 
resulting in the development of secondary brain injury. 

Intracranial pressure 

1. In the adult the neurocranium is a rigid box and its 
volume is fixed. The intracranial pressure (ICP) generated 
inside it depends on the volume of its contents. In the 
normal state these consist of brain, CSF, blood and blood 
vessels. Together, these produce an ICP of 5-13 mmHg 
when the subject lies horizontally. 

2. If the ICP is to be kept at normal levels, any increase 
in the volume of one component must be accompanied by 
a decrease in the other components. CSF can be displaced 
into the spinal system and its absorption increased. The 
volume of cerebral venous blood within the dural sinuses 
can also decrease. Furthermore, the brain is a compliant 
organ, so it can mould to accommodate changes. Once 
the limit of these compensatory mechanisms is reached, 
the ICP rises. 

3. Head trauma results not only in mass lesions but 
also in increased permeability of the intracerebral 
microvasculature. This leads to interstitial oedema and 
cerebral swelling, making the brain relatively 'stiff, so it 
is less able to adapt to changes in the intracranial con- 
tents. This situation deteriorates further if ventilation is 
impaired, as hypoxia produces additional cerebral 
swelling. Hypercarbia results in vasodilatation of the 
blood vessels in the uninjured parts of the brain (see 
below), thereby increasing intracranial pressure. 

4. Alterations in the intracranial contents, including 
haematoma, not only produce an elevated ICP but also 
make the brain, CSF and blood less adaptable to any 
further additions. Even a small rise in volume of the 
intracranial contents now causes a steep rise in the ICP. 
Eventually, the brain herniates downwards through the 
defect between the edges of the tentorium, and this ten- 
torial herniation causes ipsilateral (Greek ipsos = same) 
pupillary dilatation (Illrd cranial nerve compression) and 
contralateral (Latin contra = opposite) motor weakness 
(corticospinal tract compression). As ICP rises further, 
the brainstem is compressed within the foramen 
magnum, causing coning, leading to ischaemia. This is 
heralded by Cushing's reflex, described by the great 
American neurosurgeon (1869-1939), which is usually 
fatal: 

a. Decreased respiratory rate 

b. Decreased heart rate 

c. Increased systolic blood pressure. 



Cerebral perfusion 

Adequate ventilation and cerebral perfusion are essential 
to supply the brain with oxygenated blood. Perfusion 
depends on a difference between mean arterial pressure 
(MAP) and the resistance to blood flow due to the ICP: 
cerebral perfusion pressure (CPP) = MAP - ICP. 

In the multiply injured patient, not only is the ICP 
rising because of the head injury, but the MAP may be 
falling due to blood loss from an extracranial trauma. The 
CPP is markedly reduced. If the CPP is 50 mmHg or less, 
cerebral ischaemia develops; as described above, this 
leads to additional brain swelling and further rises in ICP 
as the cycle perpetuates itself. Make every effort to keep 
CPP at greater than 70 mmHg, as this reduces mortality. 
A CPP less than 30 mmHg is fatal. 

Consciousness 

Consciousness depends on an intact ascending reticular 
activating system, contained within the midbrain and 
brainstem, and an intact cerebral cortex. Interruption any- 
where along this pathway, either structural or metabolic, 
results in loss of consciousness. There are many possible 
causes but the mnemonic (Greek mneme = memory) 
'TIPPS on the vowels 7 recalls the important ones: 



Trauma 


Alcohol 


Infection 


Epilepsy 


Poisons 


Increase in ICP 


Psychiatric 


Opiates 


Shock 


Uraemia / metabolic 



e 



Key point 

Eliminate hypoxia and hypovolaemia; each can 
alone induce coma. If they are coupled with 
head trauma, mortality increases. 



An initial measure of consciousness is the patient's 
response to stimulation. This is graded on the AVPU scale. 



A 
V 
P 

u 



Alert 

Responds to Voice 

Responds to Pain 

No response (Unconscious) 



The Glasgow Coma Scale is a more complicated but vali- 
dated assessment based on the patient's best eye, verbal 
and motor responses to stimulation (Greek koma = deep 
sleep). The scale (Table 2.7) is an objective measure of the 
condition, used to monitor the patient's progress. The 
three scores are added; the minimum score is 3 and any 
score below 8 carries a poor prognosis. 



35 




EMERGENCY 



Table 2.7 


The 


Glasgow Coma Scale 








Eye opening 


Score 


Verbal response 


Score 


Motor response 


Score 


Spontaneous 


4 


Orientated 


5 


Obeys commands 


6 


To speech 




3 


Confused 


4 


Localizes to pain 


5 


To pain 




2 


Inappropriate words 


3 


Withdraws 


4 


None 




1 


Inappropriate sounds 


2 


Flexion to pain 


3 








None 


1 


Extension to pain 


2 












None 


1 



Fractures 

Skull fractures usually result from direct trauma and are 
classified as being linear, depressed or open. The term 
'open' implies a direct communication between the 
brain surface and either the scalp or mucous membrane 
laceration. 

Primary and secondary brain injury 

1. Neurological cells may die as a result of energy 
transferred to them by the injurious event - primary brain 
injury. Possibly, progressive primary brain damage occurs 
subsequently because of endogenous neurochemical 
changes leading to further cellular injury. At present, 
injury prevention is the only factor that reduces primary 
brain damage. 

2. Secondary brain injury is the neurological damage 
produced by subsequent insults, such as hypoxia, hypo- 
volaemia and elevation in ICP (remember CPP = MAP - 
ICP), metabolic imbalance, seizures and later diffuse 
brain swelling, and infection. Mortality can be reduced by 
appropriate resuscitation to prevent secondary brain 
injury. 

3. A purely focal injury can follow a contact force. 
However, there is usually sufficient associated diffuse 
brain injury to produce an altered level of consciousness 
from a temporary disruption of the reticular formation 
(see above). Furthermore, a space-occupying lesion is 
often accompanied by a swollen brain due to primary and 
secondary brain damage. This accelerates the rise in 
intracranial pressure and the development of additional 
brain damage. Consequently, the trauma patient invari- 
ably has diffuse and specific neurological injuries. The 
clinical features of a focal injury depend on the site 
injured, as different parts of the brain perform different 
functions; diffuse brain injuries tend to be bilateral. 

4. Selective herniation of the cerebellum through the 
foramen magnum can be produced by an expanding pos- 
terior fossa intracranial haematoma. This is the only cere- 
bral haematoma to produce neurological damage without 
a preceding deterioration in consciousness level. (See 
above for tentorial and brainstem herniation.) Among the 
features, the most common are pupillary dilatation, 



respiratory abnormalities, bradycardia, head tilt and 
cranial nerve palsies. Most alarming is sudden respiratory 
arrest resulting from distal brainstem compression. It is a 
rare condition but consider it early, especially in patients 
with an occipital fracture. 

Concussion 

Concussion (Latin con = together + quatare - to shake) 
occurs when the head is subjected to minor inertial forces. 
The patient is always amnesic of the event and there may 
also be retro- and antegrade amnesia. A transient loss of 
consciousness may occur, usually less than 5 min. These 
patients show no localizing signs but may have nausea, 
vomiting and headache. It was at first thought that no 
organic brain damage occurred but this is found not to be 
the case: microscopic changes occur, and, while the net 
effect of one episode is minor, the effect of further 
episodes can be cumulative. 

Diffuse axonal injury (DAI) and contra coup 
injury 

1. Diffuse axonal injury results from widespread, 
mainly microscopic, disruption of the brain, consisting of 
axonal damage, microscopic haemorrhages, tears in the 
brain tissue and interstitial oedema. Consequently, it can 
cause prolonged periods, for days or weeks, of coma and 
has an overall mortality rate of 33-50%. Autonomic dys- 
function is common, giving rise to high fever, hyperten- 
sion and sweating. 

2. The brain that lies beneath the impact point of a 
contact force is subjected to a series of strains resulting 
from the inward deformation of bone and the shock 
waves spreading from the site of impact. The base of the 
brain can be strained if it impinges on projections on the 
base of the skull, producing gross neurological damage, 
with haemorrhages, neuronal death and brain swelling. 
Consciousness is invariably lost at the time of the incident 
and neurological signs develop by the time it is regained. 
Common signs are altered level of consciousness, hemi- 
paresis, ataxia and seizures. 

3. The brain is not fixed within the neurocranium but 
floats in a bath of CSF, tethered by the arachnoid fibres 



36 



TRAUMA 



r 2 



and blood vessels. As the head moves because of an accel- 
erating or decelerating force, the skull, and then the brain, 
moves in the direction of the force. Consequently, strains 
develop in the brain tissue and small blood vessels oppo- 
site the impact point, producing the contusional changes 
previously described. Additionally, the brain continues to 
move until it impacts against the opposite side of the skull 
or its base, thus injuring it in two places, most severely at 
the site furthest from the impact; this is a contra coup injury 
(French = counterblow). 

Acute intracranial haematoma 

1 . Most extradural haematomas (EDHs) develop in the 
temporoparietal area following a tear in the middle 
meningeal artery. Much less commonly, they result from 
torn venous sinuses within the neurocranium. Compared 
to a venous cause, an arterially produced extradural 
haematoma develops quickly, producing a rapid rise in 
intracranial pressure. 

2. The 'classic' presentation (Fig. 2.8) occurs in only 
one-fifth of patients. Some may be unconscious from the 
time of the impact, others do not lose consciousness at the 
time but later develop neurological features. Most com- 
monly there is a deterioration of consciousness, pupil-size 
changes or a focal weakness. 

Acute intradural haematoma (IDH) 

1. This incorporates both subdural (SDH) and intra- 
cerebral (ICH) haematomas, which frequently coexist, and 
are 3-4 times more common than extradural haematomas. 
Subdural haematomas usually develop in the temporal 
lobe and may be bilateral. Following application of an 
inertiai force, some of the bridging veins tear and blood 
collects in the subdural space. Occasionally, a subdural 
haematoma develops without an accompanying intra- 
cerebral haematoma. Solitary intracerebral haematomas 
rarely develop in the frontal lobes. 

2. Small intracerebral haematomas may result from 
inertiai forces, and increase in volume over time. 
Depending on their location, they may cause localizing 
signs or a rise in the intracranial pressure, with deterio- 
ration in the patient's clinical state. 



3. The forces needed to produce an intracerebral 
haematoma are greater than those needed to produce an 
extradural haematoma, so an intracerebral haematoma is 
usually associated with cerebral contusion and cortical 
lacerations. Consequently, the patient commonly loses 
consciousness immediately and may also exhibit focal 
signs such as contralateral hemiparesis (Greek parienai = 
to relax), unilateral pupil dilatation or focal fits. With a 
solitary subdural haematoma, an initial lucid period may 
be followed by deteriorating neurological state. This 
develops more slowly than following an extradural 
haematoma because the bleeding is venous rather than 
arterial. Tears of only a few bridging veins, in the pres- 
ence of brain atrophy with enlargement of the intracranial 
space, may delay development of symptoms for several 
days. 

Subarachnoid haemorrhage (SAH) 

This occasionally follows a head injury. The patient often 
develops severe headaches and photophobia, but other 
signs of meningism can occur. Do not test for neck 
stiffness until cervical spine injury has been ruled out 
clinically and radiologically (see Ch. 1). 



SPINAL INJURIES 

In the UK, 10-15 people per million of the population 
suffer spinal injuries each year (Table 2.8). The common- 
est site is the cervical spine (55%), mainly because most 
people are injured following a road traffic accident 

(48%). 



Table 2.8 Sites of spinal injuries 



Site 



Blunt trauma 
(%) 



Penetrating trauma 



Cervical 
Thoracic 
Lumbar 
Multiple 



55 
35 
10 
10 



24 
56 
20 



• Transient loss of consciousness at the time of the injury from a momentary disruption of the 
reticular formation. 

• Patient then regains consciousness for several hours j the lucid period, 

m Localizing signs develop with neurological deficits, headache and eventually 
unconsciousness from the developing EDH, which causes the ICP to rise. 

Fig. 2.8 Classic history of an extradural haematoma (EDH). 



37 




EMERGENCY 



Primary neurological damage 

1. This results directly from the initial insult, usually 
from blunt trauma, producing abnormal movement in the 
vertebral column. Severe trauma may lead to ligamental 
rupture and vertebral fractures, reducing the space 
around the spinal canal and allowing bone and soft tissue 
to impinge directly on the cord. The potential space 
around the spinal cord may already be small, increasing 
the chance of neurological damage. 

2. Less commonly, penetrating trauma, as by stabbing, 
causes primary spinal damage. Much more extensive 
areas of destruction and oedema result when the spinal 
cord is subjected to a large force such as a gunshot. 

Secondary neurological damage 

1. The three common causes of damage following the 
initial injury are mechanical disturbance of the back, 
hypoxia and poor spinal perfusion. These effects are 
additive. 

2. Hypoxia can result from any of the causes men- 
tioned above, but significant spinal injury alone can cause 
it (Table 2.9). The underlying problem is usually a lack of 
respiratory muscle power following a high spinal lesion. 
Lesions above T12 denervate the intercostal muscles. 
Injuries above the level of C5 also block the phrenic nerve, 
paralysing the diaphragm. 

3. Inadequate spinal perfusion results either from 
general hypovolaemia or failure of the spinal cord to 
regulate its own blood supply following injury. A fall in 
mean arterial pressure therefore produces a reduced 
spinal perfusion. Conversely, if the pressure is increased 
too far it may produce a spinal haemorrhagic infarct. 
Secondary damage leads to interstitial and intracellular 



Table 2.9 Respiratory failure in spinal injury 



Tetraplegic 



Paraplegic 



Intercostal paralysis 
Phrenic nerve palsy 
Inability to expectorate 

V/Q mismatch 



Intercostal paralysis 



oedema, further aggravating the deficient spinal perfu- 
sion. As this oedema spreads, compressing neurons, it 
produces an ascending clinical deterioration. In cases of 
high spinal injury this process can lead to secondary res- 
piratory deterioration. 

Partial spinal cord injury 

Anterior spinal cord injury results from direct compres- 
sion or obstruction of the anterior spinal artery. It affects 
the spinothalamic and corticospinal tracts (Fig. 2.9), result- 
ing in loss of coarse touch, pain and temperature sensa- 
tion, and flaccid weakness. This type of injury is associated 
with fractures or dislocations in the vertebral column. 

Central spinal cord injury usually occurs in elderly 
patients with cervical spondylosis. Following a vascular 
event the corticospinal tracts are damaged, resulting in 
flaccid weakness. Because of the anatomical arrangement 
in the centre of the cord, the upper limbs are more affected 
than the lower. 

Sacral fibres in the spinothalamic tract are positioned 
laterally to corresponding fibres from other regions of the 
body (Fig. 2.9). It follows that anterior and central 
injuries, which primarily affect the midline of the spinal 



Dorsal columns (cutaneous sensation 
and proprioception from ipsi lateral) 



Lateraf corticospinal tract 

(cross motor fibres) 



Dorsal spinothalamic tract (pain 
and temperature sensation from 
opposite side of body) 



Ventral spinothalamic tract (crude touch 
and pressure from opposfte side of body) 




S: sacral area 
L: lumbar area 
T: thoracic area 
C; cervical area 



Posterior spinocerebellar tract 



Anterior spinocerebellar tract 



Anterior corticospinal tract (uncrossed motor fibres) 



Fig. 2.9 Cross-section of the spinal cord demonstrating the longitudinal tracts. (With permission from Driscoll P, 
Gwinnutt C, Jimmerson C, Goodall O. In: Trauma resuscitation: the team approach, Macmillan Press Ltd). 



38 



TRAUMA 




cord, may not affect the sacral fibres. This 'sacral sparing' 
produces sensory loss below a certain level on the trunk, 
with retention of pinprick appreciation over the sacral 
and perineal area. 

Lateral spinal cord injury (Brown-Sequard syndrome) 
is the result of penetrating trauma. All sensory and motor 
function is lost on the side of the wound at the level of the 
lesion. Below this level there is contralateral loss of pain 
and temperature sensation with ipsilateral loss of muscle 
power and tone. 

Posterior spinal cord injury is a rare condition, result- 
ing in loss of vibration sensation and proprioception. 

Spinal shock 

1. This totally functionless condition occasionally 
occurs following spinal injury. The features are general- 
ized flaccid paralysis, diaphragmatic breathing, priap- 
ism, gastric dilatation and autonomic dysfunction 
associated with neurogenic shock. The English neurolo- 
gist CE. Beevor (1854-1908) described movement of the 
umbilicus when the abdomen is stroked, resulting from 
paralysis of the lower rectus abdominis muscle. 

2. This state can last for days or weeks, but areas of the 
cord are still capable of a full recovery. Permanent 
damage results in spasticity once the flaccid state 
resolves. Upper motor neuron reflexes return below the 
level of the lesion following complete transection of the 
cord, producing exaggerated responses to stimuli; 
however, sensation is lost. 

3. During this stage there is risk of pressure sores, deep 
venous thrombosis, pulmonary emboli and acute peptic 
ulceration with either haematemesis or, occasionally, 
perforation. 



FRACTURES 

1 . Fracture occurs in normal bone as a result of trauma. 
The type of fracture depends on the direction of the viol- 
ence. A twisting injury causes a spiral or oblique fracture, 
a direct blow usually causes a transverse fracture, axial 
compression frequently results in a comminuted (Latin 
minuere = to make small) or burst fracture. 

2. Stress fractures occur when the underlying bone is 
normal. It is the repetitive application of an abnormal 
load that causes the bone to fracture. The load alone is not 
sufficient to cause the fracture but rather the cumulative 
effect of repeated loading. It is most frequently seen in 
individuals undertaking increased amounts of unaccus- 
tomed exercise, such as the 'march' metatarsal fracture in 
army recruits and dancers. 

3. Pathological fractures occur when the underlying 
bone is weak, perhaps from metastatic cancer or 



metabolic bone disease; as a result it gives way under 
minimal trauma. 



Fracture repair 

1. When a fracture occurs, not only is the bone broken 
but the encircling tissues are also damaged. The bone 
ends are surrounded by a haematoma including these 
injured tissues. Within hours an aseptic inflammatory 
response develops, comprising polymorphonuclear leu- 
cocytes, lymphocytes, macrophages and blood vessels, 
followed later by fibroblasts. Within this organized frac- 
ture haematoma, bone develops either directly or follow- 
ing the formation of cartilage with endochondral 
ossification. At the same time osteoclasts resorb the 
necrotic bone ends. The initial bone that is laid down 
(callus) consists of immature woven bone, which is gradu- 
ally converted to stable lamellar (Latin lamina - a thin 
plate) bone with consolidation of the fracture. Resorption 
occurs within the bone trabeculae as recanalizing 
haversian systems (described by the English physician 
C. Havers 1650-1702) bridge the bone ends. 

2. There are two types of callus. Primary callus results 
from proliferation of committed osteoprogenitor cells in 
periosteum and bone marrow. They produce directly 
membranous bone, a once-only phenomenon limited in 
duration. The second callus is inductive or external callus, 
derived from the surrounding tissues, formed by pluri- 
potential cells. A variety of factors, including mechanical 
and humoral factors, may induce these mesenchymal 
cells to differentiate to cartilage or bone. 

3. The mediators for callus formation are not fully 
understood. Probably the fracture ends emit osteogenic 
substances, such as bone morpho genetic protein, into the 
surrounding haematoma. This is in addition to mediators 
such as IL-1 and growth factors released from the fracture 
haematoma. Angiogenic factors probably play an import- 
ant role in the vascularization of the fracture haematoma. 

4. Movement of the fragments increases the fracture 
exudate. Rigid fixation minimizes the granulation tissue 
and external callus and may retard the release of mor- 
phogens and growth factors from the bone ends. 
Reaming of the intramedullary canal may cause addi- 
tional bone damage. Weight bearing stimulates growth 
factors and prostaglandins, which act as biochemical 
mediators. 



PERIPHERAL NERVE|NJURY 

1. Blunt trauma to a nerve may produce a temporary 
block in the conduction of impulses, leaving the axonal 
transport system intact. The axon distal to the injury 
survives and complete functional recovery can be expected; 



39 



2 



EMERGENCY 



this is neuropraxia (Greek a = not + prassein = to act). More 
severe trauma will interrupt axonal transport and cause 
wallerian (Augustus Waller 1816-1870) degeneration: the 
distal axon dies, the myelin sheath disintegrates and the 
Schwann cells turn into scavenging macrophages which 
remove the debris. The cell body then embarks on a pre- 
programmed regenerative response which is usually 
known as chromatolysis, as it involves the disappearance of 
the Nissl's granules which are the rough endoplasmic reti- 
culum of the normal cell. An entirely new set of ribosomes 
appears, dedicated to the task of reconstruction. By their 
efforts, axon sprouts emerge from the axon proximal to the 
lesion and grow distally. Injury of this severity is known as 
axonotmesis (Greek tmesis = a cutting apart). It eventually 
produces a good functional result because the endoneurial 
tubes are intact and the regenerating axons are therefore 
guaranteed to reach the correct end organs. 

2. Laceration or extreme traction producing neuro- 
tmesis also leads to wallerian distal degeneration and 
proximal chromatolysis - loosening of the chromatin of 
cell nuclei, followed by either cell death or axonal regen- 
eration. In this case, however, the final functional result is 
bound to be much worse than in any injury that leaves the 
endoneurial tubes intact. Not only do the axon sprouts 
have to traverse a gap filled with organizing repair tissue, 
but each one needs to grow down its original conduit at 
a rate of approximately 1 mm per day Axons failing to 
enter the distal stump may form a tender neuroma, often 
producing troublesome symptoms. Progress can be mon- 
itored clinically using the sign described by the French 
neurologist Jules Tinel (1879-1952), These are electric feel- 
ings in the territory of the nerve produced by light per- 
cussion over regenerating axon tips, whether in the distal 
portion of the nerve or in a neuroma. 

3. Motor axons are capable of producing collateral 
sprouts once they enter muscle, leading to abnormally 
large motor units with relatively good return of strength. 
Sensory axons often fail to reinnervate the specialized 
receptors forming the basis for the sense of touch and this, 
together with the mismatching of axons with conduits, 
invariably results in poor sensory recovery except in the 
very young. The functional result in the hand is poor. 

Compartment syndrome 

This specific type of neurovascular compromise can occur 
as part of any extremity injury. Although commonly 
caused by fractures and soft tissue injuries, the presence 
of a fracture is not essential. It is a progressive condition 
in which the elevated tissue pressure within a confined 
myofascial compartment exceeds capillary pressure, 
leading to vascular compromise of the muscles and 
nerves. It can result from a variety of causes, categorized 
as either expansive or compressive. 



External compression of compartment 

• Constricting dressing or cast 

• Closing fascial defects 

• Third degree, full thickness, burns. 

Expansion of compartment contents 

• Haemorrhage and oedema following fractures or soft 
tissue injuries 

• Haemorrhage following coagulopathy or vascular 
laceration 

• Postischaemic swelling. 

The four compartments of the lower leg are the most com- 
monly involved areas, but it can occur in the shoulder, 
arm, forearm, hand, buttock, thigh or abdomen (follow- 
ing trauma or surgery). 




Key points 



• Continuously monitor at-risk sites in order to 
detect and correct impeding compartment 
syndrome (Table 2.10). 

• Increasing pain, exacerbated by passive flexion 
and extension, is a reliable combination 
signalling compartment syndrome. 

1. Detect the condition in the early, potentially 
reversible stage or muscle may infarct, giving rise to 
rhabdomyolysis, hypovolemia, hyperkalaemia, hyper- 
phosphataemia, high levels of uric acid, metabolic acido- 
sis, renal failure and death. Locally fibrotic contractures 
may develop. 

2. Detection should be clinical but the intracompart- 
mental pressure can be monitored when clinical assess- 
ment is difficult or if you are in doubt about the clinical 



Table 2.10 Features of impending or established 
compartment syndrome 



Early 

Pain in the limb 

Pain on passive movement of the distal joints 

Paresthesia 

Loss of distal sensation 

Late 

Tension or swelling of the compartment 

Absent muscle power 

Very /ate 

Absent pulse pressure in the distal limb 



40 



TRAUMA 




2 



features. Examples of such cases are when the patient is 
unresponsive because of neurological injury or sedation, 
or has a nerve defect from other causes / or has a regional 
nerve block. Use it as an adjunct to, not a replacement for, 
clinical monitoring. 

3. Absolute pressure values are unreliable because per- 
fusion is dependent upon the difference between the arte- 
rial blood pressure and the compartmental pressure. A 
difference of less than 30 mmHg between diastolic blood 
pressure and compartment pressure is recommended as 
a threshold for releasing the tension by carrying out 
fasciotomy. A fall in the distal pulse pressure is a very 
late sign and indicates imminent tissue ischaemia. Pulse 
oximetry is not a reliable help in diagnosing or monitor- 
ing impaired perfusion secondary to raised compartment 
pressure. 



4. Myoglobinuria and raised plasma myoglobin result 
not only from direct myocyte damage but also from 
polymorphonuclear neutrophil-mediated cell lysis and 
microvascular coagulation. 

Acute renal failure complicates severe crush injury as 
a result of hypovolaemia leading to prerenal failure, 
while the released myoglobin from damaged muscle cells 
precipitates and obstructs flow in the renal tubules. 
Myoglobin and macrophage-generated cytokines experi- 
mentally induce levels of potent vasoconstrictors such as 
platelet activating factor and endothelins, causing renal 
arteriole constriction, decreased glomerular filtration and 
renal ischaemia. A high concentration of myoglobinuria 
produces a red or smoky brown discoloration of the 
urine. Look for this when you catheterize the patient and 
check the urine regularly. 



CRUSH SYNDROME 

1. Crush injuries occur in a variety of ways: for 
example, in patients becoming trapped under fallen 
masonry or in a car following a road traffic accident. The 
patient's own body weight may be sufficient to compress 
the tissue if the consciousness level is depressed for a con- 
siderable time. Severe beatings and epileptic seizures may 
also be responsible. 

2. They present both local and systemic problems. The 
local injury may be complicated with compartment syn- 
drome. Systemic concerns include intravascular volume 
depletion, electrolyte imbalance and renal injury from 
myoglobin. Until the limb is released there is little sys- 
temic effect; once reperfusion starts, plasma and blood 
leak into the previously crushed soft tissues as a result of 
the increased capillary membrane permeability and 
vessel damage. The effect depends upon the degree of 
tissue damage and in severe cases may produce hypo- 
volaemia. Devitalized tissue is at high risk of secondary 
infection with a further systematic release of toxins. 

3. Abnormal systemic blood markers of muscle infarc- 
tion include rising blood urea nitrogen, raised potassium, 
phosphate, uric acid and creatine kinase. Metabolic 
acidosis develops with an increased anion gap. 
Hypocalcaemia occurs although intracellular calcium is 
raised. The packed cell volume is raised but there is 
thrombocytopenia. 



fr"* 



Key point 

• The sudden rise in serum potassium 

concentration may produce cardiac arrhythmias 
(and arrest) soon after the patient is released. 



FAT EMBOLISM SYNDROME 

1. Ninety per cent of cases result from blunt trauma 
associated with long bone fractures. It has, however, also 
been reported following burns, decompression sickness 
and even liposuction! 

2. The classical triad of respiratory failure, neurologi- 
cal dysfunction and petechial rash is not present in all 
cases; indeed the rash, though pathognomonic, is only 
present in 50% of cases. 

3. As several organs can be affected, there is a wide 
range of possible clinical presentations, although dysp- 
noea is the commonest. The onset of symptoms is usually 
between 24 and 48 h postinjury. Pulmonary changes 
include ventilation-perfusion (V/Q) mismatch, impaired 
alveolar surfactant activity and segmental hypoper- 
fusion. Shadowing on chest X-ray is not dissimilar to 
ARDS. Neurological changes occur as a result of hypoxia 
and /or the humoral and cellular factors released from 
the bone. Effects on the heart may result in a fall in 
mechanical performance and arrhythmias. Renal damage 
can lead to lipiduria with tubular damage and ischaemic 
glomerular-tubular dysfunction. 

4. Lipid globules are formed mainly from circulating 
plasma triglycerides, carried by very low density lipopro- 
teins (VLDLs). In trauma, this is commonly a result of 
the release into the circulation of lipid globules from 
damaged bone marrow adipocytes; however, it can also 
occur with increased peripheral mobilization of fatty 
acids and increased hepatic synthesis of triglycerides or 
reduced peripheral uptake of plasma VLDLs (Fig. 2.10). It 
gives rise to thromboembolism of the microvasculature, 
with lipid globules and fibrin-platelet thrombi. In addi- 
tion, the local release of free fatty acids can cause a severe 
inflammatory reaction that initiates the SIRS chemical 



41 



2 




EMERGENCY 




t 



Clearance 



t 



Bone marrow 
release 



Plasma 
triglycerides 



{Erythrocytes {0 2 transport) 



Platelets {aggregation} 



White cells {cytokines) 



Vascular endothelium 
(coagulopathy) 




Multi-organ 

system 

dysfunction 



Fig. 2.10 The mechanism of interaction between raised plasma triglycerides and the pathogenesis of multiorgan 
system dysfunction in fat embolism. 



cascade, which is probably responsible for the high asso- 
ciation of fat emboli syndrome with both progressive 
anaemia and pyrexia (> 38.5° C). 




Key point 

Diagnosis of fat embolism rests on identifying 
fat globules in body fluids, histological 
recognition, or pulmonary involvement with at 
least one other organ system dysfunction. 



5. Search for fat globules in body fluids, such as 
sputum and urine, or lipid emboli in retinal vessels on 
fundoscopy; histological diagnosis requires demonstra- 
tion of intracellular and intravascular aggregation of lipid 
globules with Sudan black stain. 



PATHOPHYSIOLOGY OF WOUND 
HEALING 












Soft tissue injuries heal by a complex series of cellular 
events that lead to connective tissue formation and repair 
by scar formation. Three fundamental things must 
happen for wound healing to occur: (1) haemostasis must 
be achieved; (2) an inflammatory response must be 
mounted in order to defend against microbial infection as 
well as attracting and stimulating the cells needed for 
tissue repair; and (3) many different cells must proliferate 
and synthesize the proteins necessary for restoring 
integrity and strength to the damaged tissue. This is 
covered in more detail in Chapter 33. 
Wound healing therefore requires: 

• Haemostais 

• Inflammation 

• Cell proliferation and repair. 



Wound contracture 

When wounds with tissue loss are left to heal by 
secondary intention, contraction of granulation tissue 
reduces the size of the tissue defect. The cell responsible 
for this process is the myofibroblast, although the exact 
role of this cell is unresolved. Even though reducing the 
size of the tissue deficit is of benefit in wound healing, the 
distortion and scar formation produced by the process 
inhibit function in certain areas of the body (particularly 
on the face and around joints). 



PATHOPHYSIOLOGY^ 

Three risk factors for death after burn injury have been 
identified: age more than 60 years; burn surface area of 
more than 40%; and the presence of inhalational injury. 

Increased fluid losses due to uncontrolled evaporation 
are coupled with fluid shifts for the first 24-48 h after a 
major burn. Leakage of intravascular water, salt and 
protein occurs through the porous capillary bed into the 
interstitial space. This, in turn, results in loss of circulat- 
ing plasma volume, haemoconcentration and hypo- 
volaemia, the severity of which increases with the 
severity of the burn. In a burn over 15% of the total body 
surface area (TBSA), the capillary leak may be systemic, 
causing generalized oedema and a significant fall in blood 
volume. 

Shock associated with burn injuries 

The effect on the circulation is directly related to the size 
and severity of the burn wound. The body compensates 
for this loss of plasma with an increase in peripheral 
vascular resistance, and the patient will appear cool, 
pale and clammy; however, this compensation will only 
be effective in maintaining circulation for a period of 
time, depending on the severity of the burn and the 



42 



TRAUMA 



r 2 



presence of other injuries. Ultimately, the patient will 
demonstrate signs of hypovolemic shock as the cardiac 
output falls. During this time it is rarely possible to keep 
the circulating volume within normal limits. The end of 
the shock phase in the adequately resuscitated burn 
patient is usually marked by a diuresis. This occurs 
approximately 48 h after the burn and is usually associ- 
ated with a fluid balance that is more like that of an 
uninjured individual. 

A burn of greater than 15% TBSA almost always 
requires intravenous fluid administration to expand the 
depleted vascular volume. However, shock can occur 
with a burn involving as little as 10% TBSA, as a result of 
complicating factors such as age, pre-existing disease and 
other major injuries. In these circumstances, a burn of 
25^0% becomes a potentially lethal injury Numerous 
fluid regimens have been calculated to assist in burn 
resuscitation: it is sensible to use the regimen favoured by 
your local burns department. 

Depth of burn and cause of burn 

The diagnosis of the depth of burn is not always easy. If 
doubtful, it should be reassessed at 24 h, using non- 
adherent dressings between examinations. 

Superficial burns 

Superficial burns are characterized by erythema, pain and 
the absence of blisters. Typical examples of superficial 
burns would be sunburn or simple flashburns. The 
epithelium remains intact so infection is not usually a 
problem and they generally do not require fluid replace- 
ment. Healing takes place over a few days and, with the 
exception of some pigmentation changes, no scarring 
occurs. 

Partial thickness burns 

Superficial partial thickness and deep partial thickness 
burns have been described. In the superficial variety the 
epidermis and the superficial dermis are burnt. They 
appear pink, moist and have fluid-filled, thin-walled 
blisters. They are associated with more swelling and are 
painfully sensitive, even to air current. Healing is by 
epithelialization from the pilosebaceous and sweat 
glands, as well as the wound edges. Therefore healing is 
often prolonged to 3^ weeks. 

In deep partial thickness burns the reticular dermis is 
involved. The appearance is a mixture of red and white, 
with blistering also a feature. The capillary refill is often 
prolonged and two-point discrimination may well be 



diminished. Healing is from the few remaining epithelial 
appendages and can take up to 6 weeks. It results in poor 
quality skin and marked pigmentation change (either 
hyper- or hypopigmentation). Hypertrophic scar forma- 
tion may be a problem, as can wound contraction. 

Infection may complicate the recovery of any partial 
thickness burn because the epithelium has been breached. 
This may take the form of locally delayed wound healing 
or sytemically-induced multiorgan failure (MOF). Deep 
dermal burns can result from scalds, contact burns, 
chemical burns and flame burns. 

Full thickness burns 

Full thickness burns involve the destruction of both the 
epidermis and dermis. They appear white, leathery and 
have no sensation to pinprick. The diagnosis between 
deep dermal and full thickness burns can be difficult, as 
they commonly lie adjacent to each other within the same 
wound. They can only heal naturally by epithelialization 
from the wound edge, leaving a contracted, poor quality 
scar. In the acute situation, circumferential full thickness 
burns around limbs and the chest can act as tourniquets, 
impeding the distal circulation and respiration, respect- 
ively. Urgent escharotomy may be required in these 
situations so discuss the possibility early with the local 
burns centre (see Ch. 24). 

Simplistically, the depth of a burn is a product of the 
injurious temperature and the contact time. Thus the arm 
of an alert individual exposed to a hot flame, and quickly 
removed, will cause damage similar to that in a comatose 
patient lying against a warm radiator. The young and 
elderly are similarly immobile and prone to deep burns 
from relatively innocuous hazards (e.g. hot bathwater). 
Patients with peripheral neuropathies (e.g. diabetics) may 
also present with unexpectedly severe contact burns. 

Chemical injury, such as that due to hydrofluoric acid 
or strong bases, can give rise to full thickness burns 
requiring specialist treatment. A high index of suspicion 
is appropriate when dealing with electrical burns because 
current flows preferentially through the deep structures, 
and extensive tissue damage may not be evident on early 
superficial inspection. 

Patients with full thickness burns may require blood 
transfusion, as red cell haemolysis occurs with direct 
thermal injury; indeed there is generalized fragility of the 
entire red cell population leading to reduced cell lifespan. 



Toxic shock syndrome 

Toxin-producing strains of staphylococcal or streptococ- 
cal bacteria can colonize wounds. A marked cytokine 



43 



2 



EMERGENCY 



response is stimulated, leading to a severe systemic illness 
typified by: 

• Pyrexia (usually >39° C) 

• Vomiting and /or diarrhoea 

• Rash (erythematous, maculopapular) 

• Malaise, dizziness, peripheral shutdown or frank 
shock. 

It can occur even with relatively small, superficial burns 
and is more common in children. Treatment is with 
oxygen, intravenous fluids and antibiotics. 

Response of the respiratory system to 
inhalational injury 

The upper airway may receive thermal burns, and tissue 
swelling can develop very rapidly in these vascular 
tissues. Injury to the mouth and oropharynx in particular 
can cause acute respiratory obstruction. Oedema from 
these injuries may also involve the vocal cords. Dramatic 
changes in the patient's ability to maintain the airway 
have been observed over a short period of time following 
this type of injury. The lungs themselves are rarely injured 
from 'burning'. Usually laryngeal spasm occurs from the 
heat of the inspired gases, thereby protecting the lower 
airway and lungs from exposure; however, steam, with a 
heat capacity approximately 4000 times that of dry air, can 
carry heat to the lower airways, resulting in significant 
distal thermal injury. 

Smoke inhalational injury secondary to confinement in 
a house fire may be associated with a wide variety of 
concomitant chemical injuries; for example, plastic fur- 
niture and textiles will release hydrogen chloride. Not 
only does this cause irritation to the eyes and throat but 
it also causes severe pulmonary oedema. Phosgene, 
produced from the burning of polyvinyl chloride, is 
also associated with the development of significant 
pulmonary oedema. Burning mattresses can produce 
nitrogen dioxide. 

As fires can produce such a wide variety of chemicals, 
the resultant pulmonary damage may be multifactorial. 
This may result in necrosis of respiratory epithelium, 
inactivation of the respiratory cilia, and destruction of 
type II pneumocytes and alveolar macrophages. This 
leads to a decrease in lung compliance, which is seen as 
an increase in the work of breathing and an impairment 
of diffusion through the alveolar membrane. 

In view of the very large surface area of the lung, fluid 
requirements for resuscitation may increase by as much 
as 50% of the calculated values if a severe inhalation 



injury has been sustained. The severity of the injury 
will not be related to the TBSA burn size, but rather to 
the length of time and intensity of exposure to the 
inhalation. Accurate information from the prehospital 
care providers relative to these conditions is vital in 
planning the patient's care and anticipating respiratory 
complications. 

Carbon monoxide poisoning 

Systemic absorption of inhaled toxins may also occur. 
Carbon monoxide (CO) is reported to be the leading toxi- 
cological cause of death. Burning any carbon-containing 
material can release CO, a byproduct of incomplete com- 
bustion. The mechanisms of CO toxicity are multiple. CO 
competes with oxygen for binding with haemoglobin, 
myoglobin and cellular cytochrome oxidase. In addition, 
off-loading of oxygen to the tissues is impaired by the 
leftward shift of the oxygen-dissociation curve induced 
by carboxyhaemoglobinaemia. The result is profound 
hypoxia both in the intra- and extracellular environ- 
ments. The areas most affected are those with a high 
metabolic rate: heart and brain. Fetal tissue is also at 
significant risk. 

Measured carboxyhaemoglobin levels do not neces- 
sarily correspond to clinical symptoms. The duration of 
the patient's exposure to CO is significant, as short expos- 
ures to a high concentration may give high carboxy- 
haemoglobin levels but not cause significant metabolic 
effects (usually acidosis with bicarbonate deficit). 
Carboxyhaemoglobin levels greater than 10% are signi- 
ficant and levels greater than 50% are generally lethal. 
Early treatment with high concentration oxygen is 
essential. 

Carbon monoxide intoxication is the biggest cause of 
death in people caught in house fires or other types of 
closed-space fires. 

Cyanide poisoning 

When the polyurethane foam in modern furniture burns, 
a thick black smoke is produced. This not only contains 
CO and the corrosive substances mentioned above 
but also cyanide gas. The latter is another metabolic 
poison which binds to mitochondrial cytochrome oxidase. 
This leads to inhibition of adenosine triphosphate (ATP) 
production, with rapid onset of profound cellular anoxia 
and death. Cyanide gas is difficult to measure but should 
be assumed to be present if the carbon monoxide level is 
greater than 10%. Severe metabolic acidosis and raised 



44 



TRAUMA 




2 




lactate levels found on arterial blood gas analysis provide 
further clues towards the diagnosis. 



TRAUMA SEVERITY SCORING 



Essentially two separate types of trauma score have been 
developed. One type is based on the anatomical injuries 
sustained by the patient, while the other makes use of 
physiological data taken from the patient at first contact. 
They have developed in an attempt to achieve two sep- 
arate objectives: firstly, to predict the probability of sur- 
vival of an individual patient; and, secondly, to compare 
outcomes between different hospitals, or the same hospi- 
tal over time. 

The Injury Severity Score (ISS) is an anatomical scoring 
system that gives an overall score for patients with mul- 
tiple injuries. The body is divided into six regions. Within 
each region every injury is given an Abreviated Injury 
Scale (A IS) score. This is a predetermined score from 
1 (minor) to 6 (unsurvivable). The three highest grading 
scores, which are found in separate regions, are squared 
and then added together to make the final score. An 
obvious deficiency in this model is that it does not take 
account of multiple injuries within one body region. More 
recent scores such as the New Injury Severity Score (NISS) 
have been developed in an attempt to take account of 
such inaccuracies. 

The Revised Trauma Score (RTS) is a physiological 
scoring system which attempts to predict outcome based 
on the first set of data obtained on the patient. The timing 
of first data recording and the effect of any treatment pre- 
viously instigated will have a variable effect. None the 
less, it has been shown to correlate well with the proba- 
bility of survival. It is calculated by combining three 
separately weighted scores based on the observed GCS, 
respiratory rate and systolic blood pressure, 

TRISS determines the probability of survival of a 
patient by combining the ISS and RTS along with weight- 
ings to take account of the patient's age and the mechan- 
ism of injury (i.e. blunt or penetrating). The weightings 
have been calculated from a large database of trauma 
victims and allow comparative audit to be carried out. 



ACKNOWLEDGEMENTS 

Thanks are due to Geraldine M c Mahon, Richard Cowie, 
Charles Galasko, Roop Kishen, Roderick Little, David 
Marsh, Mohamed Rady, Stewart Watson and David Whitby. 



Summary 

• Trauma is an important clinical and 
economic problem because it is a major 
cause of mortality and morbidity in all 
countries of the world. 

• In order to be effective in trauma care, the 
clinician needs a good understanding of 
the biomechanics of injury and how they 
relate to specific anatomical regions of the 
body. 

• The clinician also needs to be aware of 
both the physiological and 
pathophysiological response to trauma, as 
this has direct implications for optimum 
patient resuscitation. 

• These anatomical and physiological 
assessments can be used to quantify the 
severity of the trauma so that comparisons 
between treatment methods can be made. 




References 



Department of Health 1998 Our healthier nation - a contract for 
health. DoH, London 




Further reading 

Beal AL, Cerra FB 1994 Multiple organ failure syndrome in the 

1990s. JAMA 271 :226-233 
Burgess AR, Eastridge BJ, Young JW et al 1990 Pelvic ring 

disruptions: effective classification system and treatment 

protocols. Journal of Trauma 30: 848-856 
Colucciello S 1995 The treacherous and complex spectrum of 

maxillofacial trauma: etiologies / evaluation and emergency 

stabilisation. Emergency Medicine Reports 16: 59-70 
Committee on Trauma 1997 Head trauma. In: Advanced trauma 

life support manual. American College of Surgeons, Chicago, 

pp 181-206 
Committee on Trauma 1997 Biomechanics of injury. In: 

Advanced trauma life support manual. American College of 

Surgeons, Chicago, pp 345-366 
Demling RH, Seigne P 2000 Metabolic management of patients 

with severe burns. World Journal of Surgery 24: 673-680 
Foex BA 1999 Systemic responses to trauma. British Medical 

Bulletin 55: 726-743 
Greenberg C, Sane D 1990 Coagulation problems in critical care 

medicine. Critical Care: State of the Art 11: 187-194 



45 



2 . 



EMERGENCY 



Grundy D, Swain A 1997 ABC of spinal cord injury, 3rd edn. 

British Medical Journal, London 
Irving M, Stoner H 1987 Metabolism and nutrition in trauma. 

In: Carter D, Polk H (eds) Butterworths international medical 

reviews: trauma surgery 1. Butterworths, Oxford, pp 302-314 
Lee CC, Marill KA, Carter WA, Crupi RS 2001 A current 

concept of trauma-induced multi-organ failure. Annals of 

Emergency Medicine 38: 170-176 
Little R, Kirkman E, Driscoll P, Hanson J, Mackway-Jones K 

1995 Preventable deaths after injury: why are traditional 

Vital' signs poor indicators of blood loss? Journal of Accident 

and Emergency Medicine 12: 1-14 
Mellor A, Soni N 2001 Fat embolism. Anaesthesia 56: 145-154 
Moore J, Moore E, Thompson J 1980 Abdominal injuries 

associated with penetrating trauma in the lower chest. 

American Journal of Surgery 140: 724-730 
Nathan AT, Singer M 1999 The oxygen trail: tissue oxygenation. 

British Medical Bulletin 55: 96-108 
Nicholl JP 1999 Optimal use of resources for the treatment and 

prevention of injuries. British Medical Bulletin 55: 713-725 



Proctor J, Wright S 1995 Abdominal trauma: keys to rapid 

treatment. In: Bosker G (ed). Catastrophic emergencies. 

Diagnosis and management. American Health Consultants, 

Atlanta, GA, pp 65-74 
Skinner D, Driscoll P, Earlam R 1996 ABC of major trauma. 

British Medical Journal, London 
Slater MS, Mullins RJ 1998 Rhabdomyolysis and myoglobinuric 

renal failure in trauma and surgical patients: a review. 

Journal of the American College of Surgeons 186: 693-716 
Tiwari A, Haq AI, Myint F, Hamilton G 2002 Acute 

compartment syndromes. British Journal of Surgery 

89: 397-412 
Ware LB, Matthay MA 2000 The acute respiratory distress 

syndrome. New England Journal of Medicine 342: 1334-1349 
Wyatt J, Beard D, Gray A, Busuttil A, Robertson C 1995 The 

time of death after trauma. BMJ 310: 1502 

Useful links 

www.doh.gov.uk/HPSSS Department of Health 2002 
Indicators of the nation's health 



46 



SECTION 2 




47 



This page intentionally left blank 




3 Clin 



ical diagnosis 



/?. M. Kirk 




Objectives 

Clinical diagnostic skills are the basic 

requirements for successful surgical 

practice. 

For success you need to know the range of 

normality against which to measure 

abnormalities. 

Try to be positive in your opinions. Do not 

hide behind vagueness. 



repeatedly think, T wonder if this is condition X?' - a 
hypothesis, followed by the intention to ask a further 
question or carry out a specific test to see if the idea 
survives it or is refuted - the deductive process. 

Why do we not employ computers, into which 
patients may enter information directly, for diagnosis? 
Computers are often used to harvest preliminary infor- 
mation as they can hold much more information than we 
usually have easily accessible. But they are valuable only 
when critically assessed information is entered. They are 
mere repositories, hence the pithy American acronym 
'GIGO' (garbage in, garbage out). 



Should you read this chapter? Are you already too expe- 
rienced to need further instruction? If you think so, you 
are lacking in self-knowledge. None of us is completely 
competent in the complex, and still not yet fully under- 
stood, process by which we seek out a diagnosis of our 
patients' clinical problems. 

INTRODUCTION 




^^^^v- 1 .^*;:.;^^ 



■^I^^^Mi^^^^^^^^m:^ 



Much has been spoken and written about clinical diag- 
nosis. Although Sir Peter Medawar, the Nobel Prize- 
winning immunologist, was not a clinician, he described 
the process of making a diagnosis as similar to the process 
of scientific research - hypothetico-deductive (Medawar 
1969). A hypothesis (Greek hypo = under + thesis - a 
placing) is a supposition or idea; deduction (Latin de = 
from + ducere = to lead) is the application of critical testing 
to the idea. The great scientific philosopher, Sir Karl 
Popper, uses the parallel terms, 'conjectures (Latin con = 
with + jacere - to throw) and refutations' (Latin refutare - 
to drive back), suggesting that we should rigorously 
attempt to destroy our hypotheses. If they withstand the 
critical testing, we may accept them for practical pur- 
poses. If we refute them, we are free to develop further, 
perhaps more successful ideas (Popper 1959). 

It has been said that an experienced clinician makes a 
provisional diagnosis within a few seconds of seeing most 
patients. Analyse your thought processes as you take a 
history and examine patients. You will recognize that you 



Key point 

All facts are not of equal importance. Identify, 
register and rely on the significant ones. 



Computers lack intuition - the power of perceiving truth 
without reasoning or analysis. As we communicate with 
our patients, we take in, partly consciously and partly 
unconsciously, details that weigh in the balance alongside 
the words. A quiet response to the question, 'How severe 
is the pain?' of, 'Chronic/ by a grey-faced London dock- 
worker may signal greater suffering to you than the vehe- 
ment retort of, 'Excruciating/ by someone with a more 
volatile personality. Yet the first person may enter a score 
of 6 out of 10 and the second 10 out of 10 in response to a 
computer questionnaire in which 10 signals the highest 
pain level. You have interpreted the Cockney slang word 
'chronic/ (Greek chronos = time, hence longstanding), to 
mean its opposite, 'acute'. Someone in excruciating pain 
(Latin crucifigere crux = cross + figere = to fix, hence to 
crucify; agonizing, anguished), often finds it difficult 
forcefully to express their suffering. 

HISTORY 



J£C^&^'^^^i^& ^^O&^'-'&^^&^'^S 






1 . We have traditionally prided ourselves as surgeons on 
our ability to elicit physical signs and make accurate 'spot' 



49 




PATIENT ASSESSMENT 



diagnoses. We have not always sufficiently developed our 
communication and history- taking skills. An effective 
history directs your attention to the cause of the surgical 
problem. You can apply the famous statement of Louis 
Pasteur about scientific discovery to the diagnosis of surgi- 
cal disease / which may be translated as, 'Chance favours 
the prepared mind/ The history directs you towards the 
correct area of examination and investigation. 

2. There are two, usually separate, parts of the history. 
Initially you should concentrate on the presenting com- 
plaint. Having clarified this, you need to investigate the 
general physical and mental health of your patient and 
identify coexisting or alternative disease. 

3. Taking a history requires great tact. You must control 
the direction it takes, otherwise you may be led away 
from the line of pursuit of the diagnosis. When you ask a 
question and hear the response, the timing and phrasing 
of your next question is important. Too soon, too sharp, a 
sudden change of topic, and you may prevent the patient 
from adding a vital clue. Too late and the patient may 
have led you on a false track. 

4. As you take a history you are establishing a rela- 
tionship with the patient. For this reason prefer to speak 
together in a quiet, relaxed atmosphere. You cannot take 
an accurate history unless you and the patient can com- 
municate verbally. Make sure you understand the 
meaning of the patient's statements - and the patient 
understands yours. If you do not have a common lan- 
guage, try to recruit an interpreter. 

5. Ask 'open' questions whenever possible, for example, 
'Where is your pain?' rather than Ts your pain here?' 

6. Avoid appearing judgemental; patients often with- 
hold information if you seem to disapprove. Equally, they 
may give an incorrect answer, thinking that it may elicit 
your approval. 

Presenting complaint 

1 . As you encounter each patient take in every detail of 
gender, age, expression, speech, gait, dress and attitude. 
This prejudices your interpretation of everything you 
are told and subsequently find. Do not misinterpret 



'prejudice'; it means prejudging; although it is usually 
used disparagingly, it is reprehensible only if it is rigidly 
maintained against the evidence. Treat your interpret- 
ations as working hypotheses, to be tested and abandoned 
if the evidence refutes it. By sensibly incorporating your 
impressions of the patient with the history you are more 
likely to reach a balanced judgement (Fig. 3.1). 

2. Do you think that the complaint made by the patient 
is the one that is the cause of anxiety? Sometimes patients 
find a reason to see a doctor, worried about a condition, 
yet are unable to express it, from diffidence, embarrass- 
ment or fear of the consequences. 

3. The next time you sit before a patient, try to follow 
the sequence of your questions. What is your motivation 
for asking each one? Each one should elicit a clue to the 
diagnosis, clarify the answer to the previous question or 
elicit fresh information. 

4. If you can identify the exact site of the symptoms, 
you may be able to identify the likely system. If so, ask 
about the effect of system function on the symptoms and 
the effect of symptoms on the system function. In this way 
you can sometimes recognize a pattern of features that 
form a syndrome (Greek syn = together + dromos = a 
course; hence, a concurrence of features). 

5. If you think you have identified the cause of the pre- 
senting features, do not relax. While you are questioning 
the patient the answers you receive should trigger other 
possible diagnoses and you need to ask questions that 
will substantiate or exclude them. Thus, you are running 
several lines of thought in parallel. 

6. Your targeted history is incomplete until you have 
sought out evidence of the severity of the cause of symp- 
toms, its extent and rate of progression. 



General assessment 

1. There are well-established questions to check the 
function and health of the main body systems. Employ 
them to identify or exclude coexisting problems. For 
example, the answer to, 'Can you climb stairs?' may 
reveal preliminary information about the function of the 



• Young child 

■ Young woman 

• Young man 

■ Middle-aged woman 

• Middle-aged man 

• Elderly woman 

• Elderly man 



Appendicitis 

Gynaecological 

Hernia, appendicitis 

Gynaecological, dlvertitulosis coli 

Diverticulosis coli or colon cancer 

Gynaecological; cancer or diverticular disease of the colon 

Colon cancer 



Fig. 3.1 Your intuitive diagnosis for lower abdominal pain depends upon the patient before you. These are some 
preliminary diagnoses - but do not consider them to be a final judgement. 



50 



CLINICAL DIAGNOSIS 



3 



Anatomical structures at site of lesion? 
Skin, subcutaneous tissue, fascia, blood 
vessels, lymphatics, nerves, tendons, 
muscles, bones, joints, mesothelia, viscera, etc. 



versus 



Congenital 

Traumatic 

Inflammatory 

Degenerative 

Metabolic 

Neoplastic 



Fig. 3.2 Mentally test each of the likely tissues in the detected lesion against the pathological grid. You hope to 
identify the combination that fits the information that you have acquired. 



cardiorespiratory, haematological, musculoskeletal and 
neuromuscular systems. 

2. While taking the history, carefully assess the person- 
ality and attitude of your patient. Try to identify any 
anxieties or misapprehensions that need to be discussed. 

EXAMINATION 



^ J M&$%'M'&$.'i?&'?- 



1. You cannot carry out a thorough examination in an 
atmosphere of hysteria, noisy distraction or pressure of 
time. Relax and reassure the patient, and also make an 
effort to relax yourself. 

2. When you took the history, you should have identi- 
fied the important clinical signs you need to seek, but 
seek to identify further ones as you proceed through the 
examination. 

3. Do not rush. Take each examination in turn and do 
not proceed until you have decided confidently, Is the 
sign present, or not?" 




Key points 

• You can confidently reassure your patient that 
all is well only if you know the range of 
normality. 

* You learn the range of normality only by 
assiduously building up your experience every 
time you have the opportunity. 

4. If you find a suspicious lesion, identify exactly 
where it lies both 'geographically 7 and in depth, including 



its attachments. You may then apply the anatomico- 
pathological grid (Fig. 3.2). 

5. If you find an enlarged lymph node, examine the 
whole of its potential drainage area - and remember that 
when lymphatics are blocked, the flow may become retro- 
grade (Latin retro = backward + gressus = to go). 

6. If you find an abnormality in one part of a system, 
examine the whole system, such as the reticuloendothelial, 
vascular, neurological, joint, bone, muscles, skin systems. 

7. If you need to curtail the full examination in an 
emergency, or in order to start treatment, determine to 
complete it as soon as possible. 

8. Even though you may be certain of the clinical signs, 
be prepared to repeat the examination before you take 
action. Especially in emergency circumstances, such as an 
acute abdomen, physical signs often change rapidly. 

9. Record your findings in full. If you do not record 
negative findings it may be assumed you did not seek 
them. Write legibly and do not use abbreviations or 
jargon. Write the time and date, and then sign the record. 

10. Your hope is that you will reach a likely clinical 
diagnosis, excluding other possibilities so that you may 
plan the investigations (Fig. 3.3). 




Key points 

The commonest condition is the most likely. 
Remember, though, the 'pay-off' diagnosis - the 
one that may be less common but has 
important consequences if you miss it. (Warning 
expressed by Hugh Dudley, formerly Professor of 
Surgery, St Mary's Hospital, London.) 



History 



Examination 



Investigations 



Presenting 
Feature 



Condition A 
Condition B 
Condition C 



Excluded 



Confirmed 



Possible 



Excluded 



Confirmed 



Possible 



Assess 



Exclude 



Fig. 3.3 As you proceed, you often accumulate further possible diagnoses. You run with all of them in parallel, 
hoping to exclude some. Some you confirm but need to assess the extent of disease. Others you keep in mind, hoping 
to confirm or exclude them by means of carefully chosen investigations (see Ch. 4). 



51 




PATIENT ASSESSMENT 



11. Write a brief summary of the present situation: 
what will be done, why, and with what intention. Anyone 
reading the notes can now rapidly grasp the problem and 
the intended management of the patient. 

DIAGNOSIS 



■&^%$V&9&^^ 



^&S$^W$^&sl$Z$i&$5g& 



^&&^l&:s$Wi?&;gf&?&Q!t^£&& ; W!(;# 



1- As you discover symptoms and signs, decide if they 
are significant and reliable. Sometimes you find features 
that are contradictory and must decide which ones, if any, 
to trust. 

2. Pattern recognition contributes powerfully to diag- 
nosis. The almost subconscious recognition of a type of 
patient, a particular symptom and the discovery of a sig- 
nificant feature produce a pattern. Try asking yourself to 
describe someone close to you; remarkably, you may not 
be able to articulate many observations, yet you instantly 
recognize the person in a crowd. Overreliance on pattern 
recognition is dangerous. As you become experienced, 
having become acquainted with a large number of syn- 
dromes, you risk accepting them without further corro- 
boration. Remember Karl Popper's admonition to test 
your hypothetical diagnosis. The extra effort often dis- 
closes a feature that throws doubt on the initially recog- 
nized likely diagnosis. 

3. Perhaps the most daunting declaration to your 
patient is to state that there is no disease. This demands 
confidence in your findings and your diagnosis. It is also 
one of the most satisfying acts - at least comparable with 
pulling off a dramatic life-saving action. If you can look the 
patient in the eye and say, 'It is all right/ imagine the relief 
and joy your declaration brings. In many cases you can 
send the patient away, feeling relieved and happy, or order 
carefully selected investigations to confirm your diagnosis. 

4. Not every patient's clinical features correspond to 
textbook descriptions. Be alert to the exceptions. Sometimes 
an apparently capricious finding warns you that you are 
misinterpreting the evidence; sometimes you are able to 
discover a previously undiscovered feature. 




Key point 

If investigation results do not match your 
clinical diagnosis, trust your clinical findings; 
investigations are clinical aids. 



Diagnosis not made 

1. Do not rush to order more complex investigations. 
One of the most productive methods is to put aside the 
previous notes and start afresh. This is particularly so if 
someone else previously saw the patient. A fresh person 



taking a history asks questions in a different manner and 
different order. The new history is often surprisingly 
different from the original one. 

2. Repeat the clinical examination. Do not automatic- 
ally accept the findings of someone else, however senior 
or distinguished. 




Key points 

• Did you ignore or dismiss information that 
clashed with your preconceptions? 

• Never fail to respond to changed circumstances 
or 'uncomfortable' new information. 

3. Did you order the correct investigations? Remember 
that many investigations are operator dependent. If the 
investigation does not confirm your clinical judgement, 
consider repeating it after discussion with the person 
carrying out the procedure, rather than ordering another 
one that is perhaps more complex, expensive and po- 
tentially dangerous. 

4. It is not always necessary to make a diagnosis before 
taking action. In an emergency you may need to act 
without knowing the exact cause of cardiorespiratory 
failure, calamitous bleeding or acute abdominal symptoms. 



Summary 

• Do you appreciate the immense and 
crucial value of history taking? 

• Do you recognize that to diagnose a lesion, 
or confidently reassure your patients that 
all is normal, you must be thoroughly 
familiar with the range of normality? 

• Will you remember that clinical diagnosis 
is not an end in itself? It offers a valuable 
opportunity to assess the character of the 
patient and establish a relationship. 

• Will you assiduously record what you asked, 
what you were told, what you examined, 
what you found, what it means and what 
actions you have taken or will take? 




References 



Medawar PB 1969 Induction and intuition in scientific thought. 

Methuen, London, pp 42-45 
Popper K 1959 The logic of scientific discovery. Rou Hedge, 

London 



52 




Investigations 



A/. J. W. Cheshire, C. Bicknell 




Objectives 



Define the aims of investigation used in 

surgical practice. 

Understand the principles underlying 

selection of appropriate investigations. 

Determine the limitations of commonly 

used investigations. 

Consider appropriate sequences and 

timing of multiple investigations. 

Highlight important principles of 

investigations most commonly used in 

clinical practice. 



INTRODUCTION 



ment. The most common reasons for ordering investiga- 
tions in surgical practice are outlined below. 

Confirm the diagnosis 

Use investigations to confirm a suspected clinical diag- 
nosis, if clinical features are equivocal. Do not assume that 
tests are essential to diagnose, however, as there remain 
conditions for which clinical diagnostic acumen matches 
or exceeds the accuracy of any investigative tool (acute 
appendicitis), as well as conditions whose treatment 
uncontroversially confirms the diagnosis (ischiorectal 
abscess). Nonetheless, even in these instances confirma- 
tion of the clinical diagnosis is useful, usually histologi- 
cally, to avoid missing an underlying condition, such as 
carcinoid as a cause of appendicitis or Crohn's disease 
leading to ischiorectal abscess formation. 



The use of investigations in surgical practice is no substi- 
tute for clinical skill. An investigation is only worthwhile 
when it is requested in order to answer a specific ques- 
tion, or to confirm a clinical impression prior to interven- 
tion. There is an ever-expanding range of investigative 
modalities available and unwary surgeons who are clini- 
cally uncertain can easily find themselves overwhelmed 
with information if too many poorly considered investi- 
gations are requested. Furthermore, many modern tests 
are expensive and the costs of any investigation must 
always be considered in today's financially conscious 
health service. Other important issues that govern the 
effective use of special investigations include their selec- 
tion, timing and interpretation. This chapter outlines 
some of the principles that should be applied before 
investigations are requested in surgical practice, high- 
lights the limitations and discusses the practical use of 
common investigations. 



AIMS 



WS^V&Wt&^&riS^-'&'i/: 




Investigations are performed for different reasons but all 
should share the common feature of directing manage- 



Key point 

Remember that investigations are only 
worthwhile when they direct management. 



Exclude alternative diagnoses 

Perform specific investigations in order to exclude an 
important alternative or additional diagnosis (frequently 
malignancy). Many examples of this practice exist. An older 
patient with new per-rectal bleeding presenting to the colo- 
rectal clinic may well have piles easily visible on examin- 
ation, but must undergo further examination to exclude 
colonic cancer. Remember resource and financial implica- 
tions when planning investigations in this manner; in- 
appropriate investigations need to be avoided in all the 
surgical specialities, especially when pursuing ill-defined 
abdominal pain (in general surgery), vague back pain (in 
orthopaedic surgery), 'cystitis' in young women (in gynae- 
cology and urology), chronic rhinitis (in ear, nose and throat 
(ENT) surgery), ill-defined and longstanding headaches (in 
neurosurgery). Never ignore these symptoms, but take a 



53 




PATIENT ASSESSMENT 



full history and examination to form a clinical impression 
of the likely cause and think carefully of the diagnoses that 
cannot be missed or may occur concurrently. A combina- 
tion of clinical and risk assessment for each individual 
patient should guide the investigations performed. 



B 



Key point 



Treat all patients on an individual basis when 
considering tests to exclude alternative 
diagnoses. 



criminately investigating in the domain of another special- 
ity. Consult the anaesthetist ahead of planned surgery to 
reduce avoidable cancellations on the day of surgery. 




Key point 



• You cannot undertake a full and informed 
discussion of the diagnosis, treatment options 
and likely outcomes with the patient and 
family prior to surgery until these necessary 
investigations have been performed. 



Confirm the need to intervene in the 
absence of a diagnosis 

In an emergency you may need to act after investigations 
confirm a need for emergency treatment without 
knowing the specific cause. 

Determine the extent of disease and staging 

It is considered best practice to map out the extent of the 
disease before surgery especially in the elective setting. In 
fact when treating patients with neoplasia, staging is 
essential. Although the diagnosis of oesophageal cancer 
has been made, it is necessary to map out the extent of the 
disease, as the presence of an advanced rumour stage 
negates the need for operation and the physician may 
concentrate on palliative or chemotherapy treatment. You 
should also determine the extent of disease to optimize 
the use of operating theatre time and equipment, plan the 
operation carefully, avoiding having to make hasty deci- 
sions in the operating theatre, and minimize the chances 
of the surgical team being presented with any unpleasant 
surprises during the operation. 

Evaluate comorbidity 

Assess fitness for anaesthesia using a well thought out plan 
of investigations. A patient with an asymptomatic aortic 
aneurysm typically presents with a history of smoking and 
widespread cardiovascular disease; he or she requires par- 
ticularly careful evaluation of cardiac, pulmonary and renal 
function if the risks of surgery are to be balanced against 
the risk of conservative treatment, and informed advice 
about mortality and outcome are to be given to the patient 
when consenting for operation. While in many cases a com- 
bination of the use of cardiac, renal and lung function tests 
can appropriately assess fitness for anaesthesia, expensive 
and time-consuming tests cannot be undertaken on all 
patients. If the clinical history is not straightforward, seek 
a cardiological or respiratory opinion instead of indis- 



Risk to others 

Consider all patients to be at high risk for blood-borne 
infectious disease so that the risk of needlestick injury is 
minimized. However, in some circumstances hepatitis B, 
C and human immunodeficiency virus (HIV) serology 
(with consent) may be appropriate in patients being pre- 
pared for surgery in order to determine risk to others. In 
all patients the methicillin-resistant Staphylococcus aureus 
(MRSA) status should be determined and appropriate 
isolation procedures activated where necessary. This is 
particularly true of patients who have been transferred 
from another hospital and those with leg ulcers, who may 
have colonization of the wound site with MRSA. 

Medicolegal considerations 

Although you may be certain in your own mind about the 
diagnosis and appropriate management, you may need to 
protect yourself against future claims of incompetence 
against you, or the patient may wish to have objective evi- 
dence available in claims against a third party following, 
most commonly, an accident. When in doubt take advice 
from a senior colleague or from a medicolegal expert. 



SELECTION 



i^^isss»aa«w*s»ss»^^ 



&s+¥-;*«fe:^iViM:-s^^ 



There is often more than one modality that may be used 
to answer the clinical question the surgeon is faced with, 
in which case you need to consider the selection of the 
most appropriate investigation, which varies on an indi- 
vidual basis. Various factors influence this choice. 

Sensitivity and specificity 

If one test is known to be more sensitive than the alter- 
native, this is obviously a good reason to choose it. 
Colonoscopy is more sensitive than barium enema for the 
detection of small polyps and is the investigation of 



54 



INVESTIGATIONS 



W 4 



choice with lower gastrointestinal tract bleeding. The 
investigation must be specific for the disease when alter- 
nate diagnoses are to be excluded. 123 I scintigraphy for 
investigation of thyroid nodules is hard to justify as only 
10% of low-uptake nodules are subsequently shown to be 
malignant. Sometimes the combination of tests can raise 
the sensitivity and specificity to the acceptable standards, 
such as triple assessment of a breast mass, which com- 
bines radiological, cytological and clinical assessment to 
improve the sensitivity and specificity of the assessment. 




Definitions 



Sensitivity: number of cases of the condition 
detected by the test/total number of cases in 
population studied. 

Specificity: number of truly negative results/total 
number of negative results. 

Simplicity 

A simple investigation may be the first line of investiga- 
tion and may be all that is needed. If a plain radiograph 
confirms the clinical diagnosis of osteomyelitis in a dia- 
betic foot and the management plan is clear, it is not 
necessary to order a bone scan or magnetic resonance 
imaging (MRI). Free air seen on an erect chest X-ray 
confirms the diagnosis of bowel perforation and no 
further investigation is necessary. A simple investigation 
that proves to be undiagnostic, however, will require 
more detailed studies to be performed. 

Safety 

Think carefully about the complications of an investigation. 
Endoscopy may provide useful information as to the cause 
of bowel perforation but it is not safe in this situation, nor 
is the use of barium-based contrast. While a Tru-cut biopsy 
may confirm a diagnosis, it may also result in tumour 
seeding - ask the cyto/histopathologist whether a fine 
needle aspirate (FNA) may give sufficient information for 
management decisions to be made. For example, parotid 
tumours are at high risk from wound tumour seeding if 
investigated in this way and histological confirmation of 
the diagnosis often must wait until the mass is resected. 

Cost 

If an ultrasound can show liver metastases and this is the 
only information you require to decide on appropriate 
management, then why order a computed tomography 
(CT) scan that may be up to ten times more expensive? 



Remember that resources are limited. Reassurance and cer- 
tainty are purchased at a price. Moving from a position of 
95% to 100% certainty is often very expensive. When using 
investigations it is vital to understand the need to manage 
risk while at the same time remaining accountable to the 
patient and to society for the way in which money is spent. 

Acceptability 

In general the less invasive the investigation the more 
acceptable it is to the patient. This is especially true in 
paediatric practice, where the acceptability of the investi- 
gation to the child is essential if meaningful results are to 
be gained from investigations. Consider carefully the 
acceptability of the test when patients are being screened 
for asymptomatic disease. One of the limitations of the 
use of faecal occult blood testing as a screening investi- 
gation for colorectal cancer has been the relative unaccept- 
ability of this investigation to patients. Unacceptable tests 
suffer from poor compliance and a screening programme 
may achieve poor results in this situation. 

Availability 

The gold standard may be the ideal choice of investiga- 
tion for a patient but may not be possible. For example, 
an MRI scan may provide more information about the 
brain after injury or prior to neurovascular or neurosur- 
gical intervention, but if the institution you are working 
in does not have an MR scanner and you need informa- 
tion rapidly you must make do with a CT scan. 

Routine 

Surgical departments may have their own series of inves- 
tigations set out within a protocol. You should discuss 
with your consultant and the anaesthetic staff the circum- 
stances in which investigations that do not conform to the 
categories outlined under 'Aims' should be performed. 



LIMITATIONS 



^&!S$^«i3ai^iS!**Mi^^ 



Remember that all investigations have limitations that 
need to be considered when ordering tests and interpret- 
ing results. 

Incorrect result 

Do not discard your clinical impression, if the result of 
any investigation conflicts with your clinical judgement, 
without considering the possibility that the test may 
be misleading. Check that the correct procedure was 
performed and the procedure was performed correctly. 



55 




PATIENT ASSESSMENT 



Take into account any problems encountered with the 
procedure when interpreting results. 

Gaining sufficient confidence in your clinical ability to 
question the opinion of others is difficult but also essen- 
tial if a safe and rewarding clinical practice is to be devel- 
oped. Remember that in many circumstances you, as the 
surgeon, may be the only individual who has actually 
spoken to and examined the patient and therefore you are 
in a unique position to judge the likely accuracy of the 
investigation result you are presented with. 




Key point 

Do not blindly read a test result without 
considering the clinical picture. 



The investigation may also be misleading as a result of 
the limited sensitivity of an investigation. For example, a 
technically adequate breast fine needle aspiration may 
have been taken and correctly interpreted but may miss a 
carcinoma because of a sampling error of the lump 
assessed. Remember also that an investigation may yield 
a false-positive as well as false-negative result. 

Consider repeating or choosing another test to answer 
the same question if an investigation does not support a 
firm clinical diagnosis. Discuss the test with the person who 
performed it to ensure that as much clinical information as 
possible has been passed on to the individual who is trying 
to give you a result. An inadequate report may have been 
based on inadequate information given on the request 
form. Combined clinical meetings between the surgical 
team and specialized radiologists, histopathologists, etc. 
are often the ideal forum for the presentation of clinical 
information and review of investigations. In this situation 
interpretation of radiological images or histological diag- 
noses may be revised and fit with your clinical impression. 
If a test is thought to be misleading it is often useful to 
repeat it, consulting the most clinically reliable investigator. 




Key points 

• Many investigations are operator dependent - 
subjective opinions, not objective proofs. 

• If an investigation does not conform with your 
firm clinical impression, first discuss it with the 
investigator before embarking on more 
complex tests, and consider repeating the test. 

Complications 

An investigation may be associated with a significant 
complication rate, an issue that may not only influence 



one's choice of its use, but also may have medicolegal 
implications if it has not been discussed at the time of 
consent. Is a selective carotid arteriogram really worth the 
1% stroke rate when a duplex scan may give all the 
necessary information? Think whether this complication 
rate could be reduced or should be avoided altogether. 
Hydrate the patient intravenously and consider pretreat- 
ment with N-acetylcysteine in a patient with a raised 
creatinine before giving contrast to perform CT or an 
angiogram. Give the older patient Klean-Prep rather than 
Picolax before a colonoscopy. 



SEQUENCE AND TIMING OF 

IN^STIG|mONS_ 

Organization 

Do not collect data indiscriminately when you are inves- 
tigating a patient prior to surgery or during follow-up. 
Always organize the flow of information you require so 
that it follows a logical sequence that will culminate in 
you being able to discuss the patient's condition and man- 
agement, with any attendant risks, in a fully informed 
manner and from a position of strength. During the pre- 
operative process of diagnostic confirmation, determina- 
tion of the extent of disease and exclusion of specific 
alternative diagnoses, you will frequently need more than 
one special investigation. In these circumstances thought 
must be given to determining the appropriate order of 
such investigations. Avoid the temptation to arrange all 
investigations at one sitting to prevent the patient having 
to come back repeatedly to the clinic. It is obviously inap- 
propriate to arrange cardiology and pulmonary function 
tests to assess fitness for surgery at the same time as deter- 
mining the primary disease and any spread. If the surgi- 
cal problem turns out to be inoperable, then the other 
investigations undertaken have usually been a waste of 
time and resources as well as putting the patient at poten- 
tial risk. Patients often understand the need for a logical 
sequence of investigations and the time this may require. 



Urgency 

Consider the urgency of each individual investigation 
and request appropriately. For the patient with a poten- 
tially curable carcinoma, investigations must be carried 
out quickly and efficiently. Conversely, there is no sense 
in flooding the radiology department with urgent 
requests that are to determine the cause of problems that 
have dragged on for many years. 

The purpose of investigations is to reduce the manage- 
ment options and to seek to obtain crucial information 
once, not repeatedly. Sometimes an impasse is reached. 



56 



INVESTIGATIONS 



W 4 



Reflect, reconsider and perhaps postpone a decision for a 
while, using time as a diagnostic tool. If you rush to make 
a decision where there is no indication for urgency you 
will make mistakes. A high negative laparotomy rate in a 
surgeon usually indicates an unwillingness to use time in 
this way, perhaps because of organizational constraints. 
Avoid the temptation to do a laparotomy in the middle of 
the night just because of the difficulties you might 
encounter if the need for surgery emerges the next day. 

Protocols 

Often the sequence and choice of investigations is pre- 
sented in the form of protocols, where guidelines are set 
out enabling all staff to follow the preferred investigative 
methods of a department. These are useful in common 
conditions, both as a diagnostic tool (such as the investi- 
gation of rectal bleeding) and as a preoperative work-up 
regimen (in the case of complex surgical procedures, such 
as complex aneurysm surgery or cardiac surgery, where a 
number of preoperative investigations must be per- 
formed). A well-written protocol allows the surgeon who 
is unfamiliar with the working practices of the hospital to 
be able to investigate a particular condition appropriately. 
They may also form guidelines for specialist nurses or 
nurse consultants to work from, making services more effi- 
cient and decreasing waiting times. Protocols are invalu- 
able in the procedure of audit as all staff must work to a 
standard, which they are expected to maintain. They also 
prevent unnecessary and costly investigations being per- 
formed. A rigid protocol has a number of advantages but 
you must remember that they are no substitute for clinical 
acumen and all cases must be dealt with on an individual 
basis, with investigations directed to a particular patient. 



PRACTICAL USE 






Blood tests 

Most laboratories use automated analysers that give all 
the common haematological and biochemical indices. You 
only need ask for a full blood count to receive a full set of 
haematological parameters. Interpret the results in the 
light of the patient's general condition. For example, 
dehydrated patients have a high haemoglobin and 
packed cell volume (PCV, haernatocrit) because of haemo- 
concentration; a normal haemoglobin in such patients 
may mask anaemia. 

Levels of substances may be affected by the timing of 
blood sampling. The creatinine kinase is only transiently 
raised in the plasma after myocardial infarction; other 
enzymes are increased later. There is a diurnal rhythm 
with hormones such as Cortisol that may produce 



misleading results. Binding proteins and plasma proteins 
affect hormone, enzyme and drug levels, so allow for this 
when interpreting results. 

Remember the biochemical picture is obtained from just 
a sample of plasma. You are only indirectly discovering 
what is going on inside cells. Potassium levels, for 
instance, reflect poorly the intracellular potassium. In dia- 
betic ketoacidosis the plasma potassium level is high but 
the patient is intracellularly depleted of potassium as 
insulin levels are low and potassium is not taken into cells. 

Discuss unusual cases with an expert. Examination of 
a blood film by an experienced haematologist can prove 
diagnostic in the case of a raised white cell count (WCC) 
where the cause is in doubt. Further investigation of the 
patient may also be influenced by an opinion from an 
expert. It may be that if the peripheral blood picture 
shows involvement (as in chronic lymphatic leukaemia), 
peripheral blood marker studies will lessen the need for 
lymph node biopsy. This will avoid the need for a general 
anaesthetic, and a bone marrow sample can be taken 
under local anaesthetic instead. 

Microbiology (see also Ch. 19) 

A pus swab only briefly contains a representative sample of 
organisms from an infected source. Organisms die because 
they are anaerobic (e.g. Baderoides), because they are deli- 
cate (e.g. Neisseria) or because the other organisms in the 
sample proliferate faster and overwhelm them. Therefore 
lose no time between taking the swab and transferring it to 
an appropriate medium for culture. If pus is available, 
collect a quantity and send that, rather than a swab, to the 
microbiologist. Store pus swabs (in appropriate transport 
medium) at 4°C when taken at night and ensure that they 
are sent to the laboratory the next day. Remember that prior 
consultation with a microbiologist may increase the yield of 
relevant positive cultures obtained. 

Taking many swabs for culture without clinically 
assessing the patient or careful thought may cause you to 
miss the diagnosis. Make sure you ask the correct ques- 
tion in order to select the best method of answering it. The 
detection of amoebic dysentery is not accomplished by 
taking a swab for culture but by examining a fresh speci- 
men immediately under the microscope. The positive 
identification of bacteria responsible for late vascular 
graft infections often requires special techniques (e.g. 
sonification) to separate the bacteria prior to culture and 
this requires all the clinical information to be passed on 
to the microbiologist before the arrival of the specimen. 

Inform the laboratory of all relevant clinical informa- 
tion and antibiotic treatment so that the microbiologist 
can read the results sensibly. For instance Gram-positive 
cocci within a blood culture may indicate a skin contami- 
nant, such as Staph, epidermidis, or an MRSA septicaemia. 



57 



4 



PATIENT ASSESSMENT 



In the patient with no sign of sepsis, it is sensible to wait 
for the full report from the bacteriologist. 

Always seek the help of the microbiologist whenever 
you deal with superadded infection, especially in trans- 
plant patients and in the immunocompromised (as in HIV 
infections or in patients on chemotherapy). Pneumocystis 
carinii is the commonest opportunistic infection here. The 
picture can, however, become quite complicated, partly 
because several infective agents can become involved 
(bacterial, viral or fungal) and partly because the picture 
may change from day to day. 

Radiological investigations (see also Ch. 5) 

X-ray examinations are one of the simplest and cheapest 
radiological investigations to perform. Use these as a first- 
line investigation in cases of suspected perforation and 
obstruction before more expensive and complicated tests. 
Think whether introduction of a contrast agent into a 
cavity or lumen would improve the diagnostic accuracy 
of the test if initial plain films are inconclusive. For most 
patients the radiation experienced from X-rays will not 
cause problems but the dose is cumulative, so when poss- 
ible avoid repeated tests that use radiation, especially in 
the case of long-term screening. 

Histopathology 

A biopsy is a representative sample of tissue that may 
be examined by a histopathologist. The tissue may be 
obtained in a variety of ways and biopsies are classified 
according to how they are obtained. Excision biopsies 
remove the entire lesion and undoubtedly provide the 
best tissue for histopathological examination. Wedge 
biopsies provide a section of tissue from a lesion, while a 
core biopsy is performed with a Tru-cut biopsy needle to 
take a small core of the lesion. Discuss with an expert the 
best type of biopsy to get an accurate answer and consider 
radiological methods of obtaining tissue to avoid open 
biopsy and obtain an accurate sample. Be careful when 
taking a biopsy to include a representative sample of the 
lesion. From the histologist you want to know what the 
lesion is, whether the lesion is malignant and the prog- 
nostic indicators. When taking a biopsy, therefore, be 
careful to take tissue and not only the necrotic centre; 
when obtaining samples from polyps sample the stalk, so 
that you may find out the degree of invasion; and when 
sending resected specimens orientate them appropriately. 
Talk to the pathologist, relay important clinical informa- 
tion and find out about resection margins, the grade and 
stage of disease. 

Fine needle aspiration does not give the same architec- 
tural detail as histology but it is quick, relatively painless, 
requires no anaesthetic, the complications of biopsy are 



avoided and it can provide cells from the entire lesion, as 
many passes through the lesion can be made while aspir- 
ating. For all cytological examinations there are errors that 
may occur in the sampling stage, where the lesion may be 
missed or an inadequate sample taken, or in the patholog- 
ical examination. You need to know from the cytologist 
whether the sample was adequate and whether normal or 
malignant cells were seen. If the sample is inadequate the 
test will usually need repeating. Cytological specimens can 
also be obtained from spun down samples of fluid from a 
patient. Urine, pleural aspirate and sputum can all be 
examined for malignant cells. Think of these simple ways 
of obtaining cytological evidence of malignancy. 

Invasive diagnostic procedures 

The use of endoscopy provides a direct method of visu- 
alization of pathology and also allows biopsy or definitive 
treatment of lesions. A negative endoscopy is usually 
more reliable than a negative contrast study, but remem- 
ber that it is operator dependent and that subtle lesions 
may have been missed (ask about the seniority and expe- 
rience of the operator if you did not perform the investi- 
gation yourself). It may need repeating in cases of doubt. 
Diagnostic laparotomy, and more commonly laparos- 
cope is used as a diagnostic tool in specific circumstances 
such as preoperative staging of certain cancers. The need for 
diagnostic procedures of this kind has fallen with the 
advent of high-resolution scans such as CT and MR. 

Physiological assessment 

Use this type of assessment when you require information 
on the physiological workings of an organ or part of an 
organ. Motility disorders may be investigated effectively 
by oesophageal or rectal manometry, which will supple- 
ment anatomical and pathological information that has 
been gained. Manometry will quantify the problem, as 
well as facilitate the selection of operative therapy. 



Summary 

• Do you understand the purpose of each 
investigation ordered in common 
conditions? 

• How do you decide which investigation is 
the most appropriate? 

• Can you name investigations with a 
limited reliability? 

• Which tests have serious complications? 

• Can you formulate sensible investigation 
plans for complex diagnostic problems? 



58 




Imaging techniques 

5. 1/1/. T. Gould, T. Agarwal, T. J. Beale 




Objectives 

• Become familiar with the basic techniques 
and principles of radiological investigation. 

• Be able to enumerate the different types 
of radiological modalities, together with 
their advantages and limitations. 

• Understand the principles of selection of 
the most appropriate radiological 
technique for a given clinical problem. 

• Identify the key roles of radiology in the 
diagnosis and management of surgical 
disorders. 




Key point 

* Remember the maxim, 'treat the patient and 
not the X-ray'. 



TYPES OF RADIOLOGICAL 
INVESTIGATION 



S««.*essii#iSsS» 



ai«&»we?s;!5s»*:«.S 



The wide range of imaging techniques available includes 
plain film radiographs (X-rays), fluoroscopic screening, 
ultrasound, computed tomography (CT), magnetic reson- 
ance imaging (MRI) and nuclear medicine. Each of these 
will be described briefly. 



INTRODUCTION 



t^K^^.^^^SSW!^:^! 



^•^■^■^^^^s^iV 



&fg$%&^Stt^&}i&}l$^^*tt 



Radiology is one of the most rapidly expanding special- 
ties. This is due to continuing advances in both computer 
and machine technology. New imaging techniques, dra- 
matically affecting patient assessment, are constantly 
being introduced. It is thus becoming increasingly diffi- 
cult for surgeons to keep up to date with them. There 
must therefore be close communication between surgeons 
and radiologists to ensure that the most appropriate 
imaging technique is utilized for specific surgical prob- 
lems. This is best achieved by regular interdepartmental 
meetings and individual case discussions of the more 
problematic patients. 

The correct imaging technique can be chosen only if 
you make all the facts available to the radiologist. To this 
end, include the appropriate clinical details on the 
imaging request form. 

Bear in mind the high cost and limited availability of 
some of the more sophisticated imaging techniques when 
deciding on the radiological investigation. Do not forget 
that the required information can often be obtained from 
plain X-rays and simple contrast studies. 

No radiological technique replaces clinical skills. Do 
not base clinical decision making on imaging findings 
alone. 



Plain radiographs (X-rays) 

1 . X-rays were first demonstrated by the German physi- 
cist W. K. Roentgen, in 1895. He discovered, fortuitously, 
that X-rays not only expose photographic plates, they are 
also absorbed to varying degrees by intervening structures, 
which are then projected onto the photographic plate as 
negative images. The clinical relevance of this discovery 
was immediately apparent as, for the first time, imaging of 
the living skeleton was possible, enabling deformities, frac- 
tures and dislocations to be seen. To this day the indica- 
tions for plain radiology have not changed, although X-ray 
imaging has now been used in every other system of the 
body. This has come about mainly due to the use of con- 
trast agents. Plain radiographs are used to demonstrate 
contrast between tissues of different densities and, as such, 
obviously show the skeletal system well. However, they 
also demonstrate differences between gas and fluid and are 
therefore the most sensitive imaging technique for the 
detection of free intraperitoneal air after gastrointestinal 
perforation. The use of radio-opaque contrast agents 
increases the diagnostic yield of plain radiography. For 
example, iodine-containing agents are excreted rapidly by 
the renal route and so clearly outline the kidneys, ureters 
and bladder. The same agents also delineate the internal 
characteristics of blood vessels in angiography. 



59 




PATIENT ASSESSMENT 



2. Plain radiography is the most frequently requested 
examination. It is relatively cheap and simple to perform. 
These images can, however, be difficult to interpret, par- 
ticularly soft tissue images, and of course ionizing radi- 
ation can be hazardous to health and to the developing 
fetus. The actual radiation dose to the patient varies 
greatly and depends on the density of the tissue through 
which the X-ray beam must pass. The greater the density 
of tissue, the more X-rays are absorbed in the patient and 
fewer reach the film. Table 5.1 shows the relative dose of 
common surgical requests compared to the radiation dose 
of a chest X-ray. The radiation dose of a chest X-ray is 
equivalent to 3 days of natural background radiation. 

Ultrasound 

1 . Ultrasound waves are created in a transducer (Latin 
trans = across + ducere = to lead; a device that transfers 
power from one system to another) by applying a momen- 
tary electric field to a piezoelectric crystal which vibrates 
like a cymbal, producing sound waves. The transmitted 
waves interact with soft tissue interfaces and are reflected 
back, deflected or absorbed. The sound waves that are 
reflected are alone used to make the image. The greater the 
difference in density between two adjacent tissue planes, 
the greater the amount of reflected sound waves. For 
example when the sound waves reach a solid gallstone, 
most of it is reflected back, resulting in a bright collection 
of echoes and an acoustic 'shadow' beyond the stone. 
Ultrasound waves, however, are transmitted through the 
surrounding biliary fluid, which appears black. 

2. Ultrasound examinations are useful for visualizing 
soft tissues. They easily demonstrate fluid collections in 
the subcutaneous tissues, such as breast cysts, and within 
the body cavities, as in the chest and abdomen. 
Ultrasound has become the first line of investigation in 
many conditions, such as gallstone disease. Its use is 
limited by structures that obscure the passage of the ultra- 



Table 5.1 Relative dose of 
requests 


common surgical 




Radiograph 


Equivalent number of 




chest X-rays (approx.) 


Chest PA 


1 


Abdomen AP 


50 


Pelvis AP 


35 


Lumbar spine AP and Lat 


65 


Barium meal 


150 


Sarium enema 


250 


IVU 


125 


CT head 


115 


CT chest or abdomen 


400 



sound waves, so it cannot give images of, for example, the 
brain. Large amounts of bowel gas may prevent adequate 
examination of the abdominal cavity, and the retroperi- 
toneum is often poorly visualized. It is highly operator 
dependent. It does, however, give dynamic, real time 
images and is safe to use in any patient, including those 
who are pregnant. It is relatively cheap and is mobile. It 
is also useful for guiding diagnostic procedures such as 
aspiration cytology or needle biopsy (see below). 

3. Intracavitary ultrasound has been used for 
transvaginal assessment of the pelvic organs in females 
and transrectal evaluation of the prostate gland. More 
recently endoscopic ultrasound (EUS) has been devel- 
oped, combining the benefits of high frequency ultra- 
sound and endoscopy A small ultrasonic transducer is 
incorporated into the tip of an endoscope. It is particu- 
larly useful in assessing the extent and especially the 'T' 
(tumour) staging of oesophageal, gastric, pancreatic and 
pulmonary rumours. 

4. Focused abdominal sonography in trauma (FAST) is 
gaining wide acceptance for assessing the abdomen in 
haemodynamically stable patients suspected of having 
abdominal injuries. 

Fluoroscopic imaging 

Many common requests to the radiology department 
involve the use of X-ray screening. These include all barium 
examinations, most interventional procedures (except those 
under ultrasound, CT or MRI guidance) and sinograms, 
cholangiograms, nephrostograms, etc. Each screening room 
has an image intensifier that converts the X-ray image into 
a light image, then to an electron image and finally back to 
a light image of increased brightness. Fluorescence (hence 
the term fluoroscopy) is the ability of crystals of certain 
organic salts (called phosphors) to emit light when excited 
by X-rays. This process is used both in film cassettes for 
plain radiographs and in an image intensifier. 

Barium salts are used to delineate the mucosa of the 
gastrointestinal tract and are also used in dynamic studies 
to help define the function of this system (e.g. in barium 
swallow examinations). Gastrografin is a thin, water 
soluble contrast medium which has the added advantage 
of not being a peritoneal irritant like barium. It is used for 
the evaluation of intestinal obstruction (both small bowel 
and colonic) and for confirming the presence of a sus- 
pected anastomotic leak. 

Computed tomography (CT) 

1. Some of the major advances in radiology in recent 
years have been in the field of cross-sectional imaging. 
Computed tomography (Greek tomos = slice + graphein - 
to write: abbreviated to CT) and magnetic resonance 



60 



IMAGING TECHNIQUES 



. 5 



imaging (MRI) have revolutionized the investigation of 
the central nervous system and other soft tissues. 

2. The CT image is derived from computer integration 
of multiple exposures as an X-ray tube travels in a circle 
around a patient. The circular track is called the gantry. A 
fan-shaped beam is produced by the X-ray tube(s) and is 
picked up by a row of sensitive detectors aligned directly 
opposite. The computer constructs the image by dividing 
the gantry into a grid. Each box in the grid is called a voxel 
and has a length, width and depth - slice thickness. Each 
voxel is given a value representing the average density of 
the tissue in the box; the value is measured in Hounsfield 
units (HU) after Sir Godfrey Hounsfield who invented the 
CT scanner in 1972. Water has an HU of 0, air -1000, fat 
-80 to 100, abdominal organs 30-80 and compact bone 
>250. Each voxel is assigned a shade of grey according to 
its HU. The window level (WL) is the HU number in the 
middle of the grey scale; the window width (WW) is 
the range of HUs over which the grey scale is spread. Both 
the WL and the WW can be adjusted to emphasize differ- 
ences in soft tissue / lung or bony detail on the stored data. 
These figures are always seen on the printed film. 

3. Modern three-dimensional spiral CT scanners have 
not only drastically cut down the time taken for the 
imaging but multiplanar reconstruction is now possible. 
This is particularly useful for the head, neck and face but 
has found important applications in general surgical con- 
ditions, a prime example being CT pneumocolon. 

Magnetic resonance imaging (MRI) 

1. Each body proton can be thought of as a very small 
magnet. When the body is placed in a magnetic field, 
these protons line up along the direction of that field. The 
images in MR are generated by the energy released from 
the protons when they realign within the magnetic field 
after the application of radiofrequency energy pulses. 
This electromagnetic energy is received by a 'coil' and 
converted to images by a computer. Scanning methods in 
MR are referred to as "pulse sequences' and the images 
generated are often classified as Tl -weighted or T2- 
weighted. In simple terms, in a Tl -weighted image, fat 
appears as a bright signal and water appears dark, and in 
a T2-weighted image, water appears as the brightest 
signal with fat appearing dark. There is therefore much 
scope for image manipulation by employing different 
pulse sequences during a single examination. 

2. MR images give unparalleled soft tissue resolution 
but are generally less useful than other imaging methods 
for bony structures. MR has inherent advantages over CT 
and other imaging techniques, the most important being 
the lack of ionizing radiation. It has multiplanar capa- 
bilities, allowing imaging in any arbitrary plane, not just 
the orthogonal planes (the standard projections) permitted 



by CT It has great sensitivity to flow phenomena and 
unique sensitivity for temperature changes. 

3. Its disadvantages include expense and availability. It 
is safe in the majority of patients but those with implanted 
magnetic devices or metallic objects, such as certain 
intracranial aneurysm clips, indwelling pacemakers, 
cochlear implants or metallic intraocular foreign bodies, 
cannot be safely scanned. Most orthopaedic implants, 
however, are safe. Due to the physical constraints of the 
machine, obese or claustrophobic patients may be unsuit- 
able for imaging by this technique. 

Nuclear medicine 

1. A radionuclide is administered into the body and 
subsequently undergoes radioactive decay. The common- 
est radionuclide used in medicine is technetium-99m 
( 99m Tc). The 'm' is placed after the mass number to indi- 
cate a metastable state, i.e. an intermediate species with a 
measurable half -life. " m Tc has a half-life of 6 h and is a 
pure gamma emitter. This results in a relatively low dose 
of ionizing radiation being delivered to the patient. The 
radionuclide is labelled so that it can be targeted to the 
tissue that needs to be imaged. For example, it may be 
labelled by attaching it to red or white blood cells or a 
variety of chelates. In the decay process gamma rays are 
given off. These are detected by a gamma scintillation 
camera and from them the images are formed. 

2. The latest addition to the armamentarium is PET 
(positron emission tomography), which has been useful 
in the staging of various gastrointestinal malignancies. It 
is particularly useful in preoperative assessment of nodal 
involvement and detection of recurrence and metastases. 
It is reserved for the assessment of equivocal cases, not as 
a first choice procedure. 

3. Tomographic techniques, commonly used in X-ray 
and CT, have also been developed in nuclear medicine. 
Tomography refers to the technique of 'cutting' the body 
into the required imaging planes. An example is SPECT 
(single photon emission computed tomography) and 
involves gamma camera(s) rotating around a gantry, as in 
X-ray CT. A volume of data can then be collected and 
transaxial images reconstructed. 

HOW ARE RADIOLOGICAL 
TECHNIQUES USED IN SURGERY? 

Radiological techniques are used in the management of 
surgical diseases in one of three main ways: 

1. To aid in the diagnosis of a surgical disorder 

2. As an interventional technique to treat a surgical 
disorder or one of its complications 

3. To guide a surgical procedure. 



61 




PATIENT ASSESSMENT 



Each of these main areas will be considered in turn, with 
a few specific examples. 

Aid to diagnosis 

1. This is of course the simplest and best known appli- 
cation. Examples include the use of an erect chest X-ray 
to detect free intraperitoneal gas, and CT scan of the brain 
to detect intracranial bleeding following trauma. 

2. Radiology is a valuable screening aid, as in popula- 
tion screening such as mammography, and also as part 
of protocol-based preoperative imaging such as a chest 
X-ray when preparing patients for major surgery. Always 
prefer the simple, hence cheaper, investigation before the 
complex, hence costlier, one if the simpler investigation 
has a good chance of providing the diagnosis. 

3. If possible, avoid those with a significant associated 
complication rate or inherent danger; for example, in 
pregnant women ultrasound techniques are safer than 
those using X-rays. 

4. All investigations, no matter how complex or invasive, 
have a given sensitivity and specificity and therefore there 
will always be a false-negative and a false-positive rate. 




Key point 

Prefer safer, and non-invasive tests, to 
potentially dangerous and invasive ones. 



Interventional techniques 

1. Interventional radiology has developed into a special- 
ity in its own right. There can be very few radiology depart- 
ments that do not perform at least some interventional 
techniques. Interventional radiology may be defined as the 
performance of a procedure on some part of the anatomy 
while using a radiological modality to guide that proce- 
dure. Perhaps the simplest example is image-guided 
biopsy. This is commonly performed using ultrasound or 
CT guidance, although it is now possible to perform biop- 
sies using the added advantage of MRI. In places this has 
replaced the need for an open surgical biopsy. A good 
example is stereotactic (Greek stereos = solid + tassein = to 
arrange; location within three dimensions) core biopsy of 
the breast, guided by digital mammography. The placement 
of drainage catheters using ultrasound or CT has revolu- 
tionized the management of postoperative complications 
such as subphrenic abscess. Vascular surgery has been com- 
pletely changed by the advent of interventional radiology. 
The techniques include angioplasty, catheter thrombolysis 
and stenting of aneurysmal or occlusive diseases, and novel 
techniques that replace the need for high-risk surgery, for 



example transjugular portosystemic shunting in portal 
hypertension. 

2. This is a field that is likely to improve further, given 
the rapid development and integration of computer tech- 
nology into imaging methods and the availability of new 
imaging systems, such as interventional MRI, and tissue 
destruction techniques, such as focused ultrasound and 
radiofrequency ablation systems. 

Image-guided surgery 

1. Image-guided surgery is the use of a radiological 
modality during a surgical procedure to give more infor- 
mation than is available by direct inspection of the surgi- 
cal field. The information so gained is used to influence 
or guide the performance of the operation. There are 
many examples in everyday surgical practice (Table 5.2). 
The best known are fracture manipulation using image 
intensification, and intraoperative cholangiography 
during cholecystectomy to determine the presence or 
absence of gallstones within the main bile ducts. 

2. More advanced techniques include stereotactic 
CT-guided neurosurgery and the use of intraoperative 
ultrasound in hepatic and pancreatic surgery, to deter- 
mine resectability and to determine the anatomical 
location of vital structures as resection proceeds. This 
technique may be used in both open and laparoscopic 
procedures. It has recently become possible to perform 
surgical operations within interventional MRI units, 
harnessing the soft tissue and image manipulation power 
of MR to guide the procedure. There have been recent 
reports demonstrating the use of intraoperative MR to 
guide complete tumour resection in the brain (Moriarty et 
al 1996), breast (Gould et al 1998), and soft tissues (Gould 
et al 2001). It has been shown to be a useful guide when 



Table 5.2 Examples of image-guided surgery 


Modality 


Procedure 


X-ray 


Fracture reduction 


X-ray 


Removal of foreign bodies 


X-ray 


Intraoperative cholangiography 


X-ray 


ERCP 


X-ray 


Retrograde ureterography 


X-ray 


Intraoperative arteriography 


Ultrasound 


Laparoscopic staging of pancreatic 




cancer 


Ultrasound 


Hepatic resection 


Ultrasound 


Complex anal fistula surgery 


CT 


Stereotactic neurosurgery 


MR! 


Neurosurgery 


MRI 


Breast surgery 



62 



IMAGING TECHNIQUES 



f 5 



operating on complex anal fistulae (Gould et al 2002). MR- 
guided interstitial laser thermotherapy is being carried 
out for ablation of irresectable and metastatic tumours. It 
has the added advantage of intraprocedural monitoring 
and can be performed under local anaesthesia. Some sur- 
vival benefit has already been described for this technique 
for ablation of colorectal metastases in the liver. 

3. Finally, radiological data obtained preoperatively 
can be used to plan or guide surgical procedures. The best 
examples are three-dimensional CT reconstructions of the 
face or skull for surgical planning prior to major maxillo- 
facial reconstructive surgery. This technique is now used 
to plan the best approach for major hepatic surgery for 
trauma or tumours. An extremely exciting area of current 
investigation is the combination of information obtained 
from a number of radiological techniques, such as CT, and 
conventional and functional MRI to make a comprehen- 
sive three-dimensional preoperative model of lesions and 
surrounding anatomical structures. Work is underway to 
'register' this image to the patient during surgery, so that 
it may truly be used as an intraoperative guide. 



Summary 

• Do you appreciate the wide variety of 
radiological imaging methods that are 
currently available? 

• Are you aware of the value of consulting 
your radiologist in order to select the most 
relevant investigation? 

• Do you recognize that selecting an 
appropriate investigation demands 
balancing the aim of the investigation, 
effectiveness, cost and safety? 



Are you aware that radiological images 

should not be used in isolation but must 

be used in conjunction with the rest of the 

available clinical information? 

Do you recognize the three key areas of 

diagnostic radiology, interventional 

radiology and image guidance of surgical 

procedures? 

Can you foresee the likely future 

applications of interventional radiology 

and image-guided surgery? 




References 



Gould S, Lamb G, Lomax D, Gedroyc W, Darzi A 1998 

Interventional MR-guided excisional biopsy of breast lesions. 
Journal of Magnetic Resonance Imaging 8: 26-30 

Gould SWT, Agarwal T, Benoist S, Patel B, Gedroyc W, Darzi A 
2001 Resection of soft tissue sarcomas with intraoperative 
magnetic resonance guidance. Journal of Magnetic Resonance 
Imaging 15(1): 114-119. 

Gould SWT, Agarwal T, Martin S, Gedroyc W, Darzi A 2002 
Image guided surgery for anal fistula in a 0.5T interventional 
MRI unit. Journal of Magnetic Resonance Imaging 16: 267-276 

Moriarty T, Kikinis R, Jolesz F, Alexander III E 1996 Magnetic 
resonance imaging therapy. Neurosurgical Clinics of North 
America 7: 323-330 




m Further reading 



Royal College of Radiologists 1998 Making the best use of a 
department of clinical radiology, 4th edn. Royal College of 
Radiologists, London 



63 




Influence of coexisting 
disease 

R. M. Jones, C. A. Marshall 



w 



Objectives 



Recognize which coexisting disease 

processes are associated with increased 

morbidity. 

Understand which features of the patient's 

condition can be improved. 

Realize that a simple operation does not 

always mean an equally simple or risk-free 

anaesthetic. 

Understand that sick patients are best 

managed in daylight hours with fully 

trained staff. 

Recognize that in some circumstances it 

may be better to transfer patients to 

another hospital preoperativefy if there 

are inadequate facilities for their 

postoperative care. 



INTRODUCTION 









About half of adult patients presenting to you have a 
coexisting disease unrelated to the pathological process 
necessitating surgery. The proportion is increased in the 
elderly and patients presenting for emergency surgery. 
The morbidity and mortality associated with surgery and 
anaesthesia are increased in patients with coexisting 
disease, and the more significant the coexisting disease 
the greater the risk (Buck et al 1987, Campling et al 1993). 
The medical diagnoses most commonly associated with 
increased surgical morbidity and mortality are: 

• Ischaemic heart disease 

• Congestive cardiac failure 

• Arterial hypertension 

• Chronic respiratory disease 

• Diabetes mellitus (Greek dia — through + bainein = to go 
+ mellitus = honeyed) 

• Cardiac arrhythmias 



• Anaemia 

• Obesity. 

You can see that pre-existing cardiac-related problems 
account for the most significant increase in operative 
risk. 

The National Confidential Enquiry into Perioperative 
Deaths (NCEPOD) for 1990 (Campling et al 1992) empha- 
sized the importance of discussion between surgeon and 
anaesthetist before a decision to proceed in a particular 
patient. All patients presenting for surgery should have a 
full clinical history and examination performed, includ- 
ing details of concurrent drug therapy, previous medical 
history and history of allergy. Depending on the nature of 
the coexisting medical disease and that of the planned 
surgery, additional specialized investigations may subse- 
quently be needed. Young (< 45 years), fit patients under- 
going minor elective surgery do not need routine blood 
haematology or chemistry, a chest X-ray or an electro- 
cardiogram ECG). 

The NCEPOD report for 1992-1993 (Campling et al 
1995) identified a substantial shortfall in critical care 
services, and a failure to anticipate the need for these 
services. Furthermore, it emphasized that the skills of the 
surgeon and the anaesthetist should be appropriate for 
the medical condition of the patient. These professionals 
would not always be doctors of the same grade. 

Who Operates When (Campling et al 1997), an NCEPOD 
report into timing of operations, found that the patients 
who died were for the most part elderly and in poor 
preoperative health (82% suffered from at least one 
coexisting disease, of which cardiorespiratory disease 
was the most common, followed by malignancy). 
Preoperative management was criticized as sometimes 
poor, and the rush to operate before adequate resuscita- 
tion contributed significantly to morbidity and mortal- 
ity. Particular attention was drawn to the low use of 
intravenous fluids, infrequent use of objective cardiac 
assessment, and patchy application of thromboembolic 
prophylaxis. 

The 2001 NCEPOD report Changing the Way We Operate 
noted that 95% of patients had coexisting medical prob- 
lems at the time of the operation. 



64 



INFLUENCE OF COEXISTING DISEASE 




6 




Aims of management 

• To diagnose and determine the extent of 
pre-existing medical disease. 

• To optimize the patient's medical condition 
before surgery. 

• To ensure that specialized postoperative care 
facilities are available if required. 



CARDIOVASCULAR DISEASE 



fibrillation, Q waves or left ventricular hypertrophy 
(LVH), and ventricular premature beats, all detectable on 
electrocardiography. 






Coronary artery disease 

1. Coronary atherosclerosis is the commonest type of 
cardiovascular disease; NCEPOD has not previously 
been able separately to identify patients with either a pre- 
vious myocardial infarction or ischaemic heart disease; 
for the first time, however, in 2001, NCEPOD identified 
that 60% of the patients had known ischaemic heart 
disease at the time of their final operation; an incidence 
higher than previously identified by national statistics. 

2. Established major risk factors for coronary artery 
disease include: (1) age (male > 45 years, female > 55 years); 
(2) family history of early myocardial infarction; (3) current 
or treated hypertension; (4) smoking; (5) diabetes mellitus; 
and (6) low levels of high density lipoprotein (HDL) 
cholesterol. 

3. High risk procedures (risk of perioperative cardiac 
morbidity and mortality > 5%) include major emergency 
operations, especially in the elderly, major vascular pro- 
cedures including peripheral vascular, and prolonged 
surgery (> 3 h) with major fluid shifts. 

4. In 1996, the American College of Cardiology and 
the American Heart Association issued joint guidelines 
for cardiovascular assessment for non-cardiac surgery 
(ACC/ AHA Task Force Report 1996). These utilize a pre- 
liminary screening step followed by further investiga- 
tion where necessary. 

5. Assess the degree of activity that precipitates symp- 
toms of myocardial ischaemia and note the presence or 
absence of congestive heart failure (does the patient also 
become breathless on exertion?). Enquire about a history 
of arrhythmias (palpitations) and presence of a pacemaker. 
Determine blood pressure, height of jugular venous pres- 
sure (JVP), cardiac murmurs, lung crepitations, dyspnoea 
and evidence of peripheral vascular disease. 

6. The most important routine test is the electrocardio- 
gram (ECG). Remember that the preoperative ECG is 
normal in 20-50% of patients with proven ischaemia. The 
ECG is a poor predictor of perioperative cardiac morbid- 
ity. However, features shown to be associated with 
increased risk include: rhythm other than sinus, atrial 




Key points 



You should now be able to identify three broad 
groups of patients: 

• High risk patients such as those with unstable 
coronary syndromes, or decompensated 
congestive cardiac failure (CCF): delay elective 
surgery, consult a cardiologist. 

• Intermediate risk patients: proceed with 
non-vascular surgery, possibly with the 
addition of a beta blocker. Further evaluate for 
vascular surgery. 

• Low risk patients: proceed with surgery. 

7. The basis of management depends on the fact that 
myocardial ischaemia will occur whenever the balance 
between myocardial oxygen supply and demand is dis- 
turbed, such that demand exceeds supply. The major 
determinants of myocardial oxygen supply are the 
coronary perfusion pressure (the aortic diastolic pressure 
minus the left ventricular end-diastolic pressure) and 
diastolic time. 

8. The major determinants of myocardial oxygen 
demand are increasing heart rate, increasing inotropic 
state, afterload, which is the impedance to left ventricu- 
lar ejection (the systemic arterial pressure is an approxi- 
mate determinant of afterload), and preload, which is the 
left ventricular end-diastolic pressure. 

9. In the perioperative period avoid factors that 
decrease supply and /or increase demand. Encourage 
smokers to stop for at least 12 h before surgery. Almost 
without exception, continue concurrent drug therapy 
until the time of surgery. Short term beta blockade may 
improve survival after discharge from hospital, although, 
in the study by Mangano et al (1996), atenolol was given 
under close monitoring and it may not be appropriate 
simply to adapt this as an oral premedication to be given 
on the ward. It can be seen that an increase in heart rate 
and an increase in preload is especially deleterious as 
they increase myocardial oxygen demand and decrease 
myocardial oxygen supply. During the perioperative 
period do not allow a decrease in systemic arterial pres- 
sure to a significant degree (a decrease in diastolic pres- 
sure greater than 20% of the patient's normal resting 
diastolic pressure is a useful guide) because this decreases 
coronary perfusion pressure, which is very poorly toler- 
ated in patients with multiple sites of coronary artery 
narrowing. Ensure that pain management is effective 



65 




PATIENT ASSESSMENT 



postoperatively as the presence of pain leads to hyper- 
tension and tachycardia. If necessary, refer the patient to 
the hospital's acute pain team. In addition, after major 
surgery, especially intra-abdominal or intrathoracic, 
administer supplemental oxygen for 24 h. Consider pro- 
viding supplemental oxygen overnight for the first four 
postoperative days. 

10. While myocardial ischaemia is commonest over the 
first three postoperative days, myocardial infarction tends 
to occur on the day of surgery or on the first postoper- 
ative day; therefore, institute invasive monitoring for the 
first 24-36 h postoperatively. 




Key points 

• Coronary artery disease is the commonest 
cardiac disease; it is associated with the 
majority of perioperative mortality and 
morbidity. 

• Early postoperative ischaemia is a much 
stronger predictor of morbidity and mortality 
than any identifiable preoperative factors. 

• Acute cardiac failure and unstable angina pose 
unacceptably high perioperative risks; treat it 
prior to elective non-cardiac surgery. 



be due to an increase in volume (an increase in intravas- 
cular volume or valve incompetence), or pressure (sys- 
temic arterial hypertension or aortic stenosis). It is usual 
for one ventricle to fail before the other, but disorders that 
damage or overload the left ventricle are more common 
(e.g. ischaemic heart disease and systemic arterial hyper- 
tension), and hence symptoms attributable to pulmonary 
congestion are usually the presenting ones. 

2. Left ventricular failure is the most common cause of 
right ventricular failure and, if this supervenes, dyspnoea 
may actually decrease as right ventricular output 
decreases, leading to a reduction in pulmonary conges- 
tion. Conventionally, congestive heart failure refers to the 
combination of left and right ventricular failure with 
evidence of (and symptoms relating to) systemic and 
pulmonary venous hypertension. Physiologically, heart 
failure may be thought of as the failure of the heart to 
match its output in order to meet the body's metabolic 
needs. Treatment is aimed at normalizing this imbalance. 
Thus, cardiac output can be improved or metabolic needs 
decreased. Traditionally, digitalis glycosides have been 
thought of as mediating their beneficial effects by improv- 
ing cardiac output. Their use is now superseded by 
angiotensin converting enzyme (ACE) inhibitors, often 
combined with diuretics. Vasodilator's can also be used to 
decrease peripheral demand. Digitalization is indicated in 
patients with atrial fibrillation or flutter. 



Arterial hypertension 

1. Moderate or marked, longstanding, untreated 
hypertension increases perioperative morbidity and mor- 
tality, and is a significant risk factor for the production of 
coronary atherosclerosis. Stabilize patients with sustained 
systemic arterial hypertension (systolic > 160 mmHg, 
diastolic > 110 mmHg) on antihypertensive therapy 
before proceeding with long duration elective surgery. 

2. Untreated or inadequately treated hypertensives 
respond in an exaggerated manner to the stress of surgery, 
with a resultant increase in operative morbidity and mor- 
tality. Assume that patients with longstanding moderate 
to marked hypertension have coronary atherosclerosis 
and manage them appropriately, even in the absence of 
overt signs and /or symptoms of ischaemic heart disease, 

3. Antihypertensive therapy is associated with its own 
unique considerations for anaesthetic and surgical man- 
agement, the specific issues depending upon the medica- 
tion the patient is taking (see Concurrent drug therapy, 
p. 80). 




Key points 

• Manage symptomatic heart failure by optimum 
medical therapy preoperatively in all but the 
direst of surgical emergencies. 

• Surgery in the presence of decompensated 
heart failure is associated with a high mortality. 

3. The operative mortality and morbidity of patients 
with well-compensated heart failure is small. After oper- 
ation admit the patient to a high dependency unit or an 
intensive care facility with the ability to measure and 
adjust preload, afterload and cardiac output. A principal 
recommendation of the 2001 NCEPOD report was that 
nurses and doctors on the wards need to improve their 
proficiency in interpreting and managing central venous 
pressure (CVP). Ward equipment must include facilities 
for transducer pressure monitoring, to allow accurate and 
continuous CVP monitoring. 



Heart failure 

1. This implies an inadequacy of heart muscle sec- 
ondary to intrinsic disease or overloading. The latter may 



Congenital heart disease 

1 . Congenital anomalies of the heart and cardiovascu- 
lar system occur in 7-10 per 1000 live births (0.7-1%). It is 



66 



INFLUENCE OF COEXISTING DISEASE 



. 6 



the commonest form of congenital disease and accounts 
for approximately 30% of the total burden of congenital 
disease. In affected children 10-15% have associated 
anomalies of the skeletal, genitourinary or gastrointesti- 
nal system. Nine lesions comprise more than 80% of con- 
genital heart disease; of these, ventricular septal defect is 
by far the most frequent at 35%. Approximately 10-15% 
of patients with congenital heart disease may survive 
untreated to adulthood but the majority require some 
form of cardiac surgery as children. 

2. A large cohort of patients with treated congenital 
heart disease is now surviving into adult life. Although 
these patients have traditionally returned to paediatric 
cardiac surgery centres for non-cardiac surgery as adults, 
this is not always possible. If the patient has been lost to 
cardiac follow-up, request a new cardiological opinion. 




Key points 

• Adults with congenital heart disease form a 
very high risk group, often with multiple 
anatomical and pathophysiological 
abnormalities. 

• Fully assess them preoperatively and request 
perioperative care from experts familiar with 
these problems. 



3. It is not possible to review the subject comprehen- 
sively here; read the article by Findlow et al (see Further 
reading). In summary, the problems fall into four groups: 
arrhythmias, shunts (volume and direction), pulmonary 
disease and hypertension, and ventricular dysfunction. 
Patients with Eisenmenger's syndrome (right-to-left 
shunt due to pulmonary hypertension) are very high risk 
patients. As well as circulatory failure, they run the risk 
of air embolism during surgery, postoperative deep vein 
thrombosis (DVT) and infective endocarditis. Give anti- 
biotic prophylaxis to all patients with congenital heart 
disease, and take care to avoid air in the tubing during the 
siting of intravenous lines. 

Acquired valvular heart disease 

Mitral stenosis 

This is nearly always of rheumatic origin, but symptoms 
do not appear until the valve area is reduced to less than 
2.5 cm 2 , i.e. half the normal valve area. This may take 
20 years following the episode of rheumatic fever. As valve 
area decreases below 2 cm 2 , an increase in left atrial pres- 
sure is required at rest to maintain cardiac output. A valve 
area below 1 cm 2 is classified as severe mitral stenosis and 
is associated with a left atrial pressure in excess of 



20 mmHg, and even at rest cardiac output may be barely 
adequate; there is pulmonary hypertension. Eventually 
right ventricular failure supervenes and atrial fibrillation 
is common. Patients with mild to moderate mitral stenosis 
and sinus rhythm tolerate surgery well. All patients 
should receive antibiotic prophylaxis. Fluid balance 
should be carefully monitored, as overtransfusion may 
precipitate pulmonary oedema, whereas under trans fusion 
will compromise left ventricular filling. Similarly, changes 
in heart rate are poorly tolerated, and during surgery the 
anaesthetist will use a technique which minimizes changes 
in cardiac parameters. If major surgery is to be undertaken, 
with the possibility of large blood loss, consideration 
should be given to monitoring pulmonary capillary wedge 
pressure by means of a balloon-tipped flow-directed 
catheter. Unless the patient is taking oral anticoagulants, a 
local anaesthetic technique may be used for surgery, but a 
high spinal or epidural block may be associated with 
adverse cardiovascular effects (systemic arterial hypoten- 
sion) and should be employed with caution. 

Patients who are dyspnoeic at rest and have a fixed 
and reduced cardiac output present a significant risk 
during surgery. Digoxin should be continued up until the 
time of operation and plasma electrolytes checked, as 
hypokalaemia will increase the incidence of cardiac 
rhythm disturbances. These patients may have to be 
ventilated electively postoperatively. 

Aortic stenosis 

Valvular aortic stenosis is commonest in elderly males, 
although it may occur at any time of life. The presence of 
any of the following significantly increases the likelihood of 
aortic stenosis: effort syncope, slow rise of the carotid pulse, 
late systolic murmur with radiation to the right carotid and 
absent second heart sound. The aetiology is diverse and 
includes congenital, rheumatic, senile and mixed forms. It 
must be remembered that it is most common in patients in 
whom the incidence of ischaemic heart disease is also high. 
Severe aortic stenosis is associated with an increased peri- 
operative morbidity and mortality. These patients may be 
asymptomatic even with a large (> 80 mmHg) gradient 
across the valve, if the left ventricle has not failed. A pre- 
operative echo and cardiac assessment is essential to deter- 
mine the gradient, as the risk of surgery can be predicted 
from this. The 1994-1995 NCEPOD report made the specific 
recommendation that any patient with an ejection systolic 
murmur in association with evidence of left ventricular 
hypertrophy or myocardial ischaemia requires referral to a 
cardiologist preoperatively for assessment of the aortic 
valve (Gallimore et al 1997). Systemic arterial hypotension 
must be avoided at all times because it will compromise 
coronary perfusion. Thus, peripheral vasodilatation, 
hypovolaemia and myocardial depression are all poorly 



67 




PATIENT ASSESSMENT 



tolerated. A change in cardiac rhythm is also poorly tol- 
erated, as the atrial component to ventricular filling is 
essential to maintain normal cardiac output. For major 
procedures it is advisable to monitor left ventricular filling 
pressure, as higher than normal filling pressures are needed 
to maintain cardiac output. 

Cardiomyopathies 

Using echocardiography, three principal forms of cardio- 
myopathy are described. 

1. Congestive or dilated cardiomyopathy: this may be 
associated with toxic, metabolic, neurological and inflam- 
matory diseases. There is decrease in contractile force of 
the left or right ventricle, resulting in heart failure. 

2. Hypertrophic or obstructive cardiomyopathy: this is 
an autosomal dominantly inherited condition in which 
there is hypertrophy and fibrosis; it mainly affects the 
interventricular septum but may involve the whole of the 
left ventricle. 

3. Restrictive cardiomyopathy: this is a rare form of 
cardiomyopathy and the main feature is the loss of 
ventricular distensibility due to endocardial or myocar- 
dial disease. Restrictive cardiomyopathy in many ways 
resembles constrictive pericarditis, and the endocardial 
disease may produce thromboembolic problems. 

Table 6.1 summarizes the treatment and management 
of these patients. 

Disturbances of cardiac rhythm 

Atrial fibrillation 

This is the most commonly encountered disturbance of 
cardiac rhythm and it is important to define the disease 
processes causing the fibrillation. These are: ischaemic 
heart disease, rheumatic heart disease (especially mitral 



stenosis), pulmonary embolism, bronchial carcinoma, 
thyrotoxicosis, thoracotomy, alcoholism. 

If there appears to be no underlying cause, the rhythm 
disturbance is usually termed Tone atrial fibrillation'. The 
atrial discharge rate is usually between 400 and 600 
impulses per minute, but the atrioventricular (AV) node 
cannot conduct all these impulses, so that some fail to 
reach the ventricle or only partially penetrate the node, 
and this results in a block or delay to succeeding 
impulses. Ventricular response is therefore irregular, but 
seldom more than 200 impulses per minute; the use of 
drugs or the presence of disease of the AV node often 
causes the response rate to be lower than this. The 
medical management of patients with atrial fibrillation 
must include the management of the underlying cause of 
the rhythm disturbance. It is important to ensure that the 
fibrillation is well controlled, i.e. that the response rate of 
the ventricle is not too rapid. Digitalis alkaloids remain 
the primary method of slowing AV nodal conduction, but 
if these fail to control the response rate, amiodarone is 
usually effective. Occasionally, cardioversion will restore 
sinus rhythm if the atrial fibrillation is of recent onset. 
Anticoagulate the patient prior to this. 



Atrial flutter 

The causes of this disturbance of cardiac rhythm are 
similar to those of atrial fibrillation, and the perioperative 
considerations are principally those of the underlying 
disease process* Atrial flutter is less commonly seen than 
atrial fibrillation. Although control of ventricular rate is 
more difficult in flutter, unlike fibrillation cardioversion is 
often successful. Anticoagulate the patient with warfarin 
prior to cardioversion. Second line therapy includes fle- 
cainide or digoxin. A bolus of adenosine may be used to 
aid in the differential diagnosis of atrial flutter versus 
paroxysmal supraventricular tachycardia (SVT). 



Table 6,1 Cardiomyopathies: diagnosis and treatment 



Congestive {dilated) Hypertrophic (obstructive) 



Presenting signs/symptoms 



Treatment 



Heart failure 
Rhythm disturbance 
Systemic emboli 



Restrictive 



Diuretics 
Vasodilators 
Antiarrhythmics 
Anticoagulants 



Syncope 

Dyspnoea 

Angina 

Rhythm disturbance 

Systolic murmur appearing during 

longstanding hypertension 

Antiarrhythmics 
fi-Adrenergic antagonists 
Anticoagulants 



Heart failure 
Eosinophilia 



Steroids 
Cytotoxic agents 



68 



INFLUENCE OF COEXISTING DISEASE 



6 



Heart block 

There are two basic types of heart block: atrioventricular 
heart block and intraventricular conduction defects. 

Atrioventricular heart block. This may be incom- 
plete (first- or second -degree AV block) or complete 
(third-degree AV block). In first-degree heart block the PR 
interval of the ECG exceeds 0.21 s, but there are no 
dropped beats and the QRS complex is normal. It does not 
always imply significant underlying heart disease/ but is 
seen in patients on digitalis therapy. Do not expose the 
patient to any drug in the perioperative period which will 
further decrease AV nodal conduction (e.g. halothane 
anaesthesia, p-adrenergic antagonists or verapamil). 

There are two types of second-degree heart block; 
Mobitz types 1 and 2. Mobitz type 1 block is also known 
as the 'Wenckebach phenomenon' and this is usually 
associated with ischaemia of the AV node or the effects of 
digitalis. There is progressive increase in the length of the 
PR interval until the impulse fails to excite the ventricle 
and a beat is dropped. As a generalization, patients with 
this type of heart block do not require a pacemaker prior 
to surgery, and should it be necessary the administration 
of atropine will often establish normal AV conduction. 
Mobitz type 2 block is less common than type 1; it is a 
more serious form of conduction defect and may be a 
forerunner to complete AV block. The atrial rate is normal 
and the ventricular rate depends on the number of 
dropped beats, but it is commonly 35-50 beats per 
minute. The net result is that of an irregular pulse. The 
ECG indicates that there are more P waves than QRS com- 
plexes, but the PR interval, if present, is normal. It is prob- 
ably acceptable to undertake minor surgery in patients 
with Mobitz type 2 block without the need for the inser- 
tion of a prophylactic pacemaker. However, in these cir- 
cumstances ensure that you have immediately available 
drugs such as atropine and isoprenaline, and also the 
means for temporary pacing. Prophylactic pacemaker 
insertion is indicated for major surgery, especially if this 
is likely to result in significant blood loss and associated 
haemodynamic instability. 

Third-degree heart block is also termed "complete heart 
block'. It may result from conduction defects located 
within the AV node, bundle of His, or the bundle branch 
and Purkinje fibres. An escape pacemaker emerges at a 
site distal to the block (e.g. if the impulses are blocked 
within the AV node, the bundle of His usually emerges as 
the subsidiary pacemaker). In general, the more distal the 
site of the escape pacemaker, the more likely is the patient 
to suffer symptoms such as dyspnoea, syncope or con- 
gestive heart failure and to need permanent ventricular 
pacemaker therapy. Pacemaker therapy is always indi- 
cated before surgery, although in emergency situations 
(such as complete heart block appearing intraoperatively) 



various drugs may be tried to increase the heart rate. 
Atropine may be of value if the escape pacemaker is junc- 
tional. Isoprenaline may be of value if the escape pace- 
maker is more distal. A pacing Swann-Ganz catheter or a 
transoesophageal pacemaker can be inserted in an emer- 
gency and may be easier to place than a temporary wire. 
Intraventricular conduction defects. Left bundle 
branch block is always associated with heart disease. The 
QRS complex is wide (>0.12 s). A hemiblock occurs if only 
one of the two major subdivisions (anterior and posterior) 
of the left bundle is blocked. The QRS complex is not pro- 
longed in left hemiblocks. Left anterior or posterior hemi- 
block may occur with right bundle branch block and it is 
generally considered that left anterior plus right bundle 
branch block is not an indication for temporary pace- 
maker therapy before surgery, but that left posterior plus 
right bundle branch block is an indication for a pace- 
maker. The latter patients are at risk of developing com- 
plete heart block. Right bundle branch block is not 
invariably associated with underlying heart disease. The 
principal significance lies in its association with a left pos- 
terior hemiblock, as there is then a risk of complete heart 
block; in these patients a temporary pacemaker is indi- 
cated before surgery and anaesthesia. 

Pacemakers 

The patient with a pacemaker can safely undergo surgery 
and anaesthesia, but review the medical condition that 
gave rise to the need for pacemaker therapy. The usual 
indications for a pacemaker are congenital or acquired 
complete heart block, sick sinus syndrome and brady- 
cardia, associated with syncope and /or hypotension. 

Acquired complete heart block is probably the com- 
monest indication, the underlying cause for this usually 
being ischaemic heart disease. Specifically ask the patient 
about the return of symptoms such as syncope, which 
may indicate that the pacemaker is failing to capture the 
ventricle (or atria if an atrial pacemaker is present). The 
heart rate should be within a couple of beats per minute 
of the pacemaker's original setting. It is important to 
determine the type of pacemaker that has been implanted 
and the time when it was put in. 

All patients with pacemakers are normally reviewed 
regularly in a pacemaker clinic. 




Key points 



Whenever a pacemaker is in situ, have 
atropine, adrenaline (epinephrine) and 
isoprenaline available for use in the event of 
pacemaker failure. 



69 




PATIENT ASSESSMENT 



• During surgery, diathermy is usually safe, but 
place the indifferent electrode as far from the 
pacemaker as possible, on the side of 
operation, in 1-2 s bursts more than 10 s apart 
(Simon 1977). 

• Have the anaesthetist ensure that diathermy 
has not inhibited the pacemaker function, by 
checking the pulse (Aitkenhead & Barnett 1989) 

RESPIRATORY DISEASE 



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&?3^^&^^£^$.;&%g?. 



Asthma 

Patients with asthma have bronchospasm, mucus plug- 
ging of airways and air trapping. These result in a mis- 
match of ventilation and perfusion and total effective 
ventilation may be severely impaired. A number oi exoge- 
nous and endogenous stimuli may produce reversible 
airway obstruction. The most active chemical mediators are 
histamine and the leukotrienes. Expiration is prolonged, 
functional residual capacity and residual volumes are 
increased and vital capacity is decreased. Bronchospasm 
may be aggravated by anxiety, by instrumentation of the 
upper airway by foreign material or irritants in the upper 
airway, by pain, and by drugs. The latter include morphine, 
papaveretum, unselective p-adrenergic antagonists, and 
various anaesthetic drugs including tubocurarine and anti- 
cholinesterases. In taking the clinical history, pay special 
attention to factors which precipitate an attack, and review 
the patient's normal drug therapy. If possible, arrange the 
riming of surgery to coincide with a period of remission of 
symptoms. Continue the patient's normal bronchodilator 
therapy up until the time of surgery, and consider ordering 
preoperative chest physiotherapy. Allay preoperative 
anxiety, and prescribe suitable premedication - diazepam, 
pethidine, promethazine and atropine are free from bron- 
chospastic activity. If the patient is taking steroid therapy, 
you may need to give additional doses during the peri- 
operative period (see Concurrent drug therapy, p. 80). In 
the postoperative period, pay careful attention to pain man- 
agement and give nebulized or intravenous bronchodila- 
tors if necessary. In appropriate cases consider using local 
anaesthetic techniques in severe asthmatics. Postoperative 
analgesia can be achieved with, if necessary, epidural 
blocks. 



Indications for intermittent positive 
pressure ventilation in asthmatics 

• If the patient is distressed and exhausted. 

• In the presence of systemic arterial 
hypotension or significant disturbance of 
cardiac rhythm. 




• If the arterial oxygen tension is less than 
6.7 kPa or arterial carbon dioxide tension is 
greater than 6.7 kPa, associated with an 
increasing metabolic acidosis in the face of 
maximum medical therapy. 

Chronic bronchitis and emphysema 

1. Patients who have a cough with sputum production 
on most days for 3 months of the year for at least 2 years 
have chronic bronchitis. They are often smokers (see 
below), and have irritable airways leading to coughing 
and some degree of reversible airways obstruction in 
response to minimal stimulation. 

2. Patients with destruction of alveoli distal to the ter- 
minal bronchioles and loss of pulmonary elastic tissue 
have emphysema. They experience airway closure with 
air trapping and, therefore, inefficient gaseous exchange. 

3. Chronic bronchitis and emphysema commonly 
coexist in the same patient. Many of the considerations in 
the perioperative period that apply to the asthmatic 
patient also apply to patients with chronic bronchitis and 
emphysema; there are, however, some additional points 
to note. These diseases are usually slowly progressive and 
may eventually result in a respiratory reserve which is so 
low that the patient is immobile and dyspnoeic at rest, 
and even speaking and eating may be difficult. Arrange 
elective surgery during the months in which symptoms 
are least noticeable - usually during the summer. Make 
every effort to persuade smokers to quit their habit. If the 
patient requires major surgery, and if the disease is severe, 
consider performing elective tracheostomy and arranging 
postoperative ventilation. These will facilitate the clearing 
of secretions, and thus gaseous exchange, during the post- 
operative period when diaphragmatic splinting and pain 
or respiratory depression may cause acute respiratory 
insufficiency. 

4. Smokers have about six times the incidence of post- 
operative respiratory complications compared with non- 
smokers. Cigarette smoking has wide-ranging effects on 
the cardiorespiratory and immune systems and on 
haemostasis (Jones 1985). They may have arterial carbon 
monoxide concentrations in excess of 5%; the resultant car- 
boxyhaemoglobin decreases the amount of haemoglobin 
available for combination with oxygen, and inhibits the 
ability of haemoglobin to give up oxygen (i.e. the oxygen 
dissociation curve is shifted to the left). Carbon monoxide 
also has a negative inotropic effect. Nicotine increases 
heart rate and systemic arterial blood pressure. Thus, 
carbon monoxide decreases oxygen supply, while nicotine 
increases oxygen demand, and this is of particular signi- 
ficance in patients with ischaemic heart disease. It is 
especially important that these patients stop smoking for 
12-24 h before surgery; this results in a significant 



70 



INFLUENCE OF COEXISTING DISEASE 



6 



improvement in cardiovascular function (the elimination 
half-lives of carbon monoxide and nicotine are a few 
hours). 

However, the respiratory effect of smoking, especially 
mucus hypersecretion, impairment of tracheobronchial 
clearance and small airway narrowing take at least 
6 weeks before there is any improvement in function after 
smoking cessation. Similarly, the effects of smoking on 
immune function (smokers are more susceptible to post- 
operative infections) require at least 6 weeks before 
improvement occurs. Many smokers complain that they 
find it difficult to clear their mucus if they stop smoking, 
and use this as an excuse not to stop smoking before 
surgery; there may be some substance to this claim, but it 
does not outweigh the benefits of stopping. Emphasize the 
risks of smoking to smokers, and encourage them to stop 
smoking for as long as possible before elective surgery. 



I I Key points 

• Arrange elective surgery on patients with 
chronic bronchitis and emphysema at times of 
the year when symptoms are minimal. 

• In an emergency encourage smokers to stop 
smoking for 12-24 h preoperative ly, especially 
if they also have ischaemic heart disease. 

• Before elective surgery encourage smokers to 
stop for as long as possible before operation. 



E N DOCRI N E D YSFU NCTION 

Thyroid gland 

Excluding diabetes, disorders involving the thyroid gland 
account for about 80% of endocrine disease. There are two 
practical issues for you and the anaesthetist: 

1 . Firstly, there are problems related to the local effects 
of a mass in the neck. These include airway problems and 
the potential for difficult tracheal intubation. 

2. Secondly, there are problems associated with the 
generalized effects of an excess or deficiency of 
hormone. Before surgery, prepare and render euthyroid 
patients with hyperthyroidism, to avoid problems. 
Propylthiouracil (average daily dose 300 mg) inhibits 
hormone synthesis and blocks the peripheral conversion 
of thyroxine to tri-iodothyronine. As a generalization, 
the larger the gland the longer it takes to achieve the 
euthyroid state. The vascularity of the gland can be con- 
siderably decreased by 7 days treatment with potassium 
iodide solution. Propranolol is an alternative treatment 
to thiouracil: 60-120 mg daily for 2 weeks may be the 



only treatment required, and is now routinely used at 
many centres. 

3. Avoid, if possible, an emergency operation in a 
poorly or non-prepared patient because it carries signifi- 
cant risk. Cardiovascular complications are potentially 
life-threatening so consider giving intravenous esmolol 
before induction of anaesthesia (using increments every 
5 min to decrease the resting heart rate by 10 beats per 
minute). Disturbances of cardiac rhythm, hypoxia and 
hyperthermia may all occur. If appropriate, choose a local 
anaesthetic technique. 

4. Hypothyroidism is not uncommon, especially in 
elderly patients. Cardiac output is low and blood loss is 
poorly tolerated; however, you must give blood transfu- 
sion with caution to avoid overloading the circulation. It 
has been said that in hypothyroidism the respiratory 
centre is less responsive to hypoxia and hypercarbia, so 
that it may be necessary to ventilate patients electively in 
the postoperative period. These patients are especially 
sensitive to opioid analgesics so use them with caution in 
the perioperative period. Monitor the patient's tempera- 
ture and prevent hypothermia, as this will aggravate the 
circulatory and respiratory depression. 




Key point 



• Beware the potential complications of missing, 
and therefore failing to anticipate, 
complications of hyperthyroidism and 
hypothyroidism. 

Pituitary gland 

1. In hypopituitarism, the varying involvement of the 
several hormones which the anterior pituitary produces 
leads to a variety of clinical presentations: amenorrhoea 
in females and impotence in males are common present- 
ing features. If hypopituitarism is unrecognized, there is 
a greatly increased perioperative risk of hypoglycaemia, 
hypothermia, water intoxication and respiratory failure. If 
the diagnosis is known, planned substitution therapy is 
indicated before surgery. Oral hydrocortisone (15 mg 
twice daily) is administered. This is increased during the 
operative period; thyroxine is also given and the dose 
slowly increased to about 0.15 mg daily and the plasma 
thyroxine level is measured. 

2. Acromegaly is caused by excessive production 
of pituitary growth hormone. This results in overgrowth 
of bone, leading to an enlarged jaw and kyphoscoliosis, 
as well as connective tissue and viscera. There is 
cardiomegaly, early atherosclerosis and systemic arterial 
hypertension, and diabetes mellitus is common. 



71 



61 



PATIENT ASSESSMENT 



Management should include consideration of all associated 
conditions and the anaesthetist will carefully assess the 
patient as tracheal intubation may be difficult. 

3. Diabetes insipidus (Latin in = not + sapere = to taste; 
hence tasteless as opposed to diabetes mellitus = honeyed) 
is the result of deficiency of antidiuretic hormone. A water 
deprivation test is used to differentiate diabetes insipidus 
from compulsive water drinking, and measurements are 
made of urine and plasma osmolality. When the plasma 
osmolality reaches about 295 mOsmol kg" 1 normal patients 
will concentrate their urine, but patients with diabetes 
insipidus cannot do so. If the syndrome is differentiated 
from compulsive water drinking, the operative manage- 
ment of these patients is usually uncomplicated. The 
patient should receive a bolus of 100 milliunits of vaso- 
pressin intravenously before surgery and during the oper- 
ation 100 milliunit h _1 are administered by continuous 
infusion. Isotonic solutions, such as 0.9% sodium chloride, 
may then be administered with minimal risk of water 
depletion or hypernatraemia. Plasma osmolality should 
be monitored perioperatively (the normal range is 
285-285 mOsmol kg" 1 ). 

Adrenal gland 

Adrenocorticol insufficiency is known as Addison's 
disease. It may present in acute and chronic forms and may 
be due to disease of the gland itself or to disorders of the 
anterior pituitary or hypothalamus. A patient with adreno- 
cortical insufficiency undergoing surgery presents a major 
problem. The cardiovascular status of the patient and the 
blood glucose and electrolytes must be measured. The 
patient is prepared by infusing isotonic sodium chloride 
and glucose solutions in order to correct hypernatraemia 
and hypoglycaemia. The day before surgery, an intramus- 
cular injection of 40 mg methylprednisolone is adminis- 
tered. Before induction of anaesthesia a further 100 mg 
hydrocortisone is administered, and for major surgery an 
infusion of hydrocortisone should be given during the 
operation. Hydrocortisone has approximately equal gluco- 
corticoid and mineralocorticoid effects. Postoperatively, the 
dose of hydrocortisone is decreased from 100 mg twice 
daily to a replacement dose of about 50 mg daily 

Adrenocortical hyperfunction is commonly iatrogenic. 
Whatever the aetiology, these patients will have glucose 
intolerance manifest as hyperglycaemia or frank diabetes 
mellitus, systemic arterial hypertension (possibly associ- 
ated with heart failure) and electrolyte disturbances, 
especially hypokalemia and hypernatraemia. Protein 
breakdown leads to muscle weakness and osteoporosis. 
Muscle weakness will be aggravated by obesity, and 
respiratory function should be carefully assessed before 
surgery, as well as postoperatively. Osteoporosis may lead 
to vertebral compression fractures and patients should be 



positioned with great care during surgery. Prolonged 
immobilization after surgery will lead to further de- 
mineralization of bone, and hypercalcaemia may lead to 
the formation of renal calculi. Vitamin D therapy may 
therefore be needed in the postoperative period. 

Aldosteronism may be primary (an adrenocortical 
adenoma - Conn's syndrome), or secondary, in which the 
condition is associated with an increase of plasma renin 
secretion (e.g. the nephrotic syndrome and cardiac 
failure). Patients will have hypokalemia and hyperna- 
traemia, which may be associated with systemic arterial 
hypertension. If the diagnosis is made before surgery, the 
administration of spironolactone (up to 300 mg daily) will 
reverse hypertension and hypokalemia. 

Phaeochromocytoma 

These catecholamine-secreting tumours may produce 
sustained or intermittent arterial hypertension. During 
surgery, arterial hypertension and disturbances of cardiac 
rhythm are common, due to the release of adrenaline 
(epinephrine) and noradrenaline (norepinephrine) into 
the circulation. Prolonged secretion of these produces not 
only arterial hypertension but also a contracted blood 
volume; a- and {3-adrenergic blockade will help to reverse 
both these effects. 



Preoperative a-adrenergic blockade 
must not be complete because: 

• It may cause preoperative postural syncope. 

• It may cause difficulties in controlling the 
profound hypotension that sometimes occurs 
after tumour removal. 

• A rise in systemic blood pressure on tumour 
palpation is a useful sign in searching for small 
tumours or metastases. 

Phenoxybenzamine is the agent usually used to induce 
partial a-adrenergic blockade. Careful preoperative 
preparation using a- and ^-adrenergic blockade, as well 
as the introduction of anaesthetic techniques that promote 
cardiovascular stability, have greatly decreased the 
mortality of patients undergoing surgery for removal of a 
phaeochromocytoma, from 30-45% in the early 1950s to 
less than 5% recently. 

Pancreas 

Diabetes mellitus 

Diabetes mellitus is a syndrome characterized by hyper- 
glycaemia due to insulin deficiency, impaired insulin 
action or a combination of both. It may be primary (most 




72 



INFLUENCE OF COEXISTING DISEASE 



6 



cases) or secondary diabetes associated with other 
medical problems, such as pancreatitis or steroid treat- 
ment. Primary diabetes mellitus is subdivided into type 1 
diabetes, characterized by absolute insulin deficiency 
(formerly insulin-dependent diabetes mellitus, IDDM) 
and type 2 characterized by insulin resistance and relative 
insulin deficiency (formerly non-insulin-dependent dia- 
betes mellitus, NIDDM). Type 1, which is due to auto- 
immune destruction of pancreatic islet [3 cells, is treated 
with insulin, whereas type 2 diabetes (whose pathogenesis 
is less well understood) may be managed by diet and oral 
agents, although many patients will eventually require 
insulin for optimal management. Most insulin now used is 
bioengineered human sequence insulin. Recently the first 
two artificial insulin analogues, lispro and insulin aspart, 
have been introduced to clinical practice. These have been 
developed by amino acid substitution in the insulin 
sequence in order to create an insulin which is absorbed 
more rapidly after subcutaneous administration, giving a 
faster onset and shorter duration of action. 

Sulphonylureas and metformin remain the main oral 
hypoglycaemic drugs used in the UK and are safe and 
effective. Two other types of oral agent have recently 
become available for the treatment of type 2 diabetes. 
Acarbose reduces the breakdown of complex carbohy- 
drates in the gut and reduces postprandial blood glucose 
levels; however, many patients experience excess flatu- 
lence, which limits its acceptability. The thiazolinediones 
are a new group of drugs that improve insulin sensitivity. 
Troglitazone was withdrawn after reports of severe 
hepatic toxicity but two further drugs, rosiglitazone and 
pioglitazone, have since been introduced. These appear to 
be effective when used in combination with either a 
sulphonylurea or metformin. 

The chronic complications of diabetes include large 
vessel disease, microvascular disease, coronary heart 



disease and neuropathy. Despite advances in manage- 
ment, diabetes is the single greatest cause of end-stage 
renal failure requiring replacement therapy. In addition to 
coronary heart disease there is a high incidence of asymp- 
tomatic myocardial ischaemia. Clinically significant silent 
coronary artery disease has been found in 20% of middle- 
aged men with type 2 diabetes screened by exercise 
testing. The prognosis of myocardial infarction is con- 
siderably worse in diabetic patients, with higher early and 
late mortality and a greater incidence of left ventricular 
failure after infarction. Abnormalities of peripheral or 
autonomic nerve function can be found in most patients 
with diabetes of long duration. The most common is a 
classical symmetrical sensory neuropathy which affects 
the feet and legs and can predispose the patient to the risks 
of pressure ulceration. Autonomic dysfunction is relatively 
rare and symptoms usually relate to postural hypotension. 
Before surgery, the cardiovascular status of the patient 
should be carefully reviewed and the blood pressure taken 
both supine and erect to test for the possibility of auto- 
nomic neuropathy. An association between sleep apnoea 
and autonomic neuropathy has been documented and res- 
piratory arrests have been observed following surgery and 
the use of sedative drugs. Patients with symptomatic auto- 
nomic neuropathy should therefore be considered to be 
at increased risk following anaesthesia, and appropriate 
steps taken to monitor respiratory function. 

Table 6.2 summarizes the regimens suitable for minor 
and more major surgery in diabetics patients who are 
either controlled by diet alone, by oral hypoglycaemic 
agents, or with insulin. 

Chlorpropamide is a sulphonylurea with a very long 
duration of action, and hypoglycaemia is a particular 
concern in patients taking this agent; it should be stopped 
48 h before planned surgery and the blood sugar measured 
regularly after the patient becomes nil by mouth. 



Table 6.2 Severity of diabetes 



Controlled by diet 



Controlled by oral agents 



Controlled by insulin 



Type of surgery 



Minor 



No specific precautions 



Omit medication on morning of operation 
and start when eating normally 
postoperatively 



Intermediate/major 



Measure blood glucose 4 hourly: if 
>12 mmol ! ! start glucose-potassium- 
insuiin sliding scale regimen 

Omit medication and monitor blood 
glucose 1-2 hourly; if >12 mmol I" 1 
start glucose-potassium-insulin 
sliding scale regimen 



Unless very minor procedure (omit insulin when nil by mouth) give glucose- 
potassium-insulin sliding scale regimen during surgery and until eating normally 
postoperatively 



73 




PATIENT ASSESSMENT 



Patients taking long-acting insulin preparations should 
be converted to Actrapid insulin, and surgery should be 
scheduled for the early morning if possible. A number of 
regimens for blood sugar control have been described, 
but the following is easy to use. 

Infuse 10% glucose 500 ml + 10 mmol potassium chlor- 
ide (KC1) at 100 ml h~ l . Prepare a 50 ml syringe contain- 
ing 50 units of Actrapid (short-acting) insulin in 50 ml 
normal saline (= 1 unit ml -1 ) and connect via a 3-way tap 
to a glucose infusion. Adjust the rate of the syringe driver 
according to the following sliding scale: 



Blood glucose 
<5 
5-7 


(mmol 1" 


] ) 


Rate of syringe driver (ml h ! ) 

Switch off 

1 


7-10 
10-20 
>20 






2 
3 
4 



If two successive blood glucose values are > 20 mmol 1~\ 
leave instructions to consult the duty doctor. 

The blood sugar is measured at least 2-hourly during 
surgery and the amount of insulin adjusted to maintain 
the blood sugar between 6 and 12 mmol H. Following 
surgery, blood sugar and plasma potassium are measured 
at least 4-hourly. Sepsis and high dose corticosteroid treat- 
ment markedly increase insulin requirements. 

Postoperatively, as soon as the patient starts eating, 
those who are normally treated with oral hypogly- 
caemics may need subcutaneous insulin for a few days 
before oral therapy is recommenced. Patients normally 
treated with insulin can be converted to Actrapid insulin 
to a total equal to the normal preoperative dose. After 
3 days the original regimen can usually be restarted (i.e. 
using long-acting insulins). In the perioperative period 
lactate-containing fluids (e.g. Hartmann's solution) 
should be avoided in diabetics. If oral feeding has not 
started within 72 h of surgery, consideration should be 
given to the institution of parenteral nutrition. 

Obesity 

Life expectancy is decreased by obesity, and operative 
morbidity and mortality increase with increasing weight. 
In moderate obesity, the individual presenting for surgery 
should be instructed to decrease weight and be given 
dietary advice appropriate to the patient's social and eco- 
nomic circumstances. They should also be examined care- 
fully for the presence of conditions with which obesity is 
commonly associated; these include diabetes mellitus and 
systemic arterial hypertension. Patients who are double 
or more their ideal weight are usually termed 'morbidly 
obese'. These patients present a number of problems to 
both surgeon and anaesthetist. Their preoperative cardio- 
respiratory status should be assessed carefully and, as 



these patients are at an increased risk of inhalation of 
gastric contents, all should receive appropriate antacid 
therapy before surgery. Obesity is one of a number of con- 
ditions that will lead to an increase in postoperative deep 
vein thrombosis and associated thromboembolic phe- 
nomena; obese patients should receive appropriate pre- 
operative prophylaxis for this. Transport and positioning 
of morbidly obese patients may cause difficulties, and 
occasionally two standard operating tables used side by 
side may be needed. Intravenous access may be difficult 
and non-invasive methods of monitoring arterial blood 
pressure may be inaccurate; therefore, an intra-arterial 
line is indicated for all but the most minor procedures. 
This will also enable arterial blood gases to be monitored 
in the intraoperative and postoperative periods. Patients 
may need continued ventilatory support after surgery. 



BLOOD DISORDERS 



*J0k£-£^&5-^^^ 






Primary blood disorders produce a wide range of clinical 
manifestations, which may affect any organ in the body. 
Conversely, there are nearly always some changes in the 
blood accompanying general medical and surgical dis- 
orders. Thus, haematological investigations form an 
important part of the assessment and subsequent moni- 
toring of most disease processes. 

Anaemia 

This is defined clinically as a reduction in haemoglobin 
level below the normal range for the individual's age and 
sex. It becomes clinically apparent when the oxygen 
demand of the tissues cannot be met without the use of 
compensatory mechanisms. The level of haemoglobin at 
which elective surgery should be postponed has been 
under review and many guidelines have been revised 
downwards. This is due to concern over the dangers of 
transmissible agents in blood which may not, as yet, be 
detectable. An acceptable level will depend on factors such 
as whether there is a known cause for the anaemia, the 
nature of surgery planned, and the physical fitness of the 
patient. A haemoglobin concentration of 8-10 g dl -1 may be 
adequate for minor surgery. It is important to realize that 
blood transfusion to raise the haematocrit should be 
carried out at least 48 h before the operative procedure, as 
this period of time will allow full recovery of the stored 
erythrocytes' oxygen-carrying capacity. In order to mini- 
mize the risk of transmitting the human immunodeficiency 
virus (HIV), blood transfusion should be undertaken only 
if the urgency of surgery necessitates this. Tissue oxygena- 
tion appears to be maximal at around a haemoglobin con- 
centration of 11 g dl -1 (tissue oxygenation depends upon 
cardiac output, peripheral vascular resistance, blood 



74 



INFLUENCE OF COEXISTING DISEASE 




6 



viscosity and blood oxygen-carrying capacity). Patients 
with ischaemic heart disease are likely to suffer more from 
the consequences of decreased oxygen-carrying capacity 
from untreated anaemia, and it is especially important to 
treat preoperative anaemia in these patients. 



exclude a hereditary bleeding diathesis (one-third of 
haemophilia patients show no family history). Many sys- 
temic diseases may be complicated by bleeding, as may 
treatment with a number of drugs which can cause bone 
marrow depression leading to thrombocytopenia. 



Haemoglobinopathies 

This term encompasses a range of different genetic con- 
ditions, which can be broadly divided into two groups: 
the structural variants and the thalassaemia syndromes. 
The thalassaemia syndromes are due to the abnormal pro- 
duction of one or more globin chain; there are several 
hundred variants, but they have no implications for 
anaesthetic or surgical practice. The main structural 
mutation with clinical significance is sickle haemoglobin. 
Haemoglobin S is an abnormality in the amino acid 
sequence of the haemoglobin. When a deoxygenated 
haemoglobin molecule becomes distorted, this may lead 
to capillary occlusion and tissue hypoxia. The disease is 
inherited and it may be in the heterozygous or homozy- 
gous form. The former (HbAS) does not usually cause 
problems during surgery as the molecular distortion, 
known as 'sickling', only occurs at very low oxygen satu- 
rations. However, in the homozygous state (HbSS) there 
is a real risk of sickling during surgery and this may cause 
tissue infarction. Screening tests are available for the pres- 
ence of haemoglobin S, and electrophoresis is used to 
determine the exact nature of the abnormality. During 
surgery it is important to avoid low oxygen tensions and 
thus an elevated inspired oxygen concentration is used, 
and the patient is kept warm and well hydrated in order 
to maintain cardiac output and avoid circulatory stasis. 
These patients are prone to dehydration because of renal 
papillary damage and the resultant passage of large 
volumes of dilute urine. If very major surgery is planned, 
where there is the possibility of perioperative hypoxia, for 
example pulmonary surgery, an exchange transfusion 
should be considered in an attempt to reduce the level of 
haemoglobin S to below 25%. Patients with haemoglobin 
C and haemoglobin SC should be managed in a similar 
way to those with haemoglobin SS. 

Bleeding and coagulation disorders 

As a generalization, purpura, epistaxis and prolonged 
bleeding from superficial cuts are suggestive of a platelet 
abnormality, and bleeding into joints or muscle is sug- 
gestive of a coagulation defect. Both forms may be con- 
genital or acquired and it may be possible to differentiate 
these from the patient's history, a recent onset being 
indicative of an acquired disorder. A family history 
should be sought but it must be remembered that the 
absence of other relatives with a positive history does not 



Platelet disorders 

Thrombocytopenia arises from a number of causes: 

• Failure of megakaryocyte maturation 

• Excessive platelet consumption 

• Hypersplenism. 

Bone marrow disorders leading to failure of maturation 
may be due to hypoplasia or infiltration. Increased 
consumption occurs in disseminated intravascular coagu- 
lation, idiopathic thrombocytopenic purpura and certain 
viral infections. Sequestration in an enlarged spleen 
occurs in lymphomas and liver disease. Spontaneous 
bleeding does not usually occur until the platelet count 
has decreased to 30 x 10 9 l -1 . Treatment has to be directed 
at the underlying disease, but thrombocytopenia resulting 
in clinically important bleeding necessitates a platelet 
transfusion. Ideally, the count should be increased to 
100 x 10 9 l" 1 , but transfusing platelets until a clinically 
acceptable effect is attained is often performed. Routine 
major surgery should not be undertaken in the presence 
of an abnormal platelet count until the result is confirmed 
and the cause identified. 



Haemophilia 

Before surgery in patients with haemophilia A or B, the 
concentration of the coagulation factors should be 
increased to a level that will minimize bleeding, and this 
concentration should be maintained until healing has 
occurred. It is important to seek specialist advice in deter- 
mining the dosage of factors required. Cryoprecipitate 
and fresh frozen plasma or factor IX fraction are used to 
manage bleeding episodes, but the patients should be 
tested for antibodies to the products. If these are present, 
only life-saving operations should be contemplated. If 
cryoprecipitate or freeze-dried factor IX concentrate are 
administered, complications, including viral hepatitis 
and possibly prior transmission, may occur. Recombinant 
(genetically engineered) factor VIII and IX are now avail- 
able and are the treatment of choice. 



RENAL DISEASE 

Chronic renal failure 

This is said to be present when chronic renal impairment, 
from whatever cause, results in abnormalities of plasma 



75 




PATIENT ASSESSMENT 



biochemistry. Usually, this happens when the glomerular 
nitration rate (GFR) has fallen to less than 30 ml min 1 . Fluid 
balance is precarious in these patients; they may have a 
very limited ability to excrete water and /or sodium. 
Management before surgery depends on the severity of the 
renal failure. Moreover, in a situation of renal insufficiency, 
anaesthesia and surgery may precipitate acute renal failure. 
Patients in late and terminal degrees of chronic renal failure 
(GFR < 10 ml min -1 ) may already have commenced on 
dialysis. If not, dialysis should be performed before surgery 
if at all possible. Dialysis does not reverse all the adverse 
effects of chronic renal failure; for example, systemic 
arterial hypertension and pericarditis may still be present. 
In addition, patients who are dialysed very soon before 
surgery may have cardiovascular lability during anaes- 
thesia and surgery because they may have a relatively 
contracted blood volume. These patients are also vulner- 
able to infection, anaemia, blood coagulation defects, 
electrolyte disturbances and psychological problems. 
Systemic hypertension is a constant feature of chronic renal 
failure and arteriovenous shunts may cause a hyper- 
dynamic circulation with a low systemic vascular resist- 
ance, predisposing the patient to myocardial ischaernia. 
These patients may depend on an increased minute venti- 
lation to maintain respiratory compensation for their 
metabolic acidosis, and respiratory compromise postoper- 
atively may exacerbate their poor metabolic condition. It is 
important to define the degree of renal failure present 
before surgery, and review the dialysis regimen. Blood bio- 
chemistry, coagulation and haemoglobin must be checked. 
Care should be taken when prescribing potentially nephro- 
toxic drugs and consideration given to pathways of drug 
elimination (see Concurrent drug therapy, p. 80). A careful 
search should be made for the presence of occult infection 
and all patients should have a preoperative chest X-ray. The 
susceptibility to infection is compounded in transplant 
patients by the administration of immunosuppressive 
drugs, and prophylactic antibiotics may be necessary pre- 
operatively and postoperatively. Chest physiotherapy may 
also be needed. Procedures such as arterial or central 
venous cannulation must be carried out under strict aseptic 
conditions. Before, during and after surgery, fluid and 
electrolyte balance must be very carefully monitored. 



Nephrotic syndrome 

The clinical association of heavy proteinuria, hypoalbu- 
minaemia and generalized oedema is usually referred to 
as the "nephrotic syndrome'. The hypoalbuminaemia is 
the result of urinary albumin loss and the syndrome 
becomes apparent if more than 5 g of protein are lost per 
day, and the plasma albumin concentration falls to less 
than 30 g 1 _1 . It is important to define the underlying cause 
of the nephrotic syndrome. Before surgery, the plasma 
protein and electrolyte levels must be estimated and cor- 
rected as indicated. An albumin infusion (up to 50 g) will 
restore circulating blood volume and may in itself initiate 
a diuresis. An alteration in plasma proteins will cause 
changes in drug effect due to an alteration in drug 
binding. The anaesthetist may use more conservative 
doses of some drugs. Central venous cannulation is 
advisable for all but the most minor surgery. 



U^RJCHSEASE^^ 

Chronic liver disease is a continuum of pathophysiology, 
from the patient with an abnormality of liver function 
tests with no adverse physiological consequences to the 
patient with severe end-stage liver disease who repre- 
sents an extreme surgical risk. Patients with liver disease 
were classified for general surgical risk by Child and 
Turcotte in 1964 (Table 6.3) and this is still valid today. The 
only important addition is the observation that pro- 
thrombin time is the most significant preoperative pre- 
dictor of mortality in patients undergoing surgery for 
variceal bleeding. 

A patient with moderate to severe cirrhosis has numer- 
ous pathophysiological changes affecting various organ 
systems and should always be managed by experienced 
personnel, both anaesthetic and surgical. Child and 
Turcotte grade C (even in the absence of coma) carries a 
very high perioperative mortality, even for elective 
surgery. Although it is impossible to review the patho- 
physiology of end-stage liver disease in this text, concise 
reviews are available (see Further reading). 



Tat 

L 1 l^B - BIM 



Table 6.3 Child's classification for hepatic functional reserve 



Sefum bilirubin <mg dl 1 ) 
Serum albumin (g dl *) 
Ascites controlled 
Neurological disorder 
Nutrition 



A (Minimal) 



B (Moderate) 



C (Advanced) 



<2.0 


2.0-30 


>3.5 


3.0-3.5 


None 


Easily controlled 


None 


Minimal 


Excellent 


Good 



>3.D 

<3.0 

Poorly controlled 

Advanced 'coma' 

Poor 'wasting' 



76 



INFLUENCE OF COEXISTING DISEASE 



6 




Organ systems affected by cirrhosis 

• Cardiovascular system 

• Lungs 

• Kidneys 

• Brain 

• Gut 

• Coagulation 

• Immunocompetence. 

Prior to surgery the patient's condition must be opti- 
mized. All patients should be screened routinely for 
hepatitis B viral infection. They must be kept adequately 
hydrated to preserve renal function (although paradoxi- 
cally they may be on diuretics to control ascites). 
Respiratory function may be poor due to basal atelectasis 
and/or intra pulmonary shunts. Ascitic drainage may 
improve the situation. If renal function deteriorates in the 
face of adequate filling, a low dose dopamine infusion 
should be started. These patients are prone to sepsis and 
spontaneous bacterial peritonitis so body fluids should be 
cultured and strict aseptic precautions adhered to. Finally 
their coagulation will be deranged. In patients with 
predominantly cholestatic disease this may improve with 
vitamin K injection. Patients with hepatocellular disease 
are likely to have a combination of clotting factor defi- 
ciencies, chronic fibrinolysis and a low platelet count. The 
situation is best assessed and treated using a dynamic 
measure of clotting - thromboelastography (Mallett & 
Cox 1992). 

These patients often lose large amounts of blood at 
operation due to a combination of surgical (varices) and 
medical (coagulopathy) causes; in addition they have a 
very high cardiac output and low systemic vascular re- 
sistance circulation, which is often unresponsive to nor- 
adrenaline (norepinephrine). It cannot be overemphasized 
that these are very high risk patients to operate on. 



NEUROLOGICAL DISEASE 

Multiple sclerosis 

The aetiology of this disease of temperate climates 
has become clearer in recent years. It appears that in 
genetically susceptible individuals activated T cells and 
macrophages responding to environmental triggers inter- 
act with type 1 astrocytes, causing a disruption of the 
blood-brain barrier and a leak of immune mediators into 
the nervous system. This causes demyelination. Patients 
may present for incidental surgery or surgery associated 
with alleviation of the complications, e.g. implantation of 
extradural stimulating electrodes. In order to decrease 



perioperative morbidity, careful preoperative examin- 
ation is needed. Patients may have a labile autonomic 
nervous system associated with postural hypotension. 
Muscle atrophy may lead to significant kyphoscoliosis 
and this may result in a restrictive form of pulmonary 
disease. Urinary tract infections commonly occur, but the 
patient must be carefully examined to identify other infec- 
tive foci. An elevation in temperature is the one definite 
factor known to precipitate an exacerbation of the disease, 
so all but the most urgent surgery should be postponed 
until the patient is free from infection. Epilepsy is not 
uncommon in patients with multiple sclerosis. 

Epilepsy 

This term refers to a variety of types of recurrent seizure 
produced by paroxysmal neuronal discharge from 
various parts of the brain. Seizures may have a cerebral 
cause (e.g. tumour) or be due to a systemic disorder (e.g. 
uraemia or hypercalcaemia). The symptomatology is 
variable and seizures may cause total loss of conscious- 
ness or only a minimal alteration in awareness. The 
disease occurs in all age groups, with an incidence of 
about 1%. About 75% of patients have no recognizable 
underlying cause. If there is an underlying cause, the 
surgical management should take this into account. 
Otherwise management is usually uncomplicated; it is 
important that the patient's usual anticonvulsant medi- 
cation be continued until the time of surgery and 
restarted as soon as possible postoperatively, if necessary 
using parenteral drug administration (see Concurrent 
drug therapy, p. 80). Anticonvulsant drugs such as pheny- 
toin lead to induction of liver microsomal enzymes, and 
thus the patient's response to a variety of drugs that may 
be given during the perioperative period may be altered. 

Myasthenia gravis 

This is an autoimmune disease of the neuromuscular junc- 
tion, involving the postjunctional acetylcholine receptors. 
Specific autoantibodies have been identified and micro- 
scopic changes in the membrane demonstrated. The disease 
is characterized by muscle weakness of fluctuating sever- 
ity, most commonly affecting the ocular muscles. Facial and 
pharyngeal muscle weakness also occurs, leading to 
dysarthria and dysphagia. It can occur at any age in life but 
is most frequently seen in the fourth decade. There is an 
association with thymic enlargement and thymomas, both 
benign and malignant. About two-thirds of patients 
without a thymic tumour will improve after thymectomy, 
although the outlook is less good for patients with tumour, 
whether this is excised or not. Inhibitors of the enzyme 
cholinesterase (e.g. edrophonium, neostigmine and pyrido- 
stigmine) are used in the treatment of myasthenia gravis, as 



77 




PATIENT ASSESSMENT 



are drugs which suppress the immunological response and 
eliminate circulating antibodies. The latter have now 
become the first line of treatment, and 90% of patients will 
benefit from the use of azathioprine or steroids. 

Patients may present for thymectomy or incidental 
surgery, and the surgical management depends upon the 
nature of the operation and severity of the disease. As 
usual, the patient's normal medication must be continued 
up until the time of surgery. If the disease is severe, or 
major thoracic or upper abdominal surgery is planned, 
elective postoperative ventilation is advisable and, 
occasionally, a tracheostomy will be required, but this 
should only be needed if ventilation is prolonged and 
excess secretions are a problem. Respiratory failure in 
myasthenic patients may be secondary to either a myas- 
thenic or a cholinergic crisis. Assisted ventilation should 
be instituted and anticholinesterase drug therapy 
stopped, and then cautiously reintroduced after testing 
with small doses of intravenous edrophonium (2-5 mg). 
Elective postoperative ventilation may also be advisable 
for lesser forms of surgery, including thymectomy, if the 
patient's preoperative vital capacity is less than 2 litres or 
there is a history of intercurrent respiratory problems. 
Following surgery, the requirements for anticholinester- 
ase and other drug therapy may be changed and it is 
important to titrate drug dosage against clinical response. 
It should be remembered that overtreatment can cause 
weakness, just as can undertreatment. Postoperatively, 
the adequacy of ventilation can best be assessed by 
repeated blood gas measurement and, therefore, before 
surgery there are advantages to the placement of an 
intraarterial line. This will also facilitate accurate cardio- 
vascular monitoring during surgery. 



ALCOHOLISM AND DRUG ABUSE 

Addiction is characterized by psychological dependence, 
change in tolerance and a specific withdrawal syndrome. 
Drugs, including alcohol, are used by susceptible indi- 
viduals in order to obtain oblivion or excitement. 
Aetiological factors include psychiatric illness, personal- 
ity disorders and social pressures. It should be remem- 
bered that many addicts abuse more than one drug. In 
general, it is advisable to maintain normal doses of the 
addict's usual drug in the immediate pre- and postoper- 
ative periods. The perioperative period is not the best 
time to attempt to wean a patient from an addiction and 
it may only serve to precipitate an acute withdrawal reac- 
tion. Addicts may not admit to their addiction and the 
first sign that there is a problem may be the appearance 
of a withdrawal syndrome. 

Specific organ damage may result from drug addic- 
tion. Alcohol gives rise to liver damage and can progress 



to cirrhosis, and thus a change in protein synthesis, 
altered glycogen storage and susceptibility to hypogly- 
caemia. In addition, alcoholics are prone to bleeding, 
especially from the gastrointestinal tract, and there may 
be hypomagnesaemia. They may also have cardiomy- 
opathy, and careful assessment of cardiovascular status 
is necessary in the alcoholic patient. Solvent or glue snif- 
fers may have hepatic or renal damage and bone marrow 
suppression. Addicts to opioids will often have used con- 
taminated needles and syringes, and there is a high inci- 
dence of hepatitis and liver damage and also of infection 
with the HIV virus (see below). If sudden hypotension 
occurs in the operative or postoperative period in a nar- 
cotic addict, and if other obvious causes are excluded, 
this may respond to the administration of intravenous 
morphine. 



PSYCHIATRIC DISEASE 









Anxiety and concern are a normal reaction of patients to 
forthcoming surgery and anaesthesia. A significant pro- 
portion of the population will suffer from an affective dis- 
order at some time in their lives. A depressive illness is 
the commonest affective disorder and treatment may 
involve psychotherapy, antidepressant drug therapy or, if 
the disorder is severe, electroconvulsive therapy. It is 
important that the patient's preoperative drug therapy is 
continued, although both tricyclic antidepressants and 
monoaminoxidase inhibitors significantly interact with 
the drugs used during anaesthesia (see Concurrent drug 
therapy, p. 80). Before surgery both a psychiatrist and an 
anaesthetist should be consulted. Many anaesthetists 
would prefer that the drugs be continued up until the 
time of surgery, and their anaesthetic technique modified 
to take account of the potential for drug interactions. It 
should not be forgotten that severe affective disorders are 
accompanied by a very significant mortality rate in terms 
of suicide, and supportive drug therapy should not auto- 
matically be withdrawn before planned surgery unless 
there is a very good reason to do so. The postoperative 
course in patients with a depressive illness may be more 
prolonged and these patients should be treated with 
appropriate forbearance. 



ACQUIRED IMMUNE DEFICIENCY 
SYNDROME (AIDS) 

This is caused by infection with a retrovirus, the human 
immunodeficiency virus (HIV). Acquired immunodefi- 
ciency syndrome is now a worldwide epidemic with an 
estimated 33 x 10 6 persons infected. The recent decline 



78 



INFLUENCE OF COEXISTING DISEASE 



6 



in death rates from HIV in developed countries has been 
due to the expanding use of antiviral drugs; however, 
resistance to the new drugs has developed in as many 
as 20% of patients and, although life expectancy has 
increased, these drugs do not represent a cure. HIV infec- 
tion may also be seen in patients who have received 
infected blood products (e.g. haemophiliacs). The disease 
is not very infectious and is transmitted primarily in 
blood, and there is little evidence to support transmission 
via saliva or airborne transmission. The risk of occupa- 
tionally acquired HIV is low (compared for example to 
hepatitis B) and it is estimated that the risk of develop- 
ing HIV after percutaneous exposure to HIV infected 
blood is 0.3%. The risk after comparable exposure to 
hepatitis B virus (HBV) is greater than 30%, and HCV 
1.9%. Occupational health departments all have their 
regimen of postexposure prophylaxis and should be con- 
tacted immediately in the event of a needlestick injury 
from a high risk patient. 



THE PATIENT WITH A TRANSPLANTED 
ORGAN FOR NON-TRANSPLANT 
SURGERY 









The era of transplant surgery dawned in the 1950s with 
the first kidney transplant (see Ch. 25). It is therefore not 
uncommon now to be faced with a patient with a trans- 
planted organ presenting for non-transplant surgery. 

Some aspects of management are common to all 
patients. It is essential to continue with their immuno- 
suppressant regimen but consideration should be given to 
whether they are exhibiting signs of toxicity from the 
medication. These patients are all immunosuppressed. 
Apply strict aseptic precautions. Are they suffering from 
an infectious complication that may be due to an unusual 
pathogen such as a fungus? Have they developed a 
tumour as a consequence of the immunosuppression? The 
incidence of lymphomas is increased in these patients. 
Finally, are they displaying signs of rejection? This may be 
difficult to differentiate from infection in, for example, a 
lung graft. 

Some specific considerations in a cardiac transplant 
recipient are as follows. The heart is denervated; it will be 
preload dependent to achieve an adequate cardiac output. 
There will be a delayed heart rate response (e.g. to 
hypoxia^ which will be generated by catecholamine 
secretion. These patients have accelerated coronary 
atherosclerosis but may not develop angina in response to 
myocardial ischaemia. The heart will have unusual 
responses to vasoactive drugs due to the denervation. 
Finally, arrhythmias and a low cardiac output may be 
signs of rejection. 



SURGERY IN THE ELDERLY 

Although patients over the age of 65 years comprise only 
22% of the surgical caseload/ they are reported to account 
for 79% of perioperative deaths (Buck et al 1987). The 
mortality of surgery in elderly patients is significantly 
higher in those suffering from serious coexisting medical 
conditions. In a study of 100 000 surgical operations/ the 
relative risk of dying within 7 days, comparing patients 
over 80 with those under 60 years, was 3, but the risk 
factor comparing patients having symptomatic medical 
disease with those having none was over 10 (Cohen et al 
1988). Not only do elderly patients have an increased like- 
lihood of coexisting disease, but physiological function in 
general decreases with age. As a generalization, many 
physiological functions (e.g. cardiac output, glomerular 
filtration rate and renal blood flow) decrease by about 1 % 
per annum after the age of 30 years. Respiratory function 
also declines with age (maximum breathing capacity 
decreases from about 100 1 min" 1 at 20 years to 30 1 min 1 
at 80 years). The elderly are also more sensitive to the 
majority of drugs that might be used in the perioperative 
period (e.g. diazepam has a half-life measured in hours 
that is approximately equal to subject age in years). As in 
all other situations where a patient presents for surgery 
with a significant coexisting disease, the morbidity and 
mortality associated with surgery can be reduced to a 
minimum after careful preoperative evaluation and by 
optimizing the patient's condition. 

If the decision is made to operate on an elderly patient 
then that must include a decision to provide appropriate 
postoperative care/ which may include high dependency 
or intensive care support. Hypotension and hypo- 
volemia are common and should be corrected before 
surgery whenever possible. Fluid imbalance can con- 
tribute to serious postoperative morbidity and mortality 
and is more likely in the elderly, who may have renal 
impairment or other comorbidity. Accurate monitoring, 
early recognition and appropriate treatment of fluid 
balance are essential. Non-steroidal anti-inflammatory 
drugs should be prescribed with particular caution in 
elderly patients in the postoperative period. 

Finally, the NCEPOD report Extremes of Age (1999) found 
that, in the elderly, unsuspected gastrointestinal complica- 
tions are commonly found at post mortem to be the cause, 
or contribute to the cause, of death following surgery. 




Key points 

« Fluid management in the elderly is often poor; 
it should be accorded the same status as drug 
prescription. 



79 




PATIENT ASSESSMENT 



Elderly patients have a high incidence of 
coexisting disorders and a high risk of early 
postoperative death. 



surgery, there are a number of drugs whose administra- 
tion or dosage will need to be modified before surgery 
(see Table 6.4 for the more important examples of these). 



CONCURRENT DRUG THERAPY 

It is a general rule that any patients stabilized on long-term 
drug therapy should continue to take their normal medica- 
tion until the time of surgery, and that this should be recom- 
menced as soon as possible after surgery. If the patient is 
unable to take drugs by mouth, appropriate parenteral 
administration is required. This is especially important for 
patients taking drugs such as antiepileptics, antiarrhyth- 
mics or antihypertensives. A thorough knowledge of the 
pharmacokinetic and pharmacodynamic profile of the indi- 
vidual drugs is needed in order that the appropriate doses 
and interval between doses is arrived at for parenteral 
administration. A number of drugs (e.g. propranolol) 
undergo extensive first-pass liver metabolism after oral 
administration, and drugs such as this need much lower 
doses administered parenterally than they do orally. 

Admission to hospital for surgery gives the opportu- 
nity to review the appropriateness of long-term drug 
therapy and dosage; this may be especially important in 
elderly patients as they are more likely to suffer from 
toxic symptoms. The nature of some operations may 
mean that the need for continued drug therapy has to be 
reviewed postoperatively, or the dosage of the drugs may 
need to be altered. An example of this would be a myas- 
thenic patient undergoing thymectomy. Although the 
majority of patients stabilized on long-term therapy 
should continue their normal drugs up until the time of 



Summary 

• If there is a reversible feature to the 
patient's coexisting medical disease, 
elective surgery should be postponed until 
the patient is optimally treated. 

• It may be appropriate to delay even 
emergency surgery until the patient's 
condition is stabilized or improved. 

• A patient presenting for a minor surgical 
procedure may none the less require a 
high degree of anaesthetic expertise. 




References 



ACC /AHA Task Force Report 1996 Guidelines for perioperative 
cardiovascular evaluation for non-cardiac surgery. Journal of 
the American College of Cardiology 27: 910-948 

Buck N, Devlin HB, Lunn JN 1987 The report of a confidential 
enquiry into perioperative deaths. Nuffield Provincial 
Hospitals Trust, London 

Burke M, Callum KG, Gray AJG et al 2001 Changing the way 
we operate. NCEPOD, London 

Callum KG, Gray AJG, Hoile RW 1999 Extremes of age. 
NCEPOD, London 



Table 6,4 Some important drugs, the administration or dosage of which needs to be modified before surgery 



Oral contraceptives 



Anticoagulants 

Agents used in diabetes 

Levodopa 

Monamine oxidase inhibitors 



Steroids 



Maintain for minor or peripheral procedures and institute prophylaxis against 
deep vein thrombosis before surgery. Stop one complete monthly cycle before 
abdominal (especially pelvic) surgery 

Stop oral agents several days before surgery and substitute heparin if continued 
anticoagulant is necessary. The action of heparin can be rapidty reversed 
with protamine 

See section on diabetic management 

Omit dose before surgery 

Significant potential for drug interactions, causing severe physiological 
disturbance, Discuss with psychiatrist and anaesthetist and treat each case on its 
merits 

Supplement with hydrocortisone 100 mg i.v. 30 min before surgery, repeated 
3-hourly during surgery, reducing slowly postoperatively to the patient's 
preoperative dose. Treat similarly if taking large dose regularly any time during 
3 months before surgery 



80 



INFLUENCE OF COEXISTING DISEASE 



6 



Campling EA, Devlin HB, Hoile RW, Lunn JN 1992 The report 

of the national confidential enquiry into perioperative deaths, 

1990. King's Fund Publishing, London 
Campling EA, Devlin HB, Hoile RW, Lunn JN 1993 The report 

of the national confidential enquiry into perioperative deaths, 

1991/1992. King's Fund Publishing, London 
Campling EA, Devlin HB, Hoile RW, Lunn JN 1995 The report 

of the national confidential enquiry into perioperative deaths 

1992/1993. King's Fund Publishing, London 
Campling ER et al 1997 Who operates when? NCEPOD, London 
Child CG III, Turcotte J 1965 Surgery and portal hypertension. 

In: Child CG III (ed) The liver and portal hypertension. 

Saunders, Philadelphia 
Cohen MM, Duncan PG, Tate RB 1988 Does anaesthesia 

contribute to operative mortality? JAMA 260: 2859-2863 
Gallimore SC, Hoile RW, Ingram GS, Sherry KM 1997 The 

report of the national confidential enquiry into perioperative 

deaths 1994/1995. NCEPOD, London 
Jones R M 1985 Smoking before surgery: the case for stopping. 

BMJ 290: 1763-1764 



Mallett SV, Cox D 1992 Thromboelastoplasty. British Journal of 

Anaesthesia 69: 307-313 
Mangano DT, Layug EL, Wallace A et al 1996 Effect of atenolol 

on mortality and cardio-vascular morbidity after non 

cardiac surgery. New England Journal of Medicine 

335: 1713-1720 
Simon A 1977 Perioperative management of the pacemaker 

patient. Anesthesiology 16: 127-131 




Further reading 

Find law D, Doyle E 1997 Congenital heart disease in adults. 
British Journal of Anaesthesia 78: 416-430 

Mclntyre N, Benhamon JP, Bircher J et al 1991 Oxford textbook 
of clinical hepatology. Oxford University Press, Oxford See 
especially section 31: Surgery, anaesthesia and the liver 



81 




Immunity in surgery 

P. L Amlot, C 5. Gricks 




Objectives 

Appreciate the functions and components 
of the immune system. 
Recognize that most disease processes are 
prevented by innate immunity. 
Recognize that specific disease processes 
are prevented by adaptive immunity. 
Understand the implications of immune 
processes in surgery. 



INTRODUCTION 









The immune system evolved to protect the body from infec- 
tion. Innate (inborn) immunity provides common effector 
mechanisms that protect against a wide range of pathogens. 
As pathogens evolved to escape control by the innate 
immune system, co-evolution of adaptive immune mech- 
anisms developed, providing specific and variable recep- 
tors that can recruit effector mechanisms already provided 
by innate immunity that has been evaded by the pathogen. 



mj^l^HMMUNITY 

Innate (Latin natus = to be born) immunity needs no prior 
contact with a pathogen to be activated and there is no 
'learning' phase. The innate immune mechanisms are 
maximally effective the first time a pathogen is met and 
the response does not change with repeated exposure to 
pathogens. Clinically pathogenic organisms are broadly 
defined by their ability to cross epithelial surfaces and to 
evade other innate immune mechanisms; for example, 
mycobacterial cell walls are resistant to acid, and cholera 
has a specific receptor to bind to the gut wall. 



Physical barriers 

A large part of innate immunity is mechanical and 
applies to pathogens that have no selective method of 



crossing intact epithelial surfaces. Damage to skin by pen- 
etrating wounds and burns, or to mucosal surfaces by 
perforation, allow normally non-pathogenic organisms to 
cause disease. Epithelial cells do not function purely as a 
mechanical barrier but they produce intracellular chemi- 
cal messengers known as cytokines and molecules that 
enhance the adaptive immune system's response. These 
physical barriers are reinforced by secretions. 



Secretory system 

Lysozyme in saliva and tears digests peptidoglycan in bac- 
terial cell walls. Bacteria with susceptible cell walls are 
rendered non-pathogenic. Gastric acid inhibits bacterial 
growth and mucus inhibits bacterial motility. 

The complement system consists of many proteins that 
can self-assemble to cause lysis of cells to which they 
are attached. Complement may be activated by two 
pathways: 

• Alternative pathway - initiated directly by xenogeneic 
molecules, such as sugars forming part of microbial cell 
walls 

• Classical pathway - initiated by antibody and requires 
adaptive immunity. 

Complement, C-reactive protein and mannose-binding 
protein can all coat foreign particles, making them more 
easily digestible by phagocytes in a process called 'opson- 
ization.' Opsonization (G opsonein = to prepare food for; 
hence, make more digestible by phagocytes), by comple- 
ment and antibody makes phagocytosis by granulocytes 
1000 fold more efficient. 



Cellular system 

Phagocytes - neutrophils, monocytes or tissue macrophages 
- possess a wide variety of receptors, capable of increasing 
in quantity but not in quality. The receptors recognize 
xenogeneic (Greek xenos = foreign) molecules not present 
on human tissues, such as mannose, for which receptors 
are expressed on macrophages. Other, non-phagocytic 
cells may facilitate the immune response. For example, 



82 



IMMUNITY IN SURGERY 



7 



stimulated mast cells release factors that increase vascular 
permeability, allowing more rapid access of leucocytes to 
sites of infection. Many of the receptors expressed by leu- 
cocytes enable their movement through blood vessels and 
include selectins, adhesion molecules and chemokines. 

Natural killer (NK) lymphocytes are unlike other lym- 
phocytes and lack specific receptors capable of qualitative 
change. NK cells are involved in the surveillance of 
altered cells, particularly against tumours and viruses. 
Activated NK cells are capable of killing nucleated target 
cells, unless they are inhibited. On the membranes of NK 
cells are killer inhibitory receptors (KIRs) which bind to 
self-MHC (major histocompatibility complex) class I 
molecules of target cells, protecting them from being 
killed. Both viruses and tumour cells interfere with, or 
eliminate, MHC class I on the surface of their transformed 
cells. Although this allows the cells to escape surveillance 
by the adaptive immune system, it makes them suscepti- 
ble to NK cells, since KIR now has nothing with which to 
bind and inhibition of killing does not occur. 

Dendritic cells within the epithelium, especially the epi- 
dermis where they are known as Langerhans cells, play 
an important role in carrying antigens from the skin to 
local lymph nodes, where an adaptive immune response 
can be generated. 

The response of the innate system is amplified in an 
integrated manner. For example, complement breakdown 
products are chemotactic (Greek taxis = arrangement; 
power to attract) for neutrophils, encouraging phagocytic 
removal of complement-coated bacteria. 

Deficiencies of innate immunity 

Primary immunodeficiencies affecting the innate system are 
very rare and carry the same consequences as acquired 
or iatrogenic deficiency, which is common. Operative 
surgery is naturally a major violator of epithelial barriers 
and secretions through incisions, intravascular lines, 
catheters, anaesthesia and drug use, including anaesthe- 
sia. Widespread desquamation, as with burns, severely 
compromises innate immunity. There is no known defi- 
ciency of lysozyme, but achlorhydria is associated with 
infection and malignancy. Deficiency of complement 
leads to susceptibility to infection by encapsulated bacte- 
ria or, surprisingly, to autoimmunity (Greek autos = self). 
Low neutrophil counts reflect the status of an important 
component of innate immunity and lead rapidly to severe 
consequences because of the wide range of infectious 
processes that require this final common phagocytic 
pathway. Neutropenia following administration of cyto- 
toxic drugs can lead to severe infection within a few days. 
It is a key feature of deficiencies in innate immunity that 
they lead rapidly to infectious complications because 
most, if not all, infection is ultimately controlled by it. The 



chances of meeting any of a wide range of infectious 
organisms is high and the time to a chance encounter, 
including organisms in our own digestive system, is 
therefore short. 



ADAPTIVE IMMUNITY 

In the adaptive response, exposure to infection leads to 
qualitative changes of specific receptors. The cells that 
bear these receptors compete in a darwinian fashion for 
binding to pathogens. The molecular structure that stimu- 
lates an adaptive, specific receptor is known as an antigen. 
Adaptive immunity has two collaborative branches, 
antibody- and cell-mediated immunity. 



ANTIBODY-MEDIATED IMMUNITY 



±&&m&&&&&^^ 



<- * ,- ■" * - -> * r - .- 



Antibodies belong to a class of proteins known as 
immunoglobulin. In humans, antibody-producing B lym- 
phocytes originate in the bone marrow and the B cell 
receptor is the membrane-bound form of antibody 
secreted into body fluids. Pathogens coated with antibody 
can fix complement by the classical pathway and are 
phagocytosed (Greek phagein = to eat) far more rapidly 
than uncoated pathogens. It is estimated that our B cell 
system can create more than 10 11 unique antibody 
molecules but each B cell can produce antibody of only a 
single specificity. There is not enough DNA to encode all 
the possibilities and the mechanism of shuffling and 
mixing discrete genes coding for immunoglobulin is 
known as gene rearrangement. This occurs randomly and 
allows B cells to create antibodies with diverse specifici- 
ties and includes the possibility of creating antibodies that 
react with "self, which can lead to autoimmunity. 

Antibody-binding region 

Antibody in the B cell membrane acts as a receptor for 
antigen on its surface. The B cell may be stimulated by the 
binding of an antigen to undergo proliferation, become a 
memory B cell or differentiate into a plasma cell. B cell 
stimulation by antigen occurs mainly within lymphoid 
follicles (structures in which B cells aggregate) and gen- 
erates germinal centres, where a process known as somatic 
hypermutation takes place. This occurs in 0.1% of cell divi- 
sions and allows a few B cells to develop antibodies that 
bind to antigen with greater affinity. Normally, within 2 
weeks the affinity of the antibody increases by 10- to 100- 
fold in the mutated B cells and allows them to compete 
successfully against other B cells for antigen, leading to 
their preferential proliferation- a process known as clonal 
expansion. 



83 




PATIENT ASSESSMENT 



Antibodies: structure and synthesis 

One part of the antibody, the variable or V region, binds 
to the antigen. The other part, the constant or C region, 
interacts with the invariable receptors of the innate 
immune system. An antibody is composed of at least two 
heavy and two light chains of immunoglobulin linked 
together so that there is a minimum of two antigen- 
binding sites per molecule (Fig. 7.1). This explains why 
antibodies can cross-link antigens and cause agglutina- 
tion, for example, during the testing for blood group in 
transfusion or in the immobilization of flagellated 
microorganisms. 

The constant domain is the major part of the antibody 
and is so named because it is largely invariable, which 
endows the antibody with different functional properties. 
There are five heavy chain genes giving rise to 
immunoglobulin: IgM, IgD, IgG, IgE and IgA. Immature 
B cells usually express IgM but they can switch the 



Antigen 




Granulocyte 



Macrophage 



Fig, 7.1 Antibody structure and effector relationships. 
VL, variable region of the light chain; VH, variable 
region of the heavy chain; CL r constant region of the 
light chain; CH, constant region of the heavy chain that 
consists of three domains. Note that there are two 
binding sites to the antibody molecule, each binding an 
identical antigen (1 and 2). Granulocytes and 
macrophages bind to antibody molecules via their Fc 
receptors (known as Fc because it is an old term for the 
constant region of the heavy chain of the antibody 
molecule). The complement system interacts with the 
constant region of the heavy chain and leads to lysis of 
cells. 



constant region when stimulated by antigen. The switch 
is influenced by the environment and T helper cells. This 
is called isotype switching. 

IgM is so named because in its secreted form it is a 
microglobulin composed of five immunoglobulin 
molecules bound together. Because of its large size it is 
largely retained within the vascular system, where it is 
effective at complement fixation and in protection against 
blood-borne infections. IgD is a largely membrane-bound 
immunoglobulin of unknown function. IgG is the most 
abundant isotype (Greek isos = equal; of the same type) in 
the blood and tissues. It is small enough to diffuse readily 
in the tissues and contains most of the high affinity anti- 
body. There are several subclasses, each with different 
functional properties. Apart from coating pathogens for 
phagocytosis, they are also able to induce antibody- 
dependent cellular cytotoxicity (ADCC), which may play 
a part in transplantation and tumour immunity Because 
it can cross the placental barrier it provides the fetus with 
antibody protection. IgG and IgA are also provided in 
breast milk. IgA can be transported across mucosal epithe- 
lium, resists gastrointestinal digestion and is the principal 
isotype in respiratory and gastrointestinal secretions. It is 
thought to prevent adherence of microorganisms and 
toxins to receptors and so is sometimes termed 'antiseptic 
paint". IgE is bound to receptors on blood basophils and 
mast cells, in skin, mucosa, connective tissues and along 
blood vessels. Antigen binding causes degranulation of 
mast cells, which release mediators invoking coughing, 
sneezing, vomiting and diarrhoea. IgE protects against 
infestation with worms but causes allergies such as hay 
fever, urticaria, asthma and anaphylaxis. 

Monoclonal antibodies and flow cytometry 

In a normal immune response many B cells produce many 
different types of antibodies - a polyclonal response. A 
single B cell can produce only a single antibody; when a B 
cell proliferates, each daughter cell produces the same anti- 
body - a monoclonal antibody - unless somatic mutation 
occurs during division. Monoclonality is characteristic of B 
cell malignancy and high levels of monoclonal antibody 
are recognized as paraprotein in multiple myeloma. These 
paraproteins can be detected by electrophoresis or 
immunofixation. Kohler and Milstein in 1975 fused a single 
B cell from a mouse spleen to a myeloma cell line, allow- 
ing infinite production of monoclonal antibodies with 
defined antigen specificity. Monoclonal antibodies of 
mouse or rat origin have revolutionized diagnostic pro- 
cesses and have enabled the identification of many cellular 
molecules. As monoclonal antibodies to lymphocyte recep- 
tors and antigens were being generated, a prototype 
fluorescein activated cell sorter (FACS) was being built. 
These flowcytometers are able to detect and count cell- 



84 



IMMUNITY IN SURGERY 



7 



bound fluorochromes, allowing rapid counting of cells 
expressing specific antigens. Furthermore, up to four 
different fluorochromes on the same cell can be detected. 
This has enormously increased the scope for measuring 
minor cell populations within blood and other fluids. FACS 
machines are used to count CD4 and CD8 subsets of 
patients with human immunodeficiency virus (HIV), 
identify leukaemic, lymphomatous or other malignant cells 
and assess the activation status of lymphoid cells, simply 
by counting fluorochrome labels bound to monoclonal 
antibodies of the appropriate specificity. 

Deficiency of antibody-mediated immunity 
and bacterial infections 

Antibody deficiency predisposes predominantly to bacte- 
rial infection. Immunodeficiency of B cells is relatively 
uncommon but should be excluded in patients suffering 
repeated infections, especially infections recurring after an 
adequate course of antibiotic therapy. The slow tempo of 
infection due to antibody deficiencies means that the diag- 
nosis is often delayed by several years. Antibody defi- 
ciency occurs at birth in primary agammaglobulinaemia 
(Bruton's disease) but more frequently later on in life as 
common variable immunodeficiency (CVID). Acquired 
immunodeficiency is often iatrogenic (Greek iatros = 
physician, hence resulting from medical treatment), and 
as a result of diseases affecting B cells, such as lymphoma. 
Corticosteroid therapy is the most common iatrogenic 
cause of poor antibody production. It is yet to be seen 
what effect the widespread use of the recently licensed 
anti-B cell monoclonal antibody, rituximab, will have 
upon iatrogenic immunodeficiency. Bacterial infection can 
be treated in patients with hypogammaglobulinemia by 
replacement immunoglobulin therapy every 2-A weeks, 

• Specific operations may have an effect on bacterial infec- 
tion from a combination of reduced innate immunity and 
antibody deficiency. Splenectomy in children, particu- 
larly infants, increases their susceptibility to infection 
and children should be given long-term oral penicillin. 
There is a lesser risk in older children and adults. 
Overwhelming postsplenectomy infection, usually with 
encapsulated bacteria such as Pneumococcus, Haemophilus 
or Meningococcus spp, occurs in 1-20% of splenectomized 
individuals; it is fatal in 50% of cases. 




Key point 

Give polyvalent pneumococcal vaccine, 
Haemophilus (HIB) and meningococcal vaccine 
to boost antibody levels before elective 
splenectomy. 



The small bowel is richly supplied with T, B and 
plasma cells and secretes the immunoglobulin IgA 
into the lumen. If it is diseased, it becomes suscepti- 
ble to infection with, for example, Giardia lamblia. 
Remarkably, extensive bowel resection does not 
appear to have major immunological effects. 



T CELLS AND CELL-MEDIATED 

iMjvujNmr_ _,.„„„„,„„„„,__„„ 

T lymphocytes have specialized membrane-bound T cell 
receptors (TCR) that are not secreted and remain cell 
bound. T cells arise in the bone marrow but migrate to the 
thymus, a primary lymphoid organ, in order to differen- 
tiate. The thymus is a site of enormous cellular prolifer- 
ation, like the germinal centres in B cell follicles; it is most 
active early in life and atrophies with age. 

The T cell receptor, like immunoglobulin, is made up of 
two chains. It shows remarkable similarity to the heavy 
and light chains of immunoglobulin in that they undergo 
the same process of gene rearrangement, producing a 
unique antigen-binding variable region and a conserved 
constant region which is largely anchored in the T cell 
membrane. 

T cell recognition of antigen 

T cells can recognize only protein antigens that have been 
broken down or 'processed' by antigen-presenting cells 
(APCs). Peptide fragments from proteins are incorporated 
into specialized cell surface molecules that have been 
misnamed the major histocompatibility complex (MHC) 
because of the complications this region causes in trans- 
planting tissues. The MHC is also known as HLA (human 
leucocyte antigens). T cell receptors recognize the combi- 
nation of the MHC and the peptide antigen that it 'pre- 
sents'. T cells cannot recognize free antigen or antigen 
outside the context of the MHC. 

There are two major classes of MHC molecules, struc- 
turally related but differing in their tissue expression, the 
subcellular compartment in which they process peptides 
and the presentation to separate T cell populations. 

MHC class I molecules are present on most nucleated 
cells and bind endogenous (Greek endon = within + 
gentian = to produce; formed within the cell) peptides that 
originate in the cell's cytoplasm. Cells degrade cytoplas- 
mic proteins and transport peptides to the cell surface in 
MHC class I molecules where they are recognized by 
cytotoxic T cells, identified by the CD8 molecule (a 
surface antigen that can be detected with a specific mono- 
clonal antibody - CD = cluster designation). Cytotoxic T 
cells that recognize an MHC class I viral peptide complex 
on the surface of a virally infected cell will kill the cell. 



85 




PATIENT ASSESSMENT 



MHC class II molecules are located on B lymphocytes, 
macrophages and dendritic cells, collectively known as 
antigen-presenting cells. These cells can assimilate exoge- 
nous antigen from outside the cell by phagocytosis or 
receptor-mediated endocytosis into vesicles within the 
cell. During the process of MHC class II synthesis it incor- 
porates the peptides from the vesicles and transports it to 
the cell surface. The T cell receptor of T helper cells, iden- 
tified by the CD4 molecule, is capable of binding to the 
antigen bound to the MHC class II molecule. T helper and 
cytotoxic T cells are selected in the thymus (Fig. 7.2). 

In both types of MHC a molecular groove exists into 
which peptides can fit, facilitating interaction with the 
T cell receptor. Pathogens with peptide sequences that 
cannot bind to specific MHC molecules are ignored. To 
counter this, the MHC gene cluster on chromosome 
6 accommodates highly polymorphic (Greek polys = much 
+ morphe - form; many formed) genes; this benefits the 
population at the expense of the individual and explains 




Positive 
CORTICAL 



Negative 
MEDULLARY 



Fig. 7.2 Thymic 'education' in T cell differentiation. 
CD4 = T helper cells; CDS = cytotoxic T cells. During 
'positive' selection T cells express both CD4 and CD8. 
Those cells capable of binding to MHC molecules on 
cortical epithelial cells are destined to survive. During 
'negative' selection, T cells express either CD4 or CDS, 
selected on the ability of the T cell receptor (TCR) to 
bind to MHC class II or class I, respectively. During 
'negative' selection, avid binding of TCR to MHC 
expressing self-antigens on medullary dendritic cells 
leads to the apoptotic death of such T cells, thus 
minimizing autoimmunity. Cells depicted with small 
nuclei represent apoptotic cells destined for elimination 
in the thymus. Binding ability of the TCR for MHC is 
depicted by the degree of 'fit' between the two 
molecules. 



why some individuals are more susceptible to specific 
infections than others. 



T cell function 

The T cell receptor detects MHC 'signatures' of non-self 
and in turn is linked to intracellular enzymatic pathways 
that activate the T cell via a complex of molecules known 
as CD3. The activated T cell produces intercellular 
messengers known as cytokines, of which more than 50 
have been identified, with many different effects. Most of 
them transmit between leucocytes and are therefore 
termed interleukins (IL), and the different types and actions 
are designated by a number, e.g. IL-1, IL-2 to IL-n. 
Inhibition of cytokines is the basis of selective immuno- 
suppressive drugs such as ciclosporin and tacrolimus 
which inhibit the secretion of IL-2. 

The T cell response, directed by T helper cells, is modi- 
fied by the antigenic context (microenvironment) and 
may in some situations cause cellular destruction, includ- 
ing suicide of the target cell - apoptosis (Greek apo = away 
+ ptosis = a falling), or in other situations enhance anti- 
body production in order to clear or inhibit antigens (see 
Fig. 7.3). The T cell recognition of 'self 7 is largely due to 
ignorance, in that most self-reactive T cells are eliminated 
in the thymus. 

Deficiency of cell-mediated immunity and 
infections by viral and other intracellular 
pathogens 

The rare failure to develop a thymus, resulting in severe 
deficiency of T cells, is known as DiGeorge's syndrome 




Antigen 



Fig. 7.3 T helper cell (CD4) functions. APC, antigen 
presenting cell; MHC, major histocompatibility complex; 
IL, interleukin; T H 0, T H 1, T H 2, T helper cell subsets (CD4+); 
TNF, tumour necrosis factor; IFN, interferon; TGF, T cell 
growth factor; T ct cytotoxic T cell (CD8+); Mo, 
monocyte/macrophage series; B, B cell. 



86 



IMMUNITY IN SURGERY 




7 



(after the American paediatrician who described it). 
Much more common are acquired T cell deficiencies, of 
which acquired immune deficiency syndrome (AIDS) is 
the best known. The human immunodeficiency virus 
(HIV) selectively infects T helper cells, resulting in sus- 
ceptibility to intracellular infections and virally mediated 
malignancies such as lymphomas (human herpes virus 
4-HHV-4) and Kaposi's sarcoma (HHV-8). Remarkably, 
thymectomy carried out for the treatment of myasthenia 
gravis or during cardiac surgery does not appear to have 
severe effects on immunity. Among the acquired forms of 
predominantly T cell deficiency are: 

1 . Malignant disease. 

2. Surgical operations, including the response to 
trauma as well as anaesthetic drugs such as halothane. 

3. Infection, particularly viral effects on lymphoid 
cells. 

4. AIDS, which results from infection with HIV. It ini- 
tially affected male homosexuals, intravenous drug users 
and haemophiliacs given factor VIII derived from pooled 
plasma from the USA. More recently in Europe and the 
USA and elsewhere in the world, most notably Africa, it 
has become primarily a heterosexual disease. The virus 
attaches itself to the CD4 molecule on the helper T cell, 
while cytotoxic T cells are initially unaffected. It is parti- 
cularly associated with susceptibility to opportunistic 
infections such as Pneumocystis carinii, cytomegalovirus, 
Aspergillus and in certain circumstances the development 
of Kaposi's sarcoma. 

5. Deficiency caused by radiotherapy for malignant 
disease, which produces lymphopenia, neutropenia and 
thrombocytopenia and largely depresses cellular immu- 
nity; however, the dose and rate of irradiation is such 
that marked cytopenias are rare and infection is not as 
common as with cytotoxic drugs. 

6. Deficiency resulting from the use of immuno- 
suppressant drugs such as azathioprine, cyclosporin A or 
tacrolimus used in transplantation. 

Deficiency of both T and B cell immunity 

The rare failure of lymphocyte differentiation leads to an 
absence of both B and T cells and a condition known as 
severe combined immune deficiency (SCID). This immuno- 
deficiency of the adaptive immune system is the most likely 
to present rapidly but even then takes several months from 
birth to be diagnosed, after repeated infections, failure to 
thrive and diarrhoea. As in each form of defects in adaptive 
immunity, the tempo is much slower than that seen with 
deficiency of innate immunity. Acquired forms of combined 
immunodeficiency are the result of: 

1. Poor nutrition, which affects both cell-mediated 
immunity and antibody production. 




Key point 

• Postoperative infection rates are likely to be 
higher in countries where starvation is 
common. 

2. Chemotherapy to treat malignant disease, which is 
cytotoxic to neutrophils, leucocytes and lymphocytes. It is 
associated with increased bacterial and opportunistic infec- 
tions, of which the effects on innate immunity predominate. 

3. The administration of glucocorticoid steroids, which 
are used in transplantation and in treatment of autoimmune 
diseases, with potent effects on both arms of adaptive 
immunity as well as some on innate immune mechanisms. 



AUTOIMMUNITY 



^^!£?:££!&^tf£S&^^ 



Random generation of antigen-binding sites in antibodies 
risks the development of autoimmune disease. One safe- 
guard against autoantibodies is that immature B cells 
emerging from the bone marrow are sensitive when their 
antibody receptor binds to self proteins, leading to toler- 
ance or death by apoptosis. Another safeguard is that 
B cells require a number of growth factors (cytokines) 
derived from T cells, and in their absence B cell differen- 
tiation and antibody production may fail. Autoimmunity 
arises in genetically predisposed individuals, affecting 
both B and T cells. Autoantibody may mediate disease by 
a number of immune mechanisms: 

• Binding to and blocking important physiological recep- 
tors, such as the acetylcholine receptor in myasthenia 
gravis 

• Damaging cells and tissues by complement fixation or 
antibody-dependent cellular cytotoxicity (ADCC) 

• Forming immune complexes that are deposited on 
the intimal surface of blood vessels and causing 
vasculitis. 

Immune deficiency is closely associated with auto- 
immunity; for example, Crohn's disease, which may have 
an autoimmune component and is often treated with 
immunosuppressive drugs, coeliac disease and atrophic 
gastritis are all associated with immune deficiency. 



TRANSPLANTATION 

Autotransplantation (Greek autos = self) of tissue, such as 
a skin graft, has no immunological consequences; nor does 
grafting between identical twins (isograft: Greek isos = 
equal). Non-vascularized allografts (Greek alios = other), 



87 




PATIENT ASSESSMENT 



such as corneal grafts, do not normally evoke a cellular 
rejection. On the other hand, kidney, liver, heart, lung, 
pancreas, small bowel and bone marrow grafts induce 
rejection (see Ch. 25). Allografts are mainly cadaveric 
organs but there is increasing use of live related donors. 
Bone marrow allografts are from live donors and may be 
related or unrelated. Rejection of allografts is predomi- 
nantly acute and cell-mediated early in the course of trans- 
plantation, unless the recipient has had prior contact with 
the donor tissues or is of a different blood group, in which 
case hyperacute rejection occurs. A slower onset of chronic 
Vascular' rejection, causing graft dysfunction and pro- 
gressive graft loss, is due to a variety of mechanisms, 
including cell- and antibody-mediated responses, physical 
effects, accelerated vasculopathy and immunosuppressive 
drug-induced effects. Tubular structures, such as blood 
vessels and biliary ducts, are affected by this process. 

Avoiding rejection 

1. Except when transplanting the cornea, the donor 
and recipient tissues are matched for ABO blood groups 
and as closely as possible for human leucocyte antigens 
(HLA). In addition, the recipient's serum is cross-matched 
with the donor lymphoid cells to exclude preformed cyto- 
toxic antibodies. 

2. Except when transplanting between identical twins, 
the recipient is immunosuppressed, with agents selected 
from a variety of drugs, including corticosteroids, azathio- 
prine, mycophenolate mofetil, ciclosporin, tacrolimus and 
sirolimus. The anchors of current therapy are still 
ciclosporin and tacrolimus, whose action prevents the 
development of cytotoxic T cells; however, both are nephro- 
toxic. Antilymphocytic globulin (ALG) or antithymocyte 
globulin (ATG) are polyclonal antibodies preferably raised 
in rabbits, and may be used to increase immunosuppres- 
sion early in transplantation. Monoclonal antibodies such 
as OKT3 (CD3) or Campath 1 (CDw52) have been used to 
reverse acute rejection. Newer monoclonal antibodies react- 
ing with the IL-2 receptor (CD25) are effective at prophyl- 
actically reducing acute rejection episodes. 

3. Graft versus host disease (GVHD) may develop if the 
graft contains competent T cells which react against the 
host cells that are incapable of rejecting them. This is most 
likely to develop following bone marrow transplantation. 
GVHD predominantly affects the skin, liver and gut. 



CANCER IMMUNOLOGY 



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Immunosuppressed patients have a higher than normal 
risk of malignancy, especially skin cancers and lym- 
phoid tumours. 

Cancers are often infiltrated with lymphocytes and 
macrophages - this may be associated with an 
improved prognosis. 

Latent cancers, especially of the thyroid and prostate 
glands, are often disclosed at postmortem examination, 
suggesting that the tumours develop but lie dormant 
for many years without clinical disease. This has been 
attributed to immune mechanisms. 



Tumour antigens 

Specific antigens can be found on the surface of tumour 
cells, especially those that are virally induced, without 
being present on normal cells of this type. Some tumour 
cells express antigens normally found only in fetal 
tissue, such as a-fetoprotein (AFP) and carcinoembry- 
onic antigen (CEA). These may be used as markers for 
some cancers or to monitor progress by measuring 
serum levels, but there is little evidence that they act as 
targets for the immune system. Radiolabeled mono- 
clonal antibody to CEA may be used to localize residual 
bowel tumour. Malignant cells can overexpress proto- 
oncogenes on their surface, which contribute to 
malignant behaviour; these were identified by anti- 
bodies developed for the recognition of specific tumour 
types. 

Monoclonal antibodies that attach to receptors highly 
expressed in tumours can be labelled with isotopes such 
as m In and 99m Tc. These can be identified by external 
scintigraphy. This is especially valuable in identifying 
residual tumour following treatment. 



• The occasional but well documented spontaneous 
regression of tumours suggests that immunity may 
develop against cancers. 



Immunotherapy 

The identification of immune aspects of cancer has led to 
the search for therapeutic uses, especially for dissemi- 
nated tumour cells beyond the scope of conventional 
treatment, or residual tumour following treatment. 
Antibodies alone are rarely cytotoxic to tumour cells and 
are largely restricted to haemopoietic malignancy. 
Monoclonal antibodies can be conjugated to radioiso- 
topes, immunotoxins or enzymes. Radiolabeled antibod- 
ies can target highly expressed epidermal growth factor 
receptors (GFRs) in lung and brain tumours and there is 
hope that monoclonal antibodies to GFRs will be effective 
in treating tumours. Monoclonal antibody to Her-Neu has 
proven effective in a minority of breast cancers express- 
ing this on the tumour. 



88 



IMMUNITY IN SURGERY 



7 



Summary 

• Do you understand that the immune 
system is composed of humoral and 
cellular elements and is made up of innate 
and adaptive mechanisms? 

• Are you aware that normally the immune 
system distinguishes self from non-self but 
autoimmunity may develop in predisposed 
individuals? 

• Do you recognize that immune deficiency 
arises from many causes, including 
operation, which predisposes to 
postoperative complications? 

• Are you aware that except in specific 
circumstances, organ transplants must be 
protected from rejection by 
immunosuppressive drugs and other 
techniques? 

• Can you foresee the immunological 
aspects of cancer becoming increasingly 
valuable in identifying, monitoring and 
treating malignancy? 




References 



Kohler G, Milstein C 1975 Continuous cultures of fused cells 
secreting antibody of predefined specificity. Nature 256(5517): 
495-497 




Further reading 

Goldsby RA, Kindt TJ, Osborne BA, Kuby J 2003 Immunology, 

3rd edn. W H Freeman, New York 
Janeway CA, Travers P, Walport M, Shlomchik M (eds) 2001 The 

adaptive immune response. In: Immunobiology, 5th edn. 

Churchill Livingstone, Edinburgh 
Medzhitov R, Janeway CA 2000 Innate immune recognition: 

mechanisms and pathways. Annual Review of Immunology 

173:89-97 
Norman D, Turka L 2001 Primer on transplantation, 2nd edn. 

Blackwell Science, Oxford 
Stites DP, Terr AI, Parslow TG 1997 Medical immunology. 

Appleton & Lange, Stamford CT 



89 




Haematological assessment 
and blood component therapy 



C P. F. Taylor, A. B. Mehta 




Objectives 

• Understand the need for preoperative 
detection of blood abnormalities which 
may affect the outcome of surgery and 
anaesthesia. 

• Be aware of the range of blood 
components available for clinical use. 

• Understand how to use blood components 
appropriately and the hazards associated 
with their use. 

• Be aware of alternatives to allogeneic 
blood transfusion and know when they 
are appropriate. 

• Understand the underlying mechanisms 
and management of excessive intra- or 
postoperative blood loss. 



INTRODUCTION 

This chapter outlines the investigation and management 
of patients undergoing surgery. It includes patients who 
have a prior abnormality of their blood count or blood 
plasma constituents and also discusses appropriate use of 
blood components in patients with no prior haemato- 
logical problems. 

Anaemia and excessive bleeding are symptoms and not 
diagnoses. An accurate diagnosis is an essential step in the 
formulation of a management plan. In the majority of hos- 
pitals, a clinical haematologist will be available to advise 
you on optimum use of laboratory diagnostic facilities, 
interpretation of results and appropriate therapy. Make 
sure you discuss problems early, and take advice on the 
appropriate specimens to send and tests to order. If a result 
is puzzling, go and discuss it with the haematologist. 



PREOPERATIVE ASSESSMENT 

Growing pressure on hospital beds and increasing use of 
day surgery means that the preoperative assessment 



should, wherever possible, be performed prior to admis- 
sion. This allows for efficient use of hospital resources and 
limits the number of cancelled operations. The key aims 
are to assess a patient's fitness to undergo surgery and 
anaesthesia, anticipate complications, arrange for sup- 
portive therapy to be available perioperatively and to 
liaise with the appropriate specialists regarding non- 
surgical management. This assessment needs to take 
place at a presurgical clinic at least 1 month prior to the 
planned date of surgery. 



Preoperative planning 

Arrange for the patient to attend a preoperative clinic at 
least 4-6 weeks prior to operation, to: 

• Take a full history and examination, including previous 
surgical episodes and bleeding history 

• Arrange full blood count, group and antibody screen, 
routine chemistry, coagulation screen (if indicated) and 
tube for haematinics assessment (ferritin level for iron 
stores, vitamin B 12 and folic acid), which can be put on 
hold pending full blood count (FBC) results 

• Consider autologous predeposit if the patient is fit 
enough and there is a greater than 50% likelihood of 
significant blood loss requiring transfusion 

• Consider using erythropoietin (Greek erythros = red 
+ poiesis - making), even with normal haemoglobin, 
at a dose of 600 units /kg weekly for 4 weeks 
preoperatively 

• Prescribe iron and folic acid supplement if there is any 
suspicion of iron deficiency 

• Establish whether the patient is taking regular aspirin, 
non-steroidal anti-inflammatory drugs (NSAIDs) or 
warfarin and make necessary arrangements to stop this 
drug preoperatively 

• Consider a staged surgical approach in major surgery 

After the clinic, ensure that all the results of the above 
tests are seen within a few days so that you can take necess- 
ary action. In addition, discuss with the anaesthetists 
whether acute normovolaemic haemodilution (ANH) or 
intraoperative cell salvage may be appropriate. 



90 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 




8 



Anaemia 

1. Anaemia is defined as a reduction in haemoglobin 
concentration below the normal range after correction 
for age and sex (approximately 13—16 g dl -1 in males, 
11.5-15 g dl -1 in females). The most common causes of 
anaemia in surgical patients are iron deficiency (from 
chronic blood loss) or anaemia of chronic disease. Both 
may be due to the underlying condition for which 
operation is required. 

2. Every anaemic patient, that is those whose 
haemoglobin level is below their laboratory normal range, 
should have iron studies and ferritin levels performed 
sufficiently in advance of operation to allow for corrective 
measures to take effect. A subnormal ferritin indicates iron 
deficiency and the patient should be treated preoper- 
atively with iron supplements orally or intravenously 
Defer elective surgery until the maximum haemoglobin is 
attained. One should not use allogeneic blood unless there 
are no reasonable alternatives (Table 8.1). 




Key point 



• Anaemia in elective surgical patients should be 
assessed and appropriately treated 
preoperative I y, 

3. A normal or high ferritin level does not exclude iron 
deficiency (although it is less likely), as ferritin is an acute 
phase protein. Anaemia of chronic disease (ACD) may be 
present in many presurgical patients, including those 
with malignancy or joint disease requiring orthopaedic 
surgery. ACD is usually normochromic and normocytic, 
although it is sometimes slightly microcytic. Iron levels 



Table 8.1 Reasons to reduce blood exposure 



Immunological complications 

- Red eel! alloantibodies: HTR 

- HLA antibodies; refractoriness 

- TRALI, FTP, TA-GvHD, etc 
Errors and 'wrong blood' episodes 
Infections - bacterial, viral, ? prion 
Immunomodulation - infection, malignancy 
Litigation 

Resource 



HTR, haemolytic transfusion reaction; PTP, post- 
transfusion purpura; TRALI, transfusion-related 
acute lung injury; TA-GVHD, transfusion-associated 
graft versus host disease. 



are normal but iron-binding capacity is reduced (in 
contrast to iron deficiency where iron-binding capacity 
is raised). Ferritin (an intermediary in the absorption 
of iron from the gut) may be normal or raised. ACD 
may respond to erythropoietin therapy preoperatively. 
Although iron stores may be adequate, supplemental iron 
and folic acid may be required. Anaemia accompanied by 
thrombocytopenia or neutropenia may indicate a bone 
marrow disorder, a complex autoimmune condition or 
systemic disease, so seek the advice of a haematologist, 
and other specialists, without delay 

A classification of anaemia is given below: 

• Decreased red cell production 

- Haematinic deficiency: 
Iron, vitamin B 12 , folic acid 

- Marrow failure: 

Aplastic anaemia, leukaemia, pure red cell aplasia. 

• Abnormal red cell maturation 

- Myelodysplasia 

- Sideroblastic (Greek sideros = iron) anaemia 

• Increased red cell destruction 

- Inherited haemolytic anaemia, such as sickle cell 
anaemia or thalassaemia (Greek thalassa = sea) 

- Acquired haemolytic anaemia: 
Immune (e.g. autoimmune) 

Non-immune (e.g. microangiopathic haemolytic 
anaemia, disseminated intravascular coagulation) 

• Effects of disease in other organs 

Anaemia of chronic disorder; renal, endocrine, liver 
disease. 

Examination of red cell indices provides important clues 
to the cause of anaemia. The following alterations in red 
cell indices offer a clue to the cause of anaemia. 

• Lowered mean cell volume (MCV), mean cell haemoglobin 
(MCH) 

- Iron deficiency 

- Thalassaemia trait 

- Homozygous thalassaemia 

- Hyperthyroidism 

• Raised MCV 

- Megaloblastic (Greek megalo - large) anaemia 

- Hypothyroidism 

- Liver disease 

- Reticulocytosis 

- Myelodysplasia 

- Aplastic anaemia 

- Paraproteinemia 

- Alcohol abuse 

• Normochromic normocytic 

- Anaemia of chronic disease 

- Renal failure 

- Bone marrow infiltration 

- Haemorrhage. 



91 




PATIENT ASSESSMENT 



- ■--■-■'-■■•--■ -- 



A reduction in MCV and MCH (microcytic hypochromic 
picture) is highly suggestive of iron deficiency. Nutritional 
deficiency or very slow chronic blood loss leads to a well- 
compensated anaemia of gradual onset. A raised MCV is 
highly suggestive of megaloblastic anaemia and malab- 
sorption (due to pernicious anaemia, coeliac disease, or 
after gastrectomy) or poor dietary intake are the common- 
est causes. The underlying cause of the anaemia should be 
specifically treated as far as possible and elective surgery 
delayed until this is achieved. 

Haemoglobinopathies 

These are a group of inherited disorders (autosomal recess- 
ive) of haemoglobin synthesis in which affected individ- 
uals (homozygotes) suffer a lifelong haemolytic anaemia. 
They are the commonest human inherited disorders. 

The carriers (heterozygotes) have a small degree of pro- 
tection against malaria; haemoglobinopathies are there- 
fore common in all parts of the world where malaria is (or 
was) prevalent - southern Europe, Asia, the Far East, 
Africa, South America and immigrant populations in 
northern Europe and North America. Carriers are asymp- 
tomatic and have a normal life expectancy, but may have 
a mild degree of anaemia. Haemoglobinopathies are 
divided into two types: disorders affecting haemoglobin 
structure and disorders of haemoglobin synthesis. In the 
structural haemoglobin variants, a single deoxyribo- 
nucleic acid (DNA) base mutation leads to an amino acid 
substitution in haemoglobin to give rise to a variant 
haemoglobin, e.g. haemoglobin S (sickle haemoglobin, 
which leads to sickle cell anaemia). The variant 
haemoglobin may be functionally abnormal; thus, 
haemoglobin S tends to crystallize under conditions of 
low oxygen tension and this distorts red cell shape to 
cause 'sickling'. The second type of haemoglobinopathy 
is thalassaemia, where there is no change in the amino 
acid composition of the haemoglobin molecule but there 
is deficient synthesis of one of the globin chains (a or £}), 
leading to imbalanced chain synthesis and anaemia. 
Thalassa (Greek = sea) recognizes that the disease was 
discovered in countries bordering the Mediterranean sea. 

It is important to detect carriers of some haemoglo- 
binopathies (e.g. sickle cell) prior to operation because 
anaesthesia and hypoxia can precipitate sickling. All 
patients of non-northern European origin should be 
screened prior to operation, for example in the pread- 
mission clinic, by haemoglobin electrophoresis and /or a 
sickle solubility test. Affected individuals (homozygotes) 
usually present in childhood but occasionally patients 
present incidentally. Patients with sickle cell disease 
(HbSS) should be managed jointly with a clinical haema- 
tologist. The consultant anaesthetist performing the case 
needs to know in advance of the sickle status of the 



patient because special anaesthetic precautions and prac- 
tices are required, including exchange transfusion prior to 
major surgery such as hip replacement. This involves 
venesection of the patient together with transfusion of 
donor blood (6-8 units) resulting in a postexchange 
haemoglobin S level of less than 30%. It can be performed 
manually or using a cell separator. Minor surgery such as 
dental procedures can be safely carried out without trans- 
fusion in the majority of patients. Intermediate pro- 
cedures such as cholecystectomy can be performed 
following transfusion with 2-3 units of packed red cells 
to a haemoglobin level of 10 g l" 1 (Vichinsky et al 1995). 
Pay particular attention to the hydration of the patient, at 
least 3 litres per day, and to oxygenation during anaes- 
thesia. Patients with some haemoglobinopathies, espe- 
cially HbSC disease, are at increased risk of postoperative 
thrombosis, and appropriate prophylaxis with low mole- 
cular weight heparin is desirable unless there are contra- 
indications. 

Other inherited red cell disorders 

Deficiency of the red cell enzyme gIucose-6-phosphate 
dehydrogenase (G6PD) is a sex-linked disorder affecting 
more than 400 million people worldwide. It results in a 
reduced capacity of the red cell to withstand an oxidative 
stress. Patients are asymptomatic in the steady state and 
have a near normal FBC, but may suffer haemolysis of red 
cells in response to an oxidative challenge. Common pre- 
cipitants are infection and drugs, principally antimalarials 
such as primaquine, pamaquine and pentaquine but not 
usually chloroquine or mefloquine, and sulphonamide 
antibiotics (Mehta 1994). 

Excessive bleeding 

1 . Preoperative assessment should allow us to anticipate 
problems. Many patients with an inherited or acquired 
defect of coagulation (Table 8.2) leading to peri- and post- 
operative complications cannot be detected preoperatively. 
However, take a careful history, which may reveal features 
such as excessive bleeding at times of previous surgery, 
bleeding while brushing teeth, nose bleeds, a family of 
history of bleeding disorders, spontaneous bruising, a 
history of renal or liver disease and a relevant drug history. 

2. Request a coagulation screen, prothrombin time (PT), 
activated partial thromboplastin time (APTT) and throm- 
bin time (TT) and platelet count, in any patient with a sus- 
pected bleeding disorder, although disordered platelet 
function can be difficult to detect. A bleeding time is the 
best in vivo test of platelet function and involves a stan- 
dard skin incision and timing of clot formation, provided 
the tester is expert and performs it regularly. Laboratory 
platelet function analyses may also be necessary. 



92 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 




Table 8.2 Bleeding disorders associated with 
excessive bleeding which may cause peri- or 
postoperative complications 




Congenital 
Clotting factors 

Platelets 
Vessel wait 



Acquired 
Clotting factors 



Platelets - function 



Platelets - number 



Vessel wall 



Haemophilia A, B 

von Willebrand's syndrome 

Congenital platelet disorders 

Hereditary haemorrhagic 

telangiectasia 

Drugs (anticoagulants, 

antibiotics) 

Liver disease 

DIC (in sepsis) 

Drugs (aspirin, NSAIDs) 

Liver disease, renal disease, 

myeloproliferative disorders, 

paraproteinaemic disorders 

Autoimmune 

thrombocytopenia 

Hypersplenism 

Aplastic anaemia, 

myelodysplasia 

Drugs (steroids) 

Vasculitis 

Malnutrition 



DIC, disseminated intravascular coagulation; 
NSAIDs, non-steroidal anti-inflammatory drugs. 



3. Ask advice from a haematologist specialising in 
haemostasis before elective operation on patients with 
coagulation and platelet abnormalities, since their pre- 
operative management may be complex. A very common 
cause of excessive intra-operative bleeding due to platelet 
dysfunction is pre-operative ingestion of aspirin, clopi 
dogrel, NSAIDS, or warfarin. The need for these drugs 
must be assessed at the pre-operative clinic and low dose 
aspirin should be stopped 10 days prior to surgery, unless 
this is con train dica ted. Platelets may be required to 
achieve haemostasis in bleeding patients, even with sat- 
isfactory platelet counts, if they have been taking aspirin 
within one week of surgery. 

Anticoagulation therapy 

1. The dose of oral anticoagulants such as warfarin 
(named for Winconsin /llumni Research Foundation + 
coumarm) is adjusted to maintain the international nor- 
malized ratio (INR, which is a measure of the patient's PT 
to that of a control plasma) within a therapeutic range. 



The therapeutic range varies depending upon the indica- 
tion for which the patient was warfarinized. 

2. Heparin is a parenteral anticoagulant and may be 
given in either low molecular weight or unfractionated 
forms. Low molecular weight heparin (LMWH) is not 
usually monitored at prophylactic doses, but at thera- 
peutic doses an anti-Xa assay is required for monitoring. 
Unfractionated heparin is monitored by measurement of 
the ratio of the patient's APPT compared to that of control 
plasma. The short half-life of unfractionated heparin 
allows safer management during the perioperative period. 



S™ 



Key point 



• Always check the platelet count before starting 
heparin and every second day on treatment to 
detect heparin-induced thrombocytopenia 
(HIT). 

3. For elective surgery in patients on oral anticoagu- 
lants, you must balance the risk of haemorrhage if the 
INR is not reduced against the risk of thrombosis if the 
INR is reduced for too long or by too great an amount. For 
minor surgery (e.g. dental extraction) it is normally suffi- 
cient to stop the oral anticoagulant for 2 days prior to the 
procedure and restart with the usual maintenance dose 
immediately afterwards. For high risk patients such as 
those with prosthetic heart valves, or for patients under- 
going more extensive procedures, you must stop warfarin 
and substitute heparin, either subcutaneously or by con- 
tinuous intravenous infusion, under close haematological 
supervision to provide thrombosis prophylaxis. Patients 
on warfarin who present for emergency surgery or who 
have bled as a result of anticoagulant therapy may need 
reversal of the anticoagulant. This can be done using 
vitamin K with either a concentrate of factors II, VII, IX 
and X or, if this is unavailable, fresh frozen plasma (FFP). 



ARRANGING INTRAOPERATIVE BLOOD 
ODMP^ 

Elective surgery 

1. The standard red cell product is SAG-M blood, that 
is, red cells suspended in an optimal additive solution of 
saline, adenine, glucose and mannitol, with a citrate anti- 
coagulant. Whole blood is not used in the UK, although 
it is available in some other countries in Europe, and 
plasma-reduced blood is available for specific multi- 
transfused patients. All cellular products, such as 
platelets and red cells, are leucodepleted at the blood 



93 



8 



PATIENT ASSESSMENT 



centres in the UK, and have been so since November 1999. 
There is therefore no role for an in-line white cell filter in 
these products. Special products/ such as blood with 
extended red cell phenotyping or rare blood from the frozen 
blood bank r are available after discussion with laboratory 
staff and haematology consultants at the blood service. 

2. Give the laboratory time to perform a 'group 7 and 
antibody screen on every patient before elective surgery. 
Although in most patients crossmatched blood can be 
provided/ after the group and screen (G & S) in 1 hour/ the 
1-4% of patients with atypical red cell alloantibodies 
require extra laboratory time for antibody identification 
and to obtain compatible units of blood from the blood 
centre. For this reason/ grouping and saving of blood is 
best performed at a preoperative clinic, even if this is 
several weeks in advance, and even though a new sample 
may then be required for crossmatching a day or two 
before operation, depending on local hospital policy. 

3. If no atypical antibodies are present, many proce- 
dures can now be performed after grouping and saving 
alone, blood being provided only if it is required during 
or after operation. If the antibody screen has been per- 
formed already and is negative, blood can be issued on an 
immediate spin test taking 10 min. In some hospitals a so- 
called 'electronic 7 crossmatch allows blood to be issued 
without any further wet testing. 

4. Most hospitals operate a standard, or maximum, 
blood order schedule (SBOS/MBOS) (British Committee 
for Standards in Haematology 1990). This agreed sched- 
ule for blood ordering improves efficiency within the 
blood bank and can also simplify the ordering process for 
junior doctors. An order can be placed prior to major 
vascular or hepatic operation, where there is a strong 
likelihood that FFP or platelets may be required, but the 
components are not usually issued until they are 
required; this avoids wastage. Discuss these arrange- 
ments preoperatively with a clinical haematologist and 
agree the procedures for regularly recurring events. 




Key point 

• Blood component therapy should be given 
after reviewing recent laboratory results, not 
on an empirical basis. 

5. Elective surgery should be undertaken on patients 
with thrombocytopenia, or congenital and acquired dis- 
orders of coagulation, only after careful preoperative 
assessment, and under the direction of a haematologist. 

6. Many patients can avoid allogeneic transfusion by 
normalization of haemoglobin preoperatively, using ery- 
thropoietin and iron therapy as appropriate, minimization 



of intra- and postoperative blood loss, and acceptance of 
a lower postoperative haemoglobin, such as 7-8 g dP 1 . A 
blood loss of 1.5 litres is well tolerated by most patients 
who have a normal initial blood haemoglobin, without 
the need for red cell transfusion of any sort, provided they 
are given adequate volume support with crystalloid and 
colloids. 



Preoperative autologous transfusion 

There are three kinds of autologous (derived from the 
same individual) blood transfusion that are practised to 
varying degrees at hospitals in the UK. 

1 . Intra- and postoperative cell salvage 

2. Acute normovolemic haemodilution 

3. Preoperative autologous deposit (PAD). 



Intra- and postoperative cell salvage 

A number of companies manufacture equipment that can 
be used to collect shed blood from intraoperative wounds 
and drains, and also postoperative drainage containers. 
Some of these return the blood as collected or they may 
be used to wash and process the blood to remove plasma 
constituents. If large volumes of shed blood are returned 
without processing, the patient may experience coagu- 
lation problems that can cause further bleeding. These cell 
salvage procedures have been evaluated by clinical trials 
in cardiac and orthopaedic surgery. There is definite evi- 
dence that salvage can reduce the proportion of patients 
who receive allogeneic red cell transfusion in orthopaedic 
surgery. In cardiac surgery, trials show only a slight 
reduction in transfusion of allogeneic red cells. The 
systems have also been used in liver surgery and liver 
transplantation and are increasingly used in other major 
vascular surgical procedures. Many clinicians believe 
from clinical experience that patients with major surgical 
blood losses do better if they are managed by reinfusing 
salvaged blood. These systems should not be used for 
'dirty' wounds where there is risk of infection from bowel 
contents or abscesses. Great caution is also exercised over 
the use of this equipment in patients with malignancy. 

Acute normovolaemic haemodilution 

There is some controversy over the value of this proce- 
dure, in which the anaesthetist withdraws several packs 
of the patient's blood in the anaesthetic room immedi- 
ately before surgery, replacing the volume straight away 
with crystalloid or colloid. The collected blood is then re- 
infused during or immediately after the operation. The 
blood must be taken into a clearly labelled blood pack 
containing standard anticoagulant and should remain 



94 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 




8 



with the patient until it is reinfused to avoid problems of 
transfusion to an inappropriate patient. Reinfusion must 
be completed before the patient leaves the responsibility 
of the anaesthetist- This procedure is most likely to be of 
benefit where the anticipated blood loss is greater than 
one litre and where the patient's haematocrit is relatively 
high. The degree to which the haematocrit can be lowered 
preoperatively depends on the status of the patient but 
patients who can tolerate a low haematocrit are likely to 
benefit most from this procedure. 

Preoperative autologous deposit (PAD) 

1 . It may be possible for the patient to make a preop- 
erative donation of 2-A units of red cells - typically 1 unit 
per week - for autologous transfusion at or after opera- 
tion. This is suitable for patients undergoing major 
surgery likely to require transfusion, especially if there 
are red cell phenotypying problems or refusal to receive 
donated blood. Directed donations from family or friends 
are not recommended in the UK, primarily because of 
confidence in the general safety of donor blood and 
concern that coercion may inhibit voluntary withdrawal 
of unsuitable donors. 

2. Autologous donations may not be given by patients 
with active infections, unstable angina, aortic stenosis or 
severe hypertension. A haemoglobin level of > 10 g dl" 1 is 
maintained with oral iron supplements. Trials have failed 
to demonstrate a consistent advantage from using recom- 
binant human erythropoietin (rhEPO) to accelerate 
haemopoiesis. Elective orthopaedic and gynaecological 
surgery are two areas where up to 20% of patients may be 
suitable for autologous donation. 

3. A number of issues mitigate against the wider appli- 
cability of this procedure: 

a. Late cancellation of surgery can lead to waste. 

b. Relatively few patients are suitable for PAD because 
of age, drug therapy or comorbidity. 

c. Criteria for transfusion of donated units should be 
identical to those for ordinary units and not be relaxed 
simply because it is available. 

d. Many patients become more anaemic following 
PAD and the likelihood of receiving a transfusion 
increases, whether autologous or allogeneic. 

e. Current UK guidelines (British Committee for 
Standards in Haematology, Blood Transfusion Task Force 
1993) stipulate that autologous units be tested for the 
same range of markers of transmissible disease as 
homologous donations, which increases costs and leads 
to ethical dilemmas if the results prove positive. 

f. Although some risks of transfusion are reduced by 
using autologous predeposit, errors in patient identifica- 
tion may still occur. It is possible that bacterial contami- 
nation is more likely than with standard donor blood. 



g. Hospitals need to operate secure laboratory and 
clinical protocols to ensure proper identification of auto- 
logous units and separation from homologous donation. 

h. The practice is likely to be associated with increased 
cost, and benefits are difficult to quantify. 

Emergency surgery 

1. Patients who are clinically shocked, as from sepsis or 
haemorrhage, or actively bleeding, require preoperative 
clinical and laboratory assessment. If possible, stabilize the 
patient prior to operation unless there is immediate access 
to the operating theatre to stop the bleeding. Maintain 
blood pressure, circulating volume and colloid osmotic 
pressure. First priorities in treating acute blood volume 
depletion are to maintain blood pressure, circulating 
volume and colloid osmotic pressure and then to restore 
the haemoglobin level. The appropriate initial therapy is 
to give a synthetic plasma substitute and crystalloid. 

2. Replace massive blood loss with red cells, FFP, 
platelets and cryoprecipitate, as indicated by results of 
testing for PT, APTT, TT, fibrinogen levels and platelet 
count. The thromboelastogram (TEG), which gives a 
global assessment of clotting efficiency, is used routinely 
in some hospitals. Maintain normothermia by transfusing 
all blood and fluids through a warming device. Even mild 
hypothermia can contribute to coagulopathy. 

3. In an extreme emergency you may give uncross- 
matched group O RhD negative blood, 'flying squad 
blood', immediately. As soon as a sample from the 
patient reaches the laboratory, group-compatible uncross- 
matched blood may be issued within approximately 
10 min. It requires 45-60 min for a full crossmatch. A 
retrospective crossmatch will always be performed on 
any uncrossmatched units transfused in an emergency. 

BLOODj:OMP^ 

1, The supply of blood components in the UK is based 
on unpaid volunteer donors. Over 99% of donor blood is 
separated into components, predominantly red cells in 
additive solution, fresh frozen plasma (FFP), platelets and 
cryoprecipitate. Cryosupernatant and buffy coats are also 
produced (Table 8.3). The collection, testing and process- 
ing of blood products is organised within the UK by the 
National Blood Service under the aegis of the National 
Blood Authority (NBA). Fractionated plasma products, 
produced by the Bio Products Laboratory (BPL) section of 
the NBA, are now produced entirely from imported USA 
plasma. This is because of fears about potential transmis- 
sion of variant Creutzfeldt-Jakob disease (vCJD) through 
the British blood supply. The fractionation process is used 
to produce intravenous immunglobulin (IVIg), albumin, 
specific immunglobulins and other products. 



95 




PATIENT ASSESSMENT 



Table 8.3 Blood constituents available for clinical 


use 




Whole blood* 




Blood components* 


Red cells - plasma reduced 




- leucocyte poor 




- frozen 




- phenotyped 




Platelets 




White cells (buffy coat) 




Fresh frozen plasma 




Cryoprecipitate 


Plasma products 


Human albumin solution 




Coagulation factor concentrate 




Immunoglobulin 




- specific 


*These products are 


- standard human 


not heat treated, and all may 


transmit microbial infection. 



2. The hospital transfusion laboratory is concerned 
with grouping and antibody screening of patient samples, 
compatibility testing and issuing of appropriate compo- 
nents, together with running an appropriate and accurate 
documentation system. Remember that, unlike the rest of 
pathology, the transfusion laboratory, under the direction 
of its consultant haematologist, is offering a therapy for 
patients, not merely a testing service. Seek advice regard- 
ing the appropriate use of therapeutic components from 
the haematologist in change. 

3. All the functions of the hospital transfusion laboratory 
require regulation and monitoring and both internal and 
external quality assurance schemes are performed regu- 
larly. Hospital laboratories have standard operating proce- 
dures for all the laboratory work carried out within them. 
Hospitals are also required by the Department of Health, 
via the Better Blood Transfusion initiative, to have a set of 
protocols and guidelines in place which are issued to all 
medical staff, detailing the range of components available 
together with procedures and indications for their use. The 
standard blood-ordering schedule is one of these, as men- 
tioned above. The Hospital Transfusion Committee (HTC) 
provides a forum whereby the clinical users of blood com- 
ponents can meet with the laboratory staff, the haematolo- 
gist in charge of transfusion and the local transfusion 
specialists from the blood centre. The responsibilities of 
such a committee are to organize audit so that activity can 
be assessed against protocols, to provide information on 
use of resources, to monitor inappropriate use and adverse 
effects of transfusion and to provide a mechanism whereby 
the audit loop can be completed. Plans for education and 
training in blood transfusion may be drawn up by the HTC 



along with new protocols and initiatives to improve blood 
transfusion practice within the hospital. The HTC is 
directly accountable to the Chief Executive and once again 
this pattern of responsibility is now formally expected and 
monitored by the Department of Health. Serious adverse 
events in transfusion are reported to SHOT (Serious 
Hazards of Transfusion), which is a national reporting body 
that collates anonymized data nationwide on serious 
adverse events. An annual report is brought out and actions 
are drawn up to try and improve transfusion practice in 
hospitals nationwide. In the 5 years since this scheme 
began, nearly 70% of reports to SHOT have been in the 
category of 'incorrect blood component transfused 7 . 

Blood grouping and compatibility testing 

Red cells carry antigens, which are typically glycoproteins 
or glycolipids attached to the red cell membrane. 
Antibodies to the ABO antigens are naturally occurring. 
Antibodies to other red cell antigens, such as the Rh 
group (CDEce), Kell, Duffy and Kidd, appear only after 
sensitization by transfusion or pregnancy and may cause 
haemolytic transfusion reactions and haemolytic disease 
of the fetus and newborn. 

1. Naturally occurring antibodies are usually IgM anti- 
bodies but may be IgG and are found in individuals who 
have never been transfused with red cells or who have 
not been pregnant with a fetus carrying the relevant red 
cell antigen. They are believed to be produced in response 
to exposure to substances that are found within the en- 
vironment, including the diet, which have similar struc- 
ture to red cell antigens. Naturally occurring anti-A anti-B 
and anti-AB antibodies are reactive at 37°C and are com- 
plement fixing antibodies which cause intravascular lysis 
of ABO incompatible red cells. 

2. Immune red cell antibodies are principally IgG, but 
can contain an IgM and /or an IGA component and these 
are formed as a result of exposure to foreign red cell anti- 
gens during transfusion or pregnancy. Frequency of these 
immune red cell alloantibodies is determined by the fre- 
quency of the antigen in the population and its immuno- 
genicity Of these D is by far the most immunogenic, 
followed by Kell (K) and c The concentration of the anti- 
bodies decreases over time if the individual is not 
exposed to further antigenic stimulus and they may 
become undetectable in the laboratory. 



!•• 



Key point 



• Report to the clinical haematologists and 
transfusion laboratory staff any patient with a 
history of a previous red cell alloantibody. 



96 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 




8 



3. In the blood transfusion laboratory all samples sent 
for "group and screen' or 'group and save' have the ABO 
and RhD group determined using monoclonal antibodies, 
which cause direct agglutination of red cells at room tem- 
perature if the relevant antigen is present on those red cells. 
A screen for atypical red cell alloantibodies is performed in 
which the patient's serum is incubated with reagent red 
cells, usually three different ones, which between them 
carry all the commonest red cell antigens. Any antibodies 
present in the serum will coat the reagent red cells during 
the incubation period. The red cells are then washed to 
remove free antibody, and antihuman globulin (AHG) is 
added to cause visual agglutination of any red cells that 
are coated with antibody. This is known as the indirect 
antiglobulin test (IAT) or Coombs' test. If antibodies are 
detected using this test, a more extended red cell panel is 
used to identify which alloantibodies are present, These 
techniques may be carried out in glass tubes, in microtitre 
plates or in solid phase (Diamed) columns. 

ABO, Rh compatible blood may then be crossmatched, 
or a G & S sample can be held until blood is required. A 
lower threshold for crossmatching is necessary if a patient 
has alloantibodies as this may cause delay in finding 
compatible blood at short notice. 



Red cell transfusion 

Major indications for transfusion of red cells are bleeding, 
anaemia (if severe, and the cause has been established 
and cannot be treated with alternatives) and bone marrow 
failure. 

1. The majority of red cells issued in the UK are resus- 
pended in optimum additive solution, most commonly 
SAG-M (sodium chloride, adenine, glucose and manni- 
tol). The blood is anticoagulated with a citrate anticoagu- 
lant. The approximate volume of an SAG-M unit of red 
cells is 270 ml ± 50 ml. The haematocrit is between 0.5 and 
0.7. All cellular components are leucodepleted in the UK 
and the white cell count per unit is less than 5 x 10 6 . There 
is therefore no indication for the use of a bedside in-line 
filter in the UK. 

2. The blood has a shelf life of 35 days when stored 
between 2°C and 6°C. It can be out of controlled storage 
temperature for up to a maximum of 5 h before transfu- 
sion is completed. 

3. During storage the concentration of the red cell 2,3- 
diphosphoglycerate (2,3-DPG) gradually falls, which 
increases the oxygen affinity and reduces the amount of 
oxygen the cells can deliver to tissues. Red cells in SAG- 
M are not usually used for exchange transfusion or large 
volume transfusion in neonates. An alternative product 
using citrate phosphate dextrose and adenine (CPDA) is 
used. 



4. There is almost no whole blood issued to any hospi- 
tal in the UK at present (less than 1 % of units are issued 
as whole blood), but alternative plasma-reduced products 
are sometimes available for multitransfused problem 
patients. 

5. Red cells matched for extended phenotype are 
issued for patients who are transfusion dependent and at 
risk of producing multiple red cell alloantibodies. 

6. There is a bank of frozen red cells available through 
the National Blood Service stored at Birmingham. These 
include rare units negative for specific common antigens, 
for use in patients with multiple red cell antibodies. These 
are made available for particular patients after discussion 
with the consultant haematologists in the National Blood 
Service. 

Indications 

1 . For the majority of patients undergoing elective or 
emergency surgery a transfusion trigger of 8 g dl" 1 is 
appropriate. Patients with known cardiovascular disease, 
previous myocardial infarction and the very elderly or 
infirm may require a higher haemoglobin perioper- 
atively. A patient undergoing operation with a normal 
haemoglobin of approximately 14 g dl -1 can afford to lose 
1.5 litres of blood before red cell transfusion becomes 
necessary. Clearly the patient should not be allowed to 
become hypovolaemic or hypotensive and the volume 
lost must be replaced with colloids and crystalloid as 
appropriate. Except in an emergency, patients should not 
undergo operation if they are anaemic. At preoperative 
clerking clinics, iron deficiency anaemia or anaemia of 
chronic disease can be corrected using iron therapy or 
erythropoietin as appropriate. This reduces unnecessary 
use of a limited resource and exposure of patients to 
potentially risky blood products. 

2. A recent large randomised clinical trial in critically 
ill patients demonstrated that a restrictive transfusion 
policy aimed at maintaining Hb in the range 7-9 g dl -1 
was at least equivalent, and possibly superior, to a liberal 
policy maintaining Hb at 10—12 g dl ^. A trigger 
haemoglobin of 7-8 g dl -1 is therefore appropriate even in 
the critically ill, except perhaps for those with unstable 
angina or acute myocardial infarction (MI). This leaves 
some margin of safety over the critical level of 4-5 g dl -1 . 
At this level, oxygen consumption begins to be limited by 
the amount that the circulation can supply. 

3. In those patients with abnormal bone marrow func- 
tion from bone marrow failure resulting from drugs or 
marrow infiltration, it may be less appropriate to allow the 
haemoglobin to become so low; a maintenance trough 
level of 9 g dl -1 may be appropriate. There is now some evi- 
dence that patients receiving radiotherapy for malignancy 
have better outcomes if the haemoglobin is maintained at 



97 




PATIENT ASSESSMENT 



a normal level, 12 g dl" 1 or more, throughout the period of 
radiotherapy. It relates to the effects of hypoxia on rumour 
growth and therefore on the efficacy of radiotherapy. 
Remember though, that this is a small group; the vast 
majority of elective surgical patients do not fall into this 
category. 

4. As a rule of thumb, in an average-sized adult, one 
unit of red cells raises the haemoglobin by 1 g dl -1 . There 
is only 200 mg of bioavailable iron in a unit of red cells, 
so remember that this is not an appropriate treatment 
for iron deficiency anaemia. Transfusion may correct a 
severely low haemoglobin in those who are symtomati- 
cally anaemic, but it will not correct iron deficiency. Oral 
iron replacement therapy is required for 4-6 months. 
Alternatively, give a total dose infusion of iron. 

Platelet transfusion 

Platelet concentrates may be produced by the pooling of 
platelets from four standard whole blood donations or 
may be from donors who give platelets alone via an 
apheresis (Greek apo = from + haireein = to take; to separ- 
ate) machine, in which case only one donor's platelets are 
present in each adult dose. A standard adult dose in either 
case is 2.4 x 10 11 platelets, suspended in 150-200 ml of 
plasma. This product has a shelf life of 5 days and is 
stored at 22°C on a platelet agitator. Platelets express ABO 
antigens but not Rh antigens and therefore they should be 
ABO matched as far as possible. There are a small number 
of red cells present in platelet concentrate and therefore 
women of child-bearing age should receive RhD matched 
platelets. If a RhD-negative women has to be given RhD- 
positive platelets she should be given anti-D cover as 
appropriate. A standard adult dose of platelets normally 
raises the count by 10 x 10 9 1" 1 at 1 h posttransfusion. 

Indications 

1. They are most commonly used to support patients 
with acute bone marrow failure, for instance after 
chemotherapy or stem cell transplant. If patients requir- 
ing platelet support are undergoing invasive procedures, 
a count of 50 x 10 9 l -1 may be required for line insertion 
and minor procedures, and a count of 80-100 x 10 9 \~ l for 
major surgery. 

2. Patients with platelet function disorders, whether 
inherited or acquired, may have normal platelet counts 
but abnormal platelet function. They may require platelet 
support during or after surgery. The most common 
acquired platelet function disorder results from the inges- 
tion of aspirin in the 7-10 days before operation. Platelet 
transfusion may be indicated for patients who have 
ingested aspirin within this period and who suffer from 
prolonged intra- or postoperative oozing. 



3. Platelets, together with FFP and cryoprecipitate, 
may need to be given for consumptive coagulopathy such 
as disseminated intravascular coagulation (DIC). The 
transfused blood components should be given on the 
basis of laboratory coagulation parameters and platelet 
counts. 

4. Massive red cell transfusion may eventually produce 
dilutional thrombocytopenia and require platelet transfu- 
sion, controlled as far as possible from the laboratory 
results. 

5. Patients may require platelet support when on extra- 
corporeal bypass, undergoing for example open heart 
surgery, even though the platelet count is normal or near 
normal, because the platelets are activated while in the 
extracorporeal circuit and therefore may be ineffective in 
haemostasis. 

Platelets are not indicated for: 

• Chronic thrombocytopenia, unless there are bleeding 
problems 

• Prophylatically for patients undergoing bypass 

• Immune thrombocytopenic purpura, except in the case 
of critical bleeding. 

Platelet transfusion is contraindicated because it may 
aggravate the underlying conditions in: 

• Heparin-induced thrombocytopenia, which is an 
autoimmune-mediated condition resulting in arterial 
blood clotting 

• Thrombocyte thrombocytopenic purpura. 

All patients receiving prophylatic or therapeutic heparin 
using unfractionated or low molecular weight heparin 
should have a platelet count performed prior to com- 
mencement of heparin, on the day following and every 2 
days thereafter. 




Key point 

• Suspect heparin-induced thrombocytopenia if 
there is a drop in platelet count below 
100 x 10 9 1 1 and urgently seek advice from a 
haematologist Amputation results in 30% of 
cases. Stop heparin, use an alternative 
anticoagulant. 

Fresh frozen plasma (FFP) 

1. FFP is prepared by centrifugation of donor whole 
blood within 8 h of collection, and frozen at -30°C. It may 
be stored for up to 12 months and is thawed prior to 
administration, 300 ml taking approximately 20 min to 
thaw. Once thawed it should be used within 2 h as there 



98 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 



8 



is exponential degradation of the clotting factors at room 
temperature. 

2. Compatibility testing is not required, but group 
compatible units are used. FFP contains coagulation 
factors, including the labile factors V and VIII and the 
vitamin K-dependent factors II, VII, IX and X. 

3. In clinical practice FFP is frequently given unnecess- 
arily and, when it is indicated, not enough is given. To 
correct abnormal coagulation a dose of 15 ml kg -1 is 
required. In a 70 kg adult this is almost 1 litre of FFP; cor- 
rected to the nearest whole bag this is three bags. 

4. Standard FFP carries the same risks as red cells for 
transmitting viral, bacterial and prion disease. Some 
virally inactivated plasmas are now available. Solvent 
detergent-treated plasma is created from pools of up to 
1000 donors, which are available as Octaplas™, and non- 
pooled methylene blue-treated plasma is now available 
for paediatric use via the National Blood Service. Both of 
these products are safer in terms of viral transmission 
than standard FFP, although they are still not completely 
safe and some viruses may not be inactivated. Viral inac- 
tivation procedures have no effect on possible prion trans- 
mission. Clotting factor levels are slightly diminished in 
both products, possibility resulting in the need to use a 
greater number of units per patient. 



Indications 

The indications for FFP transfusion are: 

1. Coagulation factor replacement where there is no 
concentrate available. In hospitals with an interest in 
haemophilia and haemostasis the vast majority of 
inherited clotting factor deficiencies are treated with 
specific concentrates, with the exception of factor V 
deficiency for which there is no concentrate available. 
In hospitals without a specialist unit, FFP may be 
used more widely for clotting factor deficiencies. 

2. To correct abnormal clotting in patients with DIC or 
those who have undergone massive transfusion or 
cardiopulmonary bypass. In all these give FFP 
guided by the coagulation results obtained from 
near-patient testing, or from the central laboratory 

3. To correct abnormal coagulation in patients with liver 
disease and poor synthetic function. Administration 
of vitamin K may also help in this situation. 

4. To reverse oral anticoagulation as from, for example, 
over warfarinization, if there are no concentrates 
available. 

5. Specifically indicated for plasma exchange in the 
management of thrombotic thrombocytopenic 
purpura (TTP) and haemolytic uraemic syndrome 
(HUS). Cryo-poor FFP may be a superior product in 
this setting. 



FFP should not be used: 

1. To treat hypovolaemia which can adequately be 
managed using colloid and crystalloid solutions. 

2. For plasma exchange except in the specific 
circumstances stated above. 

3. As a 'formula' replacement; for example, there is no 
need to administer two bags of FFP for every 4 or 

6 units of red cells transfused. Give replacement with 
FFP on the basis of clotting results, or, if necessary, 
for clinical indication. 

4. In the management of nutritional or 
immunodeficiency states. 

5. In bleeding due to thrombocytopenia or 
hypofibrinogenaemia, for which platelet concentrates 
and cryoprecipitate, respectively, are indicated. 

Cryoprecipitate 

1. This is prepared from FFP by freezing and thawing 
plasma and then separating the white precipitate from the 
supernatant plasma. Cryoprecipitate (Greek kryos = frost) 
contains half of the factor VIII, fibrinogen and fibronectin 
from the donation and also the majority of the von 
Willebrand factor. In common with FFP, it is stored at 
-30°C for up to 12 months. As the volume of each pack is 
only 10-20 ml, the product thaws very quickly and can be 
ordered when it is about to be given. Also, like FFP, the 
effectiveness of the product decreases rapidly once it has 
been thawed. A standard adult dose is 10 units, which 
should be ABO compatible but not crossmatched. 

2. Cryoprecipiate is indicated when replacement of fib- 
rinogen is required in those with congenital or acquired 
hypofibrinogenaemic states. In DIC, if the fibrinogen 
drops below 0.8 g l" 1 , give cryoprecipitate. Remember to 
request a fibrinogen level in patients with massive bleed- 
ing or DIC as this is not automatically performed with a 
clotting screen in most laboratories. Cryoprecipitate was 
formerly the mainstay of management of patients with 
von Willebrand' s disease but a concentrate is now avail- 
able for this condition at many centres. 

Plasma products 

These are produced by a fractionation process and are 
derived from pooled human plasma. The product is 
concentrated and sterilized and the risk of infection is 
markedly reduced. However, there is still a theoretical 
risk that they could transmit prion proteins, which are 
implicated as a transmissible cause of new variant 
Creutzfeldt-Jakob disease (nvCJD). For this reason all 
plasma for fractionation in the UK is now imported from 
the United States, where it is taken from accredited 
donors. The processing still takes place in the UK. 



99 




PATIENT ASSESSMENT 



Albumin solution 

This is usually available as 20 g albumin in 400 ml, as a 5% 
solution, or 100 ml of 20% solution. Each unit also contains 
sodium 130-150 mmol 1 _1 plus other plasma proteins and 
stabilizer. The main indications for albumin are hypo- 
proteinaemia with nephrotic syndrome (20%) and chronic 
liver disease (20%) and acute volume replacement (5%), for 
example, for plasma exchange. It may also be used in 
hypoproteinaemia following burns after the first 24 h. There 
is no evidence that albumin solutions are necessary to 
restore circulatory volume following haemorrhage, shock 
or multiple organ failure; colloid and crystalloid solutions 
are equally efficacious, cheaper and probably safer. 

Coagulation factor concentrates 

1. These are largely used in patients with congenital 
bleeding disorders, and recombinant factor VIII and 
factor IX are now widely used. Concentrates are also 
available, manufactured from pooled fractionated human 
plasma, sourced from outside the UK. 

2. Prothrombin complex concentrate contains factors 
IX, X and II and is used to treat bleeding complications in 
inherited deficiencies of these factors. When given with 
vitamin K, it is also used to treat oral anticoagulant over- 
dose, and in severe liver failure. Its use carries a risk of 
provoking thrombosis and DIC. 

3. Other concentrates include the naturally occurring 
anticoagulant factors protein C, antithrombin (see below) 
and factors VII, XI and XIII; they are used in correspond- 
ing congenital deficiencies. FEIBA (factor VIII bypassing 
activity concentrate) is used in patients with inhibitors to 
factor VIII, as is recombinant factor Vila in some circum- 
stances. Recombinant factor Vila has also recently been 
used experimentally for management of massive bleeding 
that is not responding to other clotting concentrates and 
platelet infusions. There is now a substantial body of anec- 
dotal evidence that this may be effective and life saving in 
some cases. Recombinant factor Vila has significant pro- 
thrombotic effects; it is extremely expensive and should 
only be used under the guidance of a haematologist expe- 
rienced in its use. A fibrinogen concentrate is now available 
for severe forms of hypofibrinogenaemia, both congenital 
and acquired, and fibrin sealants are also available. 

Immunoglobulins 

These are prepared from pooled donor plasma by fraction- 
ation and sterile filtration. Specific immunoglobulins 
include hepatitis B and herpes zoster and can provide 
passive immune protection. Standard human immunoglo- 
bulin for intramuscular injection is used for prophylaxis 
against hepatitis A, rubella and measles, whereas hyper- 



immune globulin is prepared from donors with high titres 
of the relevant antibodies for prophylaxis of tetanus, 
hepatitis A, diphtheria, rabies, mumps, measles, rubella, 
cytomegalovirus and Pseudomonas infections. Intravenous 
immunoglobulin is used as replacement therapy in 
patients with congenital or acquired immune deficiency 
and in autoimmune disorders (e.g. idiopathic thrombo- 
cytopenic purpura). 

Plasma substitutes 

These include products based on hydroxyethyl starch 
(HES), dextran (a branch-chained polysaccharide com- 
posed of glucose units) and modified gelatin. Such com- 
ponents remain in the circulation longer than crystalloid 
solutions - up to 6 h for modified gelatin and up to 24 h 
for some high molecular weight starch-based products. 
Other advantages are that they are relatively non- toxic, 
inexpensive, can be stored at room temperature, do not 
require compatibility testing and do not transmit infec- 
tion. Adverse effects include anaphylaxis, fever and rash, 
such effects being more frequent with starch-based prod- 
ucts. Dextran can also impair coagulation and platelet 
function and can interfere with compatibility testing. 




Key point 

• Take a blood sample for crossmatching before 
administering dextran. 

The maximum dose of synthetic plasma expanders is 
approximately 20-30 ml kg -1 . Patients receiving larger 
volumes or with significant evidence of other organ 
failure, such as pulmonary or renal disease, or a bleeding 
diathesis, may be given albumin. 



ADVERSE CONSEQUENCES OF BLOOD 
TRANSFUSION 



^^^^^^^^li^^^^i^^^'^^^^^. 



■f&^&&tfift&i&L 



In general, transfusion of blood and products is a safe and 
effective mode of treatment. 

1. The safe administration of blood components is a 
deceptively complex process involving phlebotomists, 
clerical staff, junior doctors, porters and nurses as well 
as transfusion laboratory staff. A survey in the UK 
(McClelland & Phillips 1994) suggests that a 'wrong blood 
in patient' incident occurs approximately once per 30 000 
units of red cells transfused. By far the commonest cause 
is a failure at the bedside of pretransfusion identity check- 
ing procedures, either at the time of phlebotomy or while 
setting up the actual transfusion. 



100 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 



8 




Key point 



• Pay rigorous attention to all administrative and 
clerical aspects of blood component therapy; 
they are overwhelmingly the commonest cause 
of fatal errors. 

2. In the UK all hospitals participate in the SHOT 
(Serious Hazards of Transfusion) reporting scheme which 
allows for anonymized reporting of serious transfusion 
events to a centralized data collecting body. Cumulative 
data from the past 5 years has shown that 'Incorrect blood 
component transfused' is by far the commonest reported 
event, with nearly 70% of all reports coming into this cat- 
egory. Conversely, the most feared and well-publicized 
complication, that of infectious disease transmission, is 
one of the very least common categories, with only 1-2% 
of cases. It is now mandatory for all hospitals to partici- 
pate in the SHOT scheme as set out in the Department of 
Health circular Better Blood Transfusion, published in July 
2002 (Table 8.4). 



Immune complications 

ABO-incompatible red cell transfusions lead to life- 
threatening intravascular haemolysis of transfused cells, 
manifesting as fever, rigors, haemoglobinuria, hypoten- 
sion and renal failure (immediate haemolytic transfusion 
reaction (HTR)). In the anaesthetized patient, the only 
signs may be persistent hypotension and unexplained 
oozing from the wound. 

Atypical antibodies arising from previous transfusions 
or pregnancy may cause intravascular haemolysis but 



more commonly lead to extra vascular haemolysis in liver 
and spleen and may be delayed for 1-3 weeks (delayed 
HTR). Typical manifestations are jaundice, progressive 
anaemia, fever, arthralgia and myalgia. Diagnosis is easily 
established by a positive direct antiglobulin test (DAT) 
and a positive antibody screen. Non-haemolytic febrile 
transfusion reaction (NHFTR) usually occurs within hours 
of transfusion in multitransfused patients with antibodies 
against HLA antigens or granulocyte-specific antibodies. 
The reaction is due to pyrogens released from granulo- 
cytes damaged by complement in an antigen-antibody 
reaction. It presents as a rise in temperature, with flushing, 
palpitations and tachycardia, followed by headache and 
rigors. Hypersensitivity reactions to plasma components 
may cause urticaria, wheezing, facial oedema and pyrexia, 
but can cause anaphylactic shock, for example, in patients 
with congenital IgA deficiency who have antiTgA anti- 
bodies following previous sensitization, 



Treatment 

Stop the transfusion immediately in all cases except for 
the appearance of a mild pyrexia in a multiply transfused 
patient. Check clerical details and send samples from the 
donor unit and recipient for analysis for compatibility 
and haemolysis. Have the recipient serum analysed for 
the presence of atypical red cell leucocyte HLA and 
plasma protein antibodies. Treat severe haemolytic trans- 
fusion reactions with support care to maintain blood 
pressure and renal function, to promote diuresis and 
treat shock. Intravenous steroids and antihistamines 
may be needed, with the use of adrenaline (epinephrine) 
in severe cases. Manage NHFTR by administering 
antipyretics. 



Table 8.4 


Hazards of transfusion 








Non-immune complications 




Immune complications 


Acute 


Hypothermia 




Febrile non-haemolytic transfusion reaction 




Hyperkalemia (IK 4 ) 




Acute haemolytic reaction (ABO incompatibility) 




Hypocakaemia (lCa 2+ ) 




Allergic reactions (urticarial or anaphylactic) 




Air embolism 




TftALl (transfusion-related acute lung injury) 




Bacterial (endotoxic) shock 






Delayed 


HIV 




Delayed haemolytic transfusion reaction (due to 




Hepatitis C 




red cell alloantibodies) 




Hepatitis B 




Posttransfusion purpura 




CMV 




Transfusion-associated graft versus host disease 




Parvovirus B19 




Immune modulation 




Others: e.g.: hepatitis A, ma 


laria, brucellosis, 






Syphilis, trypanosomiasis, 


vCJD? 





101 




PATIENT ASSESSMENT 



Transmission of infection 

1. Blood transfusion is an important mode of trans- 
mission of a range of viral, bacterial and protozoal infec- 
tions. There is also a theoretical risk of transmitting 
infections mediated by prion proteins such as new variant 
CJD (Flanagan & Barbara 1996, 1998), although no proven 
or even probable instances of such transmissions have 
ever been identified. However, concern has been raised 
by a study in which one (of 19) asymptomatic sheep, 318 
days after being given 5 g of brain infected with bovine 
spongiform encephalopathy (BSE) in the feed, appeared 
to transmit BSE to a second sheep via a 400 ml venous 
transfusion (Brown 2000, Houston et al 2000). A recent 
update on this study suggests that up to four sheep may 
now be suffering from transfusion transmitted prion 
disease. Therefore, until definitive evidence becomes 
available, steps have been taken to reduce the risk of 
transfusion as a possible secondary route of transmission 
of vQD (Brown et al 2001): 

• In UK from November 1999: 

- ban on using UK plasma for manufacture of frac- 
tionated products (e.g. albumin, clotting factors, 
IVIg) 

- leucodepletion of all blood, platelets, FFP, cryopre- 
cipitate (as leucocytes believed to play key role in 
vCJD pathogenesis) 

• In other countries (e.g. USA, Canada, New Zealand 
etc.): 

- exclusion as blood donors of people who have 
lived in the UK for >6 months between 1980 and 1996. 

2. It should be emphasized that the safety of blood 
components and fractionated plasma products has 



improved greatly in recent years. Bacterial infections can 
occur through failure of sterile technique at the time of 
collection, commonly by organisms such as Staphylococcus 
aureus or Staph, epidermidis, or bacteraemia in the donor - 
especially if organisms such as Yersinia, which can survive 
at 4°C, are incriminated. 

3. There are more fatalities per annum from bacterial 
or endotoxic complications, usually relating to platelets, 
than from viral transmissions. Donors at risk of 
malaria are not eligible to donate, but a malarial anti- 
body test is likely to be available for screening at-risk 
donors in the near future. Transmission of syphilis is 
now very rare. 

Viral infection 

Transmission of viruses may occur in spite of mandatory 
screening because: serological tests may not have had 
time to become positive in a potentially infectious indi- 
vidual; the virus may not have been identified; or the 
most sensitive serological tests may not be routinely 
performed. The risk of transmission is much lower, 
although still present, for those blood products that have 
undergone a manufacturing and sterilization process 
(Table 8.5). 




Key point 

The perceived risk of viral transmission is high: 
the actual risk in the UK is very low - less than 
1 in 4 million for HIV and 1 in 3 million for 
hepatitis C (Williamson et al 1996). 



Table 8.5 Risk of virus transmission 



Risk factor 



Acute haemolytk reactions 



Hepatitis B 



Hepatitis C 



HIV 



Bacterial contamination of red cell concentrates 



Estimated frequency 
per unit transfused 



1 in 250 GOO to 1 in 1 000 000 



1 in 100 000 to 1 in 400 000* 



1 in 3 000 000' 



1 in 4 000 000 



1 in S00 000 



Deaths per 
million units 

0.67 



<05 



<0.5 



<0,5 



<0 25 



*Data on viral markers from Kate Soldan, National Blood Servite/CPHL 

1 Data on hepatitis C markers from Dr Pat Hewitt and Dr John Barbara, National Blood Service. 

Adapted from British Committee for Standards in Haematoiogy, Blood Transfusion Task Force 2001 Guidelines for 
the Clinical Use of Red Cell Transfusions, British Journal of Haematology 113: 24-31 



102 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 




Other complications 

1 . There is increasing evidence that transfusion of blood 
components can cause immunosuppression in the recipi- 
ent. This may lead to earlier relapse or recurrence of malig- 
nant disease after surgical removal of malignant tumours 
(shortened disease-free interval), as well as an increased 
incidence of postoperative infection. These effects are 
probably due to defective cell-mediated immunity and are 
reduced by giving leucocyte-depleted components. 

2. Circulatory overload may result from the infusion of 
large volumes in patients with incipient heart failure. Iron 
overload occurs in patients who have received repeated 
red cell transfusions and these patients require iron chela- 
tion therapy (Greek chele - claw; attaching the iron to an 
agent that renders it harmless). 

3. Graft versus host disease may be caused by transfu- 
sion of T lymphocytes into severely immunosuppressed 
hosts, and cellular components should be irradiated prior 
to transfusion to severely immunodeficient patients. 



INTRAOPERATIVE ASSESSMENT 

1. Rapid bleeding confined to one site is almost always 
a technical problem. Suspect haemostatic failure in a high 
risk patient with multiple sites of bleeding, or if the 
pattern of bleeding is unusual; confirm it with appropri- 
ate laboratory tests. 

2. The following tests are useful in assessing the degree 
of blood loss and should serve as a guide for determining 
the need for replacement therapy; 

• Oxygen-carrying capacity of blood 

- haemoglobin concentration 

- pulse oximetry 

• Haemostatic function 

- coagulation screen: 
prothrombin time (PT) 



activated partial thromboplastin time (APTT) 
thrombin time (TT) 

- platelet count 

- fibrinogen level 

- thromboelastography. 

3. Quantification of intraoperative blood loss is impre- 
cise. Confirm clinical evaluation with laboratory tests 
(Table 8.6), many of which cannot be performed outside 
the main laboratory. Thromboelastography is a useful and 
rapid test producing a graphical record of in vitro blood 
clot formation and dissolution; it provides a global test of 
coagulation and fibrinolysis which can be performed 
rapidly within the operating suite in high risk patients. 

4. There has been a recent resurgence in other forms 
of near-patient testing, in particular in coagulometers, 
which are becoming available at the bedside in intensive 
care units, operating theatres, high dependency units and 
obstetric units, and also in accident and emergency units. 
These provide a 5 min turnaround time for PT and APPT, 
instead of over an hour when samples are sent to the 
central laboratory. The availability of a Hemacue for rapid 
haemoglobin results has also improved management of 
the bleeding patient in these sites. 

Intraoperative autologous transfusion 

1. Acute normovolemic haemodilution (ANH) involves 
removal of 1-2 units of whole blood during induction of 
anaesthesia, with replacement by crystalloid, reducing the 
haematocrit to 25-30%. Operation is usually well tolerated, 
the collected blood can be returned later during the oper- 
ation, and there is no need to undertake virological testing 
of the unit (Williamson 1994). 

2. Salvage of blood lost during an operation (British 
Committee for Standards in Haematology, Blood 
Transfusion Task Force 1997) is accomplished using a 
simple device such as Solcotrans, or a cell saver such as 
Haemonetics, Dideco or Fresenius. 



Table 8.6 Results of laboratory tests as an aid in differential diagnosis of excessive bleeding 




Cause of bleeding Laboratory test 




PT APTT TT without protamine TT with protamine 


Platelet count 



Loss of platelets 

Lack of coagulation factors 

Excess of heparin 

Hyperfibrinolysis 

DIC 

Massive blood transfusion 

Vitamin K deficiency 



N 


N 


N 


TT 


TT 


N 


T 


TT 


T 


T 


T 


TT 


TT 


TT 


TT 


t 


T 


N 


" 


T 


N 



N 

N 

N 

TT 

TT 

N 

N 



N, normal; J T, markedly raised; T p mildly raised; ii, markedly decreased; I, mildly decreased. 



U 

Nor I 
N or J^ 
Norl 

u 
i 

N 



103 




PATIENT ASSESSMENT 



3. Blood shed into the thoracic or abdominal cavity is 
aspirated and mixed with anticoagulant. It can then be 
returned to the patient (Solcotrans), or the red cells can be 
washed, suspended in saline and transfused to the 
patient (cell savers). The use of a cell saver may con- 
siderably reduce the number of units required for transfu- 
sion. Contraindications to using the blood salvage 
procedure are exposure of blood to a site of infection or 
the possibility of contamination with malignant cells. 
Postoperative blood lost into drains can also be salvaged 
using the cell saver. 

Methods of reducing intraoperative blood 
loss 

Meticulous surgical technique clearly plays a major role, 
but there is increasing interest in the use of pharmaco- 
logical agents to improve haemostasis. Desmopressin 
(DDAVP) improves platelet function by increasing 
plasma concentrations of von Willebrand factor, but has 
not been convincingly shown to reduce blood loss in 
cardiac surgery. Aprotinin is a serine protease inhibitor 
which inhibits fibrinolysis and has been shown to 
reduce blood loss and operative morbidity in cardiac 
surgery (particularly in repeat procedures) and major 
hepatic surgery such as liver transplantation (Hunt 
1991). 



2. Acidosis in the patient with severe renal or liver 
disease may be aggravated by the low pH of stored blood. 

3. Failure of haemostasis manifests as local oozing and, 
infrequently, as a generalized bleeding tendency due to 
the lack of coagulation factors and platelets in stored 
blood. Laboratory assessment is essential (see above). FFP 
(15 ml kg 1 ) corrects the abnormalities of coagulation and 
may need to be given without the benefit of laboratory 
results in an emergency if 10 units or more of red cells 
have been given. Platelet transfusion may be required 
when the platelet count is lower than 50 x 10 9 H or to 
maintain a count at 80 x 10 9 1" 1 if the patient is bleeding. 

4. Hypothermia contributes to failure of haemostasis, 
as the enzymatic clotting cascade functions best at 37°C. 
Patients receiving large quantities of red cells, colloids 
and crystalloids become hypothermic and their clotting is 
suboptimal. Anticipate this problem, as clotting tests from 
the laboratory may be normalized by being performed at 
37°C in vitro. 




Key point 

Avoid hypothermia by using a blood warmer 
and fluid warmer, and keeping the patient as 
warm as possible. 



Special situations 

Massive blood transfusion 

This is denned as transfusion of a volume greater than the 
recipient's blood volume in less than 24 h. Standard red 
cell concentrates in SAG-M can be transfused rapidly 
using a pressure infuser or a pump, and a blood warmer 
prevents the patient developing hypothermia. FFP, cryo- 
precipitate and platelet concentrates of the same blood 
group as the red cells may also be required. They should 
be given on the basis of clotting screens, fibrinogen levels 
and platelet counts as far as possible. 
Complications include: 

1. Cardiac abnormalities such as ventricular extra- 
systoles, ventricular fibrillation (rarely) and cardiac arrest 
from the combined effects of low temperature, high pot- 
assium concentration and excess citrate with low calcium 
concentration. They can be prevented by using a blood 
warmer and a slower rate of transfusion, particularly in 
patients with hepatic or renal failure. Routine adminis- 
tration of calcium gluconate is unnecessary and may even 
be dangerous unless the ionized calcium concentration in 
the plasma can be monitored. 



5. Adult respiratory distress syndrome (ARDS), also 
called non-cardiogenic pulmonary oedema, occurs in 
severely ill patients after major trauma and /or surgery. 
Clinical features include progressive respiratory distress, 
decreased lung compliance, acute hypoxaemia and diffuse 
radiographic opacification of the lungs. The mortality is 
high; post-mortem studies show widespread macroscopic 
and microscopic thrombosis in the pulmonary arteries. 
Local DIC, microvascular fluid leakage and embolization 
of leucocyte aggregates and microaggragates from stored 
blood all contribute to pathogenesis. Management consists 
of stopping the transfusion, administering corticosteroids 
and providing supportive treatment to combat pulmonary 
oedema and hypoxia, by administering oxygen and giving 
positive pressure ventilation. 

Transfusion in open heart surgery 

This requires cardiopulmonary bypass (CPB) for main- 
taining the circulation with oxygentated blood. In adults, 
blood is not required for priming of the heart-lung 
machine, but it is needed in neonates and small children. 
Usually 4 units of blood, ideally less than 5 days old, are 
initially crossmatched, or 6-8 units for repeat procedures. 



104 



HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 




8 



It is unnecessary to use albumin solutions, either for 
priming the heart-lung machine or postoperatively. 

Bleeding associated with CPB results from activation 
and loss of platelets and coagulation factors in the extra- 
corporeal circulation, failure of heparin neutralization by 
the first dose of protamine, activation of fibrinolysis in the 
oxygenator and pump and /or DIC in patients with poor 
cardiac output and long perfusion times. 

Management requires: 

• Administration of 1-2 pools of platelet concentrate 
when the platelet count is less than 30 x 10 9 1" 1 

• Transfusion of 15 ml kg" 1 of FFP to correct the loss of 
coagulation factors 

• Neutralization of excess heparin by protamine (1 mg 
of protamine neutralizes approximately 100 units of 
heparin) 

• Administration of tranexamic acid, or a similar anti- 
fibrinolytic agent, when hyperfibrinolysis is confirmed 
by laboratory testing 

• Treatment of DIC, in the first instance by correcting the 
underlying cause, such as poor perfusion, oligaemic 
shock, acidosis or infection, and then by transfusing 
FFP and platelet concentrate, as required. 

Prostatic surgery 

This may be followed by excessive urinary bleeding, the 
result of local fibrinolysis related to the release of high 
concentrations of urokinase. Antifibrinolytic agents, 
which include e-aminocaproic acid (EACA) and tranex- 
amic acid, are often helpful in reducing clot dissolution, 
but use them cautiously, as fibrinolytic inhibition can lead 
to ureteric obstruction, caused by clot formation, in 
patients with upper urinary tract bleeding. Patients 
undergoing prostatic surgery are frequently the same 
patients who are taking low dose aspirin prophylactically 
to reduce the risks of coronary artery disease and stroke; 
determine preoperatively if it can safely be stopped. 
Following prostate surgery, bleeding can be extreme if 
aspirin intake has resulted in platelet dysfunction. 

Liver disease 

This warrants special mention as the liver is an important 
site of manufacture of the components as well as the regu- 
latory factors of the coagulation and fibrinolytic pathways 
(Mehta & Mclntyre 1998). Vitamin K is required for 
hepatic synthesis of the coagulation factors II, VII, IX and 
X, as well as the coagulation inhibitors protein C and S. 
Impaired vitamin K absorption can occur in biliary 
obstruction, so give 10 mg vitamin K by intramuscular 



injection preoperatively. The liver is also the site of manu- 
facture of factor V and fibrinogen (factor I), the regulatory 
factors antithrombin and a 2 -antiplasmin. In addition, 
defects of both platelet function and number, such as 
thrombocytopenia due to complicating Hypersplenism, can 
occur. These patients are at increased risk of DIC and renal 
failure, and require assessment by a gastroenterologist/ 
hepatologist as well as a haematologist (see Chs 6, 15). 



POST-OPERATIVE ASSESSMENT 



£^^?§?£^-:^^ 



l->;v£VS^>^ 



1. Anaemia, coagulopathy and excessive bleeding in 
the immediate postoperative period are often the result of 
the operation or its complications. Continue blood com- 
ponent therapy that was commenced intraoperatively for 
the management of special situations, adhering to the 
same transfusion triggers for all components that were 
used intraoperatively (see above). 

2. Patients with excessive bleeding and clinical evi- 
dence of haemostatic failure require laboratory assess- 
ment (Table 8.6). The trauma of operation triggers both 
the coagulation and fibrinolytic pathways and places 
patients at increased risk of DIC. Do not routinely use red 
cell transfusions to correct postoperative anaemia, unless 
the haemoglobin falls to below 8 g dl _1 or is excessively 
symptomatic, as this practice has not been shown to 
improve wound healing or aid surgical recovery. 
Recovery of haemoglobin to normal levels may result 
from routinely giving iron and folic acid supplements 
after operation. Thromboprophylaxis is an important 
aspect of postoperative care (see Ch. 34). 



FUTURE DIRECTIONS 



^i$y;gftz!&&ti$t&'iZgff&. 



The field of transfusion medicine is rapidly developing 
and there is increasing awareness of the risks of hom- 
ologous blood (Greek homos - the same; from the same 
species. Not autologous, Greek autos - self.). The advent 
of recombinant DNA technology has already led to use 
of recombinant erythropoietin, but granulocyte and 
granulocyte-monocyte colony stimulating factors are in 
routine use to elevate the white cell count in leucopenic 
patients. Synthetic oxygen carriers ('artificial blood") 
have been under development for many years (Ogden & 
MacDonald 1995). Perfluorocarbons dissolve oxygen but 
function only in high concentrations of ambient oxygen 
and are useful only for short-term perfusion in intensive 
care unit situations, such as following coronary angio- 
plasty. Recombinant haemoglobin solutions and liposo- 
mal haemoglobin are under active development. 



105 




PATIENT ASSESSMENT 



Summary 

• Do you recognize the need for 
preoperative haematological assessment 
to identify those who are already anaemic, 
requiring investigation and treatment 
before operation? You may also detect 
inherited or acquired factors, such as 
anaemia, haemoglobinopathy, excessive 
bleeding tendency, affecting outcome of 
surgery and anaesthesia. 

• Are you aware of the available range of 
blood components and plasma products 
for intra- and postoperative use, their 
specific indications and associated risks? 

• What are the benefits of the increasingly 
used intraoperative cell salvage and 
autologous transfusion? 

• Do you accept that administrative and 
clerical failures dwarf the perceived risks 
of transmitting infection? 

• Do you appreciate the need to seek early 
advice from the clinical and scientific 
haematology staff on perioperative care of 
patients with inherited or acquired 
haematological conditions, and also in 
special situations, such as massive 
transfusion? 

• Are you aware of written policies and 
procedures in your institution governing 
the ordering, prescription, administration 
and documentation of blood components 
and plasma product therapy? 




References 



British Committee for Standards in Haematology 1990 

Guidelines for implementation of a maximum surgical blood 
order schedule. Clinical and Laboratory Haematology 
12: 321-327 

British Committee for Standards in Haematology, Blood 
Transfusion Task Force 1993 Guidelines for autologous 
transfusion. 1. Pre-operative autologous donation. 
Transfusion Medicine 3: 307-316 

British Committee for Standards in Haematology Blood 
Transfusion Task Force 1997 Guidelines for autologous 



transfusion. II. Peri-operative haemodilution and cell salvage. 

British Journal of Anaesthesia 78: 768-771 
Brown P 2000 BSE and transmission through blood. Lancet 

356: 955-956 
Brown P, Will RG, Bradley R, Asher DM, Detwiler L 2001 

Bovine spongiform encephalopathy and variant 

Creutzfeldt-Jakob disease: background, evolution and 

current concerns. Emerging Infectious Diseases 7: 6-16 
Flanagan P, Barbara J 1996 Prion disease and blood transfusion. 

Transfusion Medicine 6: 213-215 
Flanagan P, Barbara J 1998 Blood transfusion the risk: protecting 

against the unknown. BMJ 316: 717-718 
Houston F, Foster JD, Chong A, Hunter N, Bostock CJ 2000 

Transmission of BSE by blood transfusion in a sheep. Lancet 

356: 999-1000 
Hunt BJ 1991 Modifying peri-operative blood loss. Blood 

Reviews 5: 168-176 
McClelland DBL, Phillips P 1994 Errors in blood transfusion in 

Britain: survey of hospital haematology departments. BMJ 

308: 1205-1206 
Mehta AB 1994 Glucose-6-phosphate dehydrogenase deficiency 

Prescribers Journal 34: 178-182 
Mehta AB, Mclntyre N 1998 Haematological changes in liver 

disease. Trends in Experimental and Clinical Medicine 

8: 8-25 
Ogden JE, MacDonald SL 1995 Haemoglobin based red cell 

substitutes: current status. Vox Sanguinis 69: 302-308 
Vichinsky EF, Haberkern CM, Neumayr L et al 1995 A 

comparison of conservative and aggressive transfusion 

regimens in the peri-operative management of sickle cell 

disease. New England Journal of Medicine 333: 206-213 
Williamson L 1994 Homologous blood transfusion: the risks 

and alternatives. British Journal of Haematology 88: 451^458 
Williamson LM, Heptonstall J, Soldan K 1996 A SHOT in the 

arm for safer blood transfusion. BMJ 313: 1221-1222 




Further reading 

Asher D, Atterbury CLJ, Chapman C et al 2002 SHOT Report 

2000-2001. Serious Hazards of Transfusion Steering Group, 

London 
Contreras M (ed.) 1998 ABC of transfusion, 3rd edn. British 

Medical Journal, London 
McClelland DBL (ed.) 1995 Clinical Resources and Audit 

Group: optimal use of donor blood. Scottish Office, 

Edinburgh 
McClelland DBL (ed.) 2001 Handbook of transfusion medicine, 

3rd edn. HMSO, London 
Mintz P (ed.) 1999 Transfusion therapy: clinical principles and 

practice. American Association of Blood Banks, Virginia 
Regan F, Taylor C (2002) Recent developments in transfusion 

medicine. BMJ 325: 143-147 



Useful link 

www.doh.gov.uk/publications/coinh.html 
transfusion: HSC 2002/009 



Better blood 



106 




Fluid, electrolyte and 
acid-base balance 

W. Aveling, M. A. Hamilton 



w 



Objectives 



To understand: 

• The physiology of fluid distribution 
throughout the body 

• Methods of detecting hypovolaemia 

• Managing fluid balance 

• Principles of acid-base balance 

• Interpretation of arterial blood gas results. 



INTRODUCTION 



gastrointestinal tract, the cerebrospinal fluid (CSF) and 
aqueous humour). Water associated with bone and dense 
connective tissue, which is less readily exchangeable, is of 
much less importance. The partitioning of the total body 
water (TBW) with average values for a 70 kg male, who 
would contain 42 litres of water, is shown in Figure 9.1 
{Edelman & Leibman 1959). 

To understand fluid balance you need to know from 
which compartment or compartments fluid is being lost 
in various situations, and in which compartments fluids 
will end up when administered to the patient. For practi- 
cal purposes you need only consider the plasma, the 
interstitial space, the intracellular space and the barriers 
between them. 



To be able to manage the surgical patient optimally you 
must ensure that all tissues are perfused with oxygenated 
blood throughout the course of the operation and the 
postoperative recovery period. To do this well you need 
to understand the basics of fluid balance in the healthy 
person and then be able to apply this knowledge, along 
with that of basic physiology, to your patient. Understand 
the results provided by both arterial blood gas analysis 
and modern monitoring systems, including their limita- 
tions, in order to achieve optimal tissue perfusion. This 
has been shown to result in reduced mortality, morbidity 
and length of hospital stay. 



FUJIDCOiy^^ 

Every medical student knows that humans are mostly 
water. For you, the key to fluid and electrolyte balance is 
a knowledge of the various fluid compartments. An adult 
male is 60% water; a female, having more fat, is 55% 
water; newborn infants are 75% water. The most import- 
ant compartments are the intracellular fluid (ICF) - 55% 
of body water - and the extracellular fluid (ECF) - 45%. 
Extracellular fluid is further subdivided into the plasma 
(part of the intravascular space), the interstitial (Latin 
inter - between + sistere = to stand; the fluid between the 
cells) fluid, the transcellular water (e.g. fluid in the 



The capillary membrane 

1. The barrier between the plasma and interstitium 
(Latin inter = between + sistere = to stand; hence intercellu- 
lar spaces) is the capillary endothelium, which allows the 
free passage of water and electrolytes (small particles) but 
restricts the passage of larger molecules such as proteins 
(the colloids - Greek kolla = glue + eidos ~ form). Although 
no one has demonstrated holes in the membrane, capil- 
laries behave as if they had pores of 4-5 nm (Greek 
nanos = dwarf; 10~ 9 ) in most tissues. Kidney and liver 
capillaries have larger pores but brain capillaries are 
relatively impermeable. 

1. The osmotic (Greek otheein = to push) pressure 
generated by the presence of colloids on one side of a 
membrane which is impermeable to them is known as the 
colloid osmotic pressure (COP). Only a small quantity of 
albumin (mol, wt 69 000) crosses the membrane and it is 
mainly responsible for the difference in COP between 
the plasma and the interstitium. In fact any particle, elec- 
trolyte or protein, can exert an osmotic pressure, but the 
free diffusion of electrolytes across the capillary wall 
negates their osmotic effect. Passage of proteins across 
the capillary wall is impeded in the normal state. For 
this reason they exert an osmotic effect within the capil- 
lary, commonly referred to as the colloid osmotic pres- 
sure or oncotic (Greek onkos = mass; referring to the 



107 



9 




PATIENT ASSESSMENT 




7.5%=3.5I 
DCT 



i 



7.5%=3.5I 
plasma 



20%=8.5I 
interstitium 



55%=23l 
ICF 



functional ECF 





2.5% 

=11 

TCW 







Fig. 9.1 Distribution of total body water in a 70 kg man. DCT, dense connective tissue; ECF, extracellular fluid; ICF, 
intracellular fluid; TCW, transcellular water. 



larger particle size) pressure. The osmotic effect of these 
proteins is about 50% greater than would be expected 
for the proteins alone. The reason for this is that most 
proteins are negatively charged, attracting positively 
charged ions such as sodium - the Gibbs-Donnan effect. 
These positively charged ions are osmotically active and 
therefore increase the effective osmotic pressure. 

3. The COP is normally about 25 mmHg and tends to 
draw fluid into the capillary, while the hydrostatic pres- 
sure difference between capillary and interstitium tends 
to push fluid out. This balance was first described by the 
physiologist Henry Starling at University College, 
London, in 1896. 

4. Staverman (1952) introduced the concept that differ- 
ent molecules are 'reflected' to a different extent by the 
membrane. This term, the reflection coefficient, varies 
between zero (all molecules passing through the mem- 
brane) and +1 (all molecules reflected). In disease states 
when the capillary membrane becomes leaky, such as 
sepsis and the systemic inflammatory response syn- 
drome (SIRS), the reflection coefficient falls. Flow across 
the membrane is represented by the equation: 

V = K f S[P c - P lF ) - <x Up - %)] 

where V is the rate of movement of water, Kf is the capil- 
lary filtration coefficient, S is the surface area; P c and P, F 
are the capillary and interstitial hydrostatic pressures, irp 



and ir ]F are the plasma and interstitial oncotic pressures, 
and cr is the reflection coefficient. 

The cell membrane 

The barrier between the extracellular and intracellular 
space is the cell membrane. This is freely permeable to 
water but not to sodium ions, which are actively pumped 
out of cells. Sodium is therefore mainly an extracellular 
cation, while potassium is the main intracellular cation. 
Water moves across the cell membrane in either direction 
if there is any difference in osmolality between the two 
sides. Osmolality expresses the osmotic pressure across a 
selectively permeable membrane and depends on the 
number of particles in the solution, not their size. Normal 
osmolality of ECF is 280-295 mOsm kg -1 . Since each 
cation is balanced by an anion, an estimate of plasma or 
ECF osmolality can be obtained from the formula: 1 

Osmolality (mOsm kg -1 ) 
= 2 (Na + + K + ) + glucose + urea (mmol I -1 ) 



Osmolality is expressed per kilogram of solvent (usually 
water), whereas osmolality is expressed per litre of solution. 
The presence of significant amounts of protein in the solution, 
as in plasma, means that the osmolality and osmolarity will not 
be the same. 



108 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 




9 



Note that the colloids contribute very little to total osmol- 
ality as the number of particles is small, although, as we 
saw above, they play an important role in fluid movement 
across the capillaries. 



Movement of water between compartments 

1. Consider what happens when a patient takes in 
water, either by drinking or in the form of a 5% glucose 
infusion, the glucose in which is soon metabolized. It is 
rapidly distributed throughout the ECF, with a resultant 
fall in ECF osmolality. Since osmolality must be the same 
inside and outside cells, water moves from ECF to ICF 
until the osmolalities are the same. Thus 1 litre of water 
or 5% glucose given to a patient distributes itself through- 
out the body water. In spite of being infused into the 
intravascular compartment (3.5 litres) it will be dis- 
tributed throughout the body water space (42 litres) of 
which only 3.5/42, approximately 7.5%, is intravascular. 
For this reason approximately 13 litres of 5% glucose 
need to be infused to increase the plasma volume by 
1 litre. By a converse argument we can see that someone 
marooned on a life raft with no water will lose water from 
all compartments. 

2. Normal saline (0.9%) contains Na + and CI - at con- 
centrations of 150 mmol l" 1 . If this is infused into a patient 
it stays in the ECF because the water tends to follow the 
sodium ion and osmolality matches that inside the cells, 
thus there is no net movement of water into the cells. 
Therefore a volume of normal saline given intravascularly 
tends to distribute throughout the extracellular space. The 
extracellular fluid makes up approximately 45% of the 
body water, with the plasma volume being approximately 
7.5%, and therefore 1/6 remains intravascular and 6 litres 
need to be given to increase the plasma volume by 1 litre. 
Equally, a patient losing electrolytes and water together, 
as in severe diarrhoea, loses the fluid from the ECF and 
not the ICF. 




Key point 



• Only 1/6 of 0.9% saline fluid given 
intravenously remains in the vascular 
compartment, the remainder enters the 
interstitium. 

3. Finally, consider the infusion of colloid solutions 
(e.g. albumin, starch solutions and gelatins). The capillary 
membrane is impermeable to colloid and thus the 
solution stays in the plasma compartment (there are, of 
course, circumstances in which it can leak out). A burned 



patient losing plasma loses it from the vascular compart- 
ment and initially there is no shift of fluid from the inter- 
stitial space. As blood pressure falls, hydrostatic pressure 
in the capillary falls, and if colloid osmotic pressure is 
maintained, the Starling forces draw water and elec- 
trolytes into the vascular compartment from the intersti- 
tium. Because there are only 3.5 litres of plasma, losses 
from this compartment lead to hypoperfusion and 
reduced oxygen transport to tissues and are potentially 
life-threatening. The use of hypertonic saline as a resusci- 
tation fluid has become topical lately with reports of 
improved survival (Mattox et al 1991). The theoretical 
advantage of these solutions is that a small volume of 
administered fluid provides a significant plasma volume 
expansion. The high osmolarity of these solutions draws 
tissue fluid into the intravascular space and thus should 
minimize tissue oedema for a given plasma volume incre- 
ment, leading to better tissue perfusion. They are limited 
at present to single dose administrations and clinical data 
are still relatively sparse. 

4. Since the plasma is part of the ECF, any loss of ECF 
results in a corresponding decrease in circulating volume 
and is potentially much more serious than loss of an 
equivalent volume from the total body water. For 
example, compare a man losing 1 litre a day of water 
because he is marooned on a life raft with a man losing 
1 litre a day of water and electrolytes due to a bowel 
obstruction. The man on the life raft will lose 7 litres in a 
week from his total of 42 litres body water, i.e. a 17% loss. 
The plasma volume will fall by 17%, which is survivable. 
The man with a bowel obstruction, on the other hand, 
loses his 7 litres from the functional ECF of 12 litres, i.e. a 
58% loss. Losing more than half of the plasma volume is 
not compatible with life. 



NORMAL WATER AND ELECTROLYTE 

1. We take in water as food and drink and also make 
about 350 ml per day as a result of the oxidization of 
carbohydrates to water and carbon dioxide, known as the 
metabolic water. This has to balance the output. Water is 
lost through the skin and from the lungs; these insensible 
losses amount to about 1 litre a day. Urine and faeces 
account for the rest. A typical balance is shown in 
Table 9.1. 

2, The precise water requirements of a particular 
patient depend on size, age and temperature. Surface 
area (1.5 litres H 2 m -2 daily) is the most accurate guide, 
but it is more practical to use weight, giving adults 
30-40 ml kg" 1 . Children require relatively more water 
than adults, as set out in Table 9.2, Add requirements for 
the first 10 kg to the requirements for the next 10 kg and 



109 




PATIENT ASSESSMENT 



Table 9.1 


Average daily 


water balance for 


a 




sedentary adult in temperate conditions 




! 

J 


Input (mt) 
Drink 




Output (ml) 






1500 


Urine 


1500 




Food 


750 


Faeces 


100 




Metabolic 


350 


Lungs 
Skin 


400 
600 




Total 


2600 


Total 


2600 





Table 9.2 Daily water requirements by body 
weight in children 

Weight Water requirements 
(kg) 




0-10 
10-20 
>20 



4 mi kg ] h" 1 

40 ml h" 1 + 2 ml kg" 1 h T for each kg >10 kg 

60 ml h _1 + 1 ml kg" 1 h _1 for each kg >20 kg 



likewise add to subsequent weight. Therefore, for a 
25 kg child the basal requirements per hour should be: 

(10 x 4) + (10 x 2) + (5 x 1) = 65 ml h" 1 

3. The average requirements of sodium and potassium 
are 1 mmol kg" 1 day 1 of each. Humans are very efficient 
at conserving sodium and can tolerate much lower 
sodium intakes, but they are less good at conserving 
potassium. There is an obligatory loss of potassium in 
urine and faeces and patients who are not given potas- 
sium becomes hypokalaemic. As potassium is mainly an 
intracellular cation, there may be a considerable fall in 
total body potassium before the plasma potassium falls. 



PRESCRIBING FLUID REGIMENS 




When prescribing fluids, remember: 

• Basal requirements 

• Pre-existing dehydration and electrolyte loss 

• Continuing abnormal losses over and above 
basal requirements. 

Give special consideration to intraoperative fluid balance, 
as all three of the above apply. Normally nourished 
patients taking nothing orally for a few days during 
surgery unusually require intravenous feeding, although 
some reports have shown that early feeding improves 
postoperative recovery. Only in special circumstances is 



intravenous feeding required; this topic is outside the 
scope of this chapter. 

Basal requirements 

We have seen above the daily requirements of water and 
electrolytes. From the various crystalloid solutions that are 
available (Table 9.3), we can design fluid regimens for basal 
requirements. Normal (0.9%) saline, Hartmann's Ringer- 
lactate solution, 5% dextrose, and dextrose 4%-saiine 0.18% 
are the most commonly used. Note that their osmolalities 
are similar to that of ECF, that is, they are isotonic with 
plasma. The purpose of the glucose is to make the solution 
isotonic, not to provide calories, although a small amount 
of glucose does have a protein-sparing effect during the 
catabolism that follows a major operation and trauma. Our 
standard 70 kg patient can be provided with the 24 h basal 
requirements of 30-40 ml kg" 1 of water and 1 mmol kg*" 1 of 
sodium in any of the ways shown in Table 9.4. 

Potassium 

None of these regimens supply significant amounts of 
potassium. Potassium chloride can be added to the bags 
and is supplied as ampoules of 20 mmol in 10 ml or 1 g 
(=13.5 mmol) in 5 ml. Bags of crystalloid are available 
with potassium already added and this is safer than 
adding ampoules. 




Key points 



• Be aware that potassium can be dangerous; 
hyperkalemia and acute change in potassium 
levels may cause cardiac arrhythmias and 
asystole. 

• Never inject it as a bolus. 

Tragedies have been reported to the medical defence 
societies in which potassium chloride ampoules are mis- 
taken for sodium chloride and used as 'flush', with fatal 
consequences. Hyperkalaemia may also occur if potass- 
ium supplements are given to anuric patients. Usually 
wait until you are certain of reasonable urine output 
before adding potassium to the regimen postoperatively. 




Safe rules for giving potassium are: 

• Urine output at least 40 ml rr 1 

• Not more than 40 mmol added to 1 litre 

• No faster than 40 mmol h~ 1 . 



110 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 



9 



Table 9.3 Content of crystalloid solutions 












Name 


Known as 


Na + 


ci- 


K + 


HCOj Ca 2 * 


Calculated 










{mmol I -1 ) 




(mQsm I" 1 ) 


Sodium chloride 0.9% 


Normal saline 


150 


150 




300 


Sodium chloride 0.9%, 


Normal saline + KG 


150 


190 


40 




380 , 


potassium chloride 0.3% 














Sodium chloride 0.9%, 


Normal saline + KCI 


150 


170 


20 




340 


potassium chloride 0.15% 

Ringer's lactate 


Hartmann's 


131 


11 1 


5 


29 (as lactate) 


280 


Glucose 5% 


5% dextrose 










280 


Glucose 5%, potassium 


5% dextrose + KCI 




40 


40 




360 


chloride 0.3% 














Glucose 5%, potassium 


5% dextrose + KCI 




20 


20 




320 


chloride 0.15% 














Glucose 4% r sodium 


Dextrose saline 


30 


30 






286 


chloride 0.18% 














Glucose 4%, sodium 
chloride 0.18% 


Dextrose saline + KCI 


30 


70 


40 




366 


potassium chloride 0.3% 














Glucose 4%, sodium 


Dextrose saline + KCI 


30 


50 


20 




326 


chloride 0,18%, potassium 














chloride 0.15% 














Sodium chloride 0.45% 


Half normal saline 


75 


75 






150 


Sodium chloride 1.8% 


Twice normaj saline 


300 


300 






600 


Sodium bicarbonate 8.4% 


— 


1000 






1000 


2000 


Sodium bicarbonate 1.4% 


— 


167 






167 


334 



Continuing loss 

Patients with continuing losses above the basal require- 
ments need extra fluid. The commonest example in anaes- 
thetic and surgical practice is the patient with bowel 
obstruction. Fluid can be aspirated by a nasogastric tube 
to assess both volume and electrolyte content. Give saline 
with added potassium to replace it. Dextrose saline is not 
an appropriate fluid for this purpose because it contains 
only Na 30 mmol H, and 5% glucose is even worse, 
Hyponatraemia results if these solutions are used to 
replace bowel loss. 



Table 9,4 Basal water and sodium regimens for a 


70 kg patient 


on intravenous fluids 


Solution 


Volume (ml) 


Na* (mmol) K + (mmol) 


5% glucose 


2000 





0,9% saline 


500 


75 


5% glucose 


2000 


— — 


Hartmann's 


500 


65.5 2.5 


4% glucose 


2500 


75 


0.18% saline 







To keep track of the fluids, keep a fluid balance chart. 
Record all fluid in (oral and intravenous) and all fluid out 
(urine, drainage, vomit, etc.). Every 24 h total them, allow 
for insensible losses and record the balance, positive or 
negative. Any patient on intravenous fluids should have a 
daily balance, daily electrolyte measurements and a new 
regimen calculated every day. Never use the instruction 
'and repeat' in fluid management; it has led to disasters in 
the past. 

Correction of pre-existing dehydration 

Patients who arrive in a dehydrated state clearly need to 
be resuscitated with fluid over and above their basal 
requirements. Usually this will be done intravenously. 




Key points 



• Identify from which compartment or 
compartments the fluid has been lost. 

• Assess the extent of the dehydration. 

Resuscitate the patient with fluid similar in composition 
and volume to that which has been lost. From what you 
know about the movement of fluid between compartments 



111 




PATIENT ASSESSMENT 



(see above) and the patient's history, you can usually 
decide from where the losses are coming. As we have seen, 
bowel losses come from the ECF, while pure water losses 
are from the total body water. Protein-containing fluid is 
lost from the plasma, and there may sometimes be a com- 
bination of all three types of loss. 

Assessment of deficit 




Key point 



• Occult untreated intraoperative hypovolaemia 
may lead to organ failure and death long after 
the operative period. 

1 . Assessment of deficit is, by its very nature, retrospec- 
tive and reactive. It is still far better to predict loss, such 
as that experienced by patients who have received bowel 
preparation for surgery, and replace fluid prospectively. 
In estimating the extent of the losses, take into account the 
patient's history, clinical examination, measurement and 
laboratory tests. A dehydrated patient may be thirsty, 
have dry mucous membranes, sunken eyes (and in 
infants fontanelles), cheeks, loss of skin elasticity and 
weight loss. They feel weak and, in severe cases, are men- 
tally confused, all of which are soft endpoints for ade- 
quate resuscitation; do not rely upon them in isolation. 
The cardiovascular system provides harder endpoints for 
resuscitation with tachycardia and peripheral vasocon- 
striction as the body responds with an endogenous sym- 
pathetic drive, so that the patient feels cold. Prior to the 
fall in blood pressure seen in continuing haemorrhage, 
there is evidence that other organs, such as the gut, can 
suffer from occult hypoperfusion. A study by Hamilton- 
Da vies et al (1997) showed that, in progressive haemor- 
rhage, gastrointestinal tonometry demonstrated gut 
mucosal hypoperfusion greatly in advance of blood 
pressure, heart rate or arterial blood gas changes. 

The famous American surgeon, Alfred Blalock 
(1899-1964), commented in 1943 after his experiences of 
war, Tt is well known by those that are interested in this 
subject that the blood volume and cardiac output are 
usually diminished in traumatic shock before the arterial 
blood pressure declines significantly/ 

2. Next follow decreases in stroke volume, which up 
until this point have been maintained by a decrease in the 
capacitance of the vascular system. Cardiac output falls, 
causing a compensatory rise in heart rate and, eventually, 
a fall in blood pressure. At this point the protective 
autoregulation of blood flow to the brain, heart and 
kidneys may fail and severe dehydration produces cloud- 
ing of consciousness and oliguria. Carry out the simple, 
essential measurements of weight, pulse, blood pressure 



and urine output, to assess and treat fluid loss - although 
sympathetic drive from the nervous system may mis- 
leadingly maintain blood pressure until very late. 

3. Measure central venous pressure (CVP). Insert an 
intravenous catheter into a central vein. The catheter tip 
should lie within the thorax, usually in the superior vena 
cava. In this position, blood can be aspirated freely and 
there is a swing in pressure with respiration. Measure the 
pressure, usually with an electronic transducer, although it 
can be done quite simply by connecting the patient to an 
open-ended column of fluid and measuring the height 
above zero with a ruler. The zero point for measuring CVP 
is the fifth rib in the midaxillary line with the patient supine, 
corresponding to the position of the left atrium. The normal 
range for CVP is 3-8 cmH 2 (1 mmHg = 1.36 cmH 2 0). A 
low reading, particularly a negative value, confirms dehy- 
dration, but the converse is not true. A high or normal CVP 
does not indicate an adequately filled vascular system. For 
example, a patient on a noradrenaline (epinephrine) infu- 
sion or with a high intrinsic sympathetic tone may have a 
high CVP in spite of a low volume, high resistance vascu- 
lar system. CVP measurements are of more use as a guide 
to the adequacy of treatment. 




Key point 



• The response of the CVP to a fluid challenge of 
200 ml colloid tells you more about the state of 
the circulation than a single reading. 

4. A dehydrated patient's CVP rises in response to 
the challenge but then falls to the original value as the 
circulation vasodilates to accommodate the fluid. If the 
response to the challenge is a sustained rise (5 min after 
the challenge) of 2-A cmH 2 0, this indicates a well-filled 
patient. If the CVP rises by more than 4 cmH 2 and does 
not fall again, this indicates overfilling or a failing 
myocardium. A fluid challenge is the only logical way of 
attempting acutely to restore the intravascular volume. 

5. The CVP reflects the function of the right ventricle, 
which usually parallels left ventricular function. In cardiac 
disease, either primary or secondary to systemic illness, 
there may be disparity between the function of the two 
ventricles. The left ventricular function can be assessed by 
inserting a balloon-tipped catheter (Swan-Ganz) into a 
branch of the pulmonary artery. When the balloon is 
blown up to occlude the vessel, the pressure measured dis- 
tally gives a good guide to the left atrial pressure. This is 
called the pulmonary capillary wedge pressure (PCWP) 
and is normally 5-12 mmHg. In certain circumstances the 
CVP may be high when the PCWP is low, which then indi- 
cates that, although the right atrium may be well filled, the 



112 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 



9 



filling state of the systemic circulation is low. Here, as with 
the fluid challenge of the CVP, manage the filling status of 
the patient by means of fluid challenging the PCWP. 
Similar changes in level apply. 

6. Both intra opera tively and on the intensive care unit 
there are many ways to monitor flow-based values such 
as stroke volume and cardiac output. Measurement is 
easy and with minimal morbidity using simple and effec- 
tive systems such as the oesophageal Doppler monitor. 
Slightly more invasive systems, such as pulse contour 
analysis or pulmonary artery flotation catheters, also 
provide useful flow-based information but do cause a 
slightly higher morbidity. Whatever method you choose, 
and it is most likely that variants will be used on the 
general wards in the near future, they all allow you to 
challenge a haemodynamic variable with fluid to bring 
about an improvement in flow. Pressure is of secondary 
importance; it is easy to generate pressure in an occluded 
vessel but impossible to generate flow which brings with 
it oxygen and all the means by which a cell survives. 




Key points 

• Elderly patients have poor cardiovascular 
system compliance. 

• Consider frequent small volume fluid 
challenges. 

• Left ventricular failure does not equate to 
hypervolemia. 

7. Work performed by Shoemaker et al (1988) demon- 
strated that the Swan-Ganz catheter can be used to treat 
patients to oxygen delivery /consumption goals when 
undergoing high risk surgery They found that an 
improved outcome followed in those who achieved goals 
of: 



m 



• Oxygen delivery 2 > 600 ml min 

• Oxygen consumption 3 > 1 70 ml min -1 m~ 2 

• Cardiac index > 4.5 1 min -1 m~ 2 

However, one argument is that these patients are self- 
selecting and that they would have had a good outcome 
anyway as they are able to achieve these goals / thus 
demonstrating better cardiovascular function. Boyd et al 
(1993) also demonstrated an improvement in outcome in 



patients treated with the inotropic sympathomimetic 
dopexamine to achieve these goals. Again, the same argu- 
ments apply. There are now many studies based around 
boosting oxygen delivery with a combination of fluids 
and inotropes in an attempt to decrease surgical morbid- 
ity and mortality These have recently been analysed in a 
formal Cochrane meta-analysis by Grocott et al (2003), 
which proves that high risk surgical patients undergoing 
a process of optimization are not only significantly less 
likely to die as a result of surgery but may also suffer less 
morbidity as well. This is not true of an intensive care 
population where it has been shown that, if critically ill 
patients are subjected to a similar style of management by 
driving their cardiovascular systems to achieve these 
goals with fluid and inotropes, this group fare worse than 
a control group (Hayes et al 1994). This may simply 
reflect the fact that a significant insult has already 
occurred which is not remediable to boosting oxygen 
delivery. 

8. In summary, a reasonable form of management is 
to aim to achieve delivery /consumption goals in cardio- 
vascularly fit subjects undergoing high risk surgery. 
However, in patients with cardiovascular disease, seek 
to achieve these goals only using fluid and agents that 
offload the left ventricle, such as glyceryl trinitrate, thus 
reducing myocardial work. Prefer to perform this under 
Swan-Ganz monitoring of cardiac function, trans- 
oesophageal echocardiography or the more recent non- 
invasive oesophageal Doppler cardiac output monitor. 
For those in whom these goals are unattainable, turn 
your attention to ensuring an otherwise meticulous 
perioperative course. 

9. Occult hypovolaemia can be detected by measuring 
gut mtramucosal pH (pHi). This has been demonstrated 
as the area that first suffers during haemorrhagic blood 
loss (Price et al 1966) and thus is possibly the first to 
develop acidosis due to anaerobic metabolism. It can be 
assessed by means of a saline-filled balloon passed into 
the gut lumen which equilibrates with the carbon dioxide 
generated in the gut mucosa. From this can be derived the 
intramucosal pH. This value has been related to outcome 
following high risk surgery (My then et al 1993) and 
studies are currently being devised to investigate the 
effects of resuscitating patients to a pHi endpoint. The 
technology has recently been extended to an automated 
air-filled balloon in combination with an end-tidal carbon 
dioxide monitor (Tonocap), thus eliminating user bias 
due to sampling technique differences. Current trials with 
this device are in progress. 



2 Oxygen delivery = cardiac output x Hb x arterial saturation x 

1.34. 

3 Oxygen consumption = cardiac output x Hb x (arterial - mixed 

venous saturations) x 1.34. 



Quantification of plasma and ECF loss 

1. If plasma is lost from the circulation, that remaining 
still has the same albumin concentration, although the 



113 




PATIENT ASSESSMENT 



volume is diminished. Since no red cells are lost they 
become concentrated, resulting in a rise in haematocrit. 
Plasma is, of course, part of the ECF, so that losses of fluid 
and electrolytes without protein loss will cause a rise in 
haematocrit but also a rise in plasma protein concentration 
(Fig, 9.2). Changes in plasma albumin and haematocrit thus 
provide a good guide to ECF losses, while only haematocrit 
is of use in monitoring plasma loss (Robarts et al 1979). 




Key point 

• In ECF depletion, the total amount of albumin 
stays the same, although its concentration goes 
up. 

Haematocrit and plasma albumin are thus very useful in 
the assessment of ECF and plasma losses; much more so 
than the sodium which, though being lost, does not 
change in concentration. 



2. Table 9.5 summarizes the changes in volume and 
composition of various compartments in: 

• isotonic fluid loss 

• loss of water in excess of electrolytes 

• loss of sodium in excess of water. 

The corresponding expansion of compartments is also 
shown. It is a useful exercise to work through the various 
boxes predicting what change, if any, will occur. In the 
case of water loss (from both ECF and ICF) remember that 
the red cells are part of the ICF, so when water is lost from 
both compartments the haematocrit may not change. 
Similarly, when there is hypotonic expansion, red cells 
increase in volume as part of the ICF, and with the simul- 
taneous expansion of ECF there may again be no change 
in haematocrit. 

Water and electrolyte replacement 

Having assessed the amount of deficit, as discussed above, 
now decide what to give to correct it. The composition of 



plasma 



rbcs 



Interstilium 



Interstilium 



B 



fnlerstitium 



Fig. 9.2 A Loss of ECF leading to a rise in albumin concentration and haematocrit. B Loss of plasma leading to a rise 
in haematocrit but no change in albumin concentration. 



114 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 




9 





Table 9.5 Changes resulting from three kinds of expansion 


and contraction of body fluids 




Acute change 


Example 


Change in 
ECr vol 


Change in 

ICF vol 


Change in 
[Na] 

— > 

T 

I 

-> 

T 

i 


Change in 
[Hctl 


Change in 
[protein] 


Loss H 5 + NaCl 
Loss H 2 > Na 
Loss Na > H 2 
Isotonic expansion 
Hypertonic expansion 
Hypotonic expansion 


Cholera 

Excess sweating 
Addison's 
Saline infusion 
2 x normal saline 
5% glucose infusion 


i 
I 
i 
T 
T 
T 


— * 

1 

T 

— ► 

1 

T 


T 

— > 
T 

1 

i 


T 
T 
T 
i 
i 
i 



various body fluids (Table 9.6) shows us that ECF losses of 
water and electrolytes should be replaced either with 
normal saline or Ringer's lactate with added potassium 
(see Basal requirements, p. 110). The only hypotonic secre- 
tions are saliva and sweat. The sodium content of sweat 
varies and responds to aldosterone. Gastric secretion, 
although having a sodium content of only 50 mmol l" 1 , is 
isotonic with ECF because of the hydrogen it contains. 
When the losses are primarily of gastric secretion, such as 
pyloric stenosis, you might think it necessary to supply 
hydrogen ions. In fact, the kidney compensates by retain- 
ing hydrogen and excreting sodium and bicarbonate so 
that the net effect is a loss of sodium and chloride. 
Rehydrate, therefore, with normal saline with potassium. 

Plasma replacement and plasma substitutes 

1 . When you need to replace lost plasma there is a choice 
between giving plasma prepared from donated blood or 
one of the synthetic plasma substitutes. Human plasma 
protein fraction (HPPF) or human albumin solution (HAS) 
is prepared by separating red cells from donated blood. A 
bottle contains plasma from several donors and has been 
pasteurized to prevent the transmission of disease such as 
hepatitis or human immunodeficiency virus (HIV). It con- 
tains 4.5% albumin, has no clotting factors and is stable at 
room temperature. The main disadvantage is its cost (£46 in 
the UK, 1999), which reflects its limited availability. The 
costs of blood and blood derived products are higher. Blood 
is already leucodepleted to reduce the risk of infection and 



transfusion reactions, which significantly adds to the cost 
of production. A recent meta-analysis suggested that 
administration of human albumin in the critically ill 
patient may increase mortality (Schierhout & Roberts 
1998). However, this analysis included studies looking at 
albumin use for both hypoalbuminaemia, which is not 
common current clinical practice in the perioperative 
setting, and hypovolaemia. Albumin administration in 
the management of hypovolaemia is also relatively 
uncommon because of the high cost, and because the 
semisynthetic colloids are considered to be at least as 
effective. This analysis looked at a number of studies, half 
of which show benefit for this indication, in widely diver- 
gent populations and so does not provide a clear message 
to influence clinical practice. Rather, it suggests the need 
for a well-designed randomized controlled trial with 
appropriate outcome goals. A number of solutions con- 
taining molecules large enough to stay within the capil- 
laries and generate colloid osmotic pressure are available 
as plasma substitutes (Table 9.7). 

2. Dextrans are glucose polymers available in prepara- 
tions of different molecular weights. There is a large range 
of molecular weights in the solution. Dextran 70 is so 
called because the average molecular weight is supposed 
to be 70 000. In fact, the number-average molecular 
weight, which is much more relevant to the colloid 
osmotic pressure, is 38 000 (see footnote to Table 10.7) 
(Webb et al 1989). Dextran 40 has smaller molecules and 
can be nephrotoxic. Dextran 110 has larger molecules. 
Neither of these will be considered further. Dextran 70 is 



Table 9.6 Electrolyte content and dally volume of body secretions 





Na 




Mmmol 1 ') 


CI 


Volume (litres dail 


Saliva 


15 




19 


40 


1.5 


Stomach 


50 




15 


140 


2,5 


Bile, pancreas, small bowel 


130- 


145 


5-12 


70-100 


4.2 


Insensible sweat 


12 




10 


12 


0.6 


Sensible sweat 


50 




10 


50 


Variable 



115 



<n 



Table 9.7 Characteristics 


of colloid solutions 












Name 


Brand name 


No. average* 
mol. wt 


Mol. wt range Na* K* Ca 24 

(mrnol I" 1 ) 


f,^ in plasma Adverse 

reactions (%) 


Effect on 
coagulation 


Cost 

(UK 

1988) 




Mild 


Severe 


Human plasma protein 
fraction 


HPPF 


69 000 


69 000 1 50 5 2 


20 days 0.02 


0,004 


None 


£40 


Dextran 70 in saline 
0.9% or glucose 5% 


Macrodex 
Lomodex 70 
Gentran 70 


38 000 


<10 000 > 250 000 150 


12 h 0.7 


0.02 


Inhibit platelet 
aggregation 
Factor Villi 
Interfere with 
crossmatch 


£4.78 


Polygeline 
(degraded gelatin) 


Haemactel 


24 500 


<5 000-»50 000 145 5 6.25 


2.5 h 0.12 


0.04 


None 


£371 


Succinylated gelatin 


Gelofusin 


22 600 


<10 000~^ 140 000 154 0,4 0.4 


4h 0,12 


0.04 


None 


£4 r 63 


Hydroxyethyl starch 
6% in saline (hetastarch) 


Hespan 


70 000 


<10 000->10 6 154 


25 h 0.09 


0.006 


>1.5 g kg 1 day ! 
can cause 
coagulopathy 


£16.25 
rers. 


*Number-average molecu 


ar weight should not be confused with weight-average molecular 


weight, which is usua 


lly quoted by the manufactu 



Number-average molecular weight is more appropriate. 




<^> 



3 



> 

m 

LA 

to 

2 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 



9 



quite a good plasma substitute, but its use has declined in 
popularity because of its adverse effects on coagulation 
and crossmatching and the relatively high incidence of 
allergic reactions. 

3. Gelatin solutions are prepared by hydrolysis of 
bovine collagen. They have the advantage over dextrans 
of not affecting coagulation and of having a low incidence 
of allergic reactions. Being of smaller average particle 
size, they stay in the intravascular space for a shorter 
time. Haemaccel contains potassium and calcium ions, 
which can cause coagulation if mixed with citrated blood 
in a giving set. Haemaccel stays for a shorter time in the 
circulation: 30% of the molecules are dispersed to the 
interstitial tissues within 30 min. Gelofusin is probably 
preferable from this point of view. 

4. Hetastarch, 6% in saline/ has become available in the 
last few years. It has the largest average molecular weight 
of any of the plasma substitutes and therefore stays in the 
circulation longer. Limit the dose to 1500 ml 70 kg" 1 ; more 
can cause coagulation problems. About 30% of a dose is 
taken up by the reticuloendothelial system without 
apparent detriment to its function. Smaller molecules 
(mol. wt <50 000) are filtered by the kidneys. Larger ones 
are broken down by plasma amylase until small enough 
for real excretion. 

5. Electrolyte balanced colloid solutions, such as Hextend, 
represent a new area of fluid development and it is 
possible that these solutions offer increased benefit over 
currently used colloids, due to provision of a more 
favourable physiological milieu. Indeed, clinical trials to 
date with balanced colloids (Wilkes et al 2001) suggest 
those undergoing major surgery benefit from better 
acid-base profiles and end-organ perfusion than those 
receiving traditional colloids suspended in 0.9% saline. It 
is now well recognized that intravenous fluids based on 
so called 'normal saline' do not represent the physiologi- 
cal composition of plasma and in excess lead to a variety 
of organ dysfunctions, such as those reported by Wilkes 
et al, and others including cerebral, renal, gut and 
metabolic dysfunction. Until recently it has been difficult 
to explain why, but with new theories of acid-base physi- 
ology emerging (see later), the pathophysiology of why 
'normal saline' causes acidosis is easy to explain. In 
essence 0.9% saline (normal saline) is not normal at all. It 
has approximately 150 mmol of chloride and 150 mmol of 
sodium per litre. When given in excess, which may be as 
little as 2-3 litres per 24 h, it can produce high levels of 
chloride, which in turn lead to the development of a mild 
acidosis by reducing the strong ion difference (see later). 

Choice of solution for plasma expansion 

1. The intravascular space can be expanded by using 
crystalloid solutions such as saline, but because the fluid 



spreads throughout the ECF, 6 litres of crystalloid are 
needed to expand the plasma by 1 litre. In an emergency, 
crystalloid is useful. All the battle casualties in the 
Falklands War were resuscitated in the field with 
Hartmann's solution. 

2. Do not use 5% glucose from choice as it is dis- 
tributed throughout both ECF and ICF compartments; 
thus 13 litres are needed to increase the intravascular 
space by 1 litre. For most patients with acute hypo- 
volemia, the best combination of advantages at low cost 
is offered by succinylated gelatin (Gelofusin). Being rela- 
tively short acting, it is particularly useful as a holding 
measure until blood becomes available. Gelofusin proba- 
bly stays within the intravascular space for 60-90 min at 
most. 

3. In continuing hypovolemia, hetastarch gives more 
prolonged expansion and its larger molecules are better 
retained in the circulation when the capillaries are leaky, 
e.g. in septicaemic shock. 

4. There is continued debate as to whether it is better 
to resuscitate with a crystalloid or colloid, the so-called 
crystalloid versus colloid debate. There have been many 
meta-analyses that failed to prove any advantage of one 
over the other for the purpose of resuscitation. Indeed, the 
most common conclusion is that there are insufficient 
data available to recommend one rather than the other. A 
trial of sufficient power to demonstrate a mortality dif- 
ference using either crystalloid or colloid would need to 
include over 7000 patients. Trials of that size are currently 
under way in Australia but are likely to add to the debate 
rather than resolve it. 

Blood loss and blood transfusion 

1. So far we have considered plasma loss and plasma 
expansion. Most of what has been said about the assess- 
ment and replacement ot plasma volume applies to blood 
loss. Transfusion of donated blood is possible in most cir- 
cumstances, but has several disadvantages to be weighed 
against the fact that only haemoglobin carries oxygen. 
With a haemoglobin of 14 g dL\ evolution has equipped 
us with spare capacity as far as oxygen-carrying capacity 
is concerned. Indeed, as haematocrit falls, the decrease in 
oxygen carrying is compensated by better tissue perfu- 
sion due to reduced blood viscosity. 

2. It has been shown that the best balance between 
oxygen carrying and viscosity occurs around a haemato- 
crit of 30%. It is also suspected that blood transfusion at 
the time of surgery for certain cancers leads to immuno- 
logical suppression and poorer long-term survival. On 
the other hand, blood transfusion prior to transplant pro- 
cedures improves graft survival. Because of anxiety over 
HIV, and with a lack of knowledge of mechanisms of 
prion transfer relating to bovine spongiform encephalitis 



117 




PATIENT ASSESSMENT 



(BSE), there is reluctance by the public to accept blood 
transfusion. Trials in critical care suggest that restricting 
transfusion to patients with Hb below 8 g% is associated 
with a better outcome (Hebert et al 1999). 

3. For these reasons, in addition to the hazards of blood 
transfusion listed in Table 9.8, the expense of blood and 
rarity of some blood groups, there is reluctance to trans- 
fuse blood. In practical terms, operative blood loss up to 
500 ml can be replaced with saline, remembering that 
six times as much will be needed (see above), or plasma 
substitutes. Only if more than 1 litre of blood has been lost 
in a healthy adult should you consider giving blood. 
Point of care testing with Hb analysers or from arterial 
blood gases will allow you to quantify the need for trans- 
fusion; use them when possible. Anaemia alone is a diffi- 
cult clinical sign on which to base the prescription of 
blood. 

4. Rather than supply whole blood, it is more efficient 
for the transfusion service to separate it into components 
(Table 9.9). Blood cross-matched for patients undergoing 
surgery usually comes as plasma-reduced blood - 
'packed cells'. This is more viscous than whole blood so 
give it with appropriate amounts of crystalloid or colloid 
solution to restore the volume. 

5. Assess the quantity of blood lost by clinical means, 
as outlined above. At operation, watch the suction bottle 
and weigh swabs, although this generally underestimates 
the loss. The only real way of quantifying loss is by 
arterial blood gases measurement, full blood counts 
performed in the laboratory, or by bedside testing by, for 
example, Haemacue when available. In operations such 
as transurethral resection of the prostate, measurement of 
haemoglobin in the irrigating fluid gives an accurate 
measure of blood loss. Haematocrit and haemoglobin 
concentrations do not change in acute blood loss until the 
blood remaining in the patient has been diluted by shift 



Table 9.9 Blood products 




Table 9.8 The hazards of blood transfusion 



Any transfusion 

• Transmission of disease, e.g. AIDS, malaria (donor 
blood screened for HIV, hepatitis, syphilis) 

• Bacterial contamination 

■ Pyrogenic reactions (antibodies to white cells) 

• Incompatibility reactions 

• ± Haemolysis (clerical error commonest cause) 

Massive transfusion 

• Hypothermia 

■ Hyperkalaemia 

■ Citrate toxicity 

• Acidosis 

• Microaggregate embolism, 'shock lung" 

• Dilution and consumption of clotting factors 



Plasrna-reduced blood {packed cells) 

Washed red cells: if transfusion reaction a 

problem 

Plasma protein fraction (HPPF) 

Fresh frozen plasma {FFP): contains clotting 

factors more dilute than the concentrates below 

Cryopredpttate: rich in factor VIM 

Factor VIII concentrate: even richer in VIM 

Factors M, VII, IX and X concentrate 

Factor XI concentrate 

Fibrinogen 

Platelet concentrate 



of fluid from the interstitial space or intravenous infu- 
sion. Plasma-reduced blood and whole blood more than 
1 day old, which it almost always is, contain no viable 
platelets and a few clotting factors. The same applies to 
plasma protein fraction. In massive transfusion both dilu- 
tion and consumption of clotting factors make it necess- 
ary to send blood for a clotting screen and give platelets 
and fresh frozen plasma (FFP) according to the results. As 
a rule, give a unit of FFP for every 4-6 units of stored 
blood transfused. Contact haematologists for advice (see 
Ch. 8). 

6. As stored blood is generally collected into citrate- 
containing bags, remember that exogenous calcium may 
be required after massive blood transfusion, to ensure 
both adequate haemostasis and a normal vascular 
response to inotropes. 

Intraoperative fluid balance 

1. During an operation, many of the problems dis- 
cussed so far may be continuing. The patient is starved for 
6-12 h, there may be blood loss, plasma loss, ECF loss and 
evaporation of water from exposed bowel. As part of the 
stress response to surgery the patient retains water and 
sodium. The importance of careful monitoring in major 
surgery is obvious, including accurate assessment of 
blood loss, haemodynamic variables and urine output. 

2. As a rule of thumb, in intra-abdominal surgery, give 
up to 2 litres of Hartmann's solution 5 ml kg" 1 rr 1 . This 
compensates for starvation, ECF loss, evaporation and 
some blood loss. You may need to give blood or colloids 
in addition. If the patient is being treated in an attempt to 
achieve oxygen delivery /consumption goals, in cardio- 
vascularly healthy patients, continually challenge the 
central venous pressure (CVP) with fluid. In those with 
cardiac dysfunction, challenge the pulmonary capillary 
wedge pressure (PCWP) to maintain an optimal haemo- 
dynamic state. 



118 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 




9 



3. For the first 36 h postoperatively there is water 
retention, and there is sodium retention lasting 3-5 days. 
Obligatory potassium loss of 50-100 mmol per day con- 
tinues. If you give additional sodium it is simply retained, 
although the urine may show an increase in sodium 
output. Provided that intraoperative losses have been 
replaced by the end of the operation, give the basal 
requirements: 30-40 ml kg -1 day 1 H 2 + 1 mmol kg" 1 day -1 
Na + and K + , plus additional blood or colloid if there is 
significant wound drainage. 

4. Do not give potassium until urine output is estab- 
lished; the operation of inadvertent bilateral ureteric 
ligation is not unknown. 

ACID-BASE BALANCE 



X:sfii<;;5£{!&W&&&. 



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Claude Bernard was the first to recognize that to function 
effectively the body needs a stable milieu interieur. The 
hydrogen ion concentration is the most important contri- 
bution to this. An acid is a hydrogen ion (proton) donor 
and a base accepts hydrogen ions. Throughout life the 
body produces hydrogen ions and they must be excreted 
or buffered to keep the internal environment constant. It 
is testament to the importance of hydrogen ions that they 
are regulated on a nanomolar level rather than millimolar 
as are most of the principle anions and cations in the 
blood. There are currently two main ways of interpreting 
acid-base balance. The first or 'traditional view' is the 
most widespread interpretation and based on work 
by Severinghaus, Henderson-Hasselbalch and Siggard- 
Anderson among others. It evolved as technology became 
more advanced and allowed for the direct measurement of 
carbon dioxide and hydrogen ion activity and the calcula- 
tion of those values which were unmeasurable. The 'new' 
interpretation of acid-base balance takes much of this pio- 
neering work and develops it further on the basis of sound 
physicochemical principles. For the most part the new 
theory, proposed by Stewart in the early 1980s, states that 
there are only three variables that influence pH: carbon 
dioxide, the strong ion difference (SID) and weak acids. 
Both methods are described below for completeness. 

Traditional view of acid-base balance 

Terminology and definitions 

Hydrogen ion activity. This is traditionally 
expressed in pH units, pH being the negative log 10 of the 
hydrogen ion concentration: 



pH = -log [H + ] = log 



1 



[H + ] 



pH is a log scale, so that each 0.3 unit fall in pH represents 
a doubling of hydrogen ion concentration. 

Acidosis and alkalosis. The normal ECF pH is 
7.36-7.44 (44-36 nmol r 1 ). Acidaemia is a blood pH below 
this range and alkalaemia a pH above it. Acidosis is a 
condition that leads to acidaemia, or would do if no 
compensation occurred, but the terms 'acidosis' and 'aci- 
daemia' are often used loosely to mean the same thing, 
which is not strictly correct. Alkalosis and alkalaemia are 
denned in a similar way. 

• Respiratory acidosis is a fall in pH resulting from a rise 
in the Pco^ e.g. opiate overdose leading to hypo- 
ventilation causes a rise in Fco 2 . 

• Respiratory alkalosis is a rise in pH due to a lowering of 
the Pc0 2 , such as occurs in hyperventilation. 

• Metabolic acidosis is a fall in pH due to anything other 
than carbon dioxide (sometimes referred to as non- 
respiratory acidosis). There is a primary gain of acid or 
loss of bicarbonate from ECF. 

• Metabolic alkalosis is a rise in pH from non-respiratory 
causes. There is either a gain in bicarbonate or a loss of 
acid from the ECF. 

• Compensatory changes. If the initial problem is respir- 
atory, the result is called a primary respiratory acidosis or 
alkalosis. If the respiratory problem persists for more 
than a few hours, the kidney excretes or retains bicar- 
bonate to try and compensate for the respiratory dis- 
turbance. This is referred to as secondary or compensatory 
metabolic acidosis or alkalosis. 

Thus a primary respiratory acidosis may be accom- 
panied by a secondary metabolic alkalosis. For example, 
chronic obstructive airways disease leads to a rise in the 
Pco 2 : primary respiratory acidosis. To compensate for 
this the kidney retains bicarbonate, leading to a rise in 
ECF bicarbonate: secondary or compensatory metabolic 
alkalosis. 

In the same way, primary respiratory alkalosis (e.g. 
the hyperventilation that occurs at high altitude) will 
be compensated by a secondary metabolic acidosis. 



Hydrogen ion concentration can also be expressed 
directly in nanomoles per litre (Table 9.10). Note that the 



Table 9.10 


Conversion 


table for pH units and 


hydrogen i 


on concentration 




pH unit 






H* (nmol I ») 


8.00 






10 


7,70 






20 


7,44 






36 


7.40 






40 


7.36 






44 


7,10 






30 


7.00 






100 



119 




PATIENT ASSESSMENT 



Where the first disturbance is metabolic, e.g. the 
buildup of acid in diabetic ketoacidosis, the primary 
metabolic acidosis will cause hyperventilation (sec- 
ondary respiratory alkalosis), which will tend to restore 
the pH to normal. This respiratory compensation for a 
metabolic change happens much more rapidly than the 
metabolic compensation for a respiratory problem. 

The fourth possible combination of changes is to 
have a metabolic alkalosis such as loss of H + in pyloric 
stenosis, compensated by a respiratory acidosis. 
However, hypoventilation (respiratory acidosis) leads 
to a fall in Po 2 , which stimulates ventilation so that, in 
practice, compensatory respiratory acidosis is not 
usually seen. 

In deciding which is the primary and which is the 
secondary change, realize that the compensatory 
changes do not bring the pH back to normal; they 
bring it back towards the normal range. In other words, 
even after compensation the measured pH is altered in 
the direction of the primary problem (acidosis or 
alkalosis). Compensatory mechanisms merely make 
the disturbance in pH less than it otherwise would 
have been. It is also important to consider the history. 
Examiners may give candidates blood gas results to 
interpret, but in real life blood gases come from 
patients. Knowing that a patient is an unconscious 
diabetic breathing spontaneously, rather than an 
anaesthetized patient on a ventilator, certainly helps 
one's interpretation. 

Buffers. These are substances which, by their pres- 
ence in solution, minimize the change in pH for a given 
addition of acid or alkali. Three-quarters of the buffering 
power of the body is within the cells; the rest is in the 
ECF. Proteins, haemoglobin, phosphates and the bicar- 
bonate system are all important buffers. The particular 
importance of the bicarbonate system is that carbon 
dioxide is excreted in the lungs and can be regulated by 
changes in ventilation. Bicarbonate excretion in the 
kidney can also be regulated. The lungs are responsible 
for the excretion of 16 000 mmol per day of acid and the 
kidneys for only 40-80 mmol per day. The formation of 
carbonic acid from carbon dioxide and water is catalysed 
by carbonic anhydrase (present in red cells). The reaction 
may go in either direction: 

H + + HCOi <-> H 2 C0 3 <-> H 2 + C0 2 

The Henderson-Hasselbalch equation is derived from 
this and expresses the relationship between the bicarbon- 
ate concentration, the carbon dioxide and the pH: 

[HC0 3 ] 



pH = pK + log 



[HCQ 3 ] 
0.03 Pco 2 



pH = pK + log 



[H 2 C0 3 ] 



The carbonic acid can be expressed in terms of carbon 
dioxide, so that a more useful form of the equation is: 



As this is a buffer system which minimizes changes in pH, 
we can see that if the carbon dioxide rises so will the 
bicarbonate, to keep [HCO^\/Pco 2 constant. Similarly, a 
fall in bicarbonate will be accompanied by a fall in Pco 2 
to prevent a change in pH. 

Interpretation of acid-base changes 

As the patient's acid-base status varies, three things are 
changing at once: pH, IHCO3] and Pco 2 . Blood gas 
machines measure Po 2/ pH and Pco 2 directly. The actual 
bicarbonate [HCO3] is calculated from the Henderson- 
Hasselbalch equation. Blood gas machines also derive 
other variables which help in the interpretation of the 
acid-base status; however, these all attempt to describe 
the metabolic derangement. These are as follows: 

1. Standard bicarbonate (SBC) is the concentration of 
bicarbonate in the plasma of fully oxygenated blood at 
37 D C at a Pco 2 of 5.3 kPa (40 mmHg). In other words, it tells 
you what the bicarbonate would be if there were no respir- 
atory disturbance. Looking at the standard bicarbonate 
therefore tells you what is going on on the metabolic side. 
Normal standard bicarbonate is 22-26 mmol T 1 . Values 
above this indicate metabolic alkalosis, and those below, 
metabolic acidosis. 

2. Base excess (BE) is the amount of strong base or acid 
that would need to be added to whole blood to titrate the 
pH back to 7.4 at a Pco 2 of 5.3 kPa and 37°C. It tells you 
the same thing as standard bicarbonate, namely the 
metabolic status of the patient. Normal base excess is 
obviously zero (±2 mmol \" 1 ). Positive base excess occurs 
in metabolic alkalosis, and negative base excess (some- 
times called base deficit) indicates metabolic acidosis. The 
base excess is an in vitro determination in whole blood. It 
is also known as the actual base excess (ABE) or the base 
excess (blood) (BE b). 

3. Standard base excess (SBE) is an estimate of the in vivo 
base excess and takes into account the difference in buffer- 
ing capacity between the patient's ECF and the blood that 
was put in the blood gas machine. Interstitial fluid, having 
less protein and no haemoglobin, has a lower buffering 
capacity than blood. SBE is therefore 1-2 mmol 1 _1 greater 
than BE, but this makes very little difference in practice. 
SBE is sometimes called base excess (e.c.f.). 

4. Total carbon dioxide (Tco 2 ) is the total concentration of 
carbon dioxide in the plasma as bicarbonate and dis- 
solved carbon dioxide. 

Tco 2 = [HCOi] + (Pco 2 x solubility) 

5. Oxygen saturation (0 2 sat.). The percentage saturation 
of haemoglobin by oxygen is derived from the haemoglobin 



120 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 



9 



oxygen dissociation curve and the measured Po 2 . The 
normal value is >95%. Do not rely on this value to be 
accurate, as other forms of haemoglobin, such as carboxy- 
haemoglobin, are included as oxyhaemoglobin. If you 
suspect this, for example in burns patients, then use a co- 
oximeter to determine the level of oxyhaemoglobin. 

6. Po 2 and inspired oxygen (Fio 2 ). To interpret the Po 2 you 
need to know the age of the patient and the Fio 2 . Normal 
arterial Po 2 declines with age. Roughly speaking Po 2 = 100 
- age in years/3 mmHg or 13.3 - 0.044 x age kPa. 

The expected alveolar Po 2 (Fao 2 ) can be predicted from 
the inspired oxygen by the simplified alveolar gas equa- 
tion: Pao 2 = Pio 2 - Paco 2 /R, where R is the respiratory 
exchange ratio (normally 0.8). In dry gas Pio 2 (in kPa) = 
fractional inspired oxygen (Fio 2 )%. Alveolar gas is satu- 
rated with water vapour (6.3 kPa), for which allowance 
must be made. If the Fio 2 = 40% and the Pco 2 = 5.3: 



Pao, = 



(40 - 40 x 603) 5.3 



100 



0.8 



= 30.85 kPa 



As an approximate rule of thumb, deduct 10 from the 
Fio 2 % to give the expected Pao 2 in kPa (e.g. if Fio 2 = 50% 
then Pao 2 should be approximately 40 kPa). The difference 
between the estimated Pao 2 and the measured arterial Po 2 
is called the (a - a) Po 2 gradient. It is normally 0.5-3 kPa. 

Without considering the inspired oxygen it is not poss- 
ible to comment sensibly on the observed Pao 2 . A rough 
calculation of the (A - a) Po 2 gradient should be made 
when commenting on blood gas results. Some machines 
even calculate this for you as well! 

A blood gas machine usually prints out the variables 
shown in Table 9.11 There is often a haemoglobin 
measurement and the temperature of measurement 
(37°C) is quoted, and in some cases an electrolyte profile 
may be included. 

7. Temperature correction. The blood gas machine oper- 
ates at 37°C. Because gases are more soluble in liquid at 
lower temperatures (as drinkers of cold lager will know), 
the blood gases would be different if measured at another 



Table 9.11 Printout from a blood gas machine 
with normal values 



Temp. 

pH 

Pcq 2 

Po 2 

HC0 3 

Tco ? 

SBC 

BE 

SBE 

O^sat. 

Hb 



37°C 

7.36-7.44 (44-36 nmol M) 

4.6-5.6 kPa (35^12 mmHg) 

10.0-13.3 kPa (75-100 mmHg) 

22-26 mmol I 1 

24^28 mmol I ] 

22-26 mmol I ] 

-2 to +2 mmol h 1 

-3 to +3 mmol M 

>95% 

1 1.5-16.5 g dM 



temperature. Blood gas machines are programmed to 
correct the gases if you tell the machine the patient's 
actual temperature. However, there has been much debate 
as to whether it is appropriate to correct for temperature. 
Suffice it to say that the protagonists of not correcting for 
temperature (the alpha stat theory) hold sway and one 
should probably act on the blood gases as measured at 
37°C and not the temperature-corrected values. 

8. The anion gap. For electrochemical neutrality of the 
ECF the number of anions must equal the number of 
cations. The main cations are sodium and potassium and 
the main anions are chloride, bicarbonate, proteins, phos- 
phates, sulphates and organic acids. 

Normally, only Na + , K + , HCOi and CI" are measured in 
the laboratory. Thus, when we add the normal values for 
these they do not balance: 



Cations 

Na + 140 
K + 5 

Total 145 



Anions 
CI" 105 
HCOi 25 

Total 130 



The difference is known as the anion gap and represents the 
other anions not usually measured. Anion gap = (Na + + K + ) 
- (HCO3 + CI ) = 11-19 mmol H. Its significance is that in 
certain metabolic acidoses (e.g. ketoacidosis or lactic 
acidosis) the anion gap will be increased by the presence 
of organic anions. However, in metabolic acidosis in which 
chloride replaces bicarbonate (e.g. bicarbonate loss due to 
diarrhoea), the anion gap will be normal. It is simply 
another way in which to further elucidate the cause of the 
acidosis. 



New insights into acid-base physiology 

Conventional methods of interpreting acid-base balance 
are centred on the Henderson-Hasselbach equation, 
which describes a ratio of carbon dioxide to bicarbonate 
to derive the pH. The respiratory component of the equa- 
tion is easy to comprehend because carbon dioxide is part 
of the equation, but the metabolic component is less easy 
to understand. We use surrogate markers of metabolic 
disturbance, such as base excess, to quantify the degree of 
metabolic acidosis. There has been an increasing aware- 
ness that this model, which works clinically, fails to 
explain much of the associated pathophysiology, in 
particular the influence of electrolytes and proteins on 
acid-base balance. In 1981 Paul Stewart (1981) took a 
physicochemical approach to acid-base balance and came 
up with a model, which has subsequently been modified 
by Fencl, that explained many of these anomalies. He said 
that for all aqueous systems there must be electrical 
neutrality and conservation of mass, and that water will 
dissociate/ associate to give /receive hydrogen ions if the 



121 




PATIENT ASSESSMENT 




balance of either is altered. He also identified the import- 
ant factors controlling acid-base balance control. 



Only three independent factors 
control acid-base balance: 



• Pco 2 

• Strong ion difference (SID) 

• Weak acids (albumin and phosphate). 

All other variables such as hydrogen ions, hydroxide, 
bicarbonate, etc. change only if one or more of the three 
independent variables changes. 

1. Pco 2 . The change in carbon dioxide is self ex- 
planatory and influences the pH as predicted by the 
Henderson-Hasselbach equation. 

2. SID. Strong ion difference refers to the mathematical 
difference in charge between the strong ions in solution 
and is normally between 38 and 42 mmol L 1 . Strong ions 
are those ions which in solution are virtually fully dissoci- 
ated, e.g Na + , CI", K + , Ca 2+ , Mg 2+ and, for the purposes of 
the model, lactate. For example, if NaCl is added to water 
there is virtually complete dissociation and the only things 
that exist in that solution are Na + , CI", H 2 0, H + and OH" 
ions; there are no y NaCl molecules'. If there is a change in 
the concentration of one of these ions, that is an increase in 
the CI", then the SID will be reduced and electrical neu- 
trality has to be restored. This results in the dissociation of 
water, so producing hydrogen ions and decreasing the pH 
of a solution. Therefore, increasing the chloride concentra- 
tion makes the system more acidic. The increase in the 
hydrogen ion concentration, however, is only in the 
nanomolar range and does not restore electrical neutrality. 
The bulk of electrical neutrality is restored by the proteins. 

3. Weak acids. Albumin and phosphate are the pre- 
dominant weak acids. If the concentration of albumin 
decreases, the solution becomes more alkaline. This is a 
very common occurrence in the critical care patient. 

It is therefore possible, if you know the Pco 2 , the SID 
and the weak acid concentration, to work out what the 
pH will be without having to measure it. It is this degree 
of quantification that allows physicians working in com- 
plicated critical care or postoperative environments to 
understand the pathophysiology behind the disturbance 
and work out what and how to treat it effectively. 

PLAN FOR INTERPRETING BLOOD 
GASES 

1. Check for internal consistency. Remember that the 
machine measures only pH, Pco 2 and Po 2 . If it measures 
any of these wrongly, which is not infrequent, the derived 



variables are also wildly abnormal. If the results do not fit 
with the clinical picture, suspect the machine. Example: a 
patient on a ventilator in theatre with an end- tidal carbon 
dioxide of 5% has the following gases: 



Po 2 


13.0 


pH 


7.64 


Pco 2 


5.1 


hco 3 - 


37.5 


Tco 2 


38.5 


SBC 


39.0 


BE 


+15 


SBE 


+16 


2 sat. 


99% 



It is much more likely that the pH has been measured 
wrongly than that the patient has a gross metabolic 
alkalosis. 

2. Look at the pH. Remember the pH change is always 
in the direction of the primary problem acidosis or 
alkalosis. 

3. Look at the Pco 2 . Abnormality of the Pco 2 indicates 
the respiratory component. 

4. Look at the base excess or standard bicarbonate. 
Both give the same information, i.e. the metabolic 
acid-base status after correcting for the Pco 2 . 

5. Calculate the anion gap. 

6. Look at the Po 2 and calculate the A - a gradient. 

Examples of abnormal blood gases 

The alkalaemia is due to primary 
respiratory alkalosis (low Pco 2 ). 
There is no metabolic 
compensation (normal base 
excess). The Po 2 would be 
expected if breathing 40% 
oxygen Pio 2 - 10 = (40 - 10) = 30. 
The patient is 
hyperventilating. 

A respiratory acidosis with high 
PC0 2 due to hypoventilation. 
Again no metabolic compensation 
(normal SBC and BE). Low Po 2 
due to hypoventilation. 



pH 


7.51 


Pco 2 


3.7 


Po 2 


29 


HC03 


22.1 


Tco 2 


23.6 


SBC 


25 


BE 


+1.1 


SBE 


+2 


2 sat. 


100% 


(Fio 2 40%) 




pH 


7.28 


Pco 2 


7.33 


Po 2 


9.21 


HC03 


25.2 


Tco 2 


28.4 


SBC 


22.3 


BE 


-1.9 


SBE 


-2.5 


2 sat. 


91% 


(Fio 2 air) 




pH 


7.35 


Pco 2 


9.33 



Again a respiratory acidosis 
(high Pco 2 ) but this time 



122 



FLUID, ELECTROLYTE AND ACID-BASE BALANCE 



9 



Po 2 


7.11 


hco 3 


39.1 


Tco 2 


41.2 


SBC 


32.4 


BE 


+8.2 


SBE 


+9.1 


2 sat. 


85% 


(Fio 2 air) 




pH 


7.21 


Pco 2 


4.0 


Po 2 


13.3 


HCOi 


11,5 


Tco 2 


12.8 


SBC 


9.3 


BE 


-15.2 


SBE 


-16.4 


2 sat. 


99% 


(Fio 2 air) 




pH 


7.36 


Pco 2 


4.21 


Po 2 


10.49 


HCOi 


17.6 


Tco 2 


18.5 


SBC 


17.8 


BE 


-6.2 


SBE 


-6.9 


2 sat. 


96% 


(Fio 2 60%) 





compensated by metabolic 
alkalosis (high SBC and positive 
base excess). This is typical of 
chronic obstructive airways 
disease with renal 
compensation. 



The acidaemia (low pH) is 
primarily due to a metabolic 
acidosis (low SBC, base excess 
-15). Compensatory 
respiratory alkalosis (low Pco 2 ), 
does not return the pH to 
normal. Po 2 normal. 



The pH is in the normal range 
despite low Pco 2 (respiratory 
alkalosis) and low standard 
bicarbonate (metabolic 
acidosis). The important thing 
here is the Po 2 . It is apparently 
in the normal range but not 
when breathing 60% oxygen. 
The (A - a) Po 2 gradient is 
roughly 40 kPa. These gases are 
typical of a patient with adult 
respiratory distress syndrome. 



a cardiac arrest is probably unjustified. In metabolic 
acidosis due to poor perfusion of tissues the best way to 
manage this is to correct the perfusion defect, which may 
be achieved, in some instances, by improving oxygen 
delivery using fluids, vasodilators or inotropes. This may 
involve the use of invasive monitoring such as Swan- 
Ganz catheterization in order to guide therapy. Treatment 
of the metabolic acidosis due to sepsis is controversial 
and, even though goal-directed therapy may not be uni- 
versally accepted, most will still try to achieve reasonably 
high oxygen delivery targets. In sepsis, however, this does 
not give the anticipated rise in oxygen consumption, 
after allowing for the rise in oxygen consumption due 
to increased myocardial work required to achieve the 
delivery. Sepsis appears to involve a defect in tissue 
oxygen uptake /utilization. 

4. There is still a place for bicarbonate therapy in 
acidosis due to diarrhoea, renal tubular acidosis and 
uraemic acidosis, and where an imbalance of the SID exists. 
As outlined above, use the base excess to calculate the 
dose; 8.4% sodium bicarbonate is hyperosmolar and must 
be given into a large central vein. Accidental subcutaneous 
administration can cause tissue necrosis. Bear in mind 
that each millimole of HCO3 is accompanied by Na + and 
it is easy to overload the patient with sodium. 




Key point 

Frequently monitor blood gases and 
electrolytes during treatment with 
bicarbonate. 



TREATMENT OF ACID-BASE 
DISTURB^ 

1. As in any other field of medicine, direct treatment at 
the underlying cause. Correcting the Pco 2 is usually poss- 
ible by taking over the patient's ventilation and adjusting 
the minute volume to give the desired Pco 2 . 

2. Treatment of a metabolic acidosis is more contro- 
versial. It was traditional to treat a metabolic acidosis by 
giving sodium bicarbonate according to the formula (base 
excess x body weight in kg/ 3) mmol starting by giving half 
the dose; 8.4% sodium bicarbonate contains 1 mmol ml" 1 . 

3. It is now argued that, particularly in a hypoxic state 
such as exists following cardiac arrest, bicarbonate 
administration may do more harm than good (Graf & 
Arieff 1986). The bicarbonate generates carbon dioxide, 
which crosses easily into cells, making the intracellular 
acidosis worse. If ventilation is impaired the carbon 
dioxide generated is unable to escape via the lungs. The 
traditional practice of giving 50-100 mmol bicarbonate at 



Summary 

• Do you have an adequate knowledge of 
basic fluid physiology? 

• Do you recognize that visible fluid deficit 
is but a small part of the overall problem? 

• Are you aware that occult intraoperative 
hypovolaemia leads to increased 
postoperative morbidity? 

• Will you determine to monitor patients 
thoroughly to fully understand their fluid 
status? 

• Are you aware that hypovolaemia is the 
most common cause of intraoperative 
metabolic acidosis? 

• Do you recognize that hypovolaemia is 
probably the most common avoidable 
cause of multiple organ dysfunction? 



123 




PATIENT ASSESSMENT 




References 



Boyd O, Grounds RM, Bennett ED 1993 A randomised clinical 
trial of the effect of deliberate peri-operative increase of 
oxygen delivery on mortality in high-risk surgical patients. 
JAMA 270: 2699-2707 

Edelman IS, Leibman J 1959 Anatomy of body water and 
electrolytes. American Journal of Medicine 27: 256, 277 

Graf H, Arieff AI 1986 Use of sodium bicarbonate in the therapy 
of organic acidosis. Intensive Care Medicine 12: 285-288 

Grocott MPW, Hamilton MA, Rowan K 2003 Perioperative 
increase in global blood flow to explicit defined goals and 
outcomes following surger; issue 1, January, Cochrane 
Library. Update Software, Oxford 

Hamilton-Davies C, Mythen MG, Salmon JB, Jacobson D, 
Shukla A, Webb AR 1997 Comparison of commonly used 
clinical indicators of hypovolaemia with gastrointestinal 
tonometry. Intensive Care Medicine 23: 276-281 

Hayes MA, Timmins AC, Yau EH 1994 Elevation of systemic 
oxygen delivery in the treatment of critically ill patients. New 
England Journal of Medicine 330: 1717-1722 

Hebert PC, Wells G, Blajchman MA et al 1999 A multicenter, 
randomized, controlled clinical trial of transfusion 
requirements in critical care. Transfusion Requirements in 
Critical Care Investigators, Canadian Critical Care Trials 
Group [see commentsl [published erratum appears in N Engl 
J Med 1999 340(13): 1056J. New England Journal of Medicine 
340(6): 409-417 

Mattox KL, Maningas PA, Moore EE 1991 Prehospital 
hypertonic saline /dextran infusion for post-traumatic 



hypotension. Annals of Surgery 213: 482-491 
Mythen MG, Purdy G, Mackie IJ 1993 Post-operative multiple 

organ dysfunction syndrome associated with gut mucosal 

hypoperfusion, increased neutrophil degranulation and 

C-1-esterase inhibitor depletion. British Journal of 

Anaesthesia 71: 858-863 
Price HL, Deutsch S, Marshall BE 1966 Haemodynamic and 

metabolic effects of haemorrhage in man with particular 

reference to the splanchnic circulation. Circulation Research 

18: 469^74 
Robarts WM, Parkin JV, Hobsley M 1979 A simple clinical 

approach to quantifying losses from the extracellular and 

plasma compartments. Annals of the Royal College of 

Surgeons of England 61: 142-145 
Shoemaker WC, Appel PL, Kram HB 1988 Prospective trial of 

supranormal values of survivors as therapeutic goals in 

high-risk surgical patients. Chest 94: 1176-1186 
Starling EH 1896 On the absorption of fluids from the 

connective spaces. Journal of Physiology 19: 312-326 
Staverman A 1952 Apparent osmotic pressure of solutions of 

heterodisperse polymers. Rec Trav Chim 71: 623-633 
Stewart PA 1981 How to understand acid-base. A quantitative 

acid-base primer for biology and medicine. Edward Arnold, 

London 
Webb AR, Barclay SA, Bennett ED 1989 In vitro colloid pressure 

of commonly used plasma expanders and substitutes. 

Intensive Care Medicine 15: 116-120 
Wilkes NJ, Woolf R, Mutch M et al 2001 The effects of balanced 

versus saline-based hetastarch and crystalloid solutions on 

acid-base and electrolyte status and gastric mucosal 

perfusion in elderly surgical patients. Anesthesia and 

Analgesia 93(4): 811-816 



124 




Nutritional support 



J. Payne-James 



W 



Objectives 



Be aware of the incidence, causes, effects 

and assessment of protein energy 

malnutrition in surgical patients. 

Recognize when and how to administer 

oral, enteral and parenteral support, and 

when to stop it. 

Be aware of the complications of 

administering support. 

Document your findings and actions. 



INTROpUCTipN 

The metabolic response to injury, such as major trauma 
or surgical operation and sepsis, generates increased 
demand for nitrogen and energy. If the demands are not 
met, the patient develops protein-energy malnutrition 
(PEM), which is a significant and often unrecognized 
problem in hospitals, with up to 40% of patients under- 
nourished, and fewer than half of these having this fact 
documented in their notes. 

Aim to identify actual or potential malnourished patients 
and correct or improve their nutritional status to minimize 
the risks of chest, urinary or wound infection, slow healing, 
wound breakdown or even death. The optimal method of 
administering additional nutrients is by oral feeding, such 
as sip feeds and dietary supplements, both in hospital and 
community practice. A variety of flavours is available in 
order to make the supplements palatable. When oral 
feeding is not possible because the patient is incapable, or 
lacks motivation, seek other routes of administering nutri- 
ent substrates to critically ill or postoperative patients. 

ASSESSMENT 




Key points 

Assess all patients admitted to hospital, even 
for elective procedures. 



• Record the results. 

• Decide whether or not nutritional support will 
be required. 

Specific aspects help in classifying nutritional status: 

• Record height and weight for comparison with stan- 
dard charts. 

• Estimate from the dietary history and from the assump- 
tion that maximum requirements of protein and energy 
for hospitalized patients are 1.5 g kg" 1 24 h -1 , and 
40 kcal kg" 1 24 h" 1 respectively. 

• Assess body composition clinically. 

• It may be difficult to identify PEM. Look for and record 
signs such as loss of muscle power, peripheral oedema, 
skin rashes, angular stomatitis, gingivitis, nail abnor- 
malities, glossitis, paraesthesia and neuropathy. 

• Tests may have poor sensitivity. Compare midarm 
muscle circumference with tables and measure triceps 
skinfold thickness, for which you need special 
calipers. Apply dynamometric tests such as hand-grip 
strength. Assess serum albumin (normal 36^7 g l" 1 ), 
transferrin (normal 2-4 g l" 1 ) assess the lymphocyte 
count (normal 1.5-4 x 10 9 l" 1 ) and delayed hypersensi- 
tivity skin testing. 

In the absence of a specific measure, clinically place each 
patient in one of the following groups: 

1. Obvious severe malnutrition, recent or long term 
(>10% recent weight loss, serum albumin <30 g 1 _I , 
gross muscle wasting and peripheral oedema). 

2. Moderate malnutrition, with low nutritional 
parameters, impaired nutrient intake for more than 
2-4 weeks, although there may be no obvious 
physical evidence. 

3. Normal or near-normal status but at risk of 
deteriorating without support in traumatized or 
ventilated patients. 

4. Normal nutritional status which is unlikely to be 
affected by illness. 

If 1, 2, 3 nutritional support maybe needed. If so, deter- 
mine the best route of administration (Fig. 10.1). 



125 



10 



PATIENT ASSESSMENT 



Normally 
nourished 



Normal feeding 



Oral feeding! 
sip feeds/diet 
supplements 



Nutritional assessment 



I 



Normal/near-normal 

nutrition state (but 

will deteriorate if 

support withheld) 



Severe/moderate 
malnutrition 



1 



Nutrition support indicated 



Yes 



Oral nutrition possible 

I 



Yes 



EN 




Gastrointestinal tract 
functions adequately 



No 



\ 



PN 



Limited EN 
possible 



I 



Supplement 
with PN 



EN 
anticipated for < 2 weeks 



Fine-bore 
nasoenteral tube 



I 



EN 
anticipated for > 2 weeks 



I 



Consider placement of 
long-term tube 



Feeding prolonged 
> 2 weeks 



PN anticipated 
for < 2 weeks 



I 



Peripheral PN 
(PPN) 



I 



PN anticipated 
for > 2 weeks 



I 



Central venous 
PN <CPN) 

"7 



Feeding prolonged > 2 weeks y 
or poor peripheral access 



Fig. 10.1 Flow chart of options when nutritional support is required. CPN, central venous parenteral nutrition; EN, 
enteral nutrition; PN, parenteral nutrition; PPN, peripheral parenteral nutrition. 



ENTERAL AND PARENTERAL 
NUTRITION FOR SURGICAL PATIENTS 



> ;£4^'^%*l / ^!& : $$f«>i!gM : A 




Key point 

• Prefer enteral feeding for all patients with a fully 
functioning, accessible gastrointestinal tract. 

1. Enteral feeding may improve antibacterial host 
defences, blunt the hypermetabolic response to trauma, 
maintain gut mucosal mass, maintain gut barrier function 
and prevent disruption of gut flora. It may contribute to 
maintaining splanchnic blood flow and the direct provi- 
sion of nutrients for enterocytes. The gut was previously 
considered unimportant during critical illness caused by 



injury or infection. It is now recognized that the gastro- 
intestinal tract is frequently a reservoir for bacterial 
translocation across the gut wall. Gut-derived endotoxin 
may therefore be a link between gastrointestinal failure 
and multiple organ failure without overt clinical evidence 
of infection (Fig. 10.2). 

2. Research is being carried out to determine whether 
dietary manipulation, such as provision of glutamine or 
fibre, can prevent bowel atrophy and maintain intestinal 
mass, in the hope of reducing morbidity and mortality. 

3. For the majority of critically ill patients, including 
postoperative patients, the gastrointestinal tract is the 
appropriate route for nutritional support, provided it is 
functioning normally. Because small intestinal function is 
better maintained postoperatively than gastric and large 
bowel function, enteral (small bowel) feeding can start 



126 



NUTRITIONAL SUPPORT 



10 



SYSTEMIC INSULT 

(eg shock, injury, infection 

immunosuppression 

malnutrition) 



Gl INSULT 

(eg. inflammatory bowel 

disease, radiotherapy, 

chemotherapy) 



I 



i 



THERAPEUTIC AGENTS 
(antibiotics, H? blockers) 



Impaired host defences 

Physical disruption of gut mucosal barrier 

Overgrowth of pathogenic gut flora 



i 



TRANSLOCATION OF BACTERIA 



I 



SYSTEMIC RESPONSE 



MULTIPLE ORGAN DYSFUNCTION SYNDROME 

(MODS) 



Fig. 10.2 Simplified mechanism of bacterial 
translocation and multiple organ failure. 



dietary supplementation, enteral or parenteral 
nutrition. 

• Do not delay operation if the disease is 
progressing, causing the patient's condition to 
deteriorate. 

• Do not delay operation solely on account of 
borderline or mild malnutrition. 

Postoperative nutrition 

1. Consider postoperative nutrition for any patient 
with an inadequate intake after 5 days. 

2. Give parenteral nutrition if oral or enteral nutrition 
is not anticipated within 7 days post-operation in a pre- 
viously well-nourished patient and as early as possible in 
a previously malnourished or critically ill patient. 

3. Consider creating access to the gastrointestinal tract 
via a gastrostomy, a jejunostomy or a central venous 
feeding line at the time of major oropharyngeal, maxillo- 
facial or upper gastrointestinal operation. This spares the 
patient a second procedure and the access lines can be 
disconnected if they are not needed. 

4. In extreme circumstances, such as an elderly, mal- 
nourished smoker requiring ©esophagectomy, provide 
preoperative nutritional support and arrange to continue 
it afterwards. By contrast, a patient with perforation of a 
viscus from inflammatory bowel disease unresponsive to 
medical management needs operation first, nutritional 
support afterwards. 



early following operation, including major aortic and 
small bowel surgery, and following head injuries. 

4. The benefits of enteral nutrition in patients who 
would formerly have been given parenteral nutrition have 
been demonstrated, although patients in whom there is 
reasonable doubt as to the adequacy of gastrointestinal 
function should be fed by the parenteral route. There are 
no differences in major postoperative complications and 
mortality rates; however, in certain groups (e.g. malnour- 
ished gastrointestinal cancer patients) who receive early 
enteral nutrition, significantly reduced complication rates 
and shorter duration of postoperative stay may be achieved 
with enteral nutrition, although parenteral nutrition is 
better tolerated. In summary total parenteral nutrition is 
an equally effective alternative to enteral nutrition when 
a risk of malnutrition is present and enteral nutrition is 
not tolerated or when gut failure is present. 




Preoperative nutritional support 

Give a severely malnourished (e.g. more than 
10% weight loss) patient at least 10 days of 



ENERGY AND NITROGEN 

RETIREMENTS 

Many surgical patients in need of nutritional support are 
metabolically stressed, septic or traumatized by accident or 
operation. In particular, those with burns or head injuries 
are likely to be hypermetabolic as a result of neuroen- 
docrine responses. Although precise energy requirements 
can be determined by indirect calorimetry, this is not a prac- 
tical approach. Energy requirements to achieve positive 
energy balance in surgical patients are rarely more than 
2200-2400 kcal 24 h" 1 . Give 35-40 kcal kg" 1 24 h" 1 as a 
mixture of carbohydrate and fat, which is usually sufficient. 
Nitrogen requirements may be considerable; in hyper- 
metabolic, stressed and injured patients it may be imposs- 
ible to achieve a balance until the underlying cause has 
been improved. Minimize losses in order not to waste 
administered nitrogen, maintain lean body mass, allow 
an adequate supply for repair and allow active repletion 
of lean body mass in a previously compromised patient. 
For most adults 14-16 g nitrogen suffices. For those who 
require even more nitrogen, up to 0.4 g kg -1 24 h _1 has 
been suggested. 



127 



10 




PATIENT ASSESSMENT 




When patients are on nutritional 
support, frequently monitor and 
chart: 



• Diet 

• Weight 

• Haematology 

• Biochemistry. 

Keep accurate records of actual as opposed to prescribed 
intake, in order to identify any nutritional inadequacies 
promptly. They are particularly important during the 
changeover to oral feeding. Regularly weigh to ensure 
that the regimen is satisfactory, especially in those requir- 
ing body mass repletion. Weight gain may represent 
water retention, however, but this is revealed if you regu- 
larly monitor haematological and biochemical results. 
Especially in the first few days and in the malnourished 
patient, monitor the plasma potassium, phosphate and 
glucose. Measure vitamin and trace elements in patients 
on long-term feeding if appropriate. The response to 
nutritional support may be judged over days and weeks 
by the levels of plasma proteins, transferrin and thyroid 
prealbumin. 

Although anthropometric and dynamometric measure- 
ments are often considered as research tools, they offer 
sensitive, effective measurements of nutrition, so use 
them when they are available. 



Nitrogen balance 

An aim of nutritional support is to try and ensure that the 
patient is in positive nitrogen balance. This is often diffi- 
cult or impossible to achieve in patients who are very 
physiologically stressed or catabolic, the phase of destruc- 
tive metabolism, in the immediate aftermath of trauma or 
injury and in the critically ill. 

Nitrogen balance depends upon the difference between 
whole body protein synthesis and breakdown. It is more 
a measure of the metabolic than the nutritional state. In 
most patients nitrogen balance can be calculated from 
urinary and faecal nitrogen losses. Collect 24 h samples of 
urine, as faecal loss is often negligible. Urinary urea may 
reasonably be considered to account for 80% of total 
urinary nitrogen. Adjust for plasma urea levels and for 
faecal and other routes of loss of 2-3 g. 

In a severely ill patient, urinary urea may not represent 
80% of urinary nitrogen, because of excessive excretion of 
ammonia and other non-urea nitrogenous products. If 
chemiluminescence measurement of total urinary nitro- 
gen is available, there is no need to estimate output from 
urea values. 



ENTERAL JSIU 

Types of diet 

Polymeric (Greek polys = much, many + meros = part) diets 
contain whole protein as a nitrogen source, triglycerides 
and glucose polymers for energy, together with stan- 
dardized amounts of electrolytes, trace elements and vita- 
mins. Standard polymeric diets contain approximately 
6 g nitrogen 1 _1 with an energy density of 1 kcal ml" 1 . 
Energy (nitrogen dense) diets contain 8-10 g nitrogen /l 
and an energy density of 1—1.5 kcal ml" 1 . These diets are 
suitable for more than 90% of patients with normal or 
near normal gastrointestinal function. In those with 
impaired intraluminal hydrolysis from severe pancreatic 
exocrine insufficiency or intestinal failure from short 
bowel syndrome, give a predigested or elemental diet. 

Predigested or elemental diets have nitrogen sources 
derived from amino acids or oligopeptides. Their benefit 
over standard diets in acute pancreatitis has been 
established. Glucose polymer mixtures with polymers 
predominantly of chain length more than 10 glucose 
molecules provide energy. A combination of long- and 
medium-chain triglycerides provides the fat component. 

Some disease-specific diets have been developed. High 
carbohydrate loads increase carbon dioxide production in 
patients with respiratory failure who are on ventilators; 
diets containing a higher fat energy component may 
allow the patient to be weaned from the ventilator as a 
result of decreased carbon dioxide production and 
reduced respiratory quotient. 

Research is underway to design diets that modify or 
modulate stress and the immune response. No general 
recommendations are yet available but specific groups 
such as the critically ill may benefit. 

Route of administration 

Most patients require nutritional support for less than 
1 month. For these, a fine-bore nasogastric tube suffices. 
Ensure that the tube is correctly positioned, especially if the 
patient has altered swallowing, diminished gag reflex, or 
has had surgery of the pharynx or upper airway. Confirm 
that the tube is correctly placed by aspirating gastric con- 
tents. If the patient is unable to cooperate, confirm the posi- 
tion of the tube tip radiologically. It should preferably be 
sited beyond the pylorus if gastric atony and regurgitation 
are likely. Advance the tube using a combination of mani- 
pulation and administration of a motility stimulant such as 
metoclopramide. Longer term feeding may be provided by 
percutaneous endoscopically placed gastrostomy or needle 
catheter jejunostomy These techniques are valuable for 
undernourished patients at presentation, those undergoing 



128 



NUTRITIONAL SUPPORT 



10 



major upper gastrointestinal operation, adjuvant radio- 
therapy or chemotherapy, and those undergoing laparo- 
tomy following major abdominal trauma. Anticipate the 
problem at operation by placing the tube at the time; some- 
times pharyngostomy or oesophagostomy may be used. 



Anticipate and prepare for gastric 
atony or paresis in: 




• Critically ill and recumbent patients and 
following head injury 

• Patients being ventilated or needing intensive 
care 

• Following abdominal surgery 

• Diabetes with neuropathy 

• Hypothyroidism 

• Neuromotor deglutition disorder 

Preferably administer enteral diet from a large reservoir 
holding up to 2 litres, from a sterile closed system, espe- 
cially if the patient is immunosuppressed or critically ill. 
Change the reservoir and giving set every 24 h. Prefer 
continuous to intermittent bolus feeding, so avoiding 
bloating and diarrhoea. Use gravity feed or a peristaltic 
pump. A starter regimen of undiluted full-volume diet 
does not, as is commonly thought, provoke gastrointesti- 
nal side-effects in patients with normal bowel, or those 
with inflammatory bowel disease. Starting with reduced 
volume or diluting the feed limits the intake, thereby pro- 
longing the duration of negative nitrogen balance. In 
most adult patients with no other metabolic or fluid 
balance problems, prescribe 2-2.5 litres of diet each day 
from the beginning. 

Complications 

1 . Feeding tube blockage most usually occurs when the 
giving set is disconnected and the residual diet solidifies. 
Prevent it by flushing out the tube with water after dis- 
connecting it. Unblock it by instilling pancreatic enzyme 
or cola. The tube may be malpositioned or be inadver- 
tently removed. 

2. Diarrhoea, occurring in about 10% of patients, is 
multifactorial, often associated with concomitant anti- 
biotic treatment or hypoalbuminaemia. Only rarely do 
you need to discontinue feeding, as codeine phosphate or 
loperamide is usually effective. Review the drug chart fre- 
quently and stop antibiotics if they are no longer required. 

3. Nausea and vomiting are rarely caused by the feeds 
but may develop because of slow gastric emptying; try 
giving antiemetics. Too rapid administration, or bolus 
feeding, may produce bloating, abdominal pain or 



cramps. Regurgitation and pulmonary aspiration occa- 
sionally occur. 

4. Anticipate and prevent vitamin, mineral and trace 
element deficiencies. 

5. Enteral diets react with enterally administered drugs 
such as theophylline, warfarin, methyldopa and digoxin, 
especially if the patient is fed orally If drug therapy that 
was effective fails during enteral feeding, assume it 
results from the enteral feeding unless proved otherwise. 




Key point 

Exclude complications of infection originating 
in the diet reservoir or giving set. 



PARENTEjFTALJ 

The successful use of intravenous parenteral (Greek para - 
besides + enteron = gut, intestine) nutrition was first 
demonstrated three decades ago. Parenteral nutrition (PN) 
(often termed TPN - total parenteral nutrition - although 
this is only true if all macronutrients and micronutrients 
such as electrolytes, vitamins and trace elements are 
included) is required for any patient with intestinal failure 
(short term or long term). It is essential for some acutely ill 
patients, although the increasing preference for the enteral 
route is reducing this. About 25% of hospitalized patients 
requiring nutritional support need it to be administered 
parenterally. Consider it for actual or potential malnour- 
ished patients with a non-functioning, partially function- 
ing and /or inaccessible gastrointestinal tract. When in 
doubt about gastrointestinal function, use parenteral nutri- 
tion until you are reassured about gastrointestinal function- 

Access 

Parenteral nutrition solutions generally have high osmol- 
alities (Greek otheein = to push; the tendency of water to 
pass through a semipermeable membrane from the side 
of lower concentration to the side of higher concentration, 
to equalize the concentrations). Hypertonic solutions 
infused into peripheral veins damage the endothelium, 
causing thrombosis. This is overcome by introducing 
them through a catheter passed into a large central vein, 
such as the vena cava, where the concentrated fluid mixes 
rapidly with the large volume of blood and is diluted. 

The risk of introducing sepsis demands the highest 
level of technical care. The catheter is usually passed 
through a subcutaneous tunnel before entering the vein, 
to distance the vein entry from the surface. If a patient 



129 




PATIENT ASSESSMENT 



with a central venous catheter develops pyrexia and 
raised leucocyte count, and has no detectable cause after 
a rigorous search, assume it is catheter related. 

The development of lower energy regimens in which 
lipid provides a substantial part of the required calories 
allows the administration of parenteral nutrition via 
peripheral veins. Peripheral parenteral nutrition (PPN) 
without provoking thrombophlebitis is facilitated by 
using fine-bore cannulas, the use of heparin, in-line fil- 
tration, Cortisol, buffering and the local application of 
glyceryl trinitrate patches. In addition, most courses last 
no more than 10-14 days. 

Nutrients 

Macronutrients, larger molecules, contain glucose and 
lipid emulsions, usually 50:50 with nitrogen sources in the 
form of L-amino acids. New lipids with better stability in 
solution are now available; they can modulate immune 
functions, inflammatory processes and metabolism, and 
promise to become more widely used. 

Micronutrients include electrolytes, trace elements and 
vitamins, Commercial all-in-one bags contain mixed macro- 
and micronutrients which can safely be infused over 
12-24 h. They can be safely stored for several weeks. They 
suit almost 80% of patients and are widely used. Ready-to- 
use standardized formulations, either made up in pharma- 
cies or presented as commercial multichamber bags, 
simplify administration, and the most appropriate formula 
best approximating the patient's needs can be chosen. 




Key points 

• Monitor blood glucose 6-hourly for the first 
week to detect insulin resistance; you may 
need to give exogenous insulin by injection or 
infusion. 

• Monitor electrolytes daily so you can detect 
and correct imbalances. 

• Monitor liver function to check serum albumin 
and hepatobiliary dysfunction, which 
inevitably results from parenteral nutrition in 
some patients. 

Complications 



in 



Metabolic complications of parenteral nutrition, 
descending order of frequency are: hyperglycaemia, 
hypoglycaemia, hypophosphataemia, hypercalcaemia, 
hyperkalemia, hypokalaemia, hypernatraemia, hypo- 



natraemia. In the longer term, anticipate deficiencies of 
folate, zinc, magnesium, other trace elements, vitamins 
and essential fatty acids. 

Home parenteral nutrition 

Some patients require long-term nutritional support by 
virtue of loss of bowel by disease or resection. Such par- 
enteral or enteral support demands commitment by you 
as part of the surgical team, by skilled carers and by the 
patients. Although patients can often be monitored 
locally, overall management must be undertaken at a 
special centre. The principles are the same as for inpatient 
management but long-term monitoring and specific com- 
plications are more complex. Those in need of home 
nutritional support ahould be referred at an early stage. 



NUTRITION SUPPORT TEAM 



#£?^?^-W>&' 



In hospital, the best way of optimizing nutritional care is 
with a multidisciplinary support team, each member 
providing specialty expert care. They receive input from 
clinicians, dieticians, pharmacists, nurses, chemical 
pathologists and microbiologists. A central support team 
can establish specialized teams to attend to specific needs 
in, for example, intensive care and paediatrics. 



Summary 

How does malnutrition affect surgical 

outcome? 

How do you assess the nutritional state of 

your patients? 

How do you identify and treat 

malnourished patients? 

What methods are available and how do 

you select them? 

What is the make-up of a nutritional 

support team? 



Further reading 



Payne-James JJ, Wicks CW 2002 Key facts in clinical nutrition, 
2nd edn. Greenwich Medical Media, London 

Payne-James JJ, Grimble GK, Silk DBA (eds) 2001 Artificial 
nutrition support in clinical practice, 2nd edn. Greenwich 
Medical Media, London 



130 




Clinical pharmacology 



J. Robin 




Objectives 

• Understand how drugs are developed and 
licensed. 

• Know how to select drugs rationally, 
according to efficacy, safety, convenience 
and cost. 

• Learn to prescribe safely and effectively. 

• Be aware of the use of drugs in special 
situations. 

• Beware of drug interactions whenever you 
prescribe. 



Almost all doctors prescribe drugs. As a budding 
surgeon, you are no exception. You use drugs extensively 
perioperatively. You also use drugs as first line therapy 
for some conditions referred to you. Many of your 
patients have an extensive list of medications prescribed 
for coexisting diseases, some of them unfamiliar to you. 
You often continue to prescribe these drugs while the 
patient remains under your care. 

This chapter aims to teach you the principles of select- 
ing drugs rationally, and using them safely and effec- 
tively. The British National Formulary (BNF) is a source of 
much useful information for prescribers. Keep it to hand 
as you study this chapter so you can refer to it. You need 
to understand the various factors that influence your 
decision to prescribe a particular drug to your patient, 
and the consequences that flow from that decision. A drug 
(the word is of uncertain origin) is any substance used in 
the composition of a medicine. 



DRUG DEVELOPMENT AND LICENSING 

As a prescribes you need to have a basic understanding 
of the process of drug development and marketing. 



1. New drugs are continually developed and marketed 
by the major pharmaceutical companies. Development 
begins with the pharmaceutical company identifying an 
'unmet medical need', such as diseases for which no effec- 
tive therapy is available, or conditions for which the exist- 
ing therapy is considered suboptimal in terms of efficacy, 
tolerability or both. 

2. Once the need is identified, the drug company syn- 
thesizes novel compounds that might have some useful 
pharmacological activity, called 'new chemical entities' 
(NCEs). Any NCEs showing promise are immediately 
protected by a patent, giving the company 20 years exclus- 
ive rights to develop and market the drug. The attrition 
rate for NCEs is high, the majority being discarded 
because they do not work or are too toxic. Drug develop- 
ment is expensive and time consuming: it can take up to 
10 years to bring one to the market. 

3. Once a drug is successfully developed the manufac- 
turers apply for a product licence, the marketing permit, 
with specific indications, specific patient groups and for 
specific doses. Indications may be a symptom, disease or 
a physiological derangement. 

4. If a specialist chooses to prescribe a drug outside the 
terms of its product licence (an unlicensed indication), the 
prescriber, not the drug company, is responsible for any 
harmful consequences. 




Key point 

Do not prescribe a drug outside its product 
licence. Consult your senior colleagues. 



The BNF contains thousands of established drugs for a 
multitude of indications. Each year many existing drugs 
gain new indications and hundreds of new drugs or new 
formulations of existing drugs are added to the BNF. 
For some indications the choice of drugs may be 
bewildering and the marketing claims made for them 



131 




PATIENT ASSESSMENT 



*M*MtaUM*iiirifeMHft? 



may be very impressive at first glance. Sensibly evaluate 
the real worth of drugs. 




Key point 

• Select drugs for their proven efficacy 
(effectiveness), safety convenience and cost 
not on the basis of claims made for them. 

Efficacy 

1. In order to gain a product licence, the pharmaceuti- 
cal company must provide evidence from clinical trials 
that a drug is at least more effective than placebo (Latin 'I 
shall please'; treatment that pleases the patient rather 
than exerts a curative effect). It need not demonstrate that 
the drug is better than existing therapy. 

2. The benefits of a drug over existing therapy may be 
relatively small. To demonstrate a small clinical advan- 
tage over existing therapy a large, lengthy and very 
expensive clinical trial is often required. 

3. The size, length and cost of a clinical trial can be 
reduced by employing surrogate (Latin sub = in place of 
+ rogare = to ask; substitute) as opposed to real endpoints. 
A surrogate endpoint is some measurement or test that 
plausibly suggests, but does not prove, genuine benefit to 
patients, such as reduction in prostate size in benign pro- 
static hypertrophy. Real endpoints (something the patient 
will notice and is likely to bring benefit, such as a reduc- 
tion in prostatic symptoms) provide a much more secure 
basis for determining the clinical efficacy of a drug. Read 
claims critically (see Chs 12, 45, 46). 



■M* 



Key points 



• Ensure the trial patient group represents the 
likely clinical patients, not younger or healthier. 

• Has the new drug been tested against and 
shown to be more effective than existing 
therapy using real endpoints? 

4. Efficacy data are often presented in the most favour- 
able light. Reductions in relative risk are more impressive 
than reductions in absolute risk, but reduction in absolute 
risk is most important. To get a feel for the benefit of a 
drug, consider the number needed to treat (NNT): 

• Consider two drugs compared using relative risk. Drug 
A reduces the relative risk of disease X by 50%. Drug B 
reduces the relative risk of disease Y by 10%. Which is 
the more effective drug? Drug A perhaps? 

• It is impossible to say without knowing the absolute 
risks of diseases X and Y. If the absolute risk of disease 



X is 1%, drug A will reduce absolute risk by 0.5%. The 
number of patients that need to be treated for one to 
benefit (NNT) will be 100/0.5 - 200. However, if the 
absolute risk of disease X is 50%, drug A will reduce 
absolute risk by 5%. The number of patients that need 
to be treated for one to benefit (NNT) will be 100/5 = 20. 

• Now which is the most effective drug? 

Assessing safety 

1. So you have decided that a new drug offers a 
genuine and clinically significant advantage over, or in 
addition to, existing therapy. You must now investigate 
the drug's safety profile. When you assess comparative 
safety over placebo or existing therapy, again make sure 
that the selected patient group is representative of the 
patients that you actually treat. Relatively young and 
otherwise healthy individuals are less likely to experience 
significant side-effects compared with the elderly patients 
with comorbidity that you might treat. Just as the concept 
of absolute and relative risk may paint different pictures 
in terms of benefit, they may also do so in terms of harm. 

• Consider a new drug that is stated to increase only the 
absolute risk of an adverse effect by 5% only. How safe 
is the drug? 

• It is impossible to say without knowing the absolute 
risk of the adverse effect in patients not taking the drug. 
If this risk is 20%, the drug will increase the relative risk 
by 25%, but if it is 1%, the drug will increase the rela- 
tive risk by 500%! 

2, Also, make sure that, when compared to existing 
therapy, equivalent doses in terms of efficacy were used. 
Have low doses of existing therapy been used when 
making comparisons of efficacy and high doses when 
comparing safety and tolerability? 

Surely the adverse effects are already known? 

1. Most new drugs are purposely designed to enhance 
target selectivity. This is often an important part of the 
marketing message. Indeed, such an approach can poten- 
tially minimize adverse effects and enhance tolerability. 

2. New drugs, no matter how well designed, also have 
a distinct disadvantage. Prior to gaining a licence, it is 
unusual for a drug to have been tested in more than a 
couple of thousand patients. It is often many fewer. While 
dose-dependent, or predictable, adverse effects may have 
been designed out during development, idiosyncratic 
(Greek idios - one's own + syn = together + krasis = a 
mixing; individual mental or physical constitution) 
adverse effects may not yet have occurred with sufficient 
frequency to be noticed. Idiosyncratic adverse effects are 
often serious and sometimes fatal. 



132 



CLINICAL PHARMACOLOGY 




11 



3. Postmarketing surveillance is used to detect these 
adverse effects as quickly as possible. In the United 
Kingdom, the basis of postmarketing surveillance is the 
Yellow Card Scheme. It is quite common for a new 
'wonder drug 7 to be withdrawn a few months later as 
an unacceptable side-effect profile becomes apparent 
through the postmarketing surveillance. 




Key points 



• New drugs are not necessarily safer than 
existing therapy. 

• Moderately rare adverse effects are only 
detected after the drug is marketed through 
the process of postmarketing surveillance. 

The Yellow Card Scheme 

1 . This is a scheme that encourages doctors and phar- 
macists to report all suspected adverse effects of new 
drugs (marked with an ^ in the BNF) and serious and 
life-threatening adverse effects of existing drugs. 

2. Because the scheme is not compulsory, it is under- 
used and only 10% of adverse effects are reported. 




Key points 

• Be alert to the possibility of unexpected adverse 
effects, especially when prescribing drugs 
marked ▼ in the British National Formulary . 

• Report all suspected adverse effects of new 
drugs. 

• Report all serious and life-threatening adverse 
effects of established drugs. 

Convenience and cost 

1. Sometimes a drug company freely admits that its 
new drug is no safer or effective than existing therapy but 
claims that it is more convenient. For instance, a drug may 
need to be taken only once rather than twice daily. It is 
suggested that it will improve patient compliance. In fact, 
there is little evidence that once-daily preparations 
achieve significantly better compliance than twice-daily 
preparations, although both are better than three or more 
times-daily drugs. 

2. As a result of technological advances, a plethora of 
expensive long-acting or slow-release formulations are 
now marketed. As well as reducing dosing frequency, it 
is often also claimed that they achieve smoother plasma 
drug concentrations, which improves either efficacy, 



tolerability, or both. Is there genuine clinical evidence to 
support these claims? 

3. The cost of a new drug should not be a primary con- 
sideration in your decision whether or not to prescribe it 
to an individual patient, but remember that a newer, and 
inevitably more expensive, drug is not necessarily better. 
You should be persuaded to prescribe an expensive new 
drug only if you are convinced that it offers a genuine and 
worthwhile advantage over existing therapy. 

4. A number of very similar drugs may be developed 
simultaneously for the same indication by different com- 
panies. In such cases, it is sensible for you to select the 
cheapest. 




Key points 



• Once- or twice-daily dosing improves 
compliance compared with more frequent 
regimens. 

• Long-acting or slow-release formulations are 
more expensive and may not necessarily confer 
any clinical advantage. 

• Prescribe a more expensive new drug only if it 
offers worthwhile benefit over cheaper 
existing therapy. 

• When a range of very similar drugs exist, select 
the cheapest in the class. 

Gaining reliable information about drugs 

1 . Many sources are available. They are not all helpful, 
some may be misleading. Review articles or journal edi- 
torials are usually balanced, but sometimes the authors 
have links with the manufacturers. Carefully read the 
small print at the end of the article stating the author's 
potential conflicts of interest. 

2. Recommendations from expert bodies are usually 
but not always reliable, 

3. Colleagues may be a useful source of information or 
guidance. 

4. Consult independent assessments, which are avail- 
able nationally through the Drug and Therapeutics Bulletin 
(DTB) and National Prescribing Centre (NPC). Locally, 
hospital committees select new drugs from those avail- 
able to list in the hospital formulary Except in very excep- 
tional circumstances, use drugs on that list. 

5. Consult guidance produced by the National Institute 
for Clinical Excellence (NICE) on relevant drugs. Such guid- 
ance recommends what drug technology should be made 
available, but rarely how particular drugs should be inte- 
grated with other treatment you wish to offer. You remain 
responsible for deciding where and when to use the drug. 



133 




PATIENT ASSESSMENT 




Key point 

Obtain and critically evaluate the best and 
most reliable information available about 
drugs. 



USING DRUGS 



may even have a lower starting dose for elderly patients, 
so check the BNR 



'■^^'fi^'s^-^^ 



Favour prescribing from a personal selection of formulary 
drugs with which you are familiar. From time to time, as 
new evidence becomes available, you might rationally 
add or substitute new drugs according to the principles 
outlined above. You will also know that your patients 
vary in their individual clinical response to drugs. 
Therefore, in order to use drugs both safely and effec- 
tively, you should carefully tailor your prescribing to the 
characteristics of the individual patient. Individual vari- 
ability is manifested in both pharmacodynamic ('what the 
drug does to body' including both desired and adverse 
effects) and pharmacokinetic ('what the body does to the 
drug') responses, according to such factors as age, 
disease, genetic background and other drugs the patient 
is taking. 



Elderly 

1. Patients of advanced age consume most of the drugs 
that are prescribed. Although no drugs are specifically 
contraindicated in the elderly, exercise particular caution 
when prescribing drugs to this group. In particular, be 
aware that the elderly are often more sensitive to both the 
effects and adverse effects of a drug. There are many 
reasons for this. Drug elimination becomes progressively 
impaired with age, causing drug accumulation. In addi- 
tion, the adverse effects of many drugs are blunted by 
physiological compensatory responses. These compen- 
satory responses are less efficient in the elderly. 

2. Elderly patients are more likely to have coexisting 
disease that may alter their response to drugs. Other dis- 
eases mean that other doctors are involved and frequently 
this results in them taking a long list of drugs, often with 
little rational justification - 'polypharmacy' - (Greek polys 
- much, many). This significantly increases the potential 
for drug interactions. 

3. Before prescribing, ask yourself whether your 
elderly patient really requires an additional drug? If so, 
perhaps this is a good time to ask a medical colleague 
specializing in the care of the elderly to rationalize the 
patient's therapy. If you do decide to prescribe, start with 
the lowest possible dose and titrate the dose gradually 
upwards until the desired effect is achieved. Some drugs 




Key points 

• The elderly are more sensitive to the effects 
and adverse effects of drugs. 

• Polypharmacy in the elderly increases the 
potential for drug interactions. 

• Avoid prescribing additional drugs to elderly 
patients unless absolutely necessary. 

Children 

1 . As paediatricians continually point out, children are 
not just small adults. This is especially true for the way 
children respond to drugs, both in the nature and the 
extent of the response. Not surprisingly, neonates are the 
most different and, as children develop, they gradually 
respond more like adult patients. Some drugs are speci- 
fically contraindicated below a certain age and, of those 
medicines that are considered suitable, few have been 
formally tested in children. This means that they are 
unlicensed for paediatric use. 

2. Paediatricians are well aware of these difficulties. Over 
the years, they have learnt from experience what are suit- 
able drugs and suitable doses for children. Most hospitals 
have a paediatric formulary incorporating this experience; 
this will often give more age-specific dosing information 
than standard references like the BNF. Therefore, always 
refer to the paediatric formulary and always ask a paedia- 
trician for help if you are at all unsure, or if you wish to pre- 
scribe a drug not contained in the paediatric formulary. 




Key points 

• Children may respond very differently to drugs 
compared with adults. 

• Most drugs are unlicensed for paediatric use. 

• Be guided by the local paediatric formulary. 

• Always be willing to seek specialist advice. 

Pregnancy 

1. The problems with thalidomide in the 1960s have 
understandably made doctors very wary about prescrib- 
ing drugs when a patient is, or might become, pregnant. 
The drug was prescribed to pregnant women to relieve 
morning sickness, and resulted in the birth of babies with 
aplastic or hypoplastic limb deformities - phocomelia 
(Greek phoke = seal + melos - limb; from the resemblance 



134 



CLINICAL PHARMACOLOGY 



11 



to a seal's flipper). Many commonly used drugs are 
known or suspected to be harmful to the fetus, or have 
never been prescribed in pregnancy. There is, however, a 
small group of older drugs that accumulated clinical 
experience suggests are relatively safe. 

2. Often the extent and nature of the harm depends on 
the trimester of pregnancy during which the drug is pre- 
scribed. Drugs harmful in the first trimester are potential 
teratogens (Greek teras = monster + gennaein = to generate), 
whereas those prescribed in the second or third trimesters 
may adversely effect fetal development or metabolism. 
Drugs prescribed late in pregnancy may also affect labour 
and harm the child in the peri- and postnatal periods. 

3. As far as possible, avoid prescribing any drugs in 
pregnancy, but where prescription is inevitable, restrict 
yourself to those drugs that are regarded as relatively 
safe. On every occasion check in the BNF (Appendix 4) 
that the drug is appropriate for the stage in pregnancy of 
your patient. 

4. What happens if the mother is seriously ill and you 
have to prescribe a drug that may harm the fetus? This can 
be justified because the well-being of the fetus is secondary 
to the well-being of the mother. If you are faced with such 
a situation, always try to seek advice from a fetal medicine 
specialist in order to minimize risk to the unborn child. 




Key points 

• If possible, avoid all drugs in pregnancy or in 
women who might become pregnant. 

• If you must prescribe, specifically check in the 
BNF that the drug is considered safe. 

• If in doubt, or when a potentially harmful drug 
is indicated, seek specialist advice. 

Disease 

Many drugs are known to have the potential to harm 
organs or to exacerbate certain diseases. Potential organ 
damage will be listed as a specific adverse effect of a par- 
ticular drug. A disease exacerbated by the drug will be 
listed in the BNF as a specific contraindication to pre- 
scribing the drug. 

Liver and kidney disease 

1 . The kidneys and the liver are the organs principally 
involved in drug elimination. This means that both the liver 
and kidney are particularly susceptible to the harmful 
effects of drugs (hepatotoxicity and nephrotoxicity). It also 
means that pre-existing liver and renal disease may 
adversely affect the body's handling of some drugs, leading 
to drug accumulation and increased adverse effects. 



2. When prescribing hepatotoxic or nephrotoxic drugs, 
carefully consider whether the potential benefits to the 
patient outweigh the potential risks. If you do prescribe, 
monitor for organ toxicity. In those patients with either pre- 
existing liver or renal disease, the risks are usually so great 
that you should avoid prescribing drugs that are poten- 
tially toxic to the affected organ. However, in some cases, 
such prescribing is inevitable. If this is the case, make every 
attempt to minimize exposure to the drug by reducing dose 
and duration of therapy. Rigorously monitor any bio- 
chemical changes signalling worsening organ impairment. 

3. With pre-existing liver or renal disease, even if you 
prescribe drugs that are not directly toxic to the affected 
organ, you may still face difficulties due to impaired drug 
elimination. In general, reduce the dose and /or frequency 
of the prescribed drug. Appendices 2 (liver) and 3 
(kidney) of the BNF suggest appropriate dosage reduc- 
tions according to the degree of organ impairment. 




Key points 

• The liver and the kidneys are especially likely 
to be harmed by drug therapy. 

• Where the potential for harm exists, carefully 
monitor for toxicity. 

• Pre-existing liver and renal disease often causes 
drug accumulation and increase adverse effects. 

• Adjust the dose according to the BNF. 

• If possible, avoid prescribing potentially 
hepatotoxic or nephrotoxic drugs to patients 
with impairment of those organs. 

• If such prescribing is inevitable, take every step 
to minimize additional harm. 

Genetic background 

It is increasingly recognized that multiple genetic factors 
are responsible for much of the individual variability 
observed in patients' pharmacodynamic and pharmaco- 
kinetic responses to drugs. New drugs are increasingly 
designed to minimize such genetically determined vari- 
ability but, for the vast majority of patients, we have not 
reached a point where a patient's precise genetic make-up 
is a factor to consider when prescribing. The only area 
where is does matter is when prescribing for patients with 
rare single-gene disorders which affect their response to 
a wide range of drugs. The best known of these disorders 
are porphyria and glucose-6-phosphate dehydrogenase 
deficiency (G6PD deficiency). Many drugs are recognized 
to aggravate these conditions. If you have a patient with 
either of these disorders you should make sure (by check- 
ing the BNF) that the drug and dose that you prescribe is 
not regarded as potentially harmful. 



135 




PATIENT ASSESSMENT 



Interactions 

In practice, it is often drug interactions due to the co- 
prescription of other drugs that cause the most problems. 
The possibilities for interactions increase exponentially 
with each new drug that is added. Drug interactions can 
be either pharmacodynamic or pharmacokinetic. 

Pharmacodynamic interactions 

1 . Additive - where two drugs combine to produce a 
greater effect. You may on occasion exploit this 
interaction clinically to enhance a desired effect, but 
it also can unwittingly produce enhanced toxicity. 

2. Antagonistic ~ where one drug cancels or diminishes 
the effects of another. Again, you may sometimes 
wish to exploit this interaction clinically, particularly 
in the case of overdose. 

Pharmacokinetic interactions 

Any stage of the pharmacokinetic process (absorption, 
distribution, metabolism and excretion) has potential for 
drug interactions. The most common and important inter- 
actions involve drug metabolism and, in particular, 
induction and inhibition of the hepatic cytochrome P450 
(CYP450) enzyme system. This is a family of the hepatic 
enzymes responsible for the metabolism of a wide variety 
of commonly used drugs, referred to as CYP450 sub- 
strates. These enzymes can be either inhibited or induced 
by other drugs. 

1 . In the presence of a CYP450 inhibitory the substrate 
drug is metabolized more slowly, causing the plasma 
levels to rise. Examples of CYP450 inducers are cimetidine, 
ciprofloxacin and erythromycin. To compensate, reduce 
the dose of the substrate drug. 

2. In the presence of a CYP450 inducer, the substrate 
drug is metabolized more rapidly, causing the plasma 
levels to fall. Examples of CYP450 inhibitors are pheny- 
toin, carbamazepine, rifampicin and alcohol. Increase the 
dose of the substrate drug to compensate. 

3. In practice, interactions due to CYP450 inhibition or 
induction are most likely to cause you problems when the 
CYP450 substrate drug has a narrow therapeutic index. This 
means that there is only a narrow range of plasma con- 
centration in which the drug is neither subtherapeutic nor 
toxic. Common CYP450 substrates with a narrow thera- 
peutic index include theophylline, ciclosporin and war- 
farin. Your safe and practical solution with such drugs is 
to monitor the plasma level (or International Normalized 
Ratio (INR) in the case of warfarin). This monitoring 
should be more extensive (i.e. daily) when starting or 
stopping CYP450 inhibitors and inducers. 




Key points 

Drug interactions can be either 
pharmacodynamic or pharmacokinetic. 
Potential drug interactions are listed in 
Appendix 1 of the BNF. 
Identify and carefully monitor drugs with a 
narrow therapeutic index. 



Summary 

• Are you aware that even as a surgeon, 
prescribing drugs is likely to be a common 
and important part of your practice? In 
order to prescribe effectively for your 
patients, you must be able to select drugs 
rationally and use them safely. Despite the 
marketing claims, new drugs may not 
necessarily be more effective than existing 
therapy and will often be much more 
expensive. Before prescribing, you should 
look for objective and clinically relevant 
evidence of benefit from well-designed 
clinical trials. New drugs are not always safer 
than existing therapy. In fact, precisely 
because they are new, there is significantly 
less clinical experience than with older drugs. 
For this reason, new drugs are subjected to 
intensive postmarketing surveillance for 
adverse effects that are too rare to have 
been detected in prelicensing clinical trials. 

• Do you recognize the need to rely on the 
hospital formulary when you prescribe, not 
on your memory? Consult the BNF unless you 
are absolutely sure about a drug. Always use 
the BNF when prescribing for difficult 
patients, especially those who are at the 
extremes of age, pregnant, have coexisting 
disease (especially hepatic and renal) or are 
receiving other drugs. Always seek to 
minimize the number of drugs a patient is 
receiving and weigh up carefully the risks 
and benefits of using a particular drug. You 
should be alert to the problems of drug 
toxicity and interactions. If these occur, act 
quickly to prevent further harm. In difficult 
situations, never be afraid to seek advice 
from specialists who have more experience. 
Remember, they will be very keen to seek 
your help with surgical problems. 



136 



CLINICAL PHARMACOLOGY 



11 




Further reading 



British National Formulary. Published 6-monthly by the British 
Medical Association and the Royal Pharmaceutical Society of Great 
Britain, London 

Drug and Therapeutics Bulletin. Published monthly, and free to all 
NHS doctors, by Which Ltd, London, DTB reviews new and 



existing therapies. The articles are concise, independent and well 
respected and should be considered essential reading 
Ritter JM, Lewis LD, Mant TGK 1999 A textbook of clinical 
pharmacology, 4th edn. Edward Arnold, London 

Useful links 

www.bnf.org British National Formulary 
www.nice.org.uk National Institute of Clinical Excellence 
www.npc.co.uk National Prescribing Centre 



137 




Evidence-based practice 



J. W. McClenahan 




Objectives 

Understand the purpose and nature of 
valid, important and applicable evidence 
to augment personal experience. 
Recognize the factors that help and hinder 
more widespread application of 'evidence- 
based practice' to surgery. 
Identify some suggestions for action that 
you or your colleagues could take. 




Evidence-based practice is: 



INTRODUCTION 

You already use evidence (Latin e = from + videre = to 
see; hence, that can be seen) of many kinds in your sur- 
gical practice. The more systematically you can do that, 
the better a surgeon you can become. The encourage- 
ment given to evidence-based practice (EBP) seeks to 
enhance the role that systematic, critical review of valid, 
reliable and applicable evidence can play in enabling 
you to: 

• Perform more appropriate surgery 

• Inform patients better about the probable benefits 
and risks of surgery for their condition - both 
in general, and in relation to their own personal 
circumstances 

• Enlarge the range of surgical interventions that have 
been reliably shown to be worthwhile, by participation 
in higher quality research. 



WHAT IS 'EVIDENCE-BASED 

PRA^ 

1. Different authors will give varying definitions of 
what the phrase means, or even limit it to evidence-based 
medicine (excluding other clinical professions such as 
nursing or therapies). The following definition from 
McKibbon et al (1995) is the one I prefer. 



An approach to health care that promotes: 

• the collection, interpretation and integration 
(into clinical practice) of 

• valid, important and applicable 

- patient-reported 

- clinician-observed, and 

- research-derived evidence. 

2. There are several points of note about this definition. 
It is an inclusive approach to health care as a whole, not a 
narrow limitation to research-derived evidence, let alone 
just to evidence from randomized controlled trials 
(RCTs). 

3. It acknowledges the potential validity of patient per- 
ceptions, your clinical observations, and the use of judge- 
ment to integrate the different sorts of evidence. 

4. However, randomized controlled trials remain the 
'gold standard' of evidence. They are applicable if the 
types of patients included in them adequately match the 
real world of your clinical practice. 

5. The definition also emphasizes the importance of 
building the use of evidence into your routine clinical 
practice. Do not see it just as an 'off-line' educational or 
research activity done by others. Furthermore, it implies 
the development of skills and judgement to decide what 
is valid, important and applicable, both to the individual 
patient you are considering now, and the whole range of 
patients you are or should be treating. 

6. Evidence-based practice constitutes an intellectual 
revolution in the practice of medicine (in the broadest 
sense, i.e. what doctors of all kinds, including surgeons, 
do). It has been fuelled in the last decade or so particu- 
larly by five interrelated factors: 

a. The knowledge explosion - the exponential growth in 
published research and knowledge. 

b. The particular technique of meta-analysis - pooling 
the results of multiple clinical trials to derive more robust 
conclusions than any one alone can support. 



138 



EVIDENCE-BASED PRACTICE 



12 



_ ■■ [ -.:^-:^,> J . --■■...--.- .v. .■ ■ 



c. The rapid evolution of systematic review - now a 
fomalized, thorough and reproducible (but resource- 
intensive) method of finding virtually all evidence on a 
topic, grading it by quality and relevance, and summar- 
izing the results in a form able to be peer reviewed, and 
used by busy clinicians. 

d. The organization of the International Cochrane 
Collaboration. This links researchers, information analysts, 
and practising clinicians worldwide. In the UK, two 
centres of particular importance are the Cochrane Centre 
in Oxford, and the Centre for Reviews and Dissemination 
in York. The collaboration helps to resource systematic 
reviews and engages with others in doing so worldwide. 

e. Technological developments in knowledge distribution 

- particularly CD-Rom and the Internet - which make 
knowledge widely accessible easily and relatively 
cheaply. Increasingly, this means in the ward, operating 
theatre, diagnostic department, outpatient clinic, clinical 
staff's own offices and GP surgeries, as well as in libraries, 
postgraduate centre and people's own homes. 

7. Evidence-based practice aims to improve clinical 
effectiveness - doing the right things for the right people 
at the right time in the best known way in routine prac- 
tice. This means translating the findings of research which 
demonstrated efficacy - that there was a difference in a 
controlled trial in favour of one intervention over another 

- into effective use for a real population of patients. 



Achieving clinical effectiveness 
requires: 

• Professional staff who have up-to-date 
knowledge and skills, together with 
appropriate attitudes 

• Working together in a cohesive and 
coordinated fashion within clinical teams 

• The support of managers to meet both patient 
needs and strategic needs of the organization 
(Batstone & Edwards 1997). 

For surgeons, this can mean some significant personal 
changes or even challenges. Only those with strong indi- 
vidual egos seem to become surgeons, and surgery has a 
competitive culture. Acknowledging the importance of 
teamwork is perhaps easier now than allowing that man- 
agers have a valid role to play, but both run counter to 
many stereotypes if not the reality of modern surgery. 
Some of your behaviours may have to be unlearned! 

Weren't we doing it anyway? 

1. No conscientious medical practitioner I know wants 
to perform badly, and most make strenuous efforts to 




keep up to date. So it hurts to be told that your practice 
could be improved if you were to change the way you 
approach the use of evidence. You think that you already 
do the best you can with your limited time and, with help 
from your colleagues, you already use evidence - you 
were taught to do so by your professors or consultants or 
you have been challenged by your up-and-coming 
juniors. Well, yes ... up to a point. 

2. The reality, as opposed to the aspiration, is that there 
are often long delays between the production of convinc- 
ing research evidence and its widespread adoption. The 
proponents of EBP believe, often with justification, that 
these delays could and should be shortened. 

3. Things are getting better, however. A historical per- 
spective illustrates the point. Prevention of scurvy took 
roughly two centuries between the first evidence of effi- 
cacy in 1601 (James Lancaster) and its routine adoption by 
the British Navy from 1775-1814. In this century, throm- 
bolytic therapy after myocardial infarction took about 
two decades (from the 1970s to the 1990s) to be acknowl- 
edged as appropriate. Only then did it gain general 
acceptance as what ought to be done, even though the 
application is still uneven (see, for example, Antman et al 
1992). Surfactants to relieve respiratory distress syndrome 
from hyaline membrane disease for neonates were 
adopted even more quickly - in part because their effects 
were obvious and dramatic, and in part because they 
went 'with the grain' of clinical culture and experience. 



What EBP is not but is feared to be 

1 . Just cost cutting, or being banned from doing certain pro- 
cedures? Many doctors fear that EBP is just an attempt to 
reduce costs. They therefore react negatively. However, 
careful interpretation of the evidence may suggest that dif- 
ferent things be done, some of which may cost more, some 
less, and some about the same. Part of your task when you 
are a senior surgeon will be to balance the many compet- 
ing demands on resources. Evidence of effectiveness must 
play a bigger part in future decisions (see Ch. 42). 

2. Another reduction in clinical freedom, or 'cook-book' 
medicine? Appropriate integration of research evidence 
into clinical practice poses no threat to clinical freedom 
(using the McKibbon et al definition), except to help you 
avoid unnecessary or indefensible mistakes. Is that the 
freedom you want to retain? 

3. Central diktats will determine local guidelines and proto- 
cols and 'the way we do things here'? These should rather be 
determined locally, but using centrally collated and 
validated evidence. By establishing more clearly your 
own and your colleagues' understanding of what is 
known with reasonable certainty, based on research evi- 
dence, experience and patient feedback, you can make 



139 



12* 



PATIENT ASSESSMENT 



Table 12.1 Examples and issues 




Nature of evidence 



Evidence convincing, 
widely accepted, but not 
universally applied 

Evidence readily 
available but not sought 



Evidence sought, but not 
locally accessible at the 
relevant time or place 

Evidence actively 
sought, not found, 
equivocal or 
disputed 



Examples 



Early thrombolytic 
therapy for AMI 

Which surgical patients 
benefit from DVT prophylaxis? 
Whom should we treat 
for atrial fibrillation? 

As above, and ... 
Adjuvant therapy 
following surgical removal 
of cancers 

When should we remove 
catheters after paediatric 
cardiac surgery? 



Issues 



(Often mistaken) belief that 'we already do it here' 
- [ocal and national audits often show otherwise 
Achieving organisational change to allow it 

Shifting professional attitudes to seeking evidence 
CPD (continuous professional development) 
Interpretive skills {critical appraisal training) 

Organizational and technical infrastructure 
Information and library facilities and staffing 
Technical skills training 

Establishing effective local guidelines, and local 
audit or research projects 
Feedback to national R&D priority setting or 
local academic centre 



commonplace practice more consistent, and higher quality 
easier to deliver, audit and sustain. This leaves more, not 
less, freedom and time to use your judgement in areas 
where the circumstances are not routine, the research- 
based evidence is absent or equivocal, or the patient's indi- 
vidual preferences are uniquely out of the ordinary. 

4. Just for doctors, or just for clinical staff? Evidence- 
based practice is as relevant for patients and their fami- 
lies or carers, and for managers, as it is for you. Media 
attention and the internet now make much more of the 
evidence widely available. Sessions with non-clinical 
staff, including managers and non-executive directors 
from NHS organizations/ demonstrate that they can 
quickly and intelligently appraise even technical papers 
against systematic appraisal criteria. They can reach clear 
conclusions about the strength and interpretation of the 
evidence for themselves (from my personal experience 
with such groups at the King's Fund). 




Who needs information on evidence- 
based practice? 

Patients to discuss options and risks with you. 
Professionals to improve their practice. 



Providers to improve effectiveness for their 

organizations. 

Purchasers, now primary care trusts (PCTs) in 

the NHS; more generally, commissioners of 

health care, to obtain the best quality service 

they can afford. 

Public for assurance that all of the above is 

happening properly in their interests. 



HOW CAN EVIDENCE MAKE A 
DIFFERENCE? 

1. Evidence can impact practice in several different 
ways, and what needs to be done to improve things 
depends on the nature of the evidence, and what sort of 
barriers prevent its use. Examples (not exhaustive) are 
shown in Table 12.1. 

2. What helps or hinders change? The 'change equa- 
tion' (adapted from Beckhard & Harris 1987) is shown in 
Figure 12.1. You need to pay attention to all four boxes 
to maximize the likelihood of successful use of evidence 
to change practice. Acknowledge that you may be able to 
work on the perception that others have of the proposed 



Perceived 

power of 

vision 



Perceived pain 
of present 



Perceived 

feasibility of 

first steps 



Perceived pain 
of change 



Fig 12.1 Beckhard's change equation. In order to change practice you need to take account of all four boxes. Present 
a clear, persuasive view of how things might be, show the present drawbacks, devise feasible initial changes and 
minimize 'discomfort' of change perceived by those affected 



140 



EVIDENCE-BASED PRACTICE 



12 



changes as well as the 'real' content of the change, as, for 
them, their perception is the reality. 

3. To succeed: 

a. Present a clear and persuasive view of how things 
might be (the vision) in terms relevant to the intended 
audience. 

b. Show the drawbacks of the present circumstances 
(perhaps unsatisfactory or even dangerous), and ensure 
that other people become as uncomfortable with it as you 
are yourself. 

c. Devise some initial changes that people see as 
feasible to get started (so make thern as easy to adopt as 
possible). 

d. Minimize the discomfort of the change as it will be 
perceived by individuals or groups affected. 

4. Changing clinical practice is a multistage process. It 
does not happen all at once, and different influences work 
at different stages of people's readiness for change. 




Key point 

• Do not presume that a rational argument, 
clearly and forcefully presented, will of itself 
predispose people to change, especially if they 
are not yet emotionally ready even to believe 
it is necessary at all. 

5. Figure 12.2 shows one model of individual change 
(based on Prochaska & DiClemente 1984) that may be 
helpful in understanding where you and your colleagues 
stand. It is crucial to acknowledge the importance of the 
early stages - initial awareness of the possibility of change 



and recognition of a need to change. This can often take 
time (months, or occasionally years) to work through. 

Where the major personal block is an emotional one, 
restating the rational case ever more forcefully is posi- 
tively unhelpful. Ask rather than tell, and try to find out 
what emotion is being triggered by your proposal (or 
your own reaction to others' proposals) and seek to deal 
with that first. 

6. Organizational change is a slower process than you 
expect - be patient. You may be used in your surgical 
team to making decisions and seeing them implemented 
very quickly or even instantly, if the power to change lies 
wholly within the surgical team. However, much of the 
improvement in clinical practice suggested by research 
evidence requires change on a broader organizational 
front. Many people with different professions, personal 
backgrounds, beliefs and values may have to be per- 
suaded. Evaluation of change 'in the field' in response to 
evidence suggests four major hindrances to change at a 
scale larger than a single clinical team: 

a. Getting momentum going. Raising awareness and 
recognition of the need to change takes time, patience, 
and repeated application as the 'cast of characters' is con- 
stantly changing in the hectic pace of NHS reorganization. 

b. Staff turnover. Original sponsors of change may leave 
the organization. 

c. Action. Getting guidelines agreed and accepted is 
more difficult than most people initially believe is possible. 

d. Implementation and maintenance. If you think getting 
guidelines agreed is the hard part, think again. After that 
is when the most difficult (but ultimately rewarding) part 
really starts. To engage others more widely beyond the 
enthusiasts, you or a small group around you, need yet 
more patience, careful planning, wide consultation and 




Emotional 

- engagement 

- acceptance 




Rational 

- clarification 

- diagnosis 



Fig 12.2 A model of individual change 



141 



12 



PATIENT ASSESSMENT 



listening, and adequate resource to see your proposals 
into widespread and sustained use. Grol (1997) has a 
useful review of the different types of approach that could 
be adopted, and the evidence for their effectiveness. 

7. You need other sorts of information, some relatively 
obvious, others perhaps unexpected: 

a. Local demographics (population size, density and 
distribution), and prevalence of the disease or condition 
of interest. How many people does it affect? How 
seriously? 

b. Actual local practice. Audit of current practice, and 
open discussion with colleagues may reveal unexpected 
differences between what you believe should happen or 
think is already happening, and what actually does 
happen. 

c. Patients' and service users 7 views. Have you asked 
them, or looked for previous evidence of their views, rather 
than what you think their views are, or ought to be? 

d. Understand the organizational context. How does 
the diagnostic, treatment and care process actually work 
at present, and who would be affected by proposed 
changes? How are referral decisions influenced? How 
could you change that? 

e. Local 'political insighf . Who has a stake in this 
process? What do they think about the issues? What else 
is on their agenda that may help, or hinder, progress in 
the direction you want? 

f. Where might resources be obtainable? Change is 
unlikely to be completely neutral in resource terms, such 
as time, energy, money and facilities. How may they be 
freed up to pump prime change, or where can additional 
resources be sought with some chance of success? 




Key points 

• We can all identify what is wrong. 

• Merely stating problems is ineffective. Devise 
solutions. 

• The goal is not just devising solutions but 
implementing them. 

^WHELPS? 

1 . In our own research into the process of implementing 
evidence-led change in North Thames region (Smith 
& McClenahan 1997, 1998; Haines and Evans 2000; 
Wye and McClenahan 2000), six factors seem to make 
progress more likely: 

a. Support from both managers and clinicians at a 
senior level 



b. Adequate resourcing in relation to the scale of 
ambition 

c. A project management approach, with clarity 
about lead roles, and clarity of objectives for the 
change process on a realistic scale (neither 
overambitious nor too modest) 

d. Having, or putting in place, the right 
organizational infrastructure to support clinical 
service improvements 

e. An understanding of change management as a 
process 

f. Closing the loop properly - auditing whether 
clinical processes have changed to match those 
associated with efficacy in a research environment. 
It is usually not possible or necessary to audit 
outcomes themselves — that was what the research 
was about. 

2. Depending on your present level of seniority and 
influence, consider some of the following ways of 
making a difference: 

a. What is your own attitude to the possibility of 
improvement to your own practice? Talk it over 
with colleagues. Analyse your emotional reactions 
as well as the practical and rational ones. 

b. Access information sources (particularly the 
Cochrane database (CD-Rom), Medline, CINAHL 
and the internet) and learn how to make use of 
them. Encourage all your staff to use them. Get 
help from others with the relevant skills. 

c. Seek local training (if you have not already had 
some) in critical appraisal - the process of 
reviewing published research evidence to assess 
its quality and relevance to your own patients' 
circumstances. Practise it in your routine 
work. 

d. Try to make or reinforce connections between the 
clinical governance or clinical effectiveness 
committee (or its local equivalent) and its 
subgroups; clinical audit; library and information 
services; multidisciplinary team working; 
education and training; Continuous Professional 
Development/ Continuing Medical Education; 
guideline development; and patient information 
provision (see Chs 42, 43). 

e. Seek management support for implementing 
desired change processes: in your own team; 
across departments; for common clinical 
conditions; and across organizational boundaries 
with primary and tertiary care and where 
relevant, social care and support organizations. 

f. For the real enthusiast: take part in a systematic 
review of an area of practice that interests you. 



142 



EVIDENCE-BASED PRACTICE 



12 



Summary 

♦ Recognize that evidence-based practice 
encompasses not just the application of 
randomized controlled trials but all 
aspects of health care. 

* Question your practice and consider how 
much is justifiable on reliable evidence. 

• Can you offer your patients firm evidence 
on which you base your advice? 

• Do you accept that you can enlarge your 
range of surgical interventions by seeking 
trustworthy evidence and by participating 
in high quality research? 




References 



Antman EM, Lau }, Kupelnick B, Mosteller F, Chalmers TC 
1992 A comparison of results of meta-analyses of 
randomized control trials and recommendations of clinical 
experts. Treatments for myocardial infarction. JAMA 268: 
240-248 

Batstone G, Edwards M 1997 Challenges in promoting clinical 
effectiveness and the use of evidence. In: Harrison A (ed.) 



Health care UK, 1996/7. King's Fund Policy Institute, King's 

Fund, London 
Beckhard R, Harris RT 1987 Organizational transitions: 

managing complex change, 2nd edn. Addison Wesley, 

Reading, MA 
Grol R 1997 Beliefs and evidence in changing clinical practice. 

BMJ 315: 418-421 
Haines A, Evans D (eds) 2000. Evidence based change in 

healthcare. Churchill Livingstone, Oxford 
McKibbon et al 1995: see Useful links 
Prochaska J, DiClemente C 1984 The transtheoretical approach: 

crossing traditional boundaries of therapy. 

Dow Jones-Irwin, Homewood, IL 
Smith L, McClenahan JW 1997 Putting practitioners through the 

paces: initial findings in our evaluation of putting evidence 

into practice. King's Fund and North Thames R&D 

Directorate, London 
Smith L, McClenahan JW 1998 Snakes and ladders: levers, 

obstacles and solutions to putting evidence into practice. 

King's Fund and North Thames R&D Directorate, London 
Wye (nee Smith) L, McClenahan JW 2000 Getting better with 

evidence. King's Fund and North Thames R&D Directorate, 

London 

Useful links 

hiru.mcmaster.ca/hiru/medline/mdl-ebc.htm McKibbon K, 
Wilczynski N, Hayward RS, Walker-Dilks C, Haynes RB 1995 
The medical literature as a resource for evidence based care 

www.kingsfund.org.uk/eLeadership/html/publications.html 
King's Fund Publications, London 

www.doh.gov.uk/ntrd/pdf/getbtr.pdf Department of Health, 
London 



143 




Decision making 

R. M. Kirk, K. Cox 



W 



Objectives 

Recognize the complex, multiple, 
interacting factors that need to be taken 
into account when making a decision. Even 
though you may not be able to evaluate 
all of them, do not ignore them. 
Good decisions demand the best available 
evidence. Critically search out and use 
discriminant information in preference to 
equivocal and dubious evidence. 
Decisions are valid only at the time they 
are made. Be prepared to revise them if 
the circumstances change. 
Remember that your patient must be fully 
informed, and understand the information, 
in order to participate in the decision 
making and give informed consent. 
Furthermore, your patient's evaluation of a 
successful outcome may not be the same 
as yours. 



Good surgery is 25% manipulative skill and 75% decision 

making. 

Adapted from the distinguished 
American surgeon F. C. Spencer 



INTRODUCTION __ ^ _ __ 

This chapter forms the fulcrum of the book. What has 
gone before is the knowledge and evidence that you 
should have available. What follows are the actions and 
consequences of the decision or decisions that you take. 
As a surgeon you cannot merely follow a set of rigid 
instructions. You are a professional who searches for 
information, appraises it, makes decisions, acts on them, 
monitors the outcomes and accepts responsibility for 
them to your patients, your peers and your own con- 
science. However, decision making depends on a multi- 



plicity of factors, many of which may be unknown or 
even unknowable. Some are not susceptible to scientific 
or statistical evaluation, and because they are disparate, 
they cannot be listed in a ranked sequence of graded 
importance. In the past there was little appreciation of 
risk analysis, cost effectiveness and the patient's assess- 
ment of quality of life following treatment. 

Our challenge is to identify the important, discriminant 
elements from the inconsequential ones, but oversimpli- 
fication is dangerous. You must not concentrate on the 
components in isolation but consider the patient as a 
whole, not merely as an aggregation of individual parts. 
The whole has qualities beyond those of the parts. The 
term Gestalt (German = form, build, fashion), was coined 
in 1890 by a group of German psychologists to denote 
experiences that require more than basic sensory capaci- 
ties to comprehend. 

Within a simple linear system the whole behaves pre- 
cisely and predictably as the sum of the parts. A change 
of one factor produces a consistent, predictable effect. We 
are composed of multiple biochemical, cellular, physio- 
logical and psychological systems which interact by 
means that include biochemical and neuroendocrine 
feedback loops. Within such a complex system a change 
in one unit may produce unforeseeable, seemingly capri- 
cious, collective behaviour. The emerging 'complexity 
theory" takes account of the fact that complicated, self- 
organizing systems continuously adapt to and change 
their environment, but in ways that are impossible to 
predict. The theory is not yet a fully developed science, 
but seeks to identify, with the intention to predict, the 
emergence of characteristics that are not present in the 
individual components. For these reasons, reliable clini- 
cal decisions cannot be made by adhering to rigid rules. 
There is often an element of uncertainty (Plsek & 
Greenhalgh 2001, Wilson & Holt 2001). 

Data derived from linear systems is often 'Yes or No/ 
and 'Black or White/ In complex biological systems it is 
more frequently, 'Perhaps, depending on a number of 
factors/ and 'A shade of grey/ We do not judge the evi- 
dence before us with open minds because we are already 
conditioned by our previous knowledge and experience. 



144 



DECISION MAKING 



13 



Our subjective assessment may differ from that of others 
with a different knowledge background and experience. 
Our own judgement may vary resulting from a recent 
success, or series of disasters. This is not a defect in us; we 
learn to recognize patterns and make tentative prejudge- 
ments - 'prejudices'. Prejudices are reprehensible only if 
they are inflexible. 

Some surgeons are more successful than others at 
making correct decisions. Their results are superior to 
those of others, not only following operation when their 
superior skills can be invoked, but also in the one-third 
of surgical cases that are treated conservatively. They 
usually cannot give a rational explanation for their judge- 
ment and often attribute it to a "gut feeling'. Such sur- 
geons appear to anticipate and evaluate the possible risks 
instinctively. Perhaps they take time to consider all the 
possibilities, rather than settling on the first course that 
presents itself. We surgeons like to think of ourselves as 
men and women of action, that is, 'decisive 7 . Not all deci- 
sions need to be taken instantly. The increasing require- 
ment to display the arguments for or against the possible 
courses of action to colleagues and to patients should 
have a beneficial effect on decisions. 

It is remarkable that most of our major decisions are not 
made rationally. Consider your own life decisions. Can 
you logically defend your choice of profession, your life 
partner, or always justify the clinical judgement to ask 
advice, enlist assistance, conclude that you must proceed, 
or relinquish responsibility to someone better able to care 
for your patient? 

Previous generations of autonomous surgeons made 
decisions and presented them to their team and patients 
without discussion. Attitudes have gradually undergone 
a transformation. As a result, we first make our assessment 
on the basis of our training, experience and access to 
scientific and professional information. We consult other 
members of our team and specialist colleagues. When 
dealing with certain conditions, such as complex tumours, 
we form specialized groups in order to bring together all 
relevant experts. We can now offer an appraisal for dis- 
cussion with the patient, in terms that are comprehensible, 
in order to reach a mutually agreed course of action and 
receive informed consent (see Ch. 14). This entirely appro- 
priate change has, of course, added yet greater complex- 
ity to the factors that must be taken into consideration. The 
change has been from what was a virtual statement of 
intent, into a complicated group negotiation. 

Surgeons formerly dealt with a wide range of condi- 
tions and a single surgeon might see relatively few cases 
of any particular condition, making it difficult to make 
judgements for the future. Individual decisions may be 
impossible to assess in retrospect. The outcome could be 
poor in spite of good judgement and expert care, owing 
to factors that are unknown, unmeasurable or over which 



there is no control. Conversely, a robust patient may 
survive incorrect or inadequate management. 

As a result of specialization, the formation of teams, 
specialist groups, and national and international 
exchange of information, large numbers of similar cases 
can be accumulated and the outcome following different 
methods of treatment can be compared. 

The initial assessment and decision resemble the strat- 
egy (Greek stratos = an army + agein = to lead) of an army 
general. He is not, though, able to predict the response of 
the opposing general to his planned moves, so must 
closely observe and react by rearranging his plans; this is 
tactics (Greek tactikos from tassein = to arrange, hence 
rearrange). Very few decisions in life are once and for all. 



ESSENTIALS OF SURGICAL DECISION 
MAKING 






Information 

1 . Since you cannot incorporate all the information into 
a balanced judgement, you must discriminate by choos- 
ing what is relevant and reliable, what must be borne in 
mind, what can be left out of consideration for the time 
being, and what can be rejected as invalid or irrelevant. 

2. Can the published literature be applied to your 
patient? No two patients are exactly the same and some 
factors may exclude your patient from being comparable 
with the tightly selected patients assessed in statistical 
trials. However, some of the aids to decision making may 
be less constrictive (see later). 

3. Following carefully considered initial judgement, 
determine to anticipate and react to subsequent changes 
so you do not endanger recovery. 

4. Determine to monitor, analyse and record the cir- 
cumstances and outcome of your strategic planning and 
subsequent management, so you can in future adjust your 
decisions. 



Joint decision making with the patient 

1. First decide what is the professional opinion you 
will offer the patient. You should review the possible 
methods of management, with the benefits and risks. 
Patients expect you to have your facts marshalled, other- 
wise you cannot give them a clear picture. Informed 
consent (see Ch. 14) implies that patients are well 
informed. 

2. Match your explanation to patients' comprehension. 
At all costs avoid scientific terms or jargon that are likely 
to confuse rather than instruct them. From time to time 
check that they understand you by asking them to tell you 
how they view the situation (see Ch. 47). 



145 



131 



PATIENT ASSESSMENT 



3. Although patients wish to participate, you are the 
professional adviser. How you pass the information 
inevitably influences their judgement. 

4. Many patients faced with the presence of disease and 
the necessity for treatment, including perhaps an operation, 
are not in the best state of mind to make important choices. 
For this reason, whenever there is time, state the various 
possibilities and likely outcomes as simply as possible, then 
suggest that the patient returns after an interval to ask any 
supplementary questions and then reach a decision. 

5. As you point out the consequences of the proposed 
management, your measures of success are not necessarily 
in line with those of your patients. Powerful fears for many 
patients, beyond length of survival, are constant pain, loss 
of the ability to care for themselves, and loss of dignity. 
However, it is often difficult for them to anticipate what will 
be their reaction to the effects of the proposed management. 

6. Recognize your patient's right to ask for treatment 
that differs from that advised by you but do not agree to 
treatment that is harmful, ineffective or offends against 
your own moral code. 

Cost effectiveness 

This was often ignored in the past when making deci- 
sions, the only consideration being for what treatment 
best met the patient's needs. It is now openly accepted 
that in no society can treatments be offered without 
taking into account the economic implications, and the 
likely cost-benefits of other treatments (see Ch. 44). 



priority, and that you reconsider the order from time to 
time. Try not to attempt too many tasks at once - but in 
an emergency be willing to abandon a less important one 
and undertake one that is urgent. 

2. We hope to select available information with open 
minds but there is a temptation to seek and select evidence 
that confirms our prejudice. Make a deliberate effort to 
stand away from the problem so you may become aware of 
incongruities that make you revise your first assumption. 

3. Very few questions can be answered positively - 'Yes 
or No/ or 'Black or White'; the particular shade of grey is 
a subjective opinion. 

4. All clinical decisions demand some simplification of 
the multiplicity of factors, but do not lightly leave anything 
out of consideration. Albert Einstein stated, 'Everything 
should be as simple as possible, but not simpler'. The dif- 
ficulty is in allotting importance to disparate influences on 
diagnosis, extent of disease and management options. 

5. Measuring individual aspects separately does not 
provide a complete picture. You must also look at the 
patient as a whole. 

6. It is usually accepted that experience leads to 
better decision making. We learn to recognize familiar 
patterns. However, there is a temptation to identify 
resemblances early and overconfidently, thus not fully 
checking the remainder of the available evidence. Two 
similar clinical situations are rarely identical, and so 
may call for different action. 



EMERGENCIES 




Key points 



Prepare yourself; learn from experience, 

experts, surgical literature and other sources of 

evidence-based information. 

Do not overburden yourself with unreliable, 

irrelevant data - favour proven, discriminant 

facts. 

Do not obsessively limit your study to one 

possible choice. Assess the benefits and risks of 

other management options. 

Follow your patients: study the outcomes in 

the hope of improving your results. 



A sudden, urgent, unexpected incident puts great strain 
on your judgement. You are often put under pressure to 
'do something', and 'doing something' may be inappro- 
priate. Although this is an emergency (Latin e = out of + 
mergere = to plunge, to thrust suddenly), it does not 
inevitably demand instant action. Except for standardized 
situations like cardiopulmonary arrest, be willing to take 
sufficient time to assess the situation and make a decision. 
Is the required action within your capability, and is the 
required assistance and equipment available? If the action 
is beyond your normal capability, but if there is no one 
more capable, are there any effective measures you can 
perform? In such circumstances, when there is no alter- 
native, people have achieved near miracles. 



OBSTACLES TO GOOD DECISION 
MAKING 






1 . Clinicians are rarely able to concentrate on a single 
problem. You always have many tasks to fulfil. Make sure 
that you allocate each one a ranked place in order of 



AIDS TOJJEO^^ 

Clinical skills 

1. In case of difficulty, when there is no urgency, be 
willing to defer making a decision and give yourself time 



146 



DECISION MAKING 



13 



to think about the possibilities, discuss it with a trusted 
colleague, and refer to the literature to check the recent 
reports. 

2. In an emergency be willing, if time permits, to 
review the features after a short interval - they sometimes 
change dramatically. 

3. In case of doubt, ask a colleague who has no com- 
mitment to the patient's outcome, whose opinion you 
respect, to carry out a fresh and independent examination. 



Educational value 

1. Use every opportunity to learn by studying how 
each decision is reached and how it can be justified. 

On many surgical firms it is common practice for 
the senior surgeon to make an on-the-spot decision, 
which is not questioned. Complex, controversial 
problems should be used as valuable educational aids. 
Each member of the team studies the literature, considers 
the possibilities, and reaches and justifies a conclusion at 
a meeting chaired by the senior surgeon. When each 
participant has presented a well-argued viewpoint, try to 
reach a consensus judgement. Subsequently, review the 
outcome to decide if the decision was correct, or whether 
a different conclusion should be reached when a similar 
case is encountered. At intervals, review all the patients 
who have been treated for the condition under 
consideration (see Ch. 42). 

2. Can useful guidelines be drawn up for future con- 
sultation - and regular review? 

3. How do the results compare with those from other 
units? 



RISK MANAGEMENT 



ii^iv&t^s^^^ 



Organizational risk management 

1. Do not make your decision solely on clinical 
grounds. Surgical treatment demands a wide range of 
complex facilities. Your own competence, and confidence 
that the patient can withstand the proposed procedure, 
are not the only considerations when judging how to 
proceed. 

2. Before investing in an unknown business, some 
commercial firms ask for a report on its perceived 
strengths, weaknesses, opportunities and threats 
(SWOT). This stimulates the informant to stand away 
from individual problems and consider the overall 
picture. The threats in surgical decision making do not 
merely refer to patient survival versus recovery. There 
are many possible sequelae, such as unexpected findings, 
absence of vital staff, and failure of some important 



equipment. In making your decisions, ensure that you 
consider all the possibilities and take precautions against 
possible difficulties. 

3. There are many aspects to risk management. Many 
of the procedures carried out have health and safety 
implications. Make sure that you know the correct pre- 
cautions with electrical, radiation and other equipment 
(see Ch. 17). Ensure, when making your decision, that 
your requirements will be adequately met. 

4. Do you have the required support of expert staff, 
with necessary equipment such as intensive care beds 
fully staffed? 




Key points 

• Surgeons previously accepted serious support 
deficiencies, adding to the risk, because there 
was no alternative. 

• Do not undertake procedures when the 
circumstances are not ideal, except in dire 
emergency. 



Clinical risk management 

1 . Prognostic risk scores. A number of scoring methods 
have been proposed so that the chances of recovery can 
be estimated. In this way the success of various methods 
of treatment can be compared. These methods were 
developed for comparing groups rather than individuals 
but their use has often been extended to assess individual 
risks. 

a. The American Society of Anesthesiologists (ASA) 
produced a five-grade risk assessment, on to which can be 
added the effects of age, operative severity, respiratory, 
cardiac and nutritional state. 

b. The Acute Physiology and Chronic Health Evaluation 
(APACHE) score is helpful in assessing the outcome for a 
group of patients but less so for individual cases. In the 
United Kingdom the modification, labelled APACHE II, is 
most commonly used. 

2. The Physiological and Operative Severity Score for the 
enumeration of the Mortality and morbidity (POSSUM) 
and Portsmouth modification (P-POSSUM) are particularly 
valuable for assessing the operative risks in the two- thirds 
of patients who require surgical treatment (Jones & de 
Cossart 1999). They incorporate an operative severity score 
as a predictor of outcome. Proposed use of POSSUM and 
P-POSSUM for comparative audit is deprecated (Bann & 
Sarin 2001). Trauma and sepsis scores can also be calcu- 
lated. Biological age offers a better assessment of risk than 
does calendar age (Farquharson et al 2001). 



147 






PATIENT ASSESSMENT 



^4$^v3?&^^^^ 



TYPES OF DECISION 

Codified decisions 



If facts and experience can be measured and then com- 
pared with the findings in other similar situations, it 
becomes possible to make decisions for future guidance 
when faced with similar problems (Wyatt 2001). As a 
result of reviewing series of cases / various standardized 
methods of management have been devised. If the 
problem complies with previously assessed cases, a plan 
can be developed so that succeeding problems can be 
dealt with according to predetermined directions: 

• Algorithm (Arabic al-Kwarazmi, modern Khiva in 
Uzbekistan). In this city lived the 9th century mathe- 
matician Abu Ja'far Mohammed ben Musa, who devel- 
oped a rule for solving a problem in a finite number of 
steps. The sequential steps are followed automatically 
and algorithms are embodied in computer software. 

• Protocol (Greek protos = first + kolla = glue; a glued-on 
first leaf of a manuscript). Among other things it is a 
set of rules, or uniform method, of approaching a 
problem, sometimes displayed as a flow chart, with 
alternative pathways to treat differing circumstances 
and outcomes. 

• Guidelines offer a viewpoint agreed by an authoritative 
person or body They are not as reliable as evidence 
based on prospective, double-blind, trials that have 
produced statistically significant results; however, they 
are less rigid. The issuing of guidelines is contentious 
because those who, for good reason, do not follow the 
guidelines, may feel vulnerable to criticism if the 
outcome in a particular case is poor. Because guidelines 



vary in their power, they may be graded (Harbour & 
Miller 2001). 
• Decision trees are valuable in displaying and evaluat- 
ing possibilities and outcomes. Risks of treatment 
mortality and long-term survival are available for 
many conditions in the medical literature or from 
reviews such as the Cochrane collaboration or on the 
internet. In the future the National Institute for Clinical 
Excellence (NICE) will issue reports on a wide range of 
treatments. 

All the probable outcomes should add up to 1 
(Fig. 13.1). In addition to the objective outcome 
measure, there is a subjective value, called a "utility/ 
your evaluation and the patient's may differ - but it is 
the patient's valuation that must prevail. However, it 
may be difficult or impossible for the patient to antici- 
pate the effect of the outcome on the quality of his or 
her life, often calculated as quality adjusted life years 
(QALYs). The quality of each year of life is subjectively 
judged by the patient. A year during which the patient 
enjoys full fitness is 1 QALY. A 2 year survival, each 
judged to have provided 50% of full fitness and enjoy- 
ment, is also judged to be 1 QALY. You may be able to 
advise, or put the patient in contact with others who 
have been treated for the same condition. The sum of 
the probability and utility produces a figure for the 
'expected utility 7 , and the course of management 
earning the highest mark is the preferred one (Fig. 13.2) 
(Birkmeyer & Welch 1997). 

Although the objective evidence for all the possible 
courses of action may not be available, forming a deci- 
sion tree is a valuable exercise for displaying the range 
of possibilities. 



Surgical 



oO 



Malignant condition 



^ 



f. 


Improved 


p = 0.6 


1 ^ 






>=► 


Same 


p=0,3 






^==►1 


Worse 


p = 0.1 






p=!> 


Improved 


p=0.3 






)=> 


Same 


p = 0.5 


U 




Worse 


p= 0.2 



Fig. 13.1 A simple decision tree comparing the probability (p) of outcomes for two methods of treating a malignant 
condition. ■ Denotes a decision node; O denotes possible outcomes. 



148 



DECISION MAKING 



13 



=> 



Surgical 



r^ 



Improved 



^>o=* 



p= 0.6 




Utility Expected utility Sum 



10 

5 





0.6x10 = 6 



0.3x5 = 1.5 } 



0.1x0 = 



7.5 



Radiotherapy b 




Improved 



Same 



Worse 



p = 0.3 



P-0-5| 



p = 0.2 



10 
5 





0.3x10 = 3 
0.5x5 = 2.5 
0.2x0 = 



5.5 



Fig. 13.2 The utility (subjective benefit or disability) resulting from the outcome is graded from 10 (good) to (bad). 
The product of probability (p) and utility is the 'expected utility'. Finally, the sum of the expected utilities for each 
decision can be compared. The course scoring the highest mark is the preferred one, in this case surgery. ■ Denotes a 
decision node; O denotes possible outcomes. 



^ 



Key point 



• Review guidelines, algorithms, protocols and 
decision trees from time to time (Fig. 13.3). 
They may require modification in the light of 
audited results of previous outcomes, 
comparison with published data from other 
units, and advances in diagnosis and 
management. 



Personalized decisions 

1 . Many decisions are complex and cannot be made in 
a standardized, codified manner. The condition may be 
complicated by cofactors, or may have unusual features. 
The decision is unique and may be challenging or even 
controversial. Some of the factors may be indefinable and 
difficult to weigh in the balance. It is in such circum- 
stances that opinions differ between specialists because 
of individual selection of evidence and the importance 
given to it. 



Examine 



Investigate 



Assess 



=> 



o 



PROBLEM <= 



Surgeon < 3 
+ 
Team (Anaesthetist etc) 



DETERIORATION OR 
FAILURE TO RECOVER 



HZ 



ACTION 



£ 



MONITOR 



$> Co-factors 



Patient 



DECISION j^» 



<3= 




Risk analysis 



Cost effectiveness 



Algorithm 

Protocol 

Guidelines 



Decision tree? 



RECOVERY 



Fig. 13.3 Some of the complex, and disparate, considerations to be taken into account when making a decision, 
acting on it and monitoring the result. 



149 




PATIENT ASSESSMENT 



2. Knowledge that cannot be transferred verbally can 
be labelled 'tacit/ (Wyatt 2001) (Latin tacere = to be 
silent). The decision-maker cannot justify the decision in 
scientifically acceptable terms. Some surgeons produce 
better results than average; they may be technically 
superior but an alternative or additional reason is that 
they make a higher proportion than average of correct 
decisions. 

3. The likelihood is that good decisions are made by 
an intuitive selection of the most important factors, 
while discounting less important factors. Combined 
with this is the selection of treatment that is appropriate 
for that particular patient. Some surgeons say, T know 
what I can get away with'; others are overoptimistic of 
their ability to achieve success with poor risk patients 
subjected to overaggressive treatment. Other surgeons 
are dissuaded from embarking on potentially highly suc- 
cessful treatment for fear of failure, or of 'spoiling' their 
results. Such reluctance may increase if the outcomes for 
individual surgeons or units become accessible to the 
general public. 

4. Personal experience, especially of rare problems, is 
a powerful influence on decisions, so that senior sur- 
geons are usually trusted to deal with them. A particular 
example is the recognition of postoperative complica- 
tions, or of failure to recover as expected; if you are in- 
experienced, you do not know how to recognize what is 
normal and what is important. In some cases the experi- 
enced colleague may be unable to explain a suspicion, 
but may just acknowledge a 'gut feeling' that all is not 
well. 




Key point 

It is wasteful of resources for every decision to 
be made on a one-to-one basis if the problem 
conforms to a standardized pattern for which 
guidelines, algorithms, protocols or decision 
trees have already been published. The guides 
must be regularly reviewed and authenticated. 
Unless there is additional evidence, or 
circumstances that differ from the 
standardized description, hesitate to make a 
heterodox decision. Will you be able to justify 
it to your patient, your colleagues, and to your 
own conscience, if there is an adverse 
outcome? 



Summary 

• How many influences and factors can you 
list that must be brought into the process 
of clinical decision making? How many of 
them can be scientifically assessed? Can 
you rank them in terms of their 
importance of effect on outcome? 

• What are discriminant features? Can you 
list such features for some of the common 
clinical conditions with which you deal? 

• Do you know the published outcomes for 
three common conditions? Where would 
you look for the information in order to 
create a decision tree? 

• Can you name examples of decisions for 
which there are well-authenticated 
pathways to follow, and also those that 
are exceptional and demand your best 
judgement - or the advice of an 
experienced expert? 

• Can you recall the important 
considerations necessary when informing 
patients and making joint decisions with 
them? 

• As a surgeon committed to taking 
decisions and acting upon them, how 
would you justify demanding the facilities, 
throughout your career, to acquire and 
critically evaluate new information, both 
verbally and by association with leading 
colleagues? 




References 



Bann SD, Sarin S 2001. Comparative audit: the trouble with 

POSSUM. Journal of the Royal Society of Medicine 94: 632-634 
Birkmeyer JD, Welch HG 1997. A reader's guide to surgical 

decision analysis. Journal of the American College of 

Surgeons 184: 589-595 
Farquharson SM, Gupt A, Heald RJ, Moran BJ 2001 . Surgical 

decisions in the elderly: the importance of biological age. 

Journal of the Royal Society of Medicine 94: 232-235 
Harbour R, Miller J 2001 . A new system for grading 

recommendations in evidence based guidelines, BMJ 323: 

334-336. 
Jones HJS, deCossart L 1999. Risk scoring in surgical patients. 

British Journal of Surgery 86: 149-157 



150 



DECISION MAKING 



13 



Plsek PE, Greenhalgh T 2001. The challenge of complexity in 

health care. BMJ 323: 625-628 
Wilson T, Holt T 2001 Complexity and clinical care, BMJ 

323: 685-688. 
Wyatt JC 2001. Management of explicit and tacit knowledge. 

Journal of the Royal Society of Medicine 94: 6-9 




Further reading 

Cox K 1999 Doctor and patient: exploring clinical thinking. 
Phase 3: Deciding what to do. University of New South 



Wales Press, Sydney, pp 185-270. This thoughtful readable book 
is an account of the way in which we think and make our 
decisions 

O'Connor AM, Rostom A, Fiset V et al 1999 Decision aids for 
patients facing health treatment or screening decisions: 
system review. BMJ 319: 731-734. Patients may need help when 
they are deciding between treatment options 

Polanyi M 1958 Personal knowledge. Routledge and Keegan 
Paul, London. References and explanations throughout of tacit 
knowledge and acquisition of skills. A masterpiece from a 
Hungarian-born polymath, investigating the special wisdom of 
the expert. It explores those skills that cannot as yet be verbalized 
but need to be passed on during the master-apprenticeship 
relationship 



151 



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153 



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Consent for surgical 
treatment 

L Doyal 




Objectives 

Recognize the need to establish trust and 

confidence in patients under your care. 

Understand that a signature on a consent 

form is not legal proof that informed 

consent has been given. 

Realize that you must warn patients of the 

hazards as well as the benefits of surgical 

treatment. 

Identify and deal appropriately with 

difficulties in gaining consent. Respect the 

confidentiality of your dealings with 

patients. 



the legal right of women to choose to have an abortion 
under certain circumstances is regarded as immoral by 
those who believe that a fetus has the rights of a born 
child. In short, our beliefs about who has a right to what 
inform our decisions about how we should act toward 
others if our actions are to be deemed morally, and 
perhaps legally, acceptable. 

The general right of surgical patients to self- 
determination can be subdivided into three further rights: 
to informed consent, to the truth and to confidentiality. 
The latter two clearly follow from the first. Choices cannot 
be properly informed on the basis of deception and cannot 
be respected if what patients deem private is made public. 
Therefore, it is the principle of informed consent itself 
which is fundamental and on which both the mortality 
and the legality of good surgical practice partly depend. 



INTRODUCTION 






For surgery to be successful, there must be a relationship 
of trust and confidence between you and your patients, 
otherwise they are likely to be reticent in presenting for 
treatment or in divulging the detailed personal informa- 
tion required for recording accurate case histories and 
making successful diagnoses. Aside from the belief that 
their care will conform to a high clinical standard, the 
trust of patients also depends on their belief that their 
autonomy will be respected - that they will have the right 
to decide their own medical destiny, whatever anyone 
else may think. 

Moral rights are like that. They indicate claims that 
individuals can legitimately make against others who 
have corresponding duties to respect those claims. To the 
degree that we believe that the right to make such a claim 
exists, then those on whom it is properly made must 
respect it and act accordingly, irrespective of their prefer- 
ences. Examples of often-cited moral rights emphasize the 
entitlement of individuals to self-determination - to be 
able to pursue life goals and perceived interests in ways 
in which the individual has chosen - provided that others 
are not harmed in the process. Moral rights might or 
might not be backed up by the force of law. For example, 



THE MORAL IMPORTANCE OF 
INFORMED CONSENT 



^t^^^5^^;^?^^^7C^^^^:i 



MB 



Key point 



• The moral unacceptability of anyone exercising 
unlimited power over others is at the heart of 
many of our liberal values. 

It is our capacity for rational choice that differentiates 
humans from other creatures. Respect for this capacity - 
especially our right to be the informed gatekeepers of our 
own bodies - is an indication of the seriousness with 
which we respect the humanity and dignity of others. 

What is informed consent? 

For patients to give their informed consent to surgery - to 
be able to make a considered choice about what is in their 
personal interests — they must receive sufficient accurate 
information about their illness, the proposed treatment 
and its prognosis. For this to be more than a moral 
abstraction, you must complete four general tasks: 



155 



14 



PREPARATIONS FOR SURGERY 



1. Describe the procedure itself, including information 
about its practical implications and probable prognosis. 

2. Reveal the probability of specific associated risks or 
complications. 

3. Do not assume that the patient already knows the 
risks of other aspects of the proposed surgical 
procedure, such as the complications that might 
result from a general anaesthetic, bed rest, 
intravenous fluids or a catheter. 

4. Outline other surgical or medical alternatives to the 
proposed treatment, including non-treatment, along 
with their general advantages and disadvantages. 

Ideally, the amount of such information should be that 
which a mentally competent patient requires to make 
informed choice a realistic possibility Think of compe- 
tence here as the ability to understand, retain and delib- 
erate about such information and to accept its personal 
applicability You must remember that the amount of 
information the patient is obligated to divulge may well 
change, depending on what you should know about your 
patient as an individual. For example, it may not be 
necessary for a manual labourer to be told of an extremely 
small operative risk of minor stiffness in one finger. This 
would obviously not be true of a concert pianist, under- 
lining the importance of recording the patient's employ- 
ment in case notes and referring to it in the presentation 
of case histories. 



both. However, it is clear that you are morally respon- 
sible for attempting both to an acceptable standard. To 
achieve this, ask the patient to repeat in personal terms 
what has been said, and at various times invite questions. 
The more confident you are in exercising these skills, the 
less time is needed to obtain effective consent. 

4. We often limit the amount of information we give to 
patients on the grounds that it is potentially distressing. 
If your long-term aim is to keep the patient in ignorance, 
this is not acceptable. All competent individuals have a 
right to decide what is and is not in their best interests, 
even if what they decide is not endorsed by their profes- 
sional advisors. It would not be morally acceptable for a 
solicitor or accountant to delude their clients on the 
grounds that they did not want to distress them about the 
possibility of losing a court action or of going bankrupt. 
Why should your moral obligations be any different? 




Key points 

• It is your responsibility to provide clear 
information, and to determine whether it has 
been understood. 

* It is the patient's right to decide what is in his 
or her best interest, not yours. 



Good consenting practice 

1. As much as possible, ensure that the physical sur- 
roundings during the discussion between you and your 
patient are conducive to easy quiet conversation. Ideally 
choose somewhere private and free of disturbances and 
interruptions by junior staff or medical students follow- 
ing in retinue on a busy Nightingale ward. Do not stand 
threateningly over the patient in bed, and avoid giving 
the appearance of being rushed by other duties. Empathy 
with the patient is crucial. 

2. Use the simplest possible language, avoiding needless 
technicalities. If the patient permits it, have a relative or 
friend of the patient present when serious matters are being 
discussed. This is both for support and to help ensure that 
the patient really does understand - both at the time the 
information is given and later when the patient returns 
home. In the hospital ward, nurses familiar to the patient 
can often fulfil this role effectively Appropriate leaflets or 
booklets can be helpful, as is innovative work using 
audiorecording of interviews; patients can be encouraged 
to take the recording home to discuss with others. 

3. Having attempted to provide clear information, now 
determine whether or not the patient has actually under- 
stood it. No doubt there are time constraints on doing 



The consent form 

1. In principle, the consent form signed by the patient 
before operation is a public and permanent affirmation of 
agreement. All competent patients who are 16 years or 
older should sign the form for all surgical procedures 
involving a general anaesthetic. You should obtain 
signed consent for procedures under local anaesthetic if 
there is a risk of significant sequelae; for example, an 
excision of skin lesions. You should also sign the form 
after obtaining consent to indicate that, to the best of your 
knowledge, the patient has both received and under- 
stands the information necessary to make a considered 
judgement. 

2. However, it is unnecessary for a competent patient to 
sign for all surgical interventions. A simple investigative 
procedure such as venepuncture, involving minimal risk, 
can be undertaken after oral explanation of, and consent 
to, what it physically entails. Consent can be assumed to 
be implied if the patient then accepts the procedure. 

3. The consent form is not legal proof that consent has 
been given. Always bear this in mind if you are tempted 
to cut corners as regards good practice in obtaining 
consent. It is merely one piece of evidence that some 
attempt was made to obtain informed consent, not that it 
was a morally or legally satisfactory attempt. 



156 



CONSENT FOR SURGICAL TREATMENT 



14 



THE LEGAL IMPORTANCE OF 
INFORMED CONSENT 




Key point 

In addition to the general and clinical 
importance, your legal obligation is to respect 
the patient's right to consent to treatment. 



Battery 

1. Battery is a violation of the civil law forbidding 
intentionally touching other persons without their 
consent. For example, a woman won damages in the UK 
for this reason because she was given a hysterectomy to 
which she did not agree in the aftermath of a gynaeco- 
logical operation for another problem. In Canada, a 
woman who made it clear that she wanted to be injected 
in one arm successfully sued when she received the injec- 
tion in the other! The harm resulting from battery is not 
necessarily physical. In law, a battery can be deemed to 
have occurred without such harm having taken place. 
Here, harm should be construed as the violation of the 
right of persons to exercise autonomous control over their 
own bodies, 

2. In many situations involving minor surgical proce- 
dures or tests, it is not possible or advisable specifically to 
ask for consent every time you touch a patient. If this 
were the case, surgery would become impossible. But it 
does not follow that the patient's consent is legally irrel- 
evant. Rather, as we have just seen, a patient can be said 
to have given implied consent by virtue of presenting for 
treatment and accepting what is offered. A man once 
argued in the USA, for example, that a ship's surgeon had 
committed a battery because he was vaccinated without 
having given specific verbal permission for the injection 
to be administered. He lost on the grounds that his 
consent was implied because he was in a queue of people 
who were clearly waiting to be injected and he held out 
his arm when his turn came! 

3. Clearly, there will be many less clear-cut situations. 
Is there a risk of battery if a patient claims that surgery 
would have been refused if more information had been 
given beforehand? If you informed the patient in broad 
terms of the general nature of the condition and the 
proposed operation to try to correct it, if you did not 
deliberately deceive and the patient gave no indication of 
desiring not to proceed by asking for more information, 
and signed the appropriate consent form, then the 
answer is probably no. This presupposes that you 
have not deprived the patient of information that was 



specifically requested, and, returning to our example of 
an unwanted hysterectomy, you have not usurped a 
clinical choice legally regarded as remaining with the 
patient. 

Negligence 

1. Battery is not the only legal action you risk for in- 
adequately respecting your patient's right to informed 
consent. In an important case, Mrs Sidaway suffered 
paralysis resulting from spinal surgery to relieve pressure 
on a nerve root without being told that the operation 
carried a small risk of paralysis. Here, it was judged that 
she had not been a victim of battery because, again, she 
had given her general consent to the surgery in question. 
However, her solicitors then claimed negligence, the legal 
action now recommended in such cases. Negligence a 
potential breach of duty, concerns your professional duty 
properly to advise patients not just about the proposed 
surgery but also about its potential hazards. In such 
cases, patients argue that, had they known the risks in 
question, they would not have proceeded with the 
surgery. 

2. Do not assume that in these circumstances you are 
protected from such accusations by a signed consent form 
for treatment. The patient might still successfully argue 
that, even having signed the form, he or she was not given 
enough relevant information to make an informed deci- 
sion before signing and /or was unaware of the signifi- 
cance of the form. There is no escaping your general duty 
to disclose information about potentially harmful side- 
effects and to do so in a way that the patient can under- 
stand in principle. For example, in all cases other than 
those of acute emergencies, you must take care to provide 
translations for non-English-speaking patients. 

3. How can we establish whether or not compliance 
with this duty has been sufficient - whether or not 
enough information has been disclosed about risks so that 
the rights of patients are respected? Legal judgements 
concerning negligent standards of adequate disclosure in 
the UK are still primarily determined by the profession 
itself. Suppose that expert witnesses for the defence are 
regarded by the court as constituting a recognized body 
of professional opinion. If they agree that they would 
have communicated the same amount of information in 
similar circumstances as the defendant, this should be 
sufficient to ensure that the claimant will lose the legal 
action. In other words, in such actions the judge does not 
decide which expert witnesses are right - those for the 
claimant or defendant. All that is required to exonerate 
the latter is for a responsible body of professional opinion 
to endorse the action in dispute, even if the endorsement 
does not represent the views of the majority of members 
of the profession. 



157 



14 



PREPARATIONS FOR SURGERY 



4. Recent legal developments have underlined this 
'professional standard' in the determination of what 
constitutes negligent informed consent. In the Sidaway 
case, for example, a majority of the judges in an appeal 
to the House of Lords agreed with this approach to 
determining negligence, as have other judges since. 
However, many have also warned of the dangers of com- 
pletely equating the right of patients to information with 
standards set by the profession. Indeed, in the Sidaway 
case, one judge stated in a minority opinion that there will 
be some information about surgery, for example serious 
hazards, which any 'prudent' patient would wish to 
know before giving consent to proceed. A similar legal 
standard of negligence as regards informed consent is 
found in North America and has largely become 
accepted good practice by the medical profession in the 
UK. 

5. Therefore, do not look to the law for advice on how 
much information about risks and side-effects is morally 
required by the right of your patients to informed 
consent. Ask instead what a reasonable person would 
want to know under similar circumstances, especially in 
the context of any other personal information you have 
about the patient and his/her public and private 
interests. Disclose the same amount of information 
about risks to your patients as you would wish to be 
communicated to your close friends and relatives. The 
fact that an adequate amount of information for 
informed consent may be legally acceptable does not 
entail that this should be regarded as professionally or 
morally acceptable. 



The unconscious adult patient 

1. Suppose that you are a surgeon in the accident and 
emergency (A & E) department, confronted with the 
victim of an automobile accident who requires an imme- 
diate operation to save life or to prevent permanent and 
serious disability Here, there is a clear duty to treat, 
despite the fact that it is impossible to obtain the patient's 
consent, and there would be no risk of battery if oper- 
ation proceeded. This is not because you become the 
proxy of the patient and so make a substituted judge- 
ment on his or her behalf, one which attempts to antici- 
pate the choice the patient would make. It is because it is 
your moral and legal responsibility to act in the patient's 
best interests - to do what is 'necessary', as there is no 
way of knowing for certain what the patient might 
choose. 

2. Indeed, no adult in the UK can legally consent to 
surgery on behalf of another, including close relatives. Do 
not ask relatives to sign consent forms on behalf of uncon- 
scious or otherwise incompetent adults. It would be both 



a misrepresentation of the law and a liability risk, if the 
surgical outcome is poor. The relatives may inappropri- 
ately and harmfully blame themselves. 

3. The only circumstance that justifies surgery without 
consent is the dramatic need of patients, coupled with 
their inability to give consent. Inconvenience will not 
suffice. For example, the arrest of a life- threatening haem- 
orrhage in an otherwise healthy patient would clearly be 
in order, while the same could not be said of the repair of 
a hernia. Of course, if the patient is conscious and evi- 
dently capable of rational judgement, then even in an 
emergency offer advice on the condition and the pro- 
posed treatment. If it is physically possible, have the 
patient also sign a consent form, as would be the case in 
normal circumstances. Verbal consent is adequate if the 
patient's condition precludes giving written consent. 
However, in these circumstances, if possible, ask another 
health worker to act as a witness and to record the verbal 
consent in the notes. 



Children 

1. Ordinarily, obtain consent for elective surgery on 
young children from someone - usually the parent - 
deemed competent to make informed choices about the 
child's best interests. However, this does not suggest that 
you must always be guided solely by parental wishes. If 
you believe such a decision is necessary to save the child's 
life, the parents' wishes can be overridden. If there is time, 
apply to the court for the appropriate order. If not, you 
can still proceed. If the parents propose long-term treat- 
ment or non-treatment options which you regard as simi- 
larly inconsistent with the best interests of the child, 
again you can apply for them to be overriden by an 
appropriate court order. 

2. The legal age for medical consent is normally 16. 
However, it is legally acceptable for you to treat adoles- 
cents under the age of 16 years without parental consent, 
just as it is for general practitioners to prescribe contra- 
ceptives. If you intend to do this you must ensure that the 
young person is competent - mature enough to under- 
stand, retain and deliberate about information concerning 
the nature of the illness, the prognosis, proposed treat- 
ment and any important associated risks. The patient 
must also be able to believe that this information applies 
personally to her or him. Before proceeding without 
parental consent, encourage the young person to discuss 
the proposed treatment with the parents and so be 
assured that the treatment is in the best interests of the 
child. 

3. Nevertheless, regard treatment without parental 
consent as exceptional. Unless the adolescent has specifi- 
cally refused permission, attempt if possible to hnd and 



158 



CONSENT FOR SURGICAL TREATMENT 



14 



consult the parents if they are not already approachable. 
In the case of life-threatening illness / even young people 
below the age of 18 years do not have the right to reject 
treatment on their own which might save their lives. Only 
those with parental responsibility can exercise such 
judgement, in agreement with you. Paradoxically, the law 
appears to be that the right of a competent adolescent to 
consent to life-saving treatment does not entail the right 
to refuse it. As regards elective surgery which is not life 
saving or will not prevent serious and permanent injury 
the law is the same. Morally, however, the wishes of the 
competent young person not to proceed should be and 
are commonly respected, even where the parent dis- 
agrees. If surgical treatment is forced upon such patients 
without consent, it might undermine the relationship of 
trust and the willingness to comply with future treatment, 
both of which will be important for sustained clinical 
success. Such force can be argued not to be in the best 
clinical interests of the child. 

4. Quite young children often have a good grasp of 
their prospects and treatment, especially when they have 
already experienced distressing surgical therapy for 
an illness which they have had for some time. In such 
circumstances, before further surgery is undertaken, 
attempt to consult such a child about his or her wishes. 
Where there is disagreement between parent and child 
about the best course of action, especially in instances of 
potentially terminal disease, arrange counselling for both 
about what appears clinically to be in the child's best 
interests. Such counselling is particularly important when 
there is disagreement between you and the parent about 
the most appropriate way to proceed. Again, in the un- 
usual event that you believe parental choice dramatic- 
ally conflicts with the medical interests of the child, 
approach the court for a judgement. 

Mental handicap and psychiatric illness 

1 . In the case of adults who are judged incompetent to 
choose for themselves, we have seen that no one may 
legally act as a proxy for this purpose. However, decisions 
about incompetence are complex. For example, incompe- 
tence to consent to surgery does not follow from severe 
psychiatric illness. Just because individuals may be 
incompetent in one respect due to illness does not mean 
that they are incompetent in all respects. People may be 
detained under the 1983 Mental Health Act on the 
grounds that, because of the seriousness of their psychi- 
atric illness, they are a potential danger to themselves or 
others. As a result they may be given psychiatric treat- 
ment without their consent. However, this does not hold 
for ordinary surgical treatment. In such circumstances, 
attempt to obtain the patient's consent, even when com- 
munication is difficult and certainty of understanding not 



assured. For example, in a recent legal case in Britain, a 
judge accepted that a detained patient suffering from 
schizophrenia was competent to refuse to have a foot 
amputated if it became terminally gangrenous. 

2. With the exception of specific and extreme interven- 
tions such as psychosurgery, there are circumstances 
when surgical treatment can be given to a detained psy- 
chiatric patient who cannot consent due to extreme 
illness. There are two conditions: 

a. the treatment must be deemed necessary to protect 
life or to avoid permanent and serious disability 

b. the patient must be diagnosed as unable to give 
informed consent as a direct result of the psychiatric 
illness. 

As a consequence of psychotic delusion, for example, 
patients may believe that you are going to kill them and 
that the diagnosis of a life-threatening condition is a 
sinister plot. Here, necessary treatment can proceed, pro- 
vided that you and the relevant psychiatric team agree 
that it is in the best interests of the patient. Note that this 
exception to the consent requirement would not ordi- 
narily apply to elective surgical care, as the assumption 
should be that there will be time for patients to make up 
their own minds when their competence to do so is no 
longer being impaired by their illness. 

3. Some patients in need of surgery suffer not from 
psychiatric illness but from permanent mental disability. 
This may severely impair competence to give informed 
consent for either life-saving or elective surgery. The fact 
remains, however, that in such circumstances no adult 
can act as a legal proxy for another as regards the pro- 
vision of such consent. The only person who can make 
the decision that surgery is in the best interests of 
severely mentally handicapped patients is yourself in 
consultation with the principal carers, including close 
relatives. Take great care. As regards elective surgery, 
responsibility for promoting the interests of mentally 
handicapped patients can be a heavy burden, especially 
if there is dispute among carers about what these actu- 
ally are. The sensitivity of these issues is witnessed by 
the fact that the courts sometimes refuse to permit the 
sterilization of mentally handicapped women under the 
age of 16 years, even if the surgeon has agreed to 
perform the procedure. 



TWO PRACTICAL PROBLEMS 



^AW^S-ifesMiWiK;*©; 



The general obligation to disclose information about both 
proposed surgery and its hazards is not open to debate. 
However, putting this moral and legal imperative into 
practice does involve discretion and is not always easy, 
for two reasons. 



159 



14 " 



PREPARATIONS FOR SURGERY 



Limitations on the understanding of patients 

1 . It is sometimes unclear whether or not consent has 
really been obtained, even if you have taken care to 
explain the proposed procedure and its potential hazards. 
The comprehension of competent patients can be com- 
promised by their illness, their educational and social 
background and by other aspects of their personalities 
which may make them overly anxious or unwilling to 
listen. Difficult as such instances of impaired autonomy 
can be, especially for patients facing acute and complex 
surgery, you must still be able to show that they have 
disclosed adequate information for proper consent to be 
possible. 

2. Practically speaking, therefore, how should you 
demonstrate to yourself, and if necessary to a judge, that 
you have done your best in this regard? Most important 
of all, you need to work constantly to improve your 
ability to communicate. Both the General Medical Council 
(GMC) and the British Medical Association (BMA) stress 
this point, and its importance is underlined by the 
increasing emphasis placed on communication skills 
within medical education (see Ch. 47). You can do no 
more than your best. 

3. Keep a written record in the case notes of the main 
points about treatment which have been communicated 
prior to the signing of the consent form. Follow the model 
of the reasonable patient outlined above. Give informa- 
tion on what will be done and why, along with significant 
risks of mortality and other hazards to bodily functions 
relevant to normal social participation, such as swallow- 
ing, speaking, continence, mobility, pain and sexual per- 
formance. Record that each of these variables has been 
mentioned and will provide evidence that may be useful 
if the fact is denied by the patient in a context of a medico- 
legal dispute. 



Limitations on the right of patients to 
consent 



e 



Key point 

• Consider reinforcing information about 
proposed treatment and possible side-effects 
with written information. 

4. Even after you have followed good practice in 
obtaining consent, you may conclude that your patient 
still cannot be said to have given proper consent to treat- 
ment. Apart from life-saving emergencies, your most 
appropriate choice is to postpone treatment until you 
have achieved better communication. This may be incon- 
venient, but it is necessary to protect the patient's rights 
and to demonstrate that you have taken your moral and 
legal duties seriously. 




Key points 



• The right of a patient to consent to surgery 
does not entail (imply as an inevitable 
consequence) a right to demand and receive it. 

• You do not have a professional duty to provide 
requested surgery for a patient who has no 
need for it. 

• You may also refuse to carry out an operation 
that will be futile, no matter how much the 
patient may want it. 

1 . What happens if the patient clearly needs operation 
but does not want it? Here, respect for the autonomy of 
patients may well conflict with your other moral obliga- 
tion to protect life and health. This conflict is most acute 
when, in considered and unambiguous terms, a patient 
refuses life-saving surgery. The moral and legal emphasis 
on respect for autonomy within surgery is so strong that, 
even in such circumstances, you must not undertake 
treatment without consent, again assuming that the 
patient is conscious and competent. This fact is sometimes 
obscured because patients who are terminally ill and do 
not wish further treatment are reticent about refusing it. 
It becomes very clear, however, in the case of a Jehovah's 
Witness, who will only proceed with surgery on the 
understanding that no transfusion will be given in the 
event of haemorrhage. Legally, a competent patient has 
every right to make such a demand. If you ignore this you 
risk an action for battery. 

2. It is not suggested that you have to operate on 
patients who place stipulations on the types of life-saving 
treatment they will accept. In principle, and assuming 
that there is time, you may refer them to others who are 
more sympathetic and willing to undergo the stress that 
such restrictions inevitably carry. Equally, we have 
already seen that, if a patient is unconscious or incompe- 
tent for some other reason you must do what is necessary 
to try to save life. However, even this is changing in the 
face of so-called 'advance directives' or living wills', 
which are now regarded by expert opinion in the UK as 
having legal force. Thus any competent adult can draft a 
document specifying in advance which life-saving treat- 
ments are and are not acceptable if the patient becomes 
incompetent and contracts specific types of illnesses. 
Ideally, an advance directive should be witnessed and 
you should act upon it. Such documents are common in 
North America and will eventually be so in the UK. 

3. After consultation with you, a competent patient 
may, therefore, decide that further treatment is pointless, 



160 



CONSENT FOR SURGICAL TREATMENT 



14 



given the irreversible and terminal character of the par- 
ticular disease. If you comply with such a request to omit 
or to stop treatment, it can be argued to be neither actively 
killing nor aiding and abetting suicide. It is reasoned that, 
unlike the potential suicide, competent patients may well 
want desperately to live, but not at any cost to their 
quality of life. Furthermore, as we have seen, to treat them 
against their will constitutes a battery. Whatever the cor- 
rectness of these arguments, what patients cannot expect 
is for active steps to be taken to end their lives, although 
they do at times request this as well. 

4. Yet to go along with a patient's refusal of surgery 
when it is clear that the consequence will be death is a 
very serious moral and legal matter. Take great care to 
ensure that the patient fully understands the implications 
of refusing life-saving treatment and is competent to make 
an informed judgement, especially if the refusal is 
followed by a lapse into unconsciousness. A mistake, 
either about the patient's understanding or wishes, cannot 
be corrected. Therefore, respect prior refusal only if you 
judge it to be an autonomous decision intended to apply 
in the circumstances that have arisen. For example, a 
young adult woman in the UK refused a blood transfusion 
on the grounds of her acceptance of the doctrine of the 
Jehovah's Witnesses, despite the fact that she was not a 
Witness herself. She lost consciousness and the court over- 
ruled her refusal on the grounds that she had been unduly 
influenced by her mother and that her decision was based 
upon inadequate information about her prognosis. 



INFORMED CONSENT AND SURGICAL 



RESEARCH 



S^MS^ffi^S^iSS 



ymtfSMviteWtfmm 



1 . The availability of surgical options is dependent on 
the experimental research which makes them possible. Yet 
researchers must be careful. Without enthusiasm and con- 
viction about the importance of their work, they will not 
have the commitment that successful research requires. 
However, such commitment can lead to an underestima- 
tion of the risks or discomfort of experiments. Research 
can be either therapeutic and to the potential benefit of 
participants, or non-therapeutic with no such promise. 
Participants in the former will be patients, and in the latter 
either patients or healthy volunteers. 

2. Patients involved in research have a right to 
informed consent for the same reasons described above. 
By allowing them to make an informed evaluation for 
themselves, they exert a regulating influence on experi- 
mental zeal; this has unquestionably led to moral abuses 
in the past. A clear example is the notorious and need- 
less experiments inflicted by some Nazi doctors and sur- 
geons on Jewish prisoners. However, there have been 
more recent illustrations involving patients, some of 



whom have died as a result of their participation in 
research. 

3. The Nuremburg Code was adopted internationally 
as a result. It declared that 'the voluntary consent of a 
patient is essential' in any medical research. The later 
Declaration of Helsinki is also explicit. It states: Tn any 
research, each potential subject must be adequately 
informed of the aims, methods and anticipated benefits 
and potential hazards of the study and the discomfort it 
may entail/ After this, participants' consent must be 
obtained. 

4. The enforcement of the Helsinki Declaration in the 
UK is entrusted to research ethics committees. These are 
administered by health authorities and are responsible for 
evaluating all surgical research involving humans, wher- 
ever it might be undertaken. Under no circumstances 
should research proceed without the approval of the 
appropriate ethics committee, and academic journals 
usually publish the results only when such approval has 
been given. In principle, research ethics committees are 
supposed to ensure that the proposed protocol makes 
good scientific sense and poses no further risks than those 
of the best available treatment. Only then should patients 
be asked to consent to participate, on the basis of being 
given appropriate information about the research that the 
committee has also approved. 

5. There is, however, one remaining, significant 
problem concerning surgical research and informed 
consent. As a result of differing ability and willingness to 
understand and to question medical authority, we have 
seen that patients vary in their ability to assimilate the 
details of clinical information. Consequently, enthusiastic 
researchers are in a position, wittingly or not, to manipu- 
late patients to subject themselves to procedures that 
might not be proposed in ordinary treatment. Patients 
may be encouraged to agree to participate in the devel- 
opment of surgical procedures, for example, without 
realizing how experimental they are. Here, the general 
guidelines concerning informed consent must be fol- 
lowed with extra vigilance. For example, take care to 
identify surgical procedures that might not be regarded as 
standard professional practice and proceed only when the 
patient gives informed and written consent with the 
knowledge that this is the case. When in doubt about 
whether or not a procedure is standard, consult the 
research ethics committee. You must not pretend that a 
surgical innovation that goes beyond a minor incremen- 
tal variation on already standard procedures is not 
research that requires further ethical evaluation before 
proceeding. 

6. In non-therapeutic research with patients or healthy 
volunteers, you must be equally stringent to avoid con- 
fusing agreement to participate with informed consent to 
do so. Try to ensure that the moral legitimacy of the 



161 



14 




PREPARATIONS FOR SURGERY 



consent of the volunteer is not obtained under financial, 
social or professional duress. In the UK, for example, the 
difficulty of doing so has led to surgical research not ordi- 
narily taking place among the prison population. 



INFORMED CONSENT AND 



CONFIDENTIALITY 



*^?&j£-W£>&''^ 



1. As a corollary of their right to informed consent, 
patients have the right to control access to information 
which they give to you for the purposes of treatment. The 
General Medical Council (GMC) supports this right 
through the importance it attaches to the principle of con- 
fidentiality - obtaining the permission of patients before 
revealing clinical information about them to others. Few 
acts can more quickly lead to you being professionally 
disciplined than a proven breach of confidence in unwar- 
ranted circumstances. 

2. There are two types of justification for this empha- 
sis. First, the right to be the moral gatekeeper of one's own 
body extends to information divulged in clinical consul- 
tations. Second, if patients are frightened that their con- 
fidence might be breached, they may not be willing to 
provide the honest information on which successful 
diagnosis depends, or even to turn up for treatment at all. 
This can pose a severe danger to them and possibly to the 
general public. 

3. It is in the area of potential conflict between the 
freedom of the individual and the interest of the public 
that circumstances may arise in which you either must or 
might divulge information otherwise regarded as private. 
The same professional codes which stress the importance 
of confidentiality (the 'Duties of a Doctor' of the GMC, for 
example) also outline the exceptions to the rule. These fall 
into two general categories. 

The public interest 

1. Suppose that in a clinical consultation in the acci- 
dent and emergency department you discover that a 
highly agitated patient is armed, has committed a 
robbery and has killed a bank clerk and a customer as a 
result. Here, it seems straightforward that the confidence 
should be broken and the police informed- The patient 
may strike again. Indeed, it is legally mandatory to 
breach confidentiality where patients are suspected of 
involvement in terrorism within the UK or where they are 
found to be suffering from a highly infectious and notifi- 
able disease. 

2. How serious must a risk to the public actually be to 
breach confidentiality legitimately? For example, are you 
just as willing to report someone who confesses in confi- 
dence to stealing a badly needed winter coat? It is not 



always easy to balance the interests of the patient against 
those of the public. This can create difficult dilemmas for 
you when the two seem in direct conflict and when, as is 
often the case, there is considerable professional discre- 
tion as to how morally to proceed. Debates about HIV and 
AIDS have recently underlined these issues. 
3. Two things are clear. 

a. First, it does not follow from a claim that the public 
interest demands a breach of confidence that it actually 
does. For example, the police have no right to disclosure 
or to access clinical records that may provide evidence of 
a crime. A judge may issue a warrant legally authorizing 
such access or a subpoena demanding disclosure in court. 
However, even this does not make it morally mandatory. 
Some clinicians have felt so strongly about the immoral- 
ity of breaking a patient's confidence that they have 
risked being charged with contempt of court for refusing 
to do so. Do not fuse the law and morality, even though 
they often do overlap. 

b. Second, patients have no right to harm others 
through the exercise of their right to confidentiality. There 
is an obvious link between this right and the right of indi- 
viduals to control the use of their private property. Yet just 
as the legitimate exercise of this property right stops at the 
point at which the safety of others is threatened, the same 
can be said about clinical information. Therefore, if you 
discover that maintaining confidentiality will lead to the 
threat of serious harm to another known individual - the 
suspicion of a general threat is not sufficient - then a 
breach of confidence may be warranted. For example, 
although the legal precedent does not apply in the UK, a 
psychiatrist in the USA was successfully sued for negli- 
gence for not informing a young woman that he had 
clearly been told by a patient that he was going to kill her. 
He did. If you do consider a breach of confidence to a 
third party in these circumstances, it is always important 
to warn the patient that this is what you intend. 

The interest of the individual patient 

1. Breaches of confidence may not just be in the public 
interest. They may also be necessary in order to obtain 
information vital for successful treatment. Because of the 
physical or psychological effects of their illness, some 
patients are unable to communicate clearly about their 
medical history. Under such circumstances, you may need 
to consult relatives or friends, especially in emergencies. 

2. This said, still make strong attempts to obtain the 
patient's consent and to verify the identity of any others 
from whom information is sought. Reveal no more infor- 
mation about the patient's condition than is necessary for 
the clinical purposes at hand. Keep knowledge confiden- 
tial concerning prognosis and treatment, for example. 
Remember how its unwarranted spread might drastically 



162 



CONSENT FOR SURGICAL TREATMENT 




affect the patient's private and public life. Never com- 
municate clinical information over the phone to those not 
involved in treatment, unless it is with the patient's prior 
consent and there is a reliable way of identifying the 
person to whom you give the information. 

3. The interests of patients are also served if you share 
clinical information they have given you, with colleagues 
whose assistance you require. Patients are presumed to 
consent to such revelations by virtue of their general 
agreement to treatment. Given the complexity of its divi- 
sion of labour, surgery is an essentially cooperative exer- 
cise and its success depends on the free flow of relevant 
information. This said, allow access to information only to 
those professionals involved - something which requires 
caution, especially on open wards. 



surgical team accept that the final decision about how to 
proceed is reached after an open and reasoned discus- 
sion. Everyone then has the chance to present their 
arguments. As a result, clinicians are more willing to 
cooperate in the search for a common view, even though 
it involves a degree of what may be perceived as moral 
compromise. Open communication does not have to con- 
flict with the recognition that it is the senior clinician 
who takes responsibility for the final choice. If you are a 
surgeon in authority, always try to create space for such 
discussions, a practice that is increasingly common in the 
face of taxing moral dilemmas that have to be resolved 
in short periods of time - for example, those concerning 
the withdrawal of life sustaining treatment. 



MORAL INDETERMINACY, INFORMED 

CONSENT AND OPEN 

COMMUM 

1. Thus far, we have examined the general principles 
governing informed consent that are endorsed by the sur- 
gical profession and which are reinforced by statute and 
case law. Yet, clear as these are, their correct interpreta- 
tion may be much more obscure in practice. Such rules do 
not interpret themselves: you must interpret them as an 
individual when faced with the complexities of specific 
cases. 

2. In the majority of cases there is a consensus among 
the surgical team about the most appropriate interpreta- 
tion. It will be reasonably clear, for example, how much 
information should be communicated to knowledgeable 
patients about the hazards of a particular treatment and 
whether or not they have understood enough of it to 
warrant proceeding. Yet in some situations, such agree- 
ment does not exist and interpretations are conflicting. 
Reference to the facts of the case themselves cannot solve 
the problem. Their openness to conflicting interpretation 
is what poses it. 

3. Suppose, for example, that despite careful attempts 
to communicate the considerable risks of an urgently 
needed operative procedure there is still disagreement 
within the surgical team about whether or not the patient 
has fully understood. Against the background of the 
necessity to come to a quick decision, there may be no 
'right' interpretation as to how to proceed ethically. 

4. Another illustration might be conflicting beliefs 
about whether or not to operate urgently on a Jehovah's 
Witness who refuses a blood transfusion but seems 
to be doing so partially under pressure from family or 
congregation. 

5. What is crucial in such circumstances is that, 
despite their disagreements, individual members of the 



Summary 

• Do you respect the right of patients to 
give or withhold consent to surgical 
treatment? 

• Will you provide patients with sufficient 
information to make informed choice 
possible? 

• Even in surgical emergencies, will you 
avoid overriding the right of conscious and 
capable patients to decide on treatment? 

• Will you continue to respect the rights of 
all patients, including children, and those 
who are unconscious, mentally 
handicapped or psychiatrical ly ill? 



ACKNOWLEDGEMENTS 

Many thanks to John Cochrane, Robert Cohen, Lesley 
Doyal, John Dickenson, Arlene Klotzko, Alastair 
McDonald, Rosanne Lord, Paul Lear, Norman Williams, 
Daniel Wilsher, Christopher Wood and Richard Wood. 
Special thanks to Ian Kennedy. 




Alderson P 1993 Children's consent to surgery. Open University 

Press, Buckingham 
Beauchamp T, Childress J 1994 Principles of biomedical ethics. 

Oxford University Press, New York 
Brazier M 1992 Medicine, patients and the law. Penguin, 

Harmondsworth 
British Medical Association 2001 Withholding and withdrawing 

life-prolonging medical treatment. BMJ Books, London 



163 



14 * 



PREPARATIONS FOR SURGERY 



British Medical Association 2001 Consent, rights and choices in 

health care for children and young people. BMJ Books, London 
Buchanan A, Brock D 1989 Deciding for others: the ethics of 

surrogate decision making. Cambridge University Press / 

Cambridge 
Doyal L, Tobias J (eds) 2000 Informed consent in medical 

research- BMJ Books, London 
Harris J 1985 The value of life. Routledge, London 
Kennedy I, Grubb A 2000 Medical law. Butterworths, London 
Lipkin M, Putnam S, Lazare A (eds) 1995 The medical interview: 

clinical care, education and research. Springer, New York 
McHale J, Fox M 1997 Health care law - text and materials. 

Sweet and Maxwell,, London 



McLean S 1989 A patient's right to know: information 

disclosure, the doctor and the law. Dartmouth, 

Aldershot 
Mason J, McCall Smith R 1999 Law and medical ethics. 

Butterworths, London 
Montgomery J 2002 Healthcare law. Oxford University Press, 

Oxford 
Rothman DJ 1991 Strangers at the bedside: a history of how law 

and bioethics transformed medical decision making. Basic 

Books, New York 
Royal College of Surgeons 1997 The surgeon's duty of care. 

Royal College of Surgeons, London 
Wear S 1993 Informed consent. Kluwer, Dordrecht 



164 




Preoperative preparation for 
surgery 

S. Bhattacharya, G. M. H. Wray 




Objectives 

• Understand the general principles of 
preoperative preparation. 

• Appreciate how, in high risk patients, 
preoperative preparation may lower the 
risk. 

• Understand the principles of preparation 
for specific types of operation. 

• Appreciate the value of protocols and 
routines, and the importance of adhering 
to them, even in emergency situations. 



To obtain satisfactory results in surgery, a careful pre- 
operative preparation of the patient is vital. Attention to 
detail is the key to success. The importance of this pre- 
paration becomes more evident as the surgical procedure 
performed becomes more complex. 



ROUTINE PREOPERATIVE 
PREPARATION 



£&^&£&!^£&^*A& 



Evaluation 

1. Take a full history and exclude any significant 
medical problems (see Ch. 6). 

2. Check clinical signs against the planned surgical pro- 
cedure, in particular noting the side involved. Confirm 
that the planned operative procedure is appropriate. 




Key point 

During the interval between the decision to 
operate and the actual operation, the disease 
may have progressed, making the intended 
operation inappropriate; seek advice from a 
senior colleague. 



3. Take a full drug history with specific enquiry regard- 
ing allergic responses to drugs, latex and skin allergies. 
Continue medication over the perioperative period, espe- 
cially drugs for hypertension, ischaemic heart disease and 
bronchodilators. Give patients on oral steroid therapy 
intravenous hydrocortisone. Stop oral warfarin anticoag- 
ulation 3^1 days preoperatively and check the prothom- 
bin time prior to surgery. If the prothrombin time remains 
unacceptably high, the patient may require an infusion of 
fresh frozen plasma. Those on warfarin who have had a 
life-threatening thrombotic episode (e.g. pulmonary 
embolus) within the previous 3 months should be 
switched to heparin intravenously until 6h before 
surgery; the heparin can usually be recommenced 4 h after 
surgery Patients taking aspirin or other antiplatelet medi- 
cation (e.g. clopidogrel) may have an increased risk of 
bleeding; stop these drugs for at least 48 h preoperatively 
for major surgery. Stop drugs, over the perioperative 
period, that may interfere with anaesthetic agents, includ- 
ing monoamine oxidase inhibitors, lithium, tricyclic 
antidepressants and phenothiazines. If possible, stop the 
oral contraceptive pill 4 weeks prior to any major surgery. 
Postmenopausal patients on hormone replacement 
therapy do not need to have their medication stopped 
before an operation. 

4. There is a clear correlation between malnutrition in 
the preoperative period and an increased morbidity and 
mortality from surgery (see Ch. 10). Nutritional assess- 
ment can be based on total body weight loss, anthropo- 
morphic measurements such as skinfold thickness to 
assess the amount of subcutaneous fat, or biochemical 
tests that reflect protein deficiency, such as the measure- 
ment of serum albumin, prealbumin or transferrin. Such 
preoperative nutritional assessment may detect patients 
in whom malnutrition is a major concern for their oper- 
ative procedure, but the correction of this malnourished 
state, which in part reflects their underlying disease 
process, may be impossible in the preoperative period. 
Highlight the problem to allow you to commence nutri- 
tional support at an early stage and consider inserting a 
feeding enterostomy or a designated central venous 
feeding line at the time of operation. Do not consider 



165 




PREPARATIONS FOR SURGERY 



correcting a low preoperative serum albumin level with 
human albumin solution except as an adjuvant to full 
parenteral or enteral nutrition. It is an ineffective and 
expensive method of providing nutritional support. 

5. Young and fit patients undergoing minor procedures 
do not require any preoperative investigations {see Ch. 4). 
In older patients or those with significant medical prob- 
lems, standard investigation would include a full blood 
count, urea and electrolytes, chest X-ray and electrocar- 
diogram. For a critical evaluation of routine preoperative 
investigations see Velanovich (1994). 

Routine preoperative measures 

1. Each clinical firm evolves a standard protocol for 
preoperative preparation appropriate for its patients. 
Adhere to the protocol followed by your firm. Use a 
checklist - these are very useful to ensure that you do not 
leave out an important step. 

2. Prohibit solid diet to adult patients for 6 h, and clear 
fluids for 4 h, prior to an elective general anaesthetic. 
Fasting times for children vary in different hospitals and 
they are also age dependent. A suggested regimen is 
summarized in Table 15.1. 

3. The operation site must be prepared by the removal 
of hair, if this is necessary for access, using a depilatory 
cream. Shaving or clipping hair from the operation site 
increases the risk of infection, unless the skin preparation 
is carried out immediately prior to surgery. 




Table 15.1 Preoperative fasting times for children 



i 



Bab/es under 1 year 

No breast milk for 2-3 h before anaesthesia 

Mo formula feed for 6 h before anaesthesia 

Clear fluids may be given up to 3 h before 

anaesthesia 

Children over 7 year 

No food/milk for 6 h before anaesthesia 

Clear fluids up to 3 h before anaesthesia 



Key point 

• Mark a unilateral operation site on the skin 
with an indelible marker pen. 

4. Explain to the patient (or guardian) the procedure 
and any likely complications, answer questions the 
patient may have, and only then have them sign the 
consent form. If you are unable to answer the patient's 
questions, seek help from a senior colleague. It is good 
practice for the operating surgeon to obtain the patient's 
consent; failing that, it may be done by another member 
of the team who is familiar with the operation and its 
aftercare. Consent should ideally be obtained from 
patients not immediately before an operation but some 
time ahead, so that they may have a period of reflection, 
and an opportunity to ask further questions that may 
arise. 

5. Antibiotic administration is guided by the surgical 
procedure involved and is discussed below, as is prophy- 
laxis against deep vein thrombosis. 

6. If specific services, such as frozen section histo- 
pathology or intraoperative radiography are likely to 
be required during the operation, organize these in 
advance. 



THHEJJSE^ 

1 . As a general rule, treat patients with clinical infec- 
tion using systemic antibiotics before they undergo 
operation. 

2. Antibiotic prophylaxis for an elective operation 
depends on the procedure being performed (Table 15.2). 

3. Clean procedures, as for varicose veins, do not 
require antibiotic prophylaxis. Abdominal operations not 
associated with significant contamination, such as chole- 
cystectomy, demand only a single dose of prophylactic 
antibiotic given on induction of anaesthesia. 



Table 15.2 The risk of infection 



Type of wound 



Clean 



Cfean-contaminated 



Contaminated 



Description 




Incidence of wound infection (%) 



^ 



No violation of mucosa 


2 


No inflammation 




No drains 




Incision of mucosa but no spillage, or 


10 


Clean procedure in immunocompromised 




Pre-existing infection 


20-40 


Spillage of viscus contents 





166 



PREOPERATIVE PREPARATION FOR SURGERY 



15 



4. Procedures in a contaminated field, such as appen- 
dicitis, require a preoperative dose and two postoperative 
doses. This regimen is also satisfactory for most other gas- 
trointestinal tract procedures, including gastric surgery, 
and colonic operations on prepared bowel. 

5. The choice of antibiotic prophylaxis is determined 
by the surgical procedure itself. Operations potentially 
contaminated by skin flora require prophylaxis against 
staphylococcal infection with flucloxacillin 500 mg intra- 
venously. Procedures involving the bowel require broad- 
spectrum cover for Gram-positive and Gram-negative 
organisms and anaerobes. Commonly used regimens 
include co-amoxiclav or a cephalosporin with metronida- 
zole. Biliary tract procedures rarely involve anaerobic 
contamination: a cephalosporin alone is satisfactory. 



Table 153 Risk factors for deep vein thrombosis 




Key point 



If a patient has a penicillin allergy, avoid not 
just penicillin but also drugs such as ampicillin 
and amoxicillin. Cephalosporins have a 10% 
chance of crossreactivity in patients with 
penicillin allergy; prescribe them with caution. 



PROPHYLAXIS AGAINST DEEP VEIN 
THROMBOSIS AND PULMONARY 
EMBOLI __ 

Pulmonary emboli are a major cause of mortality for sur- 
gical patients, accounting for 10% of inpatient deaths in the 
United Kingdom. Recent operation, immobilization and 
trauma were responsible for 50% of deep vein thrombosis 
(DVT) in a review by Cogo et al (1994), but there are other 
important predisposing factors, such as the high oestrogen 
content oral contraceptive pill, and significant obesity 
(Table 15.3). Many risk factors cannot be avoided, but take 
measures to avoid propagation of any thrombosis: 

1. Subcutaneous heparin may reduce the incidence of 
DVT by 50%; it is generally well tolerated but very occa- 
sionally causes thrombocytopenia. Systemic anticoagula- 
tion effects of low dose subcutaneous heparin are 
minimal and haemostasis is not impaired. Newer low 
molecular weight heparins (LMWHs), as effective as 
standard heparin, need only once a day dosage. 




Key point 



Recent surgery 

Immobilization 

Trauma 

Orat contraceptive pill 

Obesity 

Heart failure 

Arteriopathy 

Cancer 

Age > 60 years 



Adapted from Cogo et al (1994), 



Epidural anaesthesia? Take precautions against 
epidural haematoma. 



Epidural (or spinal) anaesthesia significantly reduces 
postoperative morbidity and mortality (Rodgers et al 
2000) and is used for perioperative analgesia (see also 
Chs 16, 35). Insertion and removal of epidural catheters 
have been associated with the development of epidural 
haematomas in anticoagulated patients with potentially 
serious neurological consequences. Current recommen- 
dations are to delay insertion or removal of an epidural 
catheter for 12 h after a dose of LMWH. Delay subsequent 
doses of LMWH for 2 h following catheter insertion or 
removal (Wheatley & Veitch 1997). 

2, Graduated compression stockings and intraoper- 
ative intermittent pneumatic calf compression are also 
effective in reducing deep venous thrombosis. 

PREF^ATI^ 

For the management of specific preexisting comorbidity, 
such as heart disease or diabetes, see Chapter 6. Risk 
assessment is an important part of the preoperative 
anaesthetic assessment. You may use the ASA (American 
Society for Anesthesiologists) scoring system to assess 
the overall risk (Table 15.4). The functional status of 
patients with cardiac disease may be stratified using the 
NYHA (New York Heart Association) classification 
(Table 15.5). Risk stratification in patients in intensive 
care may be done using more complex systems such as 
the APACHE (Acute Physiology and Chronic Health 
Evaluation) score (Knaus et al 1985). 

Emergency surgery 

1, The results of emergency surgery are less satisfac- 
tory than those of elective procedures. The emergency 
nature of the surgery may not allow sufficient time for 
investigation and treatment of associated medical prob- 
lems. Do not cut corners, and adhere to your elective pre- 
operative protocols as far as possible. These patients are 
commonly dehydrated and hypovolemic; if that is the 



167 




PREPARATIONS FOR SURGERY 





Table 15.4 


American Society for Anesthesiologists (ASA) status 






Category 


Description 




Perioperative mortality (%) 


I 

II 

III 

IV 

V 


Healthy patient 

Mild systemic disease - no functional limitations 

Severe systemic disease - definite functional limitation 

Severe systemic disease that is a constant threat to life 

Moribund patient not expected to survive 24 h with or without 


surgery 


0.1 
0.2 
1.8 
7.8 
94 




Table 15.5 


New York Heart Association classification 






Class 


Description 







IV 



No functional limitation 

Slight functional limitation. Fatigue, palpitations, dyspnoea or angina on ordinary physical activity but 

asymptomatic at rest 

Marked functional limitation. Symptoms on less than ordinary activity, but asymptomatic at rest 

Inability to perform any physical activity, with or without symptoms at rest 



case, their initial management must include insertion of 
wide-bore venous access lines and prompt rehydration. 
Consider inserting a central venous line, and also a 
urinary catheter to assess the adequacy of rehydration. 
Such patients may have sepsis, requiring systemic anti- 
biotic treatment. Insert a nasogastric tube if there is insuffi- 
cient time to allow for the usual period of fasting, or if you 
suspect bowel obstruction. 




Key point 

• As far as possible adhere to your elective 
preoperative routines. 

2. Carefully judge the timing of the operation, and 
involve senior colleagues in the decision making. The 
morbidity and mortality audit (National Confidential 
Enquiry into Perioperative Deaths, NCEPOD) performed 
by the Royal College of Surgeons of England (Campling 
et al 1993) suggests that the majority of patients with 
acute surgical problems are better managed by active 
resuscitation prior to operation performed on a scheduled 
operating list by an experienced surgeon. 



(ICU) preoperatively to undergo 'preoptimization'. The 
value of this high standard of care has been recognized 
for many years. 

2. Survival following operation requires adequate 
cardiac reserve. It is possible that the perioperative course 
can be improved by setting targets for improving circu- 
lating blood volume and cardiac function measured by 
cardiac output, oxygen delivery and oxygen consump- 
tion. The targets were originally defined by Shoemaker 
et al in 1988, and are known as 'Shoemaker's goals': 

• Cardiac index (CI) > 4.2 ml min" 1 m" 2 

• Oxygen delivery (Do 2 ) > 600 ml min" 1 m~ 2 

• Oxygen consumption (Vo 2 ) > 170 ml min" 1 m~ 2 

They were chosen as representing 'survivor values' when 
high risk surgical patients were studied retrospectively 
and are claimed to improve survival if achieved preoper- 
atively (Wilson et al 1999, Takala et al 2000). This involves 
the insertion of a central line or pulmonary artery catheter 
sufficiently early before operation to allow manipulation 
of haemodynamics using fluid resuscitation, with or 
without the addition of an inotrope such as dopexamine. 
Beware of the risks of using high levels of inotropic drugs 
to achieve Shoemaker's goals in those who fail to respond 
to treatment or are in the late stages of septic shock. 



Very high risk patients 

1. Some patients are at particularly high risk because 
they have significant comorbidity and may require a 
major or emergency operation. If possible, admit them to 
a high dependency unit (HDU) or intensive care unit 



PREPARATION FOR SURGERY OF 
SPECIFIC PATIENT GROUPS 



r^^^y^<;i^-^^^^^t^::^i^ 



*ft&^?&% :: &^^ 






Preparation must be tailored to the procedures to be 
performed and the stage of the underlying pathology 



168 



PREOPERATIVE PREPARATION FOR SURGERY 



15 



Large bowel operations 

1. Most surgeons consider bowel preparation essential 
to reduce the risk of sepsis, although some recent con- 
trolled studies failed to prove any benefit from it. For elec- 
tive operations, institute a liquid diet for several days 
and administer oral purgatives on the preoperative day. 
Sodium picosulphate (Picolax) 10 mg morning and night, 
or polyethylene glycol /sodium salts (Klean-Prep) four 
sachets in 4 litres of water taken 250 ml every 15 min, are 
suitable. If they fail to cleanse the bowel, combine them 
with mechanical washouts via a rectal tube. Elderly 
patients may require intravenous hydration while under- 
going bowel purgation to compensate for associated fluid 
loss. Bowel preparation is usually contraindicated in 
obstructed patients, although some surgeons advocate 
on-table colonic lavage with the infusion of fluid through 
a caecostomy or append icostomy; the effluent drains 
through a wide-bore tube inserted proximal to the 
obstruction. 




Key point 

• Warn all patients undergoing bowel surgery of 
the possible need to create a colostomy or 
ileostomy. 

2. Before operation ask the stoma care nurse to select 
and mark the most practical site for a colostomy on the 
abdominal wall. 

3. Counsel patients undergoing rectal surgery about 
the risks of pelvic nerve injury with consequent impo- 
tence and loss of bladder control. 

4. Inform patients with Crohn's disease of the poss- 
ibility of recurrence and anastomotic breakdown. 
Similarly, discuss with patients undergoing pouch 
surgery the likelihood of bowel frequency and inconti- 
nence. Those undergoing anal surgery, especially for high 
fistula, need to know about the risks of incontinence. 



Upper gastrointestinal surgery 

1 . Patients may be anorexic, in a poor nutritional state, 
requiring correction by enteral or parenteral feeding 
before and after operation. If the patient is vomiting, 
detect and correct dehydration, electrolyte depletion and 
possible acid-base imbalance. If there is evidence of 
gastric delay or obstruction, insert a nasogastric tube to 
empty the stomach and prevent aspiration at the time of 
induction of anaesthesia. Vomiting may be associated 
with episodes of aspiration so assess and if necesssary 
correct respiratory function. 



2. The oesophageal lumen becomes rapidly contami- 
nated in the presence of disease or partial obstruction. For 
24 h before operation give 10 ml of 0.2% chlorhexidine 
mouthwash and swallow, 6-hour ly. 

Liver, biliary and pancreatic operations 

1. Jaundiced patients may be deficient in the vitamin 
K-dependent clotting factors II, V, VII, IX and X, resulting 
in a bleeding tendency. Give vitamin K (10 mg intra- 
muscularly or intravenously) to patients with obstructive 
jaundice prior to surgery, if their prothrombin time is 
abnormal. Be ready to give fresh frozen plasma to those 
in whom there is a significant coagulopathy and who 
require urgent operation. 

2. Preoperative insertion of a biliary endoprosthesis to 
correct obstructive jaundice in the hope of reducing oper- 
ative risk is controversial. There is also little evidence that 
routine preoperative biliary stenting or drainage by endo- 
scopic retrograde cholangiopancreatoscopy (ERCP), or 
percutaneous transhepatic cholangiography (PTC), is 
helpful in these patients. However, consider preoperative 
drainage in patients who are elderly, deeply jaundiced or 
with biliary tract sepsis. 

3. Avoid or reduce renal failure secondary to obstruc- 
tive jaundice (hepatorenal syndrome) by ensuring ade- 
quate preoperative hydration; do not stop oral fluids 
pre-operatively without intravenous fluid replacement. 
The value of the osmotic diuretic mannitol and the 
ino trope dopamine (in a low dose resulting in renal 
vasodilatation) to prevent hepatorenal failure is unproven. 

4. Infective complications are common after operations 
for obstructive jaundice, so always give antibiotics as 
prophylaxis. 

5. Acute cholangitis demands systemic administration 
of fluids, antibiotics and urgent biliary tract drainage, 
either endoscopically or percutaneously. Patients with 
biliary obstruction who undergo an unsuccessful ERCP 
(where the duct is entered but not stented) are at a high 
risk of developing cholangitis. They require antibiotic 
cover and urgent consideration of a PTC. 

6. If you intend that the procedure will be carried out 
laparoscopically on a patient with severe pulmonary 
disease, take advice from the anaesthetist. Inducing 
pneumoperitoneum increases intra-abdominal pressure 
and may render ventilation difficult. 




Key point 



Before laparoscopic biliary operations, inform 
the patient about the possibility of conversion 
to an open procedure. 



169 



15* 



PREPARATIONS FOR SURGERY 



7. Hepatic cirrhosis is a particularly high risk disorder, 
requiring treatment by an experienced team. Clotting is 
often deranged, and may need elective correction with 
vitamin K or emergency infusion of fresh frozen plasma 
and clotting factors. 

8. The presence of portal hypertension raises operative 
risks. The operation may be technically difficult, with 
excessive venous bleeding. Patients tolerate major fluid 
shifts badly and become encephalopathy as a conse- 
quence, or may develop renal failure. Avoid operating on 
those with decompensated cirrhosis (Child-Pugh C) 
unless it is absolutely essential. 

9. In patients requiring pancreatic resection, consider 
giving octreotide (a somatostatin analogue that suppresses 
pancreatic secretion) in the perioperative phase to reduce 
the risk of leakage from the pancreatojejunal anastomosis. 
Several trials have shown probable but not certain benefit. 
In operations on the pancreatic tail, with the possibility of 
splenectomy, be prepared to inject the patient preoper- 
atively with vaccines against pneumococcal, meningococcal 
and Haemophilus influenzae type B infections. 

Endocrine surgery 

1. Thyrotoxic patients require preoperative treatment 
to reduce thyroid activity, such as carbimazole 10-15 mg 
three times daily, and a beta blocker such as propranolol 
20-40 mg, 8-hourly for 10 days preoperatively, to prevent 
thyrotoxic crisis. 

2. Have the movement of the vocal cords checked by 
indirect laryngoscopy prior to operation, to exclude an 
unsuspected idiopathic unilateral palsy. 

3. Demonstrate the extent of a retrosternal goitre with 
computed tomography. 

4. Patients with phaeochromocytoma require preoper- 
ative medication to block the a- and p-adrenergic effects 
of catecholamines, and may require admission a week 
before operation. As a rule, start with a-blockade using 
phenoxybenzamine, followed 48 h later by (3-blockade 
with atenolol or metoprolol. 

Paediatric patients 

1. The common surgical procedures in childhood are 
often performed by general surgeons with special train- 
ing and interest in paediatric surgery. Complex congeni- 
tal defects and surgery in neonates require specialist 
surgical expertise and specific preoperative preparation. 



■■*► 



Key point 



Manage all paediatric patients together with a 
paediatrician. 



2. Although comorbidity is unusual in children, 
exclude upper respiratory tract infection or cold, which 
can cause potentially life-threatening laryngeal spasm 
due to the sensitivity of the inflamed airway. Discuss this 
with the anaesthetist and be willing to postpone any but 
an emergency operation. 

3. Arrange elective procedures for children at the 
beginning of the operating list to minimize the period of 
fasting. If operation is delayed, give fluids intra- 
venously; insert venous cannulae after applying topical 
anaesthetic cream to reduce discomfort. Administer 
fluids according to body weight (40-60 ml kg^ 1 24 h" 1 ). 
Heparin and antibiotics are not required for routine 
clean surgical procedures. 

Thoracic surgery 

1 . Arrange preoperative lung function tests in patients 
with severe functional limitation due to chronic airway 
disease, including arterial blood gases on room air and 
measurements of forced expiratory volume in 1 min 
(FEV}) and forced vital capacity (FVC). Patients with 
FEVj/FVC below 50% of the predicted value are at a high 
risk of respiratory failure. 

2. In patients requiring lung resection, assess the likely 
impact of this on postoperative lung function using 
radioactive isotope perfusion scans of the individual 
lungs. 

3. Arrange active preoperative physiotherapy, treat- 
ment of any respiratory infection with antibiotics and 
good postoperative analgesia in order to minimize the 
risk of postoperative respiratory failure. In this patient 
group, seek evidence of associated atherosclerotic coron- 
ary and cerebral vascular disease and obtain the advice of 
a cardiologist if necessary (Goldman et al 1977). 

4. Anticipate the possibility of pulmonary emboli and 
give routine subcutaneous heparin. 

Vascular surgery 

1. Atherosclerosis is a generalized disease so search 
carefully the complete vascular system for evidence of 
widespread insufficiency, such as cerebral, coronary, renal 
and peripheral arterial disease. Arrange for expert advice 
and management before undertaking any operation for 
peripheral vascular disease. In elective circumstances be 
willing to await improvement of severe ischaemic heart 
disease with drugs, angioplasty or coronary artery graft- 
ing. An operation within 3 months of a myocardial infarc- 
tion carries a 20-30% risk of a perioperative infarct. This 
risk decreases to 10-20% between 3 and 6 months, and 
4-5% after 6 months. This compares with a risk of 0.1-0.2% 
risk of infarction in patients with no evidence of a 
previous myocardial infarct. Remember that the risk of 



170 



PREOPERATIVE PREPARATION FOR SURGERY 



15 



death from perioperative myocardial infarction is 
extremely high, at around 70%. 

2. Diabetic patients with limb ischaemia require dia- 
betes control and treatment of infected skin lesions before 
operation. 

3. Since smoking is a common predisposing factor to 
atherosclerosis and it reduces small vessel blood flow, ask 
the patient to stop it preoperatively. Smoking also pre- 
disposes to chronic obstructive airways disease and 
bronchial carcinoma, so carefully assess respiratory func- 
tion. If there is a productive cough, send sputum for 
culture, antibiotic sensitivity and cytology. In addition, 
check the serum lipid profile to exclude correctable 
hyperlipidaemia. 

Orthopaedic surgery 

1. The most common orthopaedic operations are for 
the treatment of joint abnormalities secondary to 
osteoarthritis. Many patients are elderly, with comorbid- 
ity such as ischaemic heart disease and chronic obstruc- 
tive airways disease. Diagnose, assess and treat them 
appropriately (see Ch. 6). 

2. Crossmatch blood for joint replacement as there 
may be significant blood loss. 

3. The increased use of prostheses (Greek pros = to + 
thesis = putting) in orthopaedic surgery allows early 
mobilization, but infection is a serious risk around the 
foreign material. Administer antibiotic prophylaxis 
against contamination from skin commensals such as 
staphylococci and streptococci. 

4. Since thromboembolism is a major cause of mortal- 
ity in orthopaedic patients, especially following pelvic 
surgery, routinely give prophylaxis with standard 
heparin or LMWH. 

Patients with latex allergy 

Latex allergy is becoming more prevalent and is thought 
to result from true anaphylaxis to latex proteins. It can 
pose a serious risk to life from both anaesthetic and sur- 
gical equipment. There is an increased incidence in those 
exposed repeatedly to latex, such as healthcare workers, 
patients with spina bifida who have had repeated 
catheterization, atopic (Greek atopia = strangeness; hyper- 
sensitivity) individuals and people with banana or 
avocado allergy (crossreactiviry with similar proteins). 
Plan operations on these patients so that all concerned in 
the operating theatre and hospital ward use appropriate 
equipment. The operating theatre should have a checklist 
of equipment that is safe to use in such patients, and 



ideally there should be a 'latex allergy box' containing 
most of these items. 



Summary 

• Do you realize the importance of 
preoperative preparation with close 
attention to detail? 

• Are you aware of the specific needs of 
different patients undergoing different 
procedures? 

• Can you recognize the need to identify 
high risk patients early so you can institute 
appropriate measures at once? 

• Do you accept the need for a 
multidisciplinary approach, requiring good 
communication within the team? 




References 



Campling EA, Devlin HB, Hoile RW, Lunn JN 1993 Report of 

the national confidential enquiry into perioperative deaths 

1991/1992. King's Fund Publishing, London 
Cogo A, Bernardi E, Prandoni P et al 1994 Acquired risk factors 

for deep vein thrombosis in symptomatic outpatients. 

Archives of Internal Medicine 154: 164-168 
Goldman L, Caldera DL, Nussbaum SR 1977 Multifactorial 

index of cardiac risk in noncardiac procedures. New England 

Journal of Medicine 297: 845-850 
Knaus WA, Draper EA, Wagner DP et al 1985 APACHE II: a 

severity of disease classification system. Critical Care 

Medicine 13: 818-824 
Rodgers A, Walker N, Schug S et al 2000 Reduction of 

postoperative mortality and morbidity with epidural or 

spinal anaesthesia: results from overview of randomized 

trials. BMJ 321: 1493-1497 
Shoemaker WC, Appel PL, Kram HB et al 1988 Prospective trial 

of supranormal values for survivors as therapeutic goals in 

high-risk surgical patients. Chest 94:1176-1186 
Takala J, Meier-Hellman A, Eddlston J et al 2000 Effect of 

dopexamine on outcome after major abdominal surgery: a 

prospective, randomized, controlled multicentre study. 

Critical Care Medicine 28 : 341 7-3423 
Velanovich V 1994 Preoperative laboratory screening based on 

age, gender and concomitant medical diseases. Surgery 

115: 56-61 
Wheatley T, Veitch PS 1997 Recent advances in prophylaxis 

against deep vein thrombosis. British Journal of Anaesthesia 

78: 118-120 
Wilson J, Woods I, Fawcett J et al 1999 Reducing the risk of 

major elective surgery: randomized controlled trial of 

preoperative optimization of oxygen delivery. BMJ 318: 

1099-1103 



171 




Preoperative assessment and 
anaesthesia 



M. 1/1/. Piatt 




Objectives 

Understand the rote of the preoperative 
assessment in the work-up for surgery. 
Gain a general understanding of the 
function of the anaesthetist, the effects of 
anaesthesia and the perioperative medical 
management of the patient. 
Realize the importance of analgesia in 
minimizing the stress response and its 
significance in reducing postoperative 
complications. 

Understand the basic pharmacology and 
toxicology of local anaesthetic agents and 
their use. 




PREOPERATIVE ASSESSMENT AND 
PREMEDj™ 

Ideally, an anaesthetist should assess all patients preop- 
eratively. Often, daycare (or ambulatory care) patients 
attend the hospital only on the morning of operation. 
The anaesthetist carries out the assessment in the ward 
just before the list begins, or even in the anaesthetic 
room. Patients with significant intercurrent disease have 
normally been assessed at a booking clinic and admitted 
before the day of surgery to optimize their physical state. 
An anaesthetist is usually asked to assess risk factors 
involved. 

The anaesthetic assessment evaluates the patient's 
physiological status, vital organ functional reserve and 
any concurrent disease states, including diabetes, thyroid 
and cardiac diseases (see Chs 6, 15). This is in order to 
judge the patient's ability to withstand the stress of 
surgery and anaesthesia, and to check that the patient 
has not eaten or drunk for 4 h, although this is slightly 
modified for young children by allowing clear, glucose- 
containing fluids up to 2 h preoperatively. Physical exam- 
ination focuses on the cardiovascular, respiratory, hepatic, 
renal, and central nervous systems. 



Key point 

• Are there any drug allergies, intercurrent 
medications, history of personal or family 
anaesthetic problems? 

The anaesthetist then prescribes premedication, the drugs 
administered preoperatively, including any essential 
intercurrent medication. They are usually prescribed by 
the anaesthetist at the preoperative visit to allay anxiety, 
relieve pain and, occasionally, to dry saliva and oral 
secretions. 

Intercurrent medication 

Many patients requiring operation have other medical 
problems that are treated by a variety of different drugs 
(see Ch. 6). Especially consider those on antihypertensive 
therapy, antiarrhythmic therapy, anticoagulation regi- 
mens, oral or insulin therapy for diabetes, endocrine 
replacement therapy (particularly thyroxin), adrenocorti- 
cal replacement or augmentation therapy, asthma or 
chronic obstructive airways disease treated with bron- 
chodilators and allied drugs, cardiac failure therapy, and 
those requiring diuretics. Because of fasting, or the oper- 
ation itself, it may not be possible to continue the medi- 
cation. Many drugs must be continued up to the time of 
operation and some agents can be administered par- 
enterally. Antihypertensives, anticonvulsants, antiar- 
rhythmics and other essential medications can often be 
given 2 h preoperatively with a small sip of water. 

Anaesthetic premedication 

Anxiolysis (Table 16.1) 

Patients attending for surgery are normally anxious about 
the outcome. They may have a fear of the unknown, of 
pain, of dying, of cancer, or non-specific fears. Although 
the preoperative visit by the anaesthetist does much to 
allay anxiety by reducing the unknown element, waiting 
for an operation may be unpleasant. Anxiolytics calm the 



172 



PREOPERATIVE ASSESSMENT AND ANAESTHESIA 



16 



Table 16.1 Anxiolytic agents in common use 




Benzodiazepines 

Diazepam 

Temazepam 

Lorazepam 

Midazolam 



0.05-03 mg kg ] 
0.15-0,5 mg kg- 1 
0.015-0.06 |±g kg" 1 
0.07-0. OS mg kg" 1 



Phen o Xh is zin es 

Promethazine 0.2-0.5 mg kg _1 

Prochlorperazine 0.1-02 mg kg" 1 



36-200 
5-20 

10-20 
0.5-2 

8-12 

a-12 



patient and help to reduce time spent 'dwelling' on fears. 
Agents specifically used for anxiolysis are the benzo- 
diazepines, particularly the shorter-acting agents such as 
temazepam, usually given orally 2h preoperatively. 
Midazolam can be given intranasally, intramuscularly or 
intravenously. It is a potent benzodiazepine and often 
produces unconsciousness! Opioid analgesics calm and 
sedate the patient and are used especially if analgesia is 
required (see below). 

Phenothiazines are usually given in combination with 
an opioid. Promethazine is frequently combined with 
pethidine. These agents are useful, especially in the 
elderly, as they calm but do not oversedate. Pheno- 
thiazines are also appropriate in atopic individuals, such 
as asthmatics; their antihistaminic action may be useful. 
Prochlorperazine has combined sedative and antiemetic 
properties. 

Analgesia (Table 16.2) 

There are two main reasons for using opioid analgesia as 
part of the anaesthetic premedication, apart from the 
excellent sedative properties. These analgesics ease 
patients with painful conditions such as fractured hips 
and other types of trauma for comfortable transfer to 
theatre. They also provide a continuous background of 
analgesia to aid the anaesthetic and extend analgesia into 
the postoperative period. Recent evidence suggests that 
preoperative medication with analgesics such as opioids 
or non-steroidal anti-inflammatory drugs reduces post- 
operative analgesic requirements. Recent evidence also 
suggests that preoperative administration of cyclo- 
oxygenase (COX) 2 inhibitors, such as rofecoxib, can 
significantly reduce postoperative pain, probably by 
reducing neurosensitization by prostaglandin release. 
Take care when using these drugs, as they can aggravate 
renal failure and may cause gastric bleeding, although 
this is much less than with COX 1 drugs. 



Table 16.2 Analgesic agents in common use 



: 



Agent 



Dose 
(mg kg-1) 



Approx. duration, 
i.m, (h) 



Morphine 

Diamorphine 

Papaveretum 



0.1-0.2 

0.05-0.1 

0.2-0,4 



4 
4 
3 



Notes 

1, Papaveretum is a mixture of alkaloids which 
contains morphine (45-55% dry weight), codeine, 
papaverine, thebaineand noscopine. It should not 
be used in women of child-bearing aye, because 
noscopine has been shown to be a gene toxin. 

Papaveretum is most commonly used as a 
premedication in combination with hyoscine, and 
comes in a premixed ampoule containing 
papaveretum 20 mg ml" 1 and hyoscine 0,4 mg ml \ 

2. Morphine, often used alone for both its sedative 
and analgesic properties, is usually combined with a 
drying agent such as atropine (also useful to 
prevent bradycardia), or in combination with an 
antiemetic drug. 



Opioid premedication is usually combined with anti- 
cholinergic agents, such as glycopyrrolate, to dry secre- 
tions and, in the case of hyoscine, to potentiate sedation. 

The choice of premedication depends very much on the 
individual patient. A moribund patient does not benefit, 
and may indeed suffer, from such side-effects as respira- 
tory or cardiovascular depression. In contrast, a young, 
fit, anxious patient could benefit from anxiolysis or seda- 
tion, besides possible analgesic requirements, especially 
in trauma. 

Drying secretions (Table 16.3) 

When ether anaesthesia was used, it was important to dry 
oral secretions, because ether stimulates salivary secre- 
tions on induction, with the risk of laryngospasm. With 
modern anaesthesia it is less of a requirement, although 
it may be useful to dry secretions before dental surgery, 



Table 163 Drying agents in common use 



Agent 



Dose 
(mg kg- 1 ) 



Approx. duration 



J 



i.v. 



i.m 



Atropine 
Hyoscine 
Glycopyrrolate 


0.02 

0.008 

0.01 


15-30 min 
30-60 min 
1-A h 


2-4 h 
4-6 h 

6-8 h 

1 



173 



16 



PREPARATIONS FOR SURGERY 



bronchoscopy, operations on the lung, and for paediatric 
patients in whom salivation can be troublesome, In addi- 
tion to drying secretions, muscarinic receptor antagonists 
also prevent bradycardia, a common side-effect of general 
anaesthesia, especially in very young children. 

Hyoscine, in contrast to atropine, contributes to the 
sedative properties of premedication. Glycopyrrolate 
does not cross the blood-brain barrier, and is an inhibitor 
of salivary secretions, with little effect on the vagus nerve 
and hence on the heart rate. Atropine has also been shown 
to have a small antiemetic effect, presumably by inhibit- 
ing vagal activity, as well as a slight bronchodilator effect. 



5. The advent of newer, more specifically acting agents, 
such as the muscle relaxants, has enabled modern general 
anaesthesia to be considered as a balance between the 
triad of 'relaxation', 'analgesia' and 'hypnosis' (lack of 
awareness). 

Phases 

A general anaesthetic may be considered in three phases, 
analogous to an aircraft flight. I shall consider each part 
of the triad separately, under the heading of each phase 
of the anaesthetic. 



GENERAL ANAESTHESIA 

1. The anaesthetist is responsible for managing the 
patient peroperatively. This includes managing acute 
blood loss, maintaining normal cardiorespiratory physi- 
ology and protecting organ function. It may include min- 
imizing the stress response to surgery and the effects of 
the stress hormones on organ function, such as the heart 
and kidneys. General anaesthesia is a reversible, drug- 
induced state of unresponsiveness to outside stimuli, 
characterized by lack of awareness, by analgesia and 
relaxation of striated muscle. Older agents such as ether 
need to be given in high dosage, and take a long time for 
induction and recovery. 

2. The mechanisms of general anaesthesia are complex 
and ill understood. Current knowledge suggests that 
general anaesthesia is produced when certain molecules 
interact with multiple hydrophobic pockets, often within 
complex protein molecules, such as those forming part of 
the potassium channel of a cell membrane, as well as 
certain neuron receptors, such as those for the inhibitory 
transmitter gamma-aminobutyric acid (GAB A). It is clear 
that short-term memory mechanisms are disrupted, in 
addition to 'normal' brain function. These changes are 
completely reversible, as normal function resumes on 
removal of the anaesthetic agents. General anaesthesia is 
an 'all-or-none' phenomenon, as the patient is either 
anaesthetized or not, with no in between state. 

3. Deep anaesthesia obtunds (blunts) the neurohu- 
moral stress response to surgery. Modern anaesthesia is 
usually at a much lighter plane, and some responses may 
be seen. Ultra short-acting opioids help inhibit the stress 
response; this is believed to be better for the patient. 
Alternatively, regional anaesthetic techniques prevent the 
stress response by blocking afferent nerve fibres. 

4. Sedation is not general anaesthesia. Agents used 
include benzodiazepines (for example midazolam), or 
propofol in subanaesthetic doses. The patient continues to 
respond to spoken command, but may not remember the 
procedure later. 



Take off: induction of anaesthesia 

1. Hypnosis (Greek hypnos = sleep) at induction of 
anaesthesia. In the anaesthetic room patients are induced 
using one of several intravenous anaesthetics. In approx- 
imate order of frequency, those shown in Table 16.4 are 
the most commonly used agents. When drugs are taken 
up in the bloodstream, initial distribution is to Vessel- 
rich' tissues and those taking a large fraction of the 
cardiac output. Thus the brain, which is vessel-rich and 
also taking a large fraction of the cardiac output, receives 
a considerable portion of intravenous anaesthetic given as 
a bolus. Subsequently, drugs diffuse out of the brain, 
down a concentration gradient formed by the falling 
blood concentration, and are redistributed to other vessel- 
poor tissues. This results in an initial short redistribution 
half-life. The longer elimination half-life of a drug repre- 
sents its metabolism and elimination from the body. In 
some instances, this can appear to take a long time, due 
to the slow leaching out of drug from vessel-poor fat 
tissues. 

2. Thiopental, a very short-acting barbiturate, was the 
first widely used intravenous induction agent. It was first 
used to great effect on casualties from the bombing of 
Pearl Harbor in 1942. However, its ability to depress the 
myocardium was tragically evident in the deaths of young 
sailors already shocked from hypovolemia. It was soon 



Table 1 6.4 


Anaesthetic 




agents 




Drug 


Dose 


Distribution 


Elimination 


Thiopental 


(mg kg -1 ) 
3-5 


half-life (min) 


half-life (h) 


3-14 


5-17 


Propofol 


1-3 


2-4 


4-5 


Etoimidate 


0,3 


2-6 


1-5 


Ketarnine 








i.v. 


1-2 


10 


2-3 


i.m. 


5-10 


15 


2-3 


Midazolam 


0.03-0.3 


6-20 


1-4 



174 



PREOPERATIVE ASSESSMENT AND ANAESTHESIA 



16 



appreciated that the dose should be reduced, giving only 
enough to cause sleep (a 'sleep dose')/ titrated carefully for 
each patient, especially those with a low cardiac reserve. 

3. Propofol has a very short half-life, and is used partic- 
ularly in daycase surgery, where rapid recovery is neces- 
sary. It is also used to abate the effects of procedures 
which occasionally cause laryngospasm, such as laryn- 
geal mask placement and anal stretching. It is sometimes 
infused intravenously to maintain anaesthesia, because of 
its short half-life. The initial bolus of propofol sometimes 
causes a profound fall in blood pressure and inhibits com- 
pensatory increases in heart rate; this can be attenuated 
by administering glycopyrrolate or atropine before the 
induction. Small doses of propofol are sometimes used to 
produce sedation for procedures carried out under local 
anaesthetic. 

4. Etomidate is indicated only for induction of anaes- 
thesia. As a side-effect, it causes a reversible suppression 
of an enzyme in the adrenal cortex, leading to inhibition 
of Cortisol secretion - this is especially important if it is 
used as an infusion. It is indicated in patients with poor 
cardiac reserve, or those in whom a fall in cardiac output 
could prove catastrophic, because it tends to maintain 
cardiac output. It is relatively long acting, and may cause 
postoperative nausea and vomiting. 

5. Ketamirte, structurally related to LSD, is used in 
shocked patients because it stimulates the sympathetic 
nervous system and prevents a fall in cardiac output. 
However, patients who are already on full sympathetic 
drive still suffer a reduction in cardiac output and blood 
pressure. It produces a state known as 'dissociative 
anaesthesia' with profound analgesia. 

6. Benzodiazepines, and particularly midazolam, which 
is the most efficacious in this respect when given intra- 
venously, are occasionally used to induce or assist induc- 
tion of anaesthesia and are commonly used for sedation. 

7. Opioids in very high doses are used to induce anaes- 
thesia in some situations. The most commonly used 
agents for this are the highly potent synthetic derivatives 
fentanyl, alfentanil and sufentanil. Fentanyl is used in a 
dosage of up to 1.0 mg kg -1 , particularly in cardiac anaes- 
thesia, as it avoids hypotension and maintains cardiac 
output. Unless other agents are added, awareness may 
occur. Chest rigidity, preventing adequate ventilation, 
occasionally occurs but is easily reversed using muscle 
relaxants. 




Key point 



Apart from the exceptions mentioned, all 
intravenous anaesthetic agents depress the 
myocardium. 



Relaxation at induction 

Muscle relaxation is necessary at induction to facilitate 
tracheal intubation. Relaxation during maintenance of 
anaesthesia is discussed below. 

Suxamethonium is a depolarizing relaxant used primar- 
ily for difficult intubation and crash induction. It lasts 
only approximately 5 min following a dose of 1 .5 mg kg" 1 . 
It is essentially two acetylcholine molecules joined 
together. This similarity to acetylcholine results in activa- 
tion of the receptor and depolarization of the muscle 
membrane, lasting some 5—10 min, and muscles become 
unresponsive to acetylcholine. Because of its short action 
it is useful, apart from intubation, for very short surgical 
procedures. Side-effects include the following. 

• Histamine release. 'Scoline rash' is very common fol- 
lowing intravenous administration of suxamethonium. 
An erythematous rash is seen spreading over the upper 
trunk and lower neck anteriorly. Very occasionally, 
suxamethonium will cause bronchospasm and other 
more severe sequelae. 

• Bradycardia (Greek bradys = slow) occurs particularly 
if a second or subsequent dose is given, especially in 
children. Give atropine to prevent or reverse this effect. 

• Generalized somatic pain of unknown cause may 
result from widespread fleeting muscle contractions, 
termed 'fasciculations', caused by the depolarization of 
muscle fascicles. 

• Hyperkalemia (Greek kalium - potassium) results 
because suxamethonium causes the release of potas- 
sium from muscle cells and can lead to cardiac arrest 

• Persistent neuromuscular blockade may occur from the 
genetically related deficiency or abnormality of plasma 
pseudocholinesterase. The result is prolonged action of 
suxamethonium, sometimes called 'scoline apnoea'. 
The completely silent gene is rare, occurring in approx- 
imately 1:7000 of the population. 

• Malignant hyperthermia occurs in some 1:100 000 of 
the population. It is a reaction to certain anaesthetic 
drugs, of which suxamethonium and halothane are the 
commonest. Muscle metabolism becomes uncontrolled 
because of an abnormality of intracellular calcium flux. 
Body temperature rises at the rate of at least 2°C every 
15 min, and Paco 2 , reflecting the massively raised 
metabolic rate, also increases with alacrity. Treat with 
ventilation, surface cooling and intravenous dantrolene 
sodium (Dantrium), given promptly before death 
ensues. 

'Crash induction' 

1, This is necessary when you assume that the patient 
has a full stomach (see below). The technique consists of 
a rapid-sequence intravenous induction, cricoid pressure 



175 



16 . 



PREPARATIONS FOR SURGERY 



and tracheal intubation, with the aim of preventing regur- 
gitation and aspiration of stomach contents. 

2. Immediately following a preplanned dose of thiopen- 
tal (3-5 mg kg -1 ), give suxamethonium (1.5 mg kg" 1 )/ cur- 
rently the fastest muscle relaxant, acting within one 
circulation time. Rocuronium, a newer non-depolarizing 
relaxant, is also used, but has a longer duration of action. 
Have a trained assistant apply pressure to the cricoid 
cartilage, simultaneously compressing the oesophagus 
between the cricoid ring and the vertebral column. 
Intubate the trachea with a cuffed tube, and inflate the cuff. 
When the anaesthetic circuit is attached and cuff seal con- 
firmed/ only then have the cricoid pressure relaxed. 

3. The following patients are at risk of aspiration of 
stomach contents on induction of anaesthesia: 

a. All non-fasted patients 

b. Patients with a history suggestive of hiatus hernia 

c. In an emergency, any traumatized patient, as trauma 
slows stomach emptying 

d. Those with intestinal or gastric obstruction or stasis 

e. Pregnant women in whom stomach emptying is 
slowed and the cardiac sphincter relaxed 

f. Those with intra-abdominal tumours that may slow 
gastric emptying. 

'Cruising': maintenance of anaesthesia 

1. Hypnosis during anaesthesia is usually maintained 
with volatile agents/ which are hydrocarbons/ liquid at 
room temperature/ with high saturated vapour pressures 
and lipid solubility. Diethyl ether, inflammable and explo- 
sive, was the earliest agent used, and is still popular in 
some parts of the world. The addition of fluoride and 
other halogens makes the hydrocarbon molecule much 
more stable. Modern agents are non-flammable, non- 
explosive, and much more potent than ether. Being less 
soluble in blood, as indicated by the blood /gas partition 
coefficient, they also have a much faster uptake and elim- 
ination time than diethyl ether. Table 16.5 shows the most 
commonly used anaesthetic volatile agents, with ether as 
a comparison. 

2. Halothane is a hydrocarbon with fluorine, chlorine 
and bromine atoms. It was the first modern volatile 
non-flammable and non-explosive anaesthetic agent. 
Synthesized in 1951 and first used clinically in 1956, it 
was the most commonly used anaesthetic agent for 
30 years. It is a potent anaesthetic, allowing a smooth 
induction, especially important for gaseous induction of 
children, and with relatively rapid onset of anaesthesia. 
In the body up to 20% is metabolized by the liver, the 
majority being eliminated unchanged via the lungs. The 
recovery time from halothane anaesthesia is also rela- 
tively brisk and smooth. The most common side-effects of 
halothane result from its effects on the heart, Halothane 



Table 16,5 


Anaesthetic volatile 


agents 




Agent 


Structure 


MAC 


Blood/gas 

partition 

coefficient 


Diethyl ethe 


r ChbCtVO-CHjCHb 


1.92 


12 


Halothane 


CF 3 CHCIBr 


0,75 


2.3 


Enflurane 


CHF ? 0-CF,CHFCI 


168 


19 


Isoflurane 


CHF ; 0-CHClCFj 


K05 


1.4 


Sevoflurane 


(CF^CHO-CF^F 


2.0 


0,6 


Desflurane 


CF 3 CfHO-CF>H 


6-9 


0.42 


Xenon 


Xe 


71 


0.14 



A/ores 

1. MAC: the minimum alveolar concentration of a 
gas or vapour in oxygen required to keep 50% of 
the population unresponsive to a standard surgical 
stimulus (opening of the abdomen). MAC is 
expressed as a percentage concentration. 

2. Blood/gas partition coefficient: indicates how 
rapidly a gas or vapour is taken up from the lungs. 
The higher the blood solubility, the longer it takes 
for the brain to gain adequate anaesthetic 
concentrations. 

3. Summary of effects of modern vapours on organ 
systems: 

a. Heart: generally cause depressed contractility: 
halothane > enflurane > isoflurane 
(halothane causes more arrhythmias) 

b. Blood vessefy. generally cause vasodilation: 
isoflurane > enflurane > halothane 

c Respiration: depressed by al\ agents; 
enflurane > isoflurane > halothane 

d. Brain: all may cause vasodilation and raised 
intracranial pressure: halothane > enflurane > 
isoflurane (isoflurane safe up to 1 MAC), 



slows the sinoatrial node, slowing heart rate and causing 
variations in the PQ interval. It reduces myocardial work- 
load. Like verapamil, halothane produces these effects by 
blocking calcium channels in the heart. However, it also 
sensitizes the heart to catecholamines and may precipi- 
tate arrhythmias - especially important in the presence of 
adrenaline (epinephrine)-supplemented local anaesthesia 
and if the arterial carbon dioxide tension, Paco 2/ is 
elevated. By reducing cardiac output, halothane attenu- 
ates splanchnic blood flow, diminishing hepatic blood 
flow and possibly aggravating its effects on the liver. 
With the aid of very fine indicators of hepatic perfor- 
mance, it has been shown that even the briefest exposure 
to halothane causes some degree of liver dysfunction, 
probably related to the large amount, up to 20%, of 
halothane that is metabolized. An idiosyncratic (Greek 
idios - one's own + syn = together + krasis = a mixing; 



176 



PREOPERATIVE ASSESSMENT AND ANAESTHESIA 



16 



hence a personal peculiarity), reaction, which occurs after 
halothane exposure in some patients, is known as 
'halothane hepatitis'; it is a fulminant centrilobular 
hepatic necrosis which appears 2-5 days postoperatively. 
The incidence is 1:35 000 of the population (National 
Halothane Study USA, 1966), with a mortality of over 
50%. Halothane is now used in only 10% of anaesthetics 
given in the UK, mainly for paediatric anaesthesia. 

3. Enflurane is an ether synthesized in 1963 and first 
used in 1966. It is halogenated with fluorine and chlorine 
atoms to render it non-explosive and non-flammable. 
Enflurane is more efficacious in reducing peripheral vas- 
cular resistance and is less likely to cause cardiac arrhyth- 
mias, nor does it sensitize the heart to catecholamines; 
however, its pungent odour makes it unsuitable for 
gaseous induction in children. Enflurane causes greater 
respiratory depression than halothane or isoflurane, and 
so it is less suitable for maintaining anaesthesia in the 
spontaneously breathing patient. Enflurane is only 
slightly metabolized by the liver (up to 2.5%) and appears 
not to cause hepatitis. 

4. Isoflurane was synthesized in 1965 and first used in 
1971. It is a structural isomer of enflurane, but with dif- 
ferent properties. Isoflurane tends to act on the peripheral 
vasculature as a calcium antagonist, reducing peripheral 
vascular resistance. Although it has minimal effects on the 
heart, isoflurane may cause 'coronary steal', whereby 
blood is diverted from stenosed coronary arteries to 
dilated unblocked coronary arteries, possibly compro- 
mising ischaemic areas of myocardium. This is still a con- 
troversial area and isoflurane generally causes minimal 
depression of contractility. In the brain, isoflurane has the 
least effect on cerebral blood flow, causing no significant 
increase up to 1 MAC (minimum alveolar concentration). 
Isoflurane causes least respiratory depression and is 
suited to the spontaneously breathing patient. Up to 0.2% 
only of isoflurane is metabolized by the liver and no cases 
of hepatitis have been reported. 

5. Desflurane is popular for anaesthetizing daycare 
patients because of the rapid recovery; however, it is very 
pungent, often causing patients to cough, so it is unsuit- 
able for gaseous induction. It is useful for patients with 
large amounts of adipose tissue, as it has the lowest fat 
solubility of all the agents used, resulting in a more rapid 
recovery, with little accumulation. 

6. Sevoflurane is very popular as a gaseous induction 
agent, especially in children, because of its rapid onset and 
non-pungent characteristics. It has a low volatility, so is 
cheaper to use at low gas flow rates, as less liquid is used. 
It is now probably the most commonly used anaesthetic 
agent. Both desflurane and sevoflurane are characterized 
by remarkable molecular stability, with very little hepatic 
metabolism. They also have a very low blood gas solubil- 
ity coefficient, resulting in very rapid onset and recovery. 



7. Xenon (Greek xenos = stranger, guest), a rare, heavy 
gas, is currently under trial as an anaesthetic agent. It is 
an extremely stable molecule and gives excellent cardio- 
vascular stability with a rapid onset and offset, and no 
metabolism. However, it is very expensive and has 
required the development of special anaesthetic machines 
which allow the gas to be recycled for further use. 

8. Nitrous oxide (N z O), unlike the volatile agents, is a gas 
at atmospheric pressure and room temperature. It has a 
MAC of 103% at sea level. The requirements of keeping the 
patient well oxygenated mean that it can never be relied 
upon to provide anaesthesia in its own right. It is, however, 
a very potent analgesic agent. Fifty per cent N 2 is equiva- 
lent in efficacy to approximately 10 mg morphine sulphate. 
It continues to enjoy popularity as the main background 
anaesthetic gas, usually given as 70% in oxygen. In concen- 
trations greater than 50% it causes amnesia and contributes 
significantly to the overall anaesthetic. 

9. General anaesthesia can also be maintained intra- 
venously using a continuous infusion of anaesthetic agents 
such as propofol, which are non-cumulative and are rapidly 
cleared. This is usually supplemented with an infusion of a 
short-acting opioid such as remifentanil or alfentanil. This 
is termed 'total intravenous anaesthesia (TIVA)'. 

Relaxation during anaesthesia 

1 . To allow the surgeon access to intra-abdominal con- 
tents, or to allow artificial ventilation of the patient in 
chest surgery, for example, muscle relaxation (paralysis) 
is required. 

2. Agents used specifically to relax muscles are called 
relaxants; they are agents which block acetylcholine 
receptors on muscle endplates. There are two types of 
relaxant: 

a. Depolarizing muscle relaxants. The only one still in 
common use is suxamethonium, which is described 
above in relation to induction. 

b. Non-depolarizing muscle relaxants. There are many 
different relaxants available today. Because of the side- 
effects of suxamethonium, researchers continue to seek a 
non-depolarizing relaxant with a very rapid onset and 
very short half-life. They have a usual onset time of 
2-3 min, and last from 20 to 60 min. They are competitive 
inhibitors of the acetylcholine receptors on muscle end- 
plates, preventing access of acetylcholine to receptor, 
blocking transmission of nerve impulse to muscle. Curare 
was the first relaxant of this class, developed from an 
arrow poison used by the indigenous people of the 
Amazonian rainforests to kill animals for food. The dex- 
trorotatory isomer alone is active; the term 'tubo-' refers to 
the bamboo tubes in which it is carried - D-tubocurarine. 
Modern relaxants tend to be shorter acting, with fewer 
side-effects (Table 16.6). 



177 



11_ 



PREPARATIONS FOR SURGERY 



Table 16.6 Non-depolarizing muscle relaxants 



Agents 



Dose (mg kg 1 ) Duration of effect (min) Side effects 



Pancuronium 


0.01 


45-120 


Vecuronium 


0.01 


30-45 


Rocuronlum 


0.05 


30^5 


Atracurium 


0.06 


15-40 


Cisatracurium 


0.15 


30-45 



Vagolytic: tachycardia, increases blood pressure 

Bradycardia 

Rapid onset 

Histamine release 

No histamine release 



Notes 

1 > With the exception of atracurium and cisatracurium, ail these agents require renal and hepatic function for 

their clearance. 

2. Atracurium and cisatracurium are excreted by two mechanisms: Hoffman elimination (up to 40% with 
atracurium, up to 70% with cisatracurium) and hepatic metabolism. Hoffman elimination results in breakdown of 
the molecule as a result of pH and temperature. It is used in those patients with renal failure. 

3. The duration of effect with each agent varies slightly according to anaesthetic technique. The use of volatile 
agents, particularly enflurane and isoflurane, potentiates the effect of non-depolarizing muscle relaxants. 
Hypothermia also potentiates non-depolarizing relaxants. 

4. The shorter-acting agents atracurium and vecuronium are often used as infusions for long cases and in 
intensive care. 

5. Muscle relaxants have no intrinsic anaesthetic effect. 



Analgesia during anaesthesia 

The final part of the triad of general anaesthesia during 
its maintenance consists of analgesia. The anaesthetized 
patient derives analgesia from three potential sources: 
from the premedication/ from anaesthesia supplementa- 
tion with opioids, and from the analgesic properties of 
volatile and gaseous agents. 

1 . Premedication. Opioids used in premedication, as dis- 
cussed earlier, tend to last intraoperatively and into the 
postoperative period. In this way, premedication affects 
both the anaesthetic and postoperative analgesia. 

2. Anaesthetic opioid supplementation is often adminis- 
tered intraoperatively to deepen the effect of the anaes- 
thetic, or to reduce the amount of volatile agent used 
(often because of their side-effects such as hypotension). 
To limit the effects of opioids to the perioperative period, 
anaesthetists often use highly potent short-acting agents 
such as fentanyl, alfentanil or sufentanil. Recently, the 
ultrashort-acting remifentanil has become available, and 
is given only by infusion. These agents are all much more 
potent than morphine, and much shorter acting, of the 
order 20-30 min. They may need to be reversed at the end 
of the operation, to facilitate spontaneous respiration. 
However, this is at the expense of analgesia. Longer 
acting opioids such as morphine, papaveretum or pethi- 
dine may also be used, especially if postoperative 
analgesia may be a problem. 

Modern non-steroidal anti-inflammatory agents, such as 
diclofenac, are used for postoperative analgesia, either on 



their own for minor surgery or in combination with opioid 
techniques to give a much better quality of analgesia. Side- 
effects include renal failure (prostaglandin inhibition may 
lead to renal shutdown), gastric ulceration and bleeding 
(inhibition of platelet function). Different agents have dif- 
ferent degrees of complications, but their careful use has 
revolutionized the aftercare of patients, particularly after 
daycare surgery. The development of COX 2 antagonists, 
such as rofecoxib, will reduce the problems of gastric 
bleeding but will still be a problem for renal function. 

3. Analgesic properties of volatile agents. Modern volatile 
anaesthetic agents have poor analgesic properties and 
contribute little to this part of the anaesthetic. However, 
nitrous oxide is a very good analgesic (see above) and is 
also used for analgesia during labour as a 50% mixture 
with oxygen, known as Entonox. 



'Landing': recovery from anaesthesia 

At the end of the operation, anaesthesia is terminated. 
Volatile agents and nitrous oxide are turned off on the 
anaesthetic machine and oxygen alone administered. 
Anaesthetic gases and vapours diffuse down concentra- 
tion gradients from the tissues to the alveoli of the lungs 
and out via the airway. 

1. Reversal of muscle relaxation: competitive muscle 
relaxants usually need to be reversed to ensure full return 
of muscle power. The degree of neuromuscular blockade 
can be monitored with a peripheral nerve stimulator. 



178 



PREOPERATIVE ASSESSMENT AND ANAESTHESIA 



f 16 



2. Neostigmine (0.05 mg kg -1 ) or edrophonium 
(0.5 mg kg -1 ) is given intravenously. They block acetyl- 
cholinesterase in the neuromuscular junction, resulting 
in accumulation of acetylcholine. This overcomes the 
competitive blockade of the relaxant molecules in favour 
of acetylcholine. However, both neostigmine and edro- 
phonium cause acetylcholine accumulation at both 
muscarinic and nicotinic sites. Muscarinic receptors are 
those cholinergic receptors in the heart, gut, sweat 
glands, etc. Therefore, to prevent bradycardia, profuse 
sweating and gut overactivity, atropine (0.02 mg kg ] ) or 
glycopyrrolate (0.01 mg kg~ ] ) must be given with the 
anticholinesterase. 

3. Full reversal of muscle relaxation is only apparent 
from appropriate neuromuscular monitoring, or when the 
patient is able to maintain head lifting. This aspect of 
recovery from anaesthesia is crucial, as full muscular 
control is necessary for coughing and for good control of 
the airway. Indeed it highlights the importance of 
adequate recovery facilities in the theatre suite. 

POSTOPERATIVE ANALGESIA 






It is important to continue good analgesia into the post- 
operative period and to continue to have a stress-free 
patient. The anaesthetist will usually ensure that suffi- 
cient longer-acting opioid such as morphine or diamor- 
phine has been administered towards the end of the 
procedure for adequate postoperative analgesia. This can 
be topped up as necessary in recovery. If an epidural or 
other regional block such as a brachial plexus block is 
sited, the analgesia can be continued with a continuous 
infusion of local anaesthetic combined with a short-acting 
opioid. The surgeon may be asked to inject local anaes- 
thetic locally at the site of wounds to minimize postoper- 
ative discomfort. 

There are several methods of managing postoperative 
pain, which can be considered as follows: 

• Systemic analgesia: intravenous, intramuscular, sub- 
cutaneous, oral, nasal or sublingual application of 
analgesics 

• Regional analgesia: usually placed before surgery, as 
part of the anaesthetic technique - continued into post- 
operative period 

• Other techniques (TENS, acupuncture): not very effec- 
tive for acute pain - used more for chronic pain. 

Pre-emptive analgesia may reduce postoperative anal- 
gesic requirements. This involves the preoperative 
administration of: nerve blocks /regional analgesia; pre- 
medication with opioids; use of supplementary agents 
with specific spinal actions such as ot 2 -agonists. 



The World Health Organization produced a simple 
pain ladder for the administration of analgesia. Originally 
designed for cancer pain, it is also appropriate for acute 
postsurgical pain: 

• Minor pain: paracetamol, aspirin, other non-steroidal 
analgesics 

• Moderate pain: above combined with minor opioids - 
co-proxamol (propoxyphene), co-dydramol (codeine); 
minor or intermediate opioids alone, e.g. tramadol, 
buprenorphine 

• Severe pain: opioids - morphine, diamorphine, oxy- 
codone, etc. 

The 'minor opioids' consist of propoxyphene, codeine 
and tramadol. Propoxyphene and codeine are often com- 
bined with paracetamol. Tramadol has the least effect on 
respiratory depression and is not a class A drug. It is 
roughly equivalent to codeine in its action. 

The "intermediate opioids' mainly consist of buprenor- 
phine, which is well absorbed sublingually. 

The 'major opioids' include morphine, diamorphine 
(heroin), oxycodone, fentanyl, sufentanil, alfentanil and 
remifentanil. 

The dose of the major opioids, of which morphine and 
diamorphine are the most commonly used, is whatever is 
required! The dosage should be carefully titrated intra- 
venously. Long-term chronic and cancer pain in those 
who can swallow can be titrated orally and converted to 
long-acting drugs such as morphine continus tablets or 
capsules. Initially, the required loading dose, titrated, 
should be given. Care may need to be taken with subse- 
quent dosage, especially in the elderly, as the half-life may 
be extended. Opioids can be given by a number of differ- 
ent routes: intravenous, intramuscular, infusion, regional 
(including spinal). They may be used in combination 
therapy with non-steroidal anti-inflammatory drugs, or 
with local anaesthetics. Opioids act on \x & 8 receptors 
in the brain and spinal cord. Mu receptors also cause 
nausea, vomiting and respiratory depression. Delta 
receptors are found mainly in the spinal cord. 

Non-steroidal anti-inflammatory drugs block the cyclo- 
oxygenase (COX) pathway. There are two forms of the 
enzyme: COX 1 and COX 2. COX 1 is always present, but 
COX 2 is only induced by inflammation, such as occurs 
with surgery or in chronic inflammatory conditions. They 
both also have a central role, where both COX 1 and COX 
2 are found as neurotransmitters. COX 2 antagonists are 
preferable where there is a high risk of peptic ulceration/ 
bleeding, however, there is still not a 100% guarantee! 
Currently the second generation of COX 2 antagonists 
are being released, some of which will be available for 
parenteral administration, enabling easier peroperative 
administration. 



179 



™ . 



PREPARATIONS FOR SURGERY 



REGIONAL ANAESTH^ 

1. Regional (local) anaesthesia is the reversible block- 
ade of nerve conduction by regionally applied agents, for 
the purpose of sensory ablation either of traumatized 
tissue or to enable minor surgery. These agents are 
referred to as 'local anaesthetics'. Both motor and 
sensory nerves may be blocked, depending on the agent 
used and the anatomical region where the agent is 
applied. 

2. Nerves may be blocked anywhere between the 
central nervous system and the site of required sensory 
loss. Local anaesthetics are used to block pain fibres as 
they enter the spinal cord: epidural, spinal and paraver- 
tebral techniques. They may also be blocked along their 
anatomical route in the neurovascular bundles: field 
blocks, or specific nerve blocks. Finally, local infiltration 
around the required site may be performed (for example, 
skin and subcutaneous infiltration) to block conduction at 
the nerve endings. 

3. Types of nerve fibre: the speed with which local 
anaesthetic agents are taken up by nerve fibres depends 
on their size and whether they are myelinated. Nerve 
fibres are classified according to their size and speed of 
conduction (Table 16.7). 

4. Sensitivity to local anaesthetics: the smaller fibres are 
more sensitive to local anaesthetic agents than the larger 
fibres. Hence, 'C fibres conducting pain are more sensi- 
tive than motor fibres in the 'A' group. This is why 
patients may still be able to move limbs, even during 
regional anaesthesia. The reason for the difference is most 
likely to be due to more rapid absorption and uptake of 
local anaesthetic into the smaller fibres within neuro- 
vascular bundles. 



Local anaesthetic agents 

Drugs used as local anaesthetics all tend to have 
'membrane-stabilizing' properties. They act by inducing 
a blockade of nerve transmission in peripheral nerve 



impulses. This occurs as a result of obstruction to sodium 
channels in the axon membrane, preventing ingress of 
sodium ions necessary for propagation of an action 
potential. 

Local anaesthetic agents belong to one of two chemical 
classes according to their structure, which consists of an 
amide or ester linkage separating an aromatic group and 
an amine: 

Aromatic group ±=r Amine group 
Amide or ester 

Ester class 

The only ester still in frequent use is cocaine, which is an 
ester of benzoic acid. It is generally used only for topical 
anaesthesia of mucous membranes in the nose and 
sinuses. Amethocaine is still used as a topical agent, as is 
benzocaine. 

Amide Class (Table 16.8) 

• Lidocaine (lignocaine) was the first amide to be synthe- 
sized. It was shown to be safer than cocaine and has 
remained a mainstay for local anaesthetic practice. The 
maximum dosage is 4 mg kg^ 1 alone or 7 mg kg -1 with 
adrenaline (epinephrine). 

• Prilocaine has the highest therapeutic index, and 
is considered the safest agent for intravenous block- 
ade. The maximum dose is 6 mg kg" 1 . Other amides in 
common use include bupivacaine, levo-bupivacaine 
and ropivacaine. 

• Bupivacaine is longer acting than lignocaine and is com- 
monly used in epidural analgesia. 

• Levobupivacaine, the isomer, is safer than the racemic 
bupivacaine in terms of cardiotoxicity and has a similar 
dosage profile. 

• Ropivacaine has less motor blockade than bupivacaine 
when used epidurally. 

Lidocaine (lignocaine), bupivacaine and levobupivacaine: 
maximum dose 2 mg kg -1 . 



Table 16.7 Types of nerve fibre 



Fibre 



B 

C 



Type 



ft 
P 

y 

a 




Function 




Conduction velocity (ms) 



Motor, proprioception 


70-120 




Touch, pressure 


30-70 




Motor (spindles) 


15-30 




Pain, temperature, touch 


12-30 




Preganglionic autonomic 


3-15 




Dorsal root: pain, reflexes 


0.5-2 




Sympathetic: postganglionic 


0,7-2.3 





Diameter (^m) 



12-20 
5-12 
3-6 
2-5 

<3 
0.4-1 
0.3-1 



180 



PREOPERATIVE ASSESSMENT AND ANAESTHESIA 



.' 16 



Table 16.8 Amide class 




Drug 



Maximum dose (nig) 



Side effects 



Lidocaine (lignocaine) 

Prilocaine 

Bupivacaine 

Levobupivacaine 
Ropivacaine 



Cocaine 



300 (500 + adr.) 

600 

175 (225 + adr.) 

175 (225 + adr.) 

2.5 per kg is recommended 
(e.g. 30 mf of 5% ropivacaine 
in a 60 kg patient) 

150 



No unusual features. CNS excitation with toxicity 

Least toxic, Methaemoglobinaemra > 600 mg 

Sudden cardiovascular collapse. Not indicated for 
intravenous blockade 

Less cardiotoxicity 

Less motor blockade in epidural administration 



Cardiac arrhythmias. CNS excitation. Topical use only 



Notes 

1, The table includes only those agents currently in common use and maximal doses relate to adult size (70 kg 
body weight). The dosages in parentheses refer to maximal doses in the presence of adrenaline (epinephrine). 

2, All local anaesthetic agents have membrane-stabilizing properties. Their toxic effects therefore relate to this 
property and involve mainly the cardiovascular and central nervous systems. 

Toxic effects on the central nervous system include fitting and coma, leading to death from hypoxia without 
adequate resuscitation. Cardiovascular effects from toxicity include hypotension, cardiac arrhythmias and acute 
cardiovascular collapse, 

Bupivacaine has a high affinity for cardiac muscle cells - a property which is thought to be responsible for the 
high incidence of cardiovascular collapse associated with its use for intravenous blockade {Bier's block), for which 
it is no longer recommended, 

3, Toxic effects may also occur with the accidental intravascular injection of drug. 

4, Concentration of local anaesthetic agents varies. Bupivacaine and levobupivacaine comes as 0.5% or 0.25%, 
with or without adrenaline (epinephrine), Lidocaine (lignocaine) generally comes as 0.5 r 1.0, 2.0% 
concentrations, again plus or minus adrenaline (epinephrine). The higher concentrations obviously have lower 
maximum safe volumes (1 % = 10 mg ml' 1 . 2% = 20 mg ml '), 

5, Local anaesthesia techniques should always be performed where adequate resuscitation facilities are present, 

6, Adrenaline (epinephrine) and other vasoconstricting agents, such as felypressin, allow higher doses of local 
anaesthetic to be used, the vasconstriction resulting in reduced absorption. 



Clinical application 

1. Local infiltration is used for surgery alone or in 
combination with general anaesthesia. Used with 
adrenaline (epinephrine), it reduces bleeding at the oper- 
ative site. It also produces good postoperative analgesia. 
EMLA (eutectic mixture of local anaesthetics), a mixture 
of lignocaine and prilocaine, produces good analgesia 
when applied topically to skin. It is useful for insertion of 
intravenous lines, arterial lines and removal of minor skin 
lesions. It needs to be applied some 2 h before the proce- 
dure. Tetracaine (amethocaine) 4% gel (Ametop) can also 
be used in the same way. 

2. 'Field 7 blocks and nerve blocks are useful for pro- 
ducing wider areas of anaesthesia and analgesia, for 
example in inguinal hernia repair, brachial plexus block- 
ade for the upper limb, and femoral and sciatic blocks of 
the lower limb. 



3. Spinal, epidural and paravertebral blockade produce 
widespread anaesthesia and analgesia. The pain of labour 
and childbirth involves nerve roots of lower thoracic, 
lumbar and sacral regions of the spinal cord. Epidural tech- 
niques, involving the epidural placement of a catheter, 
allow continuous analgesia or anaesthesia, alleviating pain 
from all these groups o( fibres. Regional anaesthesia such 
as this is frequently employed for urological and other 
surgery in the lower half of the body It should be noted, 
however, that spinal and epidural techniques also block 
sympathetic ganglia at the appropriate levels. Hypotension 
will occur unless adequate precautions are taken. 

RECENT ADVANCES 

1. Pre-emptive analgesia has gained popularity 
with the recent publication of data suggesting that the 



181 



16 



PREPARATIONS FOR SURGERY 



administration of analgesia preoperatively, either sys- 
temically as with an opioid, or regionally as in use of local 
anaesthetic techniques, reduces the patient's need for 
analgesia postoperatively. This has been reinforced by the 
finding that using epidural analgesia for 3 days prior to 
leg amputation produces a marked reduction in the inci- 
dence of phantom limb pain. Thus the use of regional 
techniques combined with general anaesthesia is becom- 
ing more popular. 

2. The widespread development of acute pain services 
is enabling the continuation of regional local analgesic 
techniques from the operating theatre into the general 
wards, improving the standards of postoperative pain 
control and perhaps reducing the incidence of postoper- 
ative nausea and vomiting secondary to opioids. 




Further reading 

Atkinson RS, Rushman GB, Lee A 1987 A synopsis of 

anaesthesia, 10th edn. Wright, London 
Barash PG, Cuplen BF, Stoelting RK 1989 Clinical anaesthesia. 

Lippincott, Philadelphia 
Gilman AG, Goodman LS, Rail TW, Murad F 1985 Goodman 

and Gilman's pharmacological basis of therapeutics, 7th edn. 

Macmillan, London 
Miller RD 1990 Anesthesia, 3rd edn. Churchill Livingstone, 

Edinburgh, vols I — II 
Nimmo WS, Smith G 1989 Anaesthesia. Blackwell Scientific, 

Oxford, vols I-II 
Stoelting RK 1987 Pharmacology and physiology in anesthetic 

practice. Lippincott, Philadelphia 
Vickers MD, Morgan M, Spencer PSJ 1991 Drugs in anaesthetic 

practice, 7th edn. Butterworths, Oxford 



Summary 

• What are the risks of failure to carry out 
preoperative assessment before an 
anaesthetic is administered? 

• Can you describe the functions of 
premedication? 

• What are the phases of general 
anaesthesia? With what other activity has 
it been compared? 

• What is a 'crash' induction? 

• What are the common types of local 
anaesthetic? Do you know their maximal 
dosage? 



182 




Operating theatres and 
special equipment 



M. K. H. Crumplin 




Objectives 

Learn the safe positioning, movement and 

care of patients while they are 

unconscious. 

Respect and understand the principles of 

diathermy, laser, cryosurgery and X-ray 

usage in a theatre environment. 

Comprehend principles of the use of all 

equipment you use, including laparoscopic 

insufflation principles and 

instrumentation, fibreoptics and 

microscopes. 

Understand the prevention of sepsis in the 

theatre. 



OPERATING THEATRE DESIGN AND 
ENVIRONMENT 






Introduction 

1 . A large proportion of your life is spent within the envi- 
ronment of an operating theatre. There are physical chemi- 
cal and infective hazards to yourself and your colleagues, 
nurses and patients, thus making the operating department 
the most hazardous part of the hospital. You must gain an 
understanding of this environment and the risks to both 
staff and patients. In the operating theatre the patient is 
totally helpless, and under full control of the theatre staff. 

2. The operating theatre environment must provide a 
safe, efficient, user-friendly environment that is as free 
from bacterial contamination as possible. Operating 
suites should be sited near to each other for efficient flex- 
ibility of staff movement, preferably on the first floor, 
away from the main hospital traffic. They should be on 
the same level as, and close to, intensive care units and 
surgical wards. The suite should incorporate the theatre 
sterile supply unit. 

3. There should be minimum distance between operat- 
ing rooms and the accident and emergency (A & E) unit 



and X-ray facilities, which will both be sited on the ground 
floor. Your hospital has a multidisciplinary user commit- 
tee to optimize efficiency and safety, comprising surgeons, 
anaesthetists, operating theatre and anaesthetic nurses, 
microbiologists, a manager and a finance officer, in line 
with updated Department of Health recommendations. 

4. Operating theatres now have an incident reporting 
system in place to audit adverse incidents in theatre. This 
is not designed to be punitive (Latin punire = to punish), 
but educational. Joint audit sessions between anaes- 
thetists and surgeons allow adverse incidents to be dis- 
cussed in an open and constructive way. 

5. An attempt was made by the Department of Health 
and Social Security in 1978 to introduce the nucleus 
concept, providing hospitals with theatre suites appro- 
priate to the average district general hospital require- 
ments. Orthopaedic, cardiac, neurosurgical, laser and 
other specialist requirements make it necessary to adjust 
the standard design. Examples are the Charnley tent, con- 
trolled areas for laser therapy, and the provision of a 
pump preparation room beside a cardiac bypass theatre. 

The antiseptic environment 
Zones 

• An outer, or general access zone for patient reception 
area and general office. 

• A clean, or limited access zone between the reception 
bay and theatre suite, and dispersal areas, corridors 
and staff rest room. 

• Restricted access zone, for those properly clothed per- 
sonnel engaged in operating theatre activities, includ- 
ing the anaesthetic room, utility and 'scrub up' rooms. 

• An aseptic or operating zone - the operating theatre. 
Keep the number of people to a minimum, as the bac- 
teriological count is related to the number of persons 
and their movement. 

Air flow 

Directional air flow (laminar air flow) may be vertical or 
horizontal. In addition to normal turbulent air flow 



183 



17 




PREPARATIONS FOR SURGERY 



through theatre, which is necessary to maintain humidity, 
temperature and air circulation, an increased rate of air 
change is necessary to reduce the number of contami- 
nated particles over the patient, that is aerobic counts of 
less than 35 microorganism-carrying particles per mm -3 . 
Air is pumped into the room through niters and passed 
out of vents in the walls of the operating room; it does not 
return into the operating suite. Most theatres have 20-40 
or more air changes per hour. 

Operating suit and tent environment 

In this system there is a high vertical laminar flow 
within a tent or designated area marked on the floor, and 
clean air from above the table is expelled down to floor 
level in a funnel shape, thereby reducing contamination. 
The number of air changes may be increased to 
400-600 per hour or more in the vertical laminar flow 
system of a Charnley tent. Orthopaedic surgeons may 
wear airtight suits and helmets, and work in a high 
velocity vertical air flow environment, which has limited 
access to other personnel. By using suitable exhaust suits 
and such tents, infection in hip replacement may be kept 
as low as 0.5%. 

Wearing of disposable, non-woven fabrics 

Reusable, comfortable cotton operating gowns, sterilized 
by heat, have the disadvantage that when they are wet, 
bacteria can pass through onto the operative field. 
Disposable gowns of less permeable fabrics reduce dis- 
persal of bacteria-laden particles that may emanate (Latin 
emanare = to flow) from the operating or nursing staff (see 
Ch. 18). Optimally, everybody should wear these gowns, 
but they are costly Although masks are not essential for 
the surgeon or nurses, wear them when the patient is 
particularly susceptible to infection, when a prosthesis is 
being inserted, or when you or the nurse has an upper 
respiratory tract infection. 

Skin preparation 

Prefer a non-spirit-based skin preparation such as 
Betadine, to minimize the risk of explosion. If you shave 
the patient, carry it out as late as possible. Skin drapes 
have limited benefit in preventing wound infection but 
help keep the skin towels in place. To prevent the ingress 
of skin bacteria apply an iodine-impregnated adhesive 
skin sheet. 



Temperature and humidity control 

These should be controlled as part of an integral air con- 
ditioning system to maintain a comfortable atmosphere, 



with a higher temperature for neonates, children, elderly 
patients and if the operation is prolonged. The tempera- 
ture range is 20-22°C (68-71 .6°F), with approximately 
20-40 air changes per hour. Patients become hypothermic 
if the temperature falls below 21 °C (69.8°F) during pro- 
longed procedures. Reduce heat loss by laying warming 
blankets on the sorbo-rubber table surface, wrap the 
patient in aluminium foil and infuse warmed intravenous 
fluids. Pass the blood, crystalloid or colloids through a 
coiled plastic infusion pipe within a heated waterbath. 
Minimize postoperative heat loss by wrapping the patient 
in metal foil. Increasing the humidity to 50% reduces 
cooling by evaporation. 



OPERATING .JfMJ^_^___ 

Operating tables need to be heavy and stable, easily 
manoeuvrable, comfortable for the patient and highly 
adjustable in terms of positioning the patient correctly for 
a particular operative procedure. There are two basic 
types of operating table. Most commonly they are com- 
pletely mobile, thus allowing replacement if necessary. A 
second type has a fixed, permanently installed column in 
the centre of the operating room on which a variety of 
table tops can be mounted; they are usually expensive 
and can be remotely controlled. The problem is that if a 
fault develops the table and theatre will be out of service; 
the advantage is that interchangeable table tops allow 
efficient patient handling and flexible operating-room 
scheduling. 

Ensure that the surface is sympathetic to the contours 
of the patient who is placed on it. This is achieved by 
using soft, moveable, easily cleaned sorbo-rubber 
padding that moulds to the patient. It raises the patient 
clear of the metal table. 




Key point 



• It is imperative that no part of the patient 
comes into contact with the metallic structure 
of the table or any metal object attached to it. 

There should be a radiolucent section on tables used for 
general surgery and urology to allow for static X-ray films 
or the use of an image intensifier. Built-in, adjustable 
lumbar supports may be useful; alternatively, use par- 
tially filled intravenous fluid bags. Make sure that motor- 
ized or hand-operated controls are easily accessible. The 
table should be capable of two-way tilt, and breaking at 
its centre to allow operations such as lateral nephrectomy, 
or jack-knife positioning. The bottom half of the table 



184 



OPERATING THEATRES AND SPECIAL EQUIPMENT 



. 17 



must be easily removed to allow various types of leg 
support and stirrups to be employed for gynaecological, 
urological, orthopaedic and pelvic operations. A variety 
of armrests, screen support bars and shoulder and pelvic 
supports should be available. 

Safety 

When using limb supports, avoid overstressing or pro- 
ducing localized pressure upon joints, ligaments, nerves, 
blood vessels, skin or any point of the patient's limbs. 
Various nerves are at risk from injury or pressure due to 
inappropriate positioning on the table. The brachial 
plexus may be stretched during arm movements, the 
ulnar nerve damaged at the elbow during pole insertion 
into the canvas sheet before transferring the patient, and 
the common fibular and saphenous nerves may be 
damaged by pressure against a leg support bar. 
Osteoarthrosis may be aggravated by rough handling 
during transfer, excessive joint movement, or distortion 
during the operative procedure, such as cervical exten- 
sion during thyroid surgery. 






Key point 



• Before induction of anaesthesia, rehearse a 
stressful position on the table with patients 
suffering from spinal or joint disorders. 

Be particularly careful when moving patients on and 
off the operating table. Check that attached tubing will 
not be dislodged. Transfer is best carried out using the 
Patslide, a tough plastic board, which acts as a bridge, on 
which the patient is slid from trolley to table, or vice 
versa. At least three people should be involved in moving 
an unconscious patient. 

Remember your own comfort in theatre. Always have 
the table adjusted so that you are not stooping or uncom- 
fortable. You should have the table at such a height that 
your elbows are flexed at about a right angle to your field 
of work. 



Operating table fixtures for specialist 
procedures 

Orthopaedic surgery 

There is a great variety of limb attachments to an operat- 
ing table, enabling circumferential access to a limb and 
manoeuvrability, and also allowing the surgical team to 
use the image intensifier following fixation or recon- 
structive procedures. 



Neurosurgery 

Access to the cranial cavity may be optimized by having 
the patient sit up, while keeping the head comfortably 
fixed using an appropriate padded head support placed 
opposite the surgical field. 




Key points 

Make sure the table is secure and the patient 

is safely positioned before you start 

operating. 

Have the table at a comfortable height for 

surgery. 



SPECIAL EQUIPMENT 









Tourniquets 

Abuse of tourniquets may lead to vascular damage or 
thrombosis. Soft tissue and nerve injury may also occur. 
Avoid these problems by: 

1. Exsanguinating the limb using an Esmarch bandage 

2. Applying the tourniquet cuff over soft padding at the 
appropriate site 

3. Inflating the tourniquet above the systolic blood 
pressure 

4. Recording the time when the tourniquet is inflated 
and not allowing it to remain inflated for more than 
2h. 

Diathermy 

Principles and effects 

A high frequency alternating current (AC) is passed 
through body tissue; where the current is locally concen- 
trated (a high current density), heat is produced, result- 
ing in temperatures up to 1000°C. Low frequency 
alternating current such as mains electricity (50 Hz), 
causes stimulation of neuromuscular tissue. The severity 
of the 'electrocution' depends on the current (amperes) 
and its pathway through the body. Five to ten milliamps 
(mA) can cause painful muscle contractions, while 
80-100 mA passing through the heart causes ventricular 
fibrillation. Increasing the current frequency reduces the 
neuromuscular response; at current frequencies above 
50 000 Hz (50 kHz) the response disappears. Surgical 
diathermy involves current frequencies in the range 
400 kHz to 10 MHz. Currents up to 500 mA may then be 
safely passed through the patient. Heat is produced wher- 
ever the current is locally concentrated. 



185 



17 




PREPARATIONS FOR SURGERY 




Fig. 17.1 Monopolar diathermy. 



diathermy an arc can be struck only between the 
limbs of the forceps. Increasingly, surgical dissection 
is now carried out with diathermy and harmonic 
scalpels. 

It will not work when a haemostat has grasped a 
vessel and is then touched with the active diathermy 
electrode. Bipolar current passes directly from one 
diathermy forceps limb to the other and no current 
passes through the tissue held by the haemostats. 



Monopolar and bipolar diathermy 

Monopolar diathermy is the most common configuration 
(Fig. 17.1). High frequency current from the diathermy 
generator (or 'machine') is delivered to an active elec- 
trode held by you. Current density is high where this 
electrode touches body tissue, producing a pronounced 
local heating effect. The current then spreads out through 
the body, returning to the diathermy generator through 
the patient plate electrode (incorrectly called the 'earth 
plate'). Having shaved an area of skin, make sure that the 
plate is in good contact over at least 70 cm 2 , and prefer- 
ably more than twice this area, to ensure that the current 
density at the plate is so low that there is minimal 
heating. 



I I Key point 

• Misapplication of the patient plate is by far the 
most common cause of inadvertent diathermy 
burns. 



Bipolar diathermy (Fig. 17.2) avoids the need for a plate 
and uses considerably less power. You hold forceps con- 
nected to the diathermy generator. The current passes 
from one limb of the forceps through the contained piece 
of tissue to be coagulated, and then back to the generator 
through the other limb of the forceps. This inherently 
safer system has not gained wide use for two main 
reasons: 

1 . It cannot be used for 'cutting' (see below), as this 
involves a continuous arc (spark) between the active 
electrode and the tissue involved. In bipolar 




Fig. 17.2 Bipolar diathermy. 



Cutting, coagulating and blend 

For cutting, the generator produces a continuous output, 
causing an arc to be struck between the active electrode 
and tissue and creating temperatures up to 1000°C. Cell 
water is instantly vaporized, causing tissue disruption 
with some coagulation of bleeding vessels. Coagulating 
diathermy current is a pulsed output resulting in desic- 
cation (Latin sicca = dry) and the sealing of blood vessels 
with the minimal tissue disruption. Most diathermy 
generators have a 'blend' facility, functioning only when 
in cutting mode, allowing a combination of cutting 
and coagulation waveforms, increasing the degree of 
haemostasis. 

Earth-referenced and isolated diathermy 
generators 

Earth-referenced generators. Older diathermy 
generators, some of which are still in everyday use, have 
valves and spark gaps to generate high frequency current. 
These unsophisticated circuits produce a wide frequency 
range, which includes frequencies above 1 MHz, and 
large earth leakage currents are unavoidable. The patient 
plate on these generators is earthed via a capacitor. The 
capacitor allows easy passage of high frequency current, 
such as in diathermy, but presents a large resistance to 
low frequency currents, such as mains electricity. (The 
patient is therefore not earthed for mains (50 Hz) current 
to reduce the risk of electrocution.) 

As long as the patient plate is correctly applied, the 
patient is kept at earth (zero) potential for alternate sites 
such as electrocardiogram (ECG) electrodes or a drip 
stand accidentally touching the patient's skin. 
Unfortunately, if the patient plate is omitted, or has 
become displaced, diathermy current will still flow 
(though a higher setting may be required) using the ECG 
electrodes or drip stand for the return pathway. An ECG 
electrode or drip stand presents skin contact of 1-5 cm 2 , 
so a severe burn is inevitable. 

Isolated generators. The more modern, often 
smaller, generators use transistors and 'solid-state' cir- 
cuitry to produce the high-frequency current. Sophisticated 
electronics result in a much tighter frequency range 



186 



OPERATING THEATRES AND SPECIAL EQUIPMENT 




17 



(400-600 kHz) and a considerable reduction in earth 
leakage currents. Some of these solid-state generators (but 
by no means all) are designated 'isolated': the diathermy 
circuit is not earthed. This type of generator is inherently 
safer than an earth-referenced machine. Diathermy current 
can only pass back to the generator via the patient plate; 
there is no pathway back via earth. If the plate is omitted, 
no current will flow. 



Safety 

General safety. Ensure that whenever electrical 
equipment is to be used on patients it meets the required 
safety standards and is properly maintained. Everyone 
using the equipment should be properly trained in its use. 
At the very least, you should read the user's manual: all 
diathermy machines are supplied with one. 

Responsibility. The decision about who has overall 
responsibility for surgical diathermy is often ignored until 
a diathermy disaster occurs. The diathermy is set up by 
nurses or operating department orderlies and the anaes- 
thetist is usually the only doctor present when the patient 
plate is applied. Few surgeons check the diathermy before 
use. 



e 



Key points 

• You are responsible for using this equipment 
correctly. Check the alarm wiring, the patient 
plate and its positioning before use. 

• Only the surgeon wielding the active electrode 
should activate the machine. 

• Always replace the electrode in an insulated 
quiver after use. 

• If diathermy performance is poor, carefully 
check the patient plate and lead rather than 
increasing the dial settings. 

Alarms. Monopolar diathermy depends on the 
patient plate for its safety. If the plate is not connected to 
the machine (plate continuity alarm), all diathermy 
machines in use will alarm when switched on; only a few 
possess an alarm system that ensures the plate is attached 
to the patient. Rigidly adhere to the safe, correct proce- 
dures: first connect the patient plate to the patient, 
connect the return lead to the plate, switch on the 
diathermy machine so the plate continuity alarm sounds. 
Only now is the return lead connected to the diathermy 
machine, thus silencing the continuity alarm. Never do 
this in the reverse order. At the end of every operation 
undo all these connections and switch off the diathermy 
machine. 



If the continuity alarm fails to silence, change the 
patient plate and lead first, not the machine. Some 
modern diathermy generators, such as the Eschmann and 
Valleylab, possess systems that monitor the patient-plate 
interface. These systems are explained in the user's 
manual. Never disregard these alarms - check the patient 
plate contact carefully. 

The patient plate. The most common cause of acci- 
dental diathermy burns is incorrect application of the 
patient plate. It may not be applied at all, but more often 
there is a failure to follow guidelines. Site the plate as 
close as possible to the operation site, while ensuring that 
diathermy current is moving away from ECG and other 
monitoring electrodes. Make sure that the area under the 
plate has a good blood supply to remove any heat gener- 
ated. Avoid bony prominences and scar tissue. The whole 
area of the plate must make good skin contact, so, shave 
hairy skin and ensure the plate is not kinked or crinkled. 
Do not allow skin preparation fluids to seep under the 
plate. 

The patient The second most common cause of 
diathermy burns occurs when the patient touches earthed 
metal objects such as drip stands, uninsulated 'screens' 
and parts of the operating table. These small skin contacts 
offer alternative return pathways for the diathermy 
current, and the local current densities may be sufficient 
to cause a burn. 

If you have used an alcohol-based skin preparation, it 
may pool, be ignited by the diathermy current and cause 
a fire. As a rule avoid such skin preparations. 



I I Key points 

• Beware of using diathermy on or inside the 
intestine - its gas contains hydrogen and 
methane, both are inflammable and explosive. 

• Beware of using diathermy on appendages 
such as salpinx or penis, or isolated tissue such 
as testis; high current density can persist 
beyond the operative site. 

• Remember that diathermy can damage other 
structures, such as sutures and endotracheal 
tubes and their balloons 

If a burn occurs. Diathermy burns are often poorly 
investigated and remain unexplained. Other skin lesions, 
such as chemical burns from preparation solutions or 
pressure sores, may masquerade as diathermy burns. 
Definite electrothermal burns usually occur because of 
lapses in procedure, rarely from faults in the diathermy 
machine. The operating theatre record for all patients sub- 
jected to diathermy should include the site of the patient 



187 



17 1 



PREPARATIONS FOR SURGERY 



plate; and when the plate and monitoring electrodes are 
removed the underlying skin should be inspected. If a 
possible burn is discovered, the patient and all attached 
equipment should remain in the operating theatre while 
you summon the electromedical safety officer. If the 
alleged burn is discovered after the patient has left the 
theatre, contact all those involved in the procedure and 
determine the precise arrangement of equipment and 
patient plate. All electrical equipment used should be 
tested, including the patient plate lead. 

Diathermy burns are usually full thickness and will 
require excision. Inform the patient of the misadventure. 

Diathermy and pacemakers. There are two poss- 
ible dangers: 

1 . The high frequency diathermy current may interact 
with pacemaker logic circuits to alter pacemaker 
function, resulting in serious arrhythmias, or even 
cardiac arrest. 

2. Diathermy close to the pacemaker box may result in 
current travelling down the pacemaker wire, causing 
a myocardial burn. The result will range from a rise 
in pacemaker threshold to cardiac arrest. 

For safe use of diathermy with pacemakers, contact a 
cardiologist and ask about the type of pacemaker, why 
and when it was inserted, whether it is functioning 
properly, and what the patient's underlying rhythm is, 
so you will know what will happen if the pacemaker 
stops functioning. 



bipolar diathermy to minimize spread of current and 
sparking. 




Key points 

• Avoid diathermy completely if possible. If not, 
consider bipolar diathermy. 

• If monopolar diathermy must be used, place 
the patient plate so that diathermy current 
flows away from the pacemaker system. 

• Use only short bursts, and stop all diathermy if 
any arrhythmias occur. 



Laparoscopic procedures. Sometimes the working 
space can be 'crowded', and inadvertent contact may be 
made between an instrument and the bowel, especially 
if there is contact between the electrode and another 
metal instrument, which is touching bowel. In a similar 
way, current can pass along an organ, which is resting 
against the gut, and pass out via the indifferent elec- 
trode. An adequate view, carbon dioxide pneumoperi- 
toneum, and use of well-insulated instruments should be 
the aim. Apply careful technique by avoiding excessive 
use of the diathermy, and 'tent' structures into space 
before applying current. Use lower voltage currents or 




Key point 

Ensure that the insulation of instruments is 
complete and undamaged, and avoid sparking 
between bowel wall and electrode. 



Lasers 

The laser is a device for producing a highly directional 
beam of coherent (monochromatic and in phase) electro- 
magnetic radiation, which may or may not be visible, 
over a wide range of power outputs. 

Laser is an acronym for Light Amplification by the 
Stimulated Emission of Radiation. This describes the prin- 
ciple of operation of a laser. Energy is pumped into the 
lasing medium to excite the atoms into a higher energy 
state to achieve a population inversion in which most of 
the atoms are in the excited state. A photon emitted as a 
result of an electron spontaneously falling from the excited 
to the ground state stimulates more photons to be emitted 
and lasing action starts. After reflection back and forth 
many times from a pair of mirrors at opposite ends of the 
resonant optical cavity containing the lasing medium, the 
number of photons is amplified, that is, the light intensity 
or power is increased. One of the mirrors is only partially 
reflecting and allows a small part of the laser light to 
emerge as the laser beam. The lasing medium is com- 
monly gaseous, such as argon or carbon dioxide, but may 
be crystalline, such as neodymium, yttrium, aluminium 
garnet (NdYAG). It is the lasing medium which deter- 
mines the wavelength emitted. It is mainly the wavelength 
of the laser which determines the degree of absorption in 
tissue. However, surgical applications also depend on the 
power density: the duration of exposure should be just 
sufficient to produce the required effect. Delivery systems 
are designed to allow the laser beam to be transported, 
aimed and focused onto the treatment site. Argon and 
NdYAG lasers, for example, are transmitted down fibre- 
optic cables to a slit lamp or into an endoscope. Carbon 
dioxide laser light is usually routed via a series of mirrors 
through an 'articulated arm', and thereafter through a 
micromanipulator attached to a microscope or colposcopy 

Types 

1 . Carbon dioxide infrared laser light has a wavelength 
of 10.6 |mm. It is invisible and is rapidly absorbed by water 
in tissue and has very little penetration. It is therefore 
useful for vaporizing the surface of tissue, and water or 



188 



OPERATING THEATRES AND SPECIAL EQUIPMENT 




17 



wet drapes can be used as a safety barrier. There is a very 

small margin of damaged tissue and healing is rapid, 
with minimal scarring. Treatment is relatively pain free. 

2. The NdYAG laser penetrates more deeply to 
3-5 mm. The wavelength is 1 .06 u.m and is in the invisible 
infrared light range. It is useful for coagulating larger tissue 
volumes and leaves behind an eschar of damaged tissue. 

Both the above types require a visible guiding beam 
which is usually a red helium/neon beam. 

3. Argon laser light is blue/green and hence absorbed 
by red pigment. The principal wavelengths are 0.49 and 
0.51 jjum. It is used principally in ophthalmology and 
dermatology. 

Clinical applications 

Gastrointestinal tract. The NdYAG laser is fre- 
quently used in the treatment of gastrointestinal pathol- 
ogy. It can be employed for vaporizing and debulking 
recurrent or untreated advanced oesophageal carcinoma. 
Its use is predominantly in fairly short malignant stric- 
tures and may be superior to intubation. However, 
expanding covered metal stents may well prove to be a 
better palliative alternative. Laser ablation is labour 
intensive and requires treatments every 6-8 weeks. This 
laser can be used for controlling gastrointestinal haemor- 
rhage from the stomach, oesophagus and duodenum, 
destruction of small ampullary tumours in the duodenum 
and palliative resection of advanced rectal carcinomas. In 
the future, photosensitization may prove to be of value. 
The use of lasers in laparoscopic surgery is, perhaps, less 
frequent at present. There is a risk of carbon dioxide gas 
embolism. 

Urology. The NdYAG laser can be used to treat low 
grade, low stage transitional cell lesions in the bladder and 
is suitable for treating outpatients under local anaesthetic. 
Here again, photosensitizing agents such as haematopor- 
phyrin (Hpd) may be used in conjunction with a laser light 
wavelength of 630 nm. The beam is directed at sensitized 
tissues which are then more easily destroyed. 

Ophthalmology. The NdYAG laser can be used to 
destroy an opaque posterior capsule during or following 
extracapsular cataract extraction. The argon laser may be 
employed for trabeculoplasty, to decrease intraocular 
pressure in patients with open-angle glaucoma. Laser 
photocoagulation is becoming standard treatment for 
patients with various retinal diseases such as diabetic 
retinopathy, and as a prophylactic measure in patients at 
risk from retinal detachment. Most ophthalmic photo- 
coagulators are argon lasers. 

Otolaryngology. A carbon dioxide laser may be 
used for haemostasis, removal of benign tumours and 
premalignant conditions. The argon laser has been used 
in middle ear surgery. 



Vascular surgery. Laser angioplasty (carbon dioxide, 
NdYAG and argon) has been used to vaporize atheroma- 
tous plaques. Only approximately 50% of patients benefit, 
and significant complications are reported, such as per- 
foration of vessel wall. 

Plastic surgery. Pulsed ruby lasers may be used to 
remove tattoos, and port wine stains selectively absorb 
the argon laser beam. The carbon dioxide laser may be 
employed to resect atretic bony plates in congenital bony 
choanal atresia. 

Gynaecology. There are several uses in gynaecology. 
Perhaps the most frequent is the treatment with a carbon 
dioxide laser of cervical and vulval precancerous lesions 
that have been identified by colposcopy. 



Classification 

Lasers are classified according to the degree of hazard: 

Class 1 (low risk). These are of low power and are 
safe. The maximum permissible exposure (MPE) cannot 
be exceeded. 

Class 2 (low risk). These are of low power, emitting 
visible radiation. They have a maximum power level of 
1 mW. Safety is normally afforded by natural aversion 
responses, such as the blink reflex. 

Class 3a (low risk). These emit visible radiation, 
with an output of up to 5 mW, Eye protection is afforded 
by natural aversion. There may be a hazard if the beam is 
focused to a point, as through an optical system. 

Class 3b (medium risk). These emit in any part of 
the spectrum and have a maximum output of 0.5 W. 
Direct viewing may be dangerous. 

Class 4 (high risk). These are high power devices 
with output in any part of the spectrum. A diffusely 
reflected beam may be dangerous and there is also a 
potential fire hazard. 




Key point 



Use high risk lasers with caution. Most medical 
lasers are in this class. 



Hazards 

The manufacturers are required to classify and label the 
product according to hazard level. 

1. Patient hazard: inevitably, burning of normal tissue or 
perforation of a hollow viscus may occur with 
increasing depth of treatment (e.g. perforation of 



189 




PREPARATIONS FOR SURGERY 



oesophagus) or damage to trachea or lungs during 
ear, nose and throat (ENT) procedures. 
2. Operator hazard: usually the operator is not exposed 
to laser beams, but if you are accidentally exposed, it 
is frequently your eyes or skin that are damaged. 
Always wear eye protection since some laser beams 
will penetrate, and be focused on, the retina. Corneal 
burns or cataract formation have also occurred with 
less penetrating beams. 

Safety measures 

1. There should be a laser protection advisor (LPA) to 
consult on the use of the instruments throughout the 
hospital and to draft local rules. 

2. A laser safety officer (LSO) should be appointed 
from the staff of the appropriate department using each 
laser. This person may well be, for example, a senior nurse 
and will have custody of the laser key. 

3. Everybody using the laser should be adequately 
trained in its use and be fully cognizant of all safety 
precautions. 

4. There should be a list of nominated users. 

5. A laser controlled area (LCA) should be established 
around the laser while it is in use, with control of 
personnel allowed to enter that area. The entrance 
should be marked with an appropriate warning sign, 
usually incorporating a light that illuminates while the 
laser is functioning. 

6. While in the laser controlled area adequate eye pro- 
tection, appropriate to the type of laser in use, must be 
worn. The laser should not be fired until it is aimed at a 
target, and usually there is an audible signal during laser 
firing. 

7. The laser should be labelled according to its classifi- 
cation. Lasers in classes 3a, 3b and 4 should be fitted with 
a key switch and the key should be kept by a specified 
person. The panels which constitute the side of the laser 
unit should have an interlocking device so that the laser 
cannot be used if the panels are damaged. 

There are various safety features that are required by 
way of shutter devices and emergency shut-off switches. 
Foot-operated pedals should be shrouded to prevent acci- 
dental activation. Medical lasers require a visible low 
power aiming beam, which may be an attenuated beam 
of the main laser, if this is visible, or a separate class 1 or 
2 laser, such as helium/ neon. The laser must be regularly 
maintained and calibrated. 

8. Environment: reflective surfaces should be avoided 
in the laser controlled area. However, matt-black surfaces 
are not necessary. Adequate ventilation must be provided 
and should include an extraction system to vent the 
fumes produced. These fumes are known as the Taser 
plume'. 




Key point 

• Pay particular attention to avoiding fire. Class 4 
lasers ignite dry drapes or swabs. Damp drapes 
effectively stop carbon dioxide laser beams. 

Fibre optics 

Flexible instruments 

Fibre optics have undoubtedly made an immense impact 
on patient management. There is little evidence, however, 
that the instruments that incorporate fibre optics neces- 
sarily reduce mortality. Their value is in allowing accurate 
diagnosis and assessment of, for example, upper gastro- 
intestinal bleeding or oesophageal obstruction. Most 
hollow viscera or tubes, even very narrow ones, may now 
be inspected. Diagnostic and therapeutic procedures can 
be performed under clear vision, such as exploration of a 
ureter for tumour or stone, or subfascial ligation of incom- 
petent perforating veins. Thin fibreoptic instruments are 
integral to the development of minimal access surgery, 
such as 5 mm telescopes used for retrieving bile duct 
stones. 

In the 1950s, Professor Harold Hopkins of Reading 
University, UK, developed the earlier work of John Logie 
Baird, the inventor of television, to further the design of 
fibreoptic bundles, which could not only transmit a pow- 
erful light beam but also, when suitably arranged, deliver 
an accurate image to the viewer. In the 1960s, urological 
instruments were developed incorporating multiple flex- 
ible glass-fibre rods. Each fine fibre rod is constructed of 
high quality optical glass and transmits the image, or 
light beam, by the process of total internal reflection. This 
principle allows light to travel around bends within the 
fibre. Each fibre is only 8-10 |xm in diameter, and to 
achieve the principle of total internal reflection it must be 
coated with glass of low refractive index, to prevent light 
dispersion. Many such coated fibres are bound together in 
bundles which can bend. For light transmission, fibres 
may be arranged in a haphazard manner (non-coherent). 
For clear-image transmission, the fibres must be arranged 
in a coaxial manner (coherent) (Fig. 17.3). The following 
are examples of currently available flexible endoscopes 
utilizing fibreoptic light bundles: 

• Oblique (for endoscopic retrograde cholangiopancre- 
atography (ERCP) and end-viewing gastroscopes 

• Laryngoscope 

• Bronchoscope 

• Fibreoptic sigmoidoscope and colonoscope 

• Cystoscope (pyeloscope) 

• Choledochoscope 

• Arterioscope. 



190 



OPERATING THEATRES AND SPECIAL EQUIPMENT 



17 




(a) 




(b) 

Fig. 17.3 (a) Non-coherent fibre bundles for light 
transmission, (b) Coherent fibre bundles for viewing. 
Reproduced from Ravenscroft & Swan (1984) by 
permission of Chapman & Hall. 



Each instrument has similar design principles incorpor- 
ating the following: 

• Coherent fibre bundles for high quality visual image 
transmission 

• Non-coherent fibreoptic bundles for light transmission 

• A lens system at the tip and near the eyepiece of the 
instrument 

• A proximal control system to manoeuvre the tip of the 
instrument and also to control suction and air/ water 
flow 

• Channels for blowing air or carbon dioxide and water 
down the instrument, and for suction - the latter 
doubles as a biopsy channel 

• A wire guide incorporated to control tip movement, 
which takes place in four directions, each usually 
allowing a deformity of greater than 180° movement 

• A cladding, consisting of a flexible, jointed construc- 
tion, covered by a tough outer vinyl sheath. 

Figures 17.4 and 17.5 show the basic structure of a typical 
endoscope, and Figure 17.6 shows the tip of an instru- 
ment, illustrating the lenses for light transmission and 
viewing, a suction channel, which should be large so it 
can be used in the presence of gastrointestinal haemor- 
rhage, and a small nipple directed over the lens, to enable 
the wash solution to clear the lens of debris. 

Light sources should emit a powerful beam and the 
intensity is usually 150 W. Many light sources employ a 
halogen bulb, which needs to be fan cooled. 

Rigid endoscopes 

Optical systems in rigid endoscopes also employ the prin- 
ciple of total internal reflection, but there are several lens 
systems in addition. The objective lens systems are nearest 
the image, and the relay lens systems are nearer the eye- 
piece of the rigid instrument, through which the observer 




Eye -piece 



External tight 
source 



Image guide 
(coherent bundle) 



Light guide 
(non-coherent 

bundle) 



Distal lip 




Fig. 17.4 Basic design of a fibreoptic endoscope. 
Reproduced from Ravenscroft & Swan (1984) by 
permission of Chapman & Hall. 




U 



M 



Fig. 17.5 Further details of the basic design of a 
fibreoptic endoscope. A, endoscopic 'umbilicus'; B, suction 
pump; C, air pump; D, water reservoir; E, endoscopic 
insertion tube; F, biopsy port; G, suction button; H, 
air/wash button; I, endoscope control head; J, combined 
suction biopsy channel; K, water channel; L, air channel; 
M, combined air/water port. Reproduced from Ravenscroft 
& Swan (1984) by permission of Chapman & Hall. 



191 



17 % 



PREPARATIONS FOR SURGERY 



B 




forcible distortion, dropping and, particularly, of crushing 
from biting by patients' teeth; always insert the peroral 
endoscope through a suitable mouth gag. Broken fibres 
appear as black dots when viewed through the instrument. 



Fig. 17.6 The top of an end-viewing fibreoptic 
instrument. A, forceps raiser; B, wash jet; C, image 
guide; D, light guide; E, biopsy/suction channel. 
Reproduced from Ravenscroft & Swan (1984) by 
permission of Chapman & Hall. 



views a rectified and magnified image. Light is transmit- 
ted through a cable of non-coherent fibres or liquid elec- 
trolyte solution. Vision is through coaxial fibres which 
direct the light coaxially through a lens system in the rigid 
tube. Some of the longer lenses are made of high quality 
optical glass and act as a single large optical fibre for 
image transmission. Examples of rigid instruments are: 

• Cystoscope, urethroscope, pyeloscope, urethroscope 

• Choledochoscope 

• Laparoscopes. 

The lenses at the far end of the instruments vary to allow 
different fields of view and minimize peripheral field 
distortion. 



Care of fibreoptic instruments 

1. They must be properly cleaned and disinfected 
before use. Debris may block channels and make suction 
and insufflation of air and liquid difficult. After use, the 
instruments should be cleaned internally by utilizing one 
of several automatic cleansing machines, and externally 
with a suitable detergent solution. 'Q-tips' may be 
employed to clean lenses. Instruments should be soaked 
for at least 5-10 min between patients, often in a 2% 
gluteraldehyde solution, although 70% alcohol and low 
molecular weight povidone-iodine are alternatives. 

2. In order to avoid instrument damage, endoscopies 
are usually performed in dedicated units under expert 
care. Damage is more likely to occur when a variety of 
people handle and clean instruments. Guard against 




Key point 

Ensure that only competent and careful people 
use and care for these expensive and valuable 
instruments. 



Autologous cell salvage 

With recent anxieties over transmitted disease, expense, 
religious views and the occasional scarcity of blood, autol- 
ogous (blood derived from the same individual) blood 
transfusion may be used. The advantages are consider- 
able: it avoids blood-related disease transmission, trans- 
fusion reactions, immnunosuppression and the need for 
grouping. A rapidly obtainable supply is available. The 
blood is collected via a sucker from the wound site, anti- 
coagulated, filtered and then passed through a washing 
phase, using saline. Washing removes all but the red cells, 
which are concentrated to an acceptable haematocrit and 
then reinfused. This technique is of particular use in car- 
diothoracic, vascular and orthopaedic surgery, especially 
when the loss of blood is expected to exceed 1 litre. It is a 
safe procedure provided you follow the rules. As a rule, 
do not use blood contaminated with septic fluids and 
malignant cells. Never use blood contaminated with bile, 
gut contents, meconium, urine or amniotic fluid. Cell 
salvage cannot be used if the blood is likely to mix with 
fluids which would lyse red cells, such as water, hydrogen 
peroxide, alcohol, povidone-iodine antiseptic, fibrin glue 
or antibiotics that are unsuitable for parenteral use. 
The alternative is predonation. 

Cryosurgery (syn. cryotherapy or 
cryocautery) 

Any application of an instrument that touches tissue at an 
extreme of temperature produces cell death. Cryosurgery 
(Greek kryos - frost) is the freezing of tissue to destruc- 
tion. Although cells are destroyed at -20°C, they may 
recover at higher temperatures than this. After freezing, 
the destroyed tissue sloughs off and reveals a clean, granu- 
lating base. The treatment is relatively pain free and 
minimizes blood loss. The object is to destroy abnormal 
tissue and preserve adjacent, healthy areas. You achieve 
this by producing an ice ball at the tip of a cryoprobe 
(Fig. 17.7). You must watch the size of the resulting ice 
ball, to control the volume of tissue destroyed. The size of 



192 



OPERATING THEATRES AND SPECIAL EQUIPMENT 




17 




Fig. 17.7 An ice ball at the tip of a cryoprobe. 
Reproduced by permission of Eugene A. Felmar, Santa 
Monica Hospital Medical Center, USA. 



the lesion produced by cryosurgery is related to the tem- 
perature at the tip of the ice probe, the size of the tip and 
the number of freeze-thaw sequences. The size of the 
iceball increases until the heat loss at the edge of the 
iceball is too small to permit further freezing of adjacent 
tissues. The size of an iceball and the extent of destruction 
can then be increased by a further freezing sequence. As 
a rule, allow the iceball to spread 2-3 mm into healthy 
tissue to ensure adequate destruction of the diseased area. 
Inevitably freezing a wart on the sole of the foot is less 




Fig. 17.8 Cross-section of a cryoprobe tip, illustrating 
the Joule-Thompson principle. Reproduced by 
permission of Eugene A. Felmar, Santa Monica Hospital 
Medical Center, USA. 



critical than reattaching a retina. Various probe tips are 
available for the different tasks demanded of cryosurgery. 

Principles of therapy 

According to the Joule-Thompson principle, when gas 
expands, heat is absorbed from the surrounding matter. 
The simplest example of this is spraying ethyl chloride 
vapour on skin, which, as it releases gas, subsequently 
freezes. With a cryoprobe, however, the liquid gas, 
usually nitrogen or carbon dioxide, is sprayed against the 
inside of a hollow metal probe. The gas then expands in 
the tip and freezes the tissue on contact (Fig. 17.8). 

Cell injury with cryotherapy 

1 . Immediate phase: ice crystals form in the cell, 
rupturing the cell membrane. This is most effective 
with rapid freezing at greater than 5°C s^ 1 . 

2. Intracellular dehydration: results in increased and toxic 
levels of intracellular electrolytes. 

3. Protein denaturation: occurs in the lipoprotein 
structure of the cell membrane, nucleus and 
mitochondria. 

4. Cellular hypermetabolism; results in enzyme inhibition. 

Later in the course of injury there is also a loss of blood 
supply, causing tissue necrosis, and the resultant slough, 
before separation, protects the tissues deep to the injury. 
When the slough separates it leaves a clean ulcer. 

As nerve endings are susceptible to cold injury, painful 
lesions can be rendered insensitive. Also, the treatment is 
not particularly painful for the patient, and local analgesia 
is usually unnecessary. Adjacent neurovascular structures 
are relatively safe, as collagen and elastic tissue resist freez- 
ing. Thus, the advantages of cryotherapy are that it is a rela- 
tively pain-free and simple method of destroying tissue, 
usually leaving clean wounds, often with a reasonable scar. 

The disadvantages of the technique are that frozen 
tissue cannot be analysed histologically, and thus this 
method of treatment is unsuitable for any lesion for which 
you will require microscopic examination. It may some- 
times be difficult to gauge the exact penetration in the 
depth of the tissues treated. Thus, its use may be limited 
in curative treatment of malignancy, and is of value in pal- 
liation. Occasionally there is some bleeding, and later dis- 
charge after the slough separates following, for example, 
cryosurgical treatment of haemorrhoids. 

Clinical applications 

Since there are various shapes of probe tips, a reasonable 
variety of therapeutic applications is available. To 
ensure that freezing occurs, there must be a wet contact 



193 



17 



PREPARATIONS FOR SURGERY 



to allow thermal conductivity. Two or three freeze-thaw 
cycles may be applied with overlap of the treated areas 
if necessary. 

Examples of the clinical application of cryosurgery 
include the following: 

• Proctology: haemorrhoids and warts 

• Gynaecology: cervical erosions and warts 

• Dermatology: warts, low grade skin cancers, herpetic 
lesions 

• ENT: pharyngeal tonsillar remnants, carcinoma of the 
trachea, hypophysectomy 

• Ophthalmology: cataract extraction, glaucoma, 
detached retina 

• Neurosurgery: Parkinson's disease and cerebral 
tumours. 

Microwave ablative techniques 

You can use this technique on prostatic tissue, for benign 
prostatic hypertrophy, and the endometrium - usually for 
menorrhagia. The principle of treatment depends on the 
transfer of energy by the use of microwaves, which are a 
form of electromagnetic energy. Penetration depths depend 
on the electrical properties of the tissues, and the frequency 
of the electromagnetic wave. Conventional microwave 
kitchen ovens use energy at a frequency of around 
2.45 GHz, which, in tissue with a high water content, 
would penetrate to a depth of approximately 18 mm. The 
microwave applicator has a strength of 9.2 GHz, uses 30 W 
of power and the treatment takes about 2-4 min. For 
endometrial ablation performed under general or regional 
anaesthesia, the cervix is dilated, the length of the uterine 
cavity is measured, and the calibrated and non-adherent 
probe is inserted to the fundus and withdrawn with 
side-to-side movements. Temperature measurement is 
monitored and probe temperatures of 80-95°C are reached 
to ablate the endometrium to a depth of 4-6 mm. 
Interestingly, with this range of endoluminal temperature, 
there is little serosal heating. 

This treatment may be safer than endometrial resection 
and hysterectomy, as there are fewer complications. The 
few serious complications of the procedure have been 
endometritis, cervical splitting during dilatation, and in one 
instance perforation of a retroverted uterus. There are other 
methods of endometrial ablation. This is merely used as an 
example of microwave energy, and you should not confuse 
it with radiofrequency endometrial ablation (RAFEA). 

Ultrasound 

Diagnostic 

Ultrasound probes provide a valuable aid during abdomi- 
nal surgery to identify tumour deposits and anatomical 



landmarks such as blood vessels. Clear guidance may be 
obtained as to the resectability of tumours or the presence 
of clinically undetected metastatic deposits. Hand-held 
ultrasound probes can be employed at open operations; 
for example, small islet cell tumours of the pancreas may 
be located accurately. 

Small laparoscopically inserted instruments are also 
used for staging and anatomical purposes when per- 
forming operations with minimal access (see Ch. 23). 
They compensate to some extent for the inability to 
palpate structures. During laparoscopic cholecystectomy, 
a probe may be used not only to identify structures but 
also to locate common bile duct stones. 



Surgical aspirator 

There are various ways in which the liver parenchyma 
may be dissected with minimal blood loss. One of these 
is the CUSA (Cavitron UltraSonic Aspirator). The oper- 
ating titanium tip of the instrument vibrates longitudi- 
nally at 23 000 oscillations per second (23 kHz). The 
instrument works by converting electromagnetic energy 
to mechanical movements. An electrical coil wrapped 
around metal laminations sets up a magnetic field, thus 
causing the metal to vibrate. The fine hollow tip of the 
instrument disrupts solid parenchyma by its fine vibra- 
tions and the heat this generates. When debris is shed, it 
is mixed with fluid jetting from the instrument and the 
mixture is sucked away. More solid and fibrous struc- 
tures, such as ducts and blood vessels, are not disrupted, 
and may then be clipped with haemostats or ligated. Not 
only may this instrument be useful for open, solid 
parenchymal dissection, but it may also be used during 
laparoscopic dissection of the gallbladder or mobiliz- 
ation of the colon. 



Ultrasonic harmonic scalpel 

Increasing use of this instrument attests to its ability to aid 
safe, careful dissection with less bleeding than accompa- 
nies diathermy dissection. The instrument works by 
transforming electrical energy from a generator into 
mechanical energy through a set of piezoelectric ceramics, 
which are contained in a hand piece. The mechanical 
energy is passed through a disposable element, often a 
hook or clip, which vibrates at approximately 55.5 kHz. 
The energy spreads a small distance around the instru- 
ment tip. The extreme vibrations fracture internal cellular 
bonds. Proteins are denatured and reorganize to form a 
sticky coagulum. Vessels up to 2 mm in diameter can be 
safely divided. Soft tissue coagulation occurs at tempera- 
tures below 100 S C, producing minimal charring and 
smoke or vapour. 



194 



OPERATING THEATRES AND SPECIAL EQUIPMENT 




17 



A real advantage of this equipment is that it reduces the 
number of instrument changes during an operation, such 
as haemostats, staples, scissors and ligatures. It is a mul- 
tifunctional instrument facilitating precise cutting with 
minimal lateral thermal damage. It does not use electric- 
ity, with all its potential risks. It was introduced in the 
mid-1990s and is used in, for example, the specialities of 
gastrointestinal surgery, gynaecology, urology and oto- 
laryngology. Do not use it for incising bone or for contra- 
ceptive tubal ligation. 

The harmonic scalpel system is valuable for soft tissue 
incisions where you require good haemostasis and 
minimal thermal injury. The instrument can be used for 
open or laparoscopic surgery as an adjunct to, or substitute 
for, diathermy, lasers or steel scalpels. 

Argon beam (plasma) coagulator (Valleylab) 

This instrument offers a thermal technique for sealing 
blood vessels from large, raw areas such as the cut surface 
of the liver and kidney. It works by passing an electrical 
current through what is called a "plasma arc', created in 
argon, not air. When electrons are fired into the gas, ion- 
ization occurs, which in turn produces further electrons. 
These then ionize more gas and a "domino" effect takes 
place. The plasma thus consists of free electrons, positive 
ions and neutral atoms (Fig. 17.9). 

The coagulator can be valuable in controlling bleeding 
resulting from coagulation disorders. It applies a direct, 
high frequency electric current to the target tissue without 
direct contact. The effect is well defined and has a self- 
limiting depth of penetration. There is minimal charring 
of the treated tissues, producing a thin and flexible eschar. 
As a result there is a minimal tendency for rebleeding. 
Because there is no contact between the instrument and 
the coagulated area, the coagulum is not pulled off and so 
is unlikely to rebleed. The tissue which has been treated 
by this technique develops a spongy appearance and 
enlarges the tissue surface. 

X-rays 

Preoperative findings 




Key point 

• It is negligent and dangerous to start an 
operation without having available all the 
radiological results and films (see Ch. 4). 

Place essential films, with the names, date and hospital 
number checked, correctly orientated, on the screen so 
you can refer to them as necessary. 



Gas no22ie 
Electrode— 



Argon gas arc 



Tissue target 




Fig. 17.9 Argon-enhanced coagulation. This is in effect 
a bipolar diathermy with the pathway from the active 
electrode to the tissue completed through argon gas. An 
arc or beam is produced with argon gas from the 
nozzle, which makes contact with the target tissue. 
Electrons are fired into it from the electrode, producing 
ionization, which, in turn, produces further electrons; 
these produce more ionization and so generate a 
domino or self -generating effect. The plasma arc is thus 
partly converted into positive ions and free electrons - 
in effect passing a current without instrument contact. 
The conventional active diathermy electrode adheres to 
the coagulum and may pull it off as it is withdrawn. The 
argon beam carrier overcomes this disadvantage, as 
there is no physical contact with the tissue coagulum. 
Capital letters indicate argon gas; capital letters such as 
+A+ indicate ionized argon, o- indicates electrons. It 
overcomes the disadvantage of adherence of the active 
diathermy electrode to the tissue coagulum. 



Intraoperative procedures 

Diagnostic help. An example is on-table cholan- 
giography. Use sufficiently dilute contrast medium to 
allow one to 'see through' the common bile duct on the 
film. Fill the biliary tree adequately to show the main 
intrahepatic ducts as well as the common bile duct. 
Contrast medium is heavier than bile and tends to gravi- 
tate to dependent ducts. If the ampulla is patent, contrast 
medium flows into the duodenum, which is clearly recog- 
nizable by its mucosal pattern. Remember to put a 20° 



195 




PREPARATIONS FOR SURGERY 



lateral tilt on the table to eliminate the overlap of contrast 
on the vertebral column. 

Intraoperative angiography can be performed follow- 
ing a steady intra-arterial injection, and provides ade- 
quate films. Adverse reactions to modern contrast media 
when the patient is generally anaesthetized are very rare. 

Therapeutic use. Imaging using fluoroscopy may facil- 
itate therapeutic procedures. It is valuable for simple pro- 
cedures, including fracture reduction. Complex techniques 
include interventional uroradiology. Many of these tech- 
niques can be performed either in the operating room or in 
the X-ray department; facilities for fluoroscopy are usually 
better in the X-ray department, but asepsis is better in the 
operating theatre. X-ray machines are difficult to clean and 
are potential sources of crossinfection. In specialist centres, 
dedicated complex X-ray rooms may be organized in a 
fashion similar to operating theatres, or the facilities for 
radiology may match those in the X-ray department. 




Key points 

• Discuss problems beforehand with a radiologist 
and subsequently report the outcome and 
anatomical findings. 

• Give adequate warning to the radiographer of 
the need for X-rays in the operating theatre. 



Equipment 

This is more likely to be mobile than static. The use of 
image intensification avoids the need for you to allow 
your eyes to become dark-adapted. Mobile image inten- 
sifiers for use in the operating theatre are mounted on a 
small C-arm. The table top must be radiolucent, with 
space beneath as well as over the table for the X-ray tube 
and the image intensiner. If films alone are required, the 
table top must have a 'tunnel' that admits the X-ray cas- 
sette beneath the patient. Alternatively, the cassette may 
be draped in sterile towels. This may be necessary, for 
example, if you need to carry out intraoperative mesen- 
teric angiography on bowel lifted out of the abdomen at 
laparotomy. For a small field, the X-ray cassette can be 
placed on the image intensifier itself to obtain a film. 
Some modern machines can produce dry silver images 
directly from the television monitor. 

Biplane screening is not usually available in the oper- 
ating theatre. The mobile C-arm is, nevertheless, quite 
versatile and the effect of 'parallax' can be used to aid the 
judgement of depth. 

Mobile X-ray sets operate from designated 13 A sockets 
that are on a separate ring main from other essential 
equipment. Modern mobile sets use 'sparkless' switching 
to avoid the danger of igniting inflammable gases. It is 



desirable to keep the mobile X-ray machine in the 
operating suite. 

X-rays and the law 

X-rays, as well as scalpels, become weapons of assault if 
not used with care. Medical staff clinically directing 
examinations employing ionizing radiation are required 
to have obtained a certificate demonstrating that they 
have received some training in radiation protection. This 
should eventually be included in the undergraduate cur- 
riculum. Equipment must be regularly serviced and cali- 
brated, and 'local rules' applied. In case of doubt, contact 
the hospital radiation protection supervisor. 




Key points 

• Only radiologists, radiographers or others 
holding an approved qualification may direct 
exposures. 

• Look after yourself, other staff in the theatre 
and the patient. Use the lead aprons. 

Safety 

• Remember that the patient 'scatters' the X-ray beam. 
The inverse square law applies, so staff should not be 
unnecessarily close. Be aware of the screening time and 
record it. 

• Do not X-ray the abdomen of pregnant patients unless 
absolutely necessary. Establish the date of the last 
menstrual period before the patient is anaesthetized. 




Key point 



• Take an interest in imaging, as 'a picture is 
worth a thousand words'. 

Microscopes 

Spectacles have been available for nearly 700 years and 
the compound microscope for about 300 years, but it was 
only 70 years ago that a microscope was used in theatre, 
and only 30 years ago that its use became more 
widespread. Although they were introduced very gradu- 
ally to the operating theatre, they have now become indis- 
pensable in a wide variety of surgical fields. They offer 
improved views of the surgical field, more precision, 
greater flexibility, and less trauma to delicate tissues. They 
provide good stereoscopic appreciation of depth, through 
a narrow surgical approach, much smaller than your own 
unaided interpupillary distance allows. 



196 



OPERATING THEATRES AND SPECIAL EQUIPMENT 



17 



A Swedish otolaryngologist, Nylen, introduced his 
monocular microscope in the surgical treatment of 
otosclerosis in 1921. A year later his chief, Professor 
Holmgren, used a binocular microscope for the same 
condition. In 1925, Hinselman used a microscope for 
colposcopy, but aside from this for three decades 
otolaryngologists alone continued to use microscopes. In 
Chicago, Perritt used a microscope for ophthalmic 
surgery in 1950, and Zeiss started to mass produce their 
Mil surgical microscope in 1953. Clinical applications 
then expanded: Jacobson in vascular surgery in 1960; 
Kurle in neurosurgery and Burke in plastic surgery in 
1962. With the increased employment of free transfer flaps 
and microvascular anastomosis, the use of the operating 
microscope reaches several surgical disciplines. 

Features of an operating microscope 

• Eyepieces provide an adjustment for interpupillary dis- 
tance and each eyepiece has a range of 5 dioptres. 

• Binocular tube may be straight or inclined. 

• Beam splitter allows for the connection of extra viewing 
tubes for observation and assistance. It also makes the 
use of still and video cameras possible as teaching aids. 

• Magnification system. Magnification is available as a 
galilean system, variable in steps (e.g. x6, xlO, x25, x40), 
or as a zoom system. 

• Objective lens allows the working distance to be altered 
by changing lenses with variable focal lengths. For 
example: 

for ophthalmology and plastic surgery 
for otology and vascular surgery 
for gynaecological tubal surgery 
for neurosurgery 
for laryngoscopy. 
Depth of field. The stereoscopic depth of field is less at 
higher magnification. Focus at higher magnification 
first, then reduce to the working magnification so as to 
have the best focus at the centre of the depth of field. 
Light . A powerful coaxial halogen light is incorporated 
in the body of the microscope. Oblique light is available 
for eye surgery. 



Instruments used with microscopes 

Each speciality has developed microsurgical instruments 
for its own needs; however, the following basic instru- 
ments are common to many specialities: 

* Spring-handled needle holder such as Borraquer or 
Castrovieso, ophthalmic. 

• Spring-handled microscissors, straight or curved. The 
straight are for cutting vessels and the curved for 
cutting tissue and thread. 



/= 150, 175, 200 
/=250 

/ = 250 or 300 
/ = 300 or 400 
/=400 



• Jezvellers' or watchmakers' forceps in a wide variety 

• Microsurgical clips such as Scoville— Lewis, or fine 
Heifetzs neurosurgical clips, can be used for vessel 
anastomosis. 

• Microelectrode: monopolar or bipolar cautery is 
necessary. 

• Suture material: (1) blood vessel anastomosis: 9/0 or 
10/0 nylon on a 3-6 mm needle with a tapered end; 
(2) nerve anastamosis: as above, but the needle has a 
cutting point; (3) fallopian tube work: 7/0 or 8/0 
absorbable non-reactive suture with a 4 mm or 6 mm 
reverse cutting needle. 

• Sterilization: sterile rubber cups or drapes are available 
to cover the controls. 

• Adjustment: versatility in position demands several 
interlocking arms and counterbalanced vertical move- 
ment, as well as a geared angled coupling between the 
microscope carriage arm and body. This enables you to 
swing the microscope from side to side while mounted 
in an oblique axis. 

• Mounting: can be on a solid, well-balanced mobile 
floor stand, or a fixed ceiling mounting. Wall-mounted 
microscopes are also available. 

Control of tremor 

Counteracting surgical tremor is of vital importance. The 
instrument or the limb on which it is held must be firmly 
supported as close to the point of work as possible. 

The future 

The combination of the laser with a micromanipulator to 
the objective lens of the microscope will enhance the use 
of both instruments in the future. 



Summary 

• Are you familiar with the requirements of 
behaviour and technique to obviate 
operating room infection? 

• Have you learned the methods of 
positioning and moving unconscious 
patients to avoid injuring them? 

• Do you accept that you are in charge of 
the tourniquet, diathermy, laser, cryoprobe 
and X-rays in theatre? 

• Will you lead by example in the operating 
room, by adopting careful and responsible 
attitudes to delicate and potentially 
dangerous equipment? 



197 




PREPARATIONS FOR SURGERY 



ACKNgwyyg^ 






I am deeply grateful for help with writing this chapter to: 
Mr John Bancroft for the diathermy section; Dr David 
Parker for the section on X-rays in theatre; Mr Derry 
Coakley for the section on microscopes; and to my wife 
for her help in the section on lasers. I should also like to 
thank Miss Sharon Langford for typing the manuscript. I 
am grateful to Ethicon Endosurgery (a Johnson & Johnson 
Company) for information on the Harmonic Scalpel 
System; to the Microsulis Group for data on their 
Microwave Endometrial Ablation System; to Frigenis for 
help with the Autologous Transfusion Cell Salvage 
System; and to Valley lab for guidance on the use of the 
argon beam coagulator. 




Further reading 

Brigden RJ 1988 Operating theatre technique, 5th edn. Churchill 

Livingstone, Edinburgh 
Douglas DM (ed.) 1972 Surgical departments in hospitals: the 

surgeon's view. Butterworth, London 
Johnston IDA, Hunter AR (eds) 1984 The design and utilization 

of operating theatres. Edward Arnold, London 



Cell salvage 

Duguid JKM 1999 Review. Autologous blood transfusion. 
Clinical and Laboratory Haematology 21: 371-376 

Diathermy 

Dobbie AK 1974 Accidental lesions in the operating theatre. 

NAT News December 
Earnshaw JJ, Keene TK 1989 Gastric explosion: a cautionary 

tale. BMJ 293: 93-94 
Editorial 1979 Surgical diathermy is still not foolproof. BMJ 

12: 755-758 
Pearce J A 1986 Electros urgery. Chapman & Hall, London 

Fibre optics 

Ravenscroft MM, Swan CMJ 1984 Gastrointestinal endoscopy 

and related procedures - a handbook for nurses and 

assistants. Chapman & Hall, London 

Lasers 

1982 General guidance on lasers in hospitals. Medical physics 
and bioengineering working group. Welsh Scientific Advisory 
Committee (WSAC) 

1983 Guidance on the safe use of lasers in medical practice. 
HMSO, London 

Murray A, Mitchell DC, Wood RFM 1992 Lasers in surgery - a 
review. British Journal of Surgery 79: 21-26 

Microscopes 

Taylor S 1977 Microscopy. Recent advances in surgery. Churchill 
Livingstone, Edinburgh, ch. 8 

X-rays 

Ionizing radiation regulations 1985, 1988 
Mound RF 1985/1988 Radiation protection in hospitals 
(Medical Sciences Series). Adam Hilger, Bristol 



198 




Adjuncts to surgery 



A L G. Peel 




Objectives 

Recognize the importance of good theatre 

management. 

Ensure basic understanding of usage and 

care of theatre instruments, accessories 

and special equipment. 

Appreciate the place of implants and tissue 

glues in modern surgical practice. 




INTRODUCT^ 

In health service economics an operating suite requires 
large capital and revenue budgets and this is favourably 
influenced by careful management of utilities. Good 
care of quality instruments ensures their long use; 
appropriate ordering and stocking means the shelf-life 
of equipment is not exceeded; wastage due to change in 
practice is reduced to a minimum; and storage space is 
efficiently used. The avoidance of an unnecessarily wide 
range of equipment and materials allows better use of 
capital. 

From the medicolegal aspect, the establishment of 
simple protocols aids efficient management within the 
theatre complex and helps to reduce errors, such as break- 
downs in sterility or retention of swabs or instruments in 
patients. 

A practical example of the rapidly changing scene in 
surgical practice is illustrated by orthopaedic surgery, 
where considerable expansion has occurred, particularly 
in prosthetic joint replacement, and in this field infection 
can result in very costly failure in terms of patient 
morbidity and financial implications to the health 
service. 

In the attempt to 'abolish' infection to elective 
orthopaedic surgery the following factors are considered 
important. 



Patient screening for occult infection 



Give particular attention to: 

• Possible urinary tract infection in females 

• Carrier status - postpone elective surgery until 
pathogens are eliminated, for example nasal 
Staphylococcus aureus. 



THEATRE MANAGEMENT 






1. Orthopaedic theatre should be dedicated to 'clean' 
orthopaedics, where no dirty or contaminated orthopaedic 
operations and no general surgery is carried out. 

2. Clean air enclosures. The routine use of clean air 
enclosures has reduced the infection rate in prosthetic 
joint surgery of hip and knee by more than half compared 
with conventionally ventilated theatres. Unidirectional 
air systems, especially with a downflow direction, 
reduces bacteria-carrying particles from 400-500 nrf 3 to 
30-40 m" 3 . Power tools produce additional problems 
because they create an aerosol spray, which effectively 
disseminates bacteria and viral particles. 

3. Theatre gowns. Airborne bacterial dispersion can be 
further reduced by the use of appropriate fabric clothing. 
It is not widely appreciated that, in either conventional or 
unidirectional airflow theatres, the use of disposable fabric 
gowns alone in lieu of cotton gowns has not achieved a 
significant reduction in bacteria-carrying particles. 




Drawbacks to conventional clothing 

Bacteria from you, the surgeon, tend to be 
pumped by air through or out of cotton 
pyjamas and gowns into theatre air. 
Bacteria from you are drawn through wet 
clothing by capillary action, contaminating the 
sterile operative area. 
Contamination of you with patient's fluids. 



199 



18 




PREPARATIONS FOR SURGERY 



Alternative clothing 

It has been stated that pharmaceutical manufacturing 
areas would be closed down if they used clothing cur- 
rently worn in the majority of operating rooms. The 
choice includes: 

• The total exhaust gown, developed by the outstanding 
orthopaedic surgeon Sir John Charnley, which is well 
established for clean orthopaedic surgery. 

• Disposable non-woven clothing such as Sonta (manu- 
factured by DuPont Ltd), which has been shown to be 
effective. 

• Breathable plastic membrane clothing which requires 
seals at the neck and trouser openings, with the result 
that the wearer soon becomes hot and uncomfortable. 

• Close woven polyester or polycotton fabrics which are 
expensive but represent a significant improvement 
over conventional garments. The cost must be 
equated with the significant costs of morbidity from 
infection. 



Theatre technique 

1 . Make sure you 'scrub up' in the prescribed manner. 
Protect your skin 'envelope'; gently scrub your nails 
but wash the remainder of skin with a suitable agent 
such as 20% chlorhexidine gluconate solution (e.g. 
Hibiscrub) or 10% aqueous povidone-iodine 
solution (e.g. Betadine) starting from fingertips, 
washing proximally avoiding subsequent 
contamination. 

2. Use closed gloving technique. 

3. Double glove when carrying out orthopaedic implant 
procedures or when using power tools. 



wm*> 



Key points 



• If your gloves become contaminated or pierced, 
change them. 

• At the conclusion of the operation check your 
gloves carefully before removing them. You 
may have sustained an unnoticed needlestick 
injury. 



DMSSII^ 

Make sure you appreciate why you are applying dress- 
ings, what you expect from them and how often they 
should be changed. 



1. If you have closed the wound and it is sealed and 
dry, a dressing may be unnecessary or be merely collo- 
dion, modern plastic spray or adherent plastic strip. 

2. For acute open wounds that are not contaminated 
the best dressing is closure by suture, flaps, grafts 
or temporary synthetic non-adherent non-allergenic 
dressings. 

3. Open wounds that are producing exudate require 
absorbent dressings. If these become soaked through to 
the surface, bacteria may penetrate through from the 
surface. Consequently, ensure that the absorbent dress- 
ings are changed regularly. Tulle (net - named after 
the French town near Limoges) of paraffin gauze or 
plastic, sometimes containing a bacteriocidal, such as 
chlorhexidine or povidone-iodine, may be applied to 
allow exudate to pass through it. The exudate can be 
absorbed into dressings placed on the tulle. Some starch- 
containing hydrogel dressings also absorb exudate. 
Hydrocolloid seals the wound, provides a moist 
environment and can be left for up to 1 week. Bead 
dressings also absorb exudate. Plastic foam can be cut 
from a sheet or poured in to set, creating a shaped filling 
for a defect. 

4. Infected wounds need bacteriological assessment, 
careful debridement of all dead tissue, and in some cases 
the application of appropriate substances or dressings. 
Eusol (Edinbugh University solution of lime) was for- 
merly popular but is now discouraged as damaging to 
tissues. Normal saline dressings, sodium hypochlorite 
solutions and hydrogen peroxide solutions may be 
applied. 

5. For the treatment of slow-healing wounds, topical 
negative pressure has been tried over an open cell foam 
dressing or saline-moistened dressing. A negative pres- 
sure of 125 mmHg can be exerted continuously for 48 h 
and then intermittently. 

6. A wide range of materials and substances is now 
available for managing chronic wounds. Of course, you 
must first exclude an underlying cause and ensure that 
the blood supply and oxygenation are satisfactory. Apart 
from skin grafts or flaps, biological techniques in use 
include: 

a. Growth factors 

b. Hyperbaric oxygen 

c. Allograft skin - prepared from porcine skin 

d. Amniotic membrane, which is thought to entrap 
inflammatory cells 

e. Chitosan - prepared from the chitin of organisms 
with an exoskeleton, used as an occlusive dressing 

f. TransCyte - human newborn fibroblasts cultured on 
nylon mesh 

g. Procuren - prepared from the patient's own blood 
platelets to stimulate wound healing. 



200 



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ADJUNCTS TO SURGERY 



18 



INSTRUMENTS 

Surgeons and instrument makers have combined to 
produce a wide range of instruments. Some, such as 
certain scissor forceps and retractors, may be used in 
several different fields of surgery. Others have more spe- 
cific functions, for example, those used in anal surgery, 
such as Park's anal retractor and Lockhart-Mummery 
fistula probes. Consider what your requirements are for 
instruments and appreciate the range and potential of dif- 
ferent instruments. One advantage of a training rotation 
scheme is that it allows you to experience a number of 
surgical disciplines and permits you to observe instru- 
ments being used in a variety of procedures. You can then 
reapply this knowledge to particular problems in what- 
ever field you subsequently work. 

Instruments are a sound investment; whenever possible 
use those of the highest quality. Of equal importance is the 
investment in maintenance care, mechanical and chemical 
cleansing, particularly of hinge joints, adjustment of mis- 
alignment and regular sharpening of cutting instruments. 
Although you cannot control the maintenance, you do 
have a responsibility to avoid damage to the instruments 
by not dropping them or using them inappropriately 

Sterilization 

The majority of instruments are autoclaved (moist heat 
under pressure for a prescribed time) and this process 
needs constant monitoring, with care in the packing of the 
autoclave and verification that the temperature, pressure 
and time are correct. 

Where steam autoclaving is impracticable and may 
cause damage, alternatives include (see Ch. 19): 

• Formaldehyde autoclave. 

• Ethylene oxide. 

• Gluteraldehyde 2% solution with prolonged immer- 
sion. It is rendered ineffective by organic debris. The 
substance is toxic and causes skin irritation so the pro- 
cedure must be carried out in a well-ventilated room. 
Alternatives are being developed. 

• 7-Irradiation, widely used for the commercial steriliza- 
tion of plastic instruments. 

Instrument sets 

It is advantageous to have the instruments required for a 
particular surgical procedure packed and sterilized in a 
single set. As far as possible, each type of instrument 
should be included in multiples of five. Each design or 
size of artery forceps is grouped in separate fives or tens, 
scissors of differing size and design are grouped in fives. 



A standardized typed, numbered, contents list is included 
in the sterilized set for each operation. This reduces the 
number of single-packed instruments that need to be 
opened and, more importantly, simplifies the instrument 
count at the beginning and end of each procedure. 

Develop a close liaison with the central sterile supply 
department (CSSD) and theatre management to ensure 
adequate supplies of trays to meet the demands of a full 
schedule of operating lists. The organization is put 
particularly under strain when carrying out many minor 
procedures with a quick turnover. 



LIGATURES, SUTURES, STAPLES AND 

CLIPS_ „_____„ „„„,__,__.„„.„.._,„ 

When selecting a ligature or suture, consider several 
factors with regard to the material itself. 

1 . Is the material to be absorbed? Catgut has been with- 
drawn because of fears that it may contain prions (coined 
from 'protein')/ which are inheritable or mutant, transmit- 
table 'rogue' proteins associated with, in particular, bovine 
spongiform encephalopathy (BSE) and scrapie in sheep. 
New synthetic materials are absorbed more reliably than 
formerly, so the strength remains long enough for healing 
to be well advanced before a suture is absorbed. In some sit- 
uations, absorbable sutures have replaced non-absorbable 
threads; for example, abdominal wounds are often closed 
using reliable, slowly absorbed, synthetic sutures. The syn- 
thetic threads may be monofilamentous, such as polydiox- 
anane (PDS), polyglyconate (Maxon) and glycomer 631 
(Biosin), or multifilamentous, such as polyglactin (Vicryl), 
poly gly colic acid (Dexon) and lactomer 9-1 (Polysorb). 

2. Non-absorbable natural threads, such as silk and 
linen, are still used. Polyesters, polypropylene and 
polyamides are synthetics that retain their strength indefi- 
nitely. Polytetrafluoroethylene (PTFE, Gortex) is also 
popular. Stainless steel was formerly popular but the 
synthetic polymers have largely replaced it. 

3. Modern suture materials have good strength-to- 
thickness properties, so ligatures and sutures tend to be 
less bulky than formerly. 

Handling properties vary. Synthetic threads are 
extruded (Latin ex = out + trudere = to thrust); a liquid is 
forced through a hole and solidifies as a thread. If the 
surface of the resulting thread is damaged, it seriously 
weakens it. Monofilamentous extruded synthetics may be 
rather stiff and often have a 'memory' so they spon- 
taneously tend to return to the straight form in which they 
were created; because the surface is so smooth it binds less 
firmly to itself. These factors make the knots less secure 
than those tied using flexible and rougher materials. 



201 



18 



PREPARATIONS FOR SURGERY 




Key point 

• Do not injure the smooth surface of extruded 
synthetic threads - it fatally weakens it. 

4. Needles are now almost universally curved and 
inserted using a 'no-touch' technique on a needle holder. 
This protects your hands from the danger of needle stick 
injury. The needles are simple round -bodied or sharp- 
edged cutting needles for penetrating tough tissues. The 
majority of sutures are now 'atraumatic', being swaged into 
eyeless needles. This facilitates passage through the tissues. 

5. Catgut was absorbed by creating an inflammatory 
reaction. Modern absorbable materials are often absorbed 
by hydrolysis and so provoke very little inflammatory 
reaction. 

6. Metal clips are valuable alternatives to ligatures 
where access is difficult. They were originally made of 
stainless steel and were frequently used to demarcate an 
area for subsequent radiotherapy, or to assess radiologi- 
cally the response of a neoplasm to treatment by radio- 
therapy or chemotherapy. Stainless steel clips may produce 
a stellate shadow, obscuring detail in computed tomogra- 
phy (CT) scans, so they are now made from titanium. 

7. Sutures or clips may be unnecessary for skin closure, 
provided the tissues are perfectly apposed. Dry the edges 
and apply plastic adhesive strips across the wound. 

8. A variety of staples are used in visceral tissues, offer- 
ing changes in practice. Be aware of the range, the indi- 
cations and contraindications for each type of instrument, 
including staple size, and the differences in design 
between manufacturers. Remember that surgical tech- 
nique may need to be adapted as compared with the stan- 
dard suture procedure. However, staple techniques are 
not as versatile as suturing. Reserve staple techniques for 
circumstances when: 

a. The procedure can be carried out with greater safety, 
for example, reducing anastomotic leakage 

b. Operative time is significantly reduced and this is an 
important factor 

c. The incidence of late complications (stenosis) is low; 
for example, low anterior resection of the rectum or 
oesophagogastric anastomosis high in the chest. 



viscera out of the operative field, for limiting gross con- 
tamination and for haemostatic control of raw surfaces. 

2. Although haemostasis is usually achieved by elec- 
trocoagulation, ligation, undersewing or the use of clips, 
in some situations it is invaluable to use manufactured 
haemostatic agents in the presence of a slow ooze. There 
is a choice between Surgicel, Oxycel or Sterispon; gain 
experience of the particular properties of each of them. 
Surgicel applied to the gallbladder bed, with overlying 
pressure from a warm, moist swab, controls a slow per- 
sistent ooze following cholecystectomy. When you care- 
fully remove the overlying swab, the haemostatic agent 
remains undisturbed. In neurosurgery you may prefer the 
more delicate Sterispon. 



DISroSMLEj^CCESSORIK 

Included in this category are accessories that remain on 
the surface of the body, skin or epithelial lining, and those 
that attain access to the interior of the body, usually for a 
limited period. Remember that they cause tissue irritation 
and create a break in the body's defence system. 

Categories 

1 . Vascular cannulae, catheters and specialized 
equipment (e.g. Fogarty embolectomy catheters, 
Swan-Ganz catheters). 

2. Urological catheters and stents. 

3. Alimentary tract stents and catheters, for example: 

a. Straight, curved, cuffed or expansile stents for 
oesophageal and biliary malignant stricture 

b. Balloon dilating catheters for strictures 

c. Enteral feeding tubes. 

4. Stoma appliances. 




Key point 

Avail yourself of the skill of a stomatherapist 
so your patient benefits from the correct 
appliance in the right place. 



SWABS AND PACKS 

1. All cotton or fabric swabs and packs used during 
operations have radio-opaque thread marking. Choose 
the size appropriate to the procedure and defined 
purpose. You may need small 'patty' swabs for neurosur- 
gical procedures and narrow swabs for tonsillar surgery. 
Use large packs or gauze rolls for retaining abdominal 



5. Neurological valved shunts. 

6. Drains. 




Key point 

Define the purpose and, therefore, duration of 
use. Use closed systems. 



202 



■ 



ADJUNCTS TO SURGERY 



18 



ENDOSCOPES 

1. Endoscopes are continuously being developed, 
together with new applications for diagnosis and therapy. 
Instruments can be passed in the upper and lower respir- 
atory tracts, the upper and lower alimentary tracts 
(including the biliary tree and pancreas), the upper and 
lower urinary tracts, the female genital tract, and into 
joints, the peritoneal cavity and along blood vessels. 
Design modifications have resulted in a wide range of 
instruments with considerable therapeutic capabilities, 
often with the use of specialized accessories. 

2. Ensure that they are carefully stored, maintained, 
cleaned, decontaminated and expertly disinfected, other- 
wise there is a risk of transmitting infection, particularly 
viruses such as hepatitis B and C and human immuno- 
deficiency virus (HIV). Flexible instruments are usually 
disinfected by immersing them in a buffered 2% solution 
of gluteraldehyde for 20 min. Modern cystoscopes, for 
instance, may now be autoclaved. 

3. Do not neglect to master the use of the simple proc- 
toscope, anal retractor, such as Park's or Eisenheimer's 
retractors, and sigmoidoscope. 



IMPLANT MATERIALS 

1. Prosthetic (Greek pros = to + thesis - putting; the 
fitting of artificial parts into the body) surgery continu- 
ously expands. Perhaps the greatest impact is in 
orthopaedic surgery, where successful joint replacement 
is well established in the hip, knee, interphalangeal joints 
and, to a more limited extent, the shoulder and elbow 
joints. 

2. Prosthetic implants are widely used in general, vas- 
cular, cardiac, urological, plastic and other branches of 
surgery, and there is wide variation in the materials 
used. Basic considerations and principles apply. They 
must be easily and reliably manufactured at reasonable 
cost. The strength and durability must be reliable, 
especially for cardiac valves, pacemakers and joint 
replacements. 

3. There must be no adverse reaction between pros- 
thetic materials themselves and the body tissues; for 
example, between the metal and plastic components of 
certain artificial hip replacements or between the joint 
prosthesis, cement and the bone. Another example is 
platelet aggregation and plasma protein precipitation 
around intravascular prostheses. 

4. The degree of incorporation into the body may be 
important; for example, metallic and silicone implants 
are isolated within a collagen capsule but polytetra- 
fluoroethylene (PTFE, Goretex) allows the ingrowth of 
fibroblasts. 



Implant materials in orthopaedic surgery 

1. Surgical-grade stainless steel is used for joint 
replacement-bearing surfaces, plates, screws and wires. 

2. Alloys, including Vitallium, are also used in joint 
replacement surfaces, wires and, less frequently now 
owing to the preference for compression steel plating for 
internal fixation, in plates. 

3. High density polyethylene (ultrahigh molecular 
weight) is used for joint replacement-bearing surfaces to 
articulate with steel or Vitallium. 

4. Silicone is used for hinge-type joint replacement, but 
not in bearing surfaces where debris produces a synovi- 
tis. It has been used very successfully in metacarpo- 
phalangeal and proximal interphalangeal joints. 

5. Dacron and PTFE are materials that can be used 
under tension (e.g. synthetic ligament repair). Carbon 
fibre has been abandoned as a result of fragmentation and 
foreign body reaction. 



The risk of infection 

This is one of the most serious complications of prosthetic 
surgery. Risk factors include: 

• Immune compromised host 

• Active infection present elsewhere in the host or in 
contacts 

• Positive carrier state in patient or staff 

• Crossinfection in hospital 

• Failure of sterilization and /or packaging 

• Inadequate air ventilation in the operating theatre and 
ineffective operating theatre clothing 

• Poor operative technique with contamination, poor 
haemostasis or ischaemic tissue 

• Inadequate antimicrobial prophylaxis. 

The time scale of presentation is of significance. Late 
infection may develop, up to a year or more after surgery, 
particularly with a deeply inserted prosthesis. A smooth- 
surfaced implant is bacteriostatic and non-wettable, 
whereas a textured surface allows the entrapment of 
blood, serum, particles and bacteria in the crevices. 

Deep infection around implants, such as of a hip 
replacement with Staphylococcus aureus , produces a cap- 
sular thickening; S. epidermidis produces a polysaccharide 
slime. The prosthesis becomes loose, causes pain and may 
need to be removed. 

Do not use an implant unless there is no natural alter- 
native. Thus, in vascular surgery prefer vein grafts for 
lower limb arterial bypass surgery such as infrainguinal 
bypass and especially for below-knee femoropopliteal 
bypass. Synthetic materials, Dacron (collagen-coated 
knitted Dacron) or Goretex (PTFE) may be used, particu- 
larly where large vessels need to be bypassed or replaced. 



203 



is ; 



PREPARATIONS FOR SURGERY 



Tissue response to foreign material 

1 . Tissue reaction varies according to the material and 
the roughness of the surface. Marked inflammatory 
response / with microabscess formation, occurs around a 
buried silk or linen knot. By comparison, minimal 
response occurs around polypropylene, with not only a 
reduced likelihood of bacterial infection but also 
increased tensile strength, depending on the material 
used, and a lack of surrounding tissue inflammatory 
infiltrate. 

2. Silicone generates the formation of a capsule. 
Fibroblasts orientate themselves to the surface of the 
foreign material and the collagen is laid down in mirror 
image to the specific surface; as it matures, it contracts. 
Fibroblasts cease to secrete collagen when they are in 
contact with other fibroblasts, but not when in contact 
with other cells. Thus, over a smooth surface sheets of col- 
lagen are produced with increased contractile force of the 
capsule. Gradually, fibroblastic activity on the free surface 
subsides, collagen deposition is completed and moulding 
takes place, producing a mature capsule at approximately 
3 months after surgery. Collagen production against the 
smooth inner capsular surface continues because the 
fibroblasts are not in contact with each other and, as a 
result, the cavity diameter decreases and the contractile 
force increases. 

3. By comparison, roughened surfaces allow fibro- 
blasts to conform to the crevices; the fibres of collagen are 
then orientated at random with counteracting contractile 
forces and the fibroblasts lie in different planes and direc- 
tions, allowing a greater chance of contact with each 
other, thus reducing the collagen deposition and resulting 
in a thinner capsule. Silicone particles are found in phago- 
cytes in the capsule wall adjacent to lymphatic vessels, in 
the outer layer of capsules, and may reach the lumen of 
lymphatic vessels, as they are found in regional lymph 
nodes. 

4. Metal-on-metal joint replacement produces small 
particulate debris which is incorporated into the syn- 
ovium, producing foreign-body giant cells. 

5. Acrylic cement (polymethylmethacrylate), used in 
the fixation of prostheses, becomes encapsulated by 
fibrous tissue, the inner layer of which is sometimes 
hyaline and acellular and sometimes contains histiocytes 
and multinucleate giant cells. There is no evidence for 
malignant transformation or chronic inflammatory reac- 
tion with sinus formation (Charnley 1970). Revisional 
surgery of the cemented prosthesis is difficult. 
Alternatives under trial are based on isoelastic or mesh 
coating of the prosthesis to allow fibrous tissue to grow 
in. 



The controversy over the safety of silicone 
mammary prostheses 

In 1992 in the USA a moratorium {Latin mora = delay) was 
placed on the use of silicone gel breast implants because 
of the possible association with connective tissue dis- 
orders. In the UK, an independent expert advisory group 
reported to the Department of Health in 1993 that there 
was no evidence of an increased risk in implanted patients 
(Park et al 1993). In 1994, the Medical Devices Directory 
supported the Chief Medical Officer in stating that there 
was no evidence for a change in policy. As always, absence 
of evidence is not evidence of absence. Since the incidence 
of connective tissue disorders in the population is low and 
the latent period is long, large numbers and prolonged 
follow-up are needed. Silicone, like any foreign body, may 
initiate an antibody and cell-mediated inflammatory 
response, but this is not in itself suggestive of an adverse 
effect on the immune system. There is currently no evi- 
dence that breast-implanted patients have an enhanced 
risk of developing either autoimmune connective tissue 
disease or mammary carcinoma. Silicone implants do, 
however, reduce the value of mammography. Alternative 
filler substances, developed to allow mammograph and 
avoid silicone reaction locally, include triglyceride and 
saccharides. They were withdrawn because of adverse 
reactions in some patients (Medical Devices Agency 2001) 
and patients are advised to have them removed, to be 
replaced by silicone gel or saline filled prosthetics if 
desired. All of them have textured silicone shells. 



ITSSUEjGI^ 

Glues have been used for many years. Collodion, a cellu- 
lose nitrate, has been used for many years as a wound 
seal. Karaya gum is routinely used to attach stoma bags 
to the skin; it has also been used as a slow release vehicle 
for caffeine and diclofenac. Cyanoacrylate 'instant glue' is 
used as a tissue glue. Gelatine-resocinol-formaldehyde 
has been used, for example, as an adhesive to fix a patch 
sealing an intraventricular septal defect. 

Research into new methods of surgical tissue repair has 
yielded the prospect of wide use of tissue glues. One such 
method is fibrin adhesion, based on the conversion of 
fibrinogen into fibrin on a tissue surface by the action of 
thrombin. The fibrin is then crosslinked by factor XHIa to 
create a firm stable fibrin network with good adhesive 
properties. Fibrin foam may be valuable in controlling 
tumour bleeding. The addition of aprotinin prevents pre- 
mature dissolution of the fibrin clot by plasmin. In the 
presence of heavy bleeding the fibrin glue tends to be 



204 



ADJUNCTS TO SURGERY 




18 



washed away before sufficient polymerization of the 
fibrin has occurred. The use of collagen mesh sheet with 
fibrin glue dispersed over the surface has been of con- 
siderable practical value. Note that the sheet should be 
kept in contact with the surface by gentle pressure for 3-5 
min. The indications are for tissue adhesion, haemostasis 
and suture support (Table 18.1). 

Concern has been expressed that the use of human fib- 
rinogen and factor XIII might allow the transmission 
of viral agents such as hepatitis B, hepatitis C or HIV. 
Commercial inactivation of a virus is achieved by pas- 
teurization with purification of the proteins and then 
heating the solution for 10 h at 60°C. Laboratory studies 
demonstrated that this process not only inactivates the 
hepatitis B and HIV viruses, but also herpes simplex virus 
and cytomegalovirus. Particular care is taken to use 
human fibrinogen from hepatitis B antigen-negative, 



ji 



Table 18.1 Examples of the use of tissue glues 



General surgery 

Trauma to or surgery of liver, spleen, pancreas 

Haemostasis in gallbladder bed (cheaper agents 

currently available) 
Support anastomosis eg, pancreaticojejunal 

anastomosis 
Neurosurgery 
Repair of dural tear, sealing cerebrospinal fluid 

leak 
Peripheral nerve anastomosis 
Orthopaedic surgery 
Acetabuloplasty (cement-free prosthesis) 
Tendon repair 

Re-attaching osteochondral fragments 
Cardiovascular and thoracic surgery 
Prosthetic implant in combination with collagen 

sheet to seal lung air leaks 
Ophthalmic surgery 
Cataract operations 
£ NT surgery 

Tympanic membrane surgery 
Sealing CSF leaks 
Urology 

Haemostasis, especially after TURP 
Plastic surgery 
Attaching skin grafts 



anti-HIV-negative and anti-hepatitis C-negative plasma 
of healthy donors. 

Marked arterial or venous bleeding renders the system 
ineffective. Hypersensitivity reactions have been 
described. The process is under evaluation in the UK. 



Summary 

• Do you recognize the safety factors and 
cost effectiveness of good theatre 
management for you and your patient? 

• Do you know the basic principles of 
sterilization? 

• Will you contribute to cost savings by 
using only the smallest range of effective 
instruments, equipment and consumable 
materials? 

• Implants can transform a patient's quality 
of life but the surgery is costly and 
complications can be serious and 
prolonged. 




Further reading 

Detweiler MB, Detweiler ]G, Fenton J 1999 Sutureless and 
reduced suture anastomosis of hollow vessels with fibrin 
glue: a review. Journal of Investigative Surgery 12: 245-262 

Gosden PE, MacGowan AP, Bannister GC 1998 Importance of 
air quality and related factors in the prevention of infection 
in orthopaedic surgery. Journal of Hospital Infection 
39: 173-180 

Harding KG, Jones V, Price P 2000 Topical treatment: which 
dressing to choose. Diabetes/ Metabolism Research Reviews 
16 (suppl. 1): S47-S50 




References 



Charnley J 1970 Acrylic cement in orthopaedic surgery. E and S 

Livingstone, Edinburgh 
Park AL Black RJ, Watson ACH 1993 Silicone gel breast 

implants, breast cancer and connective tissue disorder, British 

Journal of Surgery 80: 1097-1100 



205 




1Q Prevention of infection in 
I Z7 surgical practice 



K. E. Orr, F. K. Gould 



H 



Objectives 



Appreciate the importance of surgical 

sepsis as a significant cause of morbidity. 

Understand the principles of infection 

control and its role in preventing 

infections. 

Be aware of methods by which asepsis and 

antisepsis are achieved, and when they are 

necessary. 

Know when antibiotic prophylaxis is 

desirable and when it is not. 

Recognize the benefit of infection audit 

with feedback to surgeons as a means of 

reducing the infection rate. 



INTRODI^^ 

The Hungarian obstetrician Ignaz Semmelweiss was the 
first to demonstrate the importance of antisepsis, 
working in Vienna in the early 1850s. He found that on 
his obstetric ward attended by medical students almost 
one-fifth of all his patients died, usually of puerperal 
(Latin puer = child + parere = to bear) sepsis. On another 
ward, without medical students, the mortality was about 
3 in 100. He realized that the medical students came 
straight from the autopsy room and proceeded to 
examine his patients without so much as washing their 
hands. Having insisted that each student should do so 
with soap and water and then in chlorinated lime solu- 
tion before entering the ward, he saw the mortality rate 
drop to less than 2 in 100. Despite this dramatic result, 
Semmelweiss was largely ignored and even ridiculed. It 
was not until Joseph Lister built on Pasteur's germ theory 
of disease in Glasgow in the late 1860s that antisepsis was 
looked at seriously. 

Since then, the improved prevention and management 
of infections in surgical practice has been one of the most 
important factors allowing the development of surgery as 



we now know it. Even so, surgical wound infections 
remain an important cause of morbidity. Over 70% of 
hospital-acquired infections occur in patients who have 
undergone a surgical procedure. Of these, wound infec- 
tions are those that increase hospital costs and length of 
hospital stay the most. On average, wound infections 
prolong the hospital stay of the patient by 7 days. 
Surgical wounds are traditionally classified as follows: 

Clean (Class I) 

These are wounds created during surgical procedures in 
which the respiratory, genitourinary or gastrointestinal 
tracts have not been entered. The usual causes of infec- 
tions in these wounds are airborne or exogenous bacteria 
that have entered the wound during surgery, or, in the 
case of prosthetic implants, the patient's own skin flora. 
The infection rate should not exceed 2%. 

Clean-contaminated (Class II) 

This term (Latin con - together + tangere = to touch; 
hence, soiled) describes wounds in elective surgery 
where the respiratory, gastrointestinal or genitourinary 
tracts have been entered. The primary cause of infection 
is the endogenous flora of the organ that has been 
breached surgically. The infection rate has been found to 
be approximately 5%. 

Contaminated (Class III) 

These are wounds where acute inflammation (but not 
pus) was found at surgery, or where there was spillage of 
gastrointestinal contents. They become infected with 
bowel /endogenous flora at a rate of about 20%. 

Dirty (Class IV) 

These are wounds where pus was found at operation, 
usually following organ perforation, although this cat- 
egory also includes contaminated traumatic wounds. The 
infection rate is up to 40%. 



206 



PREVENTION OF INFECTION IN SURGICAL PRACTICE 



19 



Not only are surgical infections extremely important 
to the outcome for individual patients and costly for 
hospitals, but they have also assumed medicolegal sig- 
nificance. All departments and surgeons should ensure 
that their infection rates are compatible with those in 
other units, using methods that will be discussed later in 
this chapter. 

You cannot reduce infection by 
concentrating attention in a single 
area 

• Control resistant organisms in all areas within 
the hospital. 

• Unfailingly adhere to aseptic and antiseptic 
principles. 

• Practise the highest standards of surgical 
technique. 

• Use prophylactic antibiotics logically. 

• Audit your results to maintain and improve 
standards. 




CONTROL OF RESISTANT ORGANISMS 

1. Antibiotics have been in use for more than 50 years 
and many organisms are now resistant to the older 
agents. For example, in many hospitals more than 50% 
of isolates of Escherichia coli are resistant to ampicillin. 
The development of newer agents with increased 
activity and wider spectrum has allowed the benefits 
of antimicrobial therapy to be maintained and even 
improved. However, increasing use of these has led to 
the emergence of resistance in some important pathogen 
groups. 

2. The most obvious example is methicillin-resistant 
Staphylococcus aureus (MRSA). This is resistant to the com- 
monly used antistaphylococcal agent flucloxacillin and 
has to be treated with drugs such as the glycopeptides, 
vancomycin and teicoplanin. As well as being more toxic, 
these agents penetrate less well into soft tissues and 
wounds, can only be given parenterally and are expen- 
sive, MRSA is of particular concern in fields such as 
burns, plastic surgery and orthopaedics where tissue pen- 
etration of the antibiotic is of paramount importance and 
where an infection may result in removal of a prosthesis 
or failure of a graft. Even more worrying is the reported 
emergence in Japan and the USA of vancomycin interme- 
diate S. aureus (VISA) with reduced susceptibility to 
vancomycin. So far this does not appear to be a common 
cause of clinical infections, however there is a danger 
that in the future we shall again be unable to treat 
S. aureus infection. 



3. Enterococci are also posing major problems with 
resistance; glycopeptide-resistant enterococci (GRE) are 
now found in many UK hospitals and, although they are 
less virulent than MRSA, they may cause life-threatening 
infections in immunocompromised patients. 

4. Gram-negative organisms such as Pseudomonas aeru- 
ginosa may also be multiresistant. The increasing use of 
third-generation cephalosporins appears to be encouraging 
the emergence of Gram-negative bacilli such as Klebsiella 
pneumoniae and Enterobacter cloacae resistant to these and 
other beta- lactams. 




Key point 



• Make every effort to keep the prevalence of 
resistant organisms within the unit to a 
minimum, and prevent their spread between 
patients. 

5. Handwashing and basic infection control practices 
cannot be overemphasized. Handwashing has been high- 
lighted in recent national evidence-based guidelines for 
preventing healthcare-associated infections (Pratt et al 
2001). Most hospital acquired (nosocomial from Greek 
nosos = sickness + komeein = to tend; hospital) infections 
are transmitted on the hands of staff and many studies 
have shown that handwashing is the single most import- 
ant and successful method of controlling the spread of 
infection in hospital. Wash your hands before and after 
physical contact with any patient, and after any activity 
where they are likely to become contaminated. Wash 
them with soap, detergent, or with alcohol rubs or gels if 
your hands are not visibly soiled. Before carrying out 
aseptic procedures, wash with an antiseptic solution such 
as povidone-iodine or chlorhexidine. 




Key points 



• Wash your hands, and see that all members of 
your team do so, before and after contact with 
every patient. 

• Rigorously apply universal precautions when 
appropriate, to minimize risk of infection for 
colleagues and patients (see Ch. 20). 

6. Screen at-risk patients to identify those who are col- 
onized. Reserve this, as a rule, for detecting MRSA so you 
can implement precautions to prevent spread of the 
organism to other patients, and also to reduce the risk of 
infection in those planned for high risk surgery such as 



207 



19 



PREPARATIONS FOR SURGERY 



vascular graft procedures and prosthetic orthopaedic 
surgery. Take swabs of nose, throat and perineum. 
Colonized patients are asymptomatic and do not require 
systemic antibiotic treatment unless they show clinical 
evidence of infection. Consider using topical agents in an 
attempt to eradicate MRS A carriage in colonized patients; 
however, this is unlikely to succeed in the presence of 
foreign bodies such as percutaneous feeding tubes, and 
persisting wounds. If there is evidence of an outbreak on 
your unit, the infection control team may advise you to 
screen the unit staff, in case there are carriers. In most UK 
hospitals the management of patients and staff in units 
affected by MRSA is based upon national guidelines 
(Duckworth et al 1998). 

7. Isolate patients found to be colonized with a sig- 
nificant multiresistant organism, usually in a side room 
- "wound and enteric' or 'source' isolation. All staff wear 
disposable gloves and aprons when in contact with the 
patient. You and your medical colleagues remove your 
white coats before entering the side room. Ideally the 
same nurses should care for the patient throughout the 
shift. All other staff, such as porters, physiotherapists, 
phlebotomists and domestics, must be aware of, and 
take relevant precautions for, 'wound and enteric/ 
source isolation.' 

8. Control the movement of colonized patients 
between departments. Whenever possible, arrange for 
those carrying multiresistant organisms to be operated 
upon at the end of the surgical list, so that the theatre can 
be cleaned thoroughly afterwards with minimum disrup- 
tion. Warn the theatre staff of the patient's status in 
advance. The same applies to visits to other departments, 
such as radiology, physiotherapy and the gymnasium. 
Keep patient movement within the hospital to a 
minimum and transfer patients between wards only 
when absolutely necessary 

9. Use antibiotics judiciously, only when there is evi- 
dence of clinical infection or as part of a policy regarding 
perioperative prophylaxis. Choose the antibiotic ratio- 
nally; if in doubt, consult the microbiologist earlier rather 
than later. Overuse of antibiotics encourages develop- 
ment of resistance in exposed organisms. It also destroys 
patients' normal flora so they are more susceptible to 
colonization with hospital organisms. Furthermore, it 
predisposes to infection with Clostridium difficile, which 
can lead to pseudomembranous colitis: third- generation 
cephalosporins are notorious for this. 



ASEPSIS AND ANTISEPSIS 



■rH~^-?'&&i^'&%?&£&£ 



■Wi 



Key point 



• Adopt locally agreed guidelines for antibiotic 
prescribing, and audit your infection rates. 



The term 'asepsis' (Greek a - deprive + $ey$i$ - sepsis = 
putrefaction) describes methods preventing contamin- 
ation of wounds and other sites by ensuring that only 
sterile objects and fluids come into contact with them; the 
risks of airborne contamination are minimized. Antisepsis 
(Greek and = against) is the use of solutions, such as 
chlorhexidine, iodine or alcohol, for disinfection. 

Theatre clothing 

1. Gowns. Woven cotton clothing is relatively ineffec- 
tive at preventing the passage of bacteria. Choose 
disposable non-woven fabric, Goretex or tightly woven 
polycottons. The Charnley exhaust gown is of some 
benefit in prosthetic implant surgery. It is an important 
part of theatre discipline to change into fresh theatre 
clothing when entering the theatre suite because clothing 
worn in ward areas has been shown to be more heavily 
contaminated with microorganisms than freshly laun- 
dered 'scrub suits'. 

Normal cotton clothing does little to prevent the 
passage of bacteria, especially those on skin scales, as the 
diameter of holes at the interstices of the cloth is usually 
greater than 80 iJim. In addition, once cotton material is 
wet its barrier properties are much reduced, allowing 
bacteria to penetrate through from the wearer's skin; 
therefore, if clothes become wet, change them. 'Soak 
through' of blood has been shown to occur in over one- 
third of orthopaedic and general surgical operations and 
may present a risk to the wearer. Reduce the risk by 
using impermeable gowns or by wearing plastic aprons 
under linen gowns in situations where 'soak through' is 
likely. 

Materials that reduce the dispersal of skin scales and 
bacteria are restrictive to wear so a compromise has to 
be reached. Clothing made from disposable non- woven 
fabric is suitable but expensive, as the whole team must 
wear it to obtain a benefit. Breathable membrane fabrics 
such as Goretex, or other materials such as tightly-woven 
washable polycottons are also suitable. Pay special atten- 
tion to the design of the clothing so that bacteria are not 
'pumped out' at the neck or the ankles. Most effective of 
all is the Charnley exhaust gown, which for maximum 
benefit must be used in conjunction with a unidirectional 
high efficiency particulate air (HEPA) filter system. It 
is also very restrictive and so rarely used by general 
surgeons. However it can be valuable in orthopaedic 
prosthetic surgery. 

2. Mask use is controversial. Few bacteria are dis- 
charged from the mouth and nose during normal breath- 
ing and quiet conversation, and it is argued that for 
general abdominal operations masks are not required for 



208 



PREVENTION OF INFECTION IN SURGICAL PRACTICE 



19 



the protection of the patient, particularly by staff 
members in theatre who are not directly assisting. If you 
wear a mask, change it for each operation; reuse and 
manipulation simply contaminates the outside of the 
mask with skin commensals. Masks have been shown to 
reduce airborne contamination in ultraclean air theatres 
and should therefore be worn in prosthetic implant 
surgery 

An efficient mask must be capable of arresting low 
velocity droplets. Paper masks become wet within a few 
minutes and lose their barrier qualities, so do not use 
them. Disposable masks made of synthetic fibres are 
better and contain filters made of polyester or polypropyl- 
ene. Surgical antifog masks with flexible nosebands are 
available; they follow facial contours and retain a high 
efficiency of filtration. 

Masks continue to be worn to provide protection for the 
wearer against blood-borne viruses as part of a policy of 
universal (or standard) precautions. Full-face visors also 
afford similar protection. 

3. Eye protection /visors also protect mucous mem- 
branes. Wear them during any procedure that is likely to 
generate droplets of blood or other body fluids, in order 
to protect your mucous membranes from blood-borne 
viruses. A variety of lightweight anti-fog goggles, 
glasses and visors are available that do not obstruct 
vision. 

4. Tie up long hair and cover hair completely with a 
close-fitting cap made of synthetic material. Cover beards 
fully with a securely tied mask and hood of the balaclava 
type. This is especially important for prosthetic implant 
surgery. 

5. Footwear has a minor role in spreading infection. 
There is little evidence that the floor plays a significant 
role in the spread of infections in hospital. Wear clean, 
comfortable, antislip and antistatic shoes. If there is a risk 
of fluid spillage, as in genitourinary surgery, wear ankle- 
length boots that can be cleaned with warm soapy water. 
Make sure your footwear fits well and does not produce 
a "bellows' effect. Make sure they are sufficiently robust 
to protect your feet from sharps injury. Overshoes are not 
required for visitors who do not enter the operating or 
preparation rooms. 

6. Gloves protect both you and your patient from 
blood-borne viruses (see Ch, 20) and prevent the wound 
from becoming contaminated with your skin flora. Wear 
single-use surgical gloves from a reputable source, steril- 
ized by irradiation. 

Surgical gloves made of natural rubber (latex) are increas- 
ingly reported to cause hypersensitivity reactions. Non- 
latex gloves without powder are available. Worryingly, 
many gloves are found to have pre-existing holes prior 
to use, as a result of inadequate quality control and poor 
manufacture. Furthermore, during the operation, around 



20-30% develop holes of which the wearer is often 
unaware. Therefore inspect them at the end of each oper- 
ation. Avoid needlestick injury; if you sustain one, let it 
bleed, and wash well with soap and water. As soon as pos- 
sible fill in the accident form and report to the occupational 
health department. 

Double-gloving affords extra protection but at the 
expense of reduced sensitivity and dexterity, and possible 
discomfort. In appropriate circumstances protect your 
fingers with armoured gloves or thimbles, in addition to 
protective clothing. 

Theatre air 

1. Air-borne bacteria are generally believed to be a 
source of postoperative sepsis, although this has been 
unequivocally proved only in the case of prosthetic 
orthopaedic implant infections. The number of circulating 
bacteria is directly related to the number of people in 
theatre, and their movements, which should both there- 
fore be minimized. It is also affected by the type of theatre 
clothing worn. 

Carefully balanced ventilation systems will not operate 
optimally if theatre doors are left ajar. 

2. General operating theatres are equipped with posi- 
tive pressure or plenum (Latin = full) ventilation systems, 
with the pressure decreasing from theatre to anaesthetic 
room to entrance lobby. Thus air-borne microorganisms 
tend to be carried out rather than in. In a conventional 
plenum system there should be a minimum of 20 air 
changes per hour. Routine checks of bioload are not 
required. Guidelines regarding theatre air ventilation and 
theatre design can be found in the Department of Health 
documents Health Technical Memorandum 2025, 
Ventilation in Health Care Premises, and Health Building 
Note number 26, Operating Department. 

3. Ultraclean air systems are advocated for prosthetic 
implant surgery. In these systems, instead of the turbulent 
airflow associated with plenum pressure systems, there is 
unidirectional or laminar airflow at about 300 air changes 
per hour. The air is recirculated through high efficiency 
particulate air (HEPA) filters. This produces a reduction 
in circulating microorganisms compared with a conven- 
tional system. In these theatres regular bacteriological 
assessment should be undertaken. 

A large multicentre study in prosthetic orthopaedic 
surgery demonstrated that the incidence of deep peri- 
articular infections was reduced from 3.4% to 1.6% by the 
use of ultraclean air conditions. With the addition of 
prophylactic antibiotics, the infection rate was reduced 
further to 0.19%. Bear in mind that, if the level of asepsis 
is otherwise only moderate, the impact of ultraclean air 
systems may be lost. Their role in clean surgery other than 
prosthetic implant surgery is uncertain. 



209 



19 




PREPARATIONS FOR SURGERY 



Surgeon preparation 

1 . Most theatre-acquired infections are of endogenous 
origin, but the scrub team must ensure that they do not 
put their patients at risk. In order to minimize the risk of 
transmitting infection to patients, you must all satisfy 
local occupational health requirements before entering 
the operating theatre. For example, you must not operate 
with bacterial pharyngitis, during the prodromal (Greek 
pro = before + dromos = run, course; hence, incipient) 
period of a viral illness or with chronic or infected skin 
conditions. Try to avoid operating if you have cuts, 
cracks, sores or rashes on your hands or forearms. If 
in doubt take advice from the occupational health 
department. The Department of Health has issued com- 
prehensive guidance regarding healthcare workers 
infected with blood-borne viruses (see Ch. 20). 

2. The term 'scrubbing up' is unlikely to disappear 
from surgical practice but repeated scrubbing is counter- 
productive because it results in skin abrasions and more 
bacteria being brought to the surface. At the start of a list 
have an initial scrub of 3-5 minutes; thereafter, use effec- 
tive handwashing with an antiseptic between cases. Skin 
antiseptics act rapidly and some have a cumulative 
effect. Use sterile, single-use brushes of polypropylene, 
not with wood or bristles. Do not shower prior to oper- 
ating, it increases the number of bacteria shed from the 
skin. 

3. Antiseptics commonly used are: 

a. Chlorhexidine gluconate 4% (Hibiscrub), which is 
rapidly active, broad spectrum and persists with a cumu- 
lative effect, even under surgical gloves. It is easy to use 
but the detergent-like effect must be washed off with 
running water. Some surgeons are allergic to it and can 
use hexachlorophane or povidone-iodine. 

b. Hexachlorophane (pHisoHex), which is effective 
only against Gram-positive bacteria and has a slow action 
but a cumulative effect. 

c. Povidone-iodine (Betadine), which acts more 
rapidly than hexachlorophane and has a broader spec- 
trum but does not have a prolonged effect. 

4. Dry your hands thoroughly using single-use sterile 
towels. Hot-air drying machines are not recommended. 



Preparation of the patient 

1. The longer a patient stays in hospital before oper- 
ation, the greater the likelihood of a subsequent wound 
infection. Keep hospital stay as short as possible and carry 
out as many tests as possible beforehand, as an out- 
patient. Cultures from postoperative wound infections 
often suggest that organisms are transferred from other 
areas of the patient to the operative site (endogenous 



transfer) despite the use of antiseptics. Ensure that the 
patient is socially clean prior to operation. The value of 
routine preoperative showering with antiseptic solutions 
remains unproven. Infections at other sites increase the 
risk of surgical wound infection; therefore, diagnose and 
treat pre-existing infections before elective operation. 
Similarly, consider eradicating MRSA carriage in colo- 
nized patients prior to elective surgery. 

2. The patient can be transported to theatre in bed 
directly, after being changed into a clean operating gown. 
Remove ward blankets before entering theatre. There is 
no need for a special transfer area, changing trolleys, 
porters putting on plastic overshoes, or passing the 
trolley wheels over a sticky mat. Trolleys must be cleaned 
daily. 

3. Shaving of the operation site increases wound infec- 
tion rates because of injury to the skin. If hair removal is 
necessary, use clippers or depilatory cream. If it is essen- 
tial to shave the area, it should be performed as near as 
possible to the time of operation, preferably by you, prior 
to scrubbing up. 

4. Prepare the skin area around and including the oper- 
ation site. First scrub it with a sponge or swab impreg- 
nated with detergent. After the skin has been cleaned and 
degreased in this way, use antiseptic solutions. For intact 
skin consider alcoholic solutions of chlorhexidine or 
povidone-iodine rather than aqueous solutions. However, 
take care when applying alcohol solutions if you use 
diathermy; if it pools in the umbilicus or under the per- 
ineum, you may cause fire hazard. For vaginal or perineal 
disinfection consider a solution of chlorhexidine and 
cetrimide (Savlon). 

5. Traditionally the periphery of the proposed incision 
site was protected with sterile cotton drapes; however, 
these soon become wet, diminishing their protective 
properties. Incisional plastic drapes have been advocated 
but Cruse & Foord (1980) showed that applying adhesive 
plastic drapes to the operation area does not decrease the 
wound infection rate; this has since been confirmed in a 
study of caesarean section. 

Cleaning and disinfection 

1. Decontamination, or the process of removing micro- 
bial contaminants, can be carried out by cleaning, dis- 
infection or sterilization. The appropriate method of 
decontamination is determined by the risk of infection 
associated with the object or procedure. 

a. Cleaning is a process that removes visible contami- 
nation but does not necessarily destroy microorganisms. 
It is a necessary prerequisite to effective disinfection or 
sterilization. 

b. Disinfection is a process that reduces the number of 
viable microorganisms to an acceptable level but may not 



210 



PREVENTION OF INFECTION IN SURGICAL PRACTICE 



19 



inactivate some viruses, hardy organisms such as 
mycobacteria and bacterial spores. A topical disinfectant 
that may safely be applied to epithelial tissues is known 
as an antiseptic. 

Where an interventional procedure is planned for a 
patient known, suspected or at risk of suffering from a 
transmissible spongiform encephalopathy (TSE) such as 
Creutzfeldt-Jakob disease (CJD) or variant CJD, seek 
advice from the infection control team and sterile service 
department. 

2. Disinfection of heat-tolerant items can be achieved 
reliably by exposure to moist heat; for items such as sur- 
gical equipment and bedpans it can be carried out using 
a washer-disinfector. Recommended time-temperature 
combinations are 71 °C for 3 min, 80°C for 1 min or 90°C 
for 12 s. Boiling water kills bacteria, some viruses (includ- 
ing human immunodeficiency virus (HIV) and hepatitis 
B virus (HBV)) and some spores. It does not sterilize. Soft 
water at 100°C at normal pressure for 10 min is satisfac- 
tory. Suitable instruments include specula, proctoscopes 
and sigmoidoscopes. This method is now rarely used in 
secondary care. 

3. Chemical disinfection can be used where heat 
cannot. A good example is the use of glutaraldehyde 2% 
(Cidex) to decontaminate flexible endoscopes. It is rapidly 
active against most vegetative bacteria and viruses 
(including HIV and HBV), and slowly effective against 
tuberculosis and spores. It is toxic, irritant and allergenic. 

Other chemical disinfectants include hypochlorite solu- 
tions, chlorine dioxide, superoxidized water and peracetic 
acid. 

Those involved in the purchase and development of 
new instrumentation for surgery or investigation need 
to consider how it may be decontaminated at the end of 
the procedure. Recent years have seen the introduction 
of increasing numbers of instruments that cannot be 
sterilized and can be disinfected only with difficulty. As 
sterilization by heat is the most reliable and easily moni- 
tored method, choose reusable instruments that will 
withstand autoclaving, if possible. Reprocessing of dis- 
posable equipment is hazardous and must not be carried 
out. 

Antiseptics include chlorhexidine, iodophors such as 
povidone-iodine, triclosan and 70% alcohol. 

Sterilization 

This is defined as the complete destruction of all viable 
microorganisms, including spores, viruses and mycobac- 
teria. It is, in practice, defined in terms of the probability 
of a single viable microorganism surviving on 1 million 
items. The term sterilization (Latin sterilis = barren) can be 
applied only to equipment and not to the skin, where 
antisepsis alone can be achieved. 



1. Steam under pressure attains a higher temperature 
than boiling water and the final temperature is directly 
related to the pressure. Instruments can be cleaned, then 
reliably sterilized by steam under pressure using auto- 
claves. The process can kilUbacteria, including Myco- 
bacterium tuberculosis, viruses and heat-resistant spores. 
The preferred cycle is 134°C at 2 atmospheres for a 
holding time of 3 min, which entails a total cycle time of 
at least 30 min to reach the required temperature. 
Autoclaves should be centralized in specialized units, e.g. 
the sterile service department (SSD) or theatre sterile 
service unit (TSSU) and maintained by highly trained 
personnel. Maintenance and performance tests are very 
strictly controlled. In the future there will be a require- 
ment for systems tracing the decontamination processes 
of surgical instruments. 

Small portable autoclaves are used in some theatres for 
convenience. There is a potential danger in that they are 
used by staff untrained in scrutinizing and maintaining 
them. Many portable autoclaves are unsuitable for pro- 
cessing wrapped instruments or those with a narrow 
lumen. 

In patients at risk of TSE, for procedures not involving 
high risk tissues, use the autoclave, after thorough clean- 
ing of the instruments, with a cycle of 18 min at 134°C or 
six cycles of 3 min. 

2. Destroy instruments used for invasive procedures 
on patients known to have TSE, using incineration (ACDP 
1998). The same applies to instruments used on patients 
suspected of having TSE, unless an alternative diagnosis 
is established, and for instruments coming into contact 
with high risk tissues, such as brain, spinal cord or the 
eye, in patients at risk of developing TSE. Therefore, 
when possible use single-use instruments. 

3. Sterilization can be achieved by dry heat at 160°C 
for a holding time of 1 h. The process is inefficient com- 
pared with steam sterilization, but has the advantage of 
being able to treat non-aqueous liquids, ointments and 
airtight containers. It is also useful for avoiding corrosion 
of non-stainless metals and instruments with fine cutting 
edges, such as ophthalmic instruments. Do not use it for 
aqueous fluids or for materials that are likely to be 
damaged by the process, such as rubber and plastics. 
This equipment is subject to rigorous checks and 
maintenance. 

4. Sterilants are chemical compounds that, under 
defined conditions, are able to kill bacterial spores: 

a. Ethylene oxide (EO) is a highly penetrative, non- 
corrosive agent with a broad cidal (Latin caedere = to kill) 
action against bacteria, spores and viruses; however, it is 
also flammable, toxic, irritant, mutagenic and poten- 
tially carcinogenic, and should not be used when heat 
sterilization is possible. Its main uses are for wrapped 
and unwrapped heat-sensitive equipment: it is ideal for 



211 



19 




PREPARATIONS FOR SURGERY 



electrical equipment, flexible-fibre endoscopes and 
photographic equipment. Do not use it for ventilatory 
equipment. It is inappropriate for items with organic 
soiling. EO sterilization is a mainly industrial process for 
single-use medical devices. There are a limited number 
of NHS regional units. It is expensive, has a slow 
turnaround time, is potentially dangerous and must be 
carefully controlled and monitored. 

b. Glutaraldehyde: shorter immersion times provide 
disinfection, but 3-10 h of exposure to 2% alkaline glu- 
taraldehyde is required for sporicidal activity. 

c. Other sterilants include peracetic acid, superoxi- 
dized water, gas plasma and chlorine dioxide; however, 
validation processes have not yet been established by 
the Department of Health for some of these newer 
technologies. 

5. Irradiation employs gamma rays or accelerated elec- 
trons. It is an industrial process suitable for sterilizing 
large batches of similar products, such as catheters and 
syringes. 



Spillages 

Have body fluid spillage removed as soon as possible. 
Gloves and a plastic apron should be worn. First, cover 
spills with an appropriate disinfectant such as hypo- 
chlorite granules (Presept), then absorbent paper towels. 
Discard as clinical waste. Do not use chlorine-releasing 
agents on urine spills or chlorine gas will be released. 



Waste disposal 

Sort hospital waste to ensure it is correctly disposed of. 
Place 'sharps' in approved containers, and clinical waste 
in yellow plastic bags. These are disposed of, usually by 
incineration, separately from domestic waste, which may 
be sent for landfill. Other categories of waste requiring 
segregation include pharmaceuticals and radioactive or 
cytotoxic waste. 



SURGICAL TECHNIQUE 

Postoperative infection rate is influenced by the following 
factors. 

• The longer the operation, the more likely is the wound 
to become infected. Perform operations as expediently 
as safety allows. 

* Keep operative trauma to a minimum and handle 
tissues gently. 



Make incisions with sharp instruments - they are less 
likely to become infected than those produced, for 
example, by cautery; however, cautery may reduce the 
need for sutures, which can act as a nidus for infection. 
Use the finest suitable ligature. 
Haematomas are at risk of becoming infected. 
Necrotic or ischaemic areas are at risk. 
Avoid leaving a dead space. 

Avoid unwarranted prophylactic drains, which increase 
the risk of infection. Insert a necessary drain through a 
separate stab, not through the wound. Use an entirely 
closed system to decrease the chance of ascending infec- 
tion, and remove it as soon as possible. 




Key point 

Why do some surgeons performing standard 
operations have minimal infection? Their 
technique is impeccable! 



PROPHYLACTIC ANTIBIOTICS 

It has been shown that, for many contaminated and clean- 
contaminated procedures, postoperative infection can be 
avoided by using appropriate prophylactic antibiotics 
given prior to surgery. The general principles of antibiotic 
prophylaxis (Greek pro = before + phylax = a guard) are as 
follows: 

1. Use antibiotic prophylaxis only when wound con- 
tamination is expected or when operations on a contami- 
nated site may lead to bacteraemia. It is not required for 
clean-wound procedures except: 

a. When you insert an implant or vascular graft 

b. In valvular heart disease to prevent infective 
endocarditis 

c. During emergency surgery in a patient with pre- 
existing or recently active infection 

d. If an infection would be very severe or have life- 
threatening consequences. 

2. There is no evidence that prolonged prophylaxis has 
any advantage over short courses - 24 h. Prolonged 
administration may lead to superinfection. Normally in a 
clean operation one dose is sufficient. In contaminated 
operations three doses are often given. 

3. Administer the antibiotic parenterally, immediately 
prior to operation to achieve effective tissue levels. If you 
give them soon afterwards they do not prevent infection. 
If the procedure continues for more than 3-4 h, or if there 



212 



PREVENTION OF INFECTION IN SURGICAL PRACTICE 



19 



is excessive blood loss, give a further dose in theatre or 
tissue levels may no longer be effective. Acrylic cement 
containing gentamicin has been used successfully in joint 
replacement surgery. 

4. Select antibiotics to cover relevant organisms after 
discussion with the microbiologist regarding likely con- 
taminants and local resistance patterns. For example, in 
orthopaedic surgery the main pathogens are staphylo- 
cocci, but in bowel surgery cover is required for anaerobic 
and Gram-negative aerobic bowel flora. Work together 
with the microbiologist to develop standard policies for 
the unit, and follow them strictly when they are in place. 



FEEDBACK TO YOU AND THE UNIT 



''Ti^^-Wi^f^V^^/^^i^^i/i/f^^^i^fi^iff: 



■f^'^^^^fm^/^^^^^^*^-i^f^l^!^^ 



Using these four strategies, aim to keep your postoper- 
ative infection rate to a minimum. Both you and the unit 
must keep aware of your infection rates and determine to 
keep them comparable with rates in other similar units. 
Achieve this by surveillance and infection audit. 

Surveillance 

This is the systematic collection, collation, analysis and 
distribution of data and it has been shown to be valuable 
in the prevention of infection. The Study on the Efficacy of 
Nosocomial Infection Control (SENIC) was carried out in 
the USA over 10 years in the 1970s. A random sample of 
1000 patients from each of 338 hospitals was studied and 
details about each patient were recorded and analysed. It 
was found that infections of the urinary tract were the 
most common nosocomial infections but, as already men- 
tioned, wound infections were the most costly both finan- 
cially and in terms of delayed discharge from hospital. 

SENIC data measured intensity of surveillance, control 
efforts, policy development and teaching and whether or 
not infection rates were fed back confidentially to indi- 
vidual surgeons. In hospitals with optimal performance 
in all these categories the wound infection rate was 38% 
lower. The key factor in this reduction appears to be con- 
fidential feedback to individual surgeons. This is known 
as the Hawthorne effect. 

There are a number of different types of surveillance of 
nosocomial infection and no clear consensus regarding the 
optimal method. Continuous hospital-wide surveillance 
may be expensive and time consuming, while targeted 
surveillance may be more practical and cost effective. 
Whichever method is employed, it is essential that the 
definitions of infection are clearly understood and reliably 
applied. Despite the drawbacks, surveillance is useful not 



only for feedback but also for identifying changes in epi- 
demiology or a rise in infection rates, or for assessing the 
effect of implementing new preventive strategies. 

Due to the increase in day surgery and shorter hospital 
stays, there is evidence suggesting that the majority of 
surgical wound infections will present after hospital dis- 
charge. The addition of postdischarge surveillance will 
therefore provide a more accurate reflection of the true 
healthcare-associated infection rate. 

Infection audit 

Although a record of overall infection rates by surveillance 
is the ideal, this may not always be practical, as discussed 
above. Clinical audit is a way of reviewing clinical practice 
and outcomes and it has also been shown to be useful in 
surgical practice. All UK NHS units are required to carry 
out audit of their practices. It is important to audit infection 
rates. An acceptable standard exists and steps can be taken 
to improve rates in the process of closing the audit loop. 



Summary 

• Do you recognize that postoperative 
wound infections cause serious morbidity 
to patients and expense to hospitals? 

• Can you classify surgical wounds? What 
are the infection rates you would expect 
for each type of surgical wound? 

• Can you outline the main strategies for 
minimizing the risk of surgical wound 
infection? 

• What is the single most important 
measure for preventing the spread of 
infection between patients? 

• What do the terms asepsis, antisepsis, 
sterilization and disinfection mean? Name 
two antiseptics. 

• Can you list the main aseptic precautions 
taken in theatre? 

• Can you list the major methods of 
sterilization and disinfection, and give 
examples of when to use them? 

• Can you describe the principles of 
antimicrobial prophylaxis and give 
examples? 

• What is the value of surveillance of 
hospital-acquired infection to surgical 
practice? 



213 



19 



PREPARATIONS FOR SURGERY 




References 



ACDP, Advisory Committee on Dangerous Pathogens 
Spongiform Encephalopathy Advisory Committee 1998 
Transmissible spongiform encephalopathy agents: safe 
working and the prevention of infection. HMSO, London 

Cruse PJE, Foord R 1 980 The epidemiology of wound infection: 
a 10-year prospective study of 62 939 wounds. Surgical 
Clinics of North America 60: 1 

Duckworth G et al 1998 Revised guidelines for the control of 
methicillin-resistant Staphylococcus aureus infection in 
hospitals. Report of a combined working party of the British 
Society for Antimicrobial Chemotherapy the Hospital 
Infection Society and the Infection Control Nurses 
Association. Journal of Hospital Infection 39: 253-290 



Pratt RJ, Pellowe C, Loveday HP et al 2001 Standard principles 
for preventing hospital acquired infections. Journal of 
Hospital Infection 47S: S21-S37 




Further reading 

Ayliffe GAJ, Fraise AP, Geddes AM, Mitchell K (eds) 2000 

Control oi hospital infection, 4th edn. Arnold, London 
Morgan D (ed.) 1995 A code of practice for sterilization of 

instruments and control of cross infection (amended). British 

Medical Association, London 
Philpot-Howard J, Casewell M 1995 Hospital infection control. 

Saunders, London 



214 







The risks to surgeons of 
nosocomial virus transmission 

D. J. Jeffries, L Ushiro-Lumb 




Objectives 



Understand the main surgically important 

viruses. 

Appreciate the sources and methods of 

viral transmission. 

Recognize how to reduce the risks of 

transmission during surgical treatment. 

Know what action to take if exposure to 

infection has occurred. 



INTRODUCTION 

Many different viruses have been associated with nosoco- 
mial (Greek nosos = disease + komeein = to tend; relating to 
hospital) spread and healthcare workers frequently 
become infected as part of a hospital outbreak. It may be 
difficult to define the extent of an outbreak of a nosocomial 
virus infection due to a virus such as influenza or respir- 
atory syncytial virus, as there is usually evidence of a par- 
allel outbreak in the community and new infections are 
likely to be introduced repeatedly by patients, visitors and 
staff. Some viruses (e.g. herpes simplex, varicella-zoster 
and viral haemorrhagic fever viruses) may be spread to 
healthcare workers by close patient contact, while others 
may be widely disseminated in a ward or outpatient unit, 
e.g. winter vomiting due to small round structured viruses 
(SRSVs). The risk of acquiring a nosocomial virus infection 
is reduced by the following measures: 

1 . Education and awareness of the risks 

2. Isolation or cohorting of patients when appropriate 

3. Good hygiene and adherence to infection control 
procedures 

4. Immunization, if vaccines are available 

5. Postexposure measures if available. 

Close collaboration between microbiologists, virologists 
and other healthcare workers ensures that staff are aware 
of the risks from individual infected patients and of the 
appropriate procedures necessary to control these risks. All 



healthcare workers in contact with patients or their samples 
are exposed to nosocomial virus infections and, provided 
that adequate protective clothing and other facilities are 
available, the risk of occupationally acquired infection is 
accepted as part of the job. Surgeons are at no greater risk 
of acquiring most of the recognized nosocomial virus 
infections than any other healthcare worker (for detailed 
reviews of specific infections and their control see Breuer & 
Jeffries (1990) and Jeffries (1995a)). The nature of your work 
exposes you to the risk of infection from blood -borne 
viruses, particularly human immunodeficiency virus 
(HIV), hepatitis B virus (HBV) and hepatitis C virus 
(HCV). All of these viruses may lead to a prolonged infec- 
tious carrier state, and demonstration of persistent infection 
in a surgeon may lead to the need to change his or her prac- 
tice to avoid exposure-prone invasive procedures or, if this 
is not possible, it may be necessary to change to another 
speciality. There are potentially serious outcomes from 
blood-borne virus infections that may be occupationally 
acquired; this chapter is therefore focused on these agents. 



THEBLOOD-B<^NEJ^IfWSES 

Blood-borne viruses posing the highest risk of nosocomial 
crossinfection are those associated with a chronic carrier 
state, where continuous viral replication leads to persist- 
ent viraemia. Currently, the three most important agents 
to consider in this setting are HIV, HBV and HCV. Seek 
expert advice if other, less common, blood-borne viruses 
are being considered. 

The main features of HIV and the hepatitis viruses are 
presented in the 1995 publication from the Advisory 
Committee on Dangerous Pathogens (ACDP), entitled 
Protection Against Bloodborne Infections in the Workplace, 
and in a review by Jeffries (1997). 



Human immunodeficiency viruses (HIV-1, 
HIV-2) 

The first cases of the acquired immune deficiency syn- 
drome (AIDS) were recognized in 1981 and in 1983 a 



215 




PREPARATIONS FOR SURGERY 



retrovirus (HIV-1) was identified and was subsequently 
shown to be the causative agent. In 1985, a second human 
immunodeficiency virus (HIV-2) was isolated from indi- 
viduals from West Africa and this has now spread to other 
parts of Africa, India and Europe. The two viruses are 
very similar and their modes of spread and clinical effects 
are identical, although there is some evidence that disease 
progression is slower in HIV-2 infection. In this chapter 
the two viruses are referred to collectively as HIV. HIV 
contains RNA and during the course of its replication the 
genetic material of the viral particle is reverse- transcribed 
by an enzyme, reverse transcriptase, into a DNA copy, 
which is inserted into the chromosomes of an infected 
cell. This integrated package of viral genetic material (or 
pro virus) produces new viral particles, which are avail- 
able to infect other cells. Thus, following primary infec- 
tion with HIV, the virus persists within cells for the life of 
the cells and, because of continual transfer to other cells 
in the immune system and central nervous system, the 
infection persists for the life of the individual. Recent 
work indicates that an HIV-infected individual produces 
very high levels of virus, 10 9 -10 10 virus particles per day, 
and is consequently potentially infectious to others for 
life. In health care, the nature of the viral particle, which 
is surrounded by a lipid-containing envelope, means that 
it is easily destroyed by heat, disinfectants and deter- 
gents. At ambient temperatures, however, the virus is pro- 
tected from desiccation and may persist in dried blood or 
secretions for several days. 

The major cellular receptor for HIV is the CD4 antigen 
which is present on helper T lymphocytes and cells of the 
antigen-presenting series. These are the main target cells 
for the virus and gradual depletion of these cells over a 
period of years leads to the opportunistic infections and 
tumours that are characteristic of AIDS. Potent and 
complex combinations of antiretroviral drugs have been 
in use for many years now, with an ensuing decline in 
morbidity and mortality among individuals who achieve 
long-term viral suppression. 

Hepatitis B virus (HBV) 

Hepatitis B virus is a DNA virus which causes acute hepa- 
titis; because of its long incubation period (45-180 days, 
mean 75 days) it was previously known as long-incubation 
hepatitis (or serum hepatitis). During the acute infection, 
and in carriers of HBV, viral particles released from the 
liver are present in the circulation. The surface coating of 
the particles is present in excess and this material, hepa- 
titis B surface antigen (HBsAg), is identified by serological 
tests as the main indicator of active infection. A second 
antigen, HBeAg, which is derived from core particles of 
the virus present in the liver, indicates continuing activity 
of the virus in the liver, and the presence of HBeAg in the 



blood correlates with high levels of infectivity. Note, 
however, that precore mutants of HBV exist, which are 
unable to express HBeAg but continue to produce infec- 
tious viral particles. Individuals carrying such HBV vari- 
ants may have high levels of viraemia despite undetectable 
serum HBeAg, which ultimately translate into higher 
levels of infectivity than previously thought. The implica- 
tions of this HBV variant in the healthcare setting will be 
further addressed when discussing the infected healthcare 
worker. 

As with all types of viral hepatitis, the degree of 
illness produced is variable and ranges in different indi- 
viduals from asymptomatic infection to acute hepatic 
failure. The immune response is a major factor in 
determining the severity of disease. In the immunologi- 
cally immature or immunocompromised, asymptomatic 
infections are common, but the risks of proceeding to 
long-term carriage of the virus are high. The long-term 
carrier rate following neonatal infection is >90%, in chil- 
dren aged 1-10 years it is 23%, and in adults 5% or less 
become carriers. This high rate of persistence following 
infection in early life largely explains the estimated 
250-300 million carriers in the world, the majority of 
whom are in resource-deprived countries, where 15-20% 
of the population may be infected. 

The carrier of HBV presents a potential risk of hori- 
zontal transmission to others, predominantly via sexual 
intercourse and blood transfer. The HBV-positive mother 
is also likely to infect her baby during delivery, with the 
highest risk amongst HBeAg-positive carriers (up to 
90%). Vertical transmission is in fact a very important 
route of HBV spread in parts of the world where the virus 
is highly endemic. 

Persistent replication of HBV in the liver of HbeAg- 
positive carriers carries a risk of progressive liver 
damage, leading to chronic active hepatitis, cirrhosis and 
an increased risk of hepatocellular carcinoma. 

Hepatitis C virus (HCV) 

Following the identification of HBV, the continued occur- 
rence of post-transfusion hepatitis led to the realization 
that there were other blood-borne hepatitis viruses 
(termed non-A, non-B hepatitis). The RNA virus, HCV, 
is now recognized as the major cause of non-A, non-B 
hepatitis, with an estimated 170 million people infected 
worldwide. Hepatitis C is predominantly blood borne 
and infection is common in injecting drug users and 
recipients of unscreened blood and /or blood products. 
The acute phase of HCV infection is usually asymp- 
tomatic and only approximately 10% of individuals have 
overt hepatitis. Following primary infection, however, 
the majority (about 80%) proceed to become persistent 
carriers of the virus and, as with HBV infection, there is 



216 



THE RISKS TO SURGEONS OF NOSOCOMIAL VIRUS TRANSMISSION 




20 



a long-term risk of chronic liver disease with cirrhosis 
(10-30%) and hepatocellular carcinoma. In the industri- 
alized world, chronic HCV infection is the leading cause 
of chronic liver disease and the most common indication 
for liver transplant. 



SOURCES OF INFECTION 

As the term implies, the major blood -borne viruses, HIV, 
HBV and HCV, are found predominantly in the circula- 
tion and most occupational infections occur as a result of 
exposure to blood. Other body fluids may contain infec- 
tious virus, however, and these are listed in Table 20.1. 
Percutaneous inoculation is the major route of infection in 
health care; there is no evidence of transmission of any of 
the common blood-borne viruses by the airborne route or 
from occupational or social contact that does not involve 
body fluid exposure. 



RISKS OF INFECTION 

Transmission of blood-borne viruses from patient to 
healthcare worker most commonly occurs following per- 
cutaneous exposure to infected blood through a 'sharps' 
injury. Although transmission may also result from con- 
tamination of broken skin, or of mucous membranes of 
the eyes or mouth, the risks are much lower. 



HIV 

The overall risk of acquiring HIV following a single per- 
cutaneous inoculation with HIV-infected blood is approx- 
imately 0.36% (1 in 275). The results of a case-control 
study of 31 healthcare workers infected occupationally, 
compared with 679 control subjects, identified several 
factors that affected the risks of percutaneous transmis- 



sion of HIV (Centers for Disease Control 1988). These are 
listed in Table 20.2. Note from the table that, in this 
case-control study, the use of the antiviral drug AZT 
reduced the transmission rate by 80%. This will be 
returned to later. The risk of acquiring HIV from mucous 
membrane or conjunctival exposure to blood from 
infected individuals is lower than from percutaneous 
inoculation. One seroconversion was reported on follow 
up of 1107 exposures (Jeffries 1995b). 

HBV 

Hepatitis B immunization has dramatically altered the 
level of risk to surgeons and other healthcare workers. 
Before the introduction of safe and potent HBV vaccines 
and subsequent checks of immune status, the risk of infec- 
tion could be as high as 30% after percutaneous injury 
involving the blood of an HbeAg-positive patient. 
Transmission of HBV has also been associated with 
mucous membrane exposure to blood and with bites from 
HBV-infected patients but the risk of infection from these 
routes has not been quantified. 

HCV 

The risk of percutaneous transmission of HCV has not been 
clearly defined and rates of 0-10% have been reported. In 
a small study of 68 healthcare workers in Japan, who sus- 
tained percutaneous exposure to the blood of HCV RNA- 
positive patients with chronic renal failure or HCV-related 
liver disease, seven (10%) developed markers of infection. 
In a survey of 3267 orthopaedic surgeons in the USA, HCV 
antibodies were present in 0.8%. The antibody prevalence 
increased from 0% in the 20-29 year age group to 1.4% in 
those over 60 years. For comparison, 12% had evidence of 
past or current HBV infection (ranging from 2.9% in the 
20-29 year age group to 26% in those 60+) and two sur- 
geons were HIV positive (both had other risk factors apart 
from surgery). 



Table 20.1 Body -fluids, etc. that should be 
handled with the same precautions as blood 



2. 
3. 



CSF 

Semen 

Vaginal secretions 

Breast milk 

Amniotic fluid 

Peritoneal fluid 

Pleural fluid 

Pericardial fluid 

Synovial fluid 

Any other body fluid containing visible blood 

Unfixed tissues and organs 



Table 20,2 Factors affecting percutaneous 
transmission of HIV during occupational exposure 



Factor 



Odds ratio* 95% CI 



Deep injury (intramuscular) 


16.1 


6.1-44.6 


Visible blood on device 


52 


1.8-17.7 


Needle used in a blood vessel 


S.1 


1.9-14.8 


Source patient with AIDS 


6.4 


2.2-18.9 


AZT prophylaxis used 


0.2 


0.1-0.6 


♦Significant at p < 0.01. 






Adapted from Centers for Disease Control (1988). 



217 




PREPARATIONS FOR SURGERY 



REDUCING THE JMSKSJW 

General measures - universal precautions 

It is neither cost effective nor reliable to embark on 
routine screening of patients for blood-borne viruses. 
The marker tests for infectivity, HIV and HCV antibodies 
and HBsAg become positive up to 12 weeks, 26 weeks 
and 26 weeks, respectively, after infection and a patient 
may be highly infectious before positivity is demon- 
strated. Similarly, it is unreliable to attempt to identify 
carriers of the viruses by designation of 'risk groups'. 
Although the blood-borne viruses HIV and HCV were 
originally associated with homosexuality and drug use, 
the spread of infection outside of perceived risk groups, 
and control of infection in those previously perceived 
to be in risk groups by education, needle exchange 
schemes, etc., means that 'risky activity' by anyone 
should raise the suspicion of possible infection. Faced 
with the ever present risk of occupational infection, you 
should adopt a policy of 'universal precautions' with 
regard to carrying out procedures with a risk of contact 
with high risk body fluids and tissues (see Table 20.1). 
The basis and procedure of using universal precautions 
was presented by the Centers for Disease Control (1987, 
1988, 1991) and by the UK Health Departments (1990, 
1998). As percutaneous inoculation is the major route of 
infection, take care when handling sharp instruments. In 
some studies, approximately 40% of inoculation injuries 
of staff have occurred during attempts to resheathe 
needles. 




Key points 

• Always pass sharp instruments to others 
through the vehicle of a rigid container, never 
directly. 

• Do not attempt to resheath needles unless 
there is a resheathing device available. Discard 
them into a 'sharps' container. 

Do not leave suture needles and scalpels on trays for 
others to clear away. Cover cuts and abrasions with 
waterproof dressings and wear disposable gloves if there 
is a risk of contamination of your hands with blood. Wear 
protective eyewear and a mask if there is likely to be any 
splashing with blood or other body fluids. 

It is possible to produce guidelines for the use of pro- 
tective clothing on the basis of an assessment of likely 
exposure to blood (Table 20.3). 

Attend to blood spillage on to a surface promptly, by 
first covering it with disposable towels, and apply a suit- 
able disinfectant, such as sodium hypochlorite (10 000 
parts per million available chlorine), in accordance to 
local infection control guidelines. 



Immune prophylaxis 

While neither passive nor active prophylaxis is available 
for HIV and HCV, HBV infection is preventable by immu- 
nization with the current, safe, genetically-engineered 



Table 203 Categorization of procedures according to risk of exposure to blood 






Category 



A(i) Contact likely: 

risk of uncontrolled 
bleedrng 

A(ii) Contact probable; 
splattering unlikely 



A(iii) Low likelihood of 
blood contact 

B No risk of blood contact 



Examples of procedures 



Major surgery 

Gynaecology 
Obstetrics 



Intra-arterial puncture 
Insertion/removal of intravenous/ 
intraarterial lines 

Dentistry 

i.m. r i.d., s,c. injections 
Most ward/clinic work 



Protective measures 



Full range of protective clothing (gloves, 
water-repellent gown and apron, 
protective headwear, mask, 
protective eyewear, protective footwear} 

Gloves to be worn 

Masks/protective eyewear to be available 



Gloves available 



None necessary 



Adapted from UK Health Departments {1990). 



218 



THE RISKS TO SURGEONS OF NOSOCOMIAL VIRUS TRANSMISSION 



20 



vaccines. All staff likely to be exposed to blood, tissues or 
other body fluids in the course of their work should be 
immunized and their antibody levels should then be 
checked to ensure that they have developed protective 
immunity. If response to the vaccine is inadequate, the 
healthcare worker's hepatitis B status should be investi- 
gated to exclude current or past HBV infection. Those 
who are susceptible to HBV and fail to mount an antibody 
response to the vaccine must be made aware that they are 
non-responders and, in the event of exposure to known or 
suspected HBV-positive blood, they should be offered 
passive protection with HBV immunoglobulin (HBIG). 

Reducing blood exposure of you and your 
patient during operation 

In an observational study by Tokars et al (1992), the rate of 
inoculation injury was recorded during the course of dif- 
ferent types of surgical operation. Percutaneous injury rates 
to the main operator per 100 procedures were 4 for 
orthopaedics, 8 for general surgery, 9 for coronary artery 
bypass grafting, 17 for gastrectomy and 21 for vaginal hys- 
terectomy Inspection of gloves after operation has revealed 
a perforation rate for single glove use of 11-54% (Church & 
Sanderson 1980, Brough et al 1988, Maffulli et al 1989, Smith 
& Grant 1990, Palmer & Rickett 1992). The wearing of two 
pairs of surgical gloves has been reported to result in per- 
foration of the inner glove in 2% of operations (Matta et al 
1988). Penetration of the glove material by a sharp instru- 
ment or needle has a significant wiping effect and this 
reduces the volume of blood and amount of virus trans- 
ferred. Studies using a paper prefilter model in vitro and an 
ex vivo porcine tissue model demonstrated a reduction of 
blood transfer of 46-86%, depending on whether a solid or 
hollow needle was used and on the gauge of the latter 
(Mast et al 1993). Thus, although standard disposable latex 
gloves offer no protection against needle penetration, this 
evidence of reduction of exposure to blood provides strong 
support for the use of gloves, even in simple procedures 
such as venepuncture, if there is a risk of injury to the oper- 
ator, for example in the case of an uncooperative patient. 

A number of aspects of surgical technique are worthy 
of appraisal in the interests of reducing the risk of percu- 
taneous injury. 




• Favour the 'hands-free' technique, in which the 
same sharp instrument is not touched by more 
than one person at the same time. 

The need for care in passing instruments to others has 
already been stressed. Needles, scalpels and other sharp 
instruments should not be left in the operating field. Have 
them removed promptly by the scrub nurse after they 
have been deposited in a neutral zone, such as a tray or 
kidney dish. Use instruments rather than fingers for 
retraction and holding tissues during suturing. Remove 
scalpel blades from handles with instruments and direct 
all needles and sharp instruments away from your own 
non-dominant, or your assistant's hand. Remove suture 
needles before tying sutures, or use instruments rather 
than fingers for tying. 

In addition to the discipline of carrying out surgical 
techniques, in appropriate circumstances consider using 
alternative equipment. Electrocautery, blunt-tipped 
needles and stapling devices may reduce the need for 
sharp instruments and needles. Avoid using sharp clips 
for surgical drapes. Prefer blunt clips or disposable 
drapes incorporating self-adhesive film. Employ scalpels 
which are disposable, have a blade release device or 
retractable blades, to remove the risk of injuries associ- 
ated with assembly or disassembly of these instruments. 

The risk of contact with infected blood varies depend- 
ing on the local prevalence of infections and the nature of 
the patient population. With the current distribution of 
blood -borne viruses, however, all operating theatre staff 
are exposed from time to time. The decision to introduce 
double-gloving for all surgical procedures may depend 
on a local risk assessment, but other measures to reduce 
exposure to blood and other body fluids can be applied 
to all operative procedures. 

Postexposure measures 




Key points 

Whenever possible have one person only 
working in an open wound or body cavity at 
any one time. 



Key point 

• As soon as possible after percutaneous 

inoculation or, in the case of operative surgery, 
as soon as the patient is stable and can be left 
to the care of others, wash the site of injury 
liberally with soap and water. 

Avoid scrubbing, encourage bleeding. Do not use anti- 
septic preparations, as the effect of these on local 
defences is unknown. Wash out splashes into the eye or 
mouth by irrigating with copious volumes of water. 



219 



20 



PREPARATIONS FOR SURGERY 



Complete an incident form and contact the occupational 
health department or another doctor designated with the 
responsibility of caring for staff, as specified in the local 
guidelines. 




Key point 



• Seek advice at once; if postexposure 
prophylactic drugs for HIV are to be 
considered, they should be started without 
delay, and ideally within 1 h of exposure. 

It is normal practice to take a blood sample from the 
staff member at this time as the stored serum can then be 
used as a baseline for further testing. Laboratory testing 
of the source patient, after pretest discussion and obtain- 
ing fully informed consent will aid further management 
by clarifying the risks, if any, of exposure to blood-borne 
viruses. 




Key point 



• Decisions on postexposure prophylaxis should 
not await results of testing the source patient. 
Immediate assessment of risk of transmission 
must include the source patient's history and 
the type and severity of the exposure. 

HIV 

Guidelines for the use of postexposure chemoprophyl- 
axis to prevent HIV infection of healthcare workers 
were issued in the UK in June 1997 (UK Health 
Departments 1997). Postexposure prophylaxis is recom- 
mended when there has been significant exposure to 
material known, or strongly suspected, to be infected 
with HIV. Significant routes of exposure are percuta- 
neous inoculation, exposure of broken skin or contact 
with mucous membranes, including the eye, and high 
risk material (listed in Table 20.1). As in equivalent 
guidelines issued in the USA, the first-line drugs for 
postexposure prophylaxis are currently combined 
zidovudine (AZT) 300 mg and lamivudine (3TC) 150 mg 
b.d., and nelfinavir 1250 mg b.d. Treatment should start 
as soon as possible, ideally within 1 h of exposure, and 
should be continued for 1 month. A negative test for HIV 
antibody 6 months after the exposure confirms the 
absence of occupationally acquired infection. 



HBV 

If the source patient is known or suspected to be an HBV 
carrier, the prophylactic regimen will depend on the 
immune status of the healthcare worker. Those who have 
never had vaccine should receive hepatitis B immuno- 
globulin (HBIG) within 48 h of exposure and a course of 
hepatitis B vaccination should be started as soon as possi- 
ble. In those who have been vaccinated, the recommenda- 
tion of the occupational health adviser is likely to depend 
on the record of the person's antibody response. If there is 
a recorded antibody response of more than 100 min ml 1 
within the previous year, no further action is necessary. If 
the person's blood has not been tested within the year, or 
if a lower titre was recorded, a booster dose of vaccine fol- 
lowed by retesting of antibody status may be necessary. 
Healthcare workers who have failed in the past to respond 
to the vaccine should be offered protection with HBIG. 

HCV 

There is currently no prophylaxis for HCV and follow up 
consists of monitoring liver function and testing for anti- 
HCV antibodies and HCV RNA. There is, however, 
growing evidence to suggest that commencement of 
antiviral therapy with interferon-a during the acute phase 
of HCV infection can prevent chronic carriage (Jaeckel et al 
2001), and occupational exposure to HCV is potentially 
the ideal indication for interventions of this nature. 



INFECTED HEALTHCARE WORKERS 



>:££i&=&^-&^^ 



••^^^^^^^^m^^/^^^\ 



Guidelines issued by the General Medical Council, 
General Dental Council and the United Kingdom Central 
Coordinating Committee for Nurses, Midwives and 
Health Visitors (UKCCC) stress the importance of health- 
care workers who consider that they have been at risk of 
infection with HBV or HIV seeking appropriate pretest 
discussion and testing. If found to be infected, they have 
a responsibility to be under regular medical supervision. 
Guidelines issued in the UK recommend that those who 
are infected with HIV or who are 'high infectivity' 
(HBeAg) carriers of HBV should not perform exposure- 
prone invasive procedures (UK Health Departments 1993, 
1994). Exposure-prone procedures are defined as: 

Those where there is a risk that injury to the worker 
may result in the exposure of the patient's open 
tissues to the blood of the worker. These procedures 
include those where the worker's gloved hands may 
be in contact with sharp instruments, needle tips or 
sharp tissues (spicules of bone or teeth) inside a 



220 



THE RISKS TO SURGEONS OF NOSOCOMIAL VIRUS TRANSMISSION 



20 



patient's body cavity, wound or confined anatomical 
space where the hands or fingertips may not be 
visible at all times. 

In the UK, until recently and according to the above 
guidelines, there were no practice restrictions to HBV car- 
riers without detectable HBeAg, unless transmission to 
patients had been demonstrated. In the light of accumu- 
lated evidence of transmission of HBV from HBeAg- 
negative carrier surgeons (harbouring precore variants of 
HBV) to their patients and better knowledge of levels of 
viraemia associated with such transmission events (The 
Incident Investigation Teams 1997), new guidelines 
became available in 2000. The Department of Health 
now recommends additional molecular-based tests for 
HBeAg-negative carriers who perform exposure-prone 
procedures (UK Health Departments 2000). Healthcare 
workers whose HBV viral load exceeds 10 3 genome 
equivalents per millilitre should not perform exposure- 
prone procedures. Those with viral loads below 10 3 are 
not restricted from any areas of work but should be 
retested at 12 monthly intervals. 

For some surgeons and other healthcare workers, con- 
fidential discussion between the person concerned and his 
or her health adviser may lead to minor changes in prac- 
tice that would allow work to continue with the avoidance 
of exposure-prone procedures. If there is any doubt, advice 
should be sought from a specialist occupational health 
physician, who may, in turn, wish to present the situation 
anonymously to the UK Advisory Panel for Health Care 
Workers Infected with Bloodborne Viruses (UKAP). 

Some specialities, e.g. dentistry, are concerned almost 
totally with activities that are, by definition, exposure 
prone. For HIV, HbeAg-positive and HBeAg-negative car- 
riers with high viral load (as defined above) working in 
such specialities, the only option in the UK is for retrain- 
ing in another speciality which does not require the use 
of exposure-prone procedures. 

No recommendations have yet been issued in the UK for 
healthcare workers found to be carriers of HCV unless they 
have been demonstrated to have transmitted their virus to 
a patient, in which case exclusion from exposure-prone 
procedures has been advised. Nevertheless, following 
several reports of transmission of HCV from healthcare 
workers to patients, the Advisory Group on Hepatitis has 
proposed new guidelines. One of the likely upcoming rec- 
ommendations is that healthcare workers who are found to 
have been infected with HCV and who are involved in 
exposure-prone procedures will have to be tested for HCV 
RNA. Demonstration of viraemia (detectable RNA) will 
preclude the individual from performing exposure-prone 
procedures, until sustained response to antiviral therapy is 



documented. A consultation exercise has recently taken 
place and implementation of the new guidelines is awaited. 



CONCLUSIONS 



%^?^<r^^^^^^^^^:. 



You will continue to be at risk, albeit small, of acquiring 
blood-borne viruses from your patients. The level of risk 
varies depending on the prevalence of viruses in the local 
population. Adoption of universal precautions and careful 
attention to operative technique reduces the risks to the 
operator and other staff to a minimum. There is consider- 
able cause for concern if you are expected to operate in 
situations where, for lack of resources, there is inadequate 
provision of protective clothing, such as impermeable 
gowns and disposable gloves, and hepatitis B vaccine. A 
significant exposure to the blood of a patient causes con- 
siderable anxiety for a period of up to 6 months and until 
laboratory tests confirm negativity. There is no reason for 
you to avoid exposure-prone procedures during this 
period, providing you are aware that there is a possibility 
of infection developing and provided that you practise a 
high standard of infection control. It may be necessary, 
however, for your medical adviser to recommend lifestyle 
changes, such as condom usage for sexual intercourse, and 
avoidance of donating blood, semen, etc. to prevent trans- 
mission to others by non-occupational routes. In the UK, 
as described earlier, guidelines for HIV- and HBV (HBeAg- 
positive, HBeAg-negative with high viral load)-infected 
healthcare workers advise strongly against participation in 
exposure-prone procedures. This is likely to be extended, 
in the very near future, to HCV-infected individuals who 
are shown to be viraemic This approach is not adopted in 
many other countries where either no restriction is placed 
on clinical practice or exposure-prone procedures can con- 
tinue providing the patient is informed of the situation. 



Summary 

• Do you recognize the procedures that 
raise the risks of viral transmission? 

• Will you determine to take precautions on 
behalf of yourself, your patients and your 
colleagues? 

• Will you resolve not to abandon universal 
precautions in emergency circumstances? 

• Do you know what to do if an incident has 
exposed you or anyone else to the risk of 
contamination? 



221 



20 ' 



PREPARATIONS FOR SURGERY 




References 



Advisory Committee on Dangerous Pathogens (ACDP) 1995 

Protection against bloodborne viruses in the workplace: HIV 

and hepatitis. HMSO, London 
Breuer J, Jeffries DJ 1990 Control of viral infections in hospital. 

Journal of Hospital Infection 16: 191-221 
Brough SJ, Hunt TM, Barrie WM 1988 Surgical glove 

perforation. British Journal of Surgery 75: 317 
Centers for Disease Control 1987 Recommendations for 

prevention of HIV transmission in health care settings. 

Morbidity and Mortality Weekly Report 36(2S): 1S-18S 
Centers for Disease Control 1988 Update: universal precautions 

for prevention of transmission of human immunodeficiency 

virus, hepatitis B virus, and other bloodborne pathogens in 

health care settings. Morbidity and Mortality Weekly Report 

37: 377-388 
Centers for Disease Control 1991. Recommendations for 

preventing transmission of human immunodeficiency virus 

and hepatitis B virus to patients during exposure prone 

invasive procedures. Morbidity and Mortality Weekly Report 

40(RR-S): 1-9 
Church J, Sanderson P 1 980 Surgical glove punctures. Journal of 

Hospital Infection 1 : 84 
Jaeckel E, Cornberg M, Wedemeyer H et al 2001 Treatment of 

acute hepatitis C with interferon alpha 2b. New England 

Journal of Medicine 345: 1452-1457 
Jeffries DJ 1995a Viral hazards to and from health care workers. 

Journal of Hospital Infection 30(suppl.): 140-155 
Jeffries DJ 1995b Surgery and bloodborne viruses. PHLS 

Microbiology Digest 12: 150-154 
Jeffries DJ 1997 Viral agents of bloodborne infections. In: Collins 

CH, Kennedy DA (eds) Occupational bloodborne infections. 

CAB International, Wellingford, pp 1-16 
Maffulli N, Capasso G, Testa V 1989 Glove perforation in 

elective orthopaedic surgery. Acta Orthopaedica Scandinavica 

60: 565-566 



Mast ST, Woolwine JD, Gerberding JL 1993 Efficacy of gloves in 

reducing blood volumes transferred during simulated 

needlestick injury. Journal of Infectious Diseases 168: 

1589-1592 
Matta H, Thompson AM, Rainey ]B 1988 Does wearing two 

pairs of gloves protect operating theatre staff from skin 

contamination? BMJ 297: 597-598 
Palmer JD, Rickett JWS 1992 The mechanisms and risks of 

surgical glove perforation, journal of Hospital Infection 

22: 279-286 
Smith JR, Grant JM 1990 The incidence of glove puncture 

during caesarean section. Journal of Obstetrics and 

Gynaecology 10: 317-318 
The Incident Investigation Teams and Others 1997 Transmission 

of hepatitis B to patients from four infected surgeons without 

hepatitis B e antigen. New England Journal of Medicine 336: 

178-185 
Tokars JL, Bell DM, Culver DH et al 1992 Percutaneous 

injuries during surgical procedures. JAMA 267: 

2899-2904 
UK Health Departments 1990 Guidance for clinical health care 

workers. Protection against infection with HIV and hepatitis 

viruses. Recommendations of the Expert Advisory Group on 

AIDS. HMSO, London 
UK Health Departments 1993 Protecting health care workers 

and patients from hepatitis B. Department of Health, 

London 
UK Health Departments 1994 AIDS /HIV-infected health care 

workers: guidance on the management of infected health care 

workers. Department of Health, London 
UK Health Departments 1997 Guidelines on post-exposure 

prophylaxis for health care workers exposed to HIV. 

Department of Health, London 
UK Health Departments 1998 Guidance for clinical health care 

workers. Protection against infection with bloodborne 

viruses. Department of Health, London 
UK Health Departments 2000 Hepatitis B infected health 

care workers. HSC 2000/020. Department of Health, 

London 



222 



SECTION 4 




223 



This page intentionally left blank 




Good surgical practice 



/?. M. Kirk, J, Dawson 




Objectives 



Understand and accept your 

responsibilities. 

Commit yourself to the care and 

well-being of your patients and preserve 

their confidentiality. 

Work within your capabilities. 

Allocate your time sensibly. 

Keep good notes. 

Be a good team player. 

Preserve your integrity. 



Try not to be a man of success, but try to be a man of 
value. Albert Einstein 

If you are going to worry about this in bed tonight, 
Doc, get it right now.' 

The peerless London surgeon Norman Tanner never 
said this; his every action proclaimed it. This chapter 
was previously contributed by the late John Dawson, 
a good friend, dedicated teacher, setter of high stan- 
dards, and, like me, privileged to train with Norman 
Tanner. 



INTRODUCTION 






^^5&S^:^S^ 



You must behave competently and honourably towards 
your patients, colleagues and society, and maintain open- 
ness to inspection. Aim to achieve high standards in all 
aspects of your life. Incompetence or dishonesty detected 
in one area implies similar failings in other areas. 

In the past we were privileged to satisfy only our own 
consciences. At the end of each day we hoped to be able 
to say, T may have made errors but not from want of 
trying to achieve the best for my patients and those with 
whom I have worked/ Most of us relied on this and 
resolved ourselves, without the need to be exhorted by 
others, to do better when we fell below the standards to 



which we aspired. However, because our profession 
sometimes failed to weed out the few identified as incom- 
petent, lazy or dishonest, we have lost some of the trust 
we formerly commanded. Society regards us more criti- 
cally than formerly, and we need to help restore our 
former high reputation. 



CLINICAL COMPETENCE 

1. This is the foundation of all your professionalism. 
You need knowledge, and skill in taking a history, exam- 
ining patients, making decisions and acting upon them. 
You constantly need to improve them by following your 
results to assess the outcomes, in the hope of learning 
how to improve them. 

2. Your competence is most under strain in emer- 
gency circumstances. When performing electively you 
can obey the rules. In an emergency you often need to 
decide in an instant whether you should or should not 
conform. There are circumstances when you need to 
interpret rules sensibly, as they are made to cover most 
but not all situations. The heroic, legless, Second World 
War airman, Douglas Bader, declared, "Rules are for the 
guidance of wise men, and the blind obedience of fools/ 
But remember that you may be called upon to justify 
your actions. 

3. Competence is not a 'once-and-for-all' achievement. 
It is a continuous process of critically noting your perfor- 
mance in all aspects, identifying your failures and learn- 
ing from them. It depends upon meeting, watching and 
listening to your colleagues, attending courses and criti- 
cally reading the literature. 




Key points 



Surgical improvement does not develop by 
merely working hard. 

Stand back, identify weaknesses, search for 
improvements and implement them. 



225 



21 




OPERATION 



PATIENT TRUST 

A vital characteristic for a medical attendant is to be trust- 
worthy. If we are trusted, our patients are open with us, 
allow us to examine them and perform procedures that 
may be difficult or impossible without their cooperation. 
They will not tell us^ the often private information we 
need to know, unless they trust us. 
To gain patients' trust we need to: 

1. Communicate with them (see Ch. 47). This implies 
not just giving them information but also being 
receptive to the verbal and non-verbal information 
they transmit. 

2. Involve them in the decision making (see Ch. 13) so 
they can give informed consent to what is agreed 
upon (see Ch. 14). Accede to a request for a second 
opinion; it is not a blow to your dignity. 

3. Be open with them in admitting ignorance, in 
admitting that there has been a failure in managing 
them, in admitting our own error of judgement or 
practice. Whenever we admit to a failure we should 
always clearly state, and be prepared to discuss, 
what we intend to do to correct it. 

4. Respond to the patients' anxieties regarding their 
outlook, discomfort or pain, complications, loss of 
function and loss of dignity. Saying 'Sorry/ is not an 
admission of guilt but an expression of sympathy. 

5. Provided the patients agree, inform and discuss with 
relatives at all stages what is happening, what is 
proposed and what is the likely outlook. Relatives 
often exert great influence in supporting and 
reassuring your patients. Conversely, they may 
undermine patients' trust in their recovery and in 
your management. 

6. Protect patients' confidentiality and preserve their 
dignity. Illness attacks not only their bodies but also 
their morale; they may wish to keep their health 
problems private. 



PROFESSIONALISM 

1. Strictly speaking surgeons (Greek cheir = hand + 
ergon = work; hence, manual workers) are not profes- 
sionals - but we now consider ourselves to be 'physicians 
who perform operations'. This is not strictly correct; 
many medical specialists perform skilful manipulations 
(Latin mantis = hand + plere - to fill). 'Professionalism' 
carries the connotation of performing competently and 
autonomously without the need to be directed, in order 
to produce a satisfactory result. 

2. The four most important qualities of a professional 
surgeon, which are often overlooked because they are not 



subject to objective assessment, are the four 'Cs' - 
common sense, competence, commitment and compas- 
sion. When you take up a task, ensure that you apply 
these qualities to achieve the best possible result. 

3. Maintain your professionalism in whatever circum- 
stances you practise: 

a. Respect the fact that some patients have different 
beliefs from you and may reject aspects of your proffered 
treatment for religious or other reasons. Jehovah's 
Witnesses, for example, may reject blood transfusion. 
Because many beliefs are subject to personal interpreta- 
tion, make sure you know what exactly are the implica- 
tions when patients declare their adherence to a particular 
sect. 

b. In an emergency your professional judgement is put 
under increased strain (see Ch. 13). You may be called on 
to carry out procedures at the edge of, or beyond, your 
capabilities. As you make your decision and act upon it, 
recognize that you will need to justify it to your patient, 
your peers and to your own conscience. 

c. If you participate in specialist procedures, such as 
organ transplantation, adhere strictly to the legal and 
ethical requirements. 

d. If you are present at an armed conflict, be aware that 
your actions may be under intense scrutiny to detect 
whether you are favouring one side over the other. Treat 
all patients who are presented to you on an equal basis 
and to the highest possible standard. 

e. Treat prisoners as you would anyone else. Refuse to 
participate in any action that may cause physical or 
mental suffering. 

f. If you work in another country, avoid offending 
against local laws and customs. Do not, however, allow 
your standards to fall, even though you may not 
have all the facilities you would normally have at your 
command. 

g. Do not perform any operations that conflict with 
your own moral values. 

4. We are all in part the products of our teachers. One 
of the privileges of being in the profession of surgery is 
that we are always trainees and at the same time we can 
all be teachers. Pass on to your juniors the ideas, the 
wisdom, the skills that you have acquired. With permis- 
sion from your seniors, delegate procedures in which you 
are skilled, while you teach and supervise your juniors. In 
the past, too much unsupervised responsibility was dele- 
gated to trainees, summed up in the aphorism, 'See one, 
do one, teach one.' This is no longer tolerated. 

5. Preparing to teach forces you to be ready to justify 
statements that you make, and actions you take. It is one 
of the most effective ways of learning for yourself and 
honing your skills. Many procedures are best taught by 
example, copied - often unconsciously - by the trainee, 
not by reading or listening. 



226 



GOOD SURGICAL PRACTICE 




21 



RECORDS 



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&^^^ 9 *^&PK 



1. We like to be considered as people of action, rather 
than reporters of action. If we are to be accountable, 
however, we must keep accurate records (see Ch. 48). It 
is not enough that you have acted correctly. Others, 
wishing to inspect your actions, must be able to confirm 
them. 

2. Write or dictate records as soon as possible after the 
event. Ensure they are comprehensive, comprehensible, 
dated and signed so they are attributable to you. Record 
not only the positive findings but also the negative ones: 
if you do not mention these it could be assumed that you 
did not examine for them. Do not use abbreviations that 
can be misconstrued: spell out 'Left/ 'Right/ Jargon that 
you use may be incomprehensible or misconstrued by 
others. 

3. There are no more important records than those 
describing surgical operations. Detail what you found, 
what you sought but did not find. Describe all the proce- 
dures, any difficulties and the situation at the end of the 
operation. It is vital to recount what must be done in the 
immediate postoperative period regarding monitoring, 
circulatory and respiratory management, pain control, 
drug treatment, and any special instructions you wish to 
be followed. Make sure you inform those who look after 
the patient under what circumstances you wish to be 
informed. 



HUBRIS 



'^<£$&&^g& 



1 . I have deliberately used this unusual word (Greek 
= excessive pride). Although it is reasonable to take 
pride in accomplishment, overweening pride is a dan- 
gerous emotion. We are all fallible. No one can claim to 
make the right decisions and perform perfectly every 
time. Protecting your pride is a dangerous path on 
which to embark; each step racks up the likelihood of 
disaster. 

2. Do not be too proud to call for - and accept - help 
or advice, or the taking over of your patient by someone 
who is more capable than you are. 

3. Do not be too proud to admit error to your patients, 
your peers and, particularly, yourself. 



TIME MANAGEMENT 

1. This is often self-management. You rarely have but 
a single commitment. More frequently you have many. 
You must rank your commitments and review the 
ranking at intervals, as a previously non-urgent problem 
may suddenly become urgent. 



2. Except in an emergency, ensure that you fully com- 
plete one task before leaving it to start another. It is 
ineffective and unprofessional to leave a trail of almost 
completed tasks. However, be aware that acute situations 
develop so that you are called urgently. Although there is 
a temptation to complete the present task, in some cases 
you must abandon whatever you are doing and return to 
it later. 




Key point 

• React to changed circumstances. Compare the 
urgency of competing demands, decide the 
correct action and carry it out. 

3. Some people apply pressure on you for immediate 
action, against your better judgement. If other problems 
are more urgent, you may need to refuse. Be as diplomatic 
as possible but do not make undeliverable promises. 



TEAM MEMBERSHIP 



:■: ^>^r&^:^'4i^i^^^^^ 



1. In the past, surgeons were undisputed team leaders 
and decision makers. We were depicted as the courageous 
pioneers, sometimes succeeding, sometimes failing to 
cure or relieve our patients. 

2. The mores (Latin moris = custom) have changed dra- 
matically. No one is immune from criticism or from com- 
parison of their results with those of their peers (Latin par, 
paris - equal). We no longer work as individuals. For 
example, anaesthetists who initially worked under orders 
from surgeons now unequivocally take charge of the 
patient's well-being, freeing us to concentrate on the deci- 
sions and technical problems of the operation. The spe- 
cialists in imaging and other diagnostic aids, assistants, 
specialist and general nurses, physiotherapists, techni- 
cians and many others form part of the team, each one 
having an input into the general decisions and necessary 
actions. The best teams work in harmony, with each 
member feeling important, respected and therefore loyal 
to the team. 

3. The change in attitude is fundamental. In the past an 
opinion carried weight according to the distinction and 
seniority of the proposer. Now each opinion is, or should 
be, judged on the merits of its logic and the evidence 
offered to support it. 

4. Being a good team member offers you many bene- 
fits. Your colleagues will celebrate your successes and 
sympathize with your failures. When you need help they 
will respond. If you are a poor team member you may not 
always rely on these important supports, or they may be 



227 




OPERATION 



given reluctantly. We all need encouragement when our 
self-esteem is reduced, as inevitably happens from time to 
time when a series of things go wrong. 

5. Team membership, however, places you in circum- 
stances of conflicting loyalties. Although you wish to 
support and protect your colleagues, this must not take 
precedence over your responsibilities to patients and 
society. If any of your colleagues fail in their duties, or 
are physically or mentally sick and present a risk to 
patients, you must encourage them to take appropriate 
treatment and inform appropriate authorities if they do 
not. 



TEACHJI|G^AND 

1 . Take every opportunity to pass on your knowledge 
to your trainees. Of course, it is not your own knowledge. 
It is mainly acquired from your own trainers and you are 
an intermediary. It is not just the facts that you transmit 
but the unconscious influence you have on their attitude, 
if your behaviour and performance are to the highest 
standards you can achieve. 

2. Always try to give those junior to you time to 
express their opinions first, to give them the opportunity 
and challenge of making and preparing to act on deci- 
sions, as they will need to do when they become 
autonomous consultants. 

3. It is often difficult to delegate responsibility to 
others, but monitored, progressive delegation is a vital 
process of preparing for tomorrow's consultants. 




Key point 

As a surgeon in training, always seek your 
chief's approval before delegating 
responsibility or practical procedures. 



4. You may find it even more difficult to delegate prac- 
tical procedures that require skilful accomplishment. 
Again, first delegate simple procedures under direct 
observation and progress to more complex ones with less 
obvious - more discreet - monitoring. 



INTEGRITY 



--3&3&&!i*:¥*^^^ 



1. Place a high value on your probity and integrity. 
Patients, colleagues and the general public will usually 
forgive you for mistakes. We all, inevitably, make them 
from time to time, as we work in a field in which we do 
not, and cannot, know all the facts in the present state of 



our knowledge. They will not so easily forgive deceit, 
dishonesty or duplicity. 

2. Moreover, once you have been found guilty of 
discreditable behaviour you have forfeited your good 
character and will never again be fully trusted. 

3. As a professional, be honest in publishing your clin- 
ical results, your research techniques and the findings. 

4. You cannot separate your professional from your 
private reputation. A surgeon who unfairly blames a col- 
league for his or her own mistake, falsifies a legal report, 
claims money illegally or is corrupt in any matter has a 
stained character. 

5. Avoid conflicts of interest. Avoid accepting gifts, 
favours, hospitality or anything that puts pressure on 
you. You must be able to make decisions on clinical neces- 
sity, not for any other reasons. 

6. Financial dishonesty arouses particular scorn. Take 
exceptional care not to take or accept any money to 
which you are not entitled or which puts you under an 
obligation, which will undoubtedly subsequently be 
called in. 



HEALTH.. 

1. In addition to the other qualities required, the prac- 
tice of surgery demands outstanding stamina. It is neces- 
sary to respond to a sudden emergency at the end of a 
long and busy routine day, or to a sudden disaster near 
the end of an arduous major operation. 

2. Avoid risking your health from accidents and infec- 
tions, including from needlestick injuries (see Ch. 20); if 
you sustain a needlestick injury, report it - do not hope for 
the best. In emergency circumstances do not unnecessar- 
ily place yourself at risk. 

3. Alcoholism and drug taking impair your judgement, 
put your patients at risk and also risk your career. 

4. If you develop any condition that places your 
patients at risk, either because it impairs your perfor- 
mance or because you may pass on an infection, you must 
immediately seek a medical opinion 

5. If one of your colleagues develops a condition that 
threatens the welfare of patients you must exhort him 
or her to seek medical care. If your advice is rejected, 
remember that your first loyalty must be to the patients. 
In the past we have placed loyalty to our colleagues above 
our responsibility to our patients. 



ERRORS 






1. There are errors of judgement. Such errors arise from 
the complexity of weighing the multiple factors to be 
taken into account. 



228 



GOOD SURGICAL PRACTICE 




21 




Key points 




• Errors of judgement are inevitable in medicine 
and surgery. The problems are too complex, 
rarely black and white, often affected by 
unknown and unknowable factors. Accept that 
you will inevitably make judgements that 
prove wrong in retrospect. 

• Success is not always a sign of good 
judgement; robust patients survive poor 
management. Equally failure may result from 
factors you could not have anticipated. 

2. We all make them. Often we recognize errors in ret- 
rospect because we have more information, especially the 
outcome of our earlier decisions. As we gain experience 
we hope to reduce the number of errors we make in the 
future. We hope to learn from our own errors and from 
the errors of others. 

3. A different type of error is sometimes called a 
'systems 7 error, perhaps because it could be prevented by 
changes in the way in which the system works. Examples 
are the administration of a harmful substance, or adminis- 
tration by an incorrect route. The first of these could be pre- 
vented by placing the harmful substance out of easy access; 
the second could be prevented by making the connection 
of a type that can be made only to the correct acceptor. 
Comparisons are often made between medical errors and 
those that occur in aeroplanes. In the former there is a ten- 
dency to apportion blame and label it, 'human error'. This 
makes no contribution to preventing repeated errors but it 
dissuades those who make errors from declaring them. If 
an airline pilot makes an error and admits it, attempts are 
made to study it and consider whether some change in the 
system could prevent it from occurring again. Be prepared 
to report when things go wrong but should have gone right 
- these are sometimes pompously called 'adverse incident 
reports 3 ' (AIR)s. In bringing them to attention you may be 
saving future patients and colleagues from disaster. 

4. As a trainee, report any error to your chief without 
delay. Do not attempt to deal with it beyond your com- 
petence, hide it or blame it on others. Honestly admitted 
errors are excusable; failure to admit to them loses the 
trust of your chief. 



Key point 

Gain and retain the trust of your chief. The 
greatest compliment your chief can pay you is 
to say, 'If that person is on call for me at night, 
I sleep well/ 



COMPLAINTS AND CLAIMS 






1. Make every effort to avoid patient dissatisfaction by 
adhering to good surgical practice and maintaining 
good, open relations with your patients. 

2. Keep complete, up-to-date, comprehensive, 
comprehensible records of what you have done, what 
is happening, what your plans are, what you have 
discussed with your patients. 

3. If, in spite of your best efforts, there are 
complications, or patients are disappointed with the 
results, openly declare the situation and state what 
you intend to do. 

4. Do not hesitate to express your compassion if 
something has gone wrong. Do not hesitate to 
declare your responsibility if you have made an 
error. 

5. Make a written record of what passes between you 
and the patients. 

6. Continue your normal careful comprehensive 
treatment. 

7. Cooperate with any investigation. 




m Further reading 



1997 The surgeon's duty of care: guidance for surgeons on 
ethical and legal issues. Senate of Surgery of Great Britain 
and Ireland, London 

2001 Good medical practice. General Medical Council, London 

2002 Good surgical practice. Royal College of Surgeons of 
England, London 

Useful link 

www.rcseng.ac.uk Code of practice for the surgical 
management of Jehovah's Witnesses. Royal College of 
Surgeons of England 1996 (available on line only) 



229 




Surgical access: incisions, and 
the management of wounds 



D. J. Leaper, L Low 




Objectives 

Be aware of the technical factors 
contributing to wound infection. 
Understand the principles underlying 
choice and techniques of wound access. 
Accept the need for aftercare of surgical 
wounds. 



There are records which describe successful wound 
management from as long ago as the time of the 
Assyrians and the ancient Egyptian Empire. Techniques 
using sutures and threads, linen adhesive strips, and 
even soldier ant heads as skin clips, have all been 
described historically. The management of wounds, their 
classification, surgical dressings and subsequent healing 
is an ever-evolving field based upon a better under- 
standing of the pathophysiological principles behind 
them. From the time of Hippocrates and Galen, who rec- 
ognized that infection impaired wound healing, to the 
development of antiseptic and aseptic technique through 
the work of Semmelweis, Pasteur and Lister, research 
continues into the factors that affect the quality of 
healing, cosmetic outcomes and the functional recovery 
of the damaged tissue. 

The development of operative surgery and anaesthesia 
seems to know no bounds, yet the fundamental process 
of wound healing must not be forgotten. The aphorism of 
'cut well, sew well, get well' depends on a knowledge of 
wound healing mechanisms and the adverse effects that 
may influence them. 



SURGICAL ACCESS AND INCISIONS 



1. Before you even consider placing a knife to skin, 
there are general steps to consider before each and every 
case. These include correct positioning of the patient, hair 



removal, sterile skin preparation and wash, and sterile 
draping. 

2. Should you give antibiotic prophylaxis, and deep 
venous thrombosis prophylaxis (see Chs 8, 15, 19)? 

3. Carefully position the patient for most advantageous 
surgical access and patient safety. Take care to avoid pres- 
sure, particularly on the skin over bony prominences, and 
on superficial arteries and nerves. Depending on the 
operation, changing body position will enhance exposure 
of the area involved. Examples are the modified Lloyd- 
Davis position for approach to the perineum, a lateral 
position for a retroperitoneal approach to the kidney, the 
prone jack-knife position for access to the rectum and 
anus, the Trendelenburg position for varicose vein 
surgery. Operator preference may also influence patient 
position. 

4. Hair removal was conventionally performed the day 
before surgery. However, it has been shown that in clean 
operations, shaving body hair more than 12 h before the 
operation doubles the rate of wound infection. If it is 
necessary, undertake shaving shortly before surgery; 
supervise and check it. Clipping of hair reduces infection 
rates to a tenth of those following shaving, and avoids the 
risk of minor skin abrasions and cuts due to inexpert or 
unsupervised shaving. Remove hair for aesthetic reasons 
and to allow painless removal of dressings. Leaving it in 
situ does not increase wound infection rates. 

5. The most popular sterile skin preparation in the 
United Kingdom is 10% povid one-iodine (1% available 
iodine) in 70% alcohol. This helps by staining the skin to 
demonstrate any areas that have been missed. If the 
patient is allergic to iodine, use 0.5% chlorhexidine in 
alcohol. 

6. Now delineate the operative field with sterile 
drapes. Conventionally these are resterilized double- 
thickness linen sheets that are held in place with towel 
clips. Take care, as they are designed for multiple use. A 
drawback is that they allow permeation by body fluids 
and, once soaked, can desterilize the operative field. Use 
waterproof disposable fabrics which do not allow this 
permeation, especially in cases of contamination, or when 
there is a risk of hepatitis or human immunodeficiency 



230 



SURGICAL ACCESS: INCISIONS, AND THE MANAGEMENT OF WOUNDS 



22 



viral contamination. They are expensive. Incise drapes 
of adhesive polyurethane film were introduced over 
30 years ago. They are most commonly used in prosthetic 
orthopaedic and vascular surgery, when there is a risk 
of opportunistic infections by skin organisms such as 
Staphylococcus epidermidis. Newer versions of antibiotic- 
impregnated drapes significantly reduce bacterial skin 
counts, but there is no definite indication that they reduce 
infection rates. In general surgery they are useful in iso- 
lating stomas or other infected areas, such as a separate 
infected wound that is close to the planned incision. 
Wound guards may also be used to reduce wound con- 
tamination during open viscus surgery but they do not 
reduce the risk of wound infection. 

Principles of access incisions 

1. In conventional open surgery the purpose of the 
incision is to allow adequate exposure of the affected area 
or organ. Careful organization and planning is essential. 
If the operation is unfamiliar to you, revise the anatomy 
or obtain help from a more senior colleague. In order to 
perform any procedure competently you must have good 
access, with a long enough incision to avoid excessive 
retraction. Plan the incision using surface landmarks as a 
guide, then perform the incision as a single movement. 
This leaves a better cosmetic result than one that has been 
extended. The exposed area then allows viewing, mani- 
pulation of tissues and control of other structures. In some 
cases, linear incisions may not provide this and angled 
incisions may offer better exposure, the side within the 
angle being widely retractable; for example, the roof-top 
abdominal incision used for pancreatic operations. 

2. When operating on limbs, do not make the incision 
cross a joint perpendicular to the flexure line, as subse- 
quent scarring and contracture may limit the function 
of the joint on recovery. Wrinkles and contour lines 
(Langer's lines) are useful to disguise resultant scars. 
With a good knowledge of the anatomy, and gentle tissue 
handling, damage to important structures will be mini- 
mized. An assistant can also warn of potential trouble. 
Nerves, tendons and vessels often lie in the most direct 
path to the area affected and damage to them can impair 
future function and healing; for example, vascular supply 
to a skin flap and subsequent necrosis. 

3. Vascular supply and wound healing. Linear incisions 
rarely fail to heal because of injury to the vascular supply, 
but angled incisions may do so. When an incision is made 
parallel to a previous scar, for example a paramedian inci- 
sion next to a midline incision, the intervening tissue is 
rendered ischaemic and healing will be prejudiced. Avoid 
this by reopening the old scar or excising it if there will 
not be any undue tension on subsequent closure. There is 
danger to underlying structures if you use an old scar 



with, for example, bowel adherent to the base of an old 
abdominal wound. 

4. Tissue planes. Acquire an intimate knowledge of 
tissue planes to obtain correct exposure. Normal anatomy 
is often distorted in the presence of disease. If you dissect 
in the wrong plane, you may cause inadvertent damage 
and also fail to encompass diseased tissue completely, as 
in cancer clearance. 

5. Cosmetic aspects. The resulting scar is the only part of 
the operation seen by the patient. This is particularly 
important in facial surgery but an ugly scar in any area 
of the body can make the patient feel self-conscious. A 
young woman may feel permanently embarrassed by an 
ill-planned and distorted breast scar. 

6. Infection. Do not allow an initially clean operation to 
become contaminated as a result of operation. In poten- 
tially clean-contaminated procedures, for example elec- 
tive large bowel resection, minimize and isolate any 
faeculent contamination by placing clean packs around 
the bowel and wound before entering the bowel. Discard 
swabs or instruments once they have been soiled, change 
to sterile gloves, and make use of peritoneal lavage to 
wash out dirty and infected material. Antibiotic prophyl- 
axis has been unequivocally shown to reduce wound 
infections. In clean procedures their use is controversial. 
Frequently, an operation is carried out for established 
infection, or you encounter infection unexpectedly. Be 
willing to limit the procedure to drainage of pus and exci- 
sion of necrotic tissue. Once the wound is clean and granu- 
lating you may then explore the wound and close it at a 
later date. This is delayed primary or secondary closure. 




Key points 



• Acquire an intimate knowledge of the anatomy 
to reach your objective safely, and in the right 
plane. 

• Remember that disease processes distort the 
anatomy and may weaken the tissues. 

Closure 

1. The ability of a wound to heal is based upon several 
factors: both local and systemic. Locally, ensure that there 
is an adequate blood supply to the tissues, avoid tension, 
dead space and haematoma formation. Deal adequately 
with infection. Systemic factors include comorbidity such 
as diabetes, jaundice or renal failure, low serum albumin 
below 30 g 1 _1 , and trace element deficiencies. Ask about 
medications such as corticosteroids, immunosuppressives 
and cytotoxics, and enquire about previous irradiation 
(see Ch. 6). 



231 



22 



OPERATION 



2. Take care to achieve the best appearance of the scar, 
as the patient's perception of success is often based on the 
resulting appearance, not on the speed of healing or its 
ultimate tensile strength. Appose the tissues on either 
side of the incision and prevent them from separating. 
Inflammatory cells and fibroblasts can then bridge the 
defect. Healing cannot take place if differing tissues are 
opposed or other structures interposed. 

3. Avoid tension when closing, particularly when 
tissues are excised and the margins of excision are 
brought together. This may demand a simple relieving 
incision, or a more complicated flap. There are circum- 
stances when tension is inevitable and you must accept 
and allow for it. 

4. As a general rule, repair each layer of tissue separ- 
ately to restore the tissue planes. You thus avoid leaving 
a potential dead space where fluid, blood or infection 
may accumulate. If this is unavoidable, consider insert- 
ing a drain tube, preferably a closed system, under 
vacuum; remove it as soon as possible to avoid an 
ascending infection. 

5. Control bleeding. If you do not, you risk haematoma 
formation, thereby separating the tissues. This prevents 
healing and becomes a nidus for infection. 

6. The opposing edges are most frequently united 
using sutures. Choose materials that provide maximum 
strength and minimum tissue reaction. Historically, 
natural substances were popular, such as silk and catgut, 
which is now avoided for fear of transmitting prion dis- 
eases. 'Prions', coined from 'proteins', are transmissible 
'rogue' proteins postulated to cause diseases. They are 
now replaced by synthetics that behave reliably, whether 
they are intended to be absorbed or to remain relatively 
unchanged. 




Key point 

The need to restore tissue planes is vital when 
structures move against each other; tendons 
adhere and become fixed if they are not 
resheathed in flexible areolar tissue. 



Laparotomy incisions 

1. Opening the abdomen has some special aspects. The 
choice of incision depends on the purpose of the 
intended operation. When it is performed to carry out 
a specific procedure, place the incision to provide 
maximum exposure (Fig. 22.1). If you are exploring the 
abdomen, use a midline vertical incision or paramedian 
approach in adults. The paramedian (Greek para - beside 
+ Latin medius = middle) incision passes through the 




Fig. 22.1 Favoured laparotomy incisions: 

A, paramedian; B, midline; C, Kocher; D, transverse; 

E, Lanz; F, Pfannenstiel. 



rectus sheath but you can draw aside the medial part of 
the intact rectus muscle. It acts as a shutter on closure 
(Fig. 22.2). In infants, transverse incisions may be more 
appropriate. 

2. Intra-abdominal pressure is unavoidable in closure 
of the abdomen, therefore tension is inevitable. If the 
abdomen is distended, this increases tension. Avoid the 
factors that increase the risks of wound dehiscence and 
incisional hernias. 

3. Delay closing the abdomen if this will so increase 
tension that it creates abdominal compartment syndrome, 
risking respiratory complications, sepsis and organ 
failure. 

4. Upper abdominal incisions are more likely to 
dehisce (Latin de - intensive + hiare = to gape) than lower 
incisions; it is rare for Pfannenstiel, transverse or appendix 
wounds to dehisce. The lateral paramedian incision is vir- 
tually free of risk of dehiscence, and has a very small risk 
of hernia formation. Hernias through laparoscopic ports 
are now well recognized and various techniques have 
been described to close them. 

5. The value of layered closure or mass closure has also 
been debated. The wound dehiscence rate following 
layered closure with catgut sutures fell from approxi- 
mately 10% to less than 1% when using a mass closure 



232 



SURGICAL ACCESS: INCISIONS, AND THE MANAGEMENT OF WOUNDS 




Standard 
paramedian 



Midline 



Lateral 
paramedian 




Fig. 22.2 Lateral and standard paramedian incisions: a = 2 cm; b = two-thirds from midline to lateral rectus sheath. 



with a non-absorbable suture. As a result of the work of 
Jenkins (1976), a surgeon at Guildford in Surrey, wound 
dehiscence occurred in only 1 in 1505 cases using a non- 
absorbable, continuous mass suture. He hypothesized 
that the suture used should be at least four times the 
length of the incision, placed 1 cm from the wound edge 
and not more than 1 cm apart. The suture tension should 
be just sufficient to oppose the edges. Do not draw sutures 
too tightly, rendering the edges ischaemic or causing the 
sutures to cut through, allowing buttonhole hernias to 
form through the lateral suture line. 

6. Use of an absorbable thread may avoid 'cutting 
through' of a suture. Polydioxanone (PDS), polyglactin 
(Vicryl), and polyglycolic acid (Dexon) are predictably 
absorbed and their tensile strength is long lasting. 

7. Prevention of intra-abdominal adhesions has gained 
interest, in the hope of avoiding the morbidity associated 
with subsequent small bowel obstruction. Minimize tissue 
trauma and irritation, handle the tissues gently, use non- 
reactive suture materials, avoid drying and cooling the 
tissues by using frequent, warmed sterile saline lavage. 
Steroids, non-steroidal anti-inflammatory drugs and 
dextran have all been used but their efficacy is unknown. 
Newer techniques involve using a sodium hyaluronate- 
based bioresorbable membrane or 0.5% ferric hyaluronate 
gel (Intergel) solution, which have been shown to be effi- 
cacious at a second look laparoscopy 6-12 weeks later. 
Whether they have a long-term prophylactic effect has not 
been proven. 




Key point 



• Avoid complications by correctly siting the 
incision, choosing the correct materials to close, 
and employing impeccable technique 
throughout. 



Chest incisions 

There are three principal routes into the chest. The lateral 
thoracotomy follows the line of the upper edge of a rib, 
avoiding the neurovascular bundle under the rib. It 
allows exploration of the hemithorax for trauma or pul- 
monary surgery. In some cases a combined thoracoab- 
dominal incision is used. This usually continues the line 
of an incision along one of the lower ribs and is carried 
through the costal margin into the abdomen. Endoscopic 
procedures can be undertaken for cervical sympathec- 
tomy It gives outstanding exposure of the lower third of 
the oesophagus and fundus. Access to the pericardium, 
heart and great vessels is achieved through a median 
sternotomy. 



PRECAUTIONS AGAINST LOSS OF 
INSTRUMENTS OR SWABS 

1 . Correctly organize instrument trays, limiting the 
number of individually packed instruments as far as 
possible. 

2. Arrange swabs and packs in 'fives' bound together 
with red cotton, or, if small, carefully packaged, for 
example on a safety pin. 

3. Check the number of instruments on trays against 
printed lists incorporated in each pack. 

4. Record all sutures, packs, swabs, needles and extras 
clearly and legibly on a board in the theatre. 

5. Use special swab racks, including the modern 
disposable wallets, which facilitate counting at the 
end of the operation. 

6. Mark radio-opaque, non-implantable, non-metallic 
equipment such as drains and the laparomat 

7. Sign the theatre record book and have it 
countersigned by the scrubbed and assistant 
nurses. 



233 



22 




OPERATION 



8. Ensure the count is complete and correct before you 
commence closure. 

9. Record and sign that the count was correct at the end 
of the operation note in the patient's record. 



tk~ 



Key points 



Establish a simple routine of accountability, 
and a permanent and accurate record. 
Precautions are like a chain - every link must 
be intact or it fails. 



SKIN CLOSURE 



^;^&'&3^^^-59&^ 



1. Close skin perfectly, avoiding tension and inversion 
of the edges. Several techniques are available: continuous 
or interrupted, simple or mattress and subcuticular. All 
are acceptable but the last gives the best results. 

2. Skin clips give a good cosmetic result, are easy to 
apply and remove, and are associated with a low infection 
rate. 

3. Tape closure using Steri-strips also gives good 
results, and does not disrupt the blood supply to the 
tissues, as sutures might They do, however, require a dry 
surface for adhesion. They act as an adjunct to sutures 
and spread wound tension to provide the best cosmetic 
effect. 

4. Cyanoacrylate skin adhesives are expensive and 
demand near perfect haemostasis. They may be most 
appropriate in children for closing lacerations. 

5. Remove sutures at, as a working rule, 3-5 days in 
head and neck, 7 days inguinal and upper limb, 10 days 
abdominal and lower limb, and up to 14 days for dorsal 
incisions. Place knots well to the side of the incision to 
facilitate removal. 



Hypertrophic skin scars 

These present as a proliferation of heaped-up and red scar 
tissue, but this stays within the boundaries of the wound 
and do not extend beyond it, as do keloids. They tend to 
occur in scars around joints and in areas of skin tension. 
With the passage of time, at least 6 months, they become 
avascular, and may regress to form a white, stretched, 
widened scar. It is alleged that covering these scars with 
a silicone gel produces a clinical improvement but the 
exact mechanism is still unknown. 

Contractures 

Do not confuse these with the normal process of wound 
contraction. Contractures follow delayed wound healing 
and occur after infection and inadequate treatment of 
deep burns in particular. Established contractures can be 
released by excising them and covering the raw area with 
split-thickness grafts or with transposition flaps. 

Keloids 

Formed by abnormal collagen metabolism, keloids (Greek 
chele = claw) result in a proliferation of scar tissue beyond 
the boundaries of the original wound. They occur in 
dorsal areas of the body and over the face and delto- 
pectoral region. Keloids occur most frequently in dark- 
skinned people and may be encouraged to form as a 
cultural body decoration. 

Simple excision is almost always followed by a more 
exuberant recurrence. X-rays have been used but topical 
steroid creams or steroid injections are more effective. 
Pressure on an excised keloid scar may also prevent recur- 
rence. Experimental work is in progress, using calcium 
antagonists and manipulating the effects of transforming 
growth factor p. 

SURGICAL DRESSINGS 



Langer's lines 

The lines described by the Viennese Carl von Langer in 
1861 mainly correspond with the skin tension lines and 
natural skin creases. An incision across them risks an 
unacceptable hypertrophic scar. Whenever possible, 
incise along the tension lines. If you have to cross them for 
surgical access, as in operations on small joints, cross the 
skin creases obliquely or employ Z-plasties, or plan an 
S-shaped incision. 



The ideal surgical dressing does not exist, but should: 

1 . Be absorbent and able to remove excess exudate 

2. Maintain a moist environment, aid tissues to remove 
necrotic material, and promote healing 

3. Prevent trauma to underlying healing granulation 
tissue and exclude foreign particles from the wound 

4. Be leak-proof, preventing "strike through' (passage of 
organisms through soaked dressings) causing 
secondary infection 

5. Maintain temperature and gaseous exchange 



234 



SURGICAL ACCESS: INCISIONS, AND THE MANAGEMENT OF WOUNDS 



22 



6. Allow easy, pain-free, simple dressing changes, with 
less frequent application and removal 

7. Be odourless, cosmetically acceptable and comfortable 

8. Be inexpensive. 

The last 30 years have seen an increasing depth of under- 
standing of wound healing processes. Many dressings are 
now manufactured to provide the requirements of the 
ideal wound environment. There is no clear-cut evidence, 
however, as to whether wounds should be left open, with 
a dry surface of fibrinous coagulum which seals the 
wound, or whether they should be covered and hidden 
from view. Exuding wounds are at risk of secondary 
infection and may not be protected by a dressing. 
Pathogenic organisms can track through a soiled wet 
dressing from its surface. Only some of the requirements 
listed above are based on sound experimental evidence. 
The armamentarium of modern surgical dressings is 
intended for managing chronic open wounds such as 
venous leg ulcers. 

Polyurethane incise drapes have become popular as a 
primary wound dressing for sutured wound and skin 
donor sites. They retain moisture, which enhances epithe- 
lial closure, and allow easy inspection and aspiration of 
excessive exudate. They are claimed to relieve pain at 
donor sites. They are gas and water- vapour permeable 
but if the wound becomes macerated (Latin macerate = to 
soak) there is a risk of secondary infection. However, the 
dressings are impermeable to organisms. More traditional 
wound dressings include perforated absorbent plastic 
film, such as Melolin, or non-adherent sheet dressings, 
which require a secondary pad dressing if there is exces- 
sive exudate. 

A wide choice exists for managing open wounds such 
as a healing pilonidal sinus cavity or a superficially rup- 
tured, infected abdominal wound. Moulded polymeric 
silicone gel foam dressing is ideal, allowing pain-free 
wound care. The patient may be able to perform this. 
Bead and powder dressings, such as the exudate- 
absorbent Iodosorb and the sterile hydrogel mtrasite, may 
be useful. Some incorporate antibiotics or antiseptics. 
They absorb exudate and maintain a moist environment. 
Reserve sheet polymeric hydrocolloid or hydrogel dress- 
ings for more superficial open wounds. They may be 
occlusive, such as Comfeel ulcer dressing and Granuflex, 
or semiocclusive, such as Geliperm. Some are biological 
alginates, such as Kaltostat and Sorbsan, and may be 
interactive, promoting granulations. The list of dressings 
increases, and satisfactory trials are required to show their 
merit and comparative worth. Biologically active dress- 
ings and living skin equivalents are examples of these. 




Key point 

Choose wound dressings of proven 
cost-effectiveness, not for novelty value. 



PRINCIPLES OF WOUND 

1. An operation is a responsibility undertaken with 
informed consent (see Ch. 14), performed in optimal cir- 
cumstances. Surgery is based on ritual and it is difficult 
to measure the quality of operative surgery, although we 
achieve much through audit and morbidity and mortal- 
ity meetings. 

2. Lord Moynihan (1865-1936) taught that an operation 
should start with a clean sweep of the knife. William 
Halsted (1852-1922) preached gentleness, haemostasis, 
asepsis and accurate apposition of tissues. While aseptic 
procedures and swab and instrument counts are easy to 
teach, gentle handling of tissues is more difficult to learn. 
Some trainee surgeons acquire it naturally, others take 
time to be able to oppose cut tissues perfectly without 
undue suture tension. It is logical to secure haemostasis 
in surgical wounds. These principles were directed to the 
whole of surgery but apply particularly to the creation 
and management of surgical wounds. 



Summary 

• Do you understand the complex influences 
acting on incidental and surgical wounds? 

• How will you select appropriate incisions, 
particularly in the abdomen, the chest and 
near joints? 

• What principles underlie surgical closure 
of wounds? 

• Can you justify your selection of wound 
dressings based on evidence or 
experience? 




References 



Jenkins TPN 1976 The burst abdominal wound: a mechanical 
approach. British Journal of Surgery 63: 873-876 



235 



22 




OPERATION 




Further reading 



Anonymous 1986 Dressings for ulcers. Drug and Therapeutics 

Bulletin 24: 9-12 
Cox PJ, Ausobsky JR, Ellis H, Pollack AV 1986 Towards no 

incisional hernias: lateral paramedian versus midline 

incisions. Journal of the Royal Society of Medicine 79: 

711-712 
Harland RNL, Irving MH 1988 Surgical drains. Surgery 

1: 1360-1362 
Leaper DJ 1985 Laparotomy closure. British Journal of Hospital 

Medicine 33: 317-322 



Leaper DJ 1992 Local effects of trauma and wound healing. In: 

Burnand KG, Young AE (eds) Ian Aird's companion to 

surgical studies. Churchill Livingstone, Edinburgh, ch. 2, 

pp 27-35 
Leaper DJ 1992 Surgical factors influencing infection. In: Taylor 

EW (ed.) Infection in surgical practice. Oxford University 

Press, Oxford, ch. 3, pp 18-27 
Leaper DJ, Foster ME 1990 Wound healing and abdominal 

wound closure. In: Taylor I (ed.) Progress in surgery. 

Churchill Livingstone, Edinburgh, vol. 3, ch. 2, pp 19-31 
Lucarotti ME, Billings PJ, Leaper DJ 1991 Laparotomy, wound 

closure and repair of incisional hernia. Surgery 10: 1-6 
Wadstrom J, Gerdin B 1990 Closure of the abdominal wall: how 

and why. Acta Chirurgica Scandinavica 156: 75-82 



236 




Minimal access surgery 



A. Darzi 




Objectives 

• Understand the nomenclature and 
boundaries of minimal access surgery. 

• Recognize that minimal access surgery 
aims to accomplish surgical therapeutic 
goals with minimal physical and 
psychological trauma. 

• Recognize the limitations of minimal 
access surgery in its current state, 
considering future improvement in 
training and technology. 



Diseases that harm call for treatments that harm less. 

William Osier 



the essential attribute is the reduction of surgical trauma. 
Other terms include endoscopic keyhole and laparo- 
scopic surgery. 

Technology has effectively miniaturized our eyes and 
extended our hands to perform microscopic and macro- 
scopic operations in places that formerly could be reached 
only through large incisions. It has also provided new 
ways to look at tissues, using light, sound waves and 
magnetic fields which can detect disease and guide 
therapy (Darzi et al 1993). These same technologies, more 
highly focused and used at much higher power, can also 
be used to give highly controlled resection and tissue 
destruction. You must understand the principles of these 
devices so that you can help to shape the future develop- 
ment of minimal access surgery and not become the 
servants of the machines you use. 



INTRODUCTION 



BOUNDARIES OF MINIMAL ACCESS 
SURGERY 



Minimal access surgery aims to accomplish surgical thera- 
peutic goals with minimal physical trauma. The properly 
controlled performance of minimal access surgery with 
well-considered pre- and postoperative management 
offers benefits, including cost benefits, without sacrificing 
the quality of care of the patient. Minimal access tech- 
niques are less invasive, less disabling and less dis- 
figuring. With increasing experience, they offer cost 
effectiveness to both health services and employers by 
shortening operating times, shortening hospital stays and 
allowing faster recuperation. State-of-the-art video 
recording can help communication, bring the patient and 
family closer to the process, improve clinical decision 
making and enhance rapport. 

The urologists Wickham and Fitzpatrick (1990), who 
were instrumental in highlighting the need for techniques 
which reduced therapeutic and surgical trauma, advo- 
cated the term "minimally invasive therapy 7 . Cuschieri 
(1992) argues that this inaccurately implies increased 
safety but there is no correlation between invasiveness 
and risk. He suggests minimal access surgery (MAS), as 



Techniques 

Minimal access surgery has crossed all traditional bound- 
aries of specialities and disciplines. Shared, borrowed and 
overlapping technologies and information are encourag- 
ing a multidisciplinary approach that serves the whole 
patient rather than a specific organ system. Broadly 
speaking, minimal access techniques can be categorized 
as follows. 

1. Laparoscopy. A rigid endoscope is introduced 
through a port in the abdominal wall into the peritoneal 
cavity, which has been inflated with carbon dioxide 
(pneumoperitoneum). Further ports are then placed in 
the abdominal wall, through which operating instru- 
ments can be introduced. Laparoscopic cholecystectomy 
has revolutionized the surgical management of chole- 
lithiasis and is now the mainstay in its management. As a 
result of improved instruments and increasing experi- 
ence, Nissen fundoplication, hiatal and inguinal hernia 
repair, appendicectomy, and colorectal surgery are now 
performed laparoscopically. 



237 



23 




OPERATION 



2. Thoracoscopy. A rigid endoscope is introduced through 
an incision in the chest to gain access to the thoracic con- 
tents. The lung is deflated, producing a natural cavity 
without the need for gas insufflation. A common thoraco- 
scope procedure is sympathectomy for hyperhydrosis. 

3. Endoluminal endoscopy. Flexible or rigid endoscopes 
can be introduced into hollow organs or systems for 
diagnosis and therapy. Examples are the urinary tract 
(cystoscopy), upper (oesophagogastroduodenoscopy) or 
lower gastrointestinal tract (colonoscopy), respiratory 
tract (bronchoscopy) and vascular systems. 

4. Perivisceral endoscopy. Body planes can be accessed 
even in the absence of a natural cavity. Examples are 
mediastinoscopy, retroperitoneoscopy, and retroperi- 
toneal approaches to the kidney aorta and lumbar sym- 
pathetic chain. A recent example is subfascial ligation of 
incompetent perforators in varicose vein surgery. 

5. Arthroscopy and intra-articular joint surgery. Ortho- 
paedic surgeons have long used arthroscopic access to the 
knee and have now extended the techniques to other 
joints, including the shoulder, wrist, elbow, hip and ankle. 
Apart from diagnosis, therapeutic procedures include 
meniscectomy. 

6. Neurosurgeons employ minimal access procedures 
within the cranial cavity and the spinal canal. 

7. Combined approaches. A diseased organ may be 
visualized and treated using a combination of endolu- 
minal and extraluminal endoscopes and other imaging 
devices. 



damage, which may be as painful as the wound itself. By 
contrast, during laparoscopy the body wall is retracted by 
the low pressure pneumoperitoneum, giving a diffuse 
force applied gently and evenly over the whole body 
wall, causing minimal trauma. 

3. Exposure of any body cavity to the atmosphere is 
harmful because of loss of heat and loss of body fluid by 
evaporation. There is evidence from the surgical literature 
that the incidence of postsurgical adhesions is reduced in 
laparoscopic compared with open procedures because 
there is less damage to the delicate serosal coverings. 
Handling of intestinal loops reduces peristaltic activity 
and provokes adynamic ileus; this is reduced following 
laparoscopic surgery. 




Key points 

Compared with laparoscopy, open laparotomy 

produces more trauma, exposure, heat loss and 

fluid evaporation. 

Postoperative pain, immobility, the risk of 

pulmonary and deep vein complications and of 

adynamic ileus are more frequent following 

open procedures. 

There is probably a lower incidence of 

postoperative adhesions following 

laparoscopy. 




Key point 

Endoscopic techniques for diagnosis and 
therapy can be adapted wherever a space 
exists or can be created. 



COMPARISON OF SURGICAL TRAUMA 
FROM OPEN AND LAPAROSCOPIC 
SURGERY 

1. Most of the trauma of an open procedure stems from 
the need for a wound large enough to give exposure for 
safe dissection at the target site. The wound is often the 
cause of morbidity, including infection, dehiscence, 
bleeding, herniation and nerve entrapment. Wound pain 
prolongs recovery time and, by reducing mobility, con- 
tributes to increased incidence of pulmonary collapse / 
chest infection and deep venous thrombosis. 

2. Mechanical and human retractors exert additional 
trauma. Body wall retractors tend to inflict localized 



LIMITATIONS OF MINIMAL ACCESS 
SURGERY 






1. When performing minimal access surgery you are 
remote from the operative field, using a two-dimensional 
imaging system to represent the operative site. You must 
learn to navigate the anatomical landscape without the 
usual clues by which you judge depth. 

2. The instruments are longer and sometimes more 
complex than those used in open operations. 

3. These two factors combine to create significant prob- 
lems of hand-eye coordination, but with experience these 
difficulties can be overcome. 

4. Three-dimensional imaging is available,, using two 
cameras side by side, delivering a stereoscopic image. It 
can be used to perform robotically assisted minimally 
invasive surgery. This confers benefits in the ability to 
perform complex laparoscopic tasks, such as intracorpo- 
real suturing. In the future, continuing cost reduction will 
make elaborate image-processing techniques available for 
a wide range of transformed presentations. Ultimately it 
will be possible to call up any view of the operative region 



238 



MINIMAL ACCESS SURGERY 




that is accessible to a camera presented stereoscopically in 
any size or orientation, superimposed on past images 
taken in other modalities. We shall need to decide which 
of these many imaginative possibilities will contribute 
most effectively. 

5. Intraoperative bleeding may be very difficult to 
control endoscopically because blood obscures the field of 
vision and there is a significant reduction in the image 
quality due to light absorption. 

6. Some of the new procedures are more technically 
demanding and are slower to perform. Indeed, on occa- 
sions a minimally invasive operation is so technically 
demanding that both you and patient are better served by 
conversion to an open procedure. Do not feel a sense of 
embarrassment or humiliation, which is quite unjustified. 
It is vital for you and your patients to appreciate that the 
decision to convert to open operation is not a complica- 
tion but rather implies sound surgical judgement. 

7. Loss of tactile feedback is a disadvantage. Laparo- 
scopic ultrasonography might provide a substitute for the 
need to 'feel' in intraoperative decision making. Although 
ultrasonography has progressed significantly, laparo- 
scopic ultrasound is still in its infancy. The rapid progress 
in advanced laparoscopic techniques, including biliary 
tract exploration and surgery for malignancy, provides a 
strong impetus for the development of laparoscopic 
ultrasound, which already offers advantages that far out- 
weigh its disadvantages: 

a. It offers a safe, easily performed and economic sub- 
stitute for a sense of touch, allowing visualization 
through tubular fluid-filled and solid organs as well as 
vascular structures. 

b. It differentiates between solid and cystic masses. 

c. The wall layers of hollow viscera can be evaluated. 

d. Better staging of tumours is possible because the 
dimensions, infiltration and dissemination can be 
detected. 

e. Guided biopsies can be obtained. 

f. It does not involve the use of ionizing radiations or 
contrast media. 

g. It has no contraindications, can be used during 
pregnancy and can be employed at any time during the 
operation. 

8. In more advanced techniques, the large piece of 
resected tissue, such as the lung or colon, must be 
extracted from the body cavity (Monson et al 1992). 
Occasionally it can be removed through a nearby natural 
orifice, such as the rectum or mouth. At other times a 
novel route can be used, such as extraction of a benign 
colonic specimen through an incision in the vault of the 
vagina. Tissue mincers, morcellators and liquidizers can 
be used but have the disadvantage of reducing the 
amount of information available to the pathologist. 



9. Minimal access techniques are applied to staging 
and resection of gastrointestinal, urological, gynaecologi- 
cal and thoracic malignant tumours. Reports of tumour 
implantation in port sites, particularly early on, are being 
studied in a prospective controlled trial (CLASICC) of 
laparoscopic colorectal resections for malignancy in the 
UK. 

10. There is a growing need for improved dissection 
techniques in laparoscopic surgery, specifically the safe 
use of electrocautery and lasers. Ultrasonic dissection and 
tissue removal is utilized in a growing number of spe- 
cialities. Adaptation of the technology to laparoscopic 
surgery grew from the search for alternative and possibly 
safer methods of dissection. Current units combine the 
functions of three or four separate instruments, reducing 
the need for instrument exchanges. This flexibility, com- 
bined with the ability to provide a clean, smoke-free field, 
saves time and improves safety. 

11. Dramatic cost savings are possible with laparo- 
scopic cholecystectomy, particularly as some can be per- 
formed as day cases, but the position is less clear for other 
procedures. In contrast, there has been a rise in the chole- 
cystectomy rate, resulting from a lower threshold for 
referral, following the introduction of the laparoscopic 
approach - increasing the overall cost of treating symp- 
tomatic gallstones. 



TRAINING FOR MINIMAL ACCESS 

It is probably true to say that no previous surgical inno- 
vation has aroused so much public questioning of how 
surgeons are trained. While the pioneers of a new tech- 
nique are inevitably self-trained, patients then rightly 
demand that their successors are properly trained to 
perform it safely and effectively. This is particularly so in 
laparoscopic surgery, which employs skills not commonly 
used in everyday life. 

The importance of training in minimal access surgery 
has been recognized with the establishment of several 
centres dedicated to teaching the fundamentals of safe 
minimal access surgery. These centres, including the 
Minimal Access Therapy Training Unit (MATTU) at the 
Royal College of Surgeons of England, are working to 
develop training methods using various methods of 
simulation, allowing surgeons to complete a significant 
part of their skills training before operating on patients. 
Virtual reality training simulators are now in use and the 
technology will improve further, to generate an artificial 
environment in which surgeons can practise in complete 
safety. 



239 



23 1 

i 



OPERATION 




Key points 

The skills you require to undertake minimal 
access surgery are exceptional. Take every 
opportunity to acquire and practise them. 
The principles of good surgery still apply: case 
selection, exposure, retraction, haemostasis, 
technical expertise. 

Minimal access has changed practice but not 
the nature of disease. A conventional 
procedure that does not make sense does not 
make sense performed by minimal access 
techniques. 



Summary 

Do you understand: 

• The scope and limits of minimal access 
surgery? 

• The potential benefits for the patients? 

• The need for careful selection and for 
conversion to open surgery in response to 
difficulties? 

• The imperative need to train yourself 
before embarking into a field requiring 
exceptional skills? 



Improvements in instrumentation and the development 
of structured training programmes are the key to the 
future of minimal access surgery. There is much that is 
new in minimal access surgery; time will tell how much 
of what is new is better. 

The cleaner and gentler the act of operation, the less 
the patient suffers, the smoother and quicker his con- 
valescence, the more exquisite his healed wound. 

Lord Moynihan of Leeds 




References 



Cuschieri A 1992 A rose by any other name: minimal access or 
minimal invasive surgery. Surgical Endoscopy 6: 214 

Darzi A, Goldin R, Guillou PJ, Monson JRT 1993 Extracorporeal 
shock wave thermotherapy: new anti tumour option. Surgical 
Oncology 2: 197-204 

Monson JRT, Darzi A, Carey PD, Guillou PJ 1992 Prospective 
evaluation of laparoscopic assisted colectomy in an 
unselected group of patients. Lancet 340: 831-833 

Wickham }, Fitzpatrick JM 1990 Minimally invasive surgery 
[editorial]. British Journal of Surgery 77: 721 



240 




24 



Principles of skin cover 

P. E. M. Butler, J. L Atkins 



E 



Objectives 



• Understand the pathophysiological 
changes accompanying, and resulting 
from, different types of skin loss. 

• Recognize the importance of pre-existing 
conditions in the skin and contiguous 
tissues before the skin loss. 

• Differentiate between the special features 
of skin in different parts of the body. 

• Identify circumstances in which primary 
closure is possible, better deferred, and 
contraindicated. 

• Recognize the available methods of 
achieving closure and their indications. 



INTRODUCTION 

The skin is the largest organ of the body, forming just 
under a sixth of the total body weight. Skin function 
varies in different parts of the body and this is reflected 
in its qualities. Although the basic structure of skin is 
constant, thickness and elasticity, pigmentation, and the 
presence or absence of specialized skin appendages, such 
as exocrine glands, nails, hair and sensory apparatus, 
differ. 

Skin provides a number of diverse but vital functions 
to the body. Most obviously, it provides a physical barrier 
to the outside world, giving limited protection against 
mechanical, chemical and thermal damage as well as pre- 
venting invasion by microorganisms, including viruses. 
Its integrity is critical for homeostasis, maintaining the 
internal milieu by providing a relatively impermeable 
barrier to the passage of water, proteins or electrolytes in 
either direction. Similarly, a vital role in thermoregulation 
is manifest by the controlled release of sweat and vari- 
ability of blood flow to the body surface, leading to heat 
loss or conservation as required. Melanin pigment within 
the dermis protects the skin by absorbing ultraviolet rays 
of long (UVA) and medium (UVB) wavelength. Sensory 



information received from sensory appendages located 
within the dermis is both vast and subtle, while the 
synthesis of vitamin D and deposition of fat in the 
subcutaneous layer are functions of metabolic import- 
ance. The appearance and feel of our skin is critical; 
abnormalities are readily visible to the world at large, can 
be socially stigmatizing and are a source of psychological 
distress as well as physical discomfort to the affected 
individual. 

Skin loss through disease or trauma exposes an indi- 
vidual to the risk of bacterial and viral infections, uncon- 
trolled loss of serous fluid, proteins and electrolytes, and 
loss of mechanical protection to vulnerable underlying 
tissue. When skin wounds are very extensive they can be 
painful, disabling and life threatening, as is seen in burn 
injuries. Smaller wounds also deserve careful attention as 
they provide a defect through which serious infections 
may enter and produce life threatening conditions such 
as gas gangrene, toxic shock syndrome and necrotizing 
fasciitis. Chronic skin wounds can undergo malignant 
transformation, as seen in Bowen's disease (intradermal 
precancerous skin lesion described by the Harvard der- 
matologist in 1912), which may progress to squamous cell 
carcinoma. 

Poorly managed wounds heal slowly, and form ugly, 
weak scars with a poor functional result. Your primary 
aims in restoring skin cover are to provide optimal func- 
tion and form in a timely fashion. Understanding how 
certain injury types affect tissue viability and lead to skin 
loss is paramount. Undertake a systematic and thorough 
assessment of the patient in general, and the wound in 
particular, before instituting an appropriate course of 
treatment and rehabilitation. 



SKIN CHARi\CTERISTICS 

1. You are not dealing with a homogeneous body 
covering but with a varied, dynamic, responsive complex 
surface overlying varying supportive tissues. 

2. Skin varies in different parts of the body in thick- 
ness, vascularity, nerve supply, ability to tolerate trauma, 



241 



24 * 



OPERATION 



mobility, and also in special attributes; for example, 
palmar skin of the hands, and especially of the fingertips 
of the index finger and thumb, are irreplaceable. Although 
it is tough and able to withstand and respond to hard 
usage, it is richly supplied with a variety of afferent nerve 
endings, enabling us to utilize our fingers as important 
sensory organs. 

3. The elasticity of the skin varies with age and the 
individual, producing tension lines. These tend to run cir- 
cumferentially around joints and the trunk, at least in 
early life. They are often named Langer's lines after Carl 
von Langer, the Austrian anatomist. By puncturing 
cadaveric skin with round spikes, he observed, in 1832, 
how the circular defects deformed as a result of skin 
tension. Incisions orientated parallel to tension lines heal 
with superior scars. 

4. Fetal skin heals without scar formation; at birth skin 
is extremely elastic but with increasing age it becomes less 
so. In old age, following loss of fat and muscle bulk, the 
inelastic skin hangs in folds, especially on the abdomen 
and neck. 

5. Viability is reduced by defective nutrition (such as 
vitamin C, zinc, protein), ischaemia, denervation, vascu- 
lar congestion, inflammation and infection. The skin is 
friable overlying an abscess and also in an area of celluli- 
tis or erysipelas (Greek erythros ~ red + pella - skin). 

6. Pathological changes may develop as a result of 
exposure to solar or ionizing radiation, cancer chemother- 
apy and various drug treatments. A variety of drugs, such 
as sulphonamides, barbiturates and non-steroidal anti- 
inflammatory substances (NSAIDs), may induce toxic 
epidermal necrolysis (TEN or LyelTs syndrome), in which 
fluid-filled bullae develop, separating sheets of epithe- 
lium from the underlying dermis. 



WOUND ASSESSMENT 






H 



Key point 



• The history is as important as the appearance 
when assessing wounds. 

1 . Ascertain the timing, nature and force of the injury 
sustained. Accurately describe the appearance of a 
wound, and recognize how this changes over time; time 
elapsed since injury influences how you manage the 
wound. Ascertain exactly what tissue has been lost and 
what remains; are tendons, bones or neurovascular struc- 
tures exposed? These may need urgent soft tissue cover 
to preserve function and prevent infection, and may 
require a more complex reconstruction. Wounds present- 



ing early (<48 h) exhibit features of an acute inflammatory 
response. Following this acute phase, observe signs of 
healing in an untreated wound with some or all of the 
features of the acute inflammatory response having 
dispersed. Identify slough and granulation tissue in the 
wound base, with an advancing epithelial edge at the 
wound margin. Chronic inflammation occurs with con- 
tinuing tissue damage; the wound exhibits features of 
ongoing tissue necrosis, acute inflammation, granulation 
tissue and fibrous scarring. 

2. If you are inexperienced you may be distracted by the 
presence of an obvious or dramatic wound from other 
pathology. Carry out a full, careful examination of trauma- 
tized patients. Give priority to potentially life-threatening 
injuries; they require urgent treatment. 

3. Different mechanisms of injury compromise tissue 
in different ways. Recognize and understand the effects 
of patterns of injury. The severity of the wound is 
affected by a number of factors. Elderly patients have 
thin, delicate skin, easily lost with relatively minor 
trauma compared with the skin of children or young 
adults. Take note of the anatomical area; pretibial skin is 
thin, vulnerable to trauma and slow to heal; skin on the 
back is thick and robust, while facial skin is delicate but 
heals quickly because it has a rich blood supply. Chronic 
systemic steroid use produces thin, atrophic skin, easily 
lost following minor trauma. Diabetics may develop 
peripheral neuropathy leading to chronic or recurrent 
ulceration of the lower limb; combined with micro- 
vascular disease and an impaired immune response, the 
ulcers heal reluctantly. 



SKIN LOSS 









Mechanical trauma 

1. Contusion (Latin tundere = to bruise) results from 
blunt trauma. This is not usually a serious skin injury, but 
if it produces a haematoma, the swelling may cause 
pressure necrosis of the overlying skin. In elderly or anti- 
coagulated patients large haematomas may develop 
following a minor blow, leading to the formation of very 
large haematomas. Incise and evacuate these urgently to 
prevent loss of the overlying skin. Blood loss may be great 
enough to require transfusion. 

2. Abrasion (Latin ab = from + radere = to scrape) is a 
superficial epidermal friction injury, often patchy. The 
epidermis regenerates by advancement of epithelium 
remaining within the skin appendages deep within the 
dermis. Healing is usually complete and can be encour- 
aged by gently and thoroughly cleaning the wound with 
a mild antiseptic to remove dirt or debris, and applying a 
moist, non-adherent occlusive dressing. Unless you 



242 



PRINCIPLES OF SKIN COVER 



24 



remove the dirt ground into the wound, permanent skin 
tattooing (Tahitian ta'tau) will develop. 

3. Retraction (Latin re = back + trahere = to draw) of skin 
edges occurs when it is lacerated (Latin lacerare = to tear). 
Skin is innately elastic, the extent varying with age, race, 
familial trait, the use of systemic steroids, smoking and 
nutrition. If you are inexperienced you may mistake skin- 
edge retraction for skin loss, most commonly seen in chil- 
dren whose greater skin elasticity may lead to dramatic 
opening up of the wound. Avoid this mistake by carefully 
examining the wound and recognizing the pattern and 
markings of one edge that match those of the opposite 
edge if the skin has merely retracted. 

4. Degloving results from severe shearing of the skin, for 
example, a pneumatic tyre running over a limb, detaching 
the skin from the underlying tissue. This separation may 
occur superficially, or beneath the layer of deep investing 
fascia, causing skin loss over a large area. The skin may 
tear, or remain intact initially, disguising the severity of 
this injury. Rupture of the vessels connecting the deeper 
tissues to the skin commonly produces ischaemic necro- 
sis of the skin and other tissues superficial to the plane of 
separation. Prejudiced skin perfusion may be apparent 
from an absence of dermal bleeding at the skin edges, as 
may the absence of blanching followed by capillary refill, 
when you apply then release pressure. Subsequently the 
area of injury becomes more defined as the skin becomes 
mottled, then necrotic. You may be able to resurface the 
underlying tissue using a split thickness skin graft, 

5. Avulsion (Latin ab = from + vellere - to pull) is the 
partial or complete tearing away of tissue and may 
involve skin, deeper structures such as bone, tendon, 
muscle and nerve, including digits, limbs or scalp. The 
force required to do this is considerable and creates a zone 
of injury around the point at which the tissue separates. 
Tissue is usually stretched, twisted and torn, leading to 
irreversible damage, in particular of neurovascular struc- 
tures. It may be possible, when you have appropriate 
experience, to reattach or replant avulsed tissue using 
microvascular techniques. Completely avulsed tissue can 
be temporarily stored in moistened sterile gauze, sealed 
in a plastic bag and placed in ice, or stored in a refrigera- 
tor at 4°C. Vascular tissue such as muscle cannot be safely 
replanted if it has been ischaemic for more than 6 h. 
Tendon, skin and bone are more tolerant of ischaemia. 
Make every effort to salvage an avulsed or amputated 
upper limb, thumb, multiple lost digits, or digits in chil- 
dren. They are important for restoration of function, and 
especially in children they offer greater potential for 
recovery. Loss of individual digits is relatively less import- 
ant in terms of benefit. An avulsed toe or foot is rarely 
suitable for microvascular replantation because sensory 
and functional recovery is poor and therefore unlikely to 
be satisfactory. If the patient has other significant life 



threatening injuries you may decide against attempting to 
reimplant divided tissues. 




Key point 



• Remember that even trivial skin loss may offer 
entry to strains of Staphylococcus aureus that 
may cause toxic shock syndrome, especially in 
vulnerable patients such as children, the elderly 
and the sick. 

Thermal injury 

1. A scald (Latin ex - from + calidus = warm, hot) is 
caused by contact with hot liquids. A variety of agents 
may cause burns, such as flames, contact with hot 
objects, radiant heat and corrosive (Latin rodere = to 
gnaw) chemicals. 

2. Through and through electrical injuries differ from 
other burns in that the passage of the electrical current 
through the body causes injury to deep tissue that may 
not be immediately apparent. A small entrance and exit 
burn of the skin may be the only visible manifestation of 
the injury. The electrolyte-rich blood acts as a conduit for 
the current flow and the vascular endothelium is 
damaged so that the vessels subsequently undergo 
thrombosis. Deep-seated tissue necrosis becomes appar- 
ent as the patient becomes increasingly unwell over hours 
or days. High voltage injuries are the most destructive, 
and alternating current is more likely to cause myocardial 
fibrillation than direct current. 

Surgical diathermy heats the tissues as a result of 
intense vibration of the ions caused by the low amperage 
high frequency, high voltage, alternating current (see 
Ch. 17). Faulty equipment and inexpert use may result in 
skin burns. 

3. Exposure to cold air may cause frostbite. Excessive 
exposure to cold causes peripheral vascular spasm, with 
ischaemia and anoxia of the extremities, affecting a local- 
ized area of soft tissue. The extent of the injury is affected 
by temperature, duration of contact and pre-existing 
hypoperfusion of tissues. Four phases of injury have been 
described. These are; 

a. Pre-freeze (3-10°C): increased vascular permeability 

b. Freeze-thaw (-6 to -14°C): formation of intra- and 
extracellular ice crystal. 

c. Vascular stasis: blood is shunted away from the 
damaged area 

d. Late ischaemic phase: cell death, gangrene. 
Thawing, with restoration of the circulation, liberates 

inflammatory mediators. Microemboli form on the 
damaged endothelium and these increase the ischaemia 
and tissue loss. Treatment includes rewarming by 



243 




OPERATION 



immersion of the affected part in circulating warm water, 
elevation and splinting. Ischaemic areas are allowed to 
demarcate prior to amputation of the necrotic parts. 

Cryosurgery (Greek kryon = frost) offers a method of 
destroying skin lesions almost painlessly (see Ch. 17). 

A lesser result of exposure to cold is chilblains (Old 
English blain = a boil or blister). 

Contact with very cold objects can result in adherence 
of the skin, which is pulled off on separation. 

4. Assess burns, in terms of site, percentage of the body 
surface damaged and depth of damage, to determine the 
prognosis and as a guide to treatment. Depth is super- 
ficial (1st degree), partial skin thickness including the 
dermis (2nd degree) and full thickness of all the layers of 
the skin (3rd degree). Burn depth is difficult to assess. 
White, insensate areas are generally full thickness. Partial 
thickness burns usually blanch on pressure and refill 
when the pressure is released; it remains sensate and may 
be blistered. Superficial burns are often erythematous, 
perfused, painful and tender to touch. 

5. Generally, full thickness burns are managed by exci- 
sion and skin grafting of the underlying tissue bed; partial 
thickness burns may be suitable for conservative treatment, 
allowing epidermal regeneration from remaining epithelial 
elements within the skin appendages of the dermis. 

Ulceration 

'Ulcer' (Greek elkos, Latin ulcus = sore) usually has a con- 
notation of chronicity. An acute loss of skin is not called 
an ulcer unless it fails to heal. 

1. Pressure sores develop from unrelieved pressure on 
the tissues in a debilitated patient, especially if there is 
neurological impairment. Other factors include nutri- 
tional deficit, diabetes mellitus, immunosuppression, 
incontinence and an inappropriate physical environment. 
The commonest affected areas are on the lower body 
within tissue overlying bony prominences. The sore 
develops as the tissue becomes compressed and oedema- 
tous; the pressure within the tissue exceeds the capillary 
perfusion pressure, leading to ischaemia and tissue necro- 
sis. The tissue adjacent to the bony prominence suffers the 
most extensive injury, with the least at the level of the 
skin; the visible skin wound belies the reality of a much 
more extensive tissue loss. 



5" 



Key point 



• Development of pressure sores represents a 
failure to protect skin at risk from continuing 
pressure or contact with damaging substances, 
including body secretions and excretions. 



Treatment is predominantly conservative. Institute 
measures to relieve pressure, such as the use of specially 
adapted wheelchairs, beds and other padding, correct any 
nutritional deficiency, eliminate infection, control incon- 
tinence and apply appropriate dressings. A minority 
require surgical intervention, such as wound debride- 
ment, excision of the bony prominence to encourage 
closure, or covering the area with a soft tissue flap. Use 
flaps cautiously in the presence of chronic predisposing 
illness such as multiple sclerosis. 

2. Other common causes of ulceration include diabetes, 
autoimmune disorders, infection, ischaemia, venous 
disease and neoplastic lesions. Identify the underlying 
cause, if necessary by obtaining an incisional or punch 
biopsy of the margin, and treat the underlying cause. Any 
chronic ulcer may undergo malignant change, with the 
formation of Bowen's disease prior to malignant invasion 
as squamous cell carcinoma. 

3. Raynaud's disease, described by the Parisian physi- 
cian in 1862, is an excessive arteriolar sensitivity to cold 
of the extremities. In Raynaud's phenomenon the spasm 
is secondary to vascular or connective tissue disease, or 
occupations in which vibrating tools need to be used. The 
spasm causes necrosis and ulceration of the extremities. 




Key point 



Record the progress by keeping serial 
photographs of wound size, extent and 
healing. 



BIOLOGY OF SKIN HEALING (see also 

Ch.33) ^ 

1. Wound healing is a multistep overlapping process 
involving an inflammatory response, granulation tissue 
formation, new blood vessel formation, wound closure 
and tissue remodelling. Tissue damage causes extra- 
vasation of blood and its constituents. Platelets and 
macrophages release a number of chemical mediators 
including transforming growth factors (TGF), fibroblast 
growth factor (FGF), vascular endothelial growth factor 
(VEGF), platelet-derived growth factor (PDGF), insulin- 
like growth factor (IGF) and keratinocyte growth factor 
(KGF). 

2. The injured cells and other cells and platelets 
generate vasoactive and chemotactic (Arabic al kimiea, 
Greek chemeia + tassein = to arrange; cell movement in 
response to a chemical stimulus) substances that attract 
inflammatory neutrophils. Monocytes are also attracted 
and convert to macrophages. These phagocytes remove 



244 



PRINCIPLES OF SKIN COVER 



24 



dead tissue and foreign material, including bacteria. As 
inflammatory exudate accumulates, there is a cascade of 
events leading to oedema, erythema, pain, heat and 
impaired function. Macrophages and factors derived 
from them are essential in stimulating repair (Singer & 
Clark 1999). 

3. Epidermal cells from skin appendages break 
desmosomal contact with each other and also with the 
basement membrane; they migrate in the plane between 
the viable and necrotic tissues by producing collagenase, 
which degrades the intercellular substance (matrix) 
reinforced by matrix metalloproteinase. Epithelial cells 
behind the migrating ones proliferate after 1 or 2 days, 
probably from the release of growth factors. As re- 
epithelialization proceeds, the epithelial cells reattach 
themselves to the basement membrane and underlying 
dermis. 

4. As a result of hypoxia, growth and angiogenesis 
factors are released by macrophages and activated 
epithelial cells. The wound is invaded by blood capil- 
laries, macrophages, fibroblasts after 3-4 days, bringing 
nutrients and oxygen. The crests of the capillary loops 
appear like small cobblestones, hence the name of 'granu- 
lation' tissue. Blood capillaries require the presence of 
perivascular fibronectins (Latin nectere - to bind, tie) in 
order to move into the wound. Vascular growth is a deli- 
cate balance of positive regulators such as VEGF and 
PDGF, and negative regulators such as angiopoietin-2, 
endostatin and angiostatin. Once the wound is covered 
with granulation tissue angiogenesis stops. The fibro- 
blasts synthesize extracellular matrix, which is later 
replaced with acellular collagen, when cells in the 
wound undergo apoptosis (Greek apo - from + piptein = 
to fall; programmed cell death). During the second week 
following injury, fibroblasts become myofibroblasts, 
acquiring actin-containing microfilaments (Greek aktinos 
= ray) and cell-to-cell and cell-to-matrix linkages. 
Probably under the influence of TGF and PDGF, the 
fibroblasts attach to the collagen matrix through integrin 
receptors and form cross-links. Myofibroblast contrac- 
tion draws together the attachments at each end of the 
cell. However, in animal experiments the evidence for 
the role of myofibroblasts has been questioned (Berry 
etal 1998). 

5. The contribution of epithelial migration and wound 
contraction to healing is not fully resolved. There are also 
differences in the factors involved between humans and 
in animal experiments. One suggestion is that wound 
contraction in granulation tissue results from the com- 
paction of collagen fibres influenced by cellular forces, 
not directly from contraction of cells pulling on the 
surrounding tissues. 

6. When closure of large raw areas has failed or is 
unavailable, healing and scar formation continues for 



weeks, months or years. This is often termed scar con- 
tracture. Powerful forces draw in skin and scar tissue is 
laid down, often causing severe limitation of function. A 
classical example is that of a young child who pulls over 
a pan of scalding water, burning the face, neck, shoulder, 
chest, axilla and upper arm. The head is permanently 
drawn to the side of the burn, the neck is webbed, the 
shoulder is drawn upwards and fixed; the shoulder 
cannot be abducted and the deltoid muscle atrophies, 
while the anterior axillary fold and skin over the chest 
circumference is tight, restricting inspiration. 

7. Collagen degradation proceeds in step with wound 
contraction. The wound gains only 20% of its final 
strength in the first 3 weeks, and the maximum strength 
it achieves is only 70% of that of normal skin. 

8. Healing is prejudiced in diabetes, especially in the 
presence of neuropathy and ischaemia. Wounds are prone 
to infection because of impaired granulocyte function and 
chemotaxis. 

9. Abnormal accumulation of collagen causes hyper- 
trophic scarring and keloid formation. Normal mature 
scars and keloids display no scar contraction and they do 
not contain any myofibroblasts. Increased levels of TGF(3, 
PDGF, interleukin 1 (IL-1) and IGF-I are present in both, 
with TGFp appearing to predominate. 

10. Growth factors have proved disappointing in 
accelerating wound healing, possibly because they need 
to be administered in carefully graded doses and 
sequence. 

11. Fetal skin wounds heal rapidly without scarring; 
the epithelial cells are drawn across the wound by con- 
traction of actin fibres. Scarring does not occur because 
there is a reduced level of TGFpl. PRX-2, a member of 
the Paired Related Homeobox gene family, is upregu- 
lated in dermal fibroblasts during scarless fetal wound 
healing. 



DEBRIDEMENT 

1. Debris, foreign material, devitalized tissue, slough, 
pus or heavy contamination with pathological bacteria 
form a focus for infection, irritate the wound, prevent the 
formation of granulation tissue and obstruct epithelial 
migration. 

2. Excise all non-viable skin under anaesthesia and, if 
you are in doubt regarding viability, return the patient to 
the operating theatre for a second inspection and debride- 
ment after 24^8 h. Debridement (French de = from + 
bridle; unbridle = release from constriction) was origi- 
nally used for releasing tension but has been extended to 
mean the removal of dead tissue. 

3. It can often be achieved non-surgically using saline 
irrigation, topical agents to lift slough or with dressings 



245 



24 



OPERATION 



or sharp dissection under anaesthesia. Debride areas with 
specialized and precious tissue, such as the fingertips, 
palm and face, adequately but minimally. If there is 
uncertainty at the time of surgery as to the viability of 
tissue or adequacy of debridement, be willing to redress 
the wound with an occlusive non-adherent dressing and 
return the patient to the operating theatre for a second 
inspection after 24-48 h. 



ACHIEVING WOUND CLOSURE AND 



SKIN COVER 

No skin loss 

1. Clean incised wounds vary, depending on where 
and how the wound is made. If it is made parallel to the 
lines of tension the edges remain closely apposed, if made 
across the tension lines they gape. There is virtually no 
damage to contiguous tissues so that, apart from the 
almost singular layer of cells along the line of division, the 
remainder of the tissues are viable. Such a wound, once 
closed, is said to heal by primary intention, and should 
heal with a fine linear scar. 

2. If the incision is only partial thickness the deeper 
intact parts maintain the edges in good apposition. If the 
wound extends through the full thickness this support is 
partially lost, depending on the strength and attachment 
of the deeper tissues. 

3. Abraded skin has intact deeper layers and will heal 
spontaneously. Torn skin dragged as a flap may initially 
appear viable; a triangular flap attached distally over 
the subcutaneous face of the tibia notoriously fails to 
survive. 

4. In wounds with very irregular margins, it is helpful 
to close the most obvious matching points first and then 
to close the other points in between. Do not be afraid to 
remove and reposition sutures until the edges are per- 
fectly matched. Small bridges of skin separating lacera- 
tions are best excised to achieve a cosmetic result. 



Skin loss 

1. When a skin or other superficial lesion has been 
excised, the surviving edges and the base are normally 
left healthy, dry and free of bacterial contamination, 
foreign material or dead tissue. 

2. Closure can usually be performed immediately 
(primary closure); indeed the excision is usually planned 
with this in mind, except in the presence of malignant 
disease, when total clearance of the tumour is paramount. 
Primary closure allows more rapid healing and an earlier 
return to normal function. 



3. In elective surgical procedures, the closure can be 
planned before operation and discussed with the patient. 
It may be possible to close the defect directly, reconstruct 
or resurface it. 

4. As far as possible, replace large defects with skin 
and tissue giving the closest possible match to the 
surrounding tissues with regard to colour, thickness and 
texture. 

5. To achieve the best results the wound edges must be 
accurately opposed. If the wound is irregular, perfect 
apposition can be aided by first identifying and apposing 
landmarks with key sutures before inserting intervening 
sutures. 

6. Perfect closure is prejudiced by unevenness, inver- 
sion of the edges and tension, as inevitable postoperative 
oedema increases the tension. 

7. Many small wounds of 1 cm in diameter or less, 
including many fingertip injuries, usually heal with 
a satisfactory result by secondary intention within 
2-3 weeks. Treat larger wounds conservatively in ill, frail 
patients, and those likely to heal within a reasonable time. 
This may include pressure sores. 




Key point 

Assess the nature of the skin at the margins of 
the defect that you intend to close. 



Complicating factors 

1. The skin may be atrophic or stretched, especially in 
elderly people, or affected by eczema, solar or ionizing 
radiation, hypertrophy or the scar of a previous oper- 
ation. Neonatal and infant skin usually heals well. 

2. Inflammation, neoplasm, ischaemia, oedema, infec- 
tion, congestion or injury - possibly with the presence of 
foreign material - of contiguous tissues such as bones, 
muscles, tendons, nerves or vessels may force a change of 
strategy. 

3. Repair is prejudiced if the patient is very old, 
undernourished, immunosuppressed is undergoing 
chemotherapy, or has general infection, neoplasia or 
organ failure. 

4. The wound may be too large to close. 

Achieving closure 

1. Grafting (Greek graphein = to write; from the 
Roman use of tree grafting using shoots sharpened like 
a pencil), may allow transfer of completely detached 
partial or full thickness skin from a donor site to a 



246 



PRINCIPLES OF SKIN COVER 




wound that cannot be closed directly. The graft adheres 
by fibrinous bonds, initially gaining nourishment by 
serum imbibition - metabolites diffusing through the 
thin film of intervening serum. Capillaries connect from 
the recipient site and are functioning by the second day 
but the connection is fragile and susceptible to shear 
stress for 2-3 weeks. The best recipient sites for skin 
grafts are clean, granulating and well vascularized; 
unsuitable sites include bone lacking periosteum, 
tendons stripped of paratenon, denuded cartilage, irra- 
diated or avascular wounds and those covered in blood 
clot. Gross contamination with microorganisms preju- 
dice graft survival and Streptococcus pyogenes is an abso- 
lute contraindication because it produces fibrinolysin, 
destroying the fibrin bond between the bed and the 
graft. The likelihood of graft movement can be reduced 
by applying moderate pressure with a conforming, tie- 
over dressing, which will also inhibit the development 
of a seroma or haematoma. 

2. A split thickness skin graft consists of epidermis 
and a variable proportion of dermis, harvested in sheets 
using a handheld knife or electronic dermatome. 
Retained epidermal components, such as pilosebaceous 
follicles, provide foci for epidermal regeneration. The 
thinner the graft harvested, the more epidermal ele- 
ments left behind, the quicker the epidermis regenerates. 
If the volume of donor skin is inadequate, split skin 
grafts can be expanded by the use of a meshing machine; 
this creates fenestrations throughout the graft, allowing 
it to expand and cover a larger area, with a net-like 
appearance. Split skin grafts can be harvested, wrapped 
in sterile saline-soaked gauze and stored in a refriger- 
ator at 4 Q C, with up to 3 weeks viability. The common- 
est donor site for these grafts is the thigh or buttock area. 
The donor site often heals with altered pigmentation, 
and occasionally with a hypertrophic scar. Split thick- 
ness grafts, especially thin ones, tend to contract during 
the healing process, limiting movement across flexor 
surfaces. The application of compression garments when 
the graft is healed improves the appearance, flattens the 
scar and minimizes contraction, aided by daily massage 
with moisturizing cream. 

3. Full thickness skin grafts comprise the epidermis 
and full thickness of the dermis. It is harvested using a 
template to plan the size and shape, and subcutaneous fat 
is removed. The donor site, such as post- or preauricular, 
supraclavicular or groin, is closed directly. It generally 
provides good colour match on the face and contracts 
minimally. Such grafts are inevitably limited in size and 
must be placed on a healthy, vascular base. 

4. Flaps are detached tissue, containing a network of 
arterial, venous and capillary vessels, transferred from 
one site to another. They can retain their intact circulation 



on the original vascular pedicle. Random pattern flaps do 
not have an anatomically recognized vascular supply and 
as a general rule the length of the flap should not exceed 
twice the length of the attached base. Some flaps have 
identified vessels supplying them - axial pattern flaps, 
including the forehead, groin and deltopectoral region; 
these may be raised on a narrow pedicle and discon- 
nected completely, for the vessels to be joined to vessels 
at the recipient site - a free flap. This is achievable as a 
result of microsurgical techniques. They may include 
other tissues, including deep fascia, muscle or bone. 
Useful sites include the forehead, groin and deltopectoral 
region. 

5. Myocutaneous flaps provide a robust vascularized 
wound cover over exposed bone, tendon or areas sub- 
jected to high mechanical demands. Skin in many areas is 
supplied by perforating vessels from the underlying 
muscle and an island of skin can be transferred with the 
muscle to provide simultaneous skin cover. The muscle is 
isolated onto its vascular pedicle alone and rotated into 
the defect. Commonly used myocutaneous flaps include 
the latissimus dorsi, rectus abdominis, pectoralis major 
and gastrocnemius. 

6. Deep fascia included with overlying layers of skin 
improves vascularity and safety; they can also be trans- 
ferred as vascularized free flaps. 

7. Tissue expansion allows the skin and subcutaneous 
tissue to be stretched in order to nil a defect nearby An 
expandable silicone (Silastic) bag is inserted beneath the 
skin and subcutaneous fat. When the wound is healed, 
the sac can be filled percutaneously with increasing 
volumes of saline though a special subcutaneous port. 
Once the overlying skin is sufficiently stretched, the 
implant is removed and the stretched excess skin can be 
advanced into the defect. 



SKIN SUBSTITUTES 



l-V^V^^^^^^^^'^^^^'' , i' 



^£&^^^&&$£-yy&&it 



Wound coverage is vitally important. If sufficient skin is 
not available it may be possible to apply a substitute. The 
main need for these substitutes is in the management of 
extensive burns. 

1. Autologous (derived from the same individual) 
cultured epidermal cells provide permanent coverage 
but they require 3 weeks in order to grow sufficient 
cells. 

2. Allografts (Greek alios = other; from another indi- 
vidual) cultured epidermal cells from living persons or 
cadavers do not appear to be rejected, possibly because 
they do not express major histocompatability complex 



247 



24 




OPERATION 



ir - ..vvjjjimmK 



class II antigens and are not contaminated with 
Langerhans cells, which are the antigen-presenting cells 
of the epidermis. They are eventually replaced by host 
cells, so they offer temporary coverage. 

3. Neonatal epidermal cells, for example from excised 
foreskins, release growth factors. Cultured cells accelerate 
healing and relieve painful chronic ulcers, 

4. A composite collagen-based dermal lattice in a sili- 
cone covering may be valuable in the treatment of burns. 
The dermal cells are gradually degraded but after 3 weeks 
the Silastic sheet cover can be removed and replaced by 
cultured autologous cells. Human epidermal cells and 
viable fibroblasts may be included in the composite. 
Viable fibroblasts may also be included in a nylon net 
cover overlaid with Silastic to reduce evaporation. 

5. In order to provide substitute dermal as well as 
epidermal cells, bovine collagen and allogeneic human 
cells may be combined. 




Summary 

• Are you aware of the multiplicity of 
factors to which the skin is exposed? 

• Do you recognize the varied causes of skin 
damage and loss? 

• Do you understand the complex biology of 
skin healing? 

• Can you discuss the methods of skin 
closure? 



References 



Berry DP, Harding K, Stanton MR, Tasani B, Ehrlich HP 1998. 

Human wound contraction: collagen organization, fibroblasts 

and myofibroblasts. Plastic and Reconstructive Surgery 102: 

124-131 
Singer AJ, Clark RA 1999. Mechanisms of disease: cutaneous 

wound healing. New England Journal of Medicine 

341: 738-746 




Further reading 

Brough M 2000. Plastic surgery in general surgical operations, 

4th edn. Churchill Livingstone Edinburgh, pp 727-773 
Kirk RM 2002 Basic surgical techniques, 5th edn. Churchill 

Livingstone, Edinburgh 
McGregor I A, McGregor AD 1 995 Fundamental techniques in 

plastic surgery and their surgical applications. Churchill 

Livingstone, Edinburgh 
Nedelec B, Ghahary A, Scott PG, Tredget EE 2000, Control of 

wound contraction. Basic and clinical features. Hand Clinics 

16: 289-302 
Richard R, DerSarkisian D, Miller SF, Johnson RM, Staley M 

1999. Directional variance in skin movement. Journal of Burn 

Care and Rehabilitation 20: 259-264 
Saba AA, Freedman BM, Gafh'eld JW, Mackay DR, Ehrlich HP 

2002. Topical platelet-derived growth factor enhances wound 

closure in the absence of wound contraction: an experimental 

study. Annals of Plastic Surgery 49: 62-66 
Witte MB, Barbul A 2002. Role of nitric oxide in wound repair. 

American Journal of Surgery 183: 406^412 
Younai S, Venters G, Vu G, Nichter L, Nimni E, Tuan TL 1996. 

Role of growth factors in scar contraction: an in vitro 

analysis. Annals of Plastic Surgery 36: 495-501 



248 




Transplantation 

P. McMaster, L. J. Buist 



w 



Objectives 



Appreciate the causes of organ rejection. 
Understand the principles of 
transplantation and immunosuppression. 
Be aware of the source of transplanted 
organs, and the associated ethical and 
legal considerations. 



Table 25.1 Forms of tissue transfer 



BASIC PRINCIPLES 



'W'^^te^^ 



ti'X&t-rSPffig&T&itf!, 



Early Christian legends attest to the attempts to replace 
diseased or destroyed organs or tissues by the transfer 
from another individual. The father of modern surgery, 
John Hunter, carried out extensive experiments on the 
transposition of tissues and concluded what he thought 
were successful experiments on the transposition of teeth! 
However, it was not until the dawn of the 20th century 
that the practical technical realities of organ transfer were 
combined with sufficient understanding of the immuno- 
logical mechanisms involved to allow transplantation to 
become a practical reality. 

While it had long been recognized that successful blood 
transfusion was in large measure dependent on matching 
donor and recipient cells, it was only in the 1950s that 
Mitchison (1953) demonstrated that, while cell-mediated 
immunity was responsible for early destruction and 
rejection, it was the humeral mechanism with cytotoxic 
antibodies that was primarily involved in the host 
response to foreign tissue. It became increasingly recog- 
nized that all tissue and fluid transfer was governed by 
basic immunomechanisms (Table 25.1). 

The need in the Second World War to find improved 
ways of treating badly burned pilots led Gibson & 
Medawar (1943) to carry out a series of classic experi- 
ments on skin transplantation. They were able to con- 
clude that the transfer of skin from one part of the body 
to another in the same individual (an autograft), survived 
indefinitely, whereas the transfer of skin from another 



• Transfer of tissue 
Blood 

Bone marrow 

* Tra nsf er o f solid o rga n 
Skin 

Cornea 

Kidney 

Heart 

Liver 

Pancreas 



individual (an allograft) was in due course destroyed and 
that the recipient retained memory of the donor tissue 
and further transfers or allografts were destroyed in an 
accelerated mechanism. Thus the wider recognition of 
the universal acceptance of autografts became realized, 
whereas the failure of an allograft was recognized as part 
of an immune response. An alternative source of organs 
is, of course, the animal world, and the transfer from 
another species is known as a xenograft. 



FIRST CLINICAL PROGRAMMES 

The recognition that an autograft would be universally 
acceptable led to the first successful attempts at organ 
grafting in humans. In the early 1950s, Murray et al (1955) 
at the Peter Bent Brigham Hospital in Boston, were able 
to demonstrate the successful transfer of a kidney graft 
from an identical twin, with acceptance and successful 
function, and to develop a programme of renal trans- 
plantation between monozygotic twins. 

Some of the recipients of kidney transplants from 
identical twins remain well more than 40 years after 
grafting; however, grafts between unrelated living indi- 
viduals performed by this same group invariably failed, 
although not as quickly as experimental studies might 
have suggested. 



249 



25 




OPERATION 



RESPONSE 

The other major human source of organs, other than from 
living relatives, is from individuals who have died as a 
result of road traffic accidents or cerebral injuries. 
Cadaveric organ grafting from non-related individuals is 
now the major source of organs. Within Europe, more 
than 80% of all organs transplanted are from brain-dead 
donors. 

Thus, although technical considerations presented the 
initial formidable barrier to organ transfer, it was increas- 
ingly the understanding of the immune response causing 
organ destruction by rejection, which led to clinical 
schedules permitting practical transplantation services to 
be established. The body's immune response to destroy 
the invading organ we now recognize as rejection. 



REJECTION 

Early experimental studies involving tissue transfer sug- 
gested genetic regulation of the rejection process. It was 
suggested in the 1930s that rejection was a response to 
specific foreign antigens (alloantigens) and that they were 
similar to blood groups of other species. The development 
of inbred lines of experimental animal models allowed 
the demonstration of antigens present on red blood cells 
and the concept of histocompatibility. This suggestion of 
an immunological theory of tissue transplantation stimu- 
lated Meda war's (1944) work in rabbits and later in mice, 
and led to similar studies in humans, with the discovery 
of the human leucocyte antigen (HLA) system. 

Further experimental studies defined the concept of 
rejection into three primary categories: hyperacute rejec- 
tion, which can occur in a matter of hours due to pre- 
formed antibodies in a sensitized recipient; acute rejection, 
which takes place in a few days or weeks and is usually 
caused by cellular mechanisms; and chronic rejection, 
which occurs over months or years and remains largely 
undefined, but involves primarily humeral antibodies. A 
detailed review of experimental and modern transplan- 
tation biology is quite beyond the scope of this chapter, 
but increasing understanding of this area will allow more 
refined changes in rejection management and increas- 
ingly successful organ grafting. 



AVOIDING REJECTION 

The degree of disparity between donor and recipient is an 
important key element in the severity of the immune 
rejection response. In xenografting (transfer between 
species) the presence of preformed antibodies leads to 
rapid endothelial damage, causing vascular thrombosis, 



gross interstitial swelling and necrosis of the graft, all 
within a matter, usually, of hours. 

Similarly, when transfer occurs between human beings, 
the degree of compatibility between donor and recipient 
is important to the success, or otherwise, of the graft. 

As indicated earlier, transfer between identical twins is 
associated with universal success, without the need to 
modulate the immune mechanism. However, transfer 
between non-identical relatives or using cadaveric 
organs produces the recognition of non-self by the re- 
cipient and the mounting of an immune response. It is 
the avoidance or modification of this immune response 
that has been the main target over the last 25 years, and 
the avoidance of overwhelming rejection has been a 
prime goal. 

Two approaches have been taken to the problem: tissue 
typing and reduction of immune response. 

Tissue typing 

In the attempt to match the donor and recipient more 
closely, the concept of typing has become widely devel- 
oped. Early work demonstrating that blood transfusion 
was dependent on matching between donor and recipient 
was extended into experimental and then clinical trans- 
plantation studies in the 1960s and 1970s. 

The human chromosome 6 contains the genetically deter- 
mined major histocompatibility complex (MHC), i.e. the 
HLA-A, HLA-B, HLA-C (class I) and HLA-DR (D-related; 
class II) loci. A whole series of additional genetic regions 
have been linked to the HLA complex, although in clinical 
terms these are probably less significant. 

Thus it has become increasingly possible, using sero- 
logical studies, to map genetically an individual on the 
basis of the HLA region of this chromosome. Since one 
chromosome is inherited from each parent and each indi- 
vidual has two HLA haplotypes, there is a 25% chance 
that two siblings will share both haplotypes (i.e. identi- 
cal) and, by standard and mendelian inheritance, a 50% 
chance that they will share one haplotype. Thus in first- 
degree relatives when the donor and recipient are 
matched for HLA-A and -B antigens there is an excellent 
likelihood of graft success, whereas because of the com- 
plexity of the MHC allele, the wide divergence of anti- 
gens and random cadaveric donors, even if matched for 
one or two antigens, there may still be very substantial 
disparity. 

Thus, in order to avoid rejection, the concept of tissue 
typing trying to match more accurately the donor and 
the recipient has gained wide acceptance. Serological 
methods allow class I HLA antigens to be defined using 
typed serum obtained from nulliparous women. Using a 
microcytotoxicity assay, multiple antisera against HLA-A, 
-B, -C and -DR antigens are provided on Terasaki trays 



250 



TRANSPLANTATION 



25 



and then frozen until required. When needed, the trays 
are thawed and the donor lymphocyte cells are added to 
the wells containing complement and the antisera against 
specific HLA types. If the antibody causes the cells to lyse, 
acrid ine orange (a dye) enters the damaged cell and 
appears orange under fluorescence microscopy. Thus, by 
using microcytotoxicity tests it is possible to identify quite 
rapidly the HLA class I antigens present in a donor. 

Until recently class II antigen typing required a mixed 
leucocyte reaction to determine individual constituents, 
but more recent techniques have avoided this laborious 
investigation. From the clinical standpoint the practical 
importance of identification of the degree of compatibil- 
ity between donor and recipient is clearly defined in 
many organ-grafting systems. Cadaveric grafting can 
only achieve this level when beneficially matched donor 
and recipient pairs r in which all major class I and class II 
antigens are identical, are grafted. This so-called 'full 
house' HLA match can give 1 year cadaveric graft sur- 
vival approaching 90%. However, this is only when com- 
bined with chemical non-specific immunosuppression. 

When grafts are transferred between cadaveric donor 
and recipient with a complete mismatch an additional 
20-25% of grafts will be lost over the ensuing 5 years. 
Thus, in cadaveric grafting the degree of matching has an 
important role in determining the severity of the immune 
response and the ultimate success, or otherwise, of the 
graft. 

Nevertheless, no matter how good the matching is in 
cadaveric situations, modulation of the immune response 
continues to be necessary to ensure graft survival. 

Reduction of immune response 

Reduction in the immune response occurs frequently in 
clinical practice in such situations as uraemia, profound 
jaundice and in patients with advanced malignancy and 
acquired immunodeficiency syndrome (AIDS). The con- 
trolled reduction of an immune response to foreign 
antigen on the graft requires careful clinical judgement. 
Initial attempts using widespread radiation produced 
severe depletion of not just lymphocytes but also a pan- 
cytopenia, and although the recipients readily accepted 
skin grafts and other organs immunologically, the major- 
ity of patients quickly died from overwhelming infection. 
A refinement of this technique, in which partial lym- 
phocyte irradiation was used, has been successful both 
experimentally and in clinical practice, depleting the 
immune response so that grafts can be accepted. 

Chemical immunosuppression 

Since the mid-1950s the primary mode of immunomodu- 
lation has been the administration of chemical agents. A 



demonstration by Hitchings & Elion (1959), over 40 years 
ago, that 6-mercaptopurine had immunosuppressive 
potential, allowed Schwartz & Dameschek (1959) to treat 
rabbits stimulated by foreign antigen. The treated 
animals did not produce antibodies to the antigen stimu- 
lation, and work by Calne in 1960 showed that 6- 
mercaptopurine could also inhibit the immune response 
in dogs. A number of other agents were studied at that 
time and those found to be of clear benefit were steroids, 
reducing the cellular response, and eventually azathio- 
prine, which showed improved results when compared 
to 6-mercaptopurine. 

For more than 20 years chemical irnmunomodulation 
with the combination of steroids (prednisolone) and 
azathioprine was to be the main non-specific immuno- 
suppressant used. They inhibited the immune response 
largely by depressing circulating T cells. 

The production of antilymphocytic globulin by sensiti- 
zation in animals was also demonstrated to inhibit the 
immune response, although variability and efficacy 
limited its clinical use. 

Ciclosporin. Clearly the ultimate goal of selectively 
inhibiting the recipient's immune response remains a 
long way off, and in clinical practice non-specific agents 
continue to be used. In 1976, Borel and colleagues 
working in Sandoz laboratories assessed the potent 
immunosuppressive properties of ciclosporin A, a cycli- 
cal peptide with 11 amino acids. The demonstration of 
both the in vitro and in vivo immunosuppressive activity 
was quickly followed by extended clinical studies. It was 
clearly demonstrated that ciclosporin could suppress 
both antibody production and cell-mediated immunity, 
exhibiting a selective inhibitory effect on T cell-dependent 
responses. Of critical importance was the observation that 
the drug was neither profoundly lympho- nor myelotoxic 
and had no influence on the viability of the mature T cells 
or the antibody-producing B cells. Further agents have 
recently been introduced to clinical practice, perhaps 
resulting in less rejection still (FK506 or tacrolimus, 
mycofenolate and monoclonal antibodies). 



CURRENT CLINICAL 
IMMUNOSUPPRESSIVE USE 



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For nearly 30 years the mainstay of clinical immuno- 
suppression was the combined use of steroids and aza- 
thioprine. With increasing clinical experience it became 
possible to adjust the dosage of these agents so that in 
many individuals it was possible to maintain immuno- 
suppression and thus prevent rejection, while minimiz- 
ing the risk to the recipient of over irnmunomodulation, 
a delicate balance that requires considerable clinical 
skill. 



251 



25 



. 



OPERATION 



Patients receiving steroids and azathioprine required 
careful monitoring for signs of early infection and the 
presence of organ rejection. Progressive reduction in 
haemopoietic production leads to thrombocytopenia and 
leucopenia, with the attendant risk of infection (bacterial/ 
fungal and viral). The major complications of long-term 
steroid and azathioprine immunosuppression are out- 
lined in Table 25.2. 

Thus, considerable clinical skill was needed to avoid 
the risks of infection, and in cadaveric grafting, when the 
degree of matching between donor and recipient was 
often less than optimal, death from infection was the 
commonest cause of death in the first 3 months after graft- 
ing. In addition, the need to administer steroids continu- 
ally became a major limiting factor, particularly in 
children, where the complications of steroids can be so 
crippling (Table 25.3). 

The results of organ grafting using prednisolone and 
azathioprine left much to be desired, and so the intro- 
duction of ciclosporin into clinical trials in the early 1980s 
was an important step forward in the more selective use 
of immunomodulation. Not only could steroids be mini- 
mized or avoided in some individuals, but also pancyto- 
penia was rarely encountered. Nevertheless, ciclosporin 
was rapidly found to have its own attendant problems 
and difficulties and nephrotoxicity remains a persistent 
problem (Table 25.4). 



Table 25.4 Side-effects of ciclosporin 



Nephrotoxicity 
Hepatotoxicity 
Tremors, convulsions 
Skin problems 
Gingival hypertrophy 
Haemolytic anaemia 
Hypertension 
Malignant change 



With increasing clinical experience, however, many of 
these toxic effects can now be minimized, such that excel- 
lent rehabilitation can be achieved and organs can now be 
grafted which previously would have been unsuccessful 
in the prednisolone and azathioprine era. The overall 
results of ciclosporin will be outlined in the individual 
sections, but there have been no clinical series in which 
the results of ciclosporin have been inferior to the treat- 
ment with azathioprine and prednisolone, and for the 
most part an improved benefit of between 15 and 20% of 
graft survival at 1 year has been reported. 

Postoperative monitoring of all patients with trans- 
planted organs involves regulation of the immunosup- 
pressive regimen, detection of the development of organ 
rejection and constant vigilance for signs of infection. 



Table 25.2 Side-effects of steroids and 
azathioprine 



Steroids. 

Avascular necrosis of bones 

Diabetes 

Obesity 

Cushing's syndrome 

Pancreatitis 

Cataract 

Skin problems 

Psychosis 

Azathioprine 

8one marrow suppression 

Polycythaemia 

Hepatotoxicity 



Table 25,3 Side-effects of steroids in children 



* Growth retardation 

* Cushingoid appearance 

• Diabetes 

• Obesity 



CADAVERIC ORGAN DONATION 

The concept of the diagnosis of brain death and 
increased awareness by both the public and doctors alike 
of the need for organ donation have improved the 
supply of cadaveric organs for grafting. In the UK, about 
half of patients who become organ donors have died 
from spontaneous intracranial haemorrhage, although 
head injuries and road traffic accidents also provide 
donors. 



SPECIFIC ORGAN TRANSPLANTATION 



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Kidney 

Kidney transplantation is now well established as the 
most effective way of helping patients with end-stage 
renal failure. Despite a significant expansion in the 
number of kidney transplants, long waiting lists exist for 
those on dialysis awaiting treatment. In the UK an 
integrated approach has shown a steady increase in the 
proportion of patients treated by transplantation, such 
that nearly 50% of patients now have a functioning 
transplant. 



252 



TRANSPLANTATION 



25 



Patient selection 

With kidney transplantation affording the optimal quality 
of rehabilitation few patients will be denied the prospect, 
although the patient's age and underlying renal condition 
may need to be taken into account. 

Age. In general, children do very well after trans- 
plantation, although infants below the age of 5 years 
present a more controversial issue because of the diffi- 
culty of management of immunosuppressive agents. The 
newer immunosuppressive regimens, however, allow 
adequate growth and physical development. The goal for 
children must be the establishment of normal renal func- 
tion before maturity and to take full advantage of the 
growth spurt that occurs at puberty. 

While in the early days patients over the age of 55 years 
were frequently denied transplantation, many centres 
now offer renal transplantation to patients over 65 or 
70 years. Patient and graft survival has been very satis- 
factory in this group, but immunosuppressive schedules 
frequently need to be reduced in the elderly to ensure that 
overwhelming infection does not occur. 

Renal disease. Renal transplantation is now offered 
for many primary and secondary renal conditions result- 
ing in chronic renal failure, including glomerulonephritis, 
pyelonephritis and polycystic disease. Some types of 
autoimmune glomerulonephritis antibodies have been 
demonstrated to cause damage to the transplanted 
kidney, but this is not a contraindication to transplanta- 
tion, as probably less than 10% of grafts will be seriously 
injured. 



Assessment of potential recipient 

Careful review of both the physical and psychological 
status of the patient is needed before transplantation, and 
factors that may increase the hazards of surgery or 
immunosuppressive management require evaluation. 
Patients in renal failure frequently suffer from cardiovas- 
cular problems (hypertension with left ventricular hyper- 
trophy, and coronary artery disease) and the symptoms 
are increased by anaemia. There is a high incidence of 
peptic ulceration in uraemic patients, and of metabolic 
bone disease, causing renal osteodystrophy All these 
associated conditions must be optimally treated or con- 
trolled before transplantation surgery. Sources of under- 
lying or potential infection, such as an infected urinary 
tract or peritoneal cavity from peritoneal dialysis, must be 
eradicated or treated and the patient's status for viruses 
such as hepatitis B, HIV and cytomegalovirus must be 
known to minimize activation following immunosup- 
pression. Careful surgical review related to previous 
abdominal operations, peripheral vascular ischaemia 
or the presence of ileal conduits following previous 



urogenital surgery needs also to be carefully taken into 
account and a surgical plan initiated. 

Careful counselling and support are also needed to 
ensure that the patient understands and is prepared for 
transplantation. 

Surgical technique 

The technique of renal implantation has remained 
unchanged now for nearly 40 years, with the donor 
kidney being implanted extraperitoneally in one of the 
iliac fossae. The renal artery is anastomosed to either the 
internal or the external iliac artery, and the renal vein to 
the recipient's external iliac vein. The donor ureter is then 
implanted into the recipient's bladder. Over 150 000 
kidney grafts have been performed around the world, but 
total transplantation rates vary significantly from one 
country to another. 

Postoperative problems 

Monitoring of the kidney allograft is required to detect 
signs of rejection, suggested by a reduction in urinary 
output and an elevation in serum creatinine, and then 
confirmed by biopsy or aspiration cytology. This allows 
the prompt recognition of an acute rejection crisis and its 
treatment by steroids. 

With increased clinical experience the hurdles of acute 
rejection and infectious complications can usually be 
overcome, and patient survival at 1 year is in excess of 
95% in many programmes, with over 85% of kidney grafts 
functioning well; however, a steady attrition of renal 
grafts will occur over the next 10 years, so that only just 
half of all renal transplants will be functioning well at 
10 years, with many having been lost from the slow 
process of chronic rejection. 

Rehabilitation can be spectacular, allowing patients the 
freedom to eat without restriction on salt, protein or 
potassium, the resolution of anaemia and infertility and 
an improvement in their overall sense of well-being. 

Renal transplantation in the diabetic patient can be 
combined with pancreas transplantation, with implanta- 
tion of the whole organ and drainage of the pancreatic 
duct into the gastrointestinal tract or the urinary bladder. 
Transplantation of isolated pancreatic islets is in its 
infancy. 

Heart 

While the patient afflicted by renal disease has the benefit 
of chronic haemodialysis, the individual with progressive 
cardiac problems has no life support system and death 
invariably ensues unless cardiac transplantation is under- 
taken. Initial efforts in the late 1960s by Barnard (1967) led 



253 



25 ■OPERATION 





to a progressive expansion of increasingly successful 
programmes. The majority of patients will suffer from 
cardiomyopathy, terminal ischaemic cardiac disease or, 
more rarely, some congenital form of cardiac disease. 
Donor selection must be rigorous because immediate life- 
sustaining function is required of the graft. 

Orthotopic replacement of the diseased heart has been 
the most frequently undertaken procedure, although the 
heterotopic placement of auxiliary cardiac implants has 
been undertaken. The donor atria are anastomosed to 
the posterior walls of the corresponding chambers of the 
recipient prior to joining the pulmonary artery and the 
aorta. 

Postoperative cardiac function is monitored and 
endomyocardial biopsy allows histological examination 
of heart muscle for ventricular cellular infiltration indica- 
tive of acute rejection. While the early attempts at cardiac 
grafting resulted in poor overall survival, the situation 
has improved remarkably. A 1 year survival of over 85% 
and a 5 year survival of 60% of patients with excellent 
quality of rehabilitation are most encouraging. 

This solid foundation of cardiac grafting inevitably led 
to an extension to combined heart and lung transplanta- 
tion, primarily for those suffering from pulmonary hyper- 
tension, or for some terminal lung diseases, such as cystic 
fibrosis or emphysema. If the recipient has lung disease 
but a good functioning heart on receipt of a combined 
heart— lung graft, the heart from the first recipient can be 
implanted into a second cardiac patient - the domino pro- 
cedure. As a result of technical advances, transplantation 
of single lung is now possible. Because of the risk of infec- 
tion in the implanted lungs, immunosuppressive man- 
agement is critical. Sputum cytology and even lung 
biopsy may be needed to differentiate infection from 
rejection. In spite of this, the Stanford University Series 
now reports 2-year survival of over 60% in heart-lung 
recipients. 

Liver 

Although the first attempts at liver transplantation were 
made in the early 1960s, the formidable technical, preser- 
vation, immunological and organ availability difficulties 
meant that it was only in the early 1980s that successful 
programmes were established. The majority of adult 
patients coming to liver grafting have extensive cirrhosis 
(primary biliary cirrhosis, chronic active hepatitis and 
hepatitis B) or, less frequently, primary liver cancer. In the 
paediatric group the most common indication for liver 
transplantation is biliary atresia. 

The liver is particularly susceptible to ischaemic injury 
and the ability to harvest and store livers for only a few 
hours led to an extremely complex surgical procedure, 
undertaken often in the most difficult emergency situations. 



The liver is placed orthotopically after removal of the 
diseased organ, and veno venous bypass is employed to 
reduce the physiological changes during the anhepatic 
phase. Improvements in organ preservation (principally 
the introduction of the University of Wisconsin solution) 
mean that livers can now be stored for 12-14 h and trans- 
ferred from one country to another. The evidence that 
tissue matching is important in liver grafting has yet to be 
fully established, but, as in other forms of transplantation, 
this may prove to be the case. 

Patients coming to liver grafting are frequently criti- 
cally ill with multisystem failure, and the complexity of 
the operation has inevitably meant that technical failures 
have been frequent. In spite of this, results have con- 
tinued to improve, and with nearly 30 000 liver trans- 
plants performed in Europe and 1 year survival of over 
85%, liver transplantation is increasingly being estab- 
lished as one of the most effective modalities of treatment 
for liver disease. In some groups the results have shown 
even more impressive improvement. Infants and children 
with biliary atresia undergoing grafting stand a greater 
than 90% chance of 1-year survival, with more than 75% 
well at 5 years. The longest survivor is now over 25 years 
after transplantation. 

The major limiting factor in liver grafting now is donor 
availability and, while in the UK some 650 grafts were 
performed in 2001, the need is probably double that. The 
most acute shortage is of paediatric organs, and often a 
larger liver has to be divided and only part transplanted 
into a child. Recently partial lobe donation has become 
possible from live donors, usually a parent, especially in 
countries where cadaveric programmes are not available, 
such as Japan. This same approach is also being explored 
in adults. 

Other organs 

Pancreas transplantation is increasingly being undertaken 
in diabetics, often in kidney failure who need a kidney 
transplant. The techniques developed allow the pancreas 
to drain through the bladder and >85% of patients are 
insulin free at 1 year. It remains to be confirmed that the 
improvement in carbohydrate control will improve the 
diabetic complications, but sugar control is excellent. 

In children, programmes of intestinal transplantation 
are also developing with encouraging results, allowing 
the children to come off total parentral nutrition and 
resume normal feeding. 



ETHICAL ISSUES 

The development of transplantation in the 1950s and 
1960s caught not just the imagination of the medical 



254 



TRANSPLANTATION 



25 



profession but that of the public as well, and led to the 
reappraisal of fundamental beliefs in many areas. The 
concept of death was challenged, from the traditional one 
of the cessation of the heart beat to that of the concept 
of brainstem death, and wide public and professional 
debates ensued. Death, the great taboo of the 20th century, 
was addressed in a new, fundamental way. The majority 
of countries enacted legislation or medical guidelines 
identifying new criteria which would allow more effec- 
tive recognition of an individual's incapacity to regain 
essential and vital functions. Some of these issues were 
challenged in courts of law and were often widely 
reported in the media. 

Thus ethical and moral issues were raised from the very 
outset of organ grafting. With the increasing success of 
organ transplantation these pressures have grown. The 
rights of the individual to dispose of his or her own 
organs as they wish has been a matter of debate, and the 
profession has loudly condemned the commercialism 
which is in danger of entering clinical practice. The pur- 
chase or sale of organs is now condemned by almost all 
international transplantation organizations. 

Should a living individual during his or her lifetime 
voluntarily donate an organ to another? The first suc- 
cessful grafts between identical twins from within a 
family were clearly perceived to be an act of great charity 
and compassion. Living-kidney grafting in the USA 
accounts for more than a third of all grafts, but should 
such altruism be permitted between non-family 
members, or those in whom a loving and caring bond 
does not exist? These new issues continue to be addressed 
by society. 

One other issue has particularly focused on cardiac and 
liver transplantation and this relates to the consumption 
of economic resources for an individual. In the UK the 
cost of renal transplantation in total is approximately 
£8000-10 000, whereas the cost of dialysis per year per 
patient approaches £15 000. While renal transplantation is 
clearly the most cost-effective way of dealing with renal 
failure, compared with some other forms of medical and 
surgical treatment and perhaps healthcare initiative, it is 
seen as being expensive. 

Cardiac and liver transplantation can equally be seen to 
consume a large amount of health resources and may be 
given a low priority in some health systems. 

The development of live related liver lobe donation is 
also giving rise to some concerns because of the potential 
risk of such major surgery to the donor. 

Each new development in science and clinical medicine 
raises its own issues, which need to be addressed, and, as 
these modalities of treatment spread to other countries, 
different cultural approaches may be required. It will be 
for the individual community to decide whether such 



treatments are appropriate for its members and to what 
extent resources can be made available. 

Clinical organ transplantation has evolved rapidly 
over the last 25 years, affording treatment to many thou- 
sands of patients who would otherwise be dead or endur- 
ing an existence of chronic illness. Further advances are 
sought in the fight against the recipient immune response 
and to procure donor organs of the highest quality, thus 
enabling even more patients to experience the increasing 
benefits of transplantation. 



Summary 

• Successful whole organ transplantation 
has depended on a number of advances in 
understanding of infection and 
immunosuppression. 

• Awareness of the public and of doctors 
has increased the supply of cadaveric 
organs but a severe shortage remains so 
that many patients who could benefit will 
die while awaiting a donor organ. 

• Results have improved because of better 
monitoring and management, rather than 
from any technical changes. 




References 



Barnard CN 1967 The operation. A human cardiac transplant: 

an interim report of a successful operation performed at 

Groote Schuur Hospital, Cape Town. South African Medical 

Journal 41: 1271-1274 
Borel JF, Feurer C, Gutter HU, Stahelin A 1976 Biological effects 

of cyclosporin A: a new antilymphocytic agent. Agents and 

Actions 6: 468-475 
Calne RY 1960 The rejection of renal homografts: inhibition in 

dogs by 6-mercaptopurine. Lancet i: 417-418 
Gibson T, Medawar FB 1943 The fate of skin homografts in 

man. Journal of Anatomy 77: 299-309 
Hitchings GH, Elion GB 1959 Activity of heterocyclic 

derivatives of 6-mercaptopurine and 6-thioguanine in 

adenocarcinoma 755. Proceedings of the American 

Association for Cancer Research 3: 27 
Medawar PB 1 944 Behaviour and fate of skin autografts and 

skin homografts in rabbits. Journal of Anatomy 78: 176-199 
Mitchison NA 1953 Passive transfer of transplantation 

immunity. Nature 171: 267-268 
Murray JE, Merrill JP, Harrison JH 1955 Renal 

homotransplantation in identical twins. Surgery Forum 

6: 423^26 
Schwartz R, Dameschek W 1959 Drug induced immunological 

tolerance. Nature 183: 1682-1683 



255 



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257 



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Pathogenesis of cancer 

P. D. Nathan, D. Hochhauser 




Objectives 

Recognize that gene defects cause cancer. 

Understand the processes involved in 

normal cell cycle control. 

Understand the genetic events leading to 

loss of cell cycle control. 

Appreciate the genetic background to 

invasion, metastasis and angiogenesis. 

Recognize that this understanding is 

leading to new therapeutic approaches. 



INTFtoDU^ 

Cellular processes are controlled by the products of gene 
expression. A gene is a unit of inheritance that carries 
information representing a protein; it is a genetic store- 
house, a stable information packet, transmitted from one 
generation to the next. Information flows from DNA to 
RNA (transcription) to proteins (translation). Some genes 
have key functions controlling cell growth, and, if these 
are damaged, abnormal cell proliferation may result. 
Deregulation (freedom from control) of genes, either 
inherited or acquired, may result from mutations (Latin 
mutate = to change), deletions and other mechanisms of 
gene 'silencing'. This may result in a breakdown of 
normal cell cycle control, including the avoidance of pro- 
grammed cell death - apoptosis (Greek apo- - from + 
piptein = to fall). 

Cancer (Latin = crab, German = krebs; possibly from 
the appearance of the distended veins extending out- 
wards in all direction, like crab's legs) is now a major 
cause of death in the United Kingdom. Cancers develop 
because of genetic alterations, including the acquisition of 
power to invade normal structures and to metastasize 
(Greek meta = often implies change + stasis - a standing). 

As our understanding of these processes develops, we 
can identify novel therapeutic targets, improving anti- 
cancer treatment. 



CJl L CYCJUE C<WT^ 

1. Successful cell cycle control is critically important. 
Fortunately, a number of key regulatory elements have 
evolved that reduce the likelihood of uncontrolled cell 
growth. Regulatory signals may be positive or negative. 
The normal cell cycle is controlled by a balance of positive 
and negative signals from both outside and inside the cell. 

2. A normal gene that exerts a positive growth signal is 
a proto-oncogene (Greek protos = first, primitive; onkos = 
tumour). If it is damaged, it gives an abnormally increased 
'on' drive to cell growth and is termed an oncogene if such 
an alteration results in development of a cancer cell. 

3. A normal gene that exerts a restraining effect on cell 
growth is a tumour suppressor gene. If it is damaged or 
lost, the cell is deprived of the 'off signal. 

4. The activation of oncogenes and absence of tumour 
suppressor genes deregulates (frees from restraint) cell 
cycle control. 

5. Under normal circumstances, environmental infor- 
mation from outside the cell is relayed to the cell via cell 
surface receptors which may bind growth factors such as 
epidermal growth factor (EGF), inhibitory factors or com- 
ponents of the extracellular matrix (ground substance). 
When a molecule such as a growth factor (a ligand, from 
Latin Hgare - to bind) unites with its receptor, this 
receptor-ligand binding induces a change of form in the 
receptor. This in turn activates an enzyme, for example a 
tyrosine kinase. Tyrosine kinases function within cells to 
attach phosphate groups to the amino acid tyrosine - 
phosphorylation. This triggers an intracellular signalling 
cascade, mediated via protein-protein interactions, 
inducing enzyme activity. The result is a change in gene 
expression, producing an increased cellular proliferation. 
Tyrosine phosphorylation is thus an early event in a 
complex signalling system. Depending upon the incom- 
ing information, the cell may respond in a variety of 
ways. If the ligand is a growth factor, the cell enters into 
the S phase of the cell cycle (Fig. 26.1). 

6. Once a resting cell is in G it can remain quiescent 
and viable, yet it can reinitiate growth after latent periods 
of months or years. When a resting cell enters the late G : 



259 




MALIGNANT DISEASE 



GO 

(quiescence) 



Growth 

factors 

mitogens 



Inhibitory 
V>x (actors 



S phase 
(DNA synthesis) 




M phase 

(mitosis) 






Fig. 26.1 Resting or quiescent cells (G ) can pass into 
the cell cycle by the action of growth factors. Once past 
the restriction point R, they are committed to progress 
through S phase where DNA synthesis occurs. The stars 
indicate checkpoints that allow the fidelity of the 
process to be monitored and errors dealt with. 

phase it passes a restrictive checkpoint where any 
damage to DNA is detected. If no abnormality is detected, 
the cell is committed to DNA synthesis (Fig. 26.1). There 
are further checkpoints at S (synthesis), G 2 (second gap) 
and M (mitosis) phases to ensure the fidelity of the DNA 
synthetic process. 




Key point 

Checkpoint controls ensure that, if an error is 
detected, further replication is prevented. 



7. Repair of an abnormality in the DNA may be poss- 
ible but, if not, the cell undergoes programmed cell death. 
Apoptosis is the final common pathway for a large 
number of cellular insults and allows cells to avoid 
passing damaged DNA sequences on to the next gener- 
ation. Under normal circumstances apoptosis is avoided 
by a combination of the presence of antiapoptotic signals 
and the absence of proapoptotic signals. 

ABNORMAL OE^^ 

1 . Oncogenes and suppressor genes have been identi- 
fied at many of those stages of cell cycle control described 
above. 



2. Cancer cells escape reliance on exogenously pro- 
duced growth factors to stimulate their growth. They may 
do this by (Fig. 26.2): 

a. Overproducing growth factors which are released 
into the cellular microenvironment and which auto- 
stimulate the cancer cells 

b. Overexpressing growth factor receptors 

c. Expressing mutated or truncated receptors that give 
constant 'on' signals 

d. Expressing altered components of the downstream 
signalling pathway. 

3. Cancer cells also avoid normal antiproliferative 
signals. For example, the effects of the antigrowth 
signal, transforming growth factor beta (TGFp), can be 
downregulated at the receptor level or within its signal 
transduction pathway (Latin trans = across, beyond + 
ducere - to lead; the path followed by the signal) in a 




Fig. 26.2 How cells escape reliance on external growth 
factors: a, overproduction of growth factors; 

b, upregulation of growth factor receptors; 

c, constitutive signalling by mutated receptor; 

d, constitutive signalling by mutated components of 
signal cascade. 



260 



PATHOGENESIS OF CANCER 



26 



similar way to those growth factors described above. 
Many antiproliferative signals ultimately appear to exert 
their action through the retinoblastoma protein (Rb) 
which inhibits E2F transcription factors; these are pro- 
teins with DNA-binding motifs. They bind to specific 
nucleotide sequences - promoters close to the initiating 
codon of each gene, thus controlling transcription. They 
control the expression of many genes involved in cell 
cycle progression and DNA synthesis. Mutations in the 
Rb gene, the archetypal tumour suppressor gene, de- 
regulate this pathway, allowing E2F transcription factors 
to exert their effect by stimulating the release of genes 
involved in proliferation. 

4. Avoidance of apoptosis is a central feature of most, 
if not all, cancers. A variety of pro- and antiapoptotic 
signals converge on a final common pathway of mito- 
chondrial release of cytochrome c, the pigment that trans- 
fers electrons in aerobic respiration. Mitochondria (Greek 
mitos = thread + chondros = granule) are cytoplasmic 
organelles involved in cellular respiration. Apoptosis is 
regulated by members of the bcl-2 gene family, an onco- 
gene, described initially in B-cell lymphoma, which pre- 
vents cell death by apoptosis. The effect of increased 
expression of bcl-2 may in part explain resistance to the 
effect of chemotherapy in cancer cells that express high 
levels. The most common proapoptotic signal lost in car- 
cinogenesis is the p53 suppressor gene, which is mutated 
in over 50% of human common solid tumours. Under 
normal circumstances, p53 plays a key role in detecting 
DNA damage, and initiating cell cycle arrest and DNA 
repair. 



New blood vessel 
formation (angiogenesis) 




=5S 



Metastatic spread 



o 



% 



o 



o 



o 
c 
c 




© 



7 



o 



O 



O 



O 



Basement 
membrane 



Blood vessel 



Fig. 26.3 Cancers must traverse the basement 
membrane before infiltrating blood vessels, 
metastasizing to distant sites and stimulating new blood 
vessel growth if they are to spread and grow. 



E 



Key point 



Loss of cell cycle regulatory control is a critical 
factor in the development of cancer cells and 
resistance to treatment. 



ANGIOGENESIS AND METASTASIS 

1. The features that differentiate benign from malig- 
nant growth are invasion and metastasis. Cells must 
traverse the basement membrane and other extracellular 
boundaries and then attract a blood supply to support 
tumour growth (Fig. 26.3). Changes in expression of 
cell-cell adhesion molecules (CAMs) and cell-matrix 
adhesion molecules (integrins) are thought to be pivotal. 
Loss of E-cadherin function, a CAM facilitating epithelial 
cell-cell interaction, occurs in many epithelial tumours. 
Integrin expression is switched on to allow movement 
through local extracellular matrix and adhesion to distant 



matrix, and enzymes which digest matrix components, 
matrix metalloproteinases (MMPs), are expressed and 
digest local stroma (connective tissue framework), facili- 
tating movement of the cell through the extracellular 
matrix. 

2. In addition to loss of adhesion, previously static, 
specialized cells may lose their special function, their 
ability to differentiate, and migrate. Many solid tumour 
cells attract fibroblasts, which lay down collagen around 
them. It is the appearance of the resulting radiating 
strands of fibrous tissue that makes cancers resemble a 
crab's body - the primary tumour, with claws - the result 
of cancer cell migration, hence the name of cancer. 




Key point 



• Angiogenesis is a key factor in development of 
tumours. 



261 



26 - 



MALIGNANT DISEASE 



■■-■■■ L. -,■■ , 



3. Control of new blood vessel formation, angiogene- 
sis, is dependent upon the interaction of pro- and anti- 
angiogenic stimuli. Vascular endothelial growth factor 
(VEGF) is upregulated in some tumours, and in animal 
models VEGF inhibitors have antitumour activity. The 
angiogenesis inhibitor thrombospondin has also been 
shown to be downregulated. Other components of this 
process are being identified and may offer future thera- 
peutic targets. 

4. Although cancer cells are thought of as being rapidly 
dividing cells, the rate of division of many cancers is not 
as high as in many normal tissues such as the gut mucosa, 
bone marrow and skin. However, the loss of apoptosis 
and the reduction of telomeric erosion mean that the 
malignant cells have increased survival, provided that 
they retain their blood supply. 



ACQUISITION AND ACCUMULATION 
OF GENETIC DAMAGE 












1 . Damaged genes may be inherited through germline 
DNA (see Ch. 40). This is responsible for cancer families 
that have a preponderance of cancer often presenting at 
an early age. A variety of genes have been identified that 
are associated with an inherited high risk of cancer. For 
example, mutations, and consequent loss of function of 
the tumour suppressor genes BRCA-1 and BRCA-2, occur 
in breast and ovarian cancer, and of the familial adeno- 
matous polyposis (FAP) gene in some forms of inherited 
colon cancer. 

2. The majority of cancers are sporadic - scattered, 
occurring casualty and caused by derangement of somatic 



(Greek soma = body) genes. It is now well recognized that 
there is a latent period, sometimes of many years, 
between the time of the initiating influence and the devel- 
opment of the cancer. Cancers do not result from a single 
mutation but from a stepwise accumulation of abnormali- 
ties. The fact that cancers arise more commonly as age 
increases is in keeping with the accumulation of muta- 
tions with time. Those who inherit a germline risk factor 
that affects every cell in their bodies are already primed, 
awaiting further stepwise mutations. 

3. Environmental factors are recognized as important, 
as the incidence of cancer arises between different stable 
populations and between stable populations and 
members who migrate elsewhere. For example, when 
Japanese migrate to Hawaii the incidence of gastric carci- 
noma is reduced, and is even further reduced if they 
move to the USA. The best known environmental cause 
of bronchial cancer is cigarette smoking. Gastric cancer is 
associated with a diet rich in smoked foods; mesothe- 
lioma is closely linked to contact with asbestos; aflatoxins 
released by the fungus Aspergillus flavus are implicated in 
hepatocellular carcinoma. 

4. Electromagnetic and particulate radiation act by 
increasing mutations. X-rays initiate them, especially in 
the bone marrow; ultraviolet light from solar radiation 
affects the skin. 

5. DNA oncogenic viruses act by encoding proteins 
that interfere with growth regulation (Table 26.1). 
Epstein-Barr virus (EBV), may promote cancers, includ- 
ing Burkitt's lymphoma and nasopharyngeal cancer. 
Hepatitis B virus (HBV) is associated with hepatocellular 
cancer. Human papillomavirus (HPV) is associated with 
cervical carcinoma. 



r. 



^— tatri" i 



Table 26.1 Carcinogenic agents 



Agent 



Viruses 

Human papilloma virus (HPV) 

Hepatitis B and C viruses (HBV, HCV) 

Epstein-Barr virus (EBV) 

Human T-lymphocyte virus 1 (HTLV-1) 

Chemical carcinogens 

Cigarette smoke 

Asbestos 

Nickel, chrornates, arsenic 

Aromatic amines 

Polyvinyl chloride 

Afiatoxin 

Radiation 
Ionizing radiation 
Ultraviolet radiation 




Tumour type 



Cervical cancer 

Hepatocellular carcinoma 

Burkitt's lymphoma, nasopharyngeal cancer 

AduftT-cell leukaemia and lymphoma 

Lung, laryngeal and bladder cancer; some increased risk of many others 

Mesothelioma 

Lung 

Bladder 

Angiosarcoma of liver 

Hepatocellular carcinoma 

Leukaemia, breast cancer, thyroid cancer 

Melanoma, basal cell and squamous cell cancers of skin 



262 



PATHOGENESIS OF CANCER 



26 



6. RNA retroviruses, single-stranded viruses, initiate 
copies into DNA pro viruses. They do not appear to cause 
human cancers directly but human immunodeficiency 
viruses (HIV) are associated with Kaposi's sarcoma. 

7. Some substances are believed to initiate cancers not 
by causing mutations directly but by increasing cell 
growth and turnover, thus increasing the opportunities 
for mutations to occur. Alcohol abuse may act by causing 
chronic liver inflammation, producing high liver cell 
turnover. Oestrogen is a stimulant for breast and endome- 
trial cell multiplication. 

8. Some substances do not initiate cancer if given first, 
but if given repeatedly following mutation from an ini- 
tiator they induce cancer development. They are called 
promoters. 

9. Parasites may be involved in the development of 
cancer, notably the liver fluke (Schistosoma spp) and 
Clonorchis sinensis, which causes bladder cancer. 




Key point 

• Most cancers are generated by factors in the 
environment, not by inherited gene mutations. 

10. Point mutations, deletions (a portion of a chromo- 
some is lost) and translocations (a chromosome segment 
is transposed to a new site) all occur and they are all 
capable of interfering with normal gene function. 

11. Every gene exists as two copies or alleles (a short- 
ened form of allelomorph: Greek allelon - of one another 
+ morpke = form; one of two or more alternative forms of 
a gene). Mutation of only one allelle of a proto-oncogene 
may result in oncogenesis if it produces much variation 
of the patient's oncogenic phenotype. The phenotype 
(Greek phainein = to show + typtein - to strike) is a struc- 
tural or functional characteristic resulting from combined 
genetic and environmental activity. Damage is required to 
both allelles of a protosuppressor gene if a tumour sup- 
pressant effect is to be overcome. This was described by 
Knudson in his 'two-hit hypothesis' (Fig. 26.4). 

12. Given the complexity of the biological processes 
that must be overcome for a cell to exert a malignant 
phenotype, it can be seen that damage to a number of 
critical genes is required. This "multi-hit hypothesis' was 



Hereditary 
retinoblastoma 



RB 



Sporadic 
retinoblastoma 



Germline mutation ^^ 



rb 



X • 



RB 



RB 



Nv 



RB 



Somatic 
mutation 



\ 



\ 



RB 



Somatic 
mutation 



rb 



X X 



rb 



rb 



X • 



RB 



rb 



* 



2nd somatic 
mutation 



rb 



Fig. 26.4 Knudson's two-hit hypothesis. RB, normal 
retinoblastoma gene; rb, mutated gene. Patients who 
inherit (i.e. in the germline) one defective (mutated) 
copy of the gene have a high chance of acquiring a 
somatic mutation at an early age, resulting in loss of RB 
function. Patients who inherit two normal genes require 
two somatic mutations, resulting in sporadic disease 
occurring at a later age. 



described by Vogelstein, who argued that the progression 
from premalignant to malignant lesions seen in colorectal 
carcinoma is associated with the accumulation of key 
mutations in oncogenes and suppressor genes (Fig 26.5). 
This model is now generally accepted as occurring in 
many cancers. 

13. It would be unlikely for a normal cell with intact 
DNA repair machinery to accumulate the significant 
amounts of genetic damage required to exert a malignant 
phenotype. The fact that cancer cells accumulate exten- 
sive DNA damage may be a reflection of their damaged 
DNA repair mechanisms and genomic instability. 





APC Ki-ras smad4 


p53 E-cadherin 


Normal 
colonic 


Small Large 
►* adenoma +- adenoma ► 


Pre-malignant Colorectal 
changes *■ carcinoma ► 



Invasion 



epithelium 



Fig. 26.5 The multi-step pathway to colorectal cancer. The accumulation of 5-10 mutations in several tumour 
suppressor genes or oncogenes over a lifetime results in cancer. 



263 




MALIGNANT DISEASE 



Summary 

• Do you understand the genetic damage to 
those genes responsible for normal cell 
cycle control and cell behaviour that result 
in cancer? 

• Do you realize that multiple events, in a 
number of oncogene and suppressor gene 
activities, are required for carcinogenesis? 

• Can you understand why therapies are 
targeted to gene products responsible for 
carcinogenesis? 




M Further reading 



Hanahan D, Weinberg RA 2000 The hallmarks of cancer. Cell 

100: 57-70 
Kinzler KW, Vogelstein B 1996 Lessons from hereditary 

colorectal cancer. Cell 87: 159-170 
Sporn MB 1991 The war on cancer. Lancet 347: 1377-1381 



264 




Principles of surgery for 
malignant disease 

P. J. Guillou, I. A. Hunter 




Objectives 

• Appreciate the importance of histological 
diagnosis. 

• Realize the multidisciplinary implications 
of management. 

• Accept that surgery may be valuable even 
when cure is no longer possible. 



INTRODUCTION 

In 2000 malignant disease was responsible for 151 200 
deaths in the UK, a figure that accounts for 25% of all 
registered deaths (Cancer Research UK). Tables 27.1 and 
27.2 indicate the contribution of different types of malig- 
nant disease to both cancer incidence and cancer-related 
mortality. Over the last 50 years there have been major 



Table 27.1 


The most common cancers in 1997 




Males Females 


Lung 
Prostate 
Breast 
Colorectal 


24 440 (19) 14 430(11) 
21 770(17) 

38 000 (29) 
18 130(14) 16 180(12) 


Values in parentheses are percentages of total 
malignancies registered. 



Table 27.2 Gastrointestinal cancer deaths, 2000 



Males 



Females 



Oesophagus 
Stomach 
Large bowel 
Pancreas 



4300 
4060 
8540 
3370 



2G20 
2530 
7730 
3530 



improvements in the survival rates of some solid 
tumours, but for many the prognoses remain poor and 
largely unchanged (Fig. 27.1). 

Despite recent advances in the use of adjuvant therapies 
(Latin ad - to + juvare = to help) such as chemotherapy and 
radiotherapy, surgery remains the main modality of treat- 
ment for many solid organ tumours, including cancer of the 
breast, lung, urogenital tract and gastrointestinal tract. You 
must fully assess the tumour and the patient before decid- 
ing on surgical intervention. This demands detection, his- 
tological diagnosis, staging and consideration of the role of 
other adjuvant interventions. The process is best planned, 
carried out, monitored and followed up in cooperation 
with a multidisciplinary team including radiologists, 
pathologists, radiotherapists and medical oncologists. 



ASSESSMENT 



Patient assessment is a vital part of operative planning. 
Establish a pathological diagnosis and the extent of 



100% 




& 



«<> 



^ 



V 






* </ jr <f 









Fig. 27.1 Changes in 5 year survival rates from 
1971-1975 to 1991-1993 according to cancer type. 
(Source Office for National Statistics, Cancer Trends in 
England and Wales 1950-1999). 



265 



27 



MALIGNANT DISEASE 



spread of the disease prior to operative intervention, as 
these factors have a major influence on the treatment you 
can offer an individual patient. Assess the patient's 
physiological and psychological status; as in all surgery 
they impact on the extent of the operative intervention 
that you can safely consider. 

Pathological diagnosis and tumour grading 

Before considering operative intervention obtain a biopsy 
specimen for histological analysis to confirm the presence 
of malignant disease and indicate its expected behaviour. 
Biopsies of gastrointestinal and urogenital tumours can 
usually be obtained by luminal endoscopy. For most solid 
organs, biopsy specimens can be obtained using needle core 
biopsy or fine needle aspiration cytology, if necessary under 
ultrasound or radiological guidance or at laparoscopy. 

Histological grading helps predict the behaviour of a 
neoplasm based on its histological appearance. Grading 
systems focus on the apparent differentiation status of the 
tumour. Simple histological grading has poor prognostic 
value and is an unreliable guide to treatment. Advances 
in molecular biology now allow specific molecules to be 
identified that more accurately predict tumour behaviour 
and response to available treatment. 

Immunohistochemical detection of oestrogen receptors in 
breast cancer tissue is a good example of the predictive 
value of identifying a molecular marker, as it gives the 
probable response of the tumour to oestrogen antagonists 
such as tamoxifen. In the future, molecular grading will 
increase in value. 



Tumour staging 

Staging often has a direct impact on the extent of surgery 
that must be performed to eradicate malignant disease, or 
may indicate that curative resection is not possible and 
that only palliative (Latin palliare = to cloak) procedures 
are worth considering. 



imaging (MRI), conventional and intraluminal ultra- 
sound and [ 18 F]-fluorodeoxyglucose-linked positron 
emission tomography (FDGPET) have greatly improved 
the quality of preoperative staging (see Ch. 5). Despite 
these advances, preoperative staging is by no means 100% 
sensitive or specific and accurate staging may still be 
possible only at, or after, operative intervention. In many 
cases true staging is determined by the histological exam- 
ination of resection specimens. Although preoperative 
assessment is essential, you must be prepared to alter 
your planned interventions in the light of the findings at 
operation. 



SURGICAL MANAGEMENT 



^&^^?^&ift7&&?> 



w^^m^^mww^^ 



The aims of surgery in malignant disease are: 

• To remove all malignant cells from the patient to 
achieve a complete cure. The complete removal of 
tumour is termed an Rq resection. 

• To maintain or restore the integrity of tissues in order 
to preserve function following tumour removal. 

Curative resection may be impossible or unsuccessful 
because: 

• The tumour has invaded vital, unresectable, local 
structures. 

• An intra-abdominal tumour has seeded into the peri- 
toneal cavity. 

• Tumour cells have metastasized into distant organs and 
still be undetectable (micrometastasis). 

• Tumour cells have metastasized into distant organs and 
these deposits cannot be safely removed. 

R resection usually involves removing the tissue con- 
taining the tumour with an intact covering of unaffected 
tissue to leave the resection margins free of disease, to 
avoid exposing and shedding viable tumour cells. 
Imaging techniques cannot yet detect individual tumour 
cells, therefore you must expect undetected local spread. 




Key point 

• In planning surgical intervention, the staging 
of tumours is of greater relevance than 
grading. 

The tumour, node, metastases (TNM) system describes 
the extent of spread and generally correlates well with 
prognosis. It is based on the size and local spread of the 
primary tumour (T), the presence of lymph node met- 
astasis (N) and distant metastasis (M). Imaging modalities 
such as computed tomography (CT), magnetic resonance 



I I Key point 

• Learn how tumours spread, in order to obtain 
clear resection margins and avoid local 
recurrences (see Ch. 26). 



Local invasion 

Tumours spread locally into the surrounding tissues. 

1. Epithelial gastrointestinal tract tumours often 
spread longitudinally in the submucosal layer or laterally 



266 



PRINCIPLES OF SURGERY FOR MALIGNANT DISEASE 




27 



through the muscular layers towards the serosa; for 
example, oesophageal tumours tend to spread longitudi- 
nally in the submucosa beyond the visible luminal limits, 
so the longitudinal resection must be extensive to avoid 
local recurrence at the resection margins. In contrast, 
rectal carcinoma spreads a relatively short distance lon- 
gitudinally, so resection margins 3 cm from the tumour 
are considered safe. 

2. If surrounding tissues are invaded, consider these 
for resection, based on the principles outlined in this 
chapter. For instance, if gastric carcinoma invades the 
body and tail of the pancreas, transverse colon, or 
retroperitoneal nodes and spleen, resect them en bloc 
(French = in one piece) with the stomach. 



Lymphatic spread 

Tumour cells also spread within draining lymphatics to 
regional nodes and may develop into metastatic foci. 
Anticipate this and, where possible, remove local nodal 
groups in continuity with the lymphatic connections to 
the primary tumour. 

1 . Colonic lymphatic drainage is initially via the para- 
colic nodes, then through the nodes lying alongside the 
supplying arteries and on into the preaortic nodes at the 
origin of the superior or inferior mesenteric arteries. The 
supplying vessels are removed at their origins in order 
to excise as many draining lymph nodes as possible. 
Therefore the full extent of colon that is dependent on 
those arteries for blood supply must be resected. Rectal 
cancers tend to spread laterally in lymphatic vessels 
within the pelvic mesorectum. Recognition of this has led 
to total mesorectal excision, resulting in a lowering of 
local recurrence rate. 

2. Lymphatic drainage of the testis is to the para- 
aortic lymph nodes (due to their embryological 
origin within the abdomen). Testicular tumours are 
treated surgically by orchiectomy, an approach that does 
not address potential lymphatic involvement; however, 
surgical treatment of anticipated lymphatic involvement 
is usually not required due to the sensitivity of semi- 
nomas to radiotherapy. Following orchiectomy for 
seminoma it is standard practice to give adjuvant radio- 
therapy to the para-aortic nodes, even in stage I disease 
(where no lymphatic metastasis are clinically or radio- 
logically evident). Such approaches have resulted in 
5 year survival rates approaching 100% in stage I 
disease. 

3. The main route of lymphatic drainage of breast 
tumours is to the ipsilateral (Latin ipse = same) axilliary 
nodes. 

a. The great American surgeon William Halsted 
(1852-1922) described in 1882 the principle of radical 



(Latin radix - root; hence, by the roots) mastectomy. The 
primary tumour should be removed together with the 
draining lymphatics and a wide margin of intervening 
tissue in one block. 

b. The psychological consequences of radical mastec- 
tomy and the development of adjuvant therapies have 
introduced alternative treatments. In wide local excision, 
the breast tumour is excised with a surrounding cuff of 
unaffected tissue. This risks leaving residual undetected 
disease in the axilliary nodes and in the breast. It is there- 
fore combined with adjuvant radiotherapy to the breast, 
and either a sampling, or partial clearance, of the ipsilat- 
eral axilliary nodes. This is potentially curative, but can 
also be considered as a form of staging surgery; later 
examination of the resected breast tissue and nodes may 
reveal the presence of residual disease or nodal involve- 
ment On the basis of postoperative staging, further 
radical surgery or systemic chemotherapy can be planned 
if necessary. 

c. Sentinel lymph node biopsy (SLNB) offers a further 
option instead of axilliary clearance or nodal sampling. 
It is based on the principle that the lymphatics will ini- 
tially drain to a single node before progressing to further 
nodal groups. A tracer molecule such as patent blue V 
dye, or radiolabeled technetium, can be injected into the 
vicinity of the primary tumour at operation, allowing it 
to enter local lymphatics and become concentrated in the 
sentinel node. Once the sentinel node has been identified 
it is removed and subjected to histological examination. 
If the node is free of metastatic deposits then the axilla 
can be considered free of disease, as it is unlikely that 
more distant nodes are involved. A positive sentinel 
node indicates axilliary spread, demanding further 
operation or adjuvant therapy. Its role is currently under 
investigation in a number of UK randomized clinical 
trials. 

4. Cutaneous malignant melanoma is another tumour 
that commonly spreads to local lymph nodes. Treatment 
of the primary tumour again follows oncological princi- 
ples and aims to remove the melanoma together with a 
clear margin of uninvolved tissue; however, this approach 
fails to address possible involvement of local lymph 
nodes. 

a. Elective lymph node dissection (ELND) of regional 
nodes has been advocated in an attempt to reduce recur- 
rence in the draining nodal basin. However, in stage I 
disease only 20% of patients are found to have histo- 
logically positive nodes, and ELND is associated with 
increased postoperative morbidity and cost. The practice 
of ELND has also failed to emerge as a statistically 
significant predictor of improved survival in several 
prospective randomized trials. 

b. SLNB can also be considered in the management of 
malignant melanoma. As with breast cancer its role is still 



267 



27 _ 



MALIGNANT DISEASE 



controversial, although it has been declared as standard 
care for patients with melanoma by the World Health 
Organization. 



Transcoelomic spread 

Tumours within intra-abdominal organs can breach the 
serosal covering to reach the peritoneal cavity - 
transcoelomic (Latin trans = across + Greek koilos = 
hollow) spread - and may there form multiple deposits. 
Clearance of all tumour cells is now practically imposs- 
ible. This accounts for the poor prognosis associated with 
serosal involvement in gastric carcinoma. Bear this in 
mind when removing tumours so that you do not spread 
or encourage the seeding of primary tumour cells within 
the peritoneal cavity. 



Haematogenous spread 

Tumour cells can gain direct access to the vascular system 
through the endothelium of their supplying vessels, or 
through lymphatics to major ducts draining into the 
bloodstream. They may then form metastatic (Greek meta, 
signifying change + stasis = a placing; a change of situ- 
ation) tumour deposits, typically in the liver, lung and 
bone marrow. These are often undetectable at the time of 
surgery and become clinically apparent months or years 
after the primary resection. Although metastatic deposits 
threaten survival, some are suitable for resection. Of the 
50-60% of patients with colorectal cancer who develop 
liver metastases, around 25% are suitable for attempted 
curative resection, with 5 year survival rates of 27-37%. 
Likewise, in selected cases, pulmonary metastases may 
also be considered for surgical treatment using solitary 
wedge resection, multiple wedge resections or lobectomy. 
Five year survival rates of 21-43% have been achieved, 
although a high preoperative carcinoembryonic antigen 
(CEA) level or lymph node metastases are both predictors 
of a poor outcome in these patients. 



Palliative procedures 

Curative (R ) resection involves the removal of the 
tumour and a large amount of unaffected tissue. 
Extensive resections increase the short- and long-term 
risks of complications; therefore, such resections are 
warranted only with the prospect of achieving a cure. If 
removal of all malignant tissue is not possible, tumour 
recurrence is inevitable unless adjuvant therapy, such as 
chemotherapy or radiotherapy, is given to destroy re- 
sidual tumour. If this is ineffective, consider a palliative 



(Latin palliare = to cloak) procedure if it offers symp- 
tomatic benefit. 

1 . Oesophageal, gastric, small bowel or colonic obstruc- 
tion can often be relieved by palliative resection, bypass or 
construction of an external stoma. Malignant oesophageal 
or colonic obstruction is often amenable to endoscopic 
insertion of a stenting tube, or a self-expanding stent 
introduced under radiological control, avoiding open 
operation. Intraluminal tumour incursion can be 
temporarily destroyed with a laser beam controlled 
endoscopically. 

2. Despite modern imaging methods it is often difficult 
to decide, preoperatively, whether malignant biliary 
obstruction is amenable to curative surgery. Potentially, 
25% of pancreatic cancer patients and 35% of those with 
ampullary carcinoma may survive 5 years following 
resection. Alternatively, a plastic stent may be inserted 
percutaneously or endoscopically, but it tends to block 
and then needs to be replaced. Metal stents are less likely 
to block but are more expensive. Consequently, there is 
considerable controversy about the management of 
malignant biliary obstruction. 

3. In some cases surgery may alleviate symptoms or 
reduce the need for treatment, even though it does not 
affect the outcome. For example, patients with incurable 
carcinoma of the stomach or colon may bleed chronically 
and require regular blood transfusions. Resection of the 
affected tissue stops the bleeding and mitigates the symp- 
toms of anaemia. 

4. Apart from relieving obstruction-related colic, 
resecting locally invasive bowel tumours rarely reduces 
pain. Neurectomy occasionally helps but often results in 
motor loss. Coeliac axis block is usually more effective 
than systemic analgesia in relieving the deep infiltrating 
pain of, for example, unresectable pancreatic cancer. 

Curative surgery for secondary malignant 
disease 

Local or locoregional malignant recurrences are not 
always irrecoverable. 

1. Regional nodal metastases from malignant 
melanoma may follow excision from a limb or trunk. If 
there are no detectable distant secondaries, block dissec- 
tion may produce 20-25% 5 year survival. 

2. Recurrent colorectal cancer suspected clinically, or 
through regular monitoring of plasma CEA (see Ch. 30) 
and liver ultrasound, may be indications for 'second look' 
surgery. Locally recurrent colorectal cancer is rarely cured 
by further resection but valuable palliation can often be 
provided. 



268 



PRINCIPLES OF SURGERY FOR MALIGNANT DISEASE 




27 



Reconstructive surgery for malignant disease 

Radical excision of malignant disease often demands 
subsequent reconstruction, restoration or replacement: 

1 . Stomach mobilized and supplied only by the right 
gastric and gastroepiploic arteries can be drawn up 
to the neck to replace the resected pharynx or 
oesophagus. 

2. Following mastectomy, a myocutaneous flap of rectus 
abdominis or of latissimus dorsi can be used for 
reconstruction. 

3. Free tissue transfer may be employed, with 
anastomosis of the divided supplying vessels to 
local vessels, using microvascular surgical 
techniques. 

4. Lost skin and tissue can sometimes be replaced by 
inserting an inflatable tissue expander to stretch the 
skin or develop a space. This is then removed, 
allowing the skin to be closed. Following mastectomy 
a silicone implant can be inserted as a substitute for 
the breast. 



ADJUVANT THERAPY 



to around 2% after two courses of adjuvant chemotherapy 
containing cisplatin. 



^^m^^^vK^:S^£;ig:i^ 



Adjuvant treatment is an extra remedy added to the treat- 
ment to increase its effectiveness (see Chs 28, 29). When 
applied before surgery it is called neoadjuvant (Greek 
neos - new - perhaps revived in a new form) therapy. 
Examples are preoperative radiotherapy for rectal cancer, 
chemoradiotherapy for oesophageal cancer and some 
stages of breast cancer. In these cases the intention is to 
'down stage' the primary tumour. 

Adjuvant therapy may be administered after surgery, 
when the histological staging is available. Patients at high 
risk of postoperative recurrence can now be identified 
and given additional therapy. An example of this is the 
administration of 5-fluorouracil and folinic acid to 
patients undergoing resection of Dukes' stage C colonic 
cancer (Cuthbert Dukes, pathologist at the famous 
St Mark's Hospital in London, classified rectal cancers as 
'A' if the tumour was limited to the rectal wall, 'B' if it 
extended through the wall but without involving 
adjacent lymph nodes, and 'O when regional nodes 
were invaded). This adjuvant therapy provides a 30% 
improvement in 5 year survival compared with surgery 
alone. 

Postoperative chemotherapy has also proved to be 
highly effective in the management of testicular cancer. 
Recurrence rates for men with high risk (those with 
vascular invasion within the resection specimen) non- 
seminomatous germ cell tumours are reduced from 50% 



THE MULTIDISCIPLINARY APPROACH 



^^^V^P^f^i^^^l^^^^-i 






The multidisciplinary approach to cancer management 
combines the expertise of pathologists, radiologists, 
oncologists, radiotherapists and surgeons. This has 
resulted in the development of new treatment protocols 
that in the case of some tumours have seen a great 
improvement in survival and functional outcome. The 
advances in the treatment of osteosarcoma provide a 
good example of how different disciplines can work 
together in the management of malignant disease. 

1. Osteosarcoma is classically a disease of young 
adults; it exhibits aggressive local invasion and a propen- 
sity to metastasize early. Historically, treatment involved 
amputation of the affected limb and achieved survival 
rates of only 10-20%. Osteosarcomas are usually con- 
tained within a pseudocapsule of reactive tissue around 
the primary tumour. Although well-defined anatomical 
compartments initially limit their spread, these tumours 
do have a tendency to metastasize via the haematogenous 
route, mainly to the lungs and other bones. As well as 
forming distant metastatic deposits, more local meta- 
stases also occur in the form of intramedullary 'skip 
lesions' within the same bone. 

2. The surgical principles applied to the treatment of 
osteosarcoma are in keeping with those outlined within 
this chapter. Ideally a tumour is removed in its entirety 
with a margin of unaffected tissue. This may have to 
include joints and other local soft tissue structures. Such 
an approach often necessitated amputation, due to bone 
loss or the removal of neurovascular bundles; however, 
advances in reconstructive surgery and neoadjuvant 
therapies have resulted in the increased success of limb- 
sparing surgery and a reduction in the occurrence of 
distant disease. 

3. A biopsy specimen is usually obtained at open 
biopsy by the surgeon planning the definitive operation. 
This allows the biopsy incision to be incorporated in the 
final resection specimen. Histological examination con- 
firms the diagnosis and also grades the tumour. 
Osteosarcoma is one example in which grade is a part of 
the staging system and therefore has an influence on 
treatment protocols. 

4. Initial assessment using combined imaging modali- 
ties such as CT, MRI and scintigraphic bone scanning 
allow accurate assessment of local and distal spread. This 
is essential in the planning of surgical intervention. The 



269 



27 ' 



MALIGNANT DISEASE 



degree of surrounding soft tissue involvement, the iden- 
tification of skip lesions and intramedullary spread will 
dictate the extent of the resection margin required for 
potentially curative surgery. The feasibility of limb 
salvage can also be assessed. Although bone and soft 
tissue will be lost in order to achieve local control, func- 
tion may be restored by the utilization of prosthetic 
implants, cadaveric bone allografts, bone autografts and 
rotationplasty. In some cases a "down staging' of the 
primary tumour can be achieved by using neoadjuvant 
chemotherapy. A good response to such therapy may 
induce necrosis in the tumour and reduce surrounding 
inflammation. This may make a surgeon more inclined to 
attempt limb salvage surgery. The use of preoperative 
chemotherapy in non-metastatic high grade resectable 
osteosarcoma is now standard. 

5. Postoperative chemotherapy is employed, even 
after a successful resection of the primary tumour, in an 
attempt to target micrometastases to distant organs. 
Following resection and reconstruction, histological 
examination of the resection specimen is used to establish 
the tumour's response to neoadjuvant chemotherapy. 
The degree of induced tumour necrosis has been shown 
to be a good predictor of clinical outcome. A poor 
histological response after neoadjuvant therapy is often 
addressed by modification of the postoperative 
chemotherapy regimen. 

6. This combined approach to the treatment of 
osteosarcoma has resulted in a reduced amputation rate 
and an improvement in long term survival rates to over 
60%. 



Summary 

Do you recognize that clinical assessment 

of patients with suspected malignant 

disease is still paramount? 

Why does early diagnosis improve the 

prognosis? 

Can you reason why emergency 

intervention carries a poorer outlook than 

elective surgery? 

Why is it inappropriate to plan operative 

treatment of malignant disease in 

isolation from other modalities? 

Why is it imperative to make a tissue 

diagnosis before embarking on ablative 

operation for suspected cancer? 

What can surgical operation offer patients 

when malignant disease has extended 

beyond curative resection? 

Have you made a decision with the 

patient, or for the patient? (see Ch. 14). 

Can you offer palliation if you cannot cure 

cancer, or if it recurs following resection? 




Taylor I, Cooke TG, Guillou PJ 1996 Essential general surgical 
oncology. Churchill Livingstone, Edinburgh 



270 




Principles of radiotherapy 



/?. A Huddart 




Objectives 



Understand the physics and biology of 

radiation, determining how radiotherapy is 

used. 

Understand the process of delivering a 

course of radiation. 

Recognize the role of radiotherapy 

treatment in modern oncology, with 

emphasis on its interaction with surgical 

oncology. 

Understand the basis of radiation 

side-effects and how they may interact 

with surgical treatment. 



beam produced by a linear accelerator has several proper- 
ties that make it well suited for present day radiotherapy: 

1. The greater penetration of the 7-rays means that a 
high proportion of the dose applied to the body surface 
reaches the tumour. 

2. All X-ray beams have a fuzzy edge (the penumbra) 
due to the reflection and scattering of the beam by tissues. 
High energy X-rays suffer relatively little sideways scatter 
as they pass through tissues, and this helps to keep the 
edge of the beam sharp. 

3. The forward scattering effect is also indirectly 
responsible for the point of maximum dose being 1-2 cm 
below the skin surface (Fig. 28.1). The skin therefore 
receives a low dose and is spared from radiation reac- 
tions. It was the high skin doses associated with low 



SOURCES OF IONIZING RADIATION 

Radiotherapy is the therapeutic use of ionizing radiation 
for the treatment of malignant disorders. Natural sources 
of radiation include radioactive isotopes which decay 
with the production of p-particles (electrons) and 7-rays 
(a form of electromagnetic radiation). Originally radium 
was used, but over the last 20 years this has been replaced 
by safer artificial isotopes such as cobalt-60, caesium-137 
and iridium-192, which are generated in nuclear reactors. 
Isotopes are used mainly as sources implanted directly 
into tissues, such as iridium needles in the treatment of 
carcinoma of the tongue, or inserted into a cavity, for 
example caesium sources inserted into the uterus and 
vagina for the treatment of carcinoma of the cervix. 
Radioactive isotopes may also be given systemically, such 
as iodine-131 in the treatment of thyroid cancer. 

External beam radiotherapy was revolutionized in the 
1950s by the advent of mega voltage treatment machines; 
initially cobalt machines and later linear accelerators. The 
linear accelerator generates a stream of electrons which is 
accelerated to high speed by microwave energy before 
hitting a tungsten target. This interaction results in the 
emission of high energy X-rays. The high energy X-ray 



Or 



cm 10 



15 




20 

Fig. 28.1 Dose distribution of a linear accelerator. Note 
the maximum dose is below the skin surface and 65% of 
the applied dose is present at 10 cm. 



271 



28 



MALIGNANT DISEASE 



energy X-ray machines that in the past caused the uncom- 
fortable skin reactions and limited treatments of deep- 
seated tumours. 

In addition, cyclotrons can be used to produce ionizing 
beams of heavier particles such as neutrons or protons; 
however these machines are yet to find a place in routine 
clinical practice. 



ACTIONS OF IONIZING RADIATION 












^^^■te^v^^^ym^^^^fftfr 



X-rays (from linear accelerators) and -y-rays (from iso- 
topes) are both forms of electromagnetic radiation and are 
biologically indistinguishable. High energy X-rays consist 
of packets of energy (photons) which interact with the 
molecules of body tissues to cause ionization and release 
electrons of high kinetic energy These electrons cause sec- 
ondary damage to adjacent molecules, including DNA, 
via an oxygen-dependent mechanism. The resultant DNA 
damage is mostly repaired by enzymes in a matter of 
hours, but certain DNA lesions are irreparable. In some 
normal cell lineages (e.g. lymphoid, myeloid, germ cells) 
the DNA damage triggers immediate programmed cell 
death (apoptosis). Non-repairable DNA damage causes a 
variety of chromosomal abnormalities. This DNA damage 
does not stop most cells from performing their normal 
physiological functions effectively, but when the cell tries 
to divide it dies in the attempt. Thus damage is expressed 
when the cell undergoes mitosis, and in fully differenti- 
ated cells incapable of further division (e.g. muscle cells) 
this damage may never be expressed. 




Key points 



• Tissues may be severely damaged by irradiation 
but appear essentially normal; damage is 
expressed only if they are stimulated to divide. 

• Response to radiotherapy by tumours may be 
delayed, especially in tumours with slow rates 
of growth (e.g. pituitary tumours). 

There are many data on the respective effects of radio- 
therapy on normal tissues and tumours. It appears that 
tumour cells may not differ greatly from the cell of origin 
in response to single doses of radiotherapy, although 
there may be differences in the ability of tumours and 
normal tissues to recover from the effects of cell damage. 
For example, normal tissues have a greater ability to 
respond to radiation-induced cell depletion by acceler- 
ated repopulation, an ability which seems to be less devel- 
oped in tumours. To eradicate a tumour within the limits 



of tolerance of surrounding normal tissues, radiotherapy 
must exploit these and other subtle differences in DNA 
repair and regrowth of normal tissues. 

In external beam treatments, therapeutic advantage is 
generally achieved by dividing the total dose of radio- 
therapy into small parts over several weeks, a practice 
called fractionation. A full discussion of the effects of frac- 
tionation is not possible in this chapter, but generally: 

1. Reducing the dose per fraction allows certain critical 
normal tissues, such as the nervous system, the lungs and 
other slowly proliferating tissues, to repair damage more 
effectively than tumours. 

2. Fractionation over a period of several days or weeks 
gives rapidly proliferating normal tissues, such as skin 
and gut, a chance to repopulate and hence recover from 
radiotherapy-induced damage faster than tumours. 

3. Many tumours contain hypoxic areas. As the major 
effect of radiotherapy is by an oxygen-dependent mech- 
anism, these areas are relatively resistant to radiotherapy. 
Each fraction of radiotherapy reduces the number of 
tumour cells and allows some hypoxic areas to become 
better oxygenated. Fractionation allows this process of 
reoxygenation, which may take hours or days to occur 
and is thought to make tumours more radiocurable. 

The above comments help to explain the empirical 
finding that radiotherapy is most effective when given 
daily over several weeks. A comparable effect to fraction- 
ation is seen with interstitial and intracavity treatments 
where a continuous low exposure over several days is 
biologically equivalent to multiple small fractions. 

The ability to cure a tumour probably depends on being 
able to eliminate every clonogenic tumour cell from the 
target volume. This is influenced by a variety of factors, 
as discussed below. 

Size of tumour 

A number of factors means that the larger the tumour the 
less successful radiotherapy tends to be: 

• The larger the tumour the greater the number of cells 
present and hence a larger number of fractions will be 
necessary to have a high probability of eliminating the 
last clonogenic tumour cell. For example, the majority 
of 2 cm carcinomas can be controlled by 60 Gy, whereas 
a 4 cm carcinoma needs 80 Gy for similar control rates. 

• Large tumours may contain large hypoxic areas which 
are relatively radioresistant and thus reduce the chance 
of cure. 

• Large tumours usually need a larger treatment volume 
than small rumours. This generally increases the volume 
of normal tissue irradiated; the greater the volume of 
normal tissue, the higher the chance that a part of that 



272 



PRINCIPLES OF RADIOTHERAPY 



28 



tissue is damaged by the radiotherapy, and hence the 
normal tissue complication rate rises. To reduce this 
complication rate a dose reduction is often necessary, 
with a corresponding reduction in the chance of cure. 

Radiosensitivity of tumour cells 

The commonest histological types of tumour have cells of 
similar radiosensitivities (e.g. squamous carcinoma cells 
and adenocarcinoma cells). Differences in tumour cure 
between these common histological types probably relate 
more to differences in tumour bulk, oxygenation and pro- 
liferation. There are exceptions, with the cells of some 
tumours being more radiosensitive, such as seminoma 
and lymphoma, and others being more radioresistant, 
such as melanoma, glioma and sarcoma. The reasons for 
these differences are not clear. Radiosensitive tumours 
may be more sensitive due to a greater tendency to 
undergo apoptosis in response to DNA damage, but there 
is evidence, at least in vitro, that a variety of other mech- 
anisms may have a role; for example, melanoma seems to 
be more resistant to radiotherapy due to an increased 
ability to repair DNA damage. 

Tolerance of normal tissues 

The total dose that can be applied to a tumour is limited 
by the tolerance of the surrounding normal tissue. This 
varies greatly between tissues. If the tumour lies close to 
a sensitive organ, such as the spinal cord, then the total 
dose that can be safely delivered is much less than if the 
tumour lies within muscle or bone, for example. Hence 
the chance of cure may be reduced. The dose that can be 
applied will also depend on the volume that needs to be 
irradiated. A good example of this is the lung. The toler- 
ance dose for whole lung to be able to function after treat- 
ment is in the region of 20 Gy in 10 fractions of 2 Gy. 
Therefore, if the whole lung or large sections need to be 
treated, as in selected cases of Hodgkin's disease, this is 
the maximal fractionated tolerated dose. However, doses 
as high as 60 Gy can be given to portions of a lung, such 
as a lobe, because small areas of permanent damage are 
acceptable and have little overall effect on lung function. 



RADIOTHERAPY PLANNING 




Key point 

The major principle of radiotherapy is to give 
the maximum possible dose to the smallest 
volume that will encompass all the tumour. 



This volume, termed the treatment volume, consists of: 

1 . The macroscopic tumour volume determined from 
clinical findings, imaging by, for example, X-rays, 
computed tomography (CT) scans and radioisotope 
scans, and operative findings, termed the gross 
tumour volume (GTV) 

2. A biological margin (often 0.5-1 cm) which allows for 
microscopic tumour; spread beyond the visible 
tumour: the clinical target volume (CTV) 

3. A technical margin, usually 0.5 cm to allow for errors 
and variability in daily set-up such as that due to 
respiratory movements of the patient: the planning 
target volume (PTV). 

Minimizing these errors and improving quality assurance 
is an area of active research. Techniques such as mega- 
voltage imaging may enter clinical practice in the future; 
in this, an X-ray image of the patient is produced as the 
treatment beam passes through the tumour, showing how 
well the area actually treated corresponds to the treatment 
plan. 

Accurately localizing the tumour in the patient is essen- 
tial to the success of radiotherapy. In most cases the 
tumour cannot be visualized directly and localization 
depends on physical examination, imaging and operative 
notes. The importance of accurate and detailed operative 
records cannot be overemphasized. An operation is a 
unique opportunity to visualize the tumour directly. Take 
full advantage of this opportunity to describe the extent 
of disease and acquire as much additional information as 
possible about local pathology. Limited information 
invariably leads to larger target volumes, increased radio- 
therapy morbidity and reduced cure rates. 

Once the radiotherapist has determined the exact size, 
shape and location of the target volume the aim is to 
encompass the target volume with a radiation dose dis- 
tributed as homogeneously as possible. A variation of 
under 10% is aimed for and achieved. Single fields are 
usually inadequate in this respect, except for superficial 
tumours. Opposing two fields at 180° to each other treats 
intervening tissue homogeneously. This arrangement is 
very simple to plan and is suitable for most low dose pal- 
liative and a few radical treatments. Two opposed fields 
usually include more normal tissue in the high dose 
volume than is strictly necessary (Fig. 28.2). Therefore, 
more complex multifield arrangements are normal for 
curative treatments to confine the high dose volume more 
closely to the target. These arrangements are usually 
planned by the cross-sectional target volume from CT 
scans of the* patient in the treatment position. 

Conventional therapy uses rectangular fields to encom- 
pass the target volume. As tumours are not cubes, an 
unnecessary amount of normal tissue is included in the 



273 




MALIGNANT DISEASE 





b. 

Fig. 28.2 Comparison of the dose distribution of 
different field arrangements. The parallel opposed field 
arrangement (a) adequately treats the target volume 
(the bladder) but gives a high rectal dose. A three-field 
arrangement (b) covers the target volume with a much 
reduced rectal dose and is therefore preferable. 

treated volume. This causes increased morbidity and 
limits the doses that can be given (e.g. for pelvic tumours 
the dose given is limited by the amount of small bowel 
included in the target volume). Conformal therapy uses 
new engineering and computer technology to generate 
irregularly shaped fields so that tumours can be encom- 
passed by high dose volumes that correspond more pre- 
cisely to the tumour's shape. A recent randomized trial in 
prostate cancer at the Royal Marsden NHS Trust has 
demonstrated a reduction in the risk of late side-effects 
and has allowed dose escalation which should improve 
cure rates (Dearnaley et al 1999). 

Directing several beams of radiation accurately to 
intersect across the target volume does not necessarily 
guarantee an even dose distribution because the X-rays 
have to pass through different amounts of tissue on the 
way from the entry point on the skin to the target 
volume. In addition, lung absorbs less energy than other 
tissues because of the air it contains. These potential 
sources of dose inhomogeneity (Greek in - not + homos 
+ genos = kind; not having the same constituent elements 



throughout) within the target volume must be calculated 
and compensated for using a number of measures that 
alter the beam shape and profile, for example different 
weightings on each X-ray beam and the introduction of 
wedge-shaped filters which absorb different amounts of 
energy across the beam (Fig. 28.3). Production of homo- 
geneous dose distributions has been greatly facilitated 
by the introduction of planning computers and CT plan- 
ning which can visualize and allow for tissue inhomo- 
geneities directly. This area continues to develop rapidly, 
and in the future more sophisticated means of compen- 
sating for potential sources of uneven dose distribution 
will come into routine practice, as will more advanced 
beam-defining devices. 

Once satisfactory dose distribution and treatment plans 
have been produced and checked, treatment of the patient 
can begin. It is important that treatment is applied in a 
reproducible fashion. The patient must be positioned, 
lying in a recorded position, with appropriate supports to 
maintain stability. Lasers are frequently used to help 
establish and monitor patient alignment. If extra accuracy 
is desirable, especially in the head and neck region, a light 





Fig. 28.3 Treating the breast without compensation for 
breast curvature produces an inhomogeneous dose 
distribution (a). When this is compensated for by a 
wedge filter (b) the dose distribution is improved. 



274 



PRINCIPLES OF RADIOTHERAPY 




28 



plastic shell may be used to immobilize the patient. The 
machine is then positioned according to skin markings 
and recorded settings determined during planning / and 
treatment is commenced. 




Planning radiotherapy 
The radiotherapist: 

• Defines the volume to be treated. 

• Designs radiation fields to encompass the 
volume to be treated. Complex 3 or 4 beam 
field arrangements are used for radical 
treatment to minimize the volume of normal 
tissue irradiated. Irregularly shaped 
('conformal') fields are now being used to 
further reduce the volume of normal tissue 
treatment. 

• Produces a radiotherapy plan which allows for 
dose inhomogeneity to produce a uniform dose 
distribution across the volume to be treated. 



In recent years several new techniques have improved the 
therapeutic ratio in selected circumstances. 



Accelerated radiotherapy 

This involves giving multiple daily treatments of the 
same size as used in conventional fractionation but given 
to shorten the overall treatment time from 6 weeks to less 
than 3 weeks. Recent research suggests that clonogenic 
tumour cells can proliferate significantly during a treat- 
ment course of 6 weeks and this could, theoretically, 
reduce the chance of tumour control. Reducing the 
overall treatment time could make an important differ- 
ence, allowing less time for proliferation and leaving 
fewer tumour cells to kill; however, reducing treatment 
time also gives normal tissues less time to recover. 
Enhanced early skin and mucosal reactions may limit this 
approach. 

Hyperfractionation 

This delivers two or three smaller fractions a day over the 
conventional treatment period; the number of treatment 
days remains the same but the number of fractions is 
increased. Reducing fraction size reduces late tissue 
damage, with relatively less effect on tumour control. 
This has allowed dose escalation, with an increased 



chance of cure, especially in head and neck cancer 
(Horiot et al 1992). 

CHART (continuous hyperfractionated 
accelerated radiotherapy) 

This new regimen aims to combine the advantages of 
accelerated and hyperfractionated radiotherapy by giving 
three treatments a day over a 12 day period with no gaps 
- including no breaks for weekends and bank holidays. 
Results from a multicentre trial have shown that CHART 
improved survival in patients with localized lung cancer 
and, to a lesser extent, local control and survival in 
patients with head and neck cancer (Dische et al 1997). 

Stereotactic radiosurgery 

This technique utilizes fixation devices adopted for 
neurosurgical practice to localize tumours precisely in 
three dimensions, using fiducial (Latin fidere = to trust; 
trustworthy) markers. By using arcing radiation beams, 
conformally shaped fixed fields or multiheaded cobalt 
units (gamma knives), radiation beams can be delivered 
to a concentrated area with a high degree of precision. 

Particularly applicable to cranial radiotherapy, this 
allows a high dose to be delivered to the target but a very 
low dose to surrounding tissue. This technique can be 
used as a boost after a conventional treatment course, 
retreatment of recurrences, or as a sole ablative treatment, 
as for arteriovenous (AV) malformations not suitable for 
surgery (Brada & Ross 1995). 

Conformal radiotherapy 

Conformal radiotherapy (see above) is now entering 
routine clinical practice. Further technical advances, 
including the use of multileaf collimators (Latin col = 
together + linea - a line; to make parallel: beam defining 
devices allowing irregular shaping of fields), which can 
vary during treatment administration, and 'inverse plan- 
ning' where the radiotherapist determines what he or she 
wishes to achieve and the computer determines optimum 
field size, shape, direction and weighting, are likely to 
lead to further sophistication in treatment administration, 
including treatment of concave or annular shapes. This 
should further reduce radiation morbidity, particularly 
near sensitive structures such as the spinal cord, optic 
chiasm and eye. 



ROLE OF RADIOTHERAPY 

Radiotherapy may be used in the management of malig- 
nant disorders in the following ways: 



275 



28 



MALIGNANT DISEASE 



• As primary treatment 

• As adjuvant treatment before or after primary surgery 
or chemotherapy 

• For palliation of symptoms 

• As a systemic treatment, either in the form of external 
beam total body irradiation or of systemic administra- 
tion of a radioactive isotope. 

Radiotherapy as primary treatment 

When radiotherapy is used as the primary treatment the 
aim is to effect cure with the minimum of side-effects. It 
is an alternative modality (method) of local control to 
surgery (Table 28.1). Radiotherapy, like surgery, is most 
effective at controlling small, well-localized and defined 
tumours, but has the advantage of preserving normal 
function. For many cancers, surgery and radiotherapy are 
equally effective modes of treatment and close liaison 
between surgeons and radiotherapists is essential if the 
appropriate modality of treatment is to be chosen for any 
given patient. This choice may vary between patients and 
depends on a variety of factors, such as tumour site, stage 
and histology, and patient age and performance status. 
Choice of treatment is not restricted to either surgery 
alone or radiotherapy alone; the patient may be best 
served by a policy of initial radiotherapy followed by 
planned salvage surgery if this fails, as in many head and 
neck tumours, or initial combination therapy. 



Radiotherapy may be indicated as the initial treatment 
by a variety of circumstances, including: 

1. Sites where surgery and radiotherapy are equally 
effective but radiotherapy gives better functional or 
cosmetic results, as in bladder cancer where radical 
radiotherapy gives good results and avoids the 
necessity for cystectomy and ileal conduit, or 
laryngeal cancer where radiotherapy gives equal 
results to surgery but allows preservation of the 
voice. 

2. Very radiosensitive tumours, such as lymph node 
metastases from testicular cancers or early Hodgkin's 
disease. 

3. Inoperable tumours; occasionally radiotherapy can 
be used for attempted cure of brainstem gliomas or 
pelvic sarcomas. 

4. At sites where operations carry a high 
morbidity /mortality and equivalent results are 
gained by radiotherapy, as for carcinoma of the 
upper or mid-oesophagus. 

5. In patients unfit for the radical surgery that would 
otherwise be the treatment of choice; for example, 
patients with bronchial cancer and chronic airways 
disease. 

All cases, however, need to be carefully assessed to decide 
the appropriate treatment option. In some cases where 
radiotherapy would normally be indicated, other factors 



Table 28.1 Results of curative radiotherapy 



Site 





Stage Five year survival {%) Comments 



Skin 


Alf 


90-95 


Head and neck 






Tongue 


Tl 


91 


Glottis 


Tl 


90 


Other sites 


All 


30-80 


Lung 






Conventional 


Tl 


30 


Gastrointestinal tract 






Oesophagus 


All 


9 


Anal canal 


All 


66 


Urofogy 






Bladder 


12/3 


34 


Prostate 


T1/2 


80 




T3 


60 


Penile 


All 


75 


Gynaecology 






Cervix 


IB 


85-90 




2A/6 


61-S5 


Endometrium 


All 


60-65 


Vagina 


Stage 1 


75 



Equivalent to surgery. Choice depends on site 

50-60% for all stages 

Local control rates with salvage surgery used for 
local relapse 

40% 2 year survival 

Equivalent to surgery 

Better results than anoperineal resection 

Salvage cystectomy for local relapse. Surgery only 28% 
5 year survival 
Equivalent to surgery 

Over 90% cure for stage 1 tumours 

Equivalent to surgery in randomized studies 

For patients unfit for surgery only 



276 



PRINCIPLES OF RADIOTHERAPY 



28 



may make surgery preferable for that patient. For 
instance, it may not be possible to apply a radical dose 
because of an adjacent sensitive structure; cystectomy 
may be indicated if small bowel is adherent to the affected 
bladder, precluding a full radical dose without a risk of 
severe morbidity. Operation may be preferred, especially 
in head and neck cancer, as the tumour may involve bone 
or cartilage, risking osteoradionecrosis following radical 
radiotherapy 




Key points 

Radiotherapy is an effective alternative 
modality to surgery to obtain local control. 



• The choice of radiotherapy versus surgery 
often depends on tumour- and patient-related 
factors. 

• Closely cooperate with the radiotherapist to 
achieve an optimum treatment strategy for 
each patient. 

Adjuvant radiotherapy 

For some tumours, preoperative or postoperative radio- 
therapy may improve local control. Adjuvant (Latin ad = 
to + juvare = to assist) radiotherapy (Table 28.2) achieves 
this by controlling microscopic spread beyond resection 
margins, tumour spilled at operation or lymph node 
metastases. The low tumour burden means that lower 
doses than those normally used in radical treatments can 



Table 282 Effect of adjuvant radiotherapy (RT) 


on local control a 


nd/or survival 


Site 


Stage 


Criteria 


Results (%) 




Comment 




No RT 


RT 


Breast 


T1/2 NO 


LC 


63 




88 


NSABP randomized trial of 
















conservative surgery 




T1/2 N + 


LC 


57 




94 




Radiotherapy 


Central nervous system 
















Astrocytoma 


Gd1 


S 


25 




58 






Oligodendroglioma 


All 


10 year S 


27 




50 






Pituitary 


All 


1 year LC 


10 




90 




RMNHST data 


Craniopharyngioma 


Incomplete excision 


S 


35 




90 




70% survival for complete excision 


Lung small cell 
















Thoracic 


Limited stage 


2 year LC 


23 




48 


} 


Overview of nine randomized 






2 year S 


16 




22 


trials* 


Cranial RT 


Limited stage 


2 year LC 
2 year S 


45 
16 




84 
25 


1 
f 


Danish trial' 


Gastrointestinal tract 
















Pancreas 


Operable tumour 


2 year S 


15 




42 




GITSG trial (NO RT versus RT with 
5-fluorouracH) 


Rectum 


Dukes' C 


LC 


65 




90 




MRC 3rd trial survival advantage 
In some series 


Gynaecology 
















Endometrium 


Stage 1 


LC 


88 




99 








Stage 1 


S 


64 




81 








Stage 2 


S 


20 




56 






Carotid 
















Carcinomas 


All 


LC 


62 




87 






Pleomorphic adenomas 


Incomplete excision 


LC 


76 




98 






Bladder 


T2fT3B 


S 


28 




45 




Nonrandomized data 


Soft tissue sarcoma 


Limited stage 


LC 


60 




75 




Review of French experience 1 



LC local control; S, survival; NSABP r National Surgical Adjuvant Breast and Bowel Project; RMNHST, Royal 
Marsden NHS Trust. 
*Warde & Payne (1992). 
! Work et al (1996). 
: Coindre et al (1996). 



277 



28 



MALIGNANT DISEASE 



be employed, with a resultant reduced morbidity, while 
obtaining a high rate of local control. If local control is an 
important determinant of survival, then this may equate 
with an improvement in overall survival. Even if meta- 
stases limit survival, adjuvant radiotherapy often has a 
valuable role in improving locoregional control and 
quality of life. This may be especially important if symp- 
toms of relapse cannot be easily controlled, for example 
in rectal cancer. 

Adjuvant treatment may be given to (1) the site of 
primary disease to reduce local recurrence or (2) sites of 
potential metastatic spread. 

Postoperative radiotherapy gives the radiotherapist the 
advantage of having details of the surgical and patho- 
logical findings in addition to the clinical and radio- 
logical assessments. This allows for accurate staging, and 
selection of those patients who will most benefit from 
radiotherapy. However, the planning of postoperative 
radiotherapy can be more difficult, as the radiotherapist 
can no longer directly image the tumour. Accurate oper- 
ation notes greatly aid localization of treatment, as does 
marking the tumour bed with clips. If it is likely that post- 
operative radiotherapy will be given, invite the radio- 
therapist to see the patient preoperatively, for example, 
before wide local excision of a small breast cancer. 
Postoperative radiotherapy is of proven value in reduc- 
ing local recurrence at many sites, some of which are dis- 
cussed below. At most sites postoperative radiotherapy is 
of no proven benefit in prolonging survival after com- 
plete resection of the primary tumour. 

In selected circumstances, preoperative radiotherapy may 
be of value. This has the potential advantage of 'down- 
staging' the tumour, potentially allowing an easier or less 
extensive operation to be performed, for example in rectal 
cancer or limb sarcomas. It may also reduce the risk of 
seeding at the time of operation and control microscopic 
disease at the edges of the tumour. Certain problems have 
limited the usefulness of this approach; foremost is the 
fear that radiotherapy increases the surgical morbidity. 
However, it is now thought that, as long as the operation 
is performed within 4 weeks of radiotherapy, this increase 
is minimal with doses of radiotherapy up to 40 Gy. A 
further problem is that the downstaging effect of the 
radiotherapy makes interpretation of the subsequent 
surgical specimen and pathological staging difficult. This 
also causes difficulties in comparing different series of 
patients, assessing prognosis and giving advice on further 
treatment. It is therefore a less established form of treat- 
ment, but has been used in bladder cancer, rectal cancer 
and sarcomas and, less often, in the treatment of 
oesophageal and endometrial cancers (Pollack & Zagars 
1996, Graf etal 1997). 



Radiotherapy to sites of lymph node spread has been 
used in the treatment of many cancers, especially when it 
was thought that blood-borne spread followed lymph 
node invasion. Increasingly, studies suggest that lymph 
node metastasis may be a marker of synchronous blood- 
borne metastasis, and at several sites prophylactic lymph 
node irradiation has been shown to be of little value in sur- 
vival terms, such as in bladder and prostate cancer ( Asbell 
et al 1988). Despite this, in a variety of cancers, lymph 
node irradiation is of value when initial spread is to lymph 
nodes and is an important determinant of survival, as in 
head and neck cancers, or relapse-free survival, as in semi- 
noma. Prophylactic lymph node irradiation is also justi- 
fied in reducing the risk of macroscopic nodal disease 
when symptomatic relapse is difficult to salvage. An 
example of this is supraclavicular fossa irradiation in axil- 
lary lymph node-positive breast cancer. Node relapse at 
this site is difficult to salvage and has a high morbidity in 
terms of lymphoedema and brachial plexus neuropathy. 
The risk of such relapse is markedly reduced by applying 
adjuvant radiotherapy. 

In a similar fashion, craniospinal irradiation improves 
prognosis when central nervous system (CNS) spread is 
common, for example, in medulloblastoma and ependy- 
momas. Chemotherapy only poorly penetrates the CNS, 
and for some otherwise chemosensirive tumours the CNS 
may act as a sanctuary site, such as in acute lymphoblas- 
tic leukaemia (ALL) and small cell lung cancer. If cerebro- 
spinal fluid (CSF) metastases are common, cranial or 
craniospinal irradiation is a highly successful form of 
prophylaxis. For example, following the introduction 
of irradiation, the incidence of CNS relapse in patients with 
acute lymphoblastic leukaemia has been dramatically 
reduced and it has had a major impact on the chances of 
cure in this illness. 




Key points 



• Adjuvant radiotherapy may significantly reduce 
the risk of locoregional recurrence, especially if 
the tumour is larger or excision is marginal. 

• Accurate preoperative staging and operation 
records improve the effectiveness of 
radiotherapy. 

Palliation 

Of all modalities used to treat advanced cancer, radio- 
therapy is the most useful for the palliation of symptoms 
either from advanced primary or metastatic disease. The 



278 



PRINCIPLES OF RADIOTHERAPY 



28 



criteria of success must be in terms of quality of life rather 
than survival. The aim is therefore to give sufficient treat- 
ment to relieve symptoms without short-term side-effects 
for as long as the patient is expected to survive. The trend 
is towards short courses delivering a few large fractions of 
radiotherapy, thereby achieving maximum symptom relief 
with minimal interference in the patient's life. Frequently, 
a single large fraction of radiotherapy is all that is necess- 
ary to palliate symptoms. For example, most patients with 
lung cancer present with disease too advanced for any 
radical treatment. Such patients are frequently symp- 
tomatic with, for example haemoptysis, dyspnoea, pain or 
cough. These are usually well controlled with one or two 
fractions of radiotherapy (Bleehen et al 1991). In certain 
circumstances in pelvic tumours, or recurrent chest wall 
breast cancer, longer fractionated courses to higher doses 
are necessary to offer a good chance of sustained symptom 
relief. In addition, palliative radiotherapy may be used for 
relief of symptoms due to metastases. The treatments of 
different types of metastasis are considered below. 

Bone metastasis 

Symptomatic bone metastases affect approximately 20% of 
patients at some stage during their illness. Radiotherapy is 
a highly effective means of controlling local pain due to 
such bone involvement. Recent work has shown that a 
single 8 Gy fraction of radiotherapy will relieve pain par- 
tially or completely in 80% of patients 4 weeks after treat- 
ment (Price et al 1986). Orthopaedic fixation followed by 
radiotherapy should be used to prevent fracture for lesions 
with substantial cortical bone erosion. Patients with exten- 
sive bone metastases, as are frequently seen in prostate 
cancer, obtain good palliation from wide-field hemibody 
irradiation given as a single treatment. The other half-body 
can be treated 4r-6 weeks later. Approximately two-thirds 
of patients will obtain good pain relief from such treat- 
ments. An alternative approach is to use a radioactive 
isotope (strontium-89) which is taken up by bone meta- 
stases. It is given as a simple intravenous injection and 
may be repeated. In randomized studies in prostate cancer, 
strontium-89 produced pain relief equivalent to local or 
hemibody irradiation, with the advantage of lower toxicity 
and the appearance of fewer new sites of pain on sub- 
sequent follow-up (Quilty et al 1994). 

Spinal cord compression 

This is an emergency which can cause devastating motor, 
sensory and sphincter disturbances. Metastatic disease can 
cause cord compression by direct extension from vertebral 
disease, epidural deposits or, rarely, intramedullary disease. 



There has been no large trial of radiotherapy versus surgery 
in the treatment of this disorder, but most series suggest 
radiotherapy alone, in most instances, is as effective as 
surgical decompression followed by radiotherapy. Surgical 
treatment should be considered when there is no diagnosis, 
in radioresistant tumours such as melanoma and sarcomas, 
where there is evidence of spinal instability or progression 
through radiotherapy. Over 70% of patients will achieve 
good pain relief and 50% a useful response if treated before 
a major neurological deficit develops. Some patients will 
regain the ability to walk, but only 10% of total paraplegics 
regain useful function (Huddart et al 1997). 

Brain metastases 

This is a frequent complication of advanced cancer and is 
associated with a high morbidity. They are especially 
common in lung cancer, breast cancer (10% of all patients 
at some stage), melanoma, kidney and colon carcinomas. 
They are usually multiple and the prognosis is poor, with 
the median survival if untreated being 6 weeks. A 50% 
symptomatic response rate to radiotherapy and dexa- 
methasone is expected, the radiosensitive tumours such 
as small cell lung, breast and colon cancers responding 
better than average. A good response to dexamethasone 
and good performance status also predict for good 
outcome. Frail patients with poor performance status 
tend to gain little and treatment may not be indicated in 
such patients. Short courses of treatment seem to be as 
effective as longer courses (Priestman et al 1996). Patients 
with a single metastasis have a better outlook, with a 
median survival of 4-6 months, and 30% of patients with 
breast cancer survive over 1 year. There is some evidence 
that surgical resection followed by whole-brain irradi- 
ation is better than whole-brain irradiation only, in 
selected patients fit for surgery. Recent work with stereo- 
tactic boost (see above) suggests that similar results may 
be obtained with radiosurgery (Wurm et al 1994). 

Superior venal caval obstruction (SVCO) 

SVCO is caused by enlarged right-sided mediastinal 
lymph nodes or tumours, especially lung cancers. It 
causes engorgement of veins to the neck, cyanosis, facial 
oedema and dyspnoea. Following mediastinal radio- 
therapy, 70% of patients gain relief within 14 days. 

Other indications 

Some other indications for palliative radiotherapy are 
retinal metastases, skin metastases and lymph node 
metastases. 



279 



28 




MALIGNANT DISEASE 




Key points 



• Radiotherapy is effective at relieving symptoms 
of advanced local or metastatic disease. 

• Short courses of treatment are usually 
sufficient to palliate symptoms. 

• Longer courses of treatment are sometimes 
justified, especially to obtain locoregional 
control. 

Radiotherapy for the treatment of systemic 
disease 

Radiotherapy is generally used to treat local disease. 
There are, however, two areas where radiotherapy is used 
to treat systemic disease: total body irradiation and 
radioactive isotopes. 

Total body irradiation 

A total body dose of >4 Gy will result in bone marrow 
failure. This has limited the usefulness of the technique for 
the treatment of malignant disease until the onset of bone 
marrow transplantation. Total body irradiation using a dose 
of 8-10 Gy as a single dose or a higher fractionated dose is 
a highly effective conditioning regimen for the treatment of 
leukaemias. It is also being examined in trials in the treat- 
ment of other radiosensitive tumours such as lymphomas. 

Radioactive isotopes 

This technique uses radioactive isotopes which emit 
short-range p-particles and /or 7-rays. If the rumour con- 
centrates the isotope compared to the surrounding tissues 
it will be preferentially irradiated. The best example is the 
use of iodine- 131 in the treatment of follicular and papil- 
lary thyroid cancer. The malignant tissue takes up and 
concentrates iodine, and hence residual tumour is irradi- 
ated to a high dose. Using this technique, lung and some- 
times bone metastases can be eliminated. Other examples 
are the use of phosphorus-32 in polycythaemia rubra vera, 
strontium-89 in metastatic prostate cancer (see above) and 
m-iodo-benzylguanidine (MIBG) in neuroblastoma. 



COMJ^G^ONS >w _ 

Normal tissue side-effects are due to cellular damage 
inflicted at the time of irradiation. This damage is largely 
expressed at the time of mitosis, so the sensitivity to and 
the expression of this damage depend on the proliferative 
characteristics of each tissue. 



Acute effects 

In some tissues, such as the epidermal layers of the skin, 
the small intestine and bone marrow stem cells, turnover 
is rapid and damage is expressed early. Skin is the classic 
example of such a tissue. Stem cells in the basal layers of 
the skin divide; the daughter cells differentiate and move 
to the surface over a 2 week period to replace shed cells. 
After irradiation, production of replacement cells is 
reduced or halted. The epidermis gradually thins and, if 
sufficient damage has occurred, epidermal integrity is lost 
and desquamation occurs. Recovery will occur over a 
period of days or weeks after the end of treatment by sur- 
viving stem cells producing enough daughter cells to 
cover the deficient area. It can be seen that: 

• The time to onset of side-effects is determined by the 
skin turnover time: 2 weeks for skin but 5 days for 
small intestine 

• The severity and length of time to recovery depend on 
the amount of damage to the stem cells and hence on 
radiation dose 

• Provided there is a certain number of clonogenic cells 
surviving, recovery is likely to be complete. 

Although this mechanism is responsible for most acute 
reactions, the clinical effect varies from site to site. For 
example, in the upper gastrointestinal tract acute reac- 
tions cause inflammation and discomfort with mucositis 
and oesophagitis; small or large bowel damage by similar 
mechanisms causes vomiting, diarrhoea or, more rarely, 
ulceration and bleeding. 

Other acute reactions, however, may operate by differ- 
ent mechanisms and are less well understood, such as 
somnolence after cranial irradiation. 



Late irradiation effects 

Although acute effects are important for the tolerance of 
radiotherapy, the dose of radiotherapy applied is usually 
limited by long-term, late radiation effects. 



Stem cell effects 

Stem cell damage usually recovers completely but, if it is 
severe, long-lasting effects can occur. The most important 
example of this is gonadal damage. Oocytes are particu- 
larly radiosensitive and even moderate doses of a few 
grays of radiation precipitate premature menopause. 
Spermatogenesis is also sensitive to radiotherapy. Doses 
in the region of 3 Gy cause oligospermia or azoospermia 
that may last 6 months to 1 year, but higher doses, more 
than 6 Gy, cause permanent sterility. 



280 



PRINCIPLES OF RADIOTHERAPY 



28 



Depletion of parenchymal or connective 
tissues 

In many tissues the parenchymal cells turn over very 
slowly. As radiation damage is expressed at mitosis, lethal 
damage will not be expressed until cells divide, weeks, 
months or even years later. Irradiation of the thyroid 
gland, for example, leads to gradual depletion of thyroid 
follicular cells and can cause hypothyroidism over a 
period of many years. 

Vascular damage 

Damage to the vasculature is a common mechanism of 
damage, especially in tissues that never replicate, such as 
neurons or cardiac muscle, or which replicate only very 
slowly, such as fibroblasts. Radiation has a wide range of 
pathological effects on the vasculature, due to damage to 
both endothelial cells and connective tissue. This leads to 
impairment of the fine vasculature, often in a patchy 
fashion. The damage can result in poor wound healing, 
tissue atrophy, ulceration, strictures and formation of 
telangectasia. 

The precise clinical effect depends on the organ 
involved. For example, in the bladder the telangiectasia 
can cause haematuria, while fibrosis, ulceration and 
tissue atrophy can cause a constricted fibrotic bladder 
resulting in frequency and nocturia. Similar changes in 
the gastrointestinal tract may cause bowel obstruction by 
stricturing of the viscus or by peritoneal adhesions. 

At other sites vascular damage manifests differently. In 
the central nervous system, glial tissues are depleted as a 
direct effect of radiation and via vascular effects, causing 
secondary demyelination and neuronal loss. Damage to 
the cardiac vasculature may result in early ischaemic 
heart disease if the dose is high enough, with myocardial 
infarction being an increasingly recognized cause of late 
morbidity and mortality in a minority of patients 15 years 
after internal mammary irradiation for breast cancer. 

Lymphatic damage 

High-dose radiotherapy can also damage lymphatic 
vessels, leading to reduced drainage and limb lymph- 
oedema. The risk is increased if there has been previous 
or successive surgery. For example, radiotherapy to the 
axilla after complete axillary dissection for early-stage 
breast cancer carries a much higher risk of arm lymph- 
oedema than either modality alone. 

Late effects are usually irrecoverable and show a dose 
response. Low doses are less likely to cause damage, 
while progressively higher doses have a greater chance of 
causing complications and this damage becomes clini- 
cally relevant at an earlier stage. The radiation dose there- 



fore has to be chosen carefully, taking into account normal 
tissue tolerance as well as predicted tumour cure dose 
and, as long as this is done, organs will function normally 
for the remainder of the patient's life. The actual dose 
chosen depends on a variety of factors. For each site an 
acceptable level of damage must first be decided and bal- 
anced against the chance of tumour control (Fig. 28.4). 
Damage to the spinal cord has such disastrous conse- 
quences that no morbidity can be accepted. A lower dose 
than that used at many other sites has to be accepted, 
even at the expense of tumour cure probability. Damage 
to other soft tissues, such as muscle and fat, is undesirable 
but of lesser importance and a higher dose and higher risk 
are accepted. As mentioned previously, the volume 
treated is important: the larger the volume, the greater the 
risk of damage and the lower the tolerable dose; for 
example, for the spinal cord a short length of cord can be 
treated to 50 Gy, but long segments, over 1 cm, will not 
tolerate more than 40 Gy. Other factors affecting tolerance 
include age, children and the elderly being less tolerant, 
or pre-existing vascular disease and previous surgery 

Second malignancy 

In addition to specific organ complications the problem 
of secondary malignancies is being increasingly recog- 
nized. This has been best studied in Hodgkin's disease, 
where an increased incidence of acute leukaemias are 
seen 3-10 years after irradiation, with a smaller increased 
risk of solid tumours following (Swerdlow et al 1992). 



100-1 



•A 



O. 



2 

E 

3 



50- 




Patients cured 

Patients with 
complications 



Dose 



Fig. 28.4 The relationship between cure and 
complications. A dose may be chosen with a very low 
risk of observable side-effects, but this may mean a very 
low chance of tumour cure as well (A). On the other 
hand, a high tumour cure rate may be associated with 
an unacceptable rate of complications (C), forcing an 
intermediate dose to be chosen as optimal under a 
particular set of clinical circumstances (B). 



281 



28 



MALIGNANT DISEASE 



The precise risk is difficult to quantify, but data give an 
overall risk of leukaemia of approximately 1-2% at 
15 years. The risk is greatest if radiotherapy is given in 
conjunction with, or is followed by, chemotherapy - 
especially chemotherapy with alkylating agents such as 
cyclophosphamide or chlormethine (mustine); in one 
series it was 0.2% if no chemotherapy was used and 8.1% 
if the patient received multiple courses. Similar increased 
incidence of leukaemia has been seen in other cohorts of 
patients, including those with ankylosing spondylitis 
who have received spinal irradiation (Weiss et al 1994). 
Of perhaps more concern is the risk of solid malignancy, 
which is increasingly recognized, estimates rising to 10% 
of patients surviving Hodgkin's disease 15-20 years 
following radiotherapy, although a disease-related 
phenomenon could also be responsible (Swerdlow et al 
1992). This risk of secondary malignancy has to be 
balanced against the risks of dying from the primary 
disease in most cancer sufferers. 

In conclusion, radiotherapy is set to remain the chief 
curative modality in patients with non-surgical cancer. As 
screening and other early detection methods diagnose an 
increasing percentage of individuals with truly localized 
disease, its importance is likely to increase. This con- 
tinued role in the curative treatment of cancer patients 
continues to stimulate research into the technical and 
biological basis of radiotherapy. In future years, further 
improvements in the efficacy and safety of radiotherapy 
should be expected to result from this research. 




Summary 

• Do you recognize that treatment with 
multiple beams of high energy X-rays given 
daily over several weeks is the optimal 
method? This is because of the physical 
and biological attributes of radiotherapy. 

• Can you identify circumstances when 
radiotherapy offers an effective 
alternative to surgery for local control of 
many cancers? 

• Do you understand what adjuvant 
radiotherapy is and its frequent value in 
improving local control? 

• In advanced cancer do you appreciate the 
value of short courses of palliative 
radiotherapy? 

• Will you remember the limitations on 
radiation dose because of possible late 
effects that may develop after months or 
years? 



References 



Asbell SO, Krall JM, Pilepich MV et al 1988 Elective pelvic 
irradiation in stage A-2, B carcinoma of the prostate: analysis 
of RTOG 77-06. International Journal of Radiation Oncology 
Biology Physics 15(6): 1307-1316 

Bleehen NM, Girling DJ, Fayers PM, Aber VR, Stephens RJ 1991 
Inoperable non-small-cell lung cancer (NSCLC): a Medical 
Research Council randomised trial of palliative radiotherapy 
with two fractions or ten fractions. British Journal of Cancer 
63(2): 265-270 

Brada M, Ross G 1995 Radiotherapy for primary and secondary 
brain tumors. Current Opinion in Oncology 7(3): 214-219 

Coindre JM, Terrier P, Nguyen-Binh B et al 1996 Prognostic 
factors in adult patients with locally controlled soft tissue 
sarcoma: a study of 546 patients from the French Federation 
of Cancer Centers sarcoma group. Journal of Clinical 
Oncology 14(3): 869-877 

Dearnaley DP, Khoo VS, Norman A et al (1999) Comparison of 
radiation side-effects of conformal and conventional 
radiotherapy in prostate cancer: a randomized trial. Lancet 
353: 267-272. 

Dische S, Saunders M, Barrett A, Harvey A, Gibson D, Parmar 
M 1997 A randomised multicentre trial of CHART versus 
conventional radiotherapy in head and neck cancer. 
Radiotherapy and Oncology 44(2): 123-136 

Graf W, Dahlberg M, Osman MM, Holmberg L, Pahlman L 7 
GHmelius B 1997 Short-term preoperative radiotherapy 
results in down-staging of rectal cancer: a study of 1316 
patients. Radiotherapy and Oncology 43(2): 133-137 

Horiot JC, Le Fur R, N' Guy en T et al 1992 Hyperfractionation 
versus conventional fractionation in oropharyngeal 
carcinoma: final analysis of a randomized trial of the EORTC 
cooperative group of radiotherapy. Radiotherapy and 
Oncology 25(4): 231-241 

Huddart RA, Rajan B, Law M, Meyer L, Dearnaley DP 1997 
Spinal cord compression in prostate cancer: treatment 
outcome and prognostic factors. Radiotherapy and Oncology 
44(3): 229-236 

Pollack A, Zagars GZ 1996 Radiotherapy for stage T3b 
transitional cell carcinoma of the bladder. Seminars in 
Urology and Oncology 14(2): 86-95 

Price P, Hoskin PJ, Easton D, Austin D, Palmer SG, Yarnold JR 
1986 Prospective randomised trial of single and multifraction 
radiotherapy schedules in the treatment of painful bony 
metastases. Radiotherapy and Oncology 6(4): 247-255 

Priestman TJ, Dunn J, Brada M, Rampling R, Baker PG 1996 
Final results of the Royal College of Radiologists' trial 
comparing two different radiotherapy schedules in the 
treatment of cerebral metastases. Clinical Oncology 
8(5): 308-315 

Quilty PM, Kirk D, Bolger JJ, Dearnaley DP et al 1994 A 
comparison of the palliative effects of strontium-89 and 
external beam radiotherapy in metastatic prostate cancer. 
Radiotherapy and Oncology 31(1): 33-40 

Swerdlow AJ, Douglas AJ, Vaughan Hudson G, Bennett MH, 
MacLennan KA 1992 Risk of second primary cancers after 
Hodgkin's disease by type of treatment: analysis of 2846 
patients in the British National Lymphoma Investigation. 
BMJ 304(6835): 1137-1143 

Warde P, Payne D 1992 Does thoracic irradiation improve 
survival and local control in limited-stage small cell 
carcinoma of the lung? A meta-analysis. Journal of Clinical 
Oncology 10(6): 890-895 



282 



PRINCIPLES OF RADIOTHERAPY 




28 



Weiss HA, Darby SC, Doll R 1994 Cancer mortality following 
x-ray treatment for ankylosing spondylitis. International 
Journal of Cancer 59(3): 327-338 

Work E, Bentzen SM, Nielsen OS et al 1996 Prophylactic cranial 
irradiation in limited stage small cell lung cancer: survival 
benefit in patients with favourable characteristics. European 
Journal of Cancer 32A(5): 772-778 

Wurm R, Warrington AP, Laing RW et al 1994 Stereotactic 
radiotherapy for solitary brain metastases as alternative to 
surgery (Meeting abstract 050). British Journal of Cancer 
70(suppl22):21 




Further reading 

Dobbs J, Barrett A 1985 Practical radiotherapy planning. 

Edward Arnold, London 
Horwich A 1995 Oncology: a multidisciplinary textbook. 

Chapman & Hall, London 
Steel GG 1993 Basic clinical radiobiology for radiation 

oncologists. Edward Arnold, London 



283 




Cancer chemotherapy 

V. M. Macau lay, C Coulter 



m 



Objectives 



Understand the actions of cytotoxic drugs, 

endocrine therapy and the new biologicals. 

Recognize the indications for, and timing 

and administration of, chemotherapy by 

multidisciplinary teams. 

Understand objective clinical response, and 

adjuvant, neoadjuvant and palliative 

chemotherapy. 

Appreciate the importance and design of 

new drug trials. 



INTRppyCTION 

Localized tumours can be cured by surgery and /or radio- 
therapy. Primary tumours are rarely the cause of death 
unless they are in critical sites such as the brain. Most cancer 
deaths are attributable to direct or indirect effects of 
metastatic disease, and this requires systemic treatment. 
There are three main types of systemic anticancer therapy: 
chemotherapy, endocrine therapy and biological therapy. 

Paul Ehrlich was the first to use the term 'chemother- 
apy', in the early 1900s. Chemotherapy was initially shown 
to be effective in the 1940s and 1950s when nitrogen 
mustard, aminopterin and actinomycin were used to treat 
lymphoma, leukaemia and Wilms' tumour. Subsequent 
work has confirmed that cytotoxic drugs can indeed cure 
disseminated disease in a significant proportion of patients 
with germ cell tumours, lymphomas, leukaemias and a 
few with small cell lung cancer and ovarian cancer. 
Unfortunately, most metastatic common solid tumours 
remain incurable, although cytotoxic and endocrine ther- 
apies undoubtedly have useful anticancer activity that can 
effectively palliate symptoms. The last 10-20 years have 
seen many advances in our knowledge of the cellular and 
molecular processes that characterize cancer cells. The 
challenge now for oncologists is to translate these advances 
into new therapeutic approaches that will improve the 
outlook for patients with common cancers. 



BASIC PRINCIPLES 

Growth characteristics of tumours 

1 . Cancers are caused by mutations in genes that influ- 
ence critical aspects of normal growth regulation (see 
Ch. 26). A common early event is the loss of ability to 
replicate (copy) faithfully deoxyribonucleic acid (DNA). 
This so-called genomic instability (genome = the full 
set of genes) leads in turn to mutations in other genes, 
including those that regulate growth and survival, drug 
resistance, cell-cell interactions, invasion, angiogenesis 
(formation of new blood vessels) and the ability to evade 
immune recognition. These changes give the cell a growth 
advantage, leading to tumour formation. 

2. Within an individual tumour only a subset of cells is 
proliferating — the growth fraction 7 . In general, small 
tumours have high growth fractions, but as the tumour 
enlarges the growth fraction often falls. Chemotherapy 
tends to be less effective in larger tumours because the 
growth fraction is smaller, and there has been a longer 
time for mutation to occur in genes that determine drug 
resistance. In addition, central regions of large tumours 
are often poorly perfused, reducing drug access, and the 
hypoxic cells are usually chemoresistant. This is why 
early diagnosis is so important. 

3. The smallest tumours currently detectable are well 
advanced in their natural history: a tumour of -1 cm 3 
weighs "1 g, contains 10 9 cells, and has gone through 
30 doublings. In only 10 more doublings it will reach 10 12 
cells, representing -1 kg of tumour, which is usually 
lethal. This problem of the threshold of detectability 
applies not only in the diagnosis of a primary tumour, but 
also in patient management after apparently curative 
resection of a localized cancer. Many such patients 
harbour tiny tumour deposits, so-called micrometastases. 
These can be found by examining bone marrow using 
specialized immunostaining or molecular techniques, but 
cannot be detected by currently available clinical scans. 
Little is understood about how tumour cells can remain 
viable but quiescent, presumably in the G phase of the 
cell cycle, and how or why they can reinitiate growth after 
latent periods of months or years. 



284 



CANCER CHEMOTHERAPY 



29 



Principles of cytotoxic chemotherapy 

Cytotoxic drugs damage DNA, inhibit DNA 
synthesis or block cell division 

Many standard cytotoxic (Greek kytos - vessel, hollow, 
cell + toxon = bow, toxikos = for the bow, toxikon = arrow 
poison) drugs kill rapidly-growing cells by damaging 
their DNA. DNA double-strand breaks are highly toxic, 
and if not repaired will lead to cell death. Other drugs act 



by interfering with DNA synthesis or cell division 
(Fig. 29.1). Cytotoxic drugs show no intrinsic specificity 
for cancer cells versus normal tissues: in addition to 
killing tumour cells, they damage normal tissues that are 
rapidly dividing, including the normal bone marrow, gut 
lining and hair follicles. An element of selectivity can be 
introduced by careful adjustment of dose and schedule to 
maximize damage to the tumour while allowing recovery 
of normal tissues (Fig. 29.2). 



Pyrimidine 
synthesis 



Cyclophosphamide 

Alkylaling agent, links R*CH 2 + to DNA 
forming inter- and inlra- strand cross- links 




Purine 

synthesis 



Ribonucleotides 



nm 



mmmmmm 



Cisplatin 

Inter- and intra- strand crass-links 

Bleomycin 

DNA strand breaks 






mvRTTPfpmfHPmii 






Doxorubicin 
Etoposide 

Inhibit Topoisomerase II causing 
DNA strand breaks 






xyribonucleotides 



i 



:..:::::::::::;::::;:: ::...:: 



Irinotecan 

Inhibits To poj some rase I 

DRUGS CAUSING DNA DAMAGE 




DNA 



_T 



RNA 



I 



Protein 





Methotrexate 

Inhibits di hydrate I ate reductase (DHFR) 



Hydroxyurea 

nhibits ribonucleotide reductase 

hmmmmmmmmmmmmimmmimimmm 

I 5 Flourouracil 

\ Inhibits thy mid y late synthetase. 
: blocks DNA synthesis 

Cytosine arabinostde 

j Cytosine analogue terminates DNA synthesis 
Inhibits DNA polymerase 

Actinomycin D 

Blocks RNA synthesis 

DRUGS BLOCKING SYNTHESIS 
OF DNA OR RNA 



Vinca alkaloids 

Btock micratubular assembly 

so block cells in M phase (mitosis) 



Taxanes 

Block disassembly of microtubules in 
mitotic spindle so block cells in M phase 



1 



DRUGS CAUSING SPINDLE DAMAGE 




Fig. 29.1 Actions of cytotoxic drugs at the molecular level. Pathways involved in DNA synthesis and gene expression, 
the process whereby information encoded in DNA is transcribed (copied into RNA) and translated into protein. 
Cytotoxic drugs in the box on the left-hand side act primarily by causing DNA damage. This may be a direct effect 
(e.g. due to bleomycin) or may occur indirectly, e.g. via inhibition of topoisomerases, enzymes that bind to DNA and 
induce and reseal strand breaks. These breaks are important for relieving torsional stress as the DNA double helix 
unwinds prior to DNA synthesis. Drugs in the box on the right-hand side block specific steps in DNA or RNA synthesis, 
and drugs in the lower box interfere with the function of tubulin, the protein in the mitotic spindle. Modified with 
permission from Grahame-Smith DG, Aronson JK 2002 Oxford textbook of clinical pharmacology and drug therapy, 
3rd edn. Oxford University Press, Oxford. 



285 



29 " 



MALIGNANT DISEASE 



^^^^^^^UHUhi 



Classification of cytotoxic drugs 

The mechanism of cell kill dictates when cytotoxic drugs 
are effective, and how cell kill varies with increasing dose 
(Table 29.1 and Figs 29.2 and 29.3): 

• Non-phase-dependent drugs: 

Are equally toxic to cycling cells and those that are non- 
cycling (i.e. G ) 
Kill by damaging DNA directly 
Kill exponentially with increasing dose. 

• Phase-dependent drugs: 

Kill cells only in a specific part of the cell cycle, usually 

S (DNA synthesis) or M (mitosis) 
Linear cell kill up to a plateau, limited by proportion of 

cells in target phase. 

Some drugs have multiple mechanisms of action. For 
example doxorubicin intercalates between the DNA 
strands, generating free radicals, and also inhibits 
the enzyme topoisomerase II (see Fig. 29.1). It is toxic 



ID 



12 






10 



11 



IHH 



Chemotherapy 
treatments 



| 10 10 - 



in 



rt 1 er- 



as 



o TQ B 1 
$ 

E 10 7 - 

z 

10 6 H 



10 5 - 




Bone 
marrow 

Tumour 



Time 

Fig. 29.2 Effect of chemotherapy cycles on tumour 
growth and blood count. The effect of repeated cycles 
of chemotherapy (arrows) on tumour growth (solid line) 
and marrow progenitor cells (hatched line). The interval 
between treatments is designed to allow normal tissue 
recovery without tumour regrowth; however, with 
repeated doses there is less killing of tumour cells, 
indicating the emergence of drug resistance. At some 
point all the sensitive tumour cells will have been killed 
and only the resistant cells remain. The marrow recovers 
quickly after initial treatments, but with repeated doses 
recovery is less complete and myelosuppression becomes 
clinically evident. Modified with permission from 
Souhami and Tobias (2002). 



Vinca alkaloids 
Taxanes 




Methotrexate 

Cytosine arabinoside 

Cam plot hecms 

Doxorubicin 
Etoposide 



J 



Fig. 29.3 Actions of cytotoxic drugs within the cell 
cycle. M, mitosis; S, DNA synthesis; G 1f first gap phase; 
G 2 , second gap phase; G , quiescent non-cycling cells. 

during all phases of the cell cycle but particularly in S 
phase. 

'Fractional cell killing' 

In 1964, Skipper showed that survival is inversely related 
to tumour burden and that for most drugs there is a clear 
relationship between drug dose and the eradication of 
tumour cells. A given dose of a drug kills a constant pro- 
portion of cells, not a constant number. The implication of 
this concept of "fractional cell killing' is that tumour eradi- 
cation requires either a sufficiently high dose of the 
drug(s) within limits tolerated by the host, or that treat- 
ment is started when the number of cells is small enough 
to allow tumour destruction at reasonably tolerated doses. 
Standard chemotherapy uses doses that often cause 
mild/ moderate side-effects, most of which can be 
controlled by simple symptomatic treatments such as 
antiemetics (see below). In contrast, high dose chemother- 
apy, used for example in the treatment of leukaemias and 
lymphomas, causes severe and sometimes life-threatening 
toxicity, including profound myelotoxicity (Greek myelos 
= marrow; bone marrow). 



286 



Tabte 29.1 Cytotoxic drugs 








Class of agent 


Mode of action 


Examples 


Uses (examples) 


Main toxicities 


Alkylating agents 


Link alkyl group (R-CH-) to 
chemicat groups in proteins 


Cyclophosphamide 


Breast, SCLC, NHL, 
Hodgkin's, sarcomas 


Marrow, cystitis 




and nucleic acids 


Cisplatin 


Ovary, teratoma, 
seminoma, bladder, lung, 
head and neck 


Neuropathy, renal (irreversible), 
deafness (irreversible) 






Carboplatin 


Ovary 


Marrow 






Gemcitabine 


Pancreatic, NSCLC 


Flu-Jike symptoms, skin rash 






Dacarbazine {OTIC) 


Melanoma 


Marrow, flu-like symptoms, arm pain 






Chlorambucil 


Low grade NHL 


Marrow, leukaemia 


Antimetabolites 


Resemble DNA precursors, 


Methotrexate 


Breast, sarcomas, NHL 


Mucositis (eyes, mouth), renal, fiver 




block DNA synthesis or 


5-Fluorouracil (5FU) 


Colorectal, breast 


Gut toxicity, hand-foot syndrome 




replication 


Capecitabine 


Colorectal 


AsSFU 


Antitumour antibiotics 


Bind to DNA, intercalate 
between base pairs. 


Doxorubicin, 


Breast, lymphomas, SCLC, 
ovary, bladder 


Marrow, cardiotoxic 




Inhibit topoisomerase II 


Epirubicin 


Breast 


Marrow, mild cardiotoxtctty 






Mitoxantrone 


NHL, breast 


Mild cardiotoxicity 




Single-and double-strand 


Bleomycin 


Teratoma, seminoma, head 


Pulmonary toxicity 




DNA breaks 




and neck, lymphomas 




Vmca alkaloids 


Bind to tubulin, prevent 


Vincristine 


NHL, SCLC 


Neuropathy, constipation 




assembly of mitotic spindle 


Vinblastine 


Testicular, NHL 


Marrow, mucositis 






Vindesine 


Melanoma 


Neuropathy 






Vinorelbine 


NSCLC, breast, ovary 


Neuropathy, constipation 


Taxanes 


Bind to tubulin, stop 


Paclitaxel (Taxol) 


Ovary, breast 


Neuropathy, rash 




disassembly of mitotic 


Docetaxel (Taxotere) 


Breast, ovary 


Neuropathy, rash 




spindle 








Epipodophylotoxins 


Inhibit topoisomerase II 


Etoposide 


Lung, testicular 


Bone marrow 


Camptothedns 


Inhibit topoisomerase I 


Irrnotecan 


Colorectal 


Gut, bone marrow 






Topotecan 


Lung, ovary 


Marrow 


NHL r non-Hodgkin's lym 


phoma; NSCLC, non-small cell lung cancer; SCLC, small ce 


>ll lung cancer. 





> 

m 

n 

X 
m 



O 

H 



30 

> 



I 



00 



ID 



29 '" 



MALIGNANT DISEASE 



Mechanisms of drug resistance 

Resistance to specific drugs can be conferred by: 

• Drug efflux, i.e. the cancer cell is able to pump the 
drug out. The product of the multidrug resistance 
(MDR) gene, a transmembrane protein (P-glycoprotein), 
acts as a drug efflux pump. Unfortunately clinical 
trials of efflux pump inhibitors have so far been dis- 
appointing, 

• Increased synthesis within the cell of: 
Cytoplasmic enzymes that detoxify the drug, e.g. over- 
expression of certain glutathione-S-transferases confers 
resistance to cyclophosphamide 

The drug target, e.g. amplification (increased copy 
number) of the dihydrofolate reductase (DHFR) 
gene confers resistance to methotrexate. 

• Reduced expression of: 

Enzymes that activate the drug, e.g. enzymes that 
convert 5-fluorouracil (5FU) to its active metabolite 
Proteins targeted by the cytotoxic drug, e.g. reduction 
in levels of the enzyme topoisomerase II confers 
resistance to topoisomerase II inhibitors e.g. anthra- 
cyclines, etoposide. 
In addition, cancer cells may become generally resist- 
ant to killing via mutation or altered expression of 
proteins that regulate cell survival and susceptibility to 
apoptosis (Greek apo = from + ptosis = a falling), such 
as Bcl-2, p53. 

Likelihood of cell killing 

This depends on: 

• Whether the cell is intrinsically sensitive or resistant to 
the action of the drug. 

• The cycling of the tumour cell (for phase-specific 
agents). 

• The concentration of drug delivered to the tumour. 
This is a function of dose and schedule. There is evi- 
dence of a dose-response relationship for some cyto- 
toxic drugs, and in breast cancer doxorubicin has been 
shown to confer greater therapeutic benefit at high 
dose. Very high dose chemotherapy, with autologous 
bone marrow or stem cell support, is a technique used 
for treatment in acute leukaemia or as second-line 
therapy in lymphomas. So far no benefit has been 
shown for trials of this approach as treatment for 
women with high risk early breast cancer or metastatic 
breast cancer. 



Combination chemotherapy 

To maximize the chance that a tumour will respond to 
therapy, cytotoxic drugs are often used in combination. 



The principles of combination chemotherapy are that the 
selected drugs should: 

• Be active against the tumour when used alone 

• Have different mechanisms of action, to maximize 
tumour cell kill 

• Have a different spectrum of side-effects, to minimize 
toxicity to the patient. 

Timing of chemotherapy 

• Primary therapy for chemosensitive tumours such as 
lymphomas, leukaemias and teratomas. Here chemo- 
therapy is the main treatment modality and can achieve 
cures. 

• Palliative chemotherapy (Latin palliate = to cloak; hence 
mitigate, extenuate). Most common cancers are less 
chemosensitive, and patients with metastatic disease 
cannot hope to be cured, but they may obtain useful 
symptomatic benefit. It is important to monitor tumour 
response and stop or change treatment if there is no 
evidence of objective response (see point 11 below). 

• Adjuvant chemotherapy (Latin ad = to + juvare = to 
help). Many patients with early cancer can be cured by 
surgery. Certain features suggest a high risk of recur- 
rence; these vary with tumour type but often include 
size of the primary, grade (i.e. degree of differentiation), 
involvement of local lymph nodes, and vascular inva- 
sion. Current imaging techniques are unable to detect 
tumour deposits smaller than 2-3 mm, so it is imposs- 
ible to know with certainty which patients have been 
cured by surgery and which have micrometa static 
disease that will later cause overt recurrence and 
death. In cancers of the breast and colon, patients at 
high risk of recurrence should be offered adjuvant 
chemotherapy and /or endocrine therapy, in an attempt 
to kill residual tumour cells remaining after apparently 
complete local resection. There is no way to judge the 
efficacy of this approach in individual patients other 
than to await relapse. Therefore, in designing adjuvant 
therapy, use only those agents shown to be active in 
advanced disease. 

• Neoadjuvant chemotherapy describes the use of 
cytotoxic drugs as initial (presurgery) treatment for 
patients who present with localized but extensive 
cancer, such as large primary breast cancers. The aim 
is to shrink the primary tumour to permit a more con- 
servative operation, and to control micrometastatic 
disease. The effect can be monitored by serial measure- 
ment of the size of the primary tumour. In patients 
with breast cancer this is most accurately done by serial 
magnetic resonance imaging (MRI) scans, or failing 
that by ultrasound; clinical measurements are notori- 
ously inaccurate. 



288 



CANCER CHEMOTHERAPY 



29 



Manage cancer patients within 
multidisciplinary teams 

• Work closely with pathologists, clinical oncologists 
(radiotherapists), medical oncologists, clinical nurse 
specialists, radiologists and palliative care physicians. 

• Unit policies for cancer treatment should be based on 
the results of published studies including randomized 
trials. 

• Make management decisions after joint consultation 
with other members of the team. 

• Offer patients treatment options appropriate for their 
age, health, tumour type and stage. 



Practicalities of administration 

• It is essential that cytotoxic drugs be given by a trained 
doctor or nurse. 

• Most standard chemotherapy regimens are given on an 
outpatient basis every 3-4 weeks. 

• The dose is usually calculated on the basis of milli- 
grams per square metre of body surface area. 

• Dose and schedule may need to be adjusted according 
to the function of: 

Liver, principal site for metabolism/excretion of doxo- 
rubicin, mitozantrone and vinca alkaloids. If the 
serum bilirubin is elevated use these agents with 
caution, at reduced dose. 

Kidneys: drugs that are cleared by the kidney may cause 
increased toxicity if the patient has impaired renal 
function. Check the renal function before each course 
of chemotherapy when giving certain drugs, espe- 
cially cisplatin, cyclophosphamide, ifosfamide and 
procarbazine, and any high dose chemotherapy. 
Ensure that the patient is well hydrated before, 
during and after drug administration. Carboplatin 
has similar activity to cisplatin and may be given to 
patients with renal impairment, tailoring the dose to 
creatinine clearance. 




Key points 

A given dose of chemotherapy kills a constant 

proportion of cells, not a constant number of 

cells. 

Cytotoxic drugs are used in combination to 

maximize tumour cell kill. 

Cancer patients should be managed by 

multidisciplinary teams. 

It is essential that cytotoxic drugs are given by 

a trained doctor or nurse. 



• Tumour responses are defined by objective 
criteria. 

• Chemotherapy works better in fit patients. 

Routes of administration 

• Intravenous injection/ infusion: the commonest route 
for cytotoxic drugs, usually via a temporary venous 
cannula (drip). Long term venous access devices may 
be required for convenience, because of poor veins or 
for infusional chemotherapy. Long term catheters are 
inserted so that the tip lies in a large central vein. 
Various catheters are available, including those suit- 
able for insertion into the subclavian or internal 
jugular veins, such as Hickman or Groshong, and 
others for insertion into a peripheral (e.g. antecubital) 
vein. 

• Oral administration, e.g. cyclophosphamide, methotrex- 
ate, etoposide, capecitabine. 

• Subcutaneous administration: commonly used for 
interferon or interleukin-2 administration. 

• Intra-arterial: an implanted pump may be placed into 
the common hepatic artery to infuse chemotherapy 
continuously into the liver. This technique is being 
evaluated in patients with liver metastases from the 
colon and rectum. 

• Intrathecal chemotherapy with methotrexate or cytosine 
arabinoside is used for brain /meningeal involvement 
by leukaemias, lymphomas, teratomas, choriocarcino- 
mas and occasionally for central nervous system (CNS) 
involvement by common solid tumours such as breast 
cancer. As with all chemotherapy, this should be 
administered only by trained personnel, to avoid the 
catastrophic and invariably fatal consequences of 
intrathecal administration of vincristine. 

Clinical assessment of response 

So that oncologists around the world can compare the 
efficacy of different agents, it is important to define what 
is meant by a response. One or more tumour deposits 
(marker lesions) are selected for measurement in two 
dimensions, on plain X-ray, ultrasound, computed 
tomography (CT) or MRI scan. This enables calculation of 
the cross-sectional area (product of the two dimensions) 
of each deposit. These measurements are made immedi- 
ately before the start of treatment and again during /after 
treatment, and responses are defined as shown below. It 
is worth remembering that tumour shrinkage need last 
for only 4 weeks to count as a response. These are the 
World Health Organization criteria: 

• Complete response (CR): no evidence of disease 
remains after treatment 



289 



29 " 



MALIGNANT DISEASE 



• Partial response (PR): marker lesion(s) shrink by 50%, 
no new lesions have appeared 

• Stable disease (SD): marker lesions remain at 50% to 
125% of pretreatment size (to allow for observer error 
in measurement) 

• Progressive disease (PD): marker lesions have 
increased to >125% of pretreatment size or appearance 
of new lesions 

• Response rate: CR plus PR. 

There has recently been a move to replace these criteria, 
emphasizing the role of CT and MRI imaging of marker 
lesions and formalizing the monitoring and analysis of 
response. Time will tell whether these new 'RECIST' 
criteria (response evaluation criteria in solid tumours) 
will replace the WHO criteria listed above. 

Fit patients do better with chemotherapy 

In general, chemotherapy has greater benefit in patients 
who have 'good performance status', that is, they are fit 
and able to walk about. In patients with 'poor perfor- 
mance status', that is, confined by their illness or by con- 
comitant disease to a bed or chair for most of the day, 
chemotherapy often has more severe side-effects and less 
benefit than in fit patients. This should not deter you from 
offering chemotherapy to a patient with a potentially 
curable tumour. However, in a patient with a cancer that 
can only be palliated by chemotherapy, it may be better 
to face the reality that such treatment may do more harm 
than good. In either case, make full use of simple 
measures such as analgesics and laxatives, which palliate 
symptoms without severe toxicity. 



TOXICITY OF CHEMOTHERAPY 



^£^^*^^X&^^^ 



?^^^^^gSSSii^ 



The dose of an anticancer drug is limited by its toxic 
effects on normal tissues. Some of these effects are mani- 
fest acutely, within minutes to weeks of administration, 
and may necessitate adjustment of dose or schedule. 
Some effects may be delayed for months or years, in some 
cases long after completion of the therapy that caused 
them, that is, when it is too late for dose modification or 
cessation of treatment. 



>~ 



Neutropenic sepsis: 



• Can cause collapse and death within a few 
hours. 

• Can occur any time after chemotherapy. 

• Greatest risk 7-14 days after most drugs. 



• Always check blood count if the patient is 
unwell. 

• Requires urgent admission and intravenous 
antibiotics. 



Acute toxicity 

Extravasation 

Doxorubicin and vinca alkaloids are vesicant (Latin vesica 
= blister) drugs; they cause tissue destruction when 
extra vasated. This leads to severe pain, burning and scar- 
ring and can be avoided by ensuring that the needle is 
within the vein and that the vein is tested using a non- 
vesicant substance before starting injection of the vesicant 
drugs. If extravasation does occur, stop drug administra- 
tion immediately. Tissue damage can be limited by 
promptly administering corticosteroids by local injection 
or topical application. 




Key point 



Every chemotherapy unit should display clear 
protocols outlining action to be taken in the 
event of extravasation. 



Bone marrow toxicity 

For many cytotoxic drugs, bone marrow toxicity is dose 
limiting. It is mandatory that a full blood count is taken 
on the day of the treatment; most treatments can go 
ahead with a white blood count of >1 .5—2 x 10 9 1~\ and 
platelets of >100 x 10 9 l 1 , although this varies with 
different protocols. Delay or modify treatment, that is 
reduce the dose, if the blood count is inadequate. The 
risk of myelosuppression is greatest approximately 
10-14 days after cycles of most sorts of chemotherapy. 
Warn patients to alert the oncology department if they 
have a fever above 37.5 D C. Act promptly, because 
patients can die from neutropenic sepsis within a few 
hours. Manage fever in a patient with an absolute neu- 
trophil count of less than 1.0 x 10 9 by urgent admission 
and treatment with intravenous broad -spectrum anti- 
biotics. Include in the investigations cultures of blood, 
urine and from any indwelling line. It is unusual to 
isolate a pathogen, although patients with indwelling 
lines are at particular risk of staphylococcal infection, 
which may necessitate line removal if it cannot be erad- 
icated with antibiotics. Spontaneous bleeding does not 
usually occur until the platelet count falls to 20 x 10 9 , but 
check patients with low counts for signs of haemorrhage. 
Give platelet support if bleeding occurs - typically on 



290 



CANCER CHEMOTHERAPY 




29 



the shins but you should check all over, including the 
mouth and ocular fundi, and prophylactically if the 
count falls below 10-20 x 10 9 per litre. 




Key points 

• Chemotherapeutic agents are dangerous. They 
must be administered only by skilled, trained 
people. 

• Monitor the white cell count assiduously and 
respond to falls by delaying or modifying 
treatment. 

• Keep neutropenic sepsis in mind - always. 



Gastrointestinal toxicity 

Nausea and vomiting are caused by many drugs and can 
be severe with cisplatin, cyclophosphamide, doxorubicin 
and actinomycin C This is probably the result of a 
combination of stimuli from the chemoreceptor trigger 
zone, the gut and the cerebral cortex. Patients receiving 
mildly emetic chemotherapy, such as cyclophosphamide, 
methotrexate, fluorouracil (CMF) for breast cancer, 
respond to metoclopramide or domperidone and dexa- 
methasone. For patients receiving highly emetogenic 
drugs such as cisplatin, give a 5-hydroxytryptamine 
antagonist such as ondansetron or tropisetron prophyl- 
actically, together with dexamethasone. Oral premedi- 
cation with lorazepam may help the patient to relax 
before treatment. Uncontrolled vomiting is not only 
extremely unpleasant, but also dangerous, as dehydra- 
tion can increase toxicity, for example, the nephrotoxic- 
ity of cisplatin. You may need to admit a patient for 
intravenous rehydration if vomiting cannot be controlled 
by oral medication. Standard dose methotrexate can 
cause mucositis, manifest as soreness of the mouth and 
eyes. If this is severe, give calcium leucovorin (folinic 
acid) for 48 h, starting 24 h after subsequent courses of 
chemotherapy. Folinic acid is an alternative intermediary 
metabolite that bypasses the block in DHFR activity, ter- 
minating the cytotoxic effect of methotrexate (note that 
folinic acid enhances the activity of 5-fluorouracil). High 
dose methotrexate requires prophylactic folinic acid, at 
doses that depend on the results of methorexate drug 
level monitoring. Vincristine may cause constipation 
and paralytic ileus, which may respond to laxatives. 
5-Fluorouracil and its oral analogue capecitabine can 
cause severe gut toxicity. Loperamide can be used pro- 
phylactically or for mild diarrhoea, but stop treatment of 
patients with severe diarrhoea - that is, 4-6 times a day 
or at night, or bloody. 



Alopecia (Greek alopex = fox; fox-like, patchy 
baldness) 

This results from treatment with doxorubicin, cyclophos- 
phamide, etoposide, vincristine, paclitaxel and docetaxel. 
Hair loss usually starts 18-21 days after the first injection 
of these drugs, but is temporary and patients can be reas- 
sured that the hair will regrow after treatment has been 
completed. Wigs are available on the National Health 
Service (NHS) and should be provided for patients before 
hair loss occurs. Alopecia due to doxorubicin and doce- 
taxel may be avoided or reduced by scalp cooling, which 
limits blood flow and hence drug access to the scalp. This 
carries a theoretical risk of scalp recurrence, but in 
practice this is very rare. 

Neuropathy 

Irreversible peripheral neuropathy and ototoxicity can be 
a serious problem with cisplatin. Vinca alkaloids and 
taxanes inhibit, respectively, the assembly and disassem- 
bly of microtubules; as well as blocking mitosis, this also 
interferes with nerve conduction. Peripheral neuropathy 
causes paraesthesia and numbness, which improve on 
stopping taxanes but can be severe and irreversible with 
pain and muscle weakness with the vinca alkaloids. 
Vincas also cause autonomic neuropathy, manifest as 
paralytic ileus and constipation. 

Long-term toxicity 

Cardiotoxicity 

This is the most important chronic and dose-limiting side- 
effect of doxorubicin, and causes arrythmias and cardiac 
failure. The risk of cardiotoxicity is dose-related (so total 
dose should not exceed 450 mg m~ 2 ) and is increased in 
patients with pre-existing heart disease, previous treat- 
ment with trastuzumab (Herceptin), or radiotherapy to 
the mediastinum or left chest, for example postmastec- 
tomy. The risk of cardiotoxicity appears to be less with the 
related drugs mitoxantrone and epirubicin. Herceptin 
itself causes cardiac dysfunction in approximately 5% of 
patients and should not be administered in combination 
with anthracyclines. 

Pulmonary toxicity 

Bleomycin can cause acute pulmonary infiltrates that may 
disappear when the drug is stopped, but which often heal 
leaving chronic fibrosis. This is a dose-related effect, com- 
monly occurring at total doses over 300 000 units, but it can 
occur after lower doses in patients with renal impairment. 
Remember to alert the anaesthetist if a patient previously 
treated with bleomycin is being prepared for operation. 



291 



29 




MALIGNANT DISEASE 



An example is a young man with a teratoma undergoing 
excision of a residual tumour mass; high concentrations 
of oxygen can acutely damage lungs exposed to 
bleomycin. Mitomycin C can also cause pulmonary infil- 
trates and fibrosis, and busulphan and other alkylating 
agents can cause fibrosis. 



form of systemic treatment offered to patients with 
cancer, when in 1896 Beatson performed oophorectomy 
for metastatic breast cancer. Surgical approaches have 
now been almost completely replaced by medical treat- 
ments designed to manipulate the levels or activity of key 
hormones (Fig. 29.4). 



Carcinogenesis 

After long-term treatment with alkylating agents such as 
chlorambucil and melphalan, patients are at risk of devel- 
oping acute leukaemia. Leukaemia with specific chromo- 
somal characteristics can develop after treatment with 
etoposide. The risk is directly related to the total dose of 
the drugs given. This is an important reason for reducing 
the length of treatment and, therefore, the cumulative 
dose of these agents. There is negligible risk of develop- 
ing a second solid tumour after chemotherapy alone, 
although the risk increases if chemotherapy is combined 
with local irradiation. 



Gonadal damage 

This can follow treatment with alkylating agents, espe- 
cially when used in combination. Ensure that patients 
receiving chemotherapy receive counselling about the 
risk of long-term infertility and the inadvisability of preg- 
nancy during chemotherapy. After combination chemo- 
therapy (e.g. MOPP; mustine, Oncovin, procarbazine, 
prednisolone) for Hodgkin's disease, the majority of men 
are azoospermia although the risk of this effect is reduced 
by using alternative regimens such as ABVD (adriamycin, 
bleomycin, vinblastine, dacarbazine). Offer all male 
patients sperm banking before starting chemotherapy. 
With modern assisted reproductive techniques it is 
possible to achieve ovum fertilization with a very low 
sperm count. Men do not need hormone replacement 
therapy. For women aged over 30 years there is a very 
high risk of permanent amenorrhoea when they have 
received combination chemotherapy for Hodgkin's 
disease. It is now possible,, but time-consuming and 
expensive, to hyperstimulate the ovaries before 
chemotherapy to obtain ova which can be fertilized and 
frozen. Female patients will need hormone replacement 
therapy. Men who receive treatment with cisplatin for 
germ cell tumours usually retain fertility, as do women 
who have received chemotherapy for choriocarcinoma. 



Breast cancer 

Breast cancer cell growth is stimulated by oestrogens, and 
hormone responsiveness is likely if the tumour cells 
express the nuclear hormone receptors oestrogen receptor 
(ER, for US spelling, estrogen) and progesterone receptor 
(PgR). Approximately one-third of all breast cancer 
patients respond to hormonal measures; response rates 
are -70% in patients with ER+, PgR+ tumours, and 
30-40% in tumours positive for ER or PgR. Active agents 
include: 

• Tamoxifen (Nolvadex): a drug that acts as an antioestro- 
gen in tumour cells, blocking activation of the ER by 
endogenous oestrogens. In the rest of the body, tamox- 
ifen acts as an oestrogen, protecting against osteopor- 
osis and cardiovascular disease but also causing a 
slightly increased incidence of endometrial cancer. 
Tamoxifen is used both in the adjuvant setting and in 
metastatic disease, and trials indicate that it can signi- 
ficantly reduce the incidence of breast cancer in women 
whose family history puts them at high risk of the 
disease.^ In recent years, pure antioestrogens have 
become available, and these are currently being 
assessed in advanced disease. 

• Anastrozole (Arimidex): an aromatase inhibitor that 
blocks the conversion of androgens to oestrogens. 
Aromatase inhibitors are effective in postmenopausal 
patients but not in premenopausal women where the 
intact hypothalamic-pituitary-gonadal axis is able to 
overcome the drug-induced enzyme block. 

• Goserelin (Zoladex): a leutinising hormone releasing 
hormone (LHRH) analogue that prevents pituitary LH 
release, leading to a fall in gonadal steroid production 
in premenopausal women. 

• Megestrol acetate (Megace) and medroxyprogesterone 
acetate (Provera): synthetic progestins that antagonize 
the cellular effects of oestrogens. These drugs are less 
active than the above and they are usually used as 
third-line therapy, for example after tamoxifen and an 
aromatase inhibitor. 



HORMONE THERAPY 

Hormone therapies (= endocrine therapies) are used in 
the management of patients with cancers of the breast, 
prostate and endometrium. Historically this was the first 



Prostate cancer 

Prostate cancer cell growth is stimulated by androgens, 
and treatment here aims to reduce circulating levels or to 
block androgen effects at the cellular level. Since Huggins 



292 



CANCER CHEMOTHERAPY 



29 



r^.^.-r^^.y,..-^.,,,,,,,:..,,^.;,, 



LHRH ANALOGUES 



Hypothalamus 




Gonad 



J=>LHRHi=> 



Pituitary s* — ^ 



Adrenal 




l. 



ADRENAUGONADAL 
STEROID SYNTHESIS 

Cholesterol 

Pregnenolone 

Progesterone 
DHT ty 

17a- Progesterone 

^> 

Testosterone < $- - !> Androstenedione 
: Oestradiol ( E 2 ) <■ ={> Oestrone 



Fig. 29.4 Endocrine pathways, sites of action of main hormonal agents. The main pathways involved in synthesis of 
adrenal and gonadal hormones (shaded box) are shown. Dihydrotestosterone (DHT) binds to and activates the 
androgen receptor (AR), which drives expression of androgen-responsive genes. Similarly, the expression of estradiol- 
responsive genes is activated by binding of oestradiol (E 2 ) to the oestrogen receptor (ER). Hormonal anticancer agents 
act either by blocking hormone production, e.g. aromatase inhibitors (note that luteinizing hormone releasing 
hormone (LHRH) analogues first stimulate then suppress luteinizing hormone (LH) release, leading to a fall in 
production of testosterone from the testis or oestrogen from the ovary). Other agents block the effect of the steroid 
hormone at the molecular level, e.g. antiandrogens, antioestrogens. ACTH, adrenocorticotrophin. 



discovered, in 1941, that metastatic prostate cancer is 
almost always androgen-dependent, orchidectomy and 
oestrogen therapy have been standard treatments. 
Nowadays hormonal control can be achieved with fewer 
side-effects using LHRH analogues such as goserelin, 
and antiandrogens such as flutamide (Drogenil) and 
bicalutamide (Casodex), which block the binding of 
dihydrotestosterone to the androgen receptor. 

Endometrial cancer 

Progestogens such as medroxyprogesterone acetate are 
useful in the treatment of patients with locally recurrent 
or metastatic endometrial cancer. Approximately one- 
third of patients respond, and responders live longer than 
non-responders. 



BIOLOGICAL THERAPY 

Biological therapy produces antitumour effects through 
the action of natural substances, or the use of agents that 
block key biological processes in tumour cells. 

Cytokines 

Recombinant cytokines are agents that have roles in 
normal physiology, and can now be made by recombinant 
technology. This means that the cytokine gene is put into 
bacteria or yeast, expression of the gene is induced, that 
is the gene is 'switched on', leading to production of 
messenger ribonucleic acid (RNA) and hence protein, and 
the protein is purified from the culture in sufficient 
quantities to be used as therapy. 



293 



29 * 



MALIGNANT DISEASE 



Interleukin 2 (IL-2) is a T-cell growth factor that is central 
to T-cell-mediated immune responses. IL-2 has been 
approved for treatment of metastatic renal cell carci- 
noma. Response rates of 20% have been observed, and 
50% of responding patients remain progression free 4-7 
years following therapy. IL-2 also has activity against 
malignant melanoma, but again the response rate is 
only -20%. 

Colony stimulating factors (CSFs) such as erythropoietin and 
granulocyte CSF (filograstin) stimulate haematopoiesis 
and immune functions. They do not have antitumour 
effects but reduce chemotherapy-induced haematologi- 
cal toxicity and are useful in the context of high dose 
chemotherapy and bone marrow transplantation. 
a-Interferon (IFNa). Interferons are made by the body in 
response to viral infection. It is they rather than the 
virus per se, that are responsible for the malaise and 
myalgia characteristic of influenza. IFNa has demon- 
strated activity against many solid and haematogenous 



malignancies. A response rate of 80-90% has been 
observed among patients with hairy cell leukaemia, 
with apparent prolongation of survival. IFNa has been 
approved for use in chronic myeloid leukaemia, 
Kaposi's sarcoma, malignant melanoma and renal 
cancer, with response rates of 20-30%. As might be 
expected from their physiological role, interferons are 
toxic, causing influenza-like symptoms which can be 
intolerable. 



Inhibitors of key biological processes 

Current research is generating many new agents of 
potential therapeutic value that interfere with tumour 
growth by blocking the function of key pathways in 
cancer cells (Fig. 29.5 and see Ch. 26). 

• Antibodies. Herceptin is a monoclonal antibody directed 
against the HER2 protein, a growth factor receptor 



HERCEPTIN 



I R ESS A 



HER2 



GLEEVEC 



FARNESYL 
TRANSFERASE 
INHIBITOR (FTI) 




Intracellular signals 

influence activity of 

cytoplasmic proteins 




V 
Enhance survival. Gene expression 

motility etc. Cell division 



Fig. 29.5 Simple growth pathways with sites of action of selected novel biological anticancer agents. A growth 
factor binds to a specific ceil surface receptor, generating intracellular signals that activate cytoplasmic proteins. 
Depending on the signal, this may lead directly to increased resistance to killing, increased motility, changes in 
attachment to other cells or substratum. Activation of cytoplasmic signalling cascades also leads to changes in gene 
expression (i.e. switching on/off protein production from specific genes) and changes in the rate of progression 
through the cell cycle (i.e. faster/slower growth). The sites of action of Herceptin, a monoclonal antibody to HER2 (a 
growth factor receptor), and of Iressa and Gleevec, small molecule inhibitors of the enzyme activity of the epidermal 
growth factor receptor (EGFR) and BCR-ABL, respectively, are shown. Farnesyl transferase inhibitors are agents that 
block the attachment to the cell membrane of ras protein, a specific signalling intermediate, so inhibiting ras 
activation and thus blocking ras-mediated proliferation. 



294 



CANCER CHEMOTHERAPY 



29 



expressed by -20% of breast cancers but not by normal 
cells. The antibody is generated in mice but has been 
'humanized' to avoid triggering immune responses to 
mouse proteins. Herceptin has been in clinical use for 
several years and has significant anticancer activity in 
patients whose breast tumours are strongly HER2 posi- 
tive. It can enhance response to cytotoxic drugs such as 
taxanes, and is now being assessed as adjuvant therapy- 
Like most new treatments, it is very expensive, and it can 
cause cardiotoxicity, but it is an extremely valuable new 
drug in the treatment of aggressive breast cancer. Several 
other antibodies have been shown to have objective anti- 
cancer activity, including anti-CD20 for B-cell lym- 
phomas and edrecolomab (Panorex) for colorectal cancer. 
Small molecule inhibitors. Chemical inhibitors are gener- 
ally more successful drugs than antibodies; the latter 
are large molecules that require administration by 
intravenous infusion, and generally penetrate poorly 
into tumours. In contrast, chemical inhibitors are small 
molecules that penetrate well, they can be modified to 
improve characteristics of specificity, stability, solubil- 
ity, etc., and they can often be administered orally. A 
recent success story is Gleevec (STI-571), rationally 
designed as a small molecule inhibitor of the enzyme 
activity of the BCR-ABL fusion protein that is produced 
as a result of the chromosomal translocation character- 
istic of chronic myeloid leukaemia (CML). Gleevec has 
recently been shown to have dramatic anticancer activ- 
ity in patients with CML. Iressa is a small molecule 
inhibitor of the epidermal growth factor receptor 
(EGFR); it has anticancer activity in cancers of the lung 
and colon that express high levels of the EGFR. Many 
other small molecule inhibitors are currently being 
developed, including those that influence the activity 
of cytoplasmic signalling pathways and regulation of 
gene expression (Fig. 29.5). 

Gene therapy. Although cancer often results from defects 
in multiple genes, it may be possible to influence its 
course by altering the expression of individual genes. 
Strategies include replacement of a missing tumour 
suppressor gene, inhibition of production of an onco- 
gene (see Ch. 26), introduction of genes that cause the 
cancer cell to convert a prodrug to a toxic product, and 
production of proteins that enhance the host immune 
response. Many trials are currently evaluating such 
approaches, and some trials are reporting clinical activ- 
ity, but at present these remain in the realms of research. 



NON-SURGICAL TREATMENT OF 



COMMON CANCERS 



fr^^^:^5^£^ 



Anticancer treatments are particularly demanding and 
have potentially serious side-effects. You must confirm 



the diagnosis histologically before treatment begins, and 
ensure that patients understand why each treatment is 
offered and what it is intended to achieve. In the treat- 
ment of early, curable cancers, ensure that patients 
understand what sort of survival benefit may accrue 
from the multiple treatment modalities on offer. In the 
management of metastatic common cancers, you must 
unfortunately explain that chemotherapy cannot cure, 
nor with certainty prolong life, but may shrink tumours 
temporarily and so give symptom relief. See Chapters 27 
and 28 for more information on cancer surgery and 
radiotherapy. 

Breast cancer 

Early breast cancer is treated surgically (see Ch. 27). 
Analysis of the resected specimen indicates the main 
prognostic factors: tumour size, grade, nodal involvement 
and tumour expression of oestrogen receptor (ER) and 
progesterone receptor (PgR)- Patients at risk of 
micrometa static disease include those with large or high 
grade tumours and /or involved axillary lymph nodes. 
These patients should be offered adjuvant or neoadjuvant 
chemotherapy (Fig. 29.6). For patients aged <50 with 
involved nodes, adjuvant chemotherapy leads to a 12% 
improvement in 10 year survival, from 41% to 53%. The 
benefit is less in patients with node-negative tumours and 
those aged over 50. Patients should have radiotherapy 
after breast-conserving surgery to reduce the risk of local 
recurrence. If the tumour was ER positive, patients 
should be offered tamoxifen 20 mg daily for 5 years. 
Tamoxifen should not be used in patients with ER- 
negative tumours. The timing of these treatments is 
shown in Figure 29.6, and the magnitude of the benefit is 
summarized in Table 29.2. You will need to explain the 
plan to patients during admission for surgery. Reassure 
them that they will be given effective antiemetics to 
combat nausea, that they may temporarily lose their hair 
(depending on the chemotherapy offered), and that radio- 
therapy can cause local skin soreness. The whole 
treatment plan is long, tiring and daunting, especially 
if reasons for giving each component are not clearly 
understood. 

Metastatic breast cancer can be treated with endocrine 
therapy and /or chemotherapy. Patients may work their 
way through a range of different regimens and agents, 
depending on the pattern of disease. Radiotherapy is 
useful for controlling local symptoms, for instance due to 
bone or brain metastases. Endocrine therapy such as 
tamoxifen or anastrozole is a good option for patients 
with slow tempo ER-positive disease involving the skin, 
lymph nodes and /or bones. Rapid tempo disease, espe- 
cially involving the viscera, for example lungs or liver, 
should be treated with chemotherapy. Many single agents 



295 




MALIGNANT DISEASE 



Diagnosis 



ADJUVANT CHEMOTHERAPY 



Surgery 



t r r 

1 2 3 



ER +ve: TAMOXIFEN for 5yr 



TT ♦ ▼¥▼▼¥ 



RADIOTHERAPY 



1 I 1 T 1 1 1 

7 8 9 10 11 12 13 14 

Months 



NEOADJUVANT 
CHEMOTHERAPY 



Diagnosis 



Surgery 



ADJUVANT 
CHEMOTHERAPY 



ER +ve: TAMOXIFEN for Syr 



I I I I 1 I I I I I 



RADIOTHERAPY 



1 T 

2 3 4 






6 



7 8 

Months 



1 1 f < 1 

9 10 11 12 13 14 



Fig. 29.6 Treatment of early breast cancer. Patients at risk of recurrence after surgery should be offered adjuvant 
chemotherapy (upper panel), usually 4-6 cycles of an anthracycline-containing combination (e.g. doxorubicin plus 
cyclophosphamide) or CMF (cyclophosphamide, methotrexate, 5FU). Patients with large tumours or those at very high 
risk of recurrence (e.g. high grade tumour) may be offered neoadjuvant chemotherapy (lower panel). This is given 
before surgery, with the aim of controlling micrometastatic disease and shrinking the tumour, enabling more 
conservative surgery. The timing of endocrine therapy and radiotherapy is also shown. ER, oestrogen receptor. 



and combinations have activity in breast cancer but the 
objective response rates are often no more than 20-50%. 
In general, as with many tumour types, responders live 
longer than non-responders, but responses are often 
short-lived, so weigh these benefits against the adverse 
effects in non-responders. 

Lung cancer 

A small proportion of patients with non-small cell lung 
cancer (NSCLC) may be cured by operation, and occa- 
sionally by radical radiotherapy if surgery is inappropri- 
ate or is refused by the patient. However, 35-65% of 
patients suffer recurrent disease within 5 years of appar- 
ently curative resection. Meta-analysis of many trials sug- 
gests a small but significant benefit from chemotherapy 
given before or after surgery or radiotherapy. Fit patients 
with metastatic disease can be offered combination 
chemotherapy; responses occur in 20-60% and are asso- 
ciated with symptomatic improvement and modest 
survival benefit. 

Small cell lung cancer (SCLC) has usually metastasized 
at the time of presentation. Even in patients with limited 
disease, such as a tumour confined to one hemithorax, 
there is a high risk of micrometastases, and so all patients 



who are fit enough should be offered combination 
chemotherapy. Unlike most common solid tumours, 
SCLC is highly chemosensitive and 70-85% of patients 
respond to combination chemotherapy; however, most 
relapse with drug-resistant disease, and only a very few 
(~8% with limited disease, 2% with extensive disease) 
survive 5 years. 

Cancers of the gastrointestinal tract 

Localized carcinomas arising in the oesophagus and 
stomach are treated surgically (see Ch. 27); however 
only 40% of patients are eligible for potentially curative 
resection, and recurrence rates are high. Recent evidence 
suggests that the survival of high risk gastric cancer 
patients can be significantly improved with postoper- 
ative irradiation and concurrent 5FU. Fit patients with 
advanced or recurrent adenocarcinoma should be 
offered chemotherapy. Compared with intermittent 
conventional dose 5FU, response rates are significantly 
better with continuous low dose infusional 5FU com- 
bined with cisplatin and epirubicin. Pancreatic cancer is 
unfortunately highly chemoresistant, and most patients 
are too unfit for systemic treatment because of advanced 
disease at presentation. 



296 



CANCER CHEMOTHERAPY 



I* 



29 





Table 29.2 Benefits of adjuvant 


therapy for 


early 


breast cancer 






Subgroup treatment 


Relapse-free(%) 


Risk reduction 


Survival (%> 


Risk reduction 


Node -ve Tamoxifen* 


79.2 




14,9 


78.9 


5.6 


Control 


64,3 






73.3 




Node +ve Tamoxifen* 


59.7 




15.2 


61.4 


10.9 


Control 


44, S 






50.6 




<50 years 












Node -ve Chemotherapy 1 


683 




10,3 


77.6 


5.7 


Control 


58.0 






71.9 




Node +ve Chemotherapy* 


47.6 




15.4 


53.8 


12.4 


Control 


32.2 






41.4 




50-69 years 












Node -ve Chemotherapy* 


65,6 




5,7 


71.2 


6,4 


Control 


59.9 






64.8 




Node +ve Chemotherapy' 


43.4 




54 


4S.6 


2,3 


Control 


38.0 






463 





TabJe shows figures at 10 years for: percent of patients free of relapse; percent surviving (including mortality 
from any cause); and reduction in risk of relapse and death. 

*Oata for -5 years tamoxifen treatment in patients with tumours that were oestrogen receptor-positive or 
unknown. 

*Data for patients involved in trials of polychemotherapy, including CMF {cyclophosphamide, methotrexate, 5FU) 
and anthracydine-containing regimens. There was clear benefit from chemotherapy in young women (<50 years) 
especially those with node-positive tumours {Early Breast Cancer Trialists* Collaborative Group, 1998a, b), A more 
recent analysis suggested that young women (<50 years) gained an average of approximately 10 months of 
relapse-free survival, and 5 months of overall survival, compared with patients receiving no adjuvant 
chemotherapy. These benefits significantly outweighed the toxicity of chemotherapy. Benefits in older women 
{50-69 years) were atso significant, though smaller, and outweighed the toxicity burden to a lesser degree (Cole 
et at 2001). 



Adjuvant 5FU-based chemotherapy has been shown to 
improve survival after surgery for localized colorectal 
cancer, and is now standard treatment for patients with 
Dukes' C colon cancer (see Ch. 27). In metastatic disease, 
20% of patients respond to 5FU, with improvement in 
tumour-associated symptoms; several studies have 
shown survival benefit. Newer drugs with activity in 
colorectal cancer include capecitabine, an orally active 
prodrug which is converted in the body to 5FU, 
irinotecan, a topoisomerase I inhibitor, and oxaliplatin, a 
cisplatin analogue. 

Urological tumours 

Renal cancer can be cured only by complete resection. If 
technically feasible, nephrectomy may also confer sur- 
vival benefit and symptom relief in fit patients with low 
volume metastatic disease. Metastatic renal cancer is 
resistant to hormone therapy and cytotoxic drugs. 
Biological therapy with IL-2 or IFNa offers a chance of 
inducing response, but only in 15-20% of patients. 



Superficial bladder cancer is treated surgically, and 
localized invasive bladder cancer is managed by surgery 
and /or radiotherapy. In approximately 50% of patients 
with advanced bladder cancer a response can be induced 
with combination chemotherapy, usually including cis- 
platin, although this may be problematic if renal function 
is compromised. 

Organ-confined prostate cancer can be cured by radical 
surgery or radiotherapy, either external beam or brachy- 
therapy, but metastatic disease is incurable. Most patients 
(80%) respond to endocrine therapy, using an LHRH 
analogue or an antiandrogen, or the two combined - 
'total androgen blockade 7 . Tumour responses are associ- 
ated with improvement in symptoms such as bone pain, 
and a fall in the tumour marker prostate-specific antigen 
(PSA, see Ch. 30). Unfortunately, all tumours become 
androgen-resistant, usually after 12-18 months of 
endocrine therapy. At this point there may be minor 
symptomatic improvement with oral steroids or mito- 
xantrone, but metastatic prostate cancer is essentially 
chemoresistant. 



297 



29 \ 



MALIGNANT DISEASE 



Gynaecological cancers 

Early stage cervical cancer can be treated with radical 
surgery or radical chemoradiation. There is a high risk of 
recurrence in those with positive lymph nodes, para- 
mesial invasion or positive resection margins. If these 
patients are fit enough they should be offered postoper- 
ative radiotherapy and concurrent cisplatin chemother- 
apy, which have recently been shown to significantly 
prolong survival. Advanced cervical cancer is treated 
with irradiation, and recurrent disease may respond tem- 
porarily to chemotherapy 

Patients with ovarian cancer often present with 
advanced disease that has spread within the peritoneal 
cavity. This is optimally treated by maximal cytoreductive 
surgery - removing all visible tumour, and platinum- 
based chemotherapy. 

Malignant melanoma 

Patients with localized melanoma may be cured by 
surgery, and thickness of the primary lesion is the most 
important prognostic factor. Patients who experience skin 
recurrence near the primary site may be salvaged by 
further resection. In the 1960s and 1970s there was a 
vogue for regional limb perfusion, usually with melpha- 
lan, in patients with skin metastases confined to one limb. 
Responses occurred in 40% but were generally short- 
lived, with no convincing survival benefit. Many trials 
have assessed the role of IFNct as adjuvant treatment in 
high risk patients. Recent analyses suggest that low dose 
adjuvant interferon confers no survival benefit. High dose 
adjuvant interferon does, however, appear to be of benefit 
but has significant toxicity. The outlook for patients with 
metastatic disease is grim; only -20% of patients respond 
to chemotherapy, usually with DTIC (dacarbazine), or to 
immunotherapy with IFNct, but these responses are 
usually brief and without survival benefit. A small per- 
centage of patients obtain durable complete remissions, 
most often those with a small tumour burden. 



Sarcomas 

The outlook for patients with osteosarcoma is signifi- 
cantly improved if surgery is followed by immediate 
adjuvant chemotherapy, typically using cisplatin, 
doxorubicin and high dose methotrexate. This cures 
approximately 60% of patients. Neoadjuvant chemo- 
therapy is increasingly used as well, to gain control of 
micrometastatic disease and to shrink the primary 
tumour to facilitate limb-sparing surgery. Pulmonary 
metastases are not necessarily incurable; patients 
with fewer than six metastases may be salvaged with 



second-line chemotherapy, thoracotomy and excision of 
metastases. The prognosis of adults with soft tissue sar- 
comas is less good: tumours often recur after surgery, 
and are relatively resistant to both chemotherapy and 
radiotherapy. 

Myeloma 

In ~75% of cases, patients with myeloma respond to oral 
melphalan and prednisolone. Younger, fitter patients 
may derive greater benefit from more complex or inten- 
sive chemotherapy regimens, such as intravenous combi- 
nation chemotherapy or high dose melphalan with bone 
marrow transplantation. 



NON-SURGICAL TREATMENT OF 
HIGHLY CHEMOSENSITIVE CANCERS 






Approximately 12% of cancer patients have tumours 
that are highly responsive to chemotherapy. These 
patients are often young, and even those with advanced 
disease may stand a good chance of being completely 
cured. Therefore it is essential that they should be 
managed in specialist centres by experienced multi- 
disciplinary teams, as this has been shown to lead to 
improved survival. 

Lymphoma 

Hodgkin's disease can now be cured in most patients. 
The best chance of cure is when the patient first presents, 
and disease recurrence worsens the outlook. Patients 
with localized disease are treated with radiotherapy (see 
Ch. 28), and those with advanced disease are offered 
combination chemotherapy. Both chemotherapy and 
irradiation are used in defined situations such as a large 
mediastinal mass. 

Non-Hodgkin's lymphomas (NHLs) are a heteroge- 
nous group of conditions for which there is a plethora of 
classifications based on cellular, immunological and 
molecular criteria. In essence the prognosis is better 
when the cellular infiltrate is comprised mainly of small 
rather than large cells, and shows evidence of organiza- 
tion into a follicular pattern rather than diffuse infiltra- 
tion. 'Low grade' lymphomas are generally treated with 
intermittent oral chlorambucil plus prednisolone. These 
lymphomas often pursue an indolent course with a long 
median survival, but cannot be cured. Approximately 
30-40% of patients with 'high grade' NHL can be cured 
with intravenous chemotherapy, typically with CHOP 
(cyclophosphamide, doxorubicin (= hydroxydauno- 
rubicin), vincristine (= Oncovin), prednisolone). 



298 



CANCER CHEMOTHERAPY 



29 



Germ cell and trophoblastic tumours 




Key point 



Germ cell tumours are highly curable. 

Teratomas limited to the testis can be cured in 80% of 
cases by orchidectomy. Combination chemotherapy is 
required in those that relapse, and in patients presenting 
with poor risk features. Most regimens are intensive, 
incorporating cisplatin, etoposide and bleomycin, and 
are often highly toxic to the gut, bone marrow, kidneys 
and lungs. Surgery may be required after chemotherapy 
to excise residual lymph node masses or pulmonary 
metastases. Modern combination chemotherapy can 
achieve cures in 80-90% of patients, although survival 
rates fall to -50—60% in poor prognosis patients with 
liver, bone or brain metastases, extreme elevation of 
tumour markers a- fetoprotein, human chorionic 
gonadotrophin or lactate dehydrogenase, or primary 
mediastinal mass. 

Seminomas are highly curable. Patients with stage 1 
disease can be treated with prophylactic para-aortic irra- 
diation or a single dose of carboplatin. Alternatively they 
can be managed by surveillance; many will be cured by 
surgery alone, and virtually all the 10-15% that relapse 
can be cured by chemotherapy or irradiation. Patients 
with stage 2-4 disease are treated with chemotherapy, 
and the majority are cured. 

Choriocarcinoma is a rare tumour which usually 
follows a pregnancy resulting in a hydatidiform mole. 
Choriocarcinomas are extremely sensitive to chemother- 
apy, which can cure virtually 100% of patients with local- 
ized disease and over 70% with advanced disease. See 
Chapter 30 for more details on the clinical monitoring and 
treatment of patients with these tumours. 



TALKING TO PATIENTS ABOUT 
CANCER 






■BSisejs? g!383Sia«5*i 



It does not need to be said that a diagnosis of cancer is a 
devastating and extremely frightening situation for any 
family. You should be aware that the way you talk to 
patients and their families can have a huge bearing on 
how they view the situation and try to come to terms with 
it. Clear, sympathetic and sensitive explanations can help 
to minimize the fear, anger and confusion that patients 
and their families experience. If people ask direct ques- 
tions about their anticancer treatments and prospects of 
survival, it usually means that they are ready to hear 



straight answers. If you need to talk to patients about 
such issues and you are not sure how much they know or 
want to know, start by asking what they understand 
about the situation. This will let you know what they 
have been told (or what they remember - not always the 
same thing), and what terminology they are comfortable 
with (e.g. lump/tumour/cancer/adenocarcinoma). Then 
explain what the situation is as you see it, using and 
expanding on the terms they are already familiar with. 
Don't use words like 'lesion' or 'neoplasm' which are 
meaningless to a non-medic. Then go on to explain what 
can be done about the situation. 

In patients embarking on complex treatments for early 
stage, potentially curable cancer, it is important to be 
encouraging and to explain the role of each component of 
therapy. If the prospects of long-term survival are poor, it 
is best not to be too brutally accurate. For example, the 
meta-analyses may suggest that a woman with high 
grade breast cancer and more than four positive nodes 
has only a 20-30% chance of survival. Knowing this 
would inevitably cause severe anxiety that may be hard 
to live with, and it may be reasonable in such a case to be 
vague about the long-term outlook. 

When discussing the prognosis with patients who 
have advanced and incurable disease, it is generally 
better to be honest. There is never 'nothing that can be 
done', and it is important to explain sympathetically 
what support and treatments are available. For each 
treatment you should highlight the main advantages and 
disadvantages, but keep it simple and avoid giving too 
much information at once. Outline the chances of 
response, and the main side-effects, and be realistic 
about the overall benefit. You could say, for example: 
This treatment has a 40% chance of shrinking the 
tumour and helping you to feel better. But I am afraid it 
is not going to cure you, and the cancer will catch up 
with you in the end/ This will give the patient the oppor- 
tunity to ask, if they wish, the $64 000 question 'How 
long have I got?' Explain that this is impossible to 
answer with accuracy. You could reply 'Months, perhaps 
many months or a few years' to a fit patient with 
metastatic cancer, but an ill patient may expect only a 
few weeks or months. If a patient is clearly terminally ill 
and could die within a few days or weeks, assess 
whether the patient can cope with this information, and 
gain his/her permission to tell the family. Many relatives 
feel a lasting sense of bitterness if they were unaware up 
to the last moment that death was imminent. Patients 
and their families usually give fairly clear verbal and 
non-verbal clues to indicate how much of this sort of 
information they can take at any one time. See Chapter 
47 for a discussion of the principles of palliative care and 
the effective use of analgesia. 



299 



29 




MALIGNANT DISEASE 



EVALUATION OF NEW ANTICANCER 
DRUGS 



^$$x&?^& 






There is intensive laboratory -based effort to address the 
urgent need for more effective anticancer therapy. These 
may be derivatives of standard cytotoxic drugs, such as 
oxaliplatin and capecitabine, which are related to cis- 
platin and 5FU, respectively. Increasingly, research is 
generating new biological agents. Drugs that block key 
biological processes can be sought by large scale screen- 
ing, such as that conducted at the National Cancer 
Institute in the USA using assays suitable for processing 



large numbers of compounds. Alternatively the first step 
can be the identification of a biological target, which 
could be a process or a specific protein, and a drug is 
designed that is capable of inhibiting the function of that 
target. Potential treatment targets include not only the 
genes that regulate growth but also those that influence 
motility, invasion, cell-cell interaction, the formation of 
new blood vessels (angiogenesis), resistance to killing, 
and the ability to evade immune recognition (see Ch. 26). 
If a drug is shown to be effective in animal models of 
cancer, the next step is to assess its effect in clinical trials 
(Table 29.3). 



Table 29.3 Organization of new drug trials 

Phase I Phase II 



Phase III 



Conducted in a range of tumour types. Assess; 

■ Maximum tolerated dose 

■ Toxicity 

■ Pharmacology 

* Therapeutic effect 



Assess: 

* Therapeutic effect in specific 
tumour types 

* Dose-response relationship 



Controlled clinical trials: 
• Compare with existing 
standard therapy 



New drug trials are conducted in distinct phases to assess toxicity and efficacy. It can take up to 10-15 years for a 
promising new agent to complete preclinical evaluation and the standard phase I, II and III clinical trials. 



Summary 

• Chemotherapy and radiotherapy should be 
used only in patients with confirmed 
histological diagnosis of malignancy. 

• Adjuvant chemotherapy definitely 
increases the proportion of patients cured 
after surgery for cancers of the breast, 
colon and osteosarcoma, and may have a 
similar effect in cancers of the stomach, 
lung and cervix. 

• Chemotherapy can cure patients with 
advanced teratoma, lymphoma, and some 
patients with SCLC and ovarian cancer. 

• Chemotherapy and endocrine therapy are 
only palliative for most patients with 
metastatic disease. 

• New biological therapies hold promise for 
the future. 




References 



Cole BF, Gelber RD, Gelber S, Coates AS, Goldhirsch A 2001 

Poly chemotherapy for early breast cancer: an overview of the 

randomised clinical trials with quality-adjusted survival 

analysis. Lancet 358: 277-286 
Early Breast Cancer Trialists' Collaborative Group 1998a 

Tamoxifen for early breast cancer: an overview of the 

randomised trials. Lancet 351: 1451-1467 
Early Breast Cancer Trialists' Collaborative Group 1998b 

Polychemotherapy for early breast cancer: an overview of the 

randomised trials. Lancet 352: 930-942 




Further reading 

Nature Reviews Cancer has regular reviews on new therapeutics, for 

example: 
Greenwood E 2002 Therapeutics: stop signals. Nature Reviews 

Cancer 2: 640 
Hurley LH 2002 DNA and its associated processes as targets for 

cancer therapy. Nature Reviews Cancer 2: 188-200 



300 



CANCER CHEMOTHERAPY 



29 



McCormick F 2001 Cancer gene therapy; fringe or cutting edge? 

Nature Reviews Cancer 1: 130-141 
De Vita V, Hellman S, Rosenberg S (eds) 2001 Cancer: principles 

and practice of oncology, 6th edn. Lippincott Williams and 

Wilkins, Philadelphia. Extremely comprehensive textbook with 

good references to primary sources. 
Souhami R, Tobias J (eds) 2002 Cancer and its management, 3rd 

edn. Blackwell Science, Oxford. Medium length texbook, 

excellent general read. 
Therasse P, Arbuck SG, Eisenhauer EA et al 2000 New 

guidelines to evaluate the response to treatment in solid 

tumors. Journal of the National Cancer Institute 

92(3):205-216 



Useful links 

www.cancerbacup.org.uk This is an extremely useful resource 
to pass on to patients for information, practical advice and 
support. 

www.cancer.gov/cancer_information/pdq The National Cancer 
Institute's 'Physicians Data Query' site, with pages for medical 
stuff and patients. Very detailed information on management of all 
types of cancer including all relevant references, levels of proof, 
updated monthly. 

www.cancerresearchuk.org Informative UK site for health care 
professionals and patients, includes general and tumour site specific 
information on incidence, diagnosis and treatment, downloadable 
leaflets, etc. 



301 




Tumour markers 

G. J. 5. Rustin, A. E. Guppy 



w 



Objectives 



Appreciate the potential uses of circulating 

tumour markers. 

Recognize which tumour markers are most 

commonly elevated in particular tumours. 

Understand how tumour markers can be 

used to affect management of certain 

tumours. 

Lead to more appropriate requesting of 

tumour marker measurements. 



INTRODUCTION 






Tumour markers are substances present in the body in a 
concentration that is related to the presence of a tumour. A 
tumour marker does not have to be tumour specific. It may 
be secreted or shed into blood and other body fluids or 
expressed at the cell surface in larger quantities by malig- 
nant cells than by non-malignant cells. Tumour markers 
can be detected either by measuring the concentration of 
the marker in body fluids (usually by immunoassay) or by 
detecting the presence of the marker on the cell surface in 
paraffin sections or fresh biopsies (by immunohistochem- 
istry). This chapter examines critically those situations 
where estimation of circulating tumour marker levels may 
be of clinical value. 



DEFIMTIONS^^^ 

The terms most commonly used to describe the useful- 
ness of a tumour marker are defined in Table 30.1. 
Sensitivity is a measure of how commonly a tumour 
marker level is elevated in the presence of that particular 
tumour. Specificity measures the proportion of patients 
without tumour who have normal marker levels, and are 
therefore the true negatives. The positive predictive value 
is the percentage of positive results (i.e. elevated marker 
levels) which are true positives. An ideal tumour marker 



would have 100% sensitivity thus detecting all cases of a 
particular tumour, and 100% specificity, being elevated 
only in the presence of that tumour and not in any other 
situation. 



POTENTIAL USES OF TUMOUR 
MARKERS 

The potential clinical uses of tumour marker estimation 
are: 

• Screening 

• Diagnosis 

• Prognostic indicator 

• Monitoring therapy 

• Early diagnosis of relapse. 

Examples of these uses will be given for the cancers 
where tumour markers are currently of greatest value. 
Although they will not be discussed in any further detail 



Table 30.1 Terms used to describe tumour markers 



Tumour 



Present 



Absent 



Assay positive TP 

Assay negative FN 

Sensitivity = 

Specificity 

Positive predictive value = 

Negative predictive value = 



TP 



TP + FN 

TN 
FP + FN 

TP 
TP + FP 

TN 
FN + TN 



FP 
TN 

x 100 
x 100 
x 100 
x 100 



TR true positive; FP, false positive; FN r false 
negative; TN, true negative. 



302 



TUMOUR MARKERS 



30 



in this chapter, the existence of cell surface tumour 
markers is being exploited to localize a tumour either for 
imaging purposes, using a radiol a belled antibody, or as a 
treatment modality, using antibodies to carry radioactiv- 
ity or toxins selectively to the tumour. 



REVIEW OF THE USE OF TUMOUR 
MARKER ESTIMATION IN THE 
MANAGEMENT OF PARTICULAR 
TUMOURS 

Gestational trophoblastic tumours (GIT) 

The role of human chorionic gonadotrophin (hCG) in the 
management of GTT comes closest to the ideal use of a 
tumour marker. hCG is a glycoprotein produced by 
trophoblast cells. The ct-subunit is identical to that of 
follicle-stimulating hormone (FSH), luteinizing hormone 
(LH) and thyroid-stimulating hormone (TSH), but the 
C-terminal end of the p-subunit is unique to hCG and 
provides the basis of the specific immunoassay There are 
many different assays for hCG available. It is essential to 
know whether the assay in use locally recognizes just the 
p-subunit or the intact complete hCG molecule, as they 
can give quite different results. 

Diagnosis and screening 

Elevated levels of hCG are found with as few as 10 5 
trophoblast cells, but elevated serum hCG levels are also 
found in normal pregnancy, in ectopic pregnancy, in 
patients with germ cell tumours and, occasionally, in 
patients with non-germ-cell tumours. Pelvic ultrasound 
examination therefore remains the best method for diag- 
nosing hydatidiform mole. The great sensitivity of hCG, 
however, allows it to be used to screen a high risk popu- 
lation. The first national screening programme for any 
cancer was set up in 1972 so that, following a diagnosis of 
hydatidiform mole, all patients are centrally registered. 
Patients are then followed using serial hCG measure- 
ments in blood or urine. This screening allows those 
patients with persistent trophoblastic disease after evacu- 
ation of hydatidiform mole to be detected on the basis of 
plateauing or rising tumour markers before any clinical 
evidence of disease develops (Bagshawe et al 1986). 

Prognosis and monitoring response to 
treatment 

Since hCG levels in patients with GTT reflect the total 
body burden of viable tumour, the level is a major factor 
in deciding whether a patient fits into a good or poor 
prognostic group. In patients with GTT, serial hCG 



estimation is used to monitor response to chemotherapy 
and to detect the development of drug resistance. The 
hCG value may initially increase after starting treatment, 
possibly due to tumour lysis or to increased syncytial dif- 
ferentiation induced by the therapy. The hCG level then 
falls at a rate which is a function of metabolic clearance 
and the rate of synthesis. Plateauing of hCG values or 
rising values during the course of chemotherapy indicate 
the development of drug resistance, and need to change 
chemotherapy. 

Detection of recurrence 

Serial measurement of hCG will detect any recurrence of 
GTT with 100% sensitivity. The accurate measurement of 
hCG in urine, which is stable in the post, increases the 
ease of monitoring and obviates the need for frequent 
hospital visits. A rise in hCG is not, however, diagnostic 
of recurrent disease, and a new pregnancy must always 
be considered and ruled out by ultrasound examination. 
Patients who have had a hydatidiform mole have a 
slightly increased risk of choriocarcinoma after any sub- 
sequent pregnancy and should have further hCG estima- 
tions at 4 and 12 weeks postpartum. 

Germ celt tumours 

a-Fetoprotein (AFP) and hCG are elevated, either singly 
or in combination, in more than 80% of patients with 
disseminated non~seminomatous germ cell tumours 
(NSGCT) and in approximately 60% of patients with 
localized, stage I disease (Bower & Rustin 1996). Other 
markers of use in patients with germ cell tumours include 
lactate dehydrogenase (LDH), but many laboratories 
only measure hydroxybutyrate dehydrogenase (HBD), 
which is mostly isoenzyme 1 and 2 of LDH. Placental 
alkaline phosphatase (PLAP), although elevated in about 
50% of patients with seminomas and in smokers, adds 
little to clinical management, as it is rarely greatly elev- 
ated and usually falls to normal so quickly on therapy 
that it adds little to monitoring (Nielsen et al 1990). 

Diagnosis and staging 

All patients who are suspected of having a germ cell 
tumour should have serum sent for tumour marker esti- 
mation before excision of the primary tumour. Patients 
whose clinical status could be compromised by a biopsy 
(e.g. a patient with severe dyspnoea due to extensive lung 
metastases) should be considered to have an NSGCT if 
the distribution of the disease is compatible with such a 
tumour and there is gross elevation of either hCG or AFP 
Elevated hCG is associated with the presence of tropho- 
blastic elements in an NSGCT, and can be produced 



303 



30 



MALIGNANT DISEASE 



by syncytial giant cells in a pure seminoma. AFP, a 
glycoprotein with a molecular weight of 63-70 kDa, is 
secreted by the yolk sac element of an NSGCT, and a 
patient with an elevated AFP should never be considered 
to have a pure seminoma, regardless of the histological 
findings. 

Failure of tumour marker levels to fall to normal post- 
operatively indicates the presence of occult metastatic 
disease, even if all other staging investigations are 
normal. One further situation in which hCG estimation 
may be of diagnostic value is in the detection of brain 
metastases. A pretreatment cerebrospinal fluid hCG level 
that is more than one-sixtieth the serum hCG level indi- 
cates the presence of brain metastases; the normal ratio, 
however, does not exclude brain metastases (Bagshawe & 
Harland 1976). 

Prognosis and staging 

Initial tumour marker levels are now recognized as the 
single best predictor of failure to achieve complete 
response following chemotherapy. An international col- 
laborative group has recently proposed a prognostic 
classification (Table 30.2) based on an analysis of 5202 
patients that found tumour marker levels and the pres- 
ence or absence of mediastinal and non-pulmonary, non- 
nodal visceral metastases as the important risk factors 
(International Germ Cell Collaborative Group 1997). 

Monitoring response to treatment 

In patients with elevated hCG or AFP, these markers are 
the most sensitive method for assessing response to treat- 
ment. Although, in general, successful chemotherapy is 
invariably accompanied by a fall in serial hCG and AFP 
levels, there are two situations in which this may not 
occur. Firstly, an initial rise in tumour marker levels may 
occur soon after starting the first course of chemotherapy 
due to tumour lysis. The second situation is a plateau or 
even a rise in AFP levels, despite evidence of response 



from all other investigations. This is thought to be due to 
AFP production by the liver in response to toxicity and 
appears to be more common in those patients receiving 
hepatotoxic drugs such as methotrexate and ifosfamide. 
The only situation where falling marker levels are not 
associated with a decreasing germ cell tumour mass is 
when there is enlargement of cystic differentiated tera- 
toma. These masses require resection before they become 
inoperable. 

Early detection of recurrence 

All patients with germ cell tumours should continue to 
have serial tumour marker estimation after completion of 
chemotherapy to detect relapse early The other situation 
in which serial marker estimation is invaluable is in 
surveillance of patients with stage I disease following 
orchidectomy. Close follow-up by clinical examination, 
tumour markers, chest X-rays and CT scans will detect 
relapse early in the 25-30% of those in whom the disease 
is destined to recur and, with adequate treatment, virtu- 
ally all patients will be cured. In view of the potential for 
tumour markers to double rapidly, it is important that 
markers are measured at least monthly, and more fre- 
quently if raised. 

Gastrointestinal tumours 

There are a number of antibodies currently available 
which detect antigens expressed by gastrointestinal 
tumours. The most widely used are the antibodies which 
react with carcinoembryonic antigen (CEA), a 200 kDa 
glycoprotein. Assays dependent on monoclonal anti- 
bodies include CA 19.9, an antigen derived from a human 
colon adenocarcinoma cell line with an epitope (the 
portion of an antigen which combines with the antibody 
binding site) structurally identical to the sialylated Lewis 
A antigen, and CA 50, which is similar but not identical 
to CA 19.9. Elevated levels of several other markers such 
as CA 72-4 have also been found. 



Table 30,2 Tumour markers 


in prognostic classification of 


germ 


cell tumours 


■ 






Marker 








AFP (ng ml" 1 ) 




hCG* (ng ml 1 ) 


LDH 1 (x N) 


Good 

Intermediate 

Poor 




<1000 

1000-10 000 
>10 000 




and <1000 

or 1000-10 000 

or >10 000 


and <1.5 
or 1.5-10 
or >10 


*For hCG, 1 ng ml 
T A/, upper limit of 


_1 is approximately equal to 5 iu 1 *■. 
normal. 









304 



TUMOUR MARKERS 



30 



Diagnosis and screening 

Serum CEA is elevated in fewer than 5% of patients with 
Dukes' grade A colorectal cancer, about 25% of Dukes' 
grade B, 44% of Dukes' grade C and about 65% of 
patients with distant metastases (Begent & Rustin 1989). 
CEA can be elevated not only in cancers of the gastro- 
intestinal tract but also in a variety of other conditions, 
including: severe benign liver disease; inflammatory 
lesions, especially of the gastrointestinal tract; trauma; 
infection; collagen disease; renal impairment; and 
smoking. The low incidence of high serum CEA levels in 
early disease and its poor specificity explain its lack of 
value in screening normal populations for colorectal 
cancer. The low sensitivity precludes it being useful 
even for screening patients with ulcerative colitis or 
familial polyposis coli; although these patients are at 
high risk of developing colorectal cancer, both condi- 
tions may cause raised serum CEA in the absence of 
malignancy. 

Prognosis and monitoring treatment 

A raised preoperative CEA level has been shown to be 
associated with a poorer prognosis, but the value of pre- 
operative CEA as an independent prognostic factor is 
unclear. Serum CEA levels should fall to normal within 
4-6 weeks of complete resection of a colorectal carcinoma, 
the mean half-life being about 10 days. Levels usually rise 
with disease and fall with response to chemotherapy or 
radiotherapy. Failure of CEA to fall during radiotherapy 
usually indicates the presence of tumour outside the radi- 
ation field. Several studies have shown that survival is 
longer in patients who have a fall in serum CEA level 
during chemotherapy than in those in whom there is no 
change or an increased level (Allen-Mersh et al 1987). CA 
19.9 is elevated in 75-90% of patients with pancreatic car- 
cinomas and is increasingly used to monitor palliative 
chemotherapy. 

Foilow-up and detection of relapse 

In approximately two-thirds of patients with recurrent 
colorectal cancer, a rise in serial serum CEA values pre- 
dicts recurrence on average 11 months before it becomes 
clinically apparent (Begent & Rustin 1989). Surgical resec- 
tion of isolated metastases of colorectal cancer has been 
advocated. Unfortunately, a randomized, multicentre trial 
under the auspices of the Cancer Research Campaign has 
failed to show any survival benefit from surgery after 
early detection of recurrence by rising CEA levels 
(Lennon et al 1994); however, further work is required to 
determine whether such patients would benefit from 
chemotherapy. 



Ovarian cancer 

The site and pattern of spread of ovarian cancer make it 
very difficult to detect and monitor using conventional 
clinical and radiological techniques, so a circulating 
tumour marker is potentially very valuable. CA 125 is the 
most commonly used tumour marker for ovarian cancer. 
CA 125 is found in derivatives of coelomic epithelium, 
including pleura, pericardium and peritoneum, but is not 
detected in normal ovarian tissue. 



Diagnosis 

CA 125 is elevated in over 95% of patients with advanced 
(stage III or IV) ovarian cancer, but in less than 50% of 
patients with stage I disease (Bast et al 1983). However, an 
elevated CA 125 is not diagnostic of ovarian cancer. 
Levels above 30 iu ml" 1 are frequently seen during the first 
trimester of pregnancy, in patients with endometriosis or 
with cirrhosis, especially if ascites is present, and in 1% of 
healthy controls. In addition, over 40% of patients with 
advanced non-ovarian intra-abdominal malignancies 
have elevated CA 125 levels. None the less, in a patient 
suspected of having ovarian cancer, the presence of an 
elevated CA 125 should prompt you either to refer the 
patient to a gynaecological oncologist or to perform the 
surgery through a more extensive midline incision to 
allow adequate debulking of tumour. 

Screening 

Despite the low sensitivity of CA 125 for potentially 
curable stage I tumours, large screening studies have been 
performed. One study at the Royal London Hospital 
measured serum CA 125 in 22 000 postmenopausal well 
women. Those women who had CA 125 levels above 
30 iu ml -1 underwent pelvic ultrasound, and if that was 
positive a laparotomy was performed. In all, there were 
11 confirmed cases of epithelial ovarian cancer (true posi- 
tives) and 11 cases in whom laparotomy did not reveal an 
ovarian tumour (false positives). Of note, however, is the 
fact that only 3 of the 11 patients with screen-detected 
ovarian cancers had stage I disease (Jacobs et al 1993). A 
large randomized trial is currently investigating whether 
serial CA 125 screening with ultrasound in patients with 
elevated or rising levels leads to improved survival. New 
research tools such as the use of proteomic (the protein 
profile) patterns in serum of patients with ovarian cancer 
which have both an increased specificity and sensitivity 
may have a future role in screening (Petricoin et al 2002). 
However until further work has been conducted, screen- 
ing for ovarian cancer should not be offered to women 
outside a clinical trial unless there is a high risk of 
familial ovarian cancer. 



305 



30 



MALIGNANT DISEASE 



Assessing completeness of excision 

In order to decide optimum postoperative management, 
it is important to know whether one is dealing with a 
patient with completely excised stage I disease, or 
whether the patient has residual tumour after surgery. A 
persistently elevated CA 125 after oophorectomy for sus- 
pected stage I disease is definite evidence of residual 
tumour. 



Prognosis and response to treatment 

Very high CA 125 levels prior to surgery are associated 
with a worse prognosis, but knowledge of this is 
unlikely to lead to any alteration in management. The 
exception is in women with stage I disease where a pre- 
operative level > 65 iu ml -1 has been shown to be a 
powerful adverse prognostic indicator (Nagele et al 
1995). Such patients are candidates for chemotherapy 
rather than surveillance. Several groups have shown that 
the CA 125 level after one, two or three courses of 
chemotherapy, a long half-life or greater than seven-fold 
fall are the most important prognostic factors for sur- 
vival. Prognostic information based on CA 125 should 
not be used to decide therapy as in nearly 20% of cases 
where CA 125 predicts a poor prognosis the patient has 
no cancer progression in the next 12 months (Fayers et al 
1993). 

Definitions for response based on serial CA 125 esti- 
mations have been proposed (Rustin et al 1995) and 
appear more accurate than scans for monitoring therapy. 
For use in clinical trials they have to be very precise and 
use mathematical logic in a computer program. Put 
simply, response according to CA 125 has occurred if 
either of the following criteria are applicable: 

• Either 50% response has occurred if there is a 50% 
decrease in serum CA 125 levels. There must be two 
initial elevated samples. The sample showing a 50% fall 
must be confirmed by a fourth sample (requires four 
CA 125 levels). 

• Or 75% response has occurred if there has been a serial 
decrease in serum CA 125 levels of more than 75% over 
three samples (requires three CA 125 levels). 

(In each the final sample has to be at least 28 days after 
the previous sample.) These definitions are particularly 
useful for clinical trials, where they indicate which new 
treatments are active more easily and cheaply than the 
use of standard response criteria. 

Detection of progression or relapse 

A serial rise of CA 125 of more than 25% appears the most 
accurate method of predicting progression of ovarian 



cancer during therapy and could lead to ineffective, toxic 
and expensive therapy being withheld. A confirmed dou- 
bling from the upper limit of normal during follow-up 
predicts relapse with almost 100% specificity. There is 
controversy about the role of serial CA 125 measure- 
ments during follow-up in asymptomatic patients, with 
the anxiety from knowing CA 125 levels often inducing 
CA 125 psychosis. Although the use of CA 125 estimation 
to define progression may reduce the number of radio- 
logical investigations performed, there is no evidence at 
present that early reintroduction of chemotherapy or 
searching for a resectable site of relapse produces any 
survival benefit A large Medical Research Council 
(MRC) and European Organization for Research and 
Treatment of Cancer (EORTC) trial is currently withold- 
ing all serial CA 125 results from clinicians and patients 
during follow-up until the levels double. Patients are 
then randomized between immediate therapy or the 
clinician not being informed of the result so the patient 
continues on observation. Until the results of this trial 
are available, monitoring by CA 125 during follow-up 
should be discouraged. 



Prostate cancer 

Prostate-specific antigen (PSA) is the most useful tumour 
marker in patients with prostate cancer. PSA is a serine 
protease, produced by prostate epithelium, with the 
function of liquefying the gel which surrounds spermata- 
zoa to enable them to become fully mobile. In serum, PSA 
is found either free or complexed to proteins. PSA esti- 
mation has superseded that of prostatic acid phosphatase 
as it is elevated in a higher proportion of men with 
prostate cancer. 



Diagnosis, screening and staging 

Elevated levels of PSA (>4 ng ml" 1 ) occur in about 53% of 
men with intracapsular microscopic prostatic cancer, and 
77% of men with intracapsular macroscopic prostatic 
cancer, but can also occur in 30-50% of men with benign 
prostatic hypertrophy (BPH), a condition common in men 
of similar age group to those who develop prostate cancer 
(Dorr et al 1993). The combination of PSA and digital 
rectal examination, followed by prostatic ultrasound in 
patients with abnormal findings, is commonly used for 
screening in the USA but is not recommended in the UK 
as there is so far no evidence of survival benefit from early 
detection of prostate cancer. There is a vocal debate 
raging, with those who advocate screening stating that an 
individual with early prostate cancer may be cured by 
radical surgery or radiotherapy. Those against screening 



306 



TUMOUR MARKERS 



30 



point out that, despite a 9% chance of developing clinical 
prostate cancer, there is only a 1 % chance of dying from 
it and we cannot predict which cancers will be aggressive, 
so most patients will suffer the side-effects of therapy 
without any benefit. Furthermore, about 40% of those 
patients with PSA levels of 4.0-9.9 ng ml -1 at screening 
will already have tumour spread outside the prostate 
(Catalona et al 1991). 

Several methods are being used to improve diagnostic 
specificity. The best appears to be the measurement of 
the ratio of free to total PSA, as more of the PSA is 
protein bound in patients with prostate cancer than in 
those with BPH. The ratio of free to total PSA is low 
(about 10%) in prostate cancer, compared with >16% in 
BPH and prostatitis. Using this ratio increases the speci- 
ficity for diagnosing prostate cancer from 30% to 61% 
(Froschermaier et al 1996). PSA density and PSA density 
of the transition zone rely on ultrasound size estimations 
leading to lack of precision, but some centres have 
shown this measurement to improve specificity. Another 
method is based on the observation that PSA levels 
generally rise by more than 20% per annum in cases of 
malignancy. The PSA velocity calculated from serial 
levels can improve specificity but at the expense of 
delaying diagnosis. 

PSA is less reliable than transurethral ultrasound in 
the detection of capsular invasion. A recently studied 
research tool is the use of the ultrasensitive reverse tran- 
scriptase polymerase chain reaction to detect PSA gene 
expression on circulating prostate cells. This technique 
might improve staging by detecting preoperatively those 
patients with extracapsular extension who do not benefit 
from radical surgery. Patients with PSA levels of 
<20 ng ml" 1 can be assumed to have no bone metastases 
and do not necessarily need bone scans. However, not all 
patients with a PSA of >20 ng ml" 1 will have distant 
metastases. Lymph node metastases are usually associ- 
ated with elevated PSA. 



Prognosis, monitoring response and 
detection of recurrence 

As the PSA level correlates with prostatic volume and 
tumour differentiation, it is not surprising that a high pre- 
treatment PSA is associated with a poor prognosis. PSA 
levels fall rapidly to normal after complete removal of 
tumour by radical prostatectomy, although the rate of fall 
is slower after successful radiotherapy or endocrine 
therapy. A serial rise in PSA frequently precedes other evi- 
dence of disease progression in the patient with a past 
history of prostate cancer. The development of back pain 
in the presence of an elevated PSA level suggests the 
development of bone metastases. 



Hepatocellular carcinoma 

Serum AFP is elevated at presentation in 50-80% of UK 
patients with hepatocellular carcinoma (HCC). Although 
HCC is one of the most common malignant tumours in 
the world today, the relatively low incidence in the UK 
does not justify general population screening, although 
such screening may be justified in areas, such as China, 
with high incidence populations. In the UK, serial AFP 
estimation and ultrasound examination can be justified, 
however, for selective screening of high risk populations 
(i.e. patients with cirrhosis, chronic hepatitis B or 
haemochromatosis) because patients who have successful 
resection of a solitary, screen-detected tumour have a 
higher chance of long-term survival. Modest elevations of 
AFP occur in about 20% of patients with hepatitis, cir- 
rhosis, biliary tract obstruction and alcoholic liver disease 
and in up to 10% of patients with hepatic metastases. 
Despite these caveats, a massively elevated AFP in a 
patient with known cirrhosis is virtually diagnostic of 
HCC. 



Breast cancer 

A variety of tumour markers have been studied in 
patients with breast cancer, including CEA and tissue 
polypeptide antigen (TPA) and several polymorphic 
epithelial mucin markers (HMFG1, HMFG2, MSA, MCA, 
CAM-26, CAM-29 and CA 15-3). The most widely inves- 
tigated mucin marker in breast cancer is CA 15-3. The 
commercially available CA 15-3 kit utilizes a sandwich 
technique which employs two monoclonal antibodies: the 
115D8 antibody as the capture antibody and the DF3 anti- 
body as the tracer antibody. 

Diagnosis and screening 

Although elevated levels of CA 15-3 are found in 
55-100% of patients with advanced breast cancer, serum 
CA 15-3 is raised in only 10-46% of patients with 
primary breast cancer and in about 10% of patients with 
early (T1/2N0M0) operable disease. As 2-20% of 
patients with benign breast disease have elevated levels, 
it is clear that mucin assays such as CA 15-3 are lacking 
in both specificity and sensitivity as a screening tool. No 
other tumour marker or combination of markers con- 
tribute to the diagnosis of breast cancer (Nicolini et al 
1991). 

Prognosis and monitoring response to 
treatment 

Elevated preoperative levels of CA 15-3 have been 
shown to be associated with a poorer prognosis 



307 



30 



uauuaiiiiiiuutfSBGttiita 



MALIGNANT DISEASE 



(Kallioniemi et al 1988). However, this may well be due 
to the association between CA 15-3 and tumour burden, 
and there is no convincing evidence to date that 
measurement of CA 15-3, or any other tumour marker, 
provides significant independent prognostic informa- 
tion. Although tumour marker levels can fall with reduc- 
tion in tumour burden following systemic therapy, the 
variation between patients makes tumour markers 
unreliable for assessing response. 

Early detection of relapse 

The observation that over 60% of patients who develop 
recurrent breast cancer have raised levels of CA 15-3 sug- 
gests a potential value in early detection of recurrence. 
The use of a panel of tumour markers might further 
increase the pick-up of recurrent disease. However, it is 
questionable whether such early detection of relapse will 
alter survival and thus whether the patient will benefit. 

Other cancers 

• Neuron-specific enolase is elevated in many patients 
with advanced small cell lung cancers and in children 
with neuroblastoma, where it is used for screening. 

• Paraprotein levels are very important in the manage- 
ment of patients with myeloma, where ^-microglobulin 
may be of prognostic value. 

• Carcinoid tumours can be monitored by urine levels of 
5-hydroxyindoleacetic acid (5HIAA), and polypeptides 
such as gastrin or glucagon are useful in the manage- 
ment of rare gastrointestinal tumours. 

• Squamous cell carcinomas are associated with elevated 
levels of squamous cell carcinoma antigen (SCC) as 
well as cytokeratin fragments. SCC and CA 125 give 
valuable prognostic information in patients with cervi- 
cal carcinoma, and may indicate relapse before scans. 

• Calcitonin and calcitonin-gene-related peptide are used 
in the diagnosis and screening for medullary thyroid 
carcinoma. 

• Serum S-100 and reverse transcriptase polymerase 
chain reaction to detect mRNA of tyrosinase on circu- 
lating melanoma cells are being studied for staging and 
following patients with melanoma. 

There are many other markers not mentioned, either 
because they are not considered to be of clinical value or 
because information related to value is inadequate. Many 
cytokines, growth factors, oncogenes and oncogene 
products are being investigated as tumour markers, and 
some may well prove to be useful. Despite many claims, 
there are no markers that are of use as general cancer 
screens. 



Summary 

• Tumour markers may have a high 
sensitivity in patients with advanced 
cancer but most have a low sensitivity in 
patients with early stage cancer. 

• When using a tumour marker to help in 
diagnosis it is essential to know its 
specificity. 

• The potential uses of tumour markers are 
best demonstrated by hCG, where it is 
used for screening, diagnosis, determining 
prognosis, monitoring therapy and in 
follow-up of patients with gestational 
trophoblastic disease. 

• The most commonly used tumour markers 
are PSA for prostate cancer, CA 125 for 
ovarian cancer, CEA for colorectal cancer, 
and hCG and AFP for germ cell tumours. 

• Before requesting detection of a tumour 
marker, always consider whether the result 
would alter your management. 




References 



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Significance of a fall in serum CEA concentration in patients 
treated with cytotoxic chemotherapy for disseminated 
colorectal cancer. Gut 12: 1625-1629 

Bagshawe KD, Harland S 1976 Immunodiagnosis and 
monitoring of gonadotrophin producing metastases in the 
central nervous system. Cancer 38: 112-118 

Bagshawe KD, Dent J, Webb J 1986 Hydatidiform mole in 
England and Wales, 1973-1983. Lancet ii: 673-677 

Bast RC, Klug TL, St John E et al 1983 A radioimmunoassay 
using a monoclonal antibody to monitor the course of 
epithelial ovarian cancer. New England Journal of Medicine 
308: 883-887 

Begent RJ, Rustin GJS 1989 Tumour markers: from 
carcinoembryonic antigen to products of hybrid oma 
technology. Cancer Surveys 8: 107-121 

Bower M, Rustin GJS 1996 Serum tumor markers and their 
role in monitoring germ cell cancers of the testis. In: 
Vogelzang NJ et al (eds) Comprehensive textbook of 
genitourinary oncology. Williams & Wilkins, Baltimore, 
pp 968-980 

Catalona WJ, Smith DS, Ratliff T L et al 1991 Measurement of 
prostate specific antigen in serum as a screening test for 
prostate cancer. New England Journal of Medicine 
324: 1156-1161 

Dorr VJ, Williamson SK, Stephens RL 1993 An evaluation of 
prostate-specific antigen as a screening test for prostate 
cancer. Archives of Internal Medicine 153: 2529-2537 



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Fayers PM, Rustin GJS, Wood R et al 1993 The prognostic 
value of serum CA 125 in patients with advanced ovarian 
cancer: an analysis of 573 patients by the Medical 
Research Council Working Party on Gynaecological 
Cancer. International Journal of Gynaecological Cancer 
3: 285-292 

Froschermaier SE, Pilarsky CP, Wirth MP 1996 Clinical 

significance of the determination of noncomplexed prostate- 
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47: 525-528 

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staging system for metastatic germ cell cancers. Journal of 
Clinical Oncology 15: 594-603 

Jacobs I, Prys Da vies A, Bridges J et al 1993 Prevalence for 
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Lennon T, Houghton J, Northover J on behalf of the CRC/NIH 
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311 



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The body's response to 
surgery 



J. P. S. Cochrane, C G. Ha rg reaves 




Objectives 

• Understand the multisystem nature of the 
impact of surgery on the body. 

• Recognize the clinical features resulting 
from the body's response. 

• Appreciate that these responses can be 
modified, resulting in improved clinical 
outcomes. 



INTRODUCTION 



^^rStf^Stf^^^^^ 



The body responds to trauma with local and systemic 
reactions that attempt to contain and heal the tissue 
damage, and to protect the body while it is injured. The 
response is remarkably similar whether the trauma is a 
fracture / burn, sepsis or a planned surgical operation, and 
the extent of the response is usually proportional to the 
severity of the trauma. 

The response, with neuroendocrine and inflammatory 
cytokine components, increases the metabolic rate, 
mobilizes carbohydrate, protein and fat stores, con- 
serves salt and water and diverts blood preferentially to 
vital organs. It also stimulates important protective 
mechanisms such as the immunological and blood clot- 
ting systems. However, the overall result is one of 
immunosuppression leading to increased vulnerability 
to infection. 

The interplay between the many inflammatory medi- 
ators and cellular responses is very complex and events 
at a molecular level are only slowly being unravelled. 
New signalling systems and feedback mechanisms con- 
tinue to be discovered. These will provide opportunities 
for future therapies aimed at blocking the unwanted 
aspects of what can be an exaggerated, detrimental 
systemic inflammatory response. 

Remember also that major surgery has other inevitable 
consequences (such as hypothermia and immobility) 
which predispose to postoperative morbidity. With 



optimal perioperative management, however, their 
impact can be minimized. Another common sequel, 
anaemia, appears to be well tolerated and physiologically 
less significant for most patients than previously 
assumed. 




Key point 

Surgical operation is a controlled form of 
trauma in which many aggravating factors can 
be manipulated. 



INITIATION OF THE RESPONSE 



£:^;^^^^^^^ 



^Vi - S^ -i ^ -\- " -s -* " 



Various noxious stimuli produce the response but they 
rarely occur alone, and multiple stimuli often produce 
greater effects than the sum of single responses. The 
response is modified by the severity of the stimulus, the 
patient's age, nutritional status, coexisting medical con- 
ditions, medication and if the trauma or operation has 
affected the function of any particular organ. Recent 
trauma or sepsis will also modify the response to a sub- 
sequent surgical operation. 

Pain. Stimuli from the skin, the musculoskeletal 
system, the visceral stretch receptors and, especially, 
pulling on the mesentery stimulate the sympathetic 
nervous system, adrenocorticotrophic hormone (ACTH) 
and arginine vasopressin (AVP). 

Tissue injury. Tissue disruption causes local cytokine 
release with capillary endothelial damage and leak. This 
in turn leads to the migration of inflammatory cells, 
amplifying the release of mediators, which can develop 
into a systemic inflammatory response. Another mech- 
anism of tissue injury is ischaemia followed by reperfu- 
sion, leading to production of oxygen free radicals 
(reactive oxygen species, ROS). 

infection. This is often the underlying reason for 
presentation in surgical patients, especially emergencies, 
and so the effects of sepsis are often present. Endotoxin 



313 



31 j 



POSTOPERATIVE 



from the cell walls of Gram-negative bacteria is the most 
powerful stimulus for release of one of the cytokines, 
tumour necrosis factor (TNF), from macrophages. 
Infection can also enter the circulation from the bowel if 
the mucosal barrier is impaired. 

Hypovolemia. Most injuries lead to hypovolemia, 
either from haemorrhage, plasma loss in burns or third- 
space losses. This stimulates baroreceptors, releasing 
vasopressin (AVP), catecholamines, renin-angiotensin 
and aldosterone, and leads to impaired excretion of 
sodium and water, manifesting clinically as oliguria. 
Hypoperfusion, especially in the presence of hypo- 
tension, can also initiate endothelial damage and progress 
to organ dysfunction. Recent evidence suggests that 
maintaining optimal circulating volume throughout the 
perioperative period can avoid these consequences and 
reduce mortality after major surgery. 

Starvation. If starvation accompanies trauma it 
causes the body to use muscle protein as a source of 
energy, leading to muscle wasting and weakness, which 
slows recovery. Failure to provide nutritional support can 
also impair the immune response, resulting in poorer 
healing and more postoperative infections, especially in 
those malnourished prior to surgery. 

Hypoxia, hypercarbia or pH changes. Chemo- 
receptors in the carotid and aortic bodies react to these 
changes and stimulate the sympathetic nervous systems, 
ACTH and AVR 

Energy substrates. Hypoglycaemia stimulates 
ACTH, growth hormone, 3 -en dorphin, AVP and cate- 
cholamines. This catabolic state also favours muscle 
breakdown. Certain amino acids also have particular 
effects. 

Fear, anxiety and emotion. These stimulate the 
sympathetic nervous system, AVP and ACTH. 

Temperature. Hypothermia, which is difficult to 
avoid in lengthy major surgery, stimulates the hypotha- 
lamus and leads to increased secretion of AVP, ACTH, 
growth hormone, thyroxine and catecholamines. Studies 
have shown improved recovery times with fewer infec- 
tions when normothermia is maintained intraoperatively. 



SYSTEMS CONTROLLING THE 

RJESPOJNSJE__^ 

The response to surgery is modulated both by the neuro- 
endocrine system and the inflammatory mediators, and 
the cells controlling their release. The effects are closely 
intertwined, with locally produced cytokines having 
systemic effects proportional to the extent and severity 
of tissue injury. There are multiple feedback loops 
which prevent excessive activation of the inflammatory 
cascades. 



Sympathetic nervous system. The immediate fight 
and flight reaction may help the injured person avoid 
further injury, but it has short-lasting effects on 
metabolism. Activation of the sympathetic pathways also 
stimulates the adrenal glands. 

Endocrine response. This includes not only the 
hypothalamic— pituitary-adrenal (HPA) axis but also 
growth hormone, AVP, thyroxine, insulin and glucagon, 
causing some metabolic effects, particularly changes 
in carbohydrate and fat metabolism. This response 
appears to protect not so much against the stress but 
more against the body's acute phase response from 
overreacting. 

Acute phase response. The wound becomes a 
'cytokine organ' whose metabolism and local healing 
responses are controlled by cytokines and other medi- 
ators that are produced locally and also released from 
activated inflammatory cells, including neutrophils and 
monocytes. In severe trauma, proinflammatory cytokines 
produce a systemic "acute phase' response, with profound 
changes in protein metabolism, and immunological acti- 
vation; these effects are mostly beneficial but in severe 
trauma can be lethal. 

Vascular endothelial cell response. This affects 

vasomotor tone and vessel permeability, so it affects per- 
fusion, circulating volume and blood pressure and can 
lead to the clinical picture of shock and lung injury. There 
are close interactions between the endothelium, acute 
phase mediators and leucocytes (neutrophils and mono- 
cytes). Endothelial damage also activates the coagulation 
cascades and can result in microvascular clotting despite 
a generalized abnormal bleeding tendency. 



Sympathetic nervous system 

The central and peripheral sympathetic systems are stimu- 
lated particularly by pain and hypovolemia and this has 
direct actions and indirect effects, by releasing adrenaline 
(epinephrine) from the adrenal medulla and nor- 
adrenaline (norepinephrine) predominately from periph- 
eral ganglia. These catecholamines have both a and p 
effects on sympathetic receptors that prepare the body 
rapidly for fight or flight by cardiovascular, visceral and 
metabolic actions. These effects begin when the operation 
starts and continue for several days into the postoperative 
period for all but minor procedures. 



Cardiovascular effects 

Blood is redistributed from the viscera and skin (ct effects) 
to the heart, brain and skeletal muscles (|3 2 effects), 
and there is an increase in heart rate and contractility 
(Pt effects). 



314 



THE BODY'S RESPONSE TO SURGERY 



31 



Visceral effects 

Non-essential visceral functions such as intestinal mo- 
tility are inhibited; resulting in paralytic ileus / and 
bladder sphincter tone is increased; other actions are; 
bronchodilatation (j3 2 ); mydriasis - dilatation of the pupil 
(a,); uterine contraction (c^); and relaxation (f* 2 ); visual 
field increases. 



Metabolic and hormonal effects 

Blood glucose rises due to increased breakdown of liver 
and muscle glycogen and by gluconeogenesis (c^), and 
indirectly by suppression of insulin secretion (a 2 ) and 
stimulation of glucagon secretion (p). Other hormonal 
actions are stimulation of growth hormone (a) and renin 
(p T ). Lipolysis is stimulated in adipose cells, and keto- 
genesis is stimulated in the liver. 

Endocrine response 

The HPA axis is stimulated mainly by the injury itself, but 
probably its most important function is to control the 
effects of systemically released cytokines. 

ACTH. This is released from the anterior pituitary by 
neurological stimuli reaching the hypothalamus, or by 
hormones such as AVP, angiotensin II or catecholamines. 
The ACTH response to stress is not inhibited by adminis- 
tered steroids. ACTH stimulates the adrenal cortex to 
release glucocorticoids and also potentiates the action of 
catecholamines on cardiac contractility. 

Glucocorticoids. These usually have only a 'per- 
missive' action (allowing other hormones to function) 
but the increased levels after trauma have important 
metabolic, cardiovascular and immunological actions 
proportional to the severity of the trauma. Cortisol is the 
main glucocorticoid and its serum level usually returns to 
normal 24 h after uncomplicated major surgery but may 
remain elevated for many days in extensive burns or if 
infection supervenes. It stimulates the conversion of 
protein to glucose (catabolic action); it stimulates the 
storage of glucose as glycogen; it is an antagonist of 
insulin and this assists gluconeogenesis to increase 
plasma glucose (diabetogenic action); it helps to maintain 
blood volume by decreasing the permeability of the vas- 
cular endothelium and enhancing vasoconstriction by cat- 
echolamines and suppressing synthesis of prostaglandins 
and leucotrienes (anti-inflammatory action); it also 
inhibits secretion of interleukin 1 (IL-1) and IL-2 antibody 
production and mobilization of lymphocytes (immuno- 
suppressant action). 

The normal glucocorticoid response can be reduced or 
absent (due to previous long-term administration of 
steroids, adrenalectomy or adrenal infarction). This 



presents with hypoglycaemia, hyponatremia and refrac- 
tory hypotension. 




Key point 



• Adrenal failure is often fatal if you fail to 
recognize it at an early stage; it requires 
immediate steroid replacement. 

Aldosterone. The inevitable release of ACTH after 
trauma stimulates a short-term release of aldosterone 
from the adrenal cortex, but the rise may be prolonged if 
other stimuli such as hypovolaemia or vasomotor 
changes (which activate the renin-angiotensin system in 
the kidney) occur. A rise in plasma potassium concentra- 
tion can also stimulate aldosterone release. Aldosterone 
causes increased reabsorption of sodium and potassium 
secretion in the distal convoluted tubules and collecting 
ducts, and hence a reduced urine volume. 

Arginine vasopressin (AVP). Also referred to as 
antidiuretic hormone (ADH), this is released from the 
posterior pituitary by pain, a rise in plasma osmolality 
(via osmoreceptors in the hypothalamus), hypovolaemia 
(via baroreceptors and left atrial stretch receptors), 
anaesthetic agents or a rise in plasma glucose. Its actions 
on the distal tubules and collecting ducts in the kidney 
lead to increased reabsorption of solute-free water; it 
causes peripheral vasoconstriction, especially in the 
splanchnic bed, and it stimulates hepatic glycogenolysis 
and gluconeogenesis. Its secretion increases for about 
24 h after operation, and during this time the kidney 
cannot excrete 'free 7 water (water that is not solute led), 
so the urine osmolality remains higher than plasma. 
After head injury, burns or prolonged hypoxia there may 
be continued secretion of AVP, resulting in oliguria and 
hyponatraemia. 

Insulin. In the ebb phase after injury, plasma insulin 
concentration falls because catecholamines and Cortisol 
make the p-islet cells of the pancreas less sensitive to 
glucose. Glucagon also inhibits insulin release and Corti- 
sol reduces the peripheral action of insulin; less carbohy- 
drate is transported into cells and blood sugar rises. In the 
flow phase, plasma insulin rises but blood sugar remains 
elevated because various intracellular changes make the 
tissues resistant to insulin. 

Glucagon. Secretion of glucagon from the a-islet cells 
of the pancreas increases after injury and this plays a small 
part in increasing blood sugar by stimulating hepatic 
glycogenolysis (Greek lyein = to loosen; hydrolysis of 
glycogen), and gluconeogenesis (Greek glykos - sweet + 
neos = new + genesis - origin; the formation of glucose 
from non-carbohydrate substances). It also stimulates 



315 



31 




POSTOPERATIVE 



hepatic ketogenesis and lipolysis in adipose tissue. 
Cortisol prolongs its actions. 

Thyroxine. Total T 4 (but not usually free T 4 ) and total 
and free T 3 (tri-iodothyronine, the more active hormone) 
decrease after injury because Cortisol impairs conversion 
of T 4 to T 3 . 

Growth hormone. Growth hormone is released 
from the anterior pituitary as a result of neurological 
stimulation of the hypothalamus or by a rise in circulat- 
ing levels of catecholamine s, ACTH, AVP, thyroxine or 
glucagon. Its plasma levels increase after trauma, hypo- 
volemia, hypoglycaemia or a decrease in plasma fatty 
acids or increase in serum arginine. Its main effects are to 
promote protein synthesis and enhance breakdown of 
lipid and carbohydrate stores. It increases plasma fatty 
acids and ketone bodies through direct stimulation of 
lipolysis and potentiation of catecholamine effects on 
adipose tissue and by stimulation of hepatic ketogenesis. 
It is also associated with a fall in insulin levels that allows 
plasma glucose to rise. 

Acute-phase response 

Local effects 

Noxious stimuli such as infection, trauma, toxins, haem- 
orrhage or malignancy attract granulocytes and mono- 
nuclear cells to the site of injury, and these cells, together 
with local fibroblasts and endothelial cells, release 
cytokines. Cytokines (Greek kytos = hollow, cell + kineein = 
to move) are peptides produced by a variety of cells 
(unlike true hormones) and produce mainly paracrine 
(direct cell-to-cell) effects. Interleukins (IL) 1, 2 and 6, TNF 
and the interferons are the main cytokines released early. 
Their actions help to contain tissue damage by contribut- 
ing to the inflammatory reaction through vasodilatation, 
increased permeability of vessels, migration of neutro- 
phils and monocytes to the wound, activation of the coag- 
ulation and complement cascades, and proliferation of 
endothelial cells and fibroblasts. 

Systemic effects 

If cytokine production is large enough, systemic (Greek 
syn = together + histanai = to set; affecting the body as a 
whole) effects occur, such as fever, malaise, headache, 
myalgia (Greek mys - muscle + algos = pain) as well as 
vasodilatation. They may also produce a leucocytosis, 
activation of immune function, release of ACTH and glu- 
cocorticoids, activation of clotting cascades, an increase in 
erythrocyte sedimentation rate (ESR), a decrease in circu- 
lating levels of zinc and iron (inhibiting the growth of 
microorganisms requiring iron). They also affect the 
serum levels of acute phase reactants (APRs) which are 



host-defence proteins synthesized in the liver; most 
increase (such as C-reactive protein, fibrinogen, comple- 
ment C3, a-antichymotrypsin, caeruloplasmin and 
haptoglobin), but the levels of albumin and transferrin 
decrease. 

• IL-6 is the main mediator of this altered hepatic protein 
synthesis. 

• TNF - tumour necrosis factor (cachectin) released pri- 
marily from macrophages by bacterial endotoxin, 
causes anorexia, tachypnoea, fever and tachycardia, 
with proliferation of fibroblasts and widespread effects 
on neutrophils; it stimulates production of other 
cytokines, ACTH, APRs and amino acids from skeletal 
muscle, hepatic amino acid uptake, and elevation of 
plasma triglycerides and free fatty acids. High concen- 
trations cause multiple organ dysfunction syndrome 
(MODS). 

• IL-2 enhances immune function by T-lymphocyte pro- 
liferation and by enhancing the activity of natural killer 
cells. 

• IL-1 in low dosage causes fever, neutrophilia, low 
serum zinc levels, increased APR synthesis, anorexia, 
malaise, release of ACTH, glucocorticoid and insulin, 
and, in high dose, the features of MODS. 

• Interferons, such as ^-interferon are glycoproteins pro- 
duced by T lymphocytes which activate macrophages, 
enhancing both antigen presenting and processing as 
well as cytocidal activity; 7-interferon is synergistic 
with TNF, inhibits viral replication, and inhibits 
prostaglandin release. 

• Prostaglandins are important components of the inflam- 
matory response. They can be produced by all nucle- 
ated cells except lymphocytes; they increase vascular 
permeability and cause vasodilatation and leucocyte 
migration. 

• Leucotrienes are 1000 times as effective as histamine 
at increasing postcapillary leakage and they cause 
increased leucocyte adhesion, vasoconstriction and 
bronchoconstriction. 

• Kallikreins and kinins. Bradykinin release is stimulated 
by hypoxia and it is a potent vasodilator that increases 
capillary permeability, producing oedema, pain and 
bronchoconstriction and affecting glucose metabolism. 

• Heat shock proteins (HSPs). These are produced by vir- 
tually all cells in response to many stresses (not just 
heat), mainly via the stimulus of the HPA axis, and they 
are also elevated in certain tissues in chronic diseases. 
The ability to produce them declines with age and they 
appear to protect cells from the deleterious effects of 
stress and to inhibit synthesis of APRs. 

• 5-Hydwxytryptamine (5HT). This is a neurotransmitter 
produced from tryptophan and found in enterochro- 
maffin cells of the intestine and platelets. It is released 



316 



THE BODY'S RESPONSE TO SURGERY 



31 



when tissue is injured and it causes vasoconstriction 
and bronchoconstriction, increases platelet aggregation 
and increases heart rate and contractility. 

• Histamine. Histamine is released from mast cells, 
platelets, neurons, and the epidermis by trauma, sepsis 
and hypotension. Its main action is to cause local 
vasodilatation and increased vascular permeability, so 
large concentrations may lead to hypotension. It acts on 
Hj cell surface receptors to increase histamine precursor 
uptake and cause bronchoconstriction, and increased 
intestinal motility and cardiac contractility; it also acts 
on H 2 receptors that inhibit histamine release and 
produce changes in gastric secretion, heart rate and 
immunological function. 

* Endogenous opioids. Endogenous opioids such as 
[J-endorphin increase after trauma and produce 
analgesia, a rise in blood sugar, a lowering of blood 
pressure and effects on immune function. 

Interactions between APRs and the 
endocrine response 

IL-l and IL-6 can activate the HPA axis by increasing 
ACTH secretion and also directly stimulating glucocorti- 
coid release from the adrenal gland. Glucocorticoids ini- 
tially help cytokines to regulate APRs, but if glucocorticoid 
levels remain elevated they inhibit cytokine production. 

The vascular endothelial response 

The scattered 'endothelial organ' weighs about 1.5 kg. 
After tissue injury it is activated locally, resulting in 
the appearance of glycoprotein selectins (adhesion 
molecules) on the endothelial cell surface along with 
intercellular adhesion molecules (ICAMs). Neutrophils 
recognize these surface molecules, begin to stick and then 
migrate out into the interstitium, with a concurrent 
increase in endothelial permeability, particularly in the 
postcapillary venules. 

Nitric oxide is a powerful vasodilator produced mainly 
by endothelial cells but also by macrophages, neutrophils, 
Kupffer cells and renal cells. It is inactivated by 
haemoglobin and opposed by endothelins. Its other 
action is to increase production of APRs. 

Endothelins are a family of potent vasoconstricting pep- 
tides with mainly paracrine actions. They are released by 
thrombin, catecholamines, hypoxia, cytokines and endo- 
toxins. They counteract nitric oxide and prostacyclins to 
maintain vasomotor tone. 

Platelet-activating factor (PAF) is released from endo- 
thelial cells by the action of TNF, IL-l, arginine vaso- 
pressin (AVP or antidiuretic hormone) and angiotensin II. 
When platelets come into contact with PAF they release 



thromboxane which causes platelet aggregation and 
vasoconstriction. PAF also reduces the permeability of 
endothelial cells to albumin and may also affect glucose 
metabolism. 

Prostaglandins cause vasodilatation and reduce platelet 
aggregation. Other arachidonic acid derivatives include 
thromboxanes, which are also produced by cyclo- 
oxygenase. An inducible form of this enzyme (COX-2) is 
activated. 

Atrial natriuretic peptides (ANPs) are potent inhibitors of 
aldosterone secretion and are released by atrial tissue 
(which is specialized endothelium) in response to changes 
in chamber distension. They can also be released by the 
CNS. It is not yet clear what role they play in the response 
to injury. 

Intracellular signalling processes and 
regulation of the acute stress response 

• Gene transcription: stimulation of cells by cytokines and 
other products of inflammatory damage, such as 
oxygen free radicals, appears to be coupled to sig- 
nalling systems that lead to upregulation of the genes 
coding for enzymes and cytokines by increasing RNA 
transcription. These inducible enzymes then greatly 
increase the production of mediators, sustaining the 
inflammatory response. Families of transcription factor 
proteins known as inhibitor of kappa B kinase /nuclear 
factor kappa B (IKK/NF kappa B) seem to be one of the 
central components. They appear to control inducible 
nitric oxide synthetase (iNOS) and COX-2, as well as 
transcription of the IL-6 and TNFa genes. 

• Apoptosis (Greek apo - from + piptein = to fall) is the pro- 
grammed death of cells which ensures turnover of 
short-lived immune cells. It increases after trauma and 
also in sepsis, contributing to immunosuppression by 
loss of lymphocytes. Apoptosis also appears to be 
under the control of complex intracellular signalling 
processes. 



CLINICALLY APPARENT SYSTEMIC 
EFFECTS OF THE RESPONSE 



'y'S&^.Mutf^i 



S>:-^T^^^;^;i: 



Body temperature 

Following correction of any intraoperative hypothermia 
in the immediate postoperative period, there is often a 
1-2°C increase in body temperature because the increased 
metabolic rate is accompanied by an upward shift in the 
thermoregulatory set point of the hypothalamus. Pyrexia 
can be difficult to interpret when infection is suspected or 
already present. Some of the effects of fever are detri- 
mental, but more are beneficial. 



317 



31 




POSTOPERATIVE 



Cardiovascular system 

A mild tachycardia is commonly seen, along with peri- 
pheral vasodilatation. Cardiac output can rise at least 
threefold provided intravascular volume is maintained. 
Hypovolaemia due to blood and other fluid losses can 
exaggerate the tachycardia and lead to hypotension 
and peripheral shutdown, indicating inadequate fluid 
replacement. The acute phase response of vasomotor 
changes and increased vessel permeability causes fluid 
loss into the 'third space', the name for a sequestered part 
of the extracellular fluid (ECF) which includes oedema 
fluid in the peripheral tissues, wound, peritoneal cavity 
or the lungs. 

Pulmonary effects 

Reduction in forced vital capacity and functional residual 
capacity lead to shunting of blood and a decreasing Pa0 2 
after major surgery. Hypoxaemia is more pronounced and 
prolonged after upper abdominal surgery. The changes 
are significantly lessened by laparoscopic compared with 
open operation and by good quality pain relief. If secre- 
tions obstruct bronchioles, basal collapse can progress to 
pneumonia after any operation, particularly in immobile 
patients recumbent in bed. Tachypnoea leads to a respir- 
atory alkalosis and a fall in Paco 2 . 

Acute lung injury is the inflammatory reaction due to 
pulmonary capillary endothelial damage and fluid leak into 
the alveoli and interstitium. This 'non-cardiogenic pul- 
monary oedema' leads to hypoxaemia due to ventilation- 
perfusion inequalities (i.e. shunt). This can be a component 
of systemic inflammation or directly triggered by specific 
factors, e.g. blood transfusion. There is a spectrum of sever- 
ity, with the most extensive, acute respiratory distress syn- 
drome (ARDS), leading to severe respiratory failure and 
widespread infiltrates on X-ray. The changes improve with 
resolution of the underlying inflammation but overall 
survival in ARDS is at best 60-70%. 



Effects on the gastrointestinal tract 

• Adynamic ileus. There is inhibition of gastric emptying 
and reduced colonic motility from increased sympa- 
thetic tone and the effects of opioid analgesics. Small 
intestine peristalsis is minimally affected. Usually, ady- 
namic (Greek a - not + dyasthai = to be able) ileus is 
transient and enteral intake can restart early in the post- 
operative period. 

• Gut mucosal barrier. Increased permeability is thought 
to allow translocation of bacterial toxins into the circu- 
lation, leading to escalation of the inflammatory 
response. It is still unclear whether this is a primary 
cause or secondary response. 



Biochemical and fluid balance disturbance 

1. Salt and water retention. This results from the miner- 
alocorticoid effects of both aldosterone and Cortisol. This 
is compounded by raised levels of AVP, further hindering 
excretion of free water and resulting in lower volumes of 
high osmolality urine. Any reduction in renal perfusion 
from hypotension secondary to hypovolaemia or from the 
administration of non-steroidal anti-inflammatory drugs 
also worsens oliguria and can lead to acute renal failure. 
Although the maintenance of intravascular volume by 
administered intravenous fluids offsets these effects, 
weight gain of several kilograms from retained fluid can 
be seen. A major but uncomplicated surgical operation 
with adequate fluid replacement is, therefore, usually fol- 
lowed by 24 h of impaired free water clearance and about 
5 days of impaired sodium excretion. This can be more 
pronounced in the presence of systemic inflammation 
where "third space' losses are greater (see Cardiovascular 
system above). The diuresis that occurs when this third 
space fluid mobilizes is a welcome sign of recovery. 

2. Hyponatraemia. This often accompanies the above 
changes, partly a dilutional effect from retained water 
(due to AVP), and partly because sodium drifts into cells 
(impaired sodium pump); it does not indicate sodium 
deficiency, as it occurs at a time when the total body 
sodium is elevated. Serum potassium may rise due to cell 
death, liberation of potassium by protein catabolism and 
from impaired potassium excretion. However, it is more 
usual to see increased urine potassium excretion, which 
can lead to an overall potassium deficit. 

3. Acid-base abnormalities. The commonest change is a 
metabolic alkalosis because intense reabsorption of 
sodium in the distal tubules of the kidney is accompanied 
by excretion of potassium and hydrogen ions; this impairs 
oxygen delivery to the tissues because it affects the 
oxygen-haemoglobin dissociation curve. In more severe 
injuries a metabolic acidosis supervenes due to poor 
tissue perfusion and anaerobic metabolism with accumu- 
lation of lactic acid. Acidosis may decrease myocardial 
contractility and produce arrhythmias, as well as decreas- 
ing the effect of catecholamines on the myocardium and 
peripheral vessels. Respiratory compensation with 
tachypnoea and reduced PaC0 2 then occurs. 



Metabolism after injury 

1. There is an initial 'ebb' phase (Fig. 31.1) of reduced 
energy expenditure after injury for up to 24 h. This 
changes to a catabolic 'flow' phase with increased 
metabolism, negative nitrogen balance, hyperglycaemia, 
increased heat production, increased oxygen consump- 
tion and lean bodyweight loss. The increase in metabolic 
rate ranges from about 10% in elective surgical operations 



318 



THE BODY'S RESPONSE TO SURGERY 



31 



EBB PHASE 



FLOW PHASE 





Catabolic Anabolic 





Injury 










T 






^^^^^^ 


o 










E 












1 


L 1 


1 1 1 


1 1 1 1 



Days 
Fig. 31.1 Change in metabolic rate relative to preoperative level. 



to 50% in multiple trauma and 200% in major burns. This 
may last for days or weeks, depending on the severity of 
the injury, previous health of the individual and medical 
intervention; it is less marked at the extremes of age or 
in previously malnourished individuals. Once started, 
it cannot be stopped rapidly by controlling infection, 
correcting hypovolaemia or blocking pain. If recovery 
occurs, it is followed by an anabolic phase in which 
weight gain is accompanied by restoration of protein and 
fat stores. This process is slow and prolonged. 

2. Lipids are the principal source of energy following 
trauma. Lipolysis is produced mainly by catecholamines 
and increased sympathetic nervous system activity and 
also by lower plasma insulin, a rise in ACTH, Cortisol, 
glucagon, growth hormone and, probably, cytokines. 
Ketones are released into the circulation and are oxidized 
by all tissue except the blood cells and the CNS. Free fatty 
acids provide energy for all tissues and for hepatic 
gluconeogenesis. 

3. Carbohydrates. Hyperglycaemia occurs immedi- 
ately after injury because glucose is mobilized from 
stored glycogen in the liver by catecholamines and glu- 
cocorticoids, and because insulin resistance of peripheral 
tissues impairs their uptake of glucose (the 'diabetes of 
injury'). Glucose provides energy for obligate tissue such 
as the CNS, leucocytes in the wound and red cells (cells 
not requiring insulin for glucose transport). In major 
injuries the inflammatory cell infiltrate can account for 
70% of glucose uptake. 



4. Body glycogen stores can only maintain blood 
glucose for about 24 h. Subsequently it is maintained by 
gluconeogenesis, stimulated by corticosteroids and 
glucagon, and this is helped by the initially suppressed 
insulin levels encouraging the release of amino acids from 
muscle. Even when insulin levels rise, they do not sup- 
press this increased hepatic gluconeogenesis because it is 
required for clearance of lactate and amino acids that are 
not used for protein synthesis. 

5. Amino acids, protein and skeletal muscle. Shortly 
after injury skeletal muscle protein breakdown supplies 
the three- to fourfold increased demand for amino acids 
(unless there is an exogenous protein source); this 
reaches a peak after 1 week and may continue for several 
weeks. The nitrogen loss is proportional to the severity 
of the trauma, the extent of sepsis and the muscle bulk 
(so it is greatest in fit young males). The mobilized 
amino acids are used for gluconeogenesis, oxidation in 
the liver and other tissues, and synthesis of APRs. 
Glutamine is a major energy source for the gastroin- 
testinal tract, for lymphocytes and for fibroblasts during 
catabolism, and may become an 'essential' amino acid at 
this time. The negative nitrogen balance and skeletal 
muscle breakdown can be offset but not reversed by 
nutritional support. The catabolic phase is followed by 
an anabolic phase produced by growth hormone, andro- 
gens and 17-keto steroids. 

6. Other reasons for skeletal muscle loss include rhab- 
domyolysis in trauma and limb ischaemia, disuse 



319 



31 




POSTOPERATIVE 



atrophy from prolonged immobility and denervation 
from the polyneuropathy of critical illness. These factors 
can all produce weakness which requires prolonged 
rehabilitation. 



Haematological changes 

Serum albumin falls after trauma because production by 
the liver decreases, and loss into damaged tissue increases 
due to the action of cytokines and prostaglandins on 
vessel permeability. The accompanying shift of fluid out 
of the intravascular compartment is a contributing cause 
of dysfunction in various organs. 

The coagulation cascade and platelet activation leads to 
a state of hypercoagulability that may be beneficial at the 
site of injury but increases the risk of venous thrombi 
forming. If coagulation is triggered away from the 
wound, for example by sepsis or hypoxic damage to 
endothelial cells, then disseminated intravascular coagu- 
lation can result. 

Leucocytosis occurs; it appears to be due mainly to 
cytokine-stimulated release of neutrophils from bone 
marrow. 



Immunological responses 

Trauma leads to impairment of the immune system, with 
defects in cell-mediated immunity, antigen presentation, 
neutrophil and macrophage function complement acti- 
vation and bacterial opsonization. This occurs at a time 
when the initial injury has usually breached mechanical 
defences, when catabolism impairs the mucosal barrier in 
the bowel and when many factors contribute to produce 
pneumonia and other infections. 

Wound healing 

The systemic responses give 'biological priority' to 
wound healing, but a wound still heals more slowly if 
there are other major injuries. 

Systemic inflammatory response syndrome 
(SIRS) 

This is defined by set criteria of fever, tachycardia, 
tachypnoea and leucocytosis. This cluster of clinical fea- 
tures is seen in a range of conditions where inflammation 
is present. These include those where infection is the 
cause, e.g. appendicitis, as well as those which can mimic 
sepsis but where infection is absent, e.g. pancreatitis or 
blunt trauma. SIRS features are often present in the post- 
operative surgical patient and reflect the extent of activa- 
tion of the inflammatory cascades. 



Multiple organ dysfunction syndrome 

In some patients the inflammatory response may become 
so amplified that shock supervenes and support of failing 
organs is required. There may then be an irreversible pro- 
gression to multiple organ failure and death. In this situ- 
ation, inflammatory damage appears to be excessive and 
uncontrolled and not amenable to treatment. The clinical 
picture is the same as that in septic shock, even though 
infection is absent. 

There is some evidence that an initial inflammatory 
stimulus, such as infection, trauma or surgery, 'primes' 
the cellular control of inflammation and that a second 
stimulus, e.g. sepsis, triggers an overwhelming response 
(two-hit theory). This may be linked to intracellular pro- 
cesses such as apoptosis. 



WAYS OF AFFECTING THE RESPONSE 



£^i>*w$^i^^ 



^^^^^^^^^f^^^^^;!/^^/^ 



Although the local response to trauma is beneficial, the 
systemic response becomes less helpful as the degree of 
trauma increases, and in a hospital setting it is an advan- 
tage to suppress and control the response. In trauma and 
emergency surgery, pain, bleeding with hypovolemia, 
hypoxia and anxiety have often been present for some 
hours before operation starts, whereas in elective surgery 
it is usually possible to control these stimuli and thereby 
reduce the systemic response. 

Recent studies demonstrate that preoperative opti- 
mization of the circulation by the use of fluid loading and 
inotropes to increase cardiac output and oxygen delivery 
can improve the outcome of major surgery. 

Beta blockers given through the perioperative period 
confer cardiac protection in vulnerable patients. There 
appears to be a prolonged survival advantage well 
beyond the duration of administration. 




Reduce stimuli causing the response 



Less trauma 

- care in handling tissues 

- minimally invasive surgery. 
Control of infection 

- remove source of toxins 

- debride wounds and drain pus 

- antibiotics (selective gut decontamination 
with antibiotic combinations is still being 
investigated). 

Nutritional support 

- enteral feeding to maintain the gut mucosal 
barrier integrity 



320 



THE BODY'S RESPONSE TO SURGERY 



31 



- 'immunonutrition' with added glutamine, 
arginine and omega-3 fatty acids may be of 
some additional benefit when delivered 
early. 

• Control of pain 

- analgesics, local and regional blockade 
(given, if feasible, before the noxious stimuli 
occur). 

• Correct hypovolaemia 

- prompt replacement of fluids and 
electrolytes lost 

- transfusion for haemorrhage only if anaemic 
with Hb < 80 g I 1 in fit patients 

- colloid for plasma losses. 

• Correct metabolic alkalosis or metabolic 
acidosis. 

• Correct hypoxaemia 

- attention to airway, breathing and 
administration of oxygen. 

• Remove fear and stress 

- give explanations 

- administer analgesics or anxiolytics. 

Metabolic manipulation 

Protein administration to malnourished patients improves 
their immune function but has no immediate benefit on 
wound healing. Enteral feeding has particular benefits over 
the parenteral route because it helps to maintain the gut 
mucosal defence barrier. Increased intake of arginine 
(which improves weight gain, nitrogen balance, wound 
healing and immune function) and glutamine (which 
improves nitrogen balance and prevents the redistribution 
of body water) can be helpful. 

Drug administration 

Ways of manipulating the body's response to trauma are 
being sought but are still experimental. Many agents are 
only effective if given before the injury or sepsis occur, 
and it is difficult to block deleterious responses and still 
preserve beneficial ones. 

Steroids, antiendotoxin antibodies, anti-TNF anti- 
bodies, IL-1 receptor antagonists and specific PAF recep- 
tor antagonists have increased survival in septic animals 
but have been disappointingly ineffective in humans. A 
recent study involving activated protein C in septic shock 
appears more promising; however, as bleeding tendency 
is increased it may not be suitable for septic patients 



undergoing surgery. Other agents that have been used 
are adrenergic blockers (decrease the metabolic rate), 
aspirin (attenuates cytokine actions), growth hormone 
and anabolic steroids (stimulate protein synthesis), 
mannitol (hydroxyl radical scavenger), propranolol 
(improves postoperative nitrogen balance), allopurinol 
(inhibits free radical formation) and atrial natriuretic 
factor (natriuretic). 



Summary 

• Do you appreciate that multiple factors in 
the underlying disease, comorbidity, and 
the effects of the trauma of a surgical 
operation cause widespread effects in the 
body? 

• Are you aware of the wide range of 
clinically detectable effects? 

• Are you aware of your potential to reduce 
the stimuli, including trauma, in order to 
alleviate the effects of surgery? 



Further reading 

Beal AL, Cerra FB 1994 Multiple organ failure syndrome in the 

1 990s. JAMA 271 (3): 226-233 
Davies MG, Hagen PO 1997 Systemic inflammatory response 

syndrome. British Journal of Surgery 84: 920-935 
Hill AG, Hill GL 1998 Metabolic response to severe injury. 

British Journal of Surgery 85: 884-890 
Holte K, Kehlet H 2000 Post-operative ileus: a preventable 

event. British Journal of Surgery 87: 1480 -1493 
Huljamae H 1993 The pathophysiology of shock. Acta 

Anaesthesiologica Scandinavica 37(suppl. 98): 3-6 
Le Quesne LP, Cochrane JPS, Fieldman NR 1985 Fluid and 

electrolyte disturbances after trauma: the role of 

adrenocortical and pituitary hormones. British Medical 

Bulletin 41(3): 212-217 
Mainous MR, Block EFJ, Deitch EA 1994 Nutritional support of 

the gut: how and why. New Horizons 2(2): 193-201 
Molloy RG et al 1 993 Cytokines, sepsis and 

immunomodulation. British Journal of Surgery 80(3): 289-297 
Schmidt H, Martindale R 2001 The gastrointestinal tract in 

critical illness. Current Opinion in Clinical Nutrition and 

Metabolic Care 4(6): 547-551 
Senftleben U, Karin M 2002 The IKK/NF-kB pathway. Critical 

Care Medicine 30(1) (SuppL): S18-S26 
Treasure T, Bennett D 1999 Reducing the risk of major elective 

surgery. BMJ 318: 1087-1088 
Woolf PD 1992 Hormonal responses to trauma. Critical Care 

Medicine 2(2): 216-226 



321 




Wound healing 

5. R. Lakhani, A. Dogan 



w 



Objectives 



Understand the stages of wound healing. 

Understand the mechanism of wound 

contracture, its usefulness and its 

complications. 

Recognize the factors that affect wound 

healing. 

Be familiar with complications that may 

arise as a result of healing and repair. 



INTRODUCTION 



>v&Z^k&Ff'&;$k>i$& 



The processes involved in wound healing are some of the 
most fascinating biological phenomena you are likely to 
encounter. In this chapter we shall examine the processes 
involved/ and hopefully appreciate the complex interplay 
that allows the body to restore the integrity of its tissues. 
As a surgeon, you rely on the normal functioning of these 
processes on a daily basis. 

Three fundamental things must happen if wound 
healing is to occur. First, the circulatory system must be 
able to control the bleeding (establish haemostasis; Greek 
haima - blood + statikos = causing to stand). Second, the 
inflammatory response must be effective and provide a 
defence against microbial infection as well as provide the 
necessary chemical environment for attracting and stimu- 
lating the cells needed for repair. Finally, the process of 
repair requires many different cell types to proliferate and 
to synthesize proteins necessary for restoring integrity 
and strength to the tissue. Although these three basic pro- 
cesses must occur in the healing of all wounds, you will 
be aware that not all your patients behave in exactly the 
same way. The process described above may be modified 
considerably by the size of the wound, the nutritional 
status of the patient, and hence his or her immune com- 
petence, the state of the vasculature at the site of injury, 
and the metabolic demands of the tissue that has been 
injured. It is not any one thing, but rather a complex and 



dynamic interplay between many factors within an intri- 
cate network, that determines the final outcome. 




Wound healing requires: 

• Haemostasis 

• Inflammation 

• Cell proliferation and repair. 



THE PROCESS OF WOUND HEALING 



^i^^^c^^ 



i^^-^^^m^j^ 



The biological objectives of wound healing are twofold: 

• To restore the integrity of epithelial surfaces if they have 
been lost, and hence protect the underlying tissues 
against infections and insults from the environment 

• To restore the tensile strength of the subepithelial tissue. 

Healing by 'primary' and 'secondary' intention 

Although the basic mechanisms involved in wound 
healing are the same, by convention the healing of cleanly 
incised wounds, where the edges are in close apposition, 
is considered separately from those in which there is 
extensive loss of epithelium, a large subepithelial tissue 
defect that has to be filled in by scar tissue and where the 
edges cannot be brought together with sutures. These two 
circumstances are described as 'healing by primary inten- 
tion" or 'healing by secondary intention'. These terms 
first appeared in a surgical treatise published in 1543, 
although Thomson (1813) in Lectures on Inflammation, 
gives the credit for introducing these terms to Galen. 



THE HEALING OF AN INCISED 
WOUND: 'HEALING BY PRIMARY 
INTENTION' 



?&&!&^^&&W&V&^& 



Incision involves the division of: 

• Epidermis 

• Dermal connective tissue fibres and matrix 



322 



WOUND HEALING 




32 



• Subcutaneous tissue 

• Blood vessels. 

The very first thing that must be established is haemosta- 
sis. Severing of blood vessels obviously leads to haemor- 
rhage, with the resulting accumulation of blood within the 
tissue defect. Injury to blood vessels leads to arteriolar con- 
traction, which helps to reduce the bleeding. Platelets and 
plasma proteins, particularly fi brinogen and fibronectin, also 
accumulate. Clotting occurs by both the 'intrinsic' and 
'extrinsic' pathways. The former is due to exposure of the 
collagen and the latter due to release of 'tissue factors 7 
from damaged cells. The platelet plug becomes converted 
to a clot consisting of polymerized fibrin, which is stabi- 
lized by fibronectin binding to it by means of a gluta- 
minase bridge. 'Fibronectin' (Latin nectere = to bind, tie) is 
the term used for a set of large, extracellular matrix glyco- 
proteins, and the gel formed by fibrin and fibronectin acts 
in the early stages of healing as a 'glue' which helps to 
keep the severed edges of the tissue apposed. Thrombin, 
which is involved in the generation of fibrin, also attracts 
macrophages and induces fibroblasts to divide. So here we 
have a molecule that not only has a role in haemostasis but 
also begins the process of repair. Platelet-derived growth 
factor (PDGF) released from degranulating platelets has a 
similar effect on fibroblasts. Transforming growth factor p 
and monocyte chemoattractant protein 1 are also respon- 
sible for pulling macrophages into the area, which in turn 
can release PDGF. 

At the same time as haemostasis is being established, 
the process of inflammation is also kicking into action. 
This involves dilatation of capillaries and the formation of 
a fluid and cellular exudate. The polymorph leucocytes 
will attack and remove any bacteria and also scavenge 
any tissue debris from the cell death. The exudate is 
responsible for the tissue swelling that occurs. This not 
only splints and immobilizes the affected area but also the 
network of fibrin within the exudate forms an infrastruc- 
ture that helps to localize the microorganisms, hence 
allowing the polymorphs easy access to them. As men- 
tioned above, one of the biological objectives is to protect 
the tissues from infectious and environmental hazards 
and the exudate performs exactly this task by clotting and 
forming a scab over the wound. 

The next important stage is one of cell proliferation and 
migration. Purely for convenience, the events are divided 
into those involving the epidermis and those involving 
the dermis. 



Epidermal events 

Within a few hours of wounding, a single layer of epi- 
dermal cells start to migrate from the wound edges to 
form a delicate covering over the raw area exposed by the 



loss of epidermis. This is a fascinating process. The epi- 
dermal cells have to undergo a phenotypic change that 
will allow them to detach from each other, from the base- 
ment membrane and hence dermal cells, and acquire 
properties that help them to move into the wound space. 
This is achieved by loss of intracellular tonofilaments, loss 
of desmosomes and formation of actin filaments, which 
allows cell movement. The cells express a family of inte- 
grin receptors that allows them to interact with extracellu- 
lar proteins, in particular fibronectin and vitronectin. 
Epidermal cell migration across the area of epithelial loss 
depends on interaction between the keratinocytes at or 
near the wound edges, fibrin and fibronectin. Fibronectins 
are present both within plasma and within tissues. 
Originally they were thought to be cell surface proteins 
but it is now realized that they constitute part of the extra- 
cellular matrix and exert much of their effect by provid- 
ing sites which act as ligands for receptors on a wide 
variety of cell types. This ligand-receptor binding medi- 
ates cell matrix adhesion. Keratinocytes from normal, 
unwounded skin do not possess receptors which bind to 
fibronectin, being tightly attached to basement mem- 
brane, which contains laminin and collagen type IV. 
Those derived from wounds, however, express a 
fibronectin receptor which is very similar to a fibronectin 
receptor expressed on fibroblasts. The cells migrate at a 
rate of approximately two cell diameters per hour. 




Key point 



• Recognize that static, adherent, epithelial cells 
have detached themselves and moved, like 
amoebae, to cover the wound. 

Epidermal cell movement can provide an initial cover- 
ing for very small wounds, but in most instances epi- 
thelial recovering cannot be accomplished without 
proliferation of epidermal cells. The new cells are derived 
from the stem cell compartment of the epidermis. From 
about 12 h after wounding, there is a marked increase in 
mitotic activity in the basal cells about 3-5 cells from the 
cut edges. The exact biological mechanisms that lead to 
this proliferation are still unclear, although release of 
growth factors and expression of growth factor receptors 
must play a role. Candidates include epidermal growth 
factor, transforming growth factor a and keratinocyte 
growth factor. The new epidermal cells grow under the 
surface fibrin /fibronectin clot and for a little distance 
down the gap between the cut edges to form a small 
'spur' of epithelium, which afterwards regresses. If the 
wound has been sutured, a similar downgrowth of new 
epidermis occurs in relation to the suture tracks and, on 



323 



32 



POSTOPERATIVE 



occasion, these may form the basis of keratin-forming 
cysts within the dermis - so-called 'implantation dermoid 
cysts'. This ability of epidermal cells to grow along tracts 
created by sutures or other foreign material is of course 
the basis for piercing of tissues for ear-rings, nose-rings, 
etc. Once re-epithelialization is complete, basement pro- 
teins will reappear and the epithelial cells revert to their 
normal non-migratory phenotype. 



vascularized gel in which both inflammatory cells and 
collagen-producing fibroblasts are present is known as 
granulation tissue. The term, coined by the great German 
pathologist Rudolf Virchow (1821-1902), is derived from 
the observation that the raw surface of a wound shows a 
granular appearance rather like that seen on the surface 
of a strawberry. Each of these 'granules' contains a loop 
of capillaries and hence bleeds easily if traumatized. 



Dermal events 

After the initial arrival of neutrophils to the site of injury, 
there is recruitment of macrophages into the area (1-2 days 
after wounding). This is a key event because it is these 
cells that orchestrate the complex interplay of chemical 
signs that now takes place. The macrophages are involved 
in: 

• Demolition and removal of any inflammatory exudate 
and tissue debris. 

• Restoring the tensile strength of the subepithelial con- 
nective tissue. This is accomplished by: (1) secretion of 
chemoattractants, which recruits cells that synthesize 
and secrete collagen and other connective tissue pro- 
teins (i.e. fibroblasts); (2) expansion of the existing 
small fibroblast population by stimulating the cells to 
proliferate; and (3) stimulation of these new fibroblasts 
to secrete extracellular connective tissue proteins. 

• The ingrowth of new small blood vessels (angiogene- 
sis) into the area undergoing repair; this is thought to 
be due to the secretion of vascular endothelial growth 
factor (3, angiogenin, angiotropin, TNF-et (tumour 
necrosis factor), hypoxia and accumulation of lactate 
that occurs in anoxic tissues. The angiogenesis 
involves: (1) budding of new endothelial cells from 
small intact blood vessels at the edges of the wound; 
and (2) chemoattraction of these new endothelial cells 
into the fibrin /fibronectin gel within the wounded 
area. 

In a surgical wound, fibroblasts and myofibroblasts 
appear in the wound between 2 and 4 days after wound- 
ing, and endothelial cells follow about 1 day later. The 
infiltration of macrophages and fibroblast proliferation 
are followed/ as stated above, by the ingrowth of new 
capillary buds, which are derived from intact dermal 
vessels at the margins of the wound. Initially these buds 
consist of solid ingrowths of endothelial cells, but they 
soon acquire a lumen. An essential starting step for the 
ingrowth of new vessels is local degradation of the base- 
ment membrane of the existing capillary, this local defect 
permitting the budding of new endothelial cells. At this 
stage newly formed capillaries have little basement 
membrane substance and, compared with a normal ca- 
pillary, are extremely leaky. This combination of a richly 



Mi 



Key point 



• Granulation tissue formation is common to all 
forms of repair. 

The ultimate development of tensile strength in a wound 
depends on the production of adequate amounts of 
collagen and on the final orientation of that collagen. 
Collagen is the only protein that contains large amounts 
of the amino acids hydroxyproline and hydroxylysine. 
Within 24 h of wounding, protein-bound hydroxyproline 
appears within the damaged area, and within 2-3 days 
some fibrillar material may be seen, although at this time 
it lacks the dimensions and the typical 64 nm banding of 
polymerized collagen. Within a few weeks, the amount of 
collagen in the wounded area is normal, although pre- 
operative tensile strength is not regained for some 
months. This suggests that replacement and remodelling 
of the collagen formed early in wound healing is an 
important part of the whole process. The final result is a 
scar composed of collagen fibres and very few cells or 
vessels. The scar therefore changes from pink to white, 
but this may take many months to occur. It will be appar- 
ent that abnormal regulation of this process is responsi- 
ble for development of keloid scars. 



HEALING OF WOUNDS ASSOCIATED 
WITH A LARGE TISSUE DEFECT: 
'HEALING BY SECONDARY 
INTENTION' 



1 ■> , ---1. *■ _ ' ^ I =, i _^ ■■"• - ■*•-> _» - i 






A large volume of tissue loss can occur in cases of severe 
trauma or extensive burns, or, much less frequently, in 
relation to certain surgical procedures. Although qualita- 
tively there are few differences between healing of an 
incised wound and healing of larger wounds, the most 
significant problem relates to filling the large defect. 
Clearly the formation of granulation tissue, and ulti- 
mately of scar tissue, occurs, albeit on a far larger scale. 
One feature, however, that helps to speed up the healing 
process, and which is not seen in relation to healing of 
incised wounds, is wound contraction. 



324 



WOUND HEALING 




32 



Wound contraction 

Two or three days after the formation of large open 
wounds, the area of raw tissue starts to decrease. This is the 
expression of a real movement of the wound margins and 
is quite independent of the rate at which covering by a new 
epithelial layer can take place. In some fur-bearing animals 
the raw area may decrease in size by as much as 80% in 
2 weeks, and sometimes the degree of contraction may be 
so great as virtually to close the wound. The wound con- 
traction occurs at a time when relatively little new collagen 
is being formed in the dermis and subcutaneous tissue, and 
it therefore seems unlikely that shortening of collagen fibres 
at the wound margins is responsible for the contraction. 
Indeed, inhibition of collagen formation does not interfere 
with the process of wound contraction. There appear to be 
two mechanisms by which wounds contract. Initially, the 
scab formed from coagulated exudate containing fibrin 
contracts. Later, contraction is brought about by the action 
of cells which appear at the margins of the wound in the 
first few days and which, on electron microscopy, show fea- 
tures suggesting both fibroblast and smooth muscle differ- 
entiation. These cells are called myofibroblasts. The cells 
contain actin, but no smooth muscle-type myosin within 
their cytoplasm. For a pulling force to be exerted there must 
be a connection between the object being pulled and what- 
ever is applying the force. In wound contraction the con- 
nection is provided by nbronectin molecules which form 
bridges between collagen fibres on the one hand and recep- 
tors on the myofibroblasts on the other. Thus strips of 
granulation tissue from healing wounds can be made to 
shorten in vitro by any pharmacological agents that cause 
actin fibrils to contract. In vivo, it appears that transform- 
ing growth factors pi and [32 may play a role. It has been 
postulated that a similar mechanism is responsible for the 
contracture of dermal connective tissue seen in such con- 
ditions as Dupuytren's contracture. 




Key point 



• Wound contraction takes place before a 
significant amount of collagen has been laid 
down or matured, to contribute to it. 

Growth factors and cytokines in wound 
healing 

It is clear from what has been said in the previous sections 
that the cellular events in wound healing must depend on 
a series of 'instructions' which: 

• Facilitate migration of fibroblasts and endothelial cells 

• Induce these cells, as well as the epithelial cells, to 
proliferate. 



These instructions consist of a set of chemical signals 
derived from a number of sources. They fall into two 
principal types: growth factors and cytokines. 



Growth factors 

Growth factors are peptides which act via one or more of 
three pathways: 

• The endocrine pathway, where the growth factors are 
synthesized at some considerable distance from their 
targets and are delivered via the bloodstream 

• The paracrine pathway, where the growth factors are 
synthesized and released by cells which are in close 
proximity to their targets 

• The autocrine pathway, in which the same cells both 
synthesize and stimulate their own growth. 

The growth factors important in wound healing include 
platelet-derived growth factor, epidermal growth factor 
and transforming growth factors a and |3. We will con- 
sider these briefly 

1. Platelet-derived growth factor. Platelet-derived growth 
factor is a basic protein which has a molecular weight of 
about 30 000. It consists of two peptides (an A chain and a 
B chain) which are bound by disulphide bridges. The 
name 'platelet-derived growth factor' is somewhat mis- 
leading in two senses. First, while it is certainly stored in 
the a granules of platelets and released from them when 
the platelets are activated, the growth factor is also syn- 
thesized and secreted from other cells. These include 
endothelial cells, macrophages, arterial smooth muscle 
cells and cells from certain tumours. Secondly, PDGF has 
a number of functions apart from its undoubted powerful 
mitogenic effect. It is chemotactic for the same cells for 
which it is a mitogen; it increases intracellular synthesis of 
cholesterol; and also increases binding of low density 
lipoprotein (LDL) by increasing the number of LDL recep- 
tors expressed on the plasma membrane of the target cell. 
It increases prostaglandin secretion, initially by making 
more of the starting material (arachidonic acid) available, 
and later by stimulating the synthesis of cyclooxygenase. 
It is able to induce changes in cell shape by a reorganiza- 
tion of actin filaments within the cells and it induces 
increased synthesis of RNA and protein. It is also a potent 
vasoconstrictor. Thus PDGF can carry out both tasks that 
were outlined at the beginning of this section. It can attract 
mesenchymal cells into the wound (with the exception of 
endothelial cells which do not possess the PDGF receptor) 
and it acts as a mitogen and stimulator of protein produc- 
tion. PDGF and other growth factors bind to receptors 
which, after ligand-receptor interaction, act as tyrosine 
kinases and hence activate the signal transduction path- 
ways for mitogenesis. 



325 




POSTOPERATIVE 



2. Epidermal growth factor and transforming growth 
factor a. Epidermal growth factor (EGF) is a 53 amino acid 
polypeptide which is cleaved from a larger precursor 
protein. It was discovered by the Nobel laureate Cohen in 
the course of experiments in which he was engaged in a 
search for a nerve growth stimulating factor in the 
salivary glands of baby mice, such a factor having been 
discovered previously in the salivary glands of snakes. 
However, extracts of these glands, when injected into 
baby mice, caused their eyes to open prematurely and 
their incisor teeth to grow faster, these effects being due 
to a stimulation of epidermally derived tissues. The factor 
was purified and is now known as epidermal growth factor, 
although it stimulates mitogenesis in connective tissue as 
well as in epithelial cells. The salivary glands and the 
lacrimal glands are storage sites for EGF, which can be 
released in saliva and tears. Thus, licking one's wounds 
in the literal rather than in the metaphorical sense may be 
of definite biological advantage, as may be the irrigation 
of the cornea by tears in corneal abrasion or ulceration. 
EGF, or a molecule with considerable homology, is also 
produced in the Brunner's glands in the duodenum, and 
its metabolite, urogastrone, may be measured in the urine. 
In rodents, EGF may be found in the plasma but in 
humans, blood-borne EGF is concentrated within the a 
granules of platelets. Since EGF protein can also be found 
in the cytoplasm of megakaryocytes in the bone marrow, 
it seems almost certain that platelet EGF is derived from 
synthesis within the megakaryocytes rather than by 
uptake from the plasma. In experimental wounds the 
application of EGF has been found to significantly accel- 
erate the rate of epidermal regeneration and it has also 
been shown to have a beneficial effect on the dermal com- 
ponent. In humans, topical application of EGF accelerates 
the healing of donor sites for skin grafts. There is no evi- 
dence that EGF is produced by any of the cells taking part 
in the healing process, although, as already stated, 
platelets store EGF. However, there is another factor, 
known as transforming growth factor a (TGF-a), which 
shows a considerable degree of homology with EGF and 
which can be produced by both epidermal cells and by 
macrophages in healing wounds. TGF-a binds to the 
same receptor on target cells as does EGF and has the 
same mitogenic effect. In this way TGF-a may be a direct 
mediator of wound healing. 

3. Transforming growth factor j8. Transforming growth 
factor p (TGF-fJ) is a polypeptide, first discovered in 
culture media conditioned by transformed cells, but pro- 
duced by almost all cell lines in culture. In the presence 
of EGF it acts as a mitogen, but in some assays it has also 
been found to inhibit growth. It is possible that these con- 
tradictory actions may be a reflection of the different 
types of assay used and may not tell us much about what 
is happening in vivo. There is, however, good evidence 



that macrophages in healing wounds express mRNA for 
TGF-fJ as well as for TGF-ct. TGF-J3 has also been shown 
to be a powerful chemoattractant for monocytes and its 
release from the first wave of inflammatory cells migrat- 
ing into the wound may act as a mechanism for recruit- 
ing additional monocytes/macrophages. Studies from 
fetal wound healing suggest that TGF-pl may be an 
important cytokine in scar formation. Fetal skin has very 
low levels of TGF-fJl and fetal wounds are able to heal 
without scarring. In animal models, antibodies to TGF-(31 
and p2 are also able to reduce scarring. 



Cytokines 

'Cytokine' (Greek kytos = vessel, cell + kineein - to move) 
is the term used for a group of protein cell regulators that 
includes such members as lymphokines, monokines, 
interleukins and interferons. These are low molecular 
weight proteins (usually less than 80 kDa). They tend to 
be produced rapidly and locally and can act in either an 
autocrine or a paracrine fashion. They are produced by a 
wide range of cells and have many overlapping actions 
which are mediated by their binding to high affinity 
receptors on their target cells. The response of an indi- 
vidual cell to a given cytokine is dependent on the cell 
type, what other chemical signals are being received at 
the same time, and the local concentration of the cytokine. 
Two cytokines which play a significant role in wound 
healing are interleukin 1 (IL-1) and tumour necrosis factor 
a (TNF-a) (syn. cachectin). 

1. IL-1 (formerly known as endogenous pyrogen) is a 
small (17 kDa) protein which is produced by a wide 
variety of cell types, including macrophages and epider- 
mal cells. IL-1 has many biological actions which, in rela- 
tion to healing, include a proliferative effect on dermal 
fibroblasts and upregulation of collagen synthesis by the 
fibroblasts. It also increases collagenase production and 
this may be one of the ways in which the collagen in 
wounds is remodelled so as to achieve maximal tensile 
strength. 

2. TNF-a is another monocyte /macrophage product 
which is released following tissue injury or infection. It is 
the main factor responsible for macrophage-mediated 
tumour cell killing and is also responsible for the wasting 
(cachexia) which is seen in certain chronic bacterial and 
parasitic infections. Its biological activity has a remark- 
able overlap with that of IL-1, although it does not appear 
to have the immunoregulatory functions of that molecule. 
Its receptors, however, are quite distinct from those of 
IL-1 and presumably the similarities in their actions indi- 
cate that they stimulate the same 'second messenger' 
systems. The expression of TNF-a by monocytes and 
macrophages requires activation of these cells. This may 



326 



WOUND HEALING 



32 



be brought about by interaction with fibrin (which is 
always present in wounds), binding of TGF-p, the action 
of a-interferon and the action of endotoxin. 

3. TNF-a is a potent stimulus for the ingrowth of new 
blood vessels in healing wounds, being not only chemo- 
tactic for endothelial cells but also the agent responsible 
for the focal degradation of capillary basement mem- 
branes which precedes the migration of endothelial cells 
into a healing wound. 

4. Both TNF-a and IL-1 play an important role in 
recruitment of inflammatory cells to the injury sites by 
regulating expression of adhesion molecules on the 
surface of endothelial cells. 




Important growth factors and 
cytokines in healing 

PDGF, EGF, TGF-a and TGF-p (which appears to 
have a role in scarring). 
IL-1 , TNF-a. 



REPAIR IN SOME SPECIALIZED 
TISSUES 

Bone 

The processes involved in the early stages of fracture 
healing are basically the same as those which have been 
described in the foregoing sections. Thus the tissue defect 
created by the fracture is, in the first instance, filled by 
granulation tissue similar to that in large open wounds. 
Later, more specific features peculiar to bone are imposed 
on the basic model of healing. These are necessary 
because bone, unlike soft tissues, has a mechanical and 
weight-bearing role. Two types of specialized cell play a 
central role: 

• The osteoblast, which lays down seams of uncalcified 
new bone (osteoid) 

* The osteoclast, a multinucleated cell, probably of 
macrophage lineage, which resorbs bone and which, 
therefore, remodels the new bone. 

Stages of fracture healing 

1 . When a bone is fractured, tearing of blood vessels 
leads to haemorrhage, hence the defect between the frac- 
tured ends of the bone becomes filled with blood clot and 
other plasma-derived proteins. As in any other tissue, the 
injury elicits an acute inflammatory reaction, although the 
degree of neutrophil infiltration is mild. The combined 
effect of the haemorrhage and the inflammatory oedema 
causes loosening of the periosteum from the underlying 



bone ends and this results in a fusiform swelling at the 
fracture site. Some degree of bone necrosis is almost 
inevitable and is due to the blood supply to some areas 
being cut off as a result of damage to blood vessels. It 
takes 24-48 h for the first morphological evidence of bone 
necrosis to become apparent, the marrow being the site of 
the first changes. Fat necrosis is seen and, if haemopoietic 
marrow is involved, the cells lose their nuclear staining. 
As far as the bony tissue itself is concerned, the extent 
of necrosis depends on the anatomy of the local blood 
supply, and some sites such as the talus, the carpal 
scaphoid and the head of the femur are particularly likely 
to show significant ischaemic necrosis after fracture. 
Empty lacunae, the dead osteocytes having disappeared, 
are a reliable indication of bone necrosis. Macrophages 
then invade the fracture site and commence the process of 
demolition. This is followed by the formation of granula- 
tion tissue, which also extends upwards and downwards 
within the marrow cavity for a considerable distance from 
the fracture site. Within the granulation tissue small 
groups of cartilage cells begin to differentiate from con- 
nective tissue stem cells. 

2. Provisional callus is the term used to describe a cuff 
of woven bone admixed with islands of cartilage which 
serves to unite the severed portions of bone on their exter- 
nal aspect but not across the gap between the bone ends. 
The origin of the callus is from two sources, and the rela- 
tive proportions of these vary depending on a number of 
factors. The first and more important is the periosteum. 
The cells on its inner aspects proliferate and begin to lay 
down woven bone (i.e. bone in which the collagenous 
osteoid tissue is not deposited in a lamellar or 'onion skin' 
fashion but in series of short bundles of parallel fibres, 
each bundle having a different orientation). Where the 
periosteum has been raised from the external surface of 
the bone, the new woven bone fills the gap so that there 
are two cuffs of new bone around the periosteal aspect 
of the separated fragments. These cuffs then extend 
upwards and downwards until they meet, although there 
is as yet no direct union across the gap between the sep- 
arated bone ends. The degree of efficiency with which the 
external callus formation occurs depends on the ade- 
quacy or otherwise of the blood supply around the frac- 
ture site. Some of the new blood vessels are derived from 
the periosteum itself, while others come from the muscle 
and other soft tissues which abut onto the fractured bone. 
The amount of cartilage admixed with this periosteal new 
bone is small in human fractures which are healing well, 
but tends to be greater in cases where the local blood 
supply is poor or where the fractured bone ends have not 
been properly immobilized. The second source of provi- 
sional callus is the medullary cavity, where, following 
the formation of granulation tissue, fibroblasts and 
osteoblasts start to proliferate and lay down bone matrix. 



327 



32 " 



POSTOPERATIVE 



Some of this is deposited on trabeculae of dead bone, 
while the remainder forms new trabeculae. Well after the 
provisional callus has been formed, the clot, which fills 
the gap between the fragments, is invaded, first by 
granulation tissue capillaries and then by osteoblasts. 
Ossification within this gap may occur as a primary event, 
the osteoblasts being derived from the provisional callus. 
In some cases the bone ends are united by fibrous tissue 
and over a period of time this is replaced by woven bone. 
This takes far longer than direct ossification and is more 
likely to occur if the fracture has not been properly immo- 
bilized or if there is any other factor present which is 
likely to inhibit healing (i.e. infection or extensive and 
severe periosteal damage). Occasionally the fibrous tissue 
filling the gap is not replaced by bone (non-union) and 
weight bearing by the affected limb is not possible. In 
cases of delayed or non-union some improvement may be 
brought about by electrical stimulation, which appears to 
accelerate ossification at fracture sites. Once union has 
occurred and the patient is bearing weight, the lumpy 
new cortical bone gradually becomes resorbed and 
smoothed out and the excess medullary new bone is simi- 
larly removed, with restoration of a normal medullary 
cavity. Woven bone, which is quite rapidly formed and 
which is much less efficient at weight bearing, is resorbed 
completely and is replaced by lamellar bone. This is a 
lengthy process of remodelling and restoration to normal 
may take up to a year. 

Nervous tissue 

Central nervous system 

Most neurons cannot be replaced once they have been 
lost, although there is some evidence to suggest that a 
limited degree of regeneration can take place in the 
hypothalamic-neurohypophyseal system. In contrast to 
the peripheral nerves, where injury is not associated with 
any marked tendency towards scarring, necrosis within 
the central nervous system elicits the proliferation of glial 
cells, which, together with the ingrowths of capillaries, 
may constitute a physical barrier to the regeneration of 
new neuronal fibres. Recent work using bone marrow- 
derived stem cells is challenging these concepts and this 
area is likely to see major advances in the next 5 years. 

Peripheral nerves 

When an axon is severed, the nerve cell shows chromato- 
lysis (i.e. it swells and the Nissl granules, which represent 
zones of the endoplasmic reticulum studded with many 
ribosomes, disappear). The axon swells and becomes ir- 
regular, and its Iipid-rich myelin sheath splits and later 
breaks up. The surrounding Schwann cells proliferate and 



accumulate some of the lipid released from the damaged 
myelin. Soon new neurofibrils start to sprout from the 
proximal end of the severed axon and these invaginate the 
Schwann cells, which act as a guide or template for the new 
fibrils. The neurofibrils push their way down through the 
Schwann cells at a rate of about 1 mm per day. Eventually 
they may reach the appropriate end organ and their myelin 
sheaths are reformed as a result of the secretory activity of 
the Schwann cells; in this way, a degree of functional recov- 
ery is attained. In some instances neurofibril sprouting 
takes place but the fibrils do not grow down existing 
endoneurial channels, and grow instead in a haphazard 
fashion. The end result may thus be a tangle of new nerve 
fibres embedded in a mass of scar tissue. This produces a 
'traumatic' or 'stump' neuroma. 



FACTORS AFFECTING WOUND 
HEAyNG 

Failure to heal satisfactorily can be the result of either 
systemic or local factors. 

Systemic factors 

Nutrition 

The state of nutrition of the patient is a potent factor in 
determining the success or failure of the healing process 
(see Ch. 10). Malnutrition causes depression of the 
immune system and hence wound infection, and the 
inflammatory response to this may delay healing. 
Deficient protein intake may inhibit collagen formation 
and so inhibit the regaining of tensile strength. In this 
regard, sulphur-containing amino acids such as methion- 
ine seem to be particularly important, and increasing the 
intake of this amino acid alone can partially offset the 
effects of a low protein intake on wound healing. Vitamin 
C has an important role in healing. It has been known 
since the seventeenth century that scurvy is associated 
with poor healing of wounds and fractures. Indeed, there 
are colourful descriptions of old wounds, acquired hon- 
ourably or otherwise in combat, breaking down after the 
onset of scurvy. Lack of vitamin C has been found to 
inhibit the secretion of collagen fibres by fibroblasts; this 
is due to a failure of hydroxylation of proline in the endo- 
plasmic reticulum of the fibroblast. In addition, vitamin C 
concentrations in biological fluids appear to affect the 
production of galactosamine and hence the deposition of 
chondroitin sulphate in the extracellular matrix of granu- 
lation tissue. Vitamin A has important functions in 
relation to morphogenesis, epithelial proliferation and 
epithelial differentiation, and the latter two are believed 
to be important in wound healing. A role for zinc in 



328 



WOUND HEALING 




2 



wound healing was discovered more or less by accident. 
In the course of a study on the effects of certain amino 
acids on wound healing, a phenylalanine analogue that 
had been expected to impair healing instead accelerated 
it. Careful study of this analogue revealed that the sample 
used had been contaminated by zinc. Further studies 
showed that zinc does indeed accelerate the healing of 
experimental wounds. Zinc deficiency such as is found in 
patients who have been on parenteral nutrition for long 
periods and in patients with severe burns, is associated 
with poor healing and this is reversed by the administra- 
tion of zinc. 

Steroid hormones 

Many studies show that glucocorticoids have an 
inhibitory effect on the healing process and on the pro- 
duction of fibrous tissue. Steroids are therefore adminis- 
tered in situations where inappropriate scarring is taking 
place, such as in interstitial fibrosis in the lung. It is still 
not clear whether steroids exert their effect indirectly by 
damping down the inflammatory process or whether they 
act directly on fibroblasts to alter collagen deposition. 

Local factors 

Presence of foreign bodies or infection 

The presence of infection or of a foreign body increases 
the intensity and prolongs the duration of the inflamma- 
tory response to injury. It is worth remembering that frag- 
ments of dead tissue, such as bone, and other elements of 
the patient's own tissues that have become misplaced, 
such as hair or keratin, act as foreign bodies. 

Excess mobility 

The oedema that occurs following tissue injury may lead 
to immobilization of that part, hence the fifth cardinal 
sign of inflammation: 'loss of function'. Although this can 
be troublesome, it also has the benefit of aiding the 
healing process. It will be clear to everyone that a frac- 
tured bone is not going to heal unless it is immobilized. 
Excess mobility in any tissue will impair healing and 
prolong the time to full recovery 

Vascuiar supply 

The degree of arterial perfusion and the efficacy of venous 
drainage play key roles in the healing of injured tissues. 
Where the arterial perfusion is compromised by stenosis 
or occlusion, a trivial injury may give rise to a dispropor- 
tionate degree of tissue damage and healing may be 
delayed or even completely inhibited. A good example is 



diabetes mellitus. In patients with longstanding disease, 
trivial injuries develop into chronic, non-healing ulcers. 
Blood vessel disease affecting both the large muscular 
arteries of the lower limb (atherosclerosis and its compli- 
cations) and changes in the walls of arterioles and capil- 
laries probably make the major contribution to failures of 
healing. These patients are of course also susceptible to 
infection (particularly if their diabetes is badly controlled) 
and may also have a sensory neuropathy which makes 
them more liable to sustain injuries to their extremities. 

Adequate venous drainage is also important, and 
impairment of this may play a part in the genesis of 
chronic ulcers, which often occur on the anterior surface 
of the legs in elderly patients. Histological examination of 
the margins of these lesions suggests that drainage is 
compromised by the presence of cuffs of polymerized 
fibrin round the venules. This can, in part, be prevented 
by administration of the synthetic steroid stanozolol. 
Suboxygenation of normally perfused tissue, such as may 
occur in the presence of severe anaemia, will also lead to 
defective healing. 




Factors modifying healing 

• Nutrition malnutrition, vitamin deficiency. 

• Steroids. 

• Systemic disorders, e.g. diabetes. 

• Vascular supply. 

• Mobility of affected tissues. 

• Infection. 



COMPLICATIONS OF HEALING 



££/*fi(-^ 



Although the basic processes involved in healing are 
designed to be protective, they do occasionally go wrong. 
This occurs as a result of a loss of control in the complex 
interplay between the many varied cellular and chemical 
processes. Two complications worthy of mention are 
hypertrophic scar and keloid. Although these haunt all 
surgeons, they are a particular problem for the plastic 
surgeon. Hypertrophic scar is simply an overgrowth of 
scar tissue which causes a raised firm ridge. When the 
tissue overgrowth is so exuberant that it greatly exceeds 
the borders of the scar, it is called a keloid. Unfortunately, 
some patients have a tendency to form keloids (more 
common in black people) and hence excision of the keloid 
only results in more keloid. 

It is worth remembering that, due to the contraction 
that occurs during wound healing, excessive tissue 
destruction, especially around joints, may result in con- 
tractures and joint deformity. 



329 



32 



POSTOPERATIVE 



Summary 

• Wound healing is a complex process 
relying on the integrated actions of the 
coagulation system, the inflammatory 
response and the chemical mediators 
required to stimulate cell proliferation and 
protein secretion. 

• The processes are fundamentally the same 
in cleanly incised wounds and in large 
open wounds. 

• A similar process also occurs in specialized 
tissues such as bone, with some changes 
related to functional demands of that 
tissue. 

• The healing process can be modified by 
many factors, including nutritional status, 
steroids, infection and excess mobility of 
affected parts. 

• Although designed to be protective, 
complications as a result of contractures 
and exuberant scar formation produce 
clinically significant morbidity. 



Further reading 

Kirsner RS, Eaglestein WH 1993 The wound healing process. 

Dermatology Clinics 11(4): 629-640 
Lakhani SR, Dilly S A, Finlayson CJ 1 998 Basic pathology: an 

introduction to the mechanisms of disease, 2nd edn. Edward 

Arnold, London, pp 78-86 
Majno G, Joris 1 1996 Wound healing. In: Cells, tissues and 

disease. Principles of general pathology. Blackwell Science, 

Oxford, pp 465-485 
Singer AJ, Clark RAF 1999 Cutaneous wound healing. 

New England Journal of Medicine 341: 738-746 
Waldorf H, Fewkes J 1995 Wound healing. Advances in 

Dermatology 10: 77-96 



330 




Responses of connective tissue 
and bone 

1/1/. J. Ribbans, M. Saleh 




Objectives 

• Appreciate that bone and connective 
tissues are not static but are living, 
dynamic and responsive to their changing 
environment. 

• Understand the responses of connective 
tissue and bone to trauma. 

• Be aware of the factors modifying the 
structure, strength, growth of bone and 
connective tissue. 

• Understand the response of bone to 
various surgical procedures. 

• Appreciate the inbuilt redundancy that 
often permits patients to overcome 
physical and functional defects. 

• Recognize the importance of restoring 
function following trauma and surgical 
intervention. 



INTRODUCTION 

We shall consider the responses of connective tissues and 
bone to their environment and stresses/ including trauma 
and iatrogenic (Greek iatros = physician + -gen = to 
produce) interventions, which include operative surgery. 
There is a tendency to regard the skeleton and connective 
tissues as static but they are responsive and dynamic 
(Greek dynasthai = to be able). Do not regard any of these 
structural tissues as being simple; they are just as complex 
as any other parts of the body. Although bone is inter- 
spersed with inorganic calcium phosphate, it is largely 
composed of type I collagen. Collagen can be laid down 
by fibroblasts or reabsorbed, and in bone, calcium phos- 
phate can be laid down, remoulded and reabsorbed. 

The dynamic properties are well illustrated by the 
response to stress. Just as muscles undergo hypertrophy 
(Greek hyper = over + trephein = to nourish) when exer- 
cised, so do the tendons that transmit their tension. If 
bone is stressed, new bone is laid down to compensate; if 



the direction of the stress changes, the architecture of the 
bone adjusts to meet it. In contrast, connective tissues and 
bones that are not stressed respond rapidly by undergo- 
ing atrophy, including bone decalcification. Striking 
examples are the changes that occur in the ligaments and 
bones of women during pregnancy, and in the muscles 
and skeleton of astronauts in space when the effects of 
gravity are removed. 

None of the tissues works in isolation and all of them 
are involved in movements that require them to function 
in concert (Latin com- = with + certare = to strive). 
Fortunately we are constructed in a fashion that has 
inbuilt redundancy (Latin re- = again + undare = rise in 
waves; to overflow). If there is a failure of one part, there 
is 'spare' function available that can compensate. For 
example, if the hip is stiff, part of its function can be taken 
over by swinging the pelvis, using vertebral flexion and 
rotation, in order to swing the affected leg forward, using 
the other hip joint as a fulcrum. Animals can survive 
happily with severe disabilities; young humans are 
remarkably adaptable when born with congenital defects 
and functional incapacities. However, it is possible to 
overcome or alleviate many functional losses; a simple 
splint may provide lost support, an ankle foot orthosis 
(Greek orthos = straight; the straightening of a distorted 
part) can compensate for foot drop. An artificial limb 
(prosthesis; Greek pros = to + thesis = putting) provides 
effective replacement of a lost limb. Orthopaedic sur- 
geons can aid fracture fixation using internal and external 
fixation, and repair or divert tendons to overcome paral- 
ysis or rupture. The field of activities constantly increases 
as joint replacement, limb lengthening, limb transplanta- 
tion and minimal access procedures are developed and 
extended. 

Make sure that you acquire a deep understanding of 
the connective tissues; they are fundamental to the 
success of surgical procedures. 



Trauma 

1. Damage can occur from sharp or blunt injury, or 
from a combination of the two. It may be direct or indirect, 



331 




POSTOPERATIVE 



open or closed (see Ch. 2). As a result of the injury, deep 
tissues may be distracted or misaligned and become 
incorporated within a large haematoma. Open, contami- 
nated wounds are at increased risk of infection. 

2. Operative surgery is a form of trauma but gentle 
handling of tissues, perfect haemostasis and meticulous 
technique, as advocated by the great American surgeon 
William Halsted (1852-1922), together with observance of 
sterile precautions minimize its effects. Injury may be 
increased by rough handling, thermal damage from using 
diathermy haemocoagulation, power-driven tools, and 
bone cement. Healing can be prejudiced by inserting 
unsuitable materials, such as excessive or irritating 
sutures. 

3. The initial injury may be compounded by the effects 
of immobilization and disuse on bones, joints, muscles, 
tendons and ligaments, including those not directly 
involved within the surgical field. 



coNi^cr^ 

Collagen 

1 . This is a family of proteins accounting for about one- 
third of the total body protein, comprising about 90% of 
the organic matrix of bone. The molecule is about 280 nm 
long. A number of polypeptide chains are involved. Type 
I is the most widely distributed in fascia, dermis, cornea 
and tendon, providing excellent tensile strength. Type II 
is the main component of hyaline (Greek hyalos = glass) 
cartilage and also occurs in the nucleus pulposus of the 
intervertebral discs. Type III forms part of the wall of 
blood vessels, heart valves, dermis and the network of 
connective tissues in the walls of organs. Type IV is 
present in basement membranes. Type V is widely dis- 
tributed in membranous sheaths of muscles, Schwann 
cells and in basement membranes. 

2. Collagen was once thought to be relatively static but 
it can be rapidly laid down or degraded. Excessive colla- 
gen formation occurs in hypertrophic and keloid scars, 
and also in rheumatoid arthritis. In old age, collagen 
atrophy is progressive. It is defective in the syndrome 
described in 1896 by the French physician Bernard 
Marfan (1858-1942) and in the overstretched collagen 
syndrome descibed by two dermatologists, Edvard 
Ehlers (1901) in Germany and Henri Danlos (1908) in 
France. 



Elastic fibre 

1. This is composed of the protein elastin enclosed 
within elastic fibrils. It occurs in the aorta and its large 
branches, in the ligamentum nuchae, the lungs and the 



skin. It may be difficult to distinguish between elastic 
fibres and altered collagen fibres. 

2. Elastin is generated by fibroblasts and elastic 
fibres appear to be produced by smooth muscle cells. 
Although stable in most circumstances, elastic fibres are 
rapidly destroyed by elastase, an enzyme produced by 
some microorganisms. Elastic fibres are reduced in old 
age, the most obvious feature being the loss of tautness 
of skin. 

Ground substance 

This consists of glycoproteins and proteoglycans (pre- 
viously called mucoproteins), which include hyaluronic 
acid and chondroitin. They are synthesized in fibroblasts 
and osteoblasts. 

Muscle 

1. Skeletal muscle is often stated to be incapable of 
regeneration but this is not entirely so. A damaged 
muscle cell initially undergoes degeneration, followed by 
regeneration. Recovery depends heavily upon the ade- 
quacy of revascularization from surrounding tissues. 
Necrotic tissue is removed initially and replaced by satel- 
lite pluripotent undifferentiated cells in the near vicinity, 
as mature myofibroblasts lack ability to regenerate and 
divide. The cells of the original syncytium dedifferenti- 
ate, undergo cell division, then fuse, recreating the fibre. 
The satellite cells may account for one-third of all muscle 
nuclei of newborns, but this falls to less than 5% in 
adults, clearly affecting the relative ability of newborns 
and adults to recover from injury. Myoblasts appear and 
fuse to form myotubes, which coalescence into muscle 
fibres. This occurs within a newly laid down extracel- 
lular matrix and basal lamina surrounding the muscle 
fibres. 

2. If part of a muscle is destroyed, function is restored, 
not by cell hyperplasia (Greek hyper - over + plassein = 
to form) but by hypertrophy (trephein - to nourish); the 
individual fibres thicken up, at best creating a muscle 
mass comparable with the original bulk. When a muscle 
is transected, the ends contract and separate, the inter- 
vening space being filled with haematoma. This is even- 
tually replaced by collagenous scar tissue, so that a 
single bellied muscle is transformed into a double bellied 
one. 

3. Muscle is frequently incised to facilitate exposure. 
Whenever possible, split muscle along the line of the 
fibres rather than dividing it across them. Incisions paral- 
lel to the fibres are expected to disrupt functional recov- 
ery less than transection of the muscle belly. However, it 
has been shown that fibroblasts lay down collagen fibrils 
at right angles to the axis of the surgical incision in the 



332 



RESPONSES OF CONNECTIVE TISSUE AND BONE 



33 



muscle. Where scar tissue intervenes between muscle 
fibres and the motor endplate, the isolated fibres exhibit 
features of denervation. Excessive scar tissue formation 
affects the ability of a muscle to contract and lengthen 
normally, A muscle transected at mid-belly recovers only 
about half its ability to develop tension and exhibits about 
20% reduction in shortening during contraction. 

4. Apart from direct laceration by scalpel, scissors or 
diathermy muscle is injured by excessive pressure from 
instruments causing contusion (Latin tundere = to bruise), 
resulting in postoperative oedema, bleeding and acute 
inflammation. Provided the muscle unit remains vascu- 
larized and the patient can mobilize, functional recovery 
is usually adequate, with minimal scarring. 

5. Ischaemia results from de vascularization, or from 
excessively long application of a tourniquet. Transient 
ischaemia usually recovers completely but, if it exceeds 
several hours, irreversible changes occur in the myo- 
fibrils, with dilatation of mitochondria and sarcoplasmic 
reticulum. 

6. Postoperatively, ischaemia may develop secondary 
to compartment syndrome. Muscle that is starved of 
blood supply undergoes fibrosis, described in 1 881 by the 
German surgeon Richard Volkmann (1830-1889). Too 
tight bandaging, or application of plaster, and limb 
swelling within them may cause ischaemia. 

7. If a muscle is denervated or transected, functional 
recovery depends upon the degree of nerve regeneration 
across the surgical incision, and the completeness of 
reinnervation. 

8. Within the healing environment, dense scar tissue 
forms and can interfere with muscle regeneration and 
functional recovery. Experiments in the small muscles of 
rodents suggests that, in a fully re vascularized area, com- 
plete muscle regeneration is possible. This seems unlikely 
in humans and partial recovery is generally the norm. The 
gap usually fills with dense scar tissue. Myotubes may 
penetrate the fibrous tissue but complete regeneration is 
unusual. 

9. Following division of the Achilles tendon, there is 
some evidence of a change in the proximal muscle fibre 
type from type I slow-twitch fibres to type II fast-twitch 
fibres. 

10. Prolonged immobilization adversely affects the 
functional recovery of muscles following injury. Indeed, 
it has been reported that protein synthesis starts to 
decrease within 6 h of applying an immobilizing cast. On 
the other hand, repetitive loading increases the number 
and size of the muscle cell mitochondria, muscle glyco- 
gen concentration and oxidative capacity. Active mobi- 
lization favours a rapid and more complete regeneration. 
Low-tension high-repetition exercise promotes muscle 
endurance, while high-tension low-repetition exercise 
promotes muscle strength. 




Key point 



• Disuse atrophy occurs in skeletal muscle 
following prolonged immobilization. 

11. These features can be minimized by immobilizing 
muscles under tension. Muscle mass and strength are lost 
quickly following immobilization, and fatiguability 
increases. For example, lying in bed with knee extended 
causes more rapid functional decline in the relatively 
relaxed quadriceps than in the hamstrings, which are 
relatively stretched. Therefore, when placing an external 
fixator fine wire through muscle and into bone, prefer- 
ably hold the muscle in an eccentric position while 
passing the wire. For instance, as a wire passes through 
the gastrocnemius-soleus complex dorsiflex the ankle to 
ensure the muscle is transfixed in a lengthened position, 
minimizing the risk of the development of an equinus 
(plantar-flexed) deformity at the ankle. 

12. Muscle sensitivity to insulin is decreased during 
immobilization so it is more difficult for glucose to enter 
it, depriving it of energy supplies and allowing lactate 
to accumulate. Aerobic metabolism of fat is reduced. 
During postoperative recovery the ability of muscle to 
synthesize protein is reduced because of increased levels 
of corticosteroids. 

13. Heterotopic (Greek heteros = other + topos = place; 
displaced) ossification occurs in some patients within soft 
tissues, especially muscle, and following certain proce- 
dures. The pathogenesis is uncertain but may involve 
damage to muscle, tendon and periosteum, residual bone 
debris, and haematoma formation in the presence of 
pluripotent (Latin pluris = more + potentia = power; 
multiple potential), uncommitted fibroblasts. On careful 
inspection, up to 30% of postoperative hip replacement 
radiographs reveal evidence of ossification although re- 
exploration and bone excision is required in less than 1 % 
of patients. The incidence is greatest in males, younger 
patients and following an anterolateral approach to the 
hip joint. The new bone is found within fascial connective 
tissue with extensions into the muscle mass. There is an 
acute rise in the levels of serum alkaline phosphatase 
during the early weeks following operation. 



Tendons 

1 . Tendons (Greek tenon = sinew) are composed of fas- 
cicles (bundles) of collagen. Each fascicle contains fibrils 
of predominantly type I collagen, produced by fibro- 
blasts, embedded in a proteoglycan matrix. Each bundle 
is surrounded by an endotenon of loose connective tissue 
and the whole tendon is surrounded by an epitenon. 



333 




POSTOPERATIVE 



2. Many tendons are enclosed in a tendon sheath, espe- 
cially those that change direction abruptly, such as flexor 
tendons of the hand. The tendon sheath acts as a pulley 
and prevents / bow-stringing / of tendons. The synovial 
membrane on its inner surface combined with the 
epitenon serve as sources of lubricating fluid for the 
tendon. The tendons themselves are relatively avascular; 
blood reaches them at isolated points through flimsy 
attachments termed vinculae (Latin vincire = to bind). 
These tendons possibly have a dual pathway for tendon 
nutrition - through blood vessels and also by synovial 
diffusion. Tendons not surrounded by a sheath have a 
paratenon surrounding them, such as the Achilles tendon; 
they are known as vascular tendons and receive vessels 
from many points. 




Key points 

• Damage to the vinculae that bring blood 
vessels to the tendons seriously prejudices 
healing. 

• Damage to tendon sheaths and paratenon 
roughens the surfaces and generates 
irregularities and adhesions. 

3. Repetitive loading is a stimulus for increase in 
strength, size, matrix organization and strength of the 
insertion into bone. Endurance training in optimal posi- 
tion, with minimal resistance, facilitates revascularization 
and can result in an increase in strength of up to 3(MrO%. 

4. However, the overall blood supply of tendons is not 
bounteous and certain areas within them are recognized as 
being relatively avascular. They are prone to damage and 
disability because of their inability to repair; for example, 
the supraspinatus tendon in the shoulder, the Achilles 
tendon, and the tibialis posterior tendon at the ankle. 

5. 'Vascular' tendons undergo repair by the normal 
inflammatory response. Macrophages and fibroblasts fill 
the tendon gap. Type I collagen predominates in the 
initial healing process, orientated at this early stage 
perpendicular to (across) the long axis of the tendon. 
Subsequent remodelling and reorientation follows but 
maximum strength is not achieved for 5-6 months. 

6. The timing of mobilization is crucial following 
tendon repair. Too early mobilization weakens the repair 
and leads to gap formation between the tendon ends. 
Early controlled passive motion appears to stimulate 
intrinsic repair from the epitenon itself, and improves 
tendon strength. 

7. Prolonged immobilization of flexor tendons of the 
hand leads to increased adhesions and stiffness resulting 
from ingrowth of scar tissue from the surrounding sheath. 



Again, early controlled passive movement gives optimal 
restoration of flexibility and strength, especially of the 
finger flexors. 

Fascia and compartment syndromes 

1. The upper and lower limbs are divided into rela- 
tively inelastic compartments bounded by fascia and 
bone (Fig. 33.1). Each contains soft tissues, principally 
muscle, tendon and neurovascular structures. The devel- 
opment of a compartment syndrome after trauma is well 
recognized (see Ch. 2). Similar changes can occur after 
elective surgery to the limbs. The boundaries of each com- 
partment allow only a finite amount of expansion before 
ischaemic changes develop. Fig. 33.2 outlines the patho- 
genesis of a compartment syndrome. 

2. Postoperative swelling and bleeding increase the 
volume, and therefore the pressure, within compartments. 

3. Monitor 'at risk' patients clinically after operation by 
testing sensation and movement; this is not possible if you 
have used nerve block anaesthesia. It is possible to measure 
objectively the pressure within, for example, the anterior 
tibial compartment, to detect an abnormal rise in pressure. 




Key points 

• Avoid excessive tourniquet inflation times 
because this results in postoperative swelling 
within compartments. 

• Drain compartments within which 
postoperative bleeding is likely. 

Ligaments 

1. Ligaments (Latin ligare = to bind) span joints and 
provide stability. Additionally, they have important pro- 
prioceptive (Latin proprius = one's own + receptive; sense 
of one's position) and nocioceptive (Latin nocere = to hurt; 
pain perception) functions because of the specialized 
nerve endings embedded within them. 

2. Fibroblasts within the ligaments lay down collagen 
(90% type I), and some elastin fibres in an extracellular 
matrix. The collagen fibres are generally laid down along 
the direction of the tensile forces but not as rigidly as in 
tendons. Ligaments are relatively avascular, the most 
important source of vessels being the surrounding soft 
tissue rather than the osseous attachments. The anterior 
cruciate ligament within the knee derives most of its 
blood supply from the synovial membrane, which 
surrounds it. 

3. Repetitive loading promotes increased strength, size, 
matrix organizition and attachment to bone. 



334 



RESPONSES OF CONNECTIVE TISSUE AND BONE 




Bone 

Anterior compartment 

Lateral compartment 

Deep posterior compartment 

Superficial posterior compartment 



Bone 

Anterior compartment 

Posterior compartment 



Tibia 




Anterior 

intermuscular 

septum 

Interosseous 

membrane 

Fibula 

Posterior 

intermuscular 

septum 

Transverse 

intermuscular 

septum 



Radius 




Interosseous 
membrane 



Ulna 



Antebrachial 
fascia 



Fig. 33.1(a) Transverse section of leg, (b) transverse section of forearm. 



4. Repair of a damaged extra-articular ligament, such 
as the medial collateral ligament of the knee, is induced 
by the normal inflammatory response. The resulting 
haematoma is rapidly invaded by inflammatory media- 
tors. Vascular granulation tissue contains many fibro- 
blasts, laying down predominantly type III collagen, 
which provides early stability. After several weeks, a 
period of remodelling and maturation commences, which 
may be completed only after a year. The collagen type is 
gradually converted back to type I. 

5. Operative repair of intra-articular ligaments, such as 
the anterior cruciate ligament of the knee, is not associated 
with great success. The blood supply is sparse and synovial 
fluid dilutes the initial haematoma, inhibiting the normal 
repair mechanisms. Usually reconstruction is necessary, 
either with a hamstring tendon or with a part of the patella 
tendon that includes at one end a portion of bone from the 
tibial tubercle and at the other end a portion of patella. 




Key point 

Careful apposition of the divided ends, with 
minimal disturbance of the local soft tissues 
which carry the blood supply, are essential 
requirements for successful repair. 



6. Immobilization of a joint following operation com- 
promises the biomechanical properties of a previously 
healthy ligament. Tensile strength, elasticity and tough- 
ness deteriorate, only slowly reversed as joint movement 
is resumed. 

7. Joints immobilized after operation need to be 
splinted in a 'position of function' to avoid unnecessary 
contractures of the ligaments. Immobilization should be 
minimized to encourage recovery of the normal biomech- 
anical properties of the stabilizing ligaments. 



Synovial membrane 

1. The function of synovium within articulations and 
around moving tendons is to provide synovial fluid for 
lubrication and nutrition and to remove unwanted ele- 
ments from the area. Its superficial cells are served by a 
dense subsynovial plexus of vessels. Muscle bellies also 
slide over each other with minimal friction, although this 
is often ignored or overlooked. The apposed smooth 
external investing fascias must be separated by some form 
of synovial fluid. A.K. Henry, the poetic Irish surgeon- 
anatomist, eloquently describes the appearance of vastus 
intermedius muscle, when the overlying muscles are sep- 
arated, as a 'silvery fish-like belly'; it is shiny and slippery 
like the scales of a freshly caught fish (Henry 1945). 



335 




POSTOPERATIVE 



Osseous 



I 




Vascular 



Tissue trauma 



— 




i 



r T £ > 



Increased 

intracompartmental fluid 



Tissue swelling 



Increased 
intracompartmental pressure 



i 



Decreased pressure gradient 

between arteriovenous 

vascular beds 



j 



Decreased blood flow 



J 



Increased metabolic deficit 



Fig. 33.2 The vicious cycle of haemodynamic changes that occurs in the development of a compartment syndrome. 



2. Although the secreted fluid resembles white of egg 
(Greek ovon - egg), the origin of the name is obscure. The 
membrane invests many tendons and joints within the 
body. Membrane injury from trauma or operation 
increases its vascularity, cellular content and permeabil- 
ity resulting in increased production of synovial fluid 
and white blood cells. Vacuum drainage of the joint may 
be valuable in removing excess synovial fluid. 

3. Synovial fluid is viscous, lubricating and nourishing 
joint and tendon surfaces. Its viscosity and pH varies in 
diseases such as osteoarthritis and rheumatoid arthritis. 
Changes in the constituents can be detected by infrared 
spectroscopy and as the viscosity falls the lubricating 
function is reduced. 

4. Haemarthrosis (Greek haima = blood + arthron = joint 
+ -osis = morbid process), following injury or operation, 
stimulates the synovial layer to phagocytose the erythro- 
cytes and haemoglobin molecules. Type A synovial cells 
are probably the most active phagocytes. Ingested blood 
may form whorled bodies, known as siderosomes (Greek 
sideros = iron), within the cells. The haemarthrosis induces 



a chronic inflammatory response within the subsynovial 
layer and there is evidence of angioneogenesis (Greek neos 
- new), cellular hyperplasia and some villous prolifera- 
tion within the membrane. Large amounts of ingested 
blood may be toxic to the phagocytic cells, killing them. 
The dead cells release enzymes such as collagenase and 
neutral proteinase, which are potentially harmful to the 
joint and, in particular, to articular cartilage. Synovial iron 
deposits can still be found for up to 2 years following a 
major haemarthrosis. 

5. Inflammatory disease processes, such as rheumatoid 
arthritis, mediate many of their pathological processes 
by direct action upon the synovium. The inflammatory 
stimulus causes cellular proliferation and increased vas- 
cularity. The inflammation, secondary to synovitis and 
effusion, causes joint swelling and distension of the joint 
capsule and ligaments. The latter may lose their stabiliz- 
ing influence upon the joint, increasing deformity and 
joint destruction. The joint articular cartilage is gradually 
destroyed by the formation of a pannus of inflammatory 
vascular tissue, which spreads from the junction of the 



336 



RESPONSES OF CONNECTIVE TISSUE AND BONE 



33 



cartilage and synovium until it envelops the whole 
articulation. The detrimental effect of the pannus is due 
to the direct proteolytic effect of its enzymes and the 
mechanical effect of its covering presence, depriving the 
articular cartilage of the benefits of the synovial fluid. 

A combination of the osteoclastic cytokine action 
within the overlying pannus, relative inactivity and drug 
treatment causes the subchondral bone to become rela- 
tively demineralized and osteoporotic. 

Joint instability can cause life-threatening changes to 
the cervical spine, affecting the safety of surgical proce- 
dures. Replacement will be undertaken in a joint more 
prone to instability and periarticular fracture. At times / 
different artificial joint designs will be required, e.g. 
increasingly stabilized prostheses. Wound healing may be 
compromised as a result of the patient's drug therapy and 
the generally more delicate nature of the adjacent soft 
tissues. Any inflamed synovial tissue, with its hypervas- 
cularity, is more at risk of infection from systemic causes. 

The extra-articular sites of synovial tissue undergo 
changes causing similar damage to tendons, affecting 
strength and ultimately leading to rupture in many cases. 
Tendon repair following rupture may be impossible 
because of the poor quality of the tissue: a series of tendon 
transfers have been described for such eventualities. 



B 



Key point 



Be aware of the changes that synovial tissue 
has undergone, and the consequent limitations 
placed upon you. 



JOINTS 



%^.^^^^i\^J^^4-^f^!M^'^'^.^Si 



Some joints may not permit movements, such as 
synarthroses (Greek syn = together) between the bones of 
the skull. Amphiarthroses (Greek amphi = both) joined by 
fibrocartilage, as in intervertebral discs, or synovial mem- 
branes, as in the pubic symphysis, permit very little 
movement, Di arthroses (Greek dia = through) are freely 
moveable, as in the hip and shoulder joints; the bone ends 
are covered in articular cartilage and they are enclosed in 
a synovial membrane (Table 33.1). 

Joints can be damaged if weight is exerted through 
them in an abnormal fashion. This is very true of the 
complex knee joint. Weight should be transmitted equi- 
tably between the femoral condyles, through the menisci 
and the tables of the tibial platform. 

Be aware of the importance of axes and alignments in 
determining the forces on joints and strains and stresses 
on musculotendinous units. In the lower limb, there are 



various lines along which bones rotate or are conceived to 
revolve, or about which the parts are symmetrically 
arranged (Greek axon, Latin axis - an axle) (Fig. 33.3): 

• Anatomical axis of bones: a line running along the 
midpoint of the femur and tibia. 

• Vertical axis: from the body's centre of gravity to the 
ground. 

• Mechanical axis: a line that normally passes from the 
centre of the femoral head to the centre of the ankle 
joint through the centre of the knee. Any deviation of 
this axis, such as congenital deformities, operative or 
post-traumatic deformity, may cause uneven loading 
on joints, with consequent arthritis and instability. 

Lubrication of synovial joints 

Synovial joints are lubricated by synovial fluid. The 
science of friction, wear and lubrication is known as 
tribology (Greek tribein = to rub). Lubrication acts to 



Hip centre 



Mechanical 
axis 



Anatomical 
axis 



Knee centre 




Ankle centre 



Body centre 

of gravity 



Vertical axis 



Fig. 33.3 Lower limb axes. 



337 




POSTOPERATIVE 



^^uaunaa^saasBasuut 



Table 33.1 Classification of joints 






Joint type 
Fibrous 


Subtype 


Examples 


Characteristics 


Movement 


Skull sutures; 


Bones joined by fibrous tissue 


Variable from nil, e.g. 






syndesmosis of the 


continuous with periosteum or 


skull sutures, to 






inferior tibiofibular 


perichondrium 


considerable, e.g. 






joint; interosseous 




interosseous membrane 






membrane of the 










forearm 






Cartilaginous 


Primary 


Physeal plate of the 
growing long bones 


May be temporary, e.g. during 
bone growth and converts to 
bone at the end of growth 


None 




Secondary 


Pubic symphysis; 
manubriosternal joint; 
intervertebral discs 


Joints are found in the midline. 
Each bone is covered with 
hyaline cartilage and joined by 
a central fibrous tissue which 


Slight movement 








may cavitate, e.g. gel for discs 




Synovial 






Bone covered by hyaline 
cartilage. Enclosed by fibrous 
capsule, which is lined by 
synovial membrane. Joint cavity 
is filled with synovial fluid 
derived from membrane 






Plane 


Acromioclavicular joint 


Flat surfaces 


Permits gliding or sliding 




Hinge 


Elbow joint 


Hinge joint 


Moves in one plane 




Saddle 


First metacarpotrapezial 
joint 


Biaxial joint 


Permits circumduction 




Condyloid 


Metacarpophalangeal 
joints 


Biaxial 


Permits movement in 

two planes 




Ball and 


Hip; shoulder 


Multiaxial 


Circumduction. Amount 




socket 






of movement depends 
upon depth of socket 
and Ifgamentous 
arrangement 




Pivot 


Forearm pronation/ 
supination; atlantoaxial 


Uniaxial 


Rotation 






joint 







reduce frictional resistance and wear. The coefficient of 
friction for a synovial joint is lower than that achieved in 
any synthetic (Greek syn - together + thesis - a placing; 
putting together) bearing surface yet designed. 
There are several mechanisms of lubrication (Fig. 33.4): 

1. Hydrodynamic 

2. Elastohydrodynamic 

3. Weeping 

4. Mixed 

5. Boundary 

6. Squeeze him 

7. Hydrostatic. 

A normal synovial joint relies predominantly upon mech- 
anisms 2, 3 and 5. Artificial joints rely on 2 and 5. 



Menisci 

1. The menisci (Greek meniskos, diminutive of mene = 
moon) increase the contact area in certain joints, partici- 
pate in load distribution, act as shock absorbers and aid 
in distribution of lubricating synovial fluid. 

2. The long-term absence of all, or a substantial part of, 
a meniscus is associated with increased risk for the devel- 
opment of osteoarthritis. 

3. The meniscus is composed primarily of type I colla- 
gen, with lesser contributions from types II, III, V and VI. 
The cellular elements responsible for the synthesis of col- 
lagen and other constituents of the extracellular matrix 
are termed fibrochondrocytes. The collagen fibres are 
orientated predominantly circumferentially with a few 



338 



RESPONSES OF CONNECTIVE TISSUE AND BONE 




3 



Types of lubrication 



jT >v 


^SrtfiPS^* 


Boundary 




Load 




Mixed 

E lastohyd rody namic 








Velocity 




Viscosity 


riw-.t ' ■ »fi n '. 




\./ 


"^V^pra^^fl^'* 15 


Hydrodynamic 


NX 







Lubrication mechanisms II 




p- 



Load 



Velocity 
Viscosity 



III INI IIIIIBMII 




Hydrostatic 



Weeping 



Squeeze film 



Classical: 

* Boundary; 

low film factor <j> (very thin film) < ralher high m and wear rate 

* Mixed: 

higher film factor ih (discontinuous film), mixture ol boundary 
and elastohydrodynamic i : highest friction and wear rate 

* E lastohyd rody namic: 

higher Itlm factor <D, film maintained through pressure shocks 
*: relatively low coefficient of friction and wear rate, occurs 
in replaced joints 

* Hyd rody namic: 

higher film lactor (D {thick film} ■: coefficient of friction and 
wear rate low 



In addition: 

• Hydrostatic: 

high pressure in fifm is maintained from external source (P) 

• Weeping: 

porous and deformable surfaces^ from which additional 
lubricant is squeezed upon relative motion (eg cartilage, 
'soft cushion bearing') 

• Squeeze film: 

structured surfaces prevent lateral flow of lubricant from 
Ihe sliding interface 



Fig. 33.4 Types and mechanisms of lubrication. 



positioned radially, tying together the other fibres and 
limiting motion. 

4. The vascular arrangement of knee menisci is import- 
ant for nutrition and the ability to repair. A circumferen- 
tially arranged perimeniscal plexus sends radially 
orientated vessels into the meniscus. Unfortunately, they 
penetrate only 10-30% of the peripheral area. This has led 
to the concept of the outer "red zone' and inner 'white 
zone'. The synovium extends for a couple of millimetres 
over the peripheral edges of the meniscus and contains 
blood vessels. Within the 'white zone', nutrition is depen- 
dent upon diffusion from the synovial fluid. 

5. The ability of the meniscus to repair following a 
sporting injury or degenerative tear depends upon the 
site of damage. Within the 'red zone', repair can take 
place along similar lines to other connective tissue struc- 
tures. Vessels from the synovium and circumferential 
plexus support this process. Success depends upon the 
size of the lesion, the delay between injury and repair, and 
the adequacy of the blood supply. Apposition of the torn 
edges can be aided by meniscal suturing. 

6. Most meniscal tears occur in the avascular zone and 
are incapable of repair. Operation, usually through the 
arthroscope, involves excision of the torn fragment to 
prevent further propagation of the tear and to abolish 



pain, clicking and occasional joint locking experienced 
by the patient. If unstable segments are excised, later 
development of osteoarthritis is minimized. While not 
capable of repair, the meniscus may undergo remodel- 
ling following partial excision in the 'white zone'. The 
'raw area' resulting from the surgical removal of the torn 
fragment fills with a fibrin clot and synovial-derived 
cells. Later, the tissue appears, on gross inspection, to be 
similar to fibrocartilage. It seems that this process is 
related to the ability of meniscal fibrochondrocytes to 
proliferate in the presence of haematoma-derived 
factors. 

Articular cartilage 

1 . Articular cartilage is composed largely of an extra- 
cellular matrix populated with relatively few chondro- 
cytes. It consists of predominantly water, collagen (mostly 
type II) and proteoglycans with link proteins. In contrast 
to the opaque fibrocartilage seen in menisci, articular car- 
tilage is hyaline. Synthesis of the matrix is increased by 
moderate repetitive loading. 

2. Mechanical loading of normal joints contributes to 
maintenance of the articular cartilage but high shear 
stress causes degeneration and loss of function. 



339 




POSTOPERATIVE 



3. Small defects may heal spontaneously. Superficial 
lesions do not provoke an inflammatory reaction because 
there is no bleeding and chondrocytes cannot repair the 
damage. They do not inevitably progress to full thickness 
damage and osteoarthritis / as a thin layer of matrix may 
form over the damaged surface. For deeper lesions, not 
only the cartilage but also the subchondral bone is 
breached. This allows bleeding from the deeper bone to 
fill the defect and induce an inflammatory response. Some 
mesenchymal cells assume the appearance of chondro- 
cytes. However even 6 months after the injury the carti- 
lage is not fully repaired. While areas of hyaline cartilage 
may appear, there is a substantial amount of fibrous tissue 
present. The ultimate composition of the repair tissue is 
usually a hybrid of hyaline and nbrocartilage. 

4. Operative repair of damaged articular cartilage rarely 
reproduces the original structure. This failure results from 
the relative avascularity of articular cartilage and a paucity 
of cells available to provide the necessary materials. A lack 
of blood vessels disrupts the normal connective tissue 
response to injury: haemorrhage, fibrin clot formation, 
inflammatory reaction, phagocytosis and the synthesis of 
extracellular matrix components. Hyaline cartilage is 
uniquely composed of predominantly type II collagen and 
large cartilaginous macromolecules. The pluripotent (Latin 
pluris = several + potentia = power), undifferentiated cells 
available for repair do not consistently metamorphose into 
mature cells capable of replacing these elements. 

5. When treating fractures involving an intra-articular 
element, aim to reduce the joint surfaces as anatomically 
as possible and stabilize the fragments to minimize steps 
and gaps that will cause later degeneration of the joint. 

6. Osteoarthritis is a condition affecting predominantly 
the articular cartilage. The severity of the wear is classi- 
fied accordingly: 

Grade I: Softening of the articular cartilage 

Grade II: Fibrillation and fissuring of articular cartilage 

Grade III: Partial thickness cartilage loss, clefts and 

chondral flaps 
Grade IV: Full thickness cartilage loss with exposed bone 

Once the articular cartilage surface is breeched, the 
hyaline structure rapidly deteriorates. There is a loss of 
the proteoglycan and collagen in the matrix. The damaged 
cartilage breaks up and becomes free within the joint. It is 
regarded as irritant to the articulation and induces a syno- 
vitis as the lining attempts to phagocytose the fragments. 



NERVOUS TISSUE 

1. The organization of peripheral nerves is well 
described. An individual nerve fibre is separated from 
others by a loose connective tissue network, known as 



endoneurium. Some nerve fibres are enveloped by myelin 
(Greek myelos - marrow). 

2. A group of nerve fibres form a fascicle, defined by a 
circumferential layer of perineurium. A group of fascicles 
forms an individual nerve. The fascicles are separated by 
epineurium, which is condensed to form a sheath around 
the whole nerve. 

3. The blood supply to a nerve has both intrinsic and 
extrinsic components. Within the nerve are vascular 
plexuses at epineurium, perineurium and endoneurium 
levels. Externally, blood reaches the nerve at intervals 
from segmental regional vessels, which run in the con- 
nective tissue around the nerves. There are longitudinal 
anastomoses between the different supplying vessels, 
ensuring a rich microvascular network to support the 
metabolic activity of the nerve. 

4. The environment of the individual nerve fibres is 
regulated and protected by the physical diffusion barrier 
of the perineurium and the structural and functional char- 
acteristics of the endoneurial capillaries, which function 
as a blood-nerve barrier similar to the blood-brain 
barrier in the central nervous system. Injury can affect 
these barriers and affect nerve function. 

5. When mobilizing a nerve, as in ulnar nerve trans- 
position, handle it and its surrounding tissue as little as 
possible to avoid damaging the nerve and its supplying 
vessels. Avoid tension and unnecessary dissection to 
minimize interruption of the longitudinal anastomoses. 
Avoid compressing the nerve (Fig. 33.5). 

Nerve injuries are classified in a number of different 
ways. In 1951, injuries were classified into five degrees 
(Table 33.2). 

6. Nerves can be damaged by undue traction during 
surgery. Depending upon the force of stretching and the 
duration of the insult, the nerve may suffer any injury 
between the first and fifth degrees. 




Key point 

• Ensure that you revise the anatomy of 
neurological structures before, not during, 
operation. 

7. Certain approaches are associated with particularly 
high rates of inadvertent nerve damage, such as the ulnar 
nerve at the elbow and radial nerve at mid-humeral level. 
At the beginning of the procedure, identify, appropriately 
mobilize and preserve the 'nerve(s) at risk'. Exercise par- 
ticular care when undertaking procedures through previ- 
ously explored areas, as the nerve position may have 
changed and identification is more difficult in dense scar 
tissue. 



340 



RESPONSES OF CONNECTIVE TISSUE AND BONE 



33 




Fig. 33.5 Protective effects of the epineurium when a nerve is subjected to mechanical trauma. Several small fascicles 
embedded in a large amount of epineurium (left) are less vulnerable to transection injuries and compression than 
large fascicles in a small amount of epineurium (right). 



8. Nerve damage at sites distant from the operative 
area may be caused during operation. Ensure that vul- 
nerable nerves are suitably protected when positioning 
the patient before operation, particularly the radial nerve 
in the arm and the common peroneal nerve in the leg. 



r^ 



Key point 

Beware prolonged inflation, and overinflation, 
of tourniquets. 



Table 33,2 Nerve injury classification 



Degree 



II 



IV 
V 



Description 



Conduction block 

Lesion confined to the axon. Wallerian degeneration occurs 

within an intact endoneural sheath 

Both the axon and endoneurium lose continuity within an 

intact perineurium 

Loss of the perineurium around the fascicles. Only the 

epineurium remains to provide continuity 

Complete loss of division of the nerve 



Previous classification (1943) 



Neurapraxia 
Axontmesis 



Neurotmesis 



341 




POSTOPERATIVE 



9. If you inflate a tourniquet much beyond the patient's 
systolic pressure, the cuff may deform and damage 
peripheral nerves beneath it. The effects are mediated by 
mechanical pressure and ischaemic change. Mechanical 
compression causes obstruction of intraneural blood 
vessels and ischaemia causes damage to the same vessels, 
affecting permeability and leading to intraneural oedema. 
To minimize the effects of tourniquet ischaemia on nerve 
and muscle, make sure the pressure in upper limb tourni- 
quets is no more than 50-100 mmHg above systolic pres- 
sure and no more than double systolic pressure in the leg. 
Do not exceed 2 h maximum tourniquet pressure. 

10. When planning surgical incisions, take into account 
the concept of 'internervous planes'. Consider the skin 
areas and muscles supplied by individual peripheral 
nerves. When possible, incise between the 'territories' of 
major nerves. For instance, Henry's approach to the volar 
(palmar) aspect of the forearm is placed between brachio- 
radialis muscle, supplied by the radial nerve, and flexor 
carpi radialis, innervated by the median nerve. 

11. Neurological structures are clearly in danger of 
thermal injury from injudicious use of diathermy close to 
nerves. In such situations, use bipolar diathermy 

12. The outcome following nerve repair depends 
heavily upon surgical technique and operator experi- 
ence. Prepare the nerve ends carefully, appose and 
realign individual fascicles, and leave a small gap 
between the ends, with minimal tension, to achieve the 
best results. 



mechanisms triggered by an intact sensory system. 
Frequently, the situation is exacerbated by a concomitant 
arteriopathy. As a result, diabetics are more prone to the 
development of ulcers, deep sepsis (including osteomyeli- 
tis), delayed wound healing postoperatively, and Charcot 
joints (after repetitive trauma). 



GAIT 



: : ^>#$&^*^^^ 



fi^^^^^,^ m ^;^t^i'i?%^^ ! : 






1 . Normal gait (Old Norse gat = way, path; a way of 
walking, pattern of leg movements) is extremely complex. 
It requires equilibrium, the ability to stand upright in 
balance, and also to initiate locomotion (Latin locus = 
place + mover e = to move). In order to achieve both of 
these requirements, the skeletal, muscular, sensory and 
motor nervous systems must work in concordance. 

2. Different people walk in a wide variety of ways, 
depending upon the body shape and weight, urgency of 
moving, and other factors. The variation is so great that it 
is often possible to identify a close companion at a dis- 
tance by recognizing the gait. 

3. Carefully observe the gait of people and identify the 
stages of the cycle (Fig. 33.6). 

4. You should be able to describe the main stages of the 
normal walking pattern. 

5. Patients may limp (Old English lemp-healt = halting) 
for several reasons. The Latin word is claudus, and the 
Emperor Claudius was so named because he was lame. 
The main causes are listed in Table 33.3. 



0mm 



Key point 



• If there is a neuropathy, always consider 
diabetes. 

13. Diabetes is frequently affected by neuropathy. 
Musculoskeletal tissue, especially in the_extremities, can 
be prone to trauma because of loss of normal protective 



BONE 









1 . Bone forms the skeleton (Greek skellein = dry; origi- 
nally + soma = body; dried body), a supporting structure. 
It is a highly vascular hard tissue with the capacity to 
grow in width (accretion, as a tree trunk expands) and 
length by endochondral ossification. The body is com- 
posed of flat bones and long bones. The long bones have 



Table 33,3 Major causes of limp 




Cause 


Example 


Pain: antalgic (Greek znti = against + afgos = pain; 


Arthritis of a joint, fracture, ligament injury 


pain relieving) gait 




Weakness: paresis (Greek parienai = to relax; 


Gluteal muscle weakness (= Trendelenburg gait); 


diminished function) or paralysis 


neurological injury 


Leg length discrepancy 


Congenital deformity; post-traumatic 


Stiffness 


Arthritis of a joint 




Post-traumatic soft tissue swelling 



342 



RESPONSES OF CONNECTIVE TISSUE AND BONE 



33 



Double limb 
support 



Single limb 
support 



Double limb 
support 



Heel 

strke 



Opp. 
toe 



Heel 
oft 



Opp. heel 
strike 



Opposite angle 
limb support 



I 



Toe 
off 



Heel 
strike 



10% 




1 5% 



30% 



30% 



50% 60% 

Percent of walk cycle 

55% 60% 



100% 



100% 



Stance phase - 60% of cycle 



Critical 
event 



Heel 
strike 



Foot 

flal 





Swing phase - 40% of cycle 





Knee Toe 
bend off 



Toe clearance 



Heel 
strike 



Fig. 33.6 Phases and events of walking cycle. Stance phase constitutes approximately 62% and swing phase 38% of 
cycle. 



a central tubular structure, the diaphysis (Greek dia = 
through + physis = nature, growth), and an expanded end, 
the metaphysis (Greek meta = after), which incorporates 
the growth plate, the physis, and the subchondral bone 
plate covered by the articular cartilage of the adjacent 
joint. At skeletal maturity the architecture of the metaph- 
ysis becomes homogeneous, with loss of the cartilaginous 
growth plate. Bone is largely composed of type I collagen. 
It contains cells (osteocytes) embedded in an amorphous, 
fibrous collagen matrix interspersed with calcium phos- 
phate, an inorganic bone salt. Osteoporosis is character- 
ized by a reduction in bone mass. Loss of structural 
strength may lead to fracture and also affects implant 
fixation. 

2. Bone exists in two forms, depending on the arrange- 
ment of the collagen fibre and the osteocytes. Immature 
bone has fibres and osteocytes irregularly arranged. The 
osteomucin is basophilic and there is a sparsity of 
calcium. It forms, during development of differentiating 
mesenchyme, into the bones of the skull vault, mandible 
and clavicle, and when bone is laid down in differenti- 
ating mesenchyme, as in fracture healing. It also occurs in 
various bone diseases, including osteogenic tumours. 

Adult bone has the collagen arranged in parallel sheets 
or bundles, as flat plates or, in long bones, as tubular 
vascular canals surrounded by concentric systems of 
cortical bone, described in 1689 by the English physician 
Clopton Havers (1650-1702). The bone is less compact in 
the central canal of long bones and is termed cancellous 



(Latin cancellus = lattice; porous). Most of the skeleton is 
formed on a cartilagenous model from ossification 
centres in the diaphysis and epiphyses (Greek epi - 
upon) which spread in all directions, replacing cartilage 
with bone. During growth, the cartilagenous physis 
grows as it is invaded from both sides, so the bone con- 
tinues to lengthen. At the interface between expanding 
ossification and the cartilage, osteoblasts, resembling 
fibroblasts, lay down collagen and osseomucin, which 
becomes osteoid, which immediately becomes calcified 
with calcium phosphate deposition. This interferes with 
cartilagenous nutrition so the chondrocytes die, being 
replaced by osteocytes, the mature osteoblasts, which 
are locked in the newly created bone. At maturity the 
cartilagenous physis plate is invaded from both sides, 
which eventually fuse across it, so further growth in 
length ceases. A similar process occurs during the 
healing of bony fractures. Adult bone replaces mem- 
brane bone so that the whole skeleton of adults is 
composed of it. 

3. There may be varied stimuli for changes in bone, 
including fatigue damage, stress-generated potentials, 
changes in the hydrostatic pressure of the extracellular 
fluid, and changes in the cell membrane diffusion 
resulting from direct loading. In 1892 the German-born 
orthopaedic surgeon Julius Wolff stated that if bone is 
mechanically stressed it is stimulated to build up bone in 
response to the force. It is considered likely that stretch 
receptors are associated with ion channels on osteocytes. 



343 



3 




POSTOPERATIVE 



A minimum level of repetitive load is necessary to 
maintain normal bone. A number of biochemical changes 
can be detected during the process including raised 
prostacyclin, prostaglandin E2, intracellular enzyme 
glucose-6-phosphate dehydrogenase (G6PD), nitrous 
oxide (NO) and growth factors, including insulin-like 
growth factor 1 (IGF-1), which is a mediator of metabolic 
activity. Bone remodelling is accomplished by large 
multinucleate osteoclasts (Greek clasis = a breaking), 
which absorb bone, creating spaces or lacunae, described 
in 1841 by the London surgeon John Howship; osteo- 
blasts lay down bone elsewhere. Cancellous bone has 
more extensive surfaces than cortical bone so it is more 
responsive to stimuli. Advances in imaging, combined 
with high-speed digital computers, have permitted 
analysis of the mechanical stresses to the level of 
individual trabeculae within bone. Bones carry electrical 
potentials at rest, resulting from metabolic processes. 
Active growth plates are electronegative. If bones are 
loaded to bend them, a negative charge develops on the 
compressed side and a positive charge is generated on 
the distracted side. Bone deposition occurs on the 
negative compressed side, and resorption on the 
positively charged distracted side. The electrical changes 
were thought to be the result of a piezo- electric {Greek 
piezein = to press) effect - compression of a crystalline 
structure generating an electrical charge. This mechan- 
ism has been challenged. Bone behaves as a composite 
viscoelastic material (Latin viscosus = sticky). It has 
multiple channels and lacunae within it, the lining of 
which may have a charge. Ions in the fluid within the 
channels tend to stay in the vicinity of the ions in the 
lining which carry an opposite charge. If the fluid flows, 
as a result of bone deformation, the ions are separated, 
resulting in an electrical field and a potential difference. 
This is called a streaming potential. The alternative 
explanation to a piezoelectrical effect is that when the 
bond is strained, movement of the non-mineralized 
matrix produces fluid movement, resulting in streaming 
potential which sensitizes the osteocytes and osteoclasts 
(Greek klasis - fracture; hence, absorption). The osteo- 
cytes respond by laying down bone and the osteoclasts 
by absorbing bone; the result is a remodelling to adapt 
the bone structure to any change in the forces exerted on 
it. In the hope of exploiting this mechanism, direct 
current, capacitative coupling, and pulsed electro- 
magnetic fields have been used to stimulate osteogenesis 
in fractures and osteoporosis. 

4. Bones and soft tissue respond to the loads placed 
upon them. Regular exercise has been shown to improve 
muscle strength and endurance and has important, 
although less obvious, ramifications for the structure and 
function of bone. This is particularly important for the 
elderly in an attempt to partially offset the development 



of osteoporosis. Bone conforms to Wolff's law. Julius 
Wolff was a German scientist, who in the late 1800s, stated 
that 'every change in the form and function of bones or of 
their function alone is followed by certain definite 
changes in their configuration in accordance with mathe- 
matical laws' — to borrow a modern sporting phrase 'use 
it or lose it!'. Increasing the load upon a bone increases the 
overall bone mass and causes remodelling of the bone to 
best withstand the types and directions of stress placed 
upon it. In normal long bones, the bone is strongest in 
resisting compressional forces, weakest in shear and 
intermediate in tension. 

5. In osteoarthritis, the subchondral bone reacts to the 
loss of cushioning from the progressively diminishing 
articular cartilage. The bone becomes thicker and radio- 
logically denser as a result of the loss of its 'stress 
shielder'. Eventually, the bone decreases in height as a 
result of successive trabecular fractures. Witness the 
increased work required to resect the medial femoral 
condyle compared to the lateral side during knee replace- 
ment surgery for a varus osteoarthritic joint. 

6. The bone is continually repairing small defects 
developing within it. Usually, that process takes place 
before more major fractures occur. However, in impaired 
bone or bone subjected to higher than normal forces, 
fractures may occur. Patients who inhale nicotine, take 
catabolic steroids, or regular long-term non-steroidal 
anti-inflammatory medication, represent common groups 
with impaired ability to heal bone under various circum- 
stances. The beneficial effect of postsurgery rehabilita- 
tion, with early weight-bearing and joint mobilization, is 
clear. 

7. Certain conditions can lead to markedly increased 
density of bone. Sickle cell anaemia causes bone to 
undergo repeated infarcts as a result of vascular insults. 
The medullary cavity of long bones can be converted 
from a lattice- work pattern to an ivory-dense bone mass. 
Be aware of this or you can experience considerable 
problems in breaching such bone, as when placing an 
intramedullary implant. 

8. Surgical operations to bone may be required for 
many reasons. The most common indication is to facilitate 
fracture healing. Bone may need to be divided to realign 
it, an osteotomy. Bone biopsy is carried out to obtain 
specimens to determine suspicious pathology. Bone may 
require resection because of infection or neoplasia. An 
increasingly common reason for operations is to replace 
worn articulations with prosthetic implants. 

9. Healing of bone may be stimulated in a number of 
ways, including the use of demineralized bone matrix 
harvested from donor bones. Electrical stimulation has 
been in use since the 1880s. It is now known that when a 
bone breaks it generates a low-level electrical field, which 
stimulates repair. 



344 



RESPONSES OF CONNECTIVE TISSUE AND BONE 



33 



MMMIM^,. 



Osteoporosis and osteomalacia 

Distinguish between osteoporosis (Greek poros = a 
passage; permeable) and osteomalacia (Greek malakos = 
soft) in terms of the way the bone responds (Fig. 33.7). In 
both pathological conditions the bone is less able to with- 
stand repetitive stresses or abnormal loads. As a result, 
such patients are more liable to develop pathological 
fractures and are at increased risk of developing peri- 
operative injury. 

Neoplastic bone lesions 

1. Bone can be affected by primary and secondary 
tumours. In primary lesions, a number of different cells of 
origin can be implicated, such as osteoblasts in osteogenic 
sarcoma and chondrocytes in chondrosarcoma. 

2. Some tumours are osteosclerotic, with increased 
bone formation, for example, prostatic secondaries, but 
the majority are osteolytic. Whatever the pattern, the bone 
involved with such lesions is abnormal and does not 
follow predictable biomechanical patterns when placed 



Normal bone 





















Osteoporosis 






















Osteomalacia 























Normal volume and 
mineralization ot bone 



^ 



Bone present is 

normally mineralized 

but of reduced volume 



Normal volume of 
bone, but bone 

present has 
reduced amount 
of mineralization 



Key 



Mineralized bone 



Unmineralized bone 



Fig. 33.7 The volume of bone is represented by the 
total number of boxes. The amount of mineralized bone 
is represented by the dark shaded boxes. 



under stress. As a result, the patient experiences pain and 
potential fracture at the point of weakness. 

3. Repeated imaging can monitor the progress of such 
lesions, and the healing response following such treat- 
ment as radiotherapy. However, there are certain param- 
eters which gauge the potential for impending fracture 
and provide information about the desirability of pro- 
phylactic surgical intervention: 

a. Long bone lesion greater than 2,5 cm increases the 
risk. 

b. Lytic destruction of more than 50% of the bone's 
circumference has a greater than 50% risk of fracture. 

c. Persistent pain on weight-bearing despite radiother- 
apy treatment is an ominous signal of impending fracture. 

Periosteum 

1 . This is a thin lining tissue which surrounds the bone. 
It consists of two layers when examined histologically, an 
outer layer and an inner cambial layer (Latin cambium, is 
the exchange layer between the bark and wood of trees), 
although the layers cannot be separated macroscopically. 
It is easily peeled off the bone except at the juxta- 
articular region, where it is densely adherent at the point 
of attachment of the joint capsule, and at the insertion of 
muscles and tendons. For example, the insertion of the 
patellar tendon into the tibial tuberosity requires sharp 
dissection. In childhood, the periosteum is thick but it 
becomes thin with age. 

2. Periosteum is relatively inelastic and is therefore dif- 
ficult to suture and repair. It has a rich blood supply, often 
with prominent blood vessels on its surface, so that it 
bleeds readily when incised. 

3. Periosteum is the most important structure involved 
in bone repair, so protect it. When performing an 
osteotomy it may be incised by cutting hard down onto 
the bone with a scalpel, elevating it to separate it from the 
bone, followed by formal bony division, or it can be per- 
forated at intervals using a drill or fine osteotome (Greek 
osteon - bone + temnein = to cut) as part of a percutaneous 
osteotomy. 

4. Occasionally it is released circumferentially in an 
attempt to accelerate growth in children. It is also 
elevated and separated from underlying bone in infection 
and in neurological conditions such as spina bifida - a 
congenital cleft of the vertebral column with meningeal 
protrusion. 

Bone blood supply 

1. The blood supply to long bones is well defined, 
coming from both endosteal (within the bone) and 
periosteal (around the bone) surfaces. Normal blood flow 
is centrifugal, vessels running distally away from the 



345 



33 * : 



POSTOPERATIVE 



heart. The bone receives most of its blood supply from 
medullary vessels, 

2. Fracture disrupts the blood supply and revascular- 
ization occurs from the periosteum and surrounding soft 
tissues. In the early stages of repair, blood flow is pre- 
dominantly centripetal (Latin petere = to seek; flowing 
proximally). 

3. There are three primary components of the blood 
supply in long bones: the nutrient artery, metaphyseal 
arteries and periosteal arterioles. The diaphyseal supply 
is from the nutrient artery, which divides into ascending 
and descending medullary arteries supplying the major- 
ity of the diaphyseal cortex. The metaphysis is supplied 
by a rich network of metaphyseal arteries. It is much 
more vascular than the diaphysis and this is reflected 
in its ability to undergo repair following a fracture or 
osteotomy. The periosteal arterioles supply the outer 
third of the diaphyseal cortex in a patchy manner and 
anastomose with terminal branches of the medullary 
arteries. 

4. The efferent vascular drainage is through large 
emissary veins and venae comitantes of the nutrient 
artery, which drain the medullary contents almost exclus- 
ively, whereas the cortex drains through cortical venous 
channels into periosteal venules. 

5. In flat bones the blood supply is closely reflected in 
its periosteal attachments and is therefore tenuous in the 
navicular and scaphoid bones, which are at risk from 
avascular necrosis following fracture and dislocation. 
Also at risk is the head of the femur following femoral 
neck fracture, as it receives one-fifth of its blood supply 
through the ligamentum teres. 

In children, haematogenous spread of osteomyelitis 
may occur to the joint if there is an intracapsular 
physis. 

6. Under certain circumstances, the vascularity of bone 
may be increased, with an effect upon surgical proce- 
dures. In Paget's disease, described in 1877 by the 
London surgeon Sir James Paget (1814-1899), the 
increased metabolic activity induced by osteoclastic and 
osteoblastic activity necessitates an increased blood 
supply and may induce a high-output cardiac failure in 
the patient. The increased activity renders the bone more 
brittle and more liable to fracture following injury or 
during operation. 

Certain tumours are associated with an increased blood 
supply. A common example that of metastatic lesions to 
bone from renal cell carcinoma. The leash of vessels 
around the deposit can cause profuse bleeding during 
surgical procedures. 

In osteoarthritis, much of the pain is thought to be 
derived from the altered subchondral bone, with its 
hypervascularity and venous stasis. 



Natural bone healing 

1. Following fracture or osteotomy, bone enters a repair 
cycle of overlapping processes involving inflammation, 
haematoma formation, development of granulation 
tissue, callus formation and remodelling. Healing is influ- 
enced by the amount of damage, and therefore the local 
tissues available for repair. Callus (Latin = hard) is woven 
bone, cartilage, or a mixture of the two. 

2. Primary callus response develops following a frac- 
ture and is initiated from the bone itself. It is short lived, 
lasting a few days to weeks, and sustained by bone 
contact. The second process is that of bridging external 
callus, which is a rapid process, tolerant of fracture move- 
ment and dependent on recruitment from the surround- 
ing soft tissues. A third response, in which fibrous tissue 
is replaced by bone, is seen within the medulla. It is 
relatively independent of movement and is termed late 
medullary callus. The response depends on the amount of 
motion at the fracture site (interfragmentary strain). 

3. If movement is obliterated, following, for example, 
rigid plate fixation, a different form of healing occurs, 
without intermediate callus formation. This is known as 
primary cortical healing. In most cases fixation reduces 
but does not entirely abolish strain, leading to the con- 
version of bridging fibrous tissue into cartilage, and, as 
the strain diminishes, bone is laid down. If tissue viabil- 
ity is poor, if there is excessive motion, a fracture gap, or 
if infection supervenes, healing is impaired. 

Implants 

Plates 

1. Plate fixation involves extensive dissection of the 
soft tissues, with incision and elevation of the peri- 
osteum. The fracture site is exposed, the haematoma is 
evacuated and the periosteal circulation of the bone is 
interrupted. Preservation of the haematoma may be 
valuable, although whether the haematoma provides 
cellular elements contributing to fracture healing is 
controversial. 

2. Following fracture or osteotomy, blood flow 
becomes centripetal and the periosteal circulation 
becomes dominant, primarily through dense connective 
tissue attachments. A plate reduces the local cortical blood 
supply. Blood perfusion is reduced by the close plate-to- 
bone contact because of periosteal damage and, by 
drilling through the bone for bicortical screw anchorage, 
both endosteal and intramedullary damage. 

3. Rigid plate fixation eliminates micromotion at the 
fracture site, facilitating primary cortical healing. 
Terminal bone death is minimized and union occurs 
slowly, mainly by creeping cortical substitution. The plate 



346 



RESPONSES OF CONNECTIVE TISSUE AND BONE 



33 



reduces stress on the bone and so may lead to bone 
atrophy, with the risk of refracture following plate 
removal. New low-contact compression plates inserted 
with minimal access may reduce the effects. 

Intramedullary nails 

1. A nail can be inserted without disturbing the frac- 
ture site or fracture haematoma. High intramedullary 
pressures may be induced while inserting the awl, guide 
rod and reamers and they may produce local damage and 
embolization. The nail is inserted down the length of the 
medullary canal, providing stability through areas of 
endosteal contact and also by the insertion of locking 
screws that pass through both cortices. Intramedullary 
nails permit more fracture motion than do compression 
plates, although nails vary significantly in their resistance 
to torsion (twisting) and to bending. 

2. Reaming (Old English ryman = to open up) may be 
used to allow larger diameter nails to be inserted, increas- 
ing the contact area between the nail and the internal 
surface of the bone; however, although this benefits frac- 
ture stability, it can weaken the bone. Rigid nails provid- 
ing stress protection may prejudice full recovery of 
strength. 

3. Cortical reaming and nail insertion both injure the 
medullary vascular system, resulting in avascularity of 
significant portions of the diaphyseal cortex; nails 
inserted without preparatory reaming show more rapid 
revascularization. 

4. Healing is more rapid than with plates, and refrac- 
ture is rare. The limb reacts to medullary damage by 
exhibiting a significantly raised extraosseous blood 
supply. Primary callus response and bridging external 
callus both occur but medullary healing is inhibited. 
Reliability and speed of healing are both affected by frac- 
ture motion. 

5. In animal studies the blood flow at the fracture site 
and within the whole bone was higher when using nails 
compared with plates, and it remained elevated for a long 
period. 

External fixation 

1. This can be applied without invading the fracture 
area. Unilateral fixators are applied with large, 5-6 mm 
diameter screws across the medullary canal, possibly tem- 
porarily disrupting the medullary blood flow. The bone is 
supported more effectively on the near cortex, referred to 
as 'cantilever loading'. Bridging external callus is seen 
more readily on the far cortex. 

2. Dynamization (permitting movement within the 
body of the fixator within 3-6 weeks of injury) reduces 
the amount of fracture movement and allows slight frac- 



ture collapse, resulting in reduced pin site stresses and 
more rapid healing. Micromotion may speed up healing 
rates. 

3. Fine-wire circular fixators are believed to produce 
less interference with the blood supply because the wires 
are only 1.5-2 mm in diameter. They provide an entirely 
different mechanical environment compared to unilateral 
fixators, with relatively even support for the whole bone 
('beam loading'), permitting more fracture motion. 
Unusually, as the limb is loaded the fixator becomes 
stiffer, hence supporting high activity levels while con- 
trolling fracture motion. Rapid healing rates with little 
visible callus may be seen, perhaps reflecting a rapid 
medullary response unique to this device. 

Osteotomy 

1. There is complete transection of the bone; studies in 
dogs have shown a 50% decrease in blood flow at 10 min 
and 66% at 4 h. Following double osteotomy in the dog 
tibia, 80% of the intermediate fragment had vessels in the 
haversian canals that were derived from the endosteal cir- 
culation. Both the intermediate fragment and the bone 
ends showed bone resorption and new bone formation in 
the haversian systems. 

2. In order to spare the tissues, corticotomy, a low- 
energy osteotomy of the cortex, preserving the local 
blood supply to both periosteum and medullary canal, 
may be used. In open corticotomy the periosteal struc- 
ture is preserved. Preservation of the periosteum and 
intramedullary vessels are both important in the forma- 
tion of new bone. 

Distraction 

1. Controlled mechanical bone distraction after 
osteotomy can produce unlimited quantities of living 
bone and direct the new bone formation in any plane fol- 
lowing the vector of applied force. The new bone sponta- 
neously bridges the gap and rapidly remodels to the 
normal macrostructure of the local bone. 

2. Within the distraction regenerate three zones can be 
recognized, according to morphology and the calcium 
content. They are a fibrous interzone, a primary mineral- 
ization front and a new bone formation zone. Other con- 
nective tissues and skin respond to the distraction 
process; the pioneer Russian surgeon Gavril Ilizarov 
(1921-1992), working in Kurgan, Siberia, described the 
Law of Tension Stress: gradual traction on living tissues. 
As ossification occurs in the callus between the bone ends, 
if the bone ends are carefully and slowly distracted the 
callus is extended in a similar manner to growth of a 
physis during normal bone growth. In consequence the 
bone lengthens. 



347 



3 




POSTOPERATIVE 



3. Taw of tension stress' - gradual traction on certain 
living tissues creates stresses that can stimulate and main- 
tain the regeneration of active growth. Slow, steady trac- 
tion of tissues causes them to become metabolically 
activated, resulting in an increase in their proliferative 
and biosynthetic functions. 

Bone cement 

1 . Polymethylmethacrylate (PMMA) has been used as 
a self-curing grout (filler) for implants since the 
Manchester orthopaedic surgeon Sir John Charnley 
(1911-1982) began replacing hips in the 1960s. Mixing the 
powder and liquid components induces polymerization. 
This is an exothermic (Greek ex = out + therme = heat) 
reaction generating significant heating of local tissue 
and the potential for bone necrosis. This has been exten- 
sively researched as a possible cause of later implant 
loosening. 

2. Orthopaedic surgeons are aware of the potential for 
cardiovascular collapse following the insertion of PMMA, 
especially into the femoral canal. It seems likely that the 
resulting elevated pressures (up to 900 mmHg) within the 
canal force fat and marrow contents from the bone into 
the circulation. These elements reach the pulmonary 
circulation within 2 min, initiating the aggregation of 
platelets and other clotting elements. 




Key point 

Cardiovascular collapse can be partially 
prevented by ensuring the patient is well 
hydrated before inserting bone cement. 



Summary 

• Have you appreciated how dynamic are 
the connective tissues, including bone? 

• Do you have a basic understanding of the 
responses of bone and connective tissues 
to trauma? 



Can you name some of the factors that 
modify the strength and growth of 
connective tissues, and how they act? 
Are you able to name some redundancies 
that function in spite of injury or disease? 
Do you appreciate the importance of 
preserving and restoring function resulting 
from injury and disease? 




Reference 

Henry AK 1945 Extensile exposure applied to limb surgery. 
Livingstone, Edinburgh, p 101 




Further reading 

Aronson ], Good B, Stewart C, Harrison B, Harp JH 1990 

Preliminary studies of mineralization during distraction 

osteogenesis. Clinical Orthopaedics 250: 43-49 
Bolander ME 1994 Regulation of fracture repair and synthesis of 

matrix molecules. In: Brighton CT, Friedlander G, Love JM 

(eds) Bone formation and repair. American Academy of 

Orthopedic Surgeons, Rosemont, pp 186-187 
McKibbin B 1978 The biology of fracture healing in long bones. 

Journal of Bone and Joint Surgery 60B: 150-162 
O'Sullivan ME, Chao EYS, Kelly PJ 1989 The effects of fixation 

on fracture healing. Journal of Bone and Joint Surgery 

71 A: 306-310 
Rhinelander FW 1968 The normal microcirculation of 

diaphyseal cortex and its response to fracture. Journal of 

Bone and Joint Surgery 50A: 784-800 
Rhinelander FW 1974 The normal circulation of bone and its 

response to surgical intervention. Journal of Biomedical 

Materials Research 8: 87-90 
Smith SR, Bronk JT, Kelly PJ 1990 Effect of fracture fixation on 

cortical bone blood flow. Journal of Orthopeadic Research 

8: 47M78 
Yang L, Nayagam S, Saleh M 2003 Stiffness characteristics and 

interfragmentary displacements with different hybrid 

external fixators. Clinical Biomechanics 18: 166-172 



348 





Postoperative care 



J. J. T. Tate 



W 



Objectives 



Understand the principles of patient 
management in the recovery phase 
immediately after surgery. 
Understand the general management of 
the surgical patient on the ward. 
Consider the initial management of 
common acute complications during the 
postoperative period. 



INTRODUCTION 



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Postoperative care of the surgical patient has three 
phases: 

1 . Immediate postoperative care (the recovery phase) 

2. Care on the ward until discharge from hospital 

3. Continuing care after discharge (e.g. stoma care, 
physiotherapy, surveillance). 

The intensity of postoperative monitoring depends upon 
the type of surgery performed and the severity of the 
patient's condition. 



THEREODVE^ 
Basic management 

Immediately after surgery patients require close monitor- 
ing, usually by one nurse per patient, in a dedicated 
recovery ward or area adjacent to the theatre. Monitoring 
of airway breathing and circulation is the main priority 
but a smooth recovery can only be achieved if pain and 
anxiety are relieved; monitoring the patient's overall 
comfort is essential. The nature of the surgery will deter- 
mine the intensity of monitoring and any special precau- 
tions, but children, the elderly patients with coexisting 
medical disease and patients who have had major surgery 
all require special care. 



Management of the general comfort of the patient 
includes: 

• Relief of pain and anxiety 

• Administering mouthwashes (a dry mouth is common 
after general anaesthesia) 

• The patient's position, including care of pressure points 

• Prophylactic measures against: 

- atelectasis by encouraging deep breathing 

- venous stasis by passive leg exercises. 

These steps, including the prophylactic measures, all 
start in the recovery area and will continue on the main 
ward. 



Airway and breathing 

Patients may have an oral airway, a nasopharyngeal 
airway or, occasionally, may still be intubated on arrival 
in recovery; all secretions must be cleared by suction and 
the artificial airway left until the patient can maintain his 
or her own airway. Breathing may be depressed and a 
patient hypoxic due to three factors: 

• Airway obstruction 

• Residual anaesthetic gases 

• The depressant effects of opioids. 

Oxygen is given, ideally by mask, and the oxygen satu- 
ration monitored by a pulse oximeter. Special care is 
needed for patients with a new tracheostomy If there is 
concern about vomiting and the risk of aspiration, 
patients can be sat up or nursed head-up rather than 
supine. 



Circulation 

Blood pressure is recorded quarter-hourly or, after major 
surgery, continuously via a radial artery cannula. The 
pulse rate is recorded regularly and continuously moni- 
tored by a pulse oximeter. The wound and any drains are 
monitored for signs of reactionary bleeding. 



349 



34 



POSTOPERATIVE 



Fluid balance 

Before patients are returned to the ward their calculated 
fluid losses should be replaced with blood, blood prod- 
ucts or crystalloids, and, ideally, fluid balance achieved. 
Monitoring of central venous pressure (CVP) can assist 
fluid balance management in severely ill patients or after 
major surgery. Urine output measurement may also 
provide useful information. 

Core temperature 

The patient's temperature is monitored, as there may be 
a significant drop during surgery, which should be cor- 
rected before the patient leaves the recovery room (e.g. 
with a space blanket). As the temperature rises, periph- 
eral vasodilatation may occur; if not anticipated this can 
lead to hypotension after the patient has returned to the 
ward. 

Special factors 

Specific medical conditions and certain types of surgery 
will require additional monitoring. Some examples are: 

• Diabetes mellitus - blood sugar monitoring 

• Cardiac disease - electrocardiogram (ECG) monitor 

• Orthopaedic surgery - monitoring of distal perfusion 
in a treated limb, position of limb, maintenance of 
fracture reduction, examination for peripheral nerve 
injury 

• Neurosurgery - quarter-hourly neurological observa- 
tions, intracranial pressure monitoring (intraventricu- 
lar catheter or a transducer in the subarachnoid space) 

• Urology - catheter output (after transurethral prostatec- 
tomy bladder irrigation is usually implemented and 
pulmonary oedema can develop if glycine has been 
absorbed into the circulation; fluid balance is particu- 
larly important) 

• Vascular surgery - distal limb perfusion. 

Pulse oximeter versus arterial blood gas 

The pulse oximeter is an essential piece of equipment for 
the management of the postoperative patient. It moni- 
tors three parameters: pulse rate, pulse volume and 
oxygen saturation. The fingertip sensor contains two 
light-emitting diodes (LEDs): one red, measuring the 
amount of oxygenated haemoglobin, the other infrared, 
measuring the total amount of haemoglobin. The actual 
amount of oxygen carried in the blood relative to the 
maximum possible amount is computed - this is 
the oxygen saturation (Sao 2 ). The delivery of oxygen to 
the tissues depends on: 



• Cardiac output 

• Haemoglobin concentration 

• Oxygen saturation (Sao 2 ). 

The relationship between oxygen in the blood and Sao 2 is 
linear and thus easy to interpret. A fall in oxygen reach- 
ing the tissues can be detected far more rapidly with Sao 2 
monitoring than by clinical observation of the lips, 
nailbeds or mucous membranes for cyanosis (which may 
only be apparent when the Sao 2 is 60-70%) or by measur- 
ing arterial blood gases. It should be noted that pulse 
oximetry does not indicate adequate ventilation; the Sao 2 
can be normal due to a high inspired oxygen level. 

Blood gases 

Arterial blood gases measure pH, arterial oxygen and 
carbon dioxide tensions (Pao 2 , Paco 2 ), bicarbonate and 
base excess. These measurements are affected by many 
variables and can be difficult to interpret. The Pao 2 has a 
non-linear relationship to the oxygen content of the blood 
(the oxygen dissociation curve), and hence oxygen satur- 
ation is easier to use in practice. 

Paco 2 reflects the rate of excretion of carbon dioxide by 
the lungs and is inversely proportional to the ventilation 
(assuming constant production of carbon dioxide by the 
body). The base excess and bicarbonate reflect acid-base 
disturbances and may be used in conjunction with the 
Paco 2 to distinguish respiratory from metabolic problems. 



r^ 



The recovery phase 

Management of pain and anxiety is as important 
as care of airway, breathing and circulation. 
Restoring body temperature is important for 
prevention of circulation and clotting problems. 
Sao 2 (pulse oximeter) has a linear relationship 
to the amount of oxygen in the blood, giving a 
sensitive indication of tissue oxygenation. 



CARE ON THE WARD 



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Patients may be discharged from the recovery area when 
they are able to maintain their vital functions indepen- 
dently (i.e. full consciousness and stable respiratory and 
cardiovascular observations). 

On the ward, the aim is to maintain a stable general 
condition and detect any complications early. Initially, 
closer and more frequent observation is necessary and the 
priorities are the same as in the recovery room. Nursing 



350 



POSTOPERATIVE CARE 



34 



staff perform routine observations; medical staff must 
undertake additional, clinical monitoring dictated by the 
nature of the case, including daily review of drug pre- 
scriptions (Table 34.1). 

General care 

General care includes those measures described pre- 
viously and control of pain. Early ambulation can reduce 
the risk of thrombotic complications. Patients who cannot 
mobilize require particular attention to skin care and 
pressure areas. Appropriate explanation of the results of 
the operation and the expected postoperative course 
should be given to the patient and relatives. The nature of 
the surgery or underlying disease will determine ad- 
ditional specific management (e.g. physiotherapy after 
orthopaedic surgery, stoma care for a new stoma). 

Pain control 

It is impossible for a patient to make a smooth recovery 
from surgery without adequate pain control (see Ch. 35). 
There has been a general shift from intermittent intra- 
muscular analgesia to intravenous analgesia, either by 
continuous infusion or patient-controlled bolus, or epi- 
dural analgesia after major surgery. An epidural is 
particularly useful after major abdominal surgery, but 
insertion of an epidural catheter in patients who have 
received a preoperative dose of heparin for deep vein 
thrombosis prophylaxis is controversial and contraindi- 
cated if the patient has a coagulopathy. 

For day surgery or minor operations oral analgesia is 
suitable and is most effective when prescribed regularly 
Narcotics can still be used if required. Non-steroidal anti- 
inflammatory drugs (NSAIDs) are popular but must be 
avoided in some patients, including asthmatics and those 
with a history of peptic ulcer or indigestion. Rectal 
administration of NSAIDs to a sedated patient should 
only be given with preoperative consent. 

Fluid balance 

Fluid balance is important after major surgery and easier 
if a urinary catheter is in situ, allowing accurate charting 
of urine output. Visible fluid losses are recorded on a fluid 
balance chart at regular intervals (e.g. hourly for urine 
output, 4-hourly for nasogastric aspirations, and 12- or 
24-hourly for output into drains) and totalled every 24 h. 
Unrecorded fluid losses (e.g. evaporation from skin and 
lungs, losses into hidden spaces such as the intestine, and 
diarrhoea) must be estimated and added to the recorded 
losses to calculate the patient's subsequent fluid require- 
ments (see Ch. 9). 



Table 34.1 The postoperative ward round: a daily 
checklist 



: 



A fresh assessment of each patient is required at 
each ward round, often daily but more frequently 
for seriously ill patients- Only a few factors may 
change on each occasion but all should be 
considered. 

Look at the patient, look at the charts, took at 
the drug chart and communicate. 
Enquire 

General comfort 

Pain control 

Thirst 

Specific symptoms 
Examine 

General condition 

Respiration and chest (oxygen saturation if 

appropriate) 

Surgical wound 

Peripheral circulation/nerves (vascular/limb 

surgery) 

Drains and tubes (content, kinks or blockage, loss 

of vacuum) 

Pressure areas 

Drip sites 
Check 

• Pulse and blood pressure 
Temperature 
Urine output 

Fluid balance (assess insensible loss. e.g. 
sweating, diarrhoea) 

Special monitoring (e.g. diabetics - blood sugars) 
Results of blood testsVinvestigations 

Review 

NutritionVoral fluid and dietary intake 

Analgesia management 

Intravenous fluid prescription (volume, sodium 

and potassium need) 

Antibiotic prescription 

Other postoperative drugs 

Regular prescription medicines (when to start 

oral medication) 
inform 

• What operation/treatment has been done and 
result 

• Comment on progress over previous 24 h 

• Expected course over next few days 

• Results of investigations/histology 

• Likely day of discharge (identify any special 
requirements early) 

Co mm uni cafe 

• Receive reports from named nurse, 
physiotherapist, etc. 

• Advise changes of management 

• Advise frequency/nature of observations required 

• Write in the notes 



351 




POSTOPERATIVE 



Fluid requirement 

For the typical 70 kg patient, intravenous fluid require- 
ment after operation is 2.5 litres per day, of which 0.5 litre 
is normal saline and the remainder 5% dextrose; potas- 
sium is added after the first 24 h once 1 .5 litres of urine 
have been passed. Typically the sodium requirement is 
1 mmol kg -1 (normal saline contains 140 mmol l" 1 of 
sodium) and potassium 1 mmol kg -1 . 

If the dissection area at operation has been large, there 
will be a greater loss of plasma into the operation site and 
this may need to be replaced with colloid (e.g. Haemaccel) 
in the early postoperative period. In addition to these 
basic requirements, gastrointestinal losses are replaced 
volume-for-volume with normal saline with added pot- 
assium. Daily plasma urea and electrolyte measurement 
are advisable while the patient is dependent on intra- 
venous fluids. 



Monitoring 

Clinical monitoring should include asking the patient 
about thirst, assessing central and peripheral perfusion, 
examination of dependent areas for oedema, and auscul- 
tation of the chest. Tachycardia is an important sign that 
can indicate fluid overload or dehydration, but is also 
caused by inadequate analgesia. 

Patients in whom fluid balance is difficult to manage, 
or where there is a particular risk of cardiac failure, may 
require central venous pressure monitoring or even left 
atrial pressure recording. 

Hypovolaemia 

Oliguria (defined as a urine output of less than 20 ml h" 1 
in each of two consecutive hours) in postoperative 
patients is caused by hypovolaemia in the majority of 
cases, but always consider a blocked catheter or cardiac 
failure. Hypovolaemia may be due to: 

• Unreplaced blood loss 

• Loss of fluid into the gastrointestinal tract 

• Loss of plasma into the wound or abdomen 

• Sequestration of extracellular fluid into the 'third' 

space. 

Blood transfusion 

Haemoglobin measurement will be a guide to the need 
for blood transfusion unless plasma or extracellular fluid 
loss causes an artificially high measurement; this is most 
likely in the first 24 h after surgery and it is generally not 
necessary to monitor haemoglobin levels more than 72 h 
postoperatively. In a stable patient, a top-up transfusion 
is indicated if the haemoglobin level is less than 8 g% 



(determined by studies in Jehovah's Witnesses), while 
above this level patients should be given oral iron. An 
unstable patient, one who may rebleed, requires a higher 
threshold for transfusion of at least 10 g%. If blood trans- 
fusion is given, frequent, regular monitoring of pulse, 
blood pressure and temperature are routine to detect a 
transfusion reaction. 



Complications 

A major ABO incompatibility can result in an anaphylac- 
tic hypersensitivity reaction (flushing /urticaria, broncho- 
spasm, hypotension). Incompatibility of minor factors is 
usually less severe and is indicated by tachycardia, 
pyrexia and possible rash and pruritus. The transfusion 
should be stopped, some blood sent for culture (both from 
patient and donor blood) and the remainder of the unit 
returned to the blood bank for further cross-matching 
against the patient's serum. However, if the reaction is 
mild it may be appropriate to give steroids or an anti- 
histamine and to continue the transfusion (see Ch. 8). 



Nutrition 

Nutrition in postoperative patients is frequently poorly 
managed and treatment delayed. Dietary intake should 
be monitored in all patients, but usually only requires 
specific management in patents undergoing major 
abdominal surgery or in whom eating or swallowing is 
impossible. A basic indication for postoperative nutri- 
tional support is inability to eat (actual or expected) for 
more than 5 days. Serum protein is a crude but easily 
measured index of nutrition, and measurement of weight 
is useful over a period of time; more specific tests such as 
skin-fold thickness or estimation of nitrogen balance are 
used infrequently (see Ch. 10). 

If nutritional support is required, enteral feeding is 
preferable, if possible, because it has a lower complica- 
tion rate than parenteral nutrition. Fluid balance and 
electrolyte monitoring are required and treatment 
should be given to reduce diarrhoea, which may be pre- 
cipitated by high calorie regimens. Parenteral feeding 
requires monitoring of the venous access point for 
sepsis, plasma and urinary electrolytes, blood sugar, 
plasma trace elements (e.g. magnesium) and liver func- 
tion. The patient's fluid balance must be carefully 
managed. 

Surgical drains 

Nasogastric tubes 

Nasogastric tubes drain fluid and swallowed air from the 
stomach and should be left on free drainage at all times 



352 



POSTOPERATIVE CARE 



34 



with intermittent aspiration (4-hourly). There is rarely a 
need to leave a nasogastric tube spigoted; once drainage 
has fallen below 100-200 ml per day the tube can be 
removed. 



Erosion by the drain of adjacent tissue 

Fracture of drain during removal (retained foreign 

body). 



Chest drains 

Pleural drains are attached to an underwater seal 
because the pleural space is at subatmospheric pressure. 
If the lung does not expand fully, then low pressure, 
high volume suction may be added. When a drain is 
bubbling it should not be clamped because there is a 
danger of tension pneumothorax if the clamp is forgot- 
ten or left too long; however, it is essential that the bottle 
is never raised above the level of the patent's chest, as 
there is a risk that fluid will syphon back into the pleural 
cavity. 
The drain is removed when: 

• Bubbling has stopped for 24 h 

• There is no bubbling when the patient coughs 

• The daily chest X-ray shows that the lung is fully 
expanded. 

Check X-rays should be taken at 24 and 48 h after removal 
of the drain. 



Drains at the operative site 

Drains at the operative site are used for the removal of 
anticipated fluid collections, not as an alternative to ade- 
quate haemostasis, and are usually simple tube drains or 
suction drains (check daily that the vacuum is main- 
tained). Such drains should be removed early; if left in 
place they will not reduce the risk of a subsequent abscess 
and may introduce infection, if there is a chronic collec- 
tion of fluid (such as an abscess or empyema) the drain 
may be left for several days to create a track. This type of 
drain is often removed a few centimetres at a time over 
several days (shortening) in an attempt to prevent the 
track closing too quickly; a sinogram may be used to 
confirm that the abscess cavity is shrinking. 



DAYCASE SURGERY 



#^^^&;^-s 



W£&& J &*?^£&Z 



After daycase operations the postoperative period is 
inevitably short, but management should follow the same 
basic principles outlined above. Special considerations are: 

* Is the patient being discharged to a suitable 
environment? 

* Can adequate, non-parenteral pain control be 
achieved? 

* Possible side-effects of sedation and anaesthesia. 

Patients who have had a general anaesthetic or sedation 
must be accompanied home and should not drive for at 
least 24 h. Written advice and instructions should be 
given both to the patient and to the accompanying 
relative or friend. 

Local anaesthetic 

The main problems with local anaesthesia are systemic 
toxicity of the anaesthetic agent and reactionary haemor- 
rhage if adrenaline (epinephrine) has been employed. 

Toxicity 

All the commonly used local anaesthetics (lidocaine 
(lignocaine), bupivicaine and prilocaine) are cardiotoxic. 
Initial symptoms are paraesthesiae around the lips, tin- 
nitus and /or visual disturbance. These are followed by 
dizziness, which may progress to convulsions and cardiac 
arrhythmia and collapse. Such complications are pre- 
vented by strict adherence to maximum dosage schedules 
(Table 34.2). 

Treatment of systemic toxicity is directed firstly 
towards maintaining ventilation (hypotension is uncom- 
mon in the absence of hypoxia): 



Complications 

All drains have similar potential complications: 

• Trauma during insertion 

• Failure to drain adequately due to 

- incorrect placement 

- too small size 

- blocked lumen 

• Complications due to disconnection 

• Introduction of infection from outside via the drain 
track 



Tabic 34.2 Maximum doses of anaesthetic agents 



Lidocaine 

(lignocaine) 

Buptvacaine 

Prilocaine 



Plain solution With adrenaline 
(mg) (epinephrine) (mg) 



200 

(20 ml of 1%) 

150 

(30 ml of 0.5%) 

400 

(80 ml of 0.5%} 



500 

(50 ml of 1%) 

200 

(40 ml of 0.5%) 

600 

(120 ml of 03%) 



353 




POSTOPERATIVE 



• Give 100% oxygen and maintain the airway (by intu- 
bation if necessary) 

• Control convulsions with intravenous diazepam 

• Establish an ECG monitor; various arrhthymias can 
occur 

• If cardiac arrest occurs, start with high energy 
(360-400 J) DC shock and continue resuscitation 
attempts for at least 1 h. 

Sedation 

For sedoanalgesia or sedation alone (e.g. endoscopy 
patients), particular attention is paid to monitoring respir- 
ation. During upper gastrointestinal endoscopy, delivery 
of oxygen by nasal spectacles is mandatory. All sedated 
patients should have a pulse oximeter attached during the 
procedure and until they are fully awake. The use of the 
antagonist flumazenil to reverse the sedative effects of 
benzodiazepines can be associated with delayed respir- 
atory depression as the reversal agent may have a shorter 
half-life than the sedative itself. Midazolam/ with a 
shorter half-life, is preferred to diazepam. All patients 
given sedation should be observed for at least 2 h before 
being sent home. 



CARE AFTER HOSPITAL DISCHARGE 

The key is good communication. The patient should 
understand what treatment he or she has had, its effect, 
the likely time period required to complete recovery and 
special restrictions on normal activity. Whenever appro- 
priate, the relatives should also have this information. As 
many complications (e.g. wound infection) occur in the 
first week or two after hospital discharge, it is essential 
that the patient's general practitioner is aware of the diag- 
nosis and treatment given and also what information the 
patient has received. Ensure arrangements are made to 
communicate histology results to the patient and plans 
for additional investigation or treatment have been made 
and explained to the patient. 




Postoperative care 

Adequate management of postoperative pain 
is essential. 

Poor management of fluid balance is probably 
the greatest cause of avoidable morbidity after 
major surgery. 



It is essential to know the maximum dosage for 

local anaesthetic agents and how to manage 

toxicity. 

Clear and concise communication with the 

patient and other health professionals 

involved in care will prevent problems and 

confusion. 



PROBLEMS IN THE POSTOPERATIVE 
PATIENT 



£^:^^t&^ 



The incidence and nature of postoperative complications 
depends upon the nature and extent of the operative 
intervention (see Ch. 36). Many are self-evident, but some 
specific problems are discussed below. 

Cyanosis/respiratory inadequacy 

The time between onset of respiratory problems and 
surgery may suggest the cause. In the recovery phase, it 
may be due to inadequate reversal of anaesthesia or 
excess opiates and the anaesthetist should be called. 

Opiate overdosage usually presents in a drowsy patient 
with shallow, infrequent breaths, while airway obstruc- 
tion is associated with obvious efforts to breathe, 
undrawn intercostal muscles and agitation. 

Airway obstruction 

If a patient is in respiratory distress, give verbal reassur- 
ance and 100% oxygen by mask. If cyanosed, check the 
pulse, as the most common cause is cardiac arrest. If 
breathing appears obstructed, call for anaesthetic help 
and: 

• Inspect the mouth for foreign bodies (e.g. vomit, 
slipped denture and surgical swab after surgery in the 
mouth). 

• Extend the neck and pull the jaw forward to clear the 
tongue from the back of the mouth and get an assistant 
to maintain the position. 

• Insert an oral airway. 

• If the patient has had a thyroidectomy, open the 
wound (skin and deep fascia) at the bedside. 

• If the patient has had surgery in the mouth, throat or 
neck, or if there is no improvement with an airway in 
place perform a cricothyroidotomy without delay. 

• Check that the patient can exhale. 

• Monitor the oxygen saturation and obtain blood gases 
and chest X-ray as soon as possible. 



354 



POSTOPERATIVE CARE 



34 



Do not attempt to intubate a patient after surgery in the 
mouth or neck unless experienced: do a cricothyroido- 
tomy and call an anaesthetist. In an emergency, a 
large-gauge intravenous cannula can be used for 
cricothyroidotomy but requires jet ventilation, whether 
the patient is breathing or not, because of the small 
lumen (attach a rigid oxygen line to the cannula via the 
barrel of a 5 ml syringe). During insertion, check that the 
needle is in the trachea, which may be displaced, by 
aspiration of air and be careful not to pass it straight 
through the back. The cannula can kink or displace and 
should be replaced as soon as possible with a purpose- 
made device. 



• Increase the rate of intravenous fluids. 

• Elevate the legs. 

• Give oxygen up to 50% by mask. 

• Obtain an ECG (dysrhythmia, acute ischaemia, signs of 
pulmonary embolus). 

If the ECG is normal, place a central venous pressure line 
while giving additional intravenous fluid. Listen to the 
chest to exclude tension pneumothorax (chest trauma, 
chest surgery, surgery around the oesophageal hiatus, or 
failed neck line) and consider pulmonary embolus and 
septicaemia. If no cause is apparent, and the blood pres- 
sure responds to volume infusion, hidden blood loss is 
likely. 



Normal breathing 

Cyanosis in a patient who appears to be breathing nor- 
mally may be due to a problem in the lungs or circulation. 
Listen to the chest for bronchospasm (wheeze is absent in 
severe bronchospasm) and for uniform air entry. Is the 
patient asthmatic? Is this a hypersensitivity reaction? Loss 
of air entry in the upper chest suggests pneumothorax, 
and in the dependent part of the chest, haemothorax or 
pleural effusion. Has the patient had attempts at intra- 
venous line insertion in the neck? 

Acute circulatory problems that can cause cyanosis 
are loss of venous return (massive sudden blood loss), 
pump failure (myocardial infarct) and obstruction 
(massive pulmonary embolus). Check the blood pres- 
sure and get an ECG. Other possible causes include 
severe adverse drug reaction and severe sepsis (air 
hunger). 



Hypotension 

The commonest cause of hypotension in a postoperative 
patient is hypovolaemia, either due to inadequate fluid 
replacement or to bleeding. Myocardial infarction needs 
to be considered and excluded. Poor management of 
pain control, either too much or too little analgesia, may 
be a factor and hypotension is a side-effect of an epi- 
dural (local anaesthetic drugs may cause dilatation of the 
main capacitance vessels). It is difficult to confirm that 
an epidural is responsible without turning it off; 
however, treatment by volume replacement is the same 
whether hypotension is caused by hypovolemia or the 
epidural. 

An assessment of the overall clinical situation may 
suggest an obvious cause of hypotension in a given 
patient If not: 



Hypertension 

This may be dangerous in patients with ischaemic heart 
disease, cerebrovascular disease or following vascular 
surgery. Obtain anaesthetic assistance with the manage- 
ment of such patients if a cause cannot be found; the 
commonest causes of hypertension are inadequate 
control of pain and /or anxiety, urinary retention and 
shivering. 

Postoperative infection 

The patient's temperature is a basic, but crude, observa- 
tion for infection. Clinical monitoring includes exami- 
nation of the chest and inspection of the wound. The 
upper limit of normal temperature is 37°C, but there 
is considerable variation and occasionally a patient may 
be pyrexial despite a temperature below this 'magic' 
figure. The timing of postoperative pyrexia may suggest 
a cause (e.g. after a large bowel resection: pyrexia within 
the first 48 h - chest infection; fifth or sixth day - an 
anastomotic leakage or wound infection; tenth day - 
venous thrombosis). 

If a patient develops a pyrexia, a routine 'infection 
screen' is carried out: 

1 . Examine the chest - chest X-ray; sputum for culture; 
ECG (if ?pulmonary embolus). 

2. Examine the wound - wound swab for culture. 

3. Enquire about urinary symptoms - urine culture. 

4. Examine for signs of deep vein thrombosis. 

5. Examine intravenous sites (phlebitis) and other 
catheter sites (epidural). 

6. Examine pressure areas. 

7. If a child - look in the ears and mouth. 

8. If cause uncertain - send blood cultures; measure 
white cell count. 



355 




POSTOPERATIVE 



9. Consider the underlying disease (e.g. pyrexia of 
malignancy). 
10. Consider hidden infection (e.g. subphrenic or pelvic 
abscess). 

Delayed gastric emptying/aspiration 

Abdominal surgery is frequently associated with 
delayed gastric emptying and impaired colonic motility, 
even though small bowel activity, and hence bowel 
sounds, may return relatively early. If there is intra- 
abdominal sepsis, metabolic disturbances or retroperi- 
toneal haematoma or inflammation there may be 
prolonged inactivity of the small bowel also (paralytic 
ileus). Colonic pseudo-obstruction occurs most often in 
elderly patients confined to bed (e.g. after fracture or 
orthopaedic surgery) and postpartum. Reintroduction of 
diet too soon can lead to gastric dilatation with vomiting 
and the risk of aspiration. Monitoring nasogastric aspir- 
ates, abdominal distension and the passage of flatus 
determines the timing of reintroduction of normal diet. 
However, a restricted intake of oral fluids (30 ml h -1 ) is 
permissible almost without exception, and increases 
patient comfort. 
Gastric aspiration can be life-threatening: 

• Place the patient head-down in the recovery position. 

• Suction out the mouth. 

• Give 100% oxygen by mask. 

• Pass a nasogastric tube to empty the stomach. 

• Examine for bronchospasm - if present, §ive nebulized 
salbutamol ± intravenous aminophylline and consider 
intubation and ventilation. 

• Obtain chest X-ray. 

• Arrange early chest physiotherapy. 

Steroids are not thought to be helpful. 



Summary 

• Postoperative care is divided into three 
phases. 

• The recovery phase is the immediate care 
of patients after surgery until they can 
maintain all vital functions independently. 

• The second phase is care on the ward, 
during which the three most important 
general considerations are pain control, 
fluid balance management and nutrition. 

• The third phase of care follows discharge 
from hospital and includes consideration of 
appropriate follow-up and/or survei Hence. 

• The intensity of monitoring in the 
postoperative phase depends on the 
severity of disease and/or the nature of 
surgery. 

• Many specialized features of postoperative 
care are determined by the type of 
operation. 

• Good communication is essential 
throughout postoperative care to ensure 
the best outcome. 




Further reading 

In addition to the chapters in this book referred to in the text, several 
pocket-sized texts aimed at trainee anaesthetists are available and 
provide useful guidelines on the management of acute postoperative 
problems, for example: 

Eaton JM, Fielden JM, Wilson ME Anaesthesia action plans. 
Abbott Laboratories Ltd, Abbott House, Norden Road, 
Maidenhead, Berks SL6 4XE 



356 




Management of postoperative 
pain 

V. Sodhi, R. Fernando 



m 



Objectives 



• Define the pathophysiology of pain. 

• Define the effects of pain on the 
postoperative patient. 

• Discuss pharmacological and non- 
pharmacological methods of analgesia. 

• Discuss the assessment of postoperative 
pain. 

• Discuss the causes and treatment of 
postoperative nausea and vomiting. 



INTRODUCTION 



^##^$,^^ 




Key points 

• Up to 75% of postoperative patients 
experience moderate to severe pain. 

• In many cases this pain is not relieved 
adequately. 

A joint working party was set up by the Royal College of 
Surgeons and College of Anaesthetists in 1990 to address 
these findings. They concluded that the main failures 
were: 

• That postoperative pain is given low priority in ward 
regimens 

• Lack of education among medical and nursing staff 

• Lack of provision of responsible personnel to manage 
postoperative pain. 

Despite some advances in our understanding of the physi- 
ology of acute pain and the introduction of some new 
analgesics, improvements in the quality of acute pain 
management in the past 10 years have tended to focus on 
using existing drugs and techniques more effectively. 
Better postoperative pain control has been demonstrated 
following the sequential introduction of a staff education 



programme, pain scoring and a more proactive regimen 
for administering intramuscular morphine. Further, 
although less dramatic, improvements were seen when 
the more expensive 'high tech' interventions, such as 
patient-controlled analgesia (PC A) and epidural infusion 
analgesia were added. 



WHAT IS PAIN? 



^i^M^^^^m^^ 



The International Association for the Study of Pain (IASP) 
defined pain as 'an unpleasant sensory and emotional 
experience associated with actual or potential tissue 
damage'. This definition is important, as it states that pain 
is never only a physical sensation but always ultimately 
a psychological event, and responses to a given stimulus 
are variable between individuals. Pain perception thresh- 
old is defined as the least experience of pain that a subject 
can recognize. It is highly reproducible in different indi- 
viduals and in the same individual at different times. Pain 
tolerance threshold, defined as the greatest level of pain 
that the subject is prepared to tolerate, is, in contrast, 
highly variable. That is, it can vary from person to person 
and within the same individual on different occasions. It 
is highly dependent on psychological variables, including 
cultural factors, past experience and the meaning of the 
pain for the individual 



HOW DOES POSTOPERATIVE PAIN 
ARISE? 



s««^iS^W!mS«^!;^SSftW^,^M^^ 






Pain involves four physiological processes: transduction, 
transmission, modulation and perception. Pain begins 
when local tissue damage, a noxious stimulus, occurs 
during surgery, causing the release of inflammatory sub- 
stances (prostaglandins, histamine, serotonin, bradykinin 
and substance P). This leads to the generation of electri- 
cal impulses (transduction) at peripheral sensory nerve 
endings, or nociceptors. These electrical impulses are con- 
ducted by nerve fibres (A-delta and C fibres) to the spinal 



357 



35 



POSTOPERATIVE 



cord (transmission). Further relay to the higher brain 
centres can be modified within the spinal cord (modula- 
tion) before an individual perceives a painful stimulus 
(perception). Therefore pain can, in theory, be blocked at 
various levels in this complex chain. Non-steroidal anti- 
inflammatory drugs (NSAIDs) can reduce the peripheral 
inflammatory response by reducing prostaglandin pro- 
duction. Local anaesthetic drugs injected into the epi- 



dural or subarachnoid spaces can block impulses to the 
spinal cord by acting on spinal nerve roots. Opioids can 
produce analgesia through modulation by binding to 
opioid receptors in the spinal cord and other higher brain 
centres such as the periaqueductal grey, the nucleus raphe 
magnus and the thalamus, whereas binding to opioid 
receptors in the cerebral cortex can affect the perception 
of pain (Fig. 35.1). 



Skin 



Post central gyrus 



Internal capsule 




Thalamus 



Dorsal root ganglion 



Spinothalamic + Spinoreticular tracts 

? 



Dorsal horn of 




* \ 

% — * 






• i 



* * 



** ** Ascending 
tracts 



Spinal cord 



Site of action 

1. Nocioceptors in skin and subcutaneous tissues 
These receptors are stimulated by inflammatory 
substances, e.g. prostaglandins 

2. A- beta fibres 

Stimulation of these fibres inhibits transmission 
of pain to higher centres 

3. Primary afferent neurons (A-delta, C fibres) 
Transmit impulses from nocioceptors to the 
spinal cord 

4. Dorsal horn of spinal cord and higher centres 
Further relay/transmission of painful stimuli to 
the cerebral cortex 



Analgesic /effect 

NSAIDS, e.g. diclofenac, ibuprofen, ketorolac, 
block pathways involved in the formation of 
inflammatory agents 

Transcutaneous electrical nerve stimulation (TENS); 
stimulates A-beta fibres 



Local anaesthetics, e.g. lidocaine, bupivacaine, 
ropivacaine. Block the transmission of impulses 
along neurons 

Opioids, e.g. morphine, pethidine, diamorphine, 
fentanyl, act as agonists at opioid receptors [also 
ketamine] 



Fig. 35.1 Sites of action of common analgesics. 



358 



MANAGEMENT OF POSTOPERATIVE PAIN 




35 



WHY SHOULD WE TREAT 
POSTOPERATIVE PAIN? 



^fflZ&%i?ffi£S;ffi$^H&i~?fffi^$&&ff/!& 1 fi^&'i'f, 



#W%Jf^&;ffi;f$iJ?£>f/> 



Apart from the humanitarian aspect, it is accepted that 
effective postoperative pain relief is fundamental to good 
quality patient care and is a legitimate therapeutic goal. 
There is increasing evidence relating good postoperative 
analgesia to reduced clinical morbidity. Some authorities 
suggest that there may be economic benefits associated 
with enhanced patient well-being and early rehabilita- 
tion. There are also several physiological reasons for treat- 
ing postoperative pain. 

Respiratory effects 

Surgery involving the upper abdomen or chest reduces 
vital capacity, functional residual capacity and the ability 
to cough and deep breathe. This in turn can lead to reten- 
tion of secretions, atelectasis and pneumonia. Inadequately 
treated pain aggravates these changes, while analgesia 
improves respiratory function. 

Cardiovascular effects 

Pain causes an increase in sympathetic output (tachycar- 
dia, hypertension and increasing blood catecholamines), 
which leads to increasing myocardial oxygen demand, 
which may in turn increase the risk of postoperative 
myocardial ischaemia, especially in those patients with 
pre-existing cardiac disease. 

Neuroendocrine effects 

The stress response to surgery and pain includes the 
secretion of catecholamines and catabolic hormones. This 
increases metabolism and oxygen consumption and pro- 
motes sodium and water retention. 

Effects on mobilization 

Mobilization of a patient in the postoperative period may 
be delayed if the patient is experiencing pain. This may 
in turn increase the risk of developing a deep vein 
thrombosis and also prolong hospital stay. 



patient preoperatively as to the nature of the operation, 
likely postoperative pain and methods of analgesia avail- 
able. Ideally, assess each patient jointly with the anaes- 
thetist and a member of the nursing staff, to discuss the 
site and nature of the surgery (Table 35.1), the extent of 
the incision and the physiological and psychological 
make-up of the patient, which are all relevant in planning 
intraoperative and postoperative analgesia. Once these 
things have been ascertained, the various methods avail- 
able for postoperative analgesia (including opioids, 
NSAIDs, isolated nerve blocks and epidural and spinal 
anaesthesia and analgesia) can be discussed between the 
patient and medical staff in order to reach a mutually 
agreeable postoperative treatment plan. 

Transcutanenous electrical nerve stimulation 
(TENS) 

A TENS machine consists of a pulse generator, an ampli- 
fier and a system of electrodes. It acts by stimulating 
afferent myelinated (A-beta) nerve fibres at a rate of 
70 Hz. This activates inhibitory circuits within the spinal 
cord that reduce the transmission of painful nerve 
impulses to the higher cortical centres, thereby theoreti- 
cally reducing the level of postoperative pain. However, 
in a systematic review of studies of TENS in postopera- 
tive pain relief, 15 out of 17 randomized control trials 
found no benefit compared with placebo. TENS has been 
shown to exert maximal relief in neurogenic pain, which 
is experienced in phantom limb pain and following nerve 
damage. 

Acupuncture 

Acupuncture has been clinically evaluated in postoper- 
ative patients. Although there is some variability in the 
way in which acupuncture is administered, there are a 
number of studies that suggest that it reduces pain and 
analgesic consumption after dental and abdominal surgery. 

Other methods 

Massage, hypnosis or application of superficial heat or 
cold are sometimes used. 



METHODS AVAILABLE TO TREAT 
POSTOPERATIVE PAIN 



NON-PHARMACOLOGICAL 




?^W&W&F&'&#W£&, 






yS^i'!;^:-^ 



Preoperative counselling 

The management of postoperative pain does not begin 
after the completion of surgery. Therefore inform your 



_ _ 

Table 35,1 Pain associated with different surgical 
procedures (decreasing order of severity) 



Thoracic surgery 
Upper abdominal surgery 
Lower abdominal surgery 
Inguinal and femoral hernia repair 
Head/neck/limb surgery 



359 



35 



POSTOPERATIVE 




Key point 

Although there is little evidence to support the 
effectiveness of unconventional methods, 
certain patients do derive some benefit from 
them, so do not dismiss them without 
consideration. 



PHARMACOLOGICAL 



i&^S-^Ss^^^ 



■'?:^^S&S^'^ 



In the majority of cases, acute pain is managed solely with 
drugs. There is good evidence that patients benefit from 
the use of multimodal, or balanced, analgesia after 
surgery. This involves the use of a variety of different 
classes of analgesics in combination, perhaps given by 
different routes, to achieve pain relief with a reduction in 
the incidence and severity of side-effects. 

Paracetamol 

Paracetamol is effective for mild to moderate pain, and as 
an adjunct to opioids in more severe pain. It has both 
analgesic and antipyretic effects but is not thought to be 
anti-inflammatory. Although there remains some contro- 
versy regarding its mechanism of action, it is generally 
thought to act by inhibiting the cyclo-oxygenase enzyme 
in the central nervous system, while sparing peripheral 
prostaglandin production. It is rapidly absorbed from the 
gut, and peak plasma levels are reached 30-60 min after 
oral administration. Paracetamol is metabolized in the 
liver and excreted by the kidneys, thus its dose should be 
decreased in renal and hepatic impairment. Contra- 
indications include acute liver disease, alcohol-induced 
liver disease and glucose-6-phosphate dehydrogenase 
deficiency. Oral paracetamol is more effective when com- 
bined with other compounds such as codeine, dihydro- 
codeine or dextropropoxyphene. Numerous different 
compound preparations are available. 




Key point 



• Be careful to avoid inadvertent overdose of 
paracetamol when prescribing by mixing 
different compound preparations. 

If the oral route is inappropriate, paracetamol may be 
given rectally. In some European countries the drug is 
given intravenously, as the precursor propacetamol, 2 g of 
which is converted to 1 g of paracetamol. Studies have 
shown propacetamol to be a more effective postoperative 



analgesic than paracetamol. A recent study demonstrated 
a 46% decrease in opioid requirement in orthopaedic 
patients given regular propacetamol. 



NSAIDs 

Sodium salicylate, a chemical manipulation of the glyco- 
side salicin obtained from extracts of willow bark, was 
introduced in 1875 to treat rheumatic fever. Acetylsalicylic 
acid (aspirin) was introduced about 25 years later and 
since then numerous NSAIDs have been marketed, 
including diclofenac, ibuprofen and ketorolac. 

NSAIDs do not relieve severe pain when used alone, 
but they are valuable in multimodal analgesia because 
they decrease opioid requirement and improve the 
quality of opioid analgesia. They have the benefit of 
improved analgesia without sedation or respiratory 
depression, and are more effective for the pain associ- 
ated with movement than opioids. There is no evidence 
that NSAIDs given rectally or by injection perform any 
better or more rapidly than the same dose given orally. 
These routes become appropriate when the patient 
cannot swallow or absorb drugs from the gastrointesti- 
nal tract. 



Km 



Key point 

The adverse effects of NSAIDs are potentially 
serious, and it is imperative that you respect 
any contraindications to their use. 



The most important adverse effects for surgical patients 
are: 

• Gastric ulceration - avoid NSAIDs in patients with 
symptoms of gastrointestinal intolerance and ulceration. 

• Nephrotoxicity - risk factors include concomitant use 
of nephrotoxic antibiotics (e.g. gentamicin), increased 
intra-abdominal pressure (e.g. at laparoscopy), hypo- 
volemia and age greater than 65 years. 

• Impaired haemostasis - NSAIDs inhibit the production 
of prostaglandin thromboxane A 2 within platelets, 
resulting in reduced platelet aggregation. They may 
also increase the risk of bleeding. 

• Aspirin-induced asthma - NSAIDs may induce bron- 
chospasm in susceptible patients. 

NSAIDs block the synthesis of prostaglandins by inhibit- 
ing the enzyme cyclo-oxygenase, of which there are at 
least two isoenzymes, COX 1 and COX 2. Research has 
shown that COX 1 synthesizes prostaglandins responsi- 
ble for physiological housekeeping functions, which 



360 



MANAGEMENT OF POSTOPERATIVE PAIN 



35 



include gastrointestinal and renal protection. COX 2, on 
the other hand, is responsible for the biosynthesis of 
inflammatory prostaglandins. Thus it would seem logical 
that by selectively inhibiting COX 2 it would be possible 
to develop an NSAID which retained the anti-inflamma- 
tory, analgesic and antipyretic actions required, without 
the undesirable side-effects of gastric irritation and renal 
injury. Two highly selective COX 2 inhibitors (celecoxib, 
rofecoxib) are now available, and have been shown to 
cause significantly less gastric mucosal injury than non- 
selective NSAIDs in patients without gastrointestinal 
pathology. However, some caution has been expressed 
over these findings. Chronic treatment with selective 
COX 2 inhibitors in patients with pre-existing gastro- 
intestinal injury or inflammation may show a significant 
increase in damage. COX 2 appears to have an important 
role in promoting the healing of ulcers. The overall effec- 
tiveness of this group of drugs therefore awaits the 
outcome of long-term trials. 



• Orally absorbed opioids from the gut reach the liver, 
via the splanchnic blood flow, where they are highly 
metabolized (first-pass metabolism), causing insuffi- 
cient plasma concentrations of drug, e.g. 70% of orally 
administered morphine is eliminated through first-pass 
metabolism. Pethidine, morphine and codeine are all 
available as oral preparations. 

The intramuscular route is the traditional method of 
administration. It is convenient and is associated with few 
side-effects, although the degree of analgesia varies 
between patients. Up to 40% of patients on a p.r.n. intra- 
muscular opioid regimen may have inadequate pain 
relief. The dose prescribed should be based on the 
patient's age and medical condition. The onset of analge- 
sia following intramuscular morphine begins after about 
20 min, with a peak effect at about 60 min. With careful 
patient selection, and nursing staff trained to use this 
administration technique correctly, intramuscular opioids 
can thus be highly effective. 



Opioids 

The analgesic properties of opium were first described 
over 6000 years ago, and opioids are still the first-line 
treatment for severe postoperative pain in most patients. 
They act at opioid receptors in the spinal cord and 
higher brain centres to produce analgesia. The three 
main subtypes of receptor have most recently been classi- 
fied as OP1 , OP2 and OP3 (formerly 8, k and (x, respec- 
tively). Opioids mimic endogenous opioid peptides at 
these receptors, causing their activation within the 
central nervous system. This decreases the activity of the 
dorsal horn relay neurons that transmit painful stimuli, 
thereby reducing the transmission of these stimuli to 
higher centres and producing analgesia. Activation of 
the receptors also causes the unwanted side-effects of 
opioids, namely, itching, sedation, respiratory depres- 
sion, nausea and vomiting, euphoria or dysphoria and 
bladder dysfunction. 

Opioids may be administered orally, intramuscularly, 
intravenously or centrally (into the epidural or subarach- 
noid space by an anaesthetist). Although novel tech- 
niques such as transdermal, inhalational and rectal 
administration of opioids have been used, and may offer 
certain advantages over conventional routes, their place 
in mainstream postoperative care is unproven. 

The oral route for opioids is not recommended initially 
after major surgery for the following reasons: 

• The use of opioids during general anaesthesia can lead 
to postoperative nausea and vomiting and delayed 
gastric emptying. 

• Intra-abdominal surgery can result in postoperative 
ileus. 




Key point 

• Take care when administering multiple doses of 
intramuscular opioids to shocked patients with 
poor peripheral perfusion. A large depot of 
opioid can accumulate intramuscularly, to be 
later released into the bloodstream when the 
peripheral circulation is restored, with 
unpredictable and often dangerous results. 

Morphine, diamorphine and pethidine are also 
commonly administered via the intravenous route. 
Intermittent intravenous bolus doses allow titration to 
effect, although care must be taken not to 'overshoot'. The 
peak effect of intravenously injected morphine is reached 
at about 15 min, and most of the effect by 5 min. Thus 
incremental titration with a 1-2 mg bolus every 5 min 
generally represents the best compromise between rapid 
pain relief and safety. Continuous infusion of opioid can 
abolish the wide swings in plasma drug concentration 
found with the intramuscular route and allow adjustment 
of the rate to the individual needs of a patient. 
Unfortunately, plasma drug concentrations may continue 
to increase with such regimens, leading to sedation and 
respiratory depression. 




Key points 



Side-effects of opioids are reversed by the drug 
naloxone, which should always be available on 
the ward. 



361 



35 * 



POSTOPERATIVE 



• Optimum safe analgesia requires reliable 
infusion devices, frequent assessment and 
monitoring, with appropriate adjustment of 
the infusion rate. In UK practice, this level of 
care may not always be achievable in a general 
ward setting. 

Intravenous opioid patient-controlled analgesia (PC A) was 
developed to address the need for an improved mode of 
administering standard opioids. The first demonstration 
of a PC A machine was in 1976 at the Welsh National 
School of Medicine, and this became the first commercially 
available PC A machine, The Cardiff Palliator'. Modern 
PCA regimens have been shown to provide greater patient 
satisfaction and improved ventilation compared with 
other conventional routes of opioid administration. 

PCA is superior to both intramuscular and continuous 
infusion routes because it allows the patient to self- 
administer small doses of opioid when pain occurs. 
PCA is administered using a special microprocessor- 
controlled pump which is triggered by depressing a 
button held in the patient's hand. When triggered, a 
preset amount (the bolus dose) is delivered to the patient, 
usually via a separate intravenous line. A timer prevents 
the administration of another bolus for a specified period 
(the lock-out interval). Before PCA is started, a loading 
dose of opioid must be given to achieve adequate anal- 
gesia. Background infusions of opioid are no longer used 
with PCA because of increasing side-effects. From a safety 
aspect, if patients become oversedated on PCA, they 
cannot give themselves another bolus. This will lead to a 
fall in plasma opioid concentration to safer levels. 
Regardless of this, regular monitoring of patients with 
PCA is essential. Naloxone should once again be available 
to treat respiratory depression and excessive sedation. 

Patient selection is again an important factor in the 
effectiveness of PCA. The patient must have adequate 
preoperative instruction in its use, and be mentally able 
to understand the concept of self -administration of pain 
relief, as well as be physically able to press the button to 
activate the device. 

PCA is suitable for many patients: 

• After major surgery and who are fasting 

• With marked 'incident pain' (e.g. pain associated with 
physiotherapy or dressing changes) 

• During acute episodic pain (e.g. vaso-occlusive sickle 
cell crisis) 

• When intramuscular injections are contraindicated (e.g. 
coagulopathy). 

Relative contraindications for use of PCA are: 

• History of illicit drug abuse 

• Major metabolic disorders (e.g. sepsis) or severe fluid 
and electrolyte abnormalities 



• End-stage renal or hepatic disease 

• Severe chronic obstructive airways disease 

• Sleep apnoea. 

Miscellaneous routes of opioid 
administration 

Transdermal. Fentanyl, a potent short-acting opioid, 
has been used in a drug-containing patch which adheres 
to the skin. The drug diffuses through the skin and into 
the bloodstream. Unfortunately the dose cannot be 
titrated to the patient's needs and it may take several 
hours to achieve adequate pain relief. 

Sublingual. Since the drug is delivered directly into 
the bloodstream via the sublingual route, first-pass 
metabolism is avoided. Sublingual buprenorphine, a 
partial agonist, is available, but has a 20% incidence of 
nausea and vomiting and a 50% incidence of sedation or 
drowsiness. 

Rectal. The rectal route is useful for providing a high 
systemic bioavailability of drugs that have a low oral 
bioavailability. Absorption, however, is slow, with peak 
concentrations being reached 3-4 h after administration. 
Pethidine and pentazocine are commonly administered 
by this route in Europe. 

Subcutaneous. Morphine is commonly administered 
by the subcutaneous route in cancer patients and is occa- 
sionally used for postoperative pain. This route is better 
tolerated than the intramuscular route of administration 
but the entry site must be changed every 24-48 h to avoid 
infection, and rapid titration of the dose of drug against 
patient response is difficult to achieve. 

Nebulizer. Morphine, diarnorphine and fentanyl have 
all been administered as nebulized solutions, with the 
advantage that the lungs can provide a large surface area 
on to which the opioids can be rapidly absorbed; 
however, systemic absorption is variable, probably 
because an indeterminate amount of the agent is swal- 
lowed by the patient. 

Intra-articular. In orthopaedic surgery, morphine may 
be of benefit by binding to opioid receptors that are 
present in inflamed tissue formed after injury within the 
joint spaces. Systematic review of the literature has so far 
failed to reveal evidence of efficacy for this route of 
administration. 

Epidural and spinal (intrathecal). These routes are dis- 
cussed below. 

Tramadol - a new opioid 

Tramadol is a synthetic analgesic, which has been used 
in Germany for over 20 years, but has only been available 
in the UK since 1994. It acts as a weak agonist at some 
opioid receptors, but also has important non-opioid and 



362 



MANAGEMENT OF POSTOPERATIVE PAIN 



35 



central nervous system effects via noradrenergic and 
serotoninergic pathways. It can therefore be classified as 
both an opioid and a non-opioid analgesic. When given 
parenterally, tramadol produces equivalent analgesia to 
morphine, except in severe postoperative pain, when it 
has been shown to be equipotent to pethidine. The 
advantage of tramadol is that it is analgesic with minimal 
respiratory depression, sedation, gastrointestinal stasis 
or abuse potential. Its disadvantages are its relative 
expense and side-effects, including dizziness, nausea, 
dry mouth and sweating. It may also lower seizure 
threshold. 

Relative efficacy of commonly used oral 
drugs and intramuscular morphine 

Relative analgesic efficacy can be expressed in terms of 
the number needed to treat (NNT); that is, the number 
of patients who need to receive the active drug for one 
to achieve at least 50% relief of pain compared with 
placebo over a treatment period of 6 h. For analgesics to 
be considered effective they require an NNT of 2-3 or 
less. Table 35.2 shows the relative efficacy of some 
common analgesics. The results have been gleaned from 
many meta-analyses of hundreds of clinical trials involv- 
ing thousands of patients. The results should, however, 
be interpreted with some caution as they may hide 
effects such as non-standardization in the pain being 
treated. 

Local anaesthetics and regional anaesthesia 

The use of local anaesthetics for the treatment of acute 
pain can be traced back to the time of the Pharaohs. 
Hieroglyphics show that the ancient Egyptians used a 



Ta bl e 3 5.2 Rel at i ve efficacy 


of common analgesics 


Analgesic 




Number needed 






to treat 


Paracetamol 1 g 




4.6 


Paracetamol 1 g + codeine 6C 


1 mg 


3 


Codeine 60 mg 




18 


Dihydrocodeine 30 mg 




10 


Tramadol 50 mg 




8.9 


Tramadol 100 mg 




4,8 


Tramadol 150 mg 




2.9 


Diclofenac 50 mg 




23 


Diclofenac 100 mg 




2.1 


Ibuprofen 200 mg 




5.5 


Ibuprofen 400 mg 




2.9 


Morphine 10 mg (single Lm. < 


dose) 


2.9 



topical substance to ease the pain of circumcision. Local 
anaesthetic (LA) drugs (e.g. bupivacaine, ropivacaine and 
lidocaine (lignocaine)) are sodium channel blockers and 
as such prevent the propagation of nerve impulses when 
applied to peripheral nerves or nerve roots. Sensory and 
sympathetic nerve fibres are blocked by smaller amounts 
of LA than are motor nerves. In the treatment of post- 
operative pain, LA drugs can be used in many ways: 

• Local wound infiltration (e.g. after an inguinal hernia 
repair) 

• Injection close to a peripheral nerve (e.g. digital nerves 
in a ring block) 

• Injection close to a plexus of nerves (e.g. brachial plexus 
in an axillary block) 

• May be used to provide central neural blockade (e.g. a 
spinal or epidural). 




Key point 

• All local anaesthetic drugs can cause toxic 
effects if given in large doses or if accidental 
intravascular injection occurs. Central nervous 
system and cardiovascular toxicity can result in 
restlessness, hypotension, convulsions, cardiac 
arrhythmias and even cardiorespiratory arrest. 

Suggested safe maximum doses of LA are 2 mg kg -1 for 
plain bupivacaine and 3 mg kg" 1 for plain lidocaine. LA 
solutions are also available with small amounts of 
adrenaline (epinephrine) (e.g. 1 in 200 000), which, acting 
as a vasoconstrictor due to its action on alpha- 1 receptors, 
reduces the absorption of the LA, thereby allowing larger 
volumes of LA to be given. Adrenaline (epinephrine) has 
also been found to act on alpha-2 receptors in the spinal 
cord, which helps to potentiate the analgesic effect of local 
anaesthetics at spinal cord level. 




Key point 

• Remember that injection of adrenaline 

(epinephrine)-containing solutions is absolutely 
contraindicated in areas supplied by end 
arteries, such as the fingers, toes and the 
penis, as prolonged ischaemia may lead to 
tissue necrosis. 

Bupivacaine is the most commonly used LA drug for 
both central and peripheral nerve blockade by virtue of its 
relatively long duration of action (2-3 h). It is prepared 
commercially as a racemic mixture of its R and S isomers. 



363 



35 

■ . -■,-.. ■■■„ „^. -...■,;-- .-^-r.^^-r^-^ 



POSTOPERATIVE 



The R isomer is thought to be responsible for the main 
drawbacks of bupivacaine, that is its greater potential for 
cardiac and central nervous system toxicity and the fact 
it can also cause profound motor block in high concen- 
tration. The drive within the pharmaceutical industry to 
produce single isomer drugs with improved safety has 
resulted in the manufacture of two new LA drugs, ropi- 
vacaine and levobupivacaine. 

Ropivacaine is the S isomer of the propyl homologue of 
bupivacaine, and was claimed by its manufacturers to be 
less cardiotoxic than its parent drug, and also to have a 
more selective blockade on A-delta and C fibres, produc- 
ing less motor blockade. However, further research has 
shown that it is about 40% less potent than racemic bupi- 
vacaine, so that in equipotent doses there may be no sig- 
nificant difference between them. 

Levobupivacaine is the S isomer of bupivacaine itself, 
and has a more favourable safety profile in laboratory 
testing than the racemate. Clinical trials have shown it to 
have similar potency to racemic bupivacaine. 

Epidural analgesia 

The epidural space is a fat-filled space within the spinal 
canal. Anaesthetists inject local anaesthetics into this 
space, and, by doing so, block nerve root transmission of 
pain. Epidural opioids can also modulate pain pathways 
once within the epidural space by diffusion through the 
dura rnater into the cerebrospinal fluid (CSF) and so to the 
opioid receptors of the spinal cord. A continuous epidural 
infusion using an indwelling epidural catheter, through 
which drugs are given for postoperative analgesia, is the 
most common catheter technique used for acute pain. 

Most hospitals in the UK nowadays use epidural infu- 
sions consisting of combinations of low dose LA (e.g. 
bupivacaine 0.1%) and opioid (e.g. fentanyl 0.0002% or 
2 (xg ml" 1 ). Such low dose combinations are synergistic. 
Side-effects related to epidural opioids alone include 
nausea and vomiting, pruritus, sedation and delayed res- 
piratory depression. Low dose mixtures, by reducing the 
amount of both LA and opioid, actually reduce the side- 
effects of both drugs. However, monitoring of the patient 
is still important. Naloxone should once again be avail- 
able to reverse opioid side-effects such as excessive 
sedation and respiratory depression. Typically, patients 
receiving low dose LA plus opioid epidural infusions 
have superior analgesia, improved cardiovascular stabil- 
ity, and the ability to mobilize due to a reduction in motor 
block. A relatively novel method of epidural pain relief, 
which may become more common, is patient-controlled 
epidural analgesia (PCEA). Similar to the PC A, it allows 
the patient to titrate the analgesia required. The same low 
dose mixture of bupivacaine and fentanyl can be used for 
a PCEA regimen. 



Indications for epidural analgesia include: 

• Surgery (intraoperative and postoperative) 

• Trauma (especially fractured ribs or pelvis) 

• Labour pain 

• Acute ischaemic pain 

• Severe angina not controlled by conventional means 
(seldom used but some papers have shown a clear 
benefit). 

Absolute contraindications are patient refusal, allergy to 
LA drugs, infection at the site of insertion, and lack of 
resuscitation equipment or skills. Relative contraindica- 
tions require an assessment of the individual's risk 
and benefit, and include hypovolemia, coexisting 
neurological disease, coagulopathy and compartment 
syndrome. 
The benefits of epidural analgesia include: 

• Effective analgesia (especially thoracic and major 
abdominal surgery) 

• Reduced opioid requirement 

• Reduction in the stress response after surgery 

• Reduction in the incidence of deep vein thrombosis and 
pulmonary embolism 

• An earlier return of gastrointestinal function after 
abdominal surgery 

• Reduction in mortality and serious morbidity post- 
operatively. 

There are, however, several complications that may arise 
following epidural analgesia: 

1. Cardiovascular. The LA causes a sympathetic block, 
which can result in hypotension due to peripheral vaso- 
dilatation. If the cardiac sympathetic fibres (T1-T4) are 
involved, this can cause bradycardia and reduced con- 
tractility. This obviously causes reduced cardiac output 
and further contributes to hypotension. 

2. Respiratory. Motor blockade of the intercostal 
muscles causes respiratory depression, and may cause res- 
piratory arrest. Epidural morphine can cause late onset 
respiratory depression (up to 24 h after administration), as 
it is the least lipophilic of the epidural opioids and hence 
takes the longest time to diffuse through the dura mater. 

3. Dural puncture. This may be caused by the epidural 
needle or catheter and, if not recognized, can result in 
extensive or total spinal block, which may require cardio- 
respiratory support. Leakage of CSF at the puncture site 
can lead to 'postdural puncture headache". 

4. Infection. This is uncommon but can result in menin- 
gitis; thus strict asepsis during epidural insertion by the 
anaesthetist is mandatory. 

5. Spinal haematoma. This is a rare but potentially dev- 
astating complication. It may occur spontaneously or be 
triggered by antiplatelet or anticoagulation therapy. 



354 



MANAGEMENT OF POSTOPERATIVE PAIN 



35 



Although it is difficult to determine the incidence rate 
accurately, a rate of 1 / 150 000 for epidurals and 1 /220 000 
for spinals has been quoted. This risk increases if there is 
a haemostatic abnormality or there has been difficulty 
with needle insertion (87% of reported cases of spinal 
haematoma had one of these problems). The signs and 
symptoms of spinal haematoma are: 

a. Increasing motor block 

b. Increasing sensory block 

c. Back pain. 

If spinal haematoma is suspected, an urgent CT or MRI 
scan and a neurosurgical opinion must be obtained. If a 
haematoma is present, a laminectomy is required to 
decompress the spinal cord and prevent or limit perma- 
nent neurological damage. (Note that epidural abscess 
presents in a similar fashion, with the additional signs of 
fever and a raised white cell count. Investigation and 
management are similar to those for spinal haematoma.) 




Key point 

• Successful acute pain management with 
epidural catheters requires regular assessment 
of the patient to detect signs of any 
complications early. Large audits of closely 
supervised epidural analgesia show the safety 
of the technique to be equivalent to traditional 
analgesic methods when coordinated by an 
acute pain service, with appropriate patient 
observations and monitoring. 

Epidurals and thromboprophylaxis. Patients at 
risk of venous thrombosis postoperatively often require 
regular subcutaneous injections of heparin. Although 
unfractionated heparin is still used, there is a growing 
move towards the use of low molecular weight heparins 
(LMWH), e.g. dalteparin and enoxaparin. Guidelines 
have therefore been drawn up to deal with the obvious 
safety issues regarding the siting and removal of epi- 
dural catheters in these patients. It is imperative that the 
nursing and medical staff caring for the patient are aware 
of these recommendations: 

• Low dose (unfractionated) heparin. Following administra- 
tion of low dose heparin, there should be a minimum 
of 4 h before the epidural is sited. A minimum of 1 h is 
recommended following the siting, or removal, of an 
epidural catheter before low dose heparin is given. 

• LMWH. An interval of 10-12 h is required after LMWH 
before performing epidural blockade. The recom- 
mended interval between epidural blockade and 
giving LMWH is 4 h. This 4 h interval also applies to 
catheter removal. 



It is accepted that aspirin and NSAID therapy per se do not 
increase risk, but in combination with low dose heparin or 
the increasingly used low molecular weight heparins, the 
risk of spinal haematoma may potentially increase. 

A caudal epidural is a single shot epidural injection via 
the sacral hiatus (sacrococcygeal membrane), which can 
be used to provide perineal analgesia for a limited 
period. It is most commonly used in children for post- 
operative pain relief after circumcision, and for some 
gynaecological procedures. 

Spinal analgesia 

Local anaesthetic drugs with or without an opioid may be 
administered intrathecally as a 'single shot" spinal injec- 
tion. An opioid such as morphine or diamorphine may 
provide useful postoperative analgesia for up to 12-24 h. 
Side-effects and complications are similar to epidural 
analgesia. Intrathecal (spinal) catheters are available, but 
owing to some case reports of cauda equina syndrome 
and arachnoiditis, they are not widely used in the UK. 




Methods of treating postoperative 
pain 

• Preoperative patient counselling and 
education. 

• Administration of opioids by various routes. 

• Wound infiltration and regional blockade with 
local anaesthetics. 

• Non-steroidal anti-inflammatory agents. 

Pre-emptive analgesia 

A hypothesis exists that surgery, which produces a 
barrage of pain signals to the spinal cord, is a 'priming' 
mechanism which sensitizes the central nervous system. 
This is said to lead to enhanced postoperative pain. The 
rationale behind several studies is that, by providing 
presurgery, or pre-emptive, analgesia using parenteral 
opioids, regional blocks or NSAIDs, either individually or 
in combination, these sensitizing neuroplastic changes 
can be prevented within the spinal cord, leading to dimin- 
ished postoperative analgesic requirements. Therefore the 
concept of pre-emptive analgesia may have implications 
in reducing not only acute postoperative pain, but also 
chronic pain states such as post-thoracotomy chest wall 
pain and postamputation lower limb stump pain. Taken 
to an extreme, a single dose of analgesic drug adminis- 
tered before surgery could theoretically abolish post- 
operative pain. Unfortunately, no current study proves 
the existence of pre-emptive analgesia in humans. 



365 



35 "• 



POSTOPERATIVE 



Specific patient groups 

Day surgical patients 

The ability to perforin increasingly complex surgery on 
a daycase basis highlights the need for appropriate 
screening, selection, preoperative preparation, treat- 
ment and discharge of these patients. The brevity of the 
patient's hospitalization and contact with healthcare 
professionals make adequate pain management a par- 
ticular challenge. 

Pharmacological options for postoperative analgesia 
include opioids, NSAIDs and local anaesthetics. Try if 
possible to prescribe opioids with shorter half-lives, to 
avoid side-effects which may delay discharge from 
hospital. The use of NSAIDs may reduce postoperative 
opioid requirements and offer a better tolerability profile, 
and is highly recommended after ambulatory surgery. 
The use of LA drugs in laparoscopic surgery, e.g. in 
wound infiltration or intraperitoneally at the time of oper- 
ation, is also effective in the treatment of postoperative 
pain, and can produce a prolonged analgesic effect. Once 
again, multimodal analgesia has been shown to be more 
effective in day surgical patients than any of these agents 
administered alone. 

Elderly patients 

When treating pain in the elderly, you must appreciate 
their generally reduced reserve and high incidence of 
concomitant disease and polypharmacy. Use NSAIDs 
with caution, as the elderly have an increased incidence 
of gastric and renal toxicity. Consider coadministration of 
a proton pump inhibitor (e.g. omeprazole) if gastric 
ulceration is of particular concern. Opioids are effective, 
with patients experiencing a higher peak and longer 
duration of pain relief, but remember that these patients 
are more sensitive to sedation and respiratory depression 
- probably as a result of altered drug distribution and 
excretion. 




Key point 



• Titrate opioid dosage carefully in the elderly to 
take into account analgesic effects and 
side-effects, including possible cognitive 
impairment. 

Children 

Preparation of the patient starts at home, as psychologi- 
cal support may decrease anxiety and fear of surgical 
procedures. The presence of parents or carers in the 



anaesthetic room decreases postoperative pain and 
reduces the risk of adverse psychological sequelae. Make 
sure that drugs are given by the least painful route, and 
analgesic efficacy is assessed at regular intervals. It has 
been clearly demonstrated that children as young as 
5 years old can understand the principles and workings 
of a PCA device. 

Opioid tolerance and addiction 

Tolerance describes the decrease in efficacy of a drug as a 
result of its previous administration. This is manifest as a 
high requirement for opioid analgesia and relative 
resistance to side-effects. Patients taking chronic opioid 
therapy require significantly increased doses of opiate in 
the acute situation. If the oral route is available, continue 
chronic oral opiates, with parenteral supplementation as 
required. Use non-opioid alternatives, if at all possible, as 
adjuncts or even as sole therapy. 




Key point 

• Surgical review is warranted if opioid 
requirements appear to increase rapidly, in 
order to rule out any surgical complication. 

Opioid addiction is unlikely to occur following the use of 
opioids for postoperative pain in opioid naive patients. 
However, when treating patients with known opioid 
dependence or addiction it is important to realize that 
pain-scoring systems are unreliable. In patients still 
using opioids, PCA may be advantageous, as it allows 
the use of high doses of opioids and may reduce con- 
frontation with staff members. Background infusions are 
a reasonable way of delivering the patient's daily 
requirement. Non-opioid therapies should always be 
considered, and epidural analgesia can be valuable after 
major surgery. In the reformed addict there is significant 
onus on clinical staff to avoid re-establishing depen- 
dency. Patients in this category presenting for major 
surgery are a particular challenge, but make every effort 
to avoid opioids without subjecting the patient to 
unrelieved pain. 



MONITORING OF POSTOPERATIVE 
ANALGESIA 






ft^;#:&*&frm^S^^ 



The effectiveness of any postoperative analgesic regimen, 
as well as any side-effects, needs to be assessed regularly. 
Ensure that the patient is monitored regularly to deter- 
mine the level of pain, sedation and respiration. 



366 



MANAGEMENT OF POSTOPERATIVE PAIN 



35 



__w.^wan-fff, 



Monitoring of pain 

The simplest method of monitoring pain is through obser- 
vation of the behaviour of the patient, for example the 
time taken for the patient to sit or stand or the ability of 
the patient to cough. You can also monitor the analgesic 
requirements of the patient (e.g. the total dose of analge- 
sia administered over a 24 h period or the number of 
demands of a PC A pump). Physiological measures such as 
heart rate and blood pressure may also increase in the 
presence of pain, but these parameters at best simply 
improve the discriminatory power of other measures. 
However, patient self-report is the most reliable and valid 
measure of pain in the clinical situation, and this is usually 
done using unidimensional scales, as illustrated (Fig. 35.2). 
Pain scores can be difficult to interpret because indi- 
vidual patients vary in their perception of pain. The 
verbal rating scale (VRS) and visual analogue scale (VAS) 
are the most commonly used methods when adjusting 



Unidimensional measures of pain Intensity 

Verbal rating scale 

The patient rates the pain verbally (e.g. none, mild, 

moderate or severe) 



Numerical rating scale 

The patient rates pain on a scale typically from 

(no pain) to 10 (severe pain) 



2 i 3 



4 S 



6 7 



8 



No pain 



To] 

Severe pain 



Visual analogue scale 

The patient indicates intensity of pain on a line typically 
10cm long marked from no pain' at one end to severe 
pain f at the other end. The pain is then scored in cm or 
mm, often with a sliding marker to aid measurement 



No pain 



Severe pain 



Faces scale 

The child indicates which face represents how much 
pain they have. Clearly this may measure other factors 
such as general distress rather than pain exclusively 




No pain 



Severe pain 



analgesic regimens such as opioid PCA or epidural 
infusions. Most pain scores only measure pain when the 
patient is resting. Obviously such a score will change 
when, for example, a patient after upper abdominal 
surgery attempts to cough to clear secretions or receives 
chest physiotherapy. Therefore pain scores on coughing 
or moving will be just as important as those at rest. 



Monitoring of sedation and respiration 

The major fear with opioids, administered by any route 
(intravenously, intramuscularly or epidurally) is that of 
respiratory depression. Epidural opioids have the added 
risk of delayed respiratory depression. This risk is 
extremely small. Highly lipid-soluble opioids such as fen- 
tanyl have a lower risk of this complication, administered 
epidurally, than does morphine, which is less lipid 
soluble. Of course you must also consider the general 
medical condition of the patient, as elderly patients with 
cardiorespiratory disease are at a higher risk of this poten- 
tially dangerous complication. Traditionally it has been 
assumed that intermittent observation of a patient's 
respiratory rate by a ward nurse is adequate to detect 
respiratory problems. It should be noted, however, that a 
decrease in respiratory rate has been found to be a late and 
unreliable indicator of respiratory depression. Sedation is 
a better indicator and all patients receiving opioids should 
be monitored using a sedation score, for example: 

= None 

1 = Mild, occasionally drowsy, easy to rouse 

2 = Moderate, constantly or frequently drowsy, easy to 

rouse 

3 = Severe, somnolent, difficult to rouse 
S = Normal sleep 




Key point 



Fig. 35.2 Commonly used pain scales. 



• A sedation score of 3 or respiratory rate less 
than 8 breaths per minute should be treated 
immediately with intravenous naloxone. 

The development of pulse oximetry, which allows a 
patient's blood oxygen saturation (Sp0 2 ) to be measured 
non-invasively using a simple finger probe, is already a 
minimum monitoring standard during anaesthesia and 
the immediate recovery period. Several studies, which 
have extended the use of pulse oximetry to the postoper- 
ative period on the ward, have detected periods of hypox- 
aemia 3-4 days after major surgery. The relationship of 
these events to the risk of myocardial ischaemia is a 
subject of ongoing research. 



367 



35 




POSTOPERATIVE 




Key point 

If using pulse oximetry, treat an Spo 2 of less 
than 94% in a patient breathing air with 
supplemental oxygen through nasal prongs or 
a face mask. 



POSTOPERATIVE NAUSEA AND 
VOMITING (PONV) 

The vomiting centre is found in the reticular formation of 
the medulla. It receives afferent impulses from various 
pathways, including the chemoreceptor trigger zone 
(CTZ). This area is located within the floor of the fourth 
ventricle and is activated by various stimuli (Fig. 35.3). 
Risk factors associated with postoperative nausea and 
vomiting include: 

• History and examination 

- Past history of PONV 

- History of motion sickness or migraine 

- Prolonged starvation 



- Recent oral intake 

- Obesity 

- Female sex 

• Type of surgery 

- Gastrointestinal 

- ENT/ophthalmic 

- Gynaecological 

- Orthopaedic 

- Emergency 

• Drugs, e.g. thiopentone, opioids. 

A number of general measures may be employed in the 
treatment of PONV, including: 

• Hydration and maintenance of adequate blood 
pressure 

• Avoiding excessive movement in the immediate post- 
operative phase 

• Reducing the patient's anxiety. 

The following agents may be useful in treating PONV: 

• Anticholinergic agents, e.g. cyclizine/hyoscine 

• Antidopaminergic agents, e.g. domperidone and 
metoclopramide 

• 5-HT3 antagonists, e.g. ondansetron. 



Oropharyngeal & 
Gut stimulation 



Raised intracranial pressure 
Hypotension Migraine 



VOMITING CENTRE 

(trans m itter : acety Ichol i ne) 

Hyoscine / Cyclizine 



-4 Vestibular stimulation 

<4 Pain 




CTZ 

(transmitter: dopamine, 5-HT) 

Domperidone, Ondansetron, 
Metaclopramide 



Hypoxaemia 




Anaesthetic drugs 



Opioid drugs 



Fig. 35.3 Management of postoperative nausea and vomiting. 



368 



MANAGEMENT OF POSTOPERATIVE PAIN 



35 



ACUTE PAIN SERVICE (APS) 



^^^^^■^ 



An anaesthesia-based multidisciplinary team approach to 
acute pain relief was first described by Ready in Seattle, 
USA. In 1990 the Royal College of Surgeons of England and 
the Royal College of Anaesthetists recommended that each 
hospital should have an APS team. The establishment of an 
APS requires medical, nursing and pharmaceutical exper- 
tise. Anaesthetists have a major role to play, as they not only 
initiate postoperative analgesic regimens, such as PCA and 
epidural infusions, but are also familiar with the drugs and 
equipment used in such cases. Many hospitals have an 
acute pain team consisting of a dedicated pain nurse, con- 
sultant anaesthetist and sometimes junior anaesthetic staff. 
The role of the acute pain team includes: 

• Devising, implementing and auditing pain protocols 

• Reviewing patients in whom postoperative analgesia is 
proving difficult 

• Reviewing patients with epidural and intravenous 
infusions 

• Managing patients with chronic pain. 



CONCLUSION 



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■f^^iT^^M^^^M^&^i^'^^^^ 



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Currently, in the treatment of postoperative pain, there is 
no single analgesic therapy that can treat all aspects of 
pain without causing side-effects. The emphasis should 
be on a 'balanced analgesic' technique, especially after 
major surgical procedures, using NSAIDs in combination 
with other drugs such as opioids or local anaesthetics. 
The future of acute pain management lies in better edu- 
cation of healthcare staff, universal introduction of pain 
scoring and improved use of existing facilities. The chal- 
lenge lies in disseminating knowledge and expertise to 
ensure that best practice is adopted universally. 



Summary 

• Pain can be treated by various methods 
which affect the transmission of a painful 
stimulus at different levels along its 
pathway to the central nervous system. 



Treatment of pain may reduce the incidence 
of some postoperative complications and 
hence reduce hospital stay. 
Opioids, given i.v. or i.m. remain common 
analgesics for the treatment of 
postoperative pain. Regional blockade 
using a low dose combination of local 
anaesthetic and opioid is also now 
popular. The concurrent use of NSAIDs is 
useful in reducing opioid requirements. 
The degree of analgesia and sedation 
must be carefully monitored on the ward. 
In most hospitals an acute pain service is 
available to advise on the methods 
available for the treatment of postoperative 
pain and potential complications associated 
with such methods. 




Further reading 

1998 Guidelines on the use of NSAIDs in the perioperative 

period. Royal College of Anaesthetists, London 
Liu S, Carpenter RL, Neal JM 1995 Epidural anesthesia and 

analgesia, their role in postoperative outcome. 

Anesthesiology 82: 1474-1506 
Lumley JSP, Craven JL (series eds) 2001 Pain, Anaesthesia and 

Intensive Care Medicine 2(11). 
McQuay HJ 1992 Pre-emptive analgesia. British Journal of 

Anaesthesia 69: 1-3 
National Health and Medical Research Council 1999 Acute pain 

management: the scientific evidence. NHMRC, Canberra 
Ogilvy AJ, Smith G 1994 Postoperative pain. In: Nimo WS, 

Rowbotham DJ, Smith G (eds) Anaesthesia. BlackweU, 

Oxford, pp 1570-1602 
Rawal N 2002 Editorial: Acute pain services revisited - good 

from far, far from good? Regional Anaesthesia and Pain 

Medicine 27: 117-121 
Ready LB 1 990 Acute postoperative pain. In: Aitkenhead AR, 

Smith G (eds) Anesthesia, 3rd edn. Churchill Livingstone, 

Edinburgh, pp 2135-2145 
Rowbotham DJ 1994 Gastric emptying, postoperative nausea 

and vomiting and antiemetics. In: Nimo WS, Rowbotham 

DJ, Smith G (eds) Anaesthesia, BlackweU, Oxford, 

pp 350-371 
Sabanathan S 1995 Has postoperative pain been eradicated? 

Annals of the Royal College of Surgeons 77: 202-209 



369 



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371 



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Complications: prevention 
and management 



J. A. R. Smith 



w 



Objectives 



Accept that complications are best 
anticipated and avoided. 
Recognize the incidence of comorbidity. 
Understand the importance of matching 
the procedure to the associated risks. 
Appreciate the importance of recognizing 
complications early and treating them 
vigorously. 



Table 36.1 Risk of cardiovascular disease with age 



RISK FACTORS 

• General - applicable to all procedures, or 

• Specific to the operation and /or the complication 
concerned. 

Old age 

In older age, some conditions are encountered more 
commonly: 

1. Neoplastic conditions. 

2. Peripheral and cardiovascular disease. The inci- 
dence of cardiovascular disease rises with age (Table 36.1) 
and this is associated with an increased risk of postoper- 
ative myocardial infarction. Over age 50 years the risk is 
6%, with a 70% mortality rate. There is also an increased 
incidence of atrial fibrillation and hypertension and 
therefore of serious dysrhythmia and death. 

3. Respiratory disease. Several changes occur in the 
elderly. These include reduced arterial oxygen tension, 
especially over 80 years of age. There are also: increased 
physiological dead space; decreased lung capacity, vital 
capacity, maximal breathing capacity, forced expiratory 
volume and peak expiratory flow rate. 

4. Renal function deteriorates with age because of 
peripheral vascular disease, loss of nephrons, and 
impaired cell function. Therefore fluid overload and dis- 
turbance of both acid-base and electrolyte balance are 
more common in the elderly. 



Age 
(years) 



Incidence of 
cardiovascular disease {%) 



40-50 


G 


60-70 


41 


70-80 


100 



5. Medication. Elderly patients are more likely to be on 
regular medication for a number of disorders. The risk of 
drug interaction is therefore increased. 

Neonatal period 

At the other end of the age spectrum, neonatal surgery is 
also hazardous: 

1. Tolerance of intravenous fluids is poor. 

2. Gastrointestinal losses by vomiting and diarrhoea 
are common and can be life threatening. There is 
increased susceptibility to disturbance of acid-base 
balance, and accurate replacement of fluid and elec- 
trolytes and correction of disturbance of pH is much more 
difficult. 

3. Thermal regulation is poor, resulting in an increased 
risk of hypothermia. Enzyme systems are immature, so 
that jaundice is more common, and both general and drug 
metabolism may be impaired. 

4. Congenital abnormalities are often multiple and 
major, and surgery is more demanding because of the 
physical size of the patient and the delicacy of the tissues. 

Obesity 

Patients may be overweight (up to 10% above their ideal 
bodyweight), obese (10-40% above) or morbidly obese 
(more than 40% above their ideal). 

Anaesthetic difficulties include difficulty in intubation 
and in the placement of intravenous lines. Chest wall 
compliance is reduced, with consequent difficulties with 
ventilation. Positioning the patient on the operating table 



373 



36 . 



COMPLICATIONS 



while avoiding pressure injuries requires considerable 
skill. In morbidly obese patients, cardiomyopathy and 
respiratory dysfunction may be severe enough to be life 
threatening. In some series, mortalities of 10-25% because 
of anaesthetic risks alone have been reported. 

Surgery is complicated by technical difficulties; these 
can include limited exposure, adipose tissue obscuring 
the view and making trauma to associated structures 
more likely and problems in minimally invasive surgery 
because of difficulty in gaining access to the peritoneal 
cavity. 

In addition, blood vessels are less well supported and 
tend to retract if divided. Control of haemorrhage is there- 
fore more difficult and haematoma formation more 
common. As a consequence, wound infection and 
impaired wound healing are encountered more often. The 
risk of venous thromboembolism is increased because fat 
patients tend to be less mobile, their weight exerts greater 
pressure on the calf veins during surgery, and there is an 
increased likelihood of endothelial trauma. In some obese 
patients there is an association with atherosclerosis and 
therefore with peripheral vascular disease. 

In orthopaedic practice, obesity increases the incidence 
of arthritis, makes joint replacement more difficult from a 
technical view point and places an extra strain on lower 
limb prostheses. Indeed, such patients may require 
bariatric surgery, such as vertical banded gastroplasty, to 
allow weight loss before joint replacement. A reduction of 
between 50 and 75% of the excess body weight over 
12 months can be anticipated. 



Table 26,2 Risk of myocardial infarction with time 



MP 



Key point 



• There is no scientific evidence that weight 
reduction is rewarded by a reduction in the 
incidence of postoperative complications. 

Cardiovascular disease 

Myocardial infarction. A recent infarct is the most 
serious predisposing factor (Table 36.2). The more recent 
the infarct, the greater the risk of a further infarct. The risk 
remains higher than normal even after an interval of 
3 years. The mortality from recurrent infarcts is also time 
related, being 75% in the first 6 months and falling to 25% 
after 1 year. Therefore, defer operations with a low risk of 
morbidity and mortality for at least 6 months post infarct. 

Angina. The severity of angina dictates the risk of 
cardiovascular complications in general and myocardial 
infarction in particular. 

Dysrhythmias. Dysrhythmias such as atrial fibrilla- 
tion and heart block carry the worst prognosis. Correction 



Time since infarct 



Incidence of further 
infarction after surgery (%) 



0-6 months 


55 


1-2 years 


22 


2-3 years 


6 


>3 years 
No infarct 


1 
0,66 



of the dysrhythmia reduces but does not abolish the risk 
of cardiovascular complications. 

Cardiac valve disease. The presence of an artificial 
valve causes a major risk of bacterial colonization follow- 
ing surgery. Administer prophylactic antibiotics for all 
procedures. Mitral valve disease increases the risk of 
atrial fibrillation and of atrial thrombosis. Significant 
valve disease impairs cardiac responses to surgery and to 
infused fluids. 

Cardiac pacemakers. These are 'foreign bodies', 
therefore administer prophylactic antibiotics. If a pace- 
maker is at a fixed rate, an inability to increase heart rate 
renders the patient vulnerable to hypovolemia. Take care 
when using diathermy, especially if it is unipolar. 

Atherosclerosis. The incidence of atherosclerosis 
tends to increase with age, e.g. at age 50 the incidence is 
23% with a 0.7% risk of myocardial infarction, while at 
age 70 the incidence of arteriosclerosis is 100%. The risk 
of cardiovascular complications shows a similar pattern 
to the incidence of atheroma. 

Hypertension. This does not increase the risk of 
myocardial infarction in abdominal surgery, but there is 
an increased risk as a result of cardiac surgery. Remember 
that surgery for phaeochromocytoma, and sometimes for 
carcinoid disease, can be associated with wide fluctu- 
ations in blood pressure. This increases the risk of cerebral 
vascular accident. 




Key points 

The combination of respiratory and 

cardiovascular disease is more serious than one 

of them alone. A combination results in arterial 

hypoxaemia and is more common in older 

patients. 

If renal function is also impaired, the risk of 

fluid overload is greatly increased. 

A normal myocardium can compensate well 

down to a haemoglobin level of 10 g dM. 

Below this level, or if there is myocardial 



374 



COMPLICATIONS: PREVENTION AND MANAGEMENT 



36 



disease, peripheral hypoxaemia is more likely. 
Even at this level, subendocardial ischaemia 
and fibrosis may occur. 



nidus for infection. Where diabetes is poorly controlled 
there may be a higher sugar level in blood and tissues; 
this also encourages bacterial growth. 



Respiratory disease 

There is an increased risk of respiratory complications in 
smokers / in patients with bronchiectasis and emphysema, 
and if surgery is undertaken in the presence of tonsillitis, 
bronchitis or even coryza (Greek kara = head + zeein = to 
boil; a head cold). In this group postpone elective surgery 
until the infection has cleared. 

As indicated above, with advancing years there is a 
reduction in arterial oxygen tension and various changes 
in lung physiology. This results in a greater difference in 
alveolar-arterial oxygen tension and thus any respiratory 
complication produces more severe hypoxaemia. 



e 



Key point 



• A combination of cor pulmonale and ischaemic 
heart disease produces a mortality of about 
50%. 

Diabetes mellitus 

Insulin-dependent diabetics are high risk patients for a 
number of different reasons. 

Metabolic factors 

The metabolic response to surgery results in hypergly- 
caemia. Maintenance of blood sugar can be difficult in the 
perioperative period and even non-insulin-dependent 
diabetics may require insulin for a short time. If compli- 
cations such as infection arise, both hyperinsulinaemia 
and hyperglycaemia may coexist - so called insulin resist- 
ance. The major danger is the development of severe 
ketoacidosis. This is seen most commonly in poorly con- 
trolled diabetic patients, or indeed in those who are pre- 
viously undiagnosed. Remember that one presentation of 
diabetic ketoacidosis is as an 'acute abdomen 7 . It is always 
sensible to measure blood and urinary glucose in all 
patients with abdominal pain. 

Infection 

In diabetes mellitus, polymorphonuclear phagocyte func- 
tion is impaired. There is an increased incidence of 
peripheral vascular disease affecting both medium and 
small vessels. Diabetic neuropathy reduces sensation to 
touch and to pain. Skin ulceration commonly acts as a 



Wound healing 

The disease in medium and small vessels reduces blood 
supply to healing tissue. The impaired polymorph phago- 
cyte function interferes with the acute inflammatory reac- 
tion. As described, there is an increased risk of infection. 
All of these factors contribute to impaired wound healing. 

Peripheral vascular disease 

The increased risk of atheroma affecting both medium 
and small arteries increases the risk of gangrene. 
Neuropathic ulcers are more common. If infection does 
occur in the presence of gangrene, wet gangrene is more 
likely to be encountered. 

Renal disease 

If diabetes mellitus has been present for 20 years there is 
a 15% incidence of glomerulosclerosis. This impairment 
of renal function makes fluid and electrolyte balance more 
complex. Diabetic patients are more sensitive to protein 
depletion, and are at increased risk of severe ketoacidosis 
during a surgical illness. 



drug™ef^ 

Antibiotics 

Misuse of antibiotics is said to be a major cause of litiga- 
tion in the USA. Anaphylactic reactions are rare but can 
be life threatening. Hypersensitivity reactions, however, 
are slightly more common and only marginally less 
serious. Ask about drug allergy during the systematic 
enquiry of every patient. 

Misuse of antibiotics may result in the development of 
resistance. The most serious from the point of view of the 
patient and the surgical department is the methicillin- 
resistant Staphylococcus aureus (MRS A). It is important to 
have a hospital antibiotics policy, with clear indications 
for the use of antibiotics. Use them for a specific period 
only and take advice from the microbiologist for complex 
infections or immunocompromised patients. 

The risk of MRSA infection in healthy individuals is 
very small but to ill patients in hospital can be life threat- 
ening. Isolate patients who have bacteriological evidence 
of MRSA infection and barrier nurse them. In patients 
who are unwell, administer appropriate antibiotic 
therapy according to advice from the microbiologist. 



375 



3il 



COMPLICATIONS 



Pseudomembranous colitis 

This may present as a surgical emergency. Exposure to 
antibiotics combined with a period of hypovolaemia or 
hypotension are joint factors in pathogenesis. Diagnosis is 
made on the basis of a frozen section biopsy taken at sig- 
moidoscopy and confirmed by the demonstration of the 
Clostridium difficile toxin in the faecal fluid. Intravenous 
vancomycin or metronidazole are usually effective in 
treatment. Occasionally total colectomy is required for 
resistant cases. 

Aminoglycocides 

Gentamicin causes ototoxicity in 3% of patients. The 
elderly and those with impaired renal function are at 
increased risk. It causes nephrotoxicity in 2% of patients. 
For that reason monitor peak and trough blood levels in 
all patients receiving this therapy. 

Corticosteroids 

The greatest risk of complications occurs in patients on 
high dosage or on long courses of therapy. 

Corticoids act to interfere with the mobility and phago- 
cytic activity of polymorphonuclear leucocytes. This means 
that acute inflammation and the handling of bacteria are 
impaired, including the inflammatory reaction which is an 
essential part in the repair of wounds. Therefore deficient 
wound healing and wound infection are more common. 

The production of ground substance is reduced. 
Therefore capillary fragility is increased and wound 
haematoma is more common. This contributes to impaired 
wound healing and also provides a nidus for infection. 
Note, however, that in experimental circumstances the 
short term use of methylprednisolone has not been asso- 
ciated with impaired healing of colonic anastomoses. 

Stress response 

Steroid therapy within the 6 months before surgery 
depresses the endogenous production of glucocorti- 
coids. The output of endogenous glucocorticoid is an 
essential part of the response to surgery and anaesthesia. 
In order to avoid this complication the patient should 
receive 100 mg of hydrocortisone intravenously at the 
induction of anaesthesia and at 6-hourly intervals for 
48 h. Over the next 5-7 days reduce the intake of gluco- 
corticoid either to zero or to the preoperative level. 

Delay in diagnosis 

Because of the depression of the acute inflammatory 
reaction, steroid therapy may delay the diagnosis of 



postoperative complications. It may also render some 
complications more likely to occur. For example, if a 
peptic ulcer perforates in someone on steroid therapy the 
diagnosis may be delayed, with resulting increase in 
morbidity and mortality. 

There is some evidence that glucocorticoids in 
dosages used for immunosuppression may encourage 
the development of certain virally induced tumours. In 
transplant patients there is evidence that the incidence 
of head and neck tumours and the virally induced 
tumours may be increased. This has not been reported in 
more common tumours of lung, breast or gastrointesti- 
nal tract. 

Orthopaedic practice 

Patients who are on steroid therapy in general, and those 
on steroids for rheumatoid arthritis in particular, have an 
increased risk of osteoporosis, which makes them more 
prone to suffer pathological fractures. Joint replacement is 
more difficult in such patients because of bone thinning 
and because of the general complications mentioned 
above. 

Cytotoxic agents 

Patients on cytotoxic chemotherapy have well-recognized 
problems of gastrointestinal upset and hair loss. 
Depression of the white cell count and white cell function 
interfere with acute inflammation. This produces an 
increased incidence of wound infection and of impaired 
wound healing. Bone marrow depression is common. This 
also increases the risk of infection, especially with oppor- 
tunistic organisms. It also risks purpuric eruption and 
frank bleeding. The expected reduction in cell-mediated 
immunity increases the risk of developing a second neo- 
plasm; for example, in patients successfully treated for 
primary lymphoma there is a 3% risk of a second tumour 
developing. 

Ciclosporin 

Ciclosporin A carries all the risks of depressing immune 
responses. More specifically it can result in depression of 
renal function. This is the usual reason for having to dis- 
continue therapy with this agent. 



BLOOD TRANSFUSION 

Incompatibility 

Major incompatibility reactions are now rare, even with 
emergency crossmatching. Minor group incompatibility 



376 



COMPLICATIONS: PREVENTION AND MANAGEMENT 




is more common, especially in patients who have had 
repeated transfusions. This involves, in order of import- 
ance, the Kell, Duffy or Kidd systems. It is common to 
attribute febrile reactions to incompatibility. Remember 
that transfusion of pyrogens or antibodies to white cells 
are alternative explanations for a febrile reaction. 

Consequences of storage 

The lifespan of red cells is finite and therefore lysis is an 
inevitable consequence of storage. This may produce 
transient jaundice but is not of dire consequence. More 
importantly there is a potential for hyperkalemia after 
massive blood transfusion because of the release of the 
intracellular potassium ion. Careful monitoring of such 
patients by regular assessment of urea and electrolytes 
and of ECG changes, which begin to occur above a level 
of 6 mmol 1"\ are essential. 

Acid citrate dextrose 

This is the most commonly used anticoagulant. 
Transfused citrate may bind free calcium, resulting in 
hypocalcaemia. Careful monitoring of the ECG is essen- 
tial. Both platelets and clotting factors are consumed 
within some hours of storage. As a consequence, trans- 
fused stored blood cannot be relied upon to correct haem- 
orrhagic tendencies and transfusion of fresh platelets or 
fresh frozen plasma may be required. 

Oxygen carriage 

The level of 2,3-diphosphoglycerate falls in stored red 
cells. This produces a shift of the oxyhaemoglobin dis- 
sociation curve to the left, resulting in an increased affin- 
ity of haemoglobin for oxygen. Delivery of oxygen at 
tissue level is therefore reduced. Stored red cells become 
more rigid. This impairs capillary circulation and encour- 
ages sludging. 

Transmission of disease 

In the past, both syphilis and hepatitis B were transmit- 
ted by transfusion (see Ch. 21). These diseases have been 
virtually abolished by stringent screening methods. 
Hepatitis C remains a significant risk in some countries 
where screening is not well established. Earlier serologi- 
cal tests were unsatisfactory but more specific immuno- 
logical tests, such as immunoblotting, are now available. 
In Britain most case of hepatitis C are associated with 
drug abuse. More recently, the human immunodeficiency 
virus (HIV) has been transfused, mainly to haemophilic 
patients, with disastrous consequences. 



Alteration in immunity 

In transplantation surgery it is clear that the risk of renal 
rejection is reduced after blood transfusion. In patients 
undergoing resection for colonic cancer, perioperative 
transfusion results in a poorer prognosis, even when 
groups are matched for stage of disease, degree of oper- 
ative trauma, age, sex and other factors. This is attributed 
to a reduction in cell-mediated immunity. Other neoplas- 
tic processes and the relevance of blood transfusion to 
prognosis remain under investigation. In colorectal 
surgery, the use of blood transfusion is also associated 
with an increased risk of infective complications in the 
postoperative period. This risk has not been identified in 
patients undergoing joint replacement in orthopaedic 
practice. 



Obstructive jaundice 

1. Effect on coagulation. Patients with obstructive jaun- 
dice have an increased risk of haemorrhage in the peri- 
operative period. The absorption of the fat-soluble 
vitamin K is impaired in the absence of bile salts. This 
interferes with the production of the vitamin K-dependent 
factors II, VII, IX and X. The liver manufactures most clot- 
ting factors and therefore back pressure from obstruction 
may interfere with the synthesis of these factors and also 
factors V, XI, XII and XIII. The liver also clears activated 
coagulation factors such as fibrin degradation products 
(FDPs). When there is severe impairment of liver function 
there may also be disseminated intravascular coagulation. 

All patients with obstructive jaundice should have a 
full clotting screen. Depending on the results of that 
screen, patients should be given systemic vitamin K a 
and /or fresh frozen plasma. The intravenous route for 
vitamin K T is recommended because it reduces the risk of 
intramuscular haematoma. 

2. Effect on wound healing. Back pressure interferes with 
hepatocellular function and therefore disturbs protein 
metabolism. There is clear evidence that where obstructive 
jaundice is due to a malignancy there is impairment of 
healing of wounds and anastomoses. It is also taught that 
the same problem occurs in all patients with obstructive 
jaundice. The evidence for this is less clear. However, 
sufficient doubt remains for all patients with obstructive 
jaundice to be considered at high risk of wound failure. 

As already indicated, an increased incidence of wound 
haematoma and infection will also interfere with wound 
healing. 

3. Effect on infective complications. Stasis within the 
biliary system increases the risk of infection, particularly 



377 



36 



COMPLICATIONS 



with Gram-negative organisms. It is well established that 
opening the common bile duct produces a threefold 
increase in the incidence of wound infection relative to 
cholecystectomy alone. Where obstructive jaundice is sec- 
ondary to stones or to postoperative stricture, the inci- 
dence of infected bile is at least 75%. With malignant 
obstruction, incidences of infection of 25% have been 
reported. The more often the bile duct is operated upon, 
the more likely there is to be infected bile with a conse- 
quent increase in postoperative infective complications. 

The whole picture is complicated by the fact that there 
is reduced efficacy of the reticuloendothelial (Kupffer) 
cells in the liver. In the presence of infected bile there is an 
increased incidence of septicaemia, but also an increase in 
the production of endotoxins. Furthermore, there is a poss- 
ibility of translocation of bacteria from the small bowel. 
This combination may overcome the capacity of the retic- 
uloendothelial system. The result is increased mortality 
and morbidity, particularly from ascending cholangitis. 
This means that the incidence of septicaemia and endo- 
toxinaemia is increased. Increased mortality and morbid- 
ity result, particularly from ascending cholangitis. 

4. Effect on renal function. Following surgery for 
obstructive jaundice, patients are at risk from acute renal 
failure - the 'hepatorenal syndrome'. There are a number 
of theories as to aetiology. 

Acute renal failure is also a. complication of Gram- 
negative septic shock, believed to be caused by the effects 
of endotoxins. The effects include activation of comple- 
ment by the alternative pathway, the release of a number 
of cell mediators, including tumour necrosis factor and 
interleukins, and inappropriate disseminated intravascu- 
lar coagulation (DIC). DIC results in microthrombi being 
found in the renal parenchyma, thus interfering with 
renal function. 

It is also said that at least some part of renal failure 
occurs because the tubules are blocked by excess biliru- 
bin. Histological evidence of this is variable and, at most, 
it is likely to be no more than a contributing factor. 

The hormones responsible for maintaining fluid and 
electrolyte balance, such as antidiuretic hormone (ADH), 
aldosterone and natriuretic factors, are metabolized in the 
liver. Disturbance of hepatic function may interfere with 
the activities of these hormones. Because of the increasing 
problems of haemorrhage, patients with obstructive jaun- 
dice are at greater risk of hypovolemia. Protection 
against the effects of obstructive jaundice on renal func- 
tion are to ensure adequate perioperative fluid infusion 
and a good diuresis, e.g. by the use of the osmotic diuretic 
mannitol. Give prophylactic antibiotics. 

5. Effects on drugs and metabolism. It is assumed that 
general drug metabolism is altered in the presence of 
obstructive jaundice. The evidence in support of this is 
not strong. However, a particular problem does arise for 



drugs which are oxidized in the liver. In surgical practice 
great caution is required with analgesic and sedative 
therapy with, for example, morphine-like agents. 

6. Take note of the specific problems relating to 
warfarin and the interference with the International 
Normalized Ratio (INR) produced by certain antibiotics. 

Neoplastic disease 

Venous thromboembolism 

The association between superficial thrombophlebitis 
migrans and pancreatic carcinoma is well established. 
However, it seems likely that malignant tumours secrete 
factors, such as thromboplastins, which affect the throm- 
botic cascade. In general terms, oncological procedures 
tend to be prolonged, they are associated with greater 
operative trauma, and they often require blood transfu- 
sion; all of this increases the incidence of deep vein 
thrombosis. Both in urology and in gynaecology, major 
procedures in the pelvis are at particular risk of this com- 
plication. In addition to the factors mentioned above, 
pressure on the iliac veins is a significant problem. 

Wound healing 

It is generally accepted that patients with carcinoma are 
at increased risk both of primary wound failure and later 
incisional herniation. This relationship has been most 
clearly confirmed in malignant obstructive jaundice. In 
this condition malnutrition is combined with impaired 
protein metabolism in the liver. 

The whole concept of cancer cachexia is complex, and 
in patients who have lost more than 10% of their premor- 
bid body weight, or who present with a serum albumin of 
less than 30 gl -1 , there is impaired healing both of 
wounds and anastomoses. 

Patients with ovarian cancer have a high incidence of 
ascites with omental and peritoneal deposits. In contrast 
to gastrointestinal malignancy, radical surgery in these 
patients can be rewarding. However, this involves the 
rapid loss of protein-rich fluid. If the ascites reaccumu- 
lates rapidly in the postoperative period there will be 
associated abdominal distension and leaking through the 
wound. Both of these factors also impair wound healing. 



TWE^OF SURGERY 
Minimally invasive surgery 

No field of surgical practice has escaped the introduction 
of minimally invasive procedures. The picture is most 
clearly established in laparoscopic cholecystectomy, 
where there is evidence of more rapid recovery from 



378 



COMPLICATIONS: PREVENTION AND MANAGEMENT 




36 



surgery, earlier discharge from hospital and earlier return 
to normal activities. The operation of minicholecystec- 
tomy has been compared with the laparoscopic route, 
with no clear benefit of the latter being proven. 

The learning curve for this new form of operation can 
be long. This is because hand-eye coordination is differ- 
ent from conventional surgery and because the handling 
of tissues at a distance means that tactile sensitivity is 
reduced. Visual fields are limited, which is of particular 
importance when diathermy, laser or intracorporeal 
suturing are being applied. Take great care to visualize 
probes and needles and to keep them within your visual 
field at all times. 

More recently, the concept of hand-assisted laparo- 
scopic surgery has been developed. This is of particular 
relevance to gastrointestinal surgery. Only time will tell 
whether such a combined approach avoids some of the 
problems of laparoscopic surgery, for example, radical 
ablation of neoplastic disease and port-site recurrence. 

A particular problem exists when diathermy is used 
when capacitance coupling may occur, resulting in burn 
injuries at the trocar sites. Initially there was a vogue for 
the use of laser-assisted dissection; this has largely been 
overtaken by diathermy. However, if you use laser, take 
all the normal precautions for the use of lasers, and gain 
a clear understanding of the characteristics of the differ- 
ent forms of laser in current use. 

With specific reference to cholecystectomy, it is clear 
that there is at least a fivefold increase in the incidence of 
bile duct injury in comparison with conventional surgery. 
Take great care to identify the anatomy and be willing to 
convert to open cholecystectomy if you encounter diffi- 
culty or if your held of view is obscured. 

Orthopaedic surgery 

Thromboembolism 

Operations on the hips and pelvis have an increased risk 
of deep venous thrombosis (DVT), so prophylactic war- 
farin is often administered. Recent reports have demon- 
strated the value of low molecular weight heparin. The 
risk is higher if surgery is performed after major trauma. 
Blood transfusion also increases the risk of DVT. 



Wound infection 

Most orthopaedic procedures are classified as clean. 
Therefore the incidence of wound infection is low. 
However, the consequence of infection, for example after 
joint replacement, is catastrophic. If a foreign body such 
as a joint prosthesis becomes infected, the chance of 
eradicating the infection by antibiotics is minimal. It is 
necessary to remove the prosthesis. 



Use of tourniquets 

In orthopaedic surgery tourniquets are widely used and 
it is recognized that tourniquet time must be kept to a 
minimum. However, it is vitally important that you assess 
the vascular supply, especially to the lower limbs. If you 
do not, the potential hazard of, for example, knee replace- 
ment is greatly increased. Remember also that skin 
ischaemia may complicate badly planned incisions. 

Steroid therapy 

The problem with steroid therapy has already been men- 
tioned. Especially in patients on steroids for rheumatoid 
arthritis, surgery is more difficult and anaesthetic problems 
may be faced, for example if the cervical spine is involved. 

Gynaecological surgery 

In operations within the pelvis, and particularly those 
lasting over 45 min, there is increased risk of trauma to the 
pelvic veins. This increases the risk of iliofemoral throm- 
bosis. Extensive oncological eradication carries, in addi- 
tion, all the risks relevant to cancer surgery (see above). 

Thoracic and upper abdominal procedures 

Incisions used for this type of surgery usually cause 
exceptional postoperative pain. Respiratory movement 
may be restricted, increasing the risk of atelectasis and 
infective complications, especially in elderly patients. 

Prolonged operations 

Traditional teaching is that prolonged operations increase 
the risk of respiratory difficulties, fluid and electrolyte 
imbalance and deep vein thrombosis. Experience with 
prolonged keyhole operations by the laparoscopic route 
have proved them relatively free of complications. This 
seems likely to be related to reducing the influence of 
such factors as: 

• Intraoperative trauma 

• Need for blood transfusion 

• Loss of fluid and heat from exposed cavities 

• Minimal damage to tissues. 




Key point 

Prolonged time spent on the operating table 
does not inevitably cause respiratory 
thrombotic, fluid balance and electroyte 
disturbances. 



379 



36 



COMPLICATIONS 



Remember that although the incidence of complications 
may be lower in minimally invasive surgery, they are not 
abolished. Deep vein thrombosis, wound infection and 
wound hernia at port sites do occur. Therefore take pro- 
phylactic measures and carefully monitor patients in the 
postoperative period. 



COMPLICATIONS AND THEIR 
MANAGEMENT 






Venous thromboembolism 

Risk factors 

These include obesity, old age and malignant disease. 
Long operations, pelvic and hip surgery, a past history of 
DVT or pulmonary embolism and varicose veins increase 
the risk. Other provoking factors are pregnancy and the 
oral contraceptive pill. 

Incidence 

The incidence varies with the type of operation and the 
risk factors mentioned. 




Key point 



• It is estimated that for every 1000 operations 
there are 100 deep vein thromboses, ten 
pulmonary emboli and one death. 

Diagnosis 

Early diagnosis is difficult and clinical diagnosis inac- 
curate. Experimentally, 125 I-hbrinogen scanning is sensi- 
tive in detecting developing thrombi but is of no value for 
established thrombosis. It is likely this test overestimates 
the incidence of clinically significant thrombi. The new 
D-dimer assay is a very sensitive screening test which can 
be performed at the bedside. Validation is still required 
but it seems likely that, if the test is negative, DVT is not 
present. Be cautious in interpreting the result as it may be 
positive, for example in the presence of an inflammatory 
process. Doppler ultrasound scans are valuable detecting 
peripheral sites. However, isolated calf vein thromboses 
are probably of no significance. 

For suspected iliofemoral thrombosis a colour duplex 
scan is the investigation of choice. Where this is negative, 
repeating the scan in 1 week is probably preferable to 
venography. Venography has been the gold standard for 
diagnosis in the past but colour duplex appears to be 
more accurate and is clearly less invasive. 



Prophylaxis 

Because of the difficulties of diagnosis, prophylaxis is the 
cornerstone of management. Correct risk factors such as 
obesity, or stop the taking of the contraceptive pill if clini- 
cally possible. The time of maximum risk of a thrombosis 
developing in surgical practice is during the operation, 
when the three factors of stasis, endothelial trauma and 
increased coagulability are most prevalent. 

Electrical methods of stimulating muscle function and 
thereby maintaining blood flow have been superseded. 
Mechanical methods, such as intermittent pumping of the 
calves by air insufflation of below knee stockings, are 
again popular. 

Subcutaneous calcium heparin (5000 units), injected 2 h 
before surgery and continued postoperatively 12-hourly 
until the patient is fully mobile, is a well-established 
method of reducing the incidence of DVT. Calcium 
heparin causes less bleeding than sodium heparin. More 
recently, the low molecular fragment heparin has been 
shown to be at least as effective for general, gynaecologi- 
cal and orthopaedic surgery. It may reduce the risk of 
perioperative bleeding, although this is still debated. A 
once per day dosage regimen saves nursing time, 
decreases patient discomfort and is cost effective. Some 
orthopaedic surgeons favour full anticoagulation with 
warfarin as prophylaxis for major joint replacement, espe- 
cially for revision surgery. Shorter operating times and 
earlier mobilization have contributed to the decreased 
risk. 



Treatment 

Do not anticoagulate the patient if the thrombus can be 
shown to be confined to the calf and is less than 5 cm 
long. Analgesics and support stockings may well be 
helpful. Take care when actively treating patients with a 
dyspeptic history or with a history of cerebrovascular 
accident. 

Most patients require intravenous heparin; give a 
loading dose of 10 000 units, followed by continuous 
intravenous infusion to prolong the activated partial 
thromboplastin time (APTT) by twice the control level. 
Thereafter, continue anticoagulation with warfarin for at 
least 3 months. Especially in hip replacement, the risk of 
DVT persists for several weeks. Low molecular weight 
heparin by subcutaneous injection is being used increas- 
ingly for established DVTs. 

Complications 

Pulmonary embolism may be fatal. Multiple emboli 
produce pulmonary hypertension. Diagnosis is on the 
basis of a radioisotope ventilation/ perfusion lung scan. 



380 



COMPLICATIONS: PREVENTION AND MANAGEMENT 



36 



More recently spinal computerized tomography (CT) scans 
have proved of greater value. If surgery is contemplated, 
as for a major embolism in a specialist centre, perform pul- 
monary angiography if time allows. Alternatively, stimu- 
late thrombolysis using streptokinase or urokinase, or fully 
anticoagulate the patient, as described for DVT. 

Postphlebitic limb is more likely to follow an occlusive 
iliofemoral thrombosis. Treatment is symptomatic with 
support stockings and analgesics or aimed at treating the 
venous ulcers, which can complicate this condition, prob- 
ably secondary to dermatoliposclerosis. 

Respiratory complications 

Postoperative respiratory complications are the most 
common, but because of the various risk factors involved 
a true incidence is difficult to establish. 

Risk factors 

Arterial oxygen tension falls gradually with age, more 
rapidly over the age of 80. Vital capacity, lung capacity, 
peak expiratory flow rate and postexpiratory volume are 
all reduced. Cardiovascular disease is more common with 
advanced years and a combination of cardiovascular and 
respiratory problems is particularly serious. 

The risk of respiratory complications is increased with 
obesity, excessive sedation, immobility, pre-existing lung 
disease and myocardial disease, especially following 
cardiothoracic, upper abdominal and vertical wounds, 
all of which reduce expiratory movements. 

Pathology 

The commonest problem after surgery is atelectasis 
(Greek a = not + telos = complete + ektasis = stretching out, 
expansion). Small plugs of mucus block minor air pas- 
sages and cause localized collapse. The plugs can usually 
be coughed clear with the aid of physiotherapy, but if 
they are not, superinfection may result. Pulmonary 
embolus (see above) may also predispose to infection. 
Pulmonary effusion often complicates pulmonary pathol- 
ogy such as infection, infarct or metastatic disease. An 
effusion may also result from a subdiaphragmatic abscess 
or pancreatitis, or complicate congestive cardiac failure 
and hypoalbuminaemia. Pneumothorax may complicate 
ventilation, or cannulation of central veins, either for 
monitoring central venous pressure or for parenteral 
nutrition. 

Adult respiratory distress syndrome (ARDS) is the 
most serious pulmonary complication in surgical practice. 
It may complicate severe sepsis, fluid overload, chest 
trauma, fat emboli, burn injury and inhalation pneu- 
monitis. The cause is unclear but contributing factors are: 






Changes in type I and II alveolar cells, resulting in loss 
of surfactant and alveolar collapse. 
Impaired capillary to alveolar diffusion. 
Arteriovenous shunts. 

The effects of endotoxin resulting in complement 
activation by the alternate pathway and disseminated 
intravascular coagulation (DIC). 

Consequent upon the effects of endotoxin, numerous 
mediatory cytokines such as tumour necrosis factor or 
interleukins are released; these contribute to pul- 
monary damage. 
The effects of hyperoxide radicals. 



Management 

Where possible, correct clinical risk factors such as obesity 
and smoking habit prior to surgery. Ensure that the 
patient receives adequate analgesia without excessive 
sedation. Encourage regular physiotherapy administered 
both by the therapist and by the nursing and medical 
staff. Time physiotherapy so that the patient is free of pain 
but not oversedated. 

Carefully monitor the pulse, respiratory rate and tem- 
perature. Administer appropriate antibiotics to patients 
who are pyrexial despite conservative measures, clinically 
ill, at high risk, especially if there is combined myocardial 
and pulmonary disease, and all patients with features of 
ARDS. 




Key point 



• Give supplementary oxygen by mask; if despite 
that, the Pao 2 falls below 75 mmHg, consider 
ventilatory support. 

Figure 36.1 illustrates the procedure when a 'trigger' 
necessitates considering transferring a patient to the high 
dependency unit for more intensive monitoring and 
treatment. 



Infective complications 

Risk factors 

Alimentary surgery generates a higher incidence of 
infection: this is often associated with endogenous 
organisms. In 'clean 7 surgery, infection is usually sec- 
ondary to exogenous agents. Wounds may be classified 



as: 



Clean, such as thyroid or hernia surgery 

Potentially contaminated, as in elective gastrointestinal 

surgery 



381 



36 



COMPLICATIONS 



Patient 'triggers' 
(using EWI) 



I 



HO review 



5 



Resolves <} 



To be reviewed by 

SHO or Reg, 
within 30 minutes 



I 



Continues to 
'trigger 1 



JL 



Critical Care 

opinion 



To be reviewed by Registrar 

and Consultant 



^^^^^^^^^™ 



Fig. 36.1 Patient referral algorithm. EWI = Early 
Warning Indicator. 



• Contaminated, as following bowel perforation 

• Dirty, when there is faecal contamination. 

The incidence of infection, morbidity and mortality 
increases from clean to dirty. The risk of infection is 
greater in all categories if surgery is performed as an 
emergency. 

In 'clean' operations, infection is usually secondary 
to exogenous agents such as Staphylococcus aureus. 
Whenever there is a series of infections in one unit fol- 
lowing clean procedures, seek a source of carriage of such 
organisms. In alimentary surgery the infecting organisms 
are usually endogenous. These are usually Gram-negative 
aerobes. Where surgery is performed in the lower ileum 
and in the large bowel, remember the importance of 
anaerobic infection. 




Key point 

• Although the incidence of wound infection is 
low after clean procedures, its consequences 
may be catastrophic, as following joint 
replacement or valvular heart surgery. 

The risk of wound infection is increased in the presence of 
obesity, in haematomas and in patients with diabetes 



mellitus. Other factors are glucocorticoid therapy, immuno- 
suppression, malnutrition and obstructive jaundice. 



Prophylaxis 

Identify the patients at risk. This includes those in whom 
the incidence of infection is higher and those for whom 
infection is particularly hazardous. Reduce or control risk 
factors if possible. Ensure that your surgical technique is 
as perfect and as meticulous as possible, with particular 
reference to haemostasis, avoiding excessive use of 
diathermy, leaving dead space or traumatizing tissues by 
rough handling. 

Select the appropriate antibiotic to give the greatest 
protection and tissue penetration at the time of surgery. 
Remember to take account of possible patient allergies 
and the cost involved. It is sufficient to give one dose 
intravenously at the time of induction. Alternatively, give 
one dose intramuscularly with the premedication. Give 
more than one dose only if the operation lasts longer than 
4 h or if there has been contamination during gastro- 
intestinal surgery. In this case you are practising 
treatment rather than prophylaxis. 

Remember the value of mechanical bowel preparation, 
which reduces loading at the time of large bowel anasto- 
mosis but does not remove pathogens from the gastro- 
intestinal tract. 

There is continuing controversy about the need for, and 
timing of, shaving the operative area (see Chs 15, 22). 
There is some evidence that shaving increases the number 
of potential pathogens on the skin. There is also contro- 
versy about the agent used for skin preparation, 
Chlorhexidine in spirit (Hibiscrub) or aqueous povidone- 
iodine (Betadine) are both acceptable. Debate continues 
about the value of intracavity antibiotics or antiseptics 
and these have probably been superseded by prophylac- 
tic antibiotics. 

In potentially contaminated surgery there is no value in 
using plastic drapes; these tend to increase the number of 
pathogens on the skin. The use of danger towels, separate 
knives for incising skin and deeper tissues and changing 
gloves after performing anastomoses are now of histori- 
cal interest only 

The principles of antibiotic prophylaxis are: 

1. Identify patients at risk. 

2. Select an appropriate antibiotic according to the type 
of operation. 

3. Take account of the patient's allergies and the costs 
involved. 

4. Administer the antibiotic, either intravenously at 
induction or intramuscularly with the premedication; 
ensure adequate serum and tissue levels at the time 
of surgery. 



382 



COMPLICATIONS: PREVENTION AND MANAGEMENT 




5. Repeat the administration of antibiotic in operations 
lasting longer than 4 h. 




E 



Key point 



• Antibiotics are no substitute for gentle 
handling of tissues, careful haemostasis, 
judicious use of diathermy and avoiding 
strangling tissues with ligatures and sutures. 

Treatment 

Wound infection. Open the wound to allow ade- 
quate drainage. Obtain pus for culture to establish the 
infecting organism(s) and their antibiotic sensitivity. 
Irrigate the wound for adequate drainage and debride- 
ment. Formally reopen and surgically debride dirty 
wounds. If clean wounds become infected, consider 
cross-infections and investigate the likely sources. 

Use antibiotics only if specifically indicated (for cellu- 
litis or septicaemia) or if the consequences of infection 
would be disastrous (see above). 

If the wound infection is chronic, consider the possibil- 
ity of specific organisms such as Actinomyces, a foreign 
body, such as a suture in the wound, an associated fistula 
as may occur in Crohn's disease/ or associated factors 
such as irradiation and perineal wounds. Remember the 
danger of synergistic infections and dermal gangrene. 

Postoperative abscess. These are usually intraperi- 
toneal but can occur deep in the wound. Localize the 
abscess and attempt drainage, if necessary under ultra- 
sound or computed tomography (CT) control. Monitor 
resolution of the cavity radiologically if necessary. 
Exclude anastomotic leakage as a cause (see below). 

If the patient remains toxic or the cavity fails to resolve, 
proceed to operative drainage and definitive treatment of 
any underlying sepsis. If you strongly suspect an abscess, 
this may involve an exploratory laparotomy, even when 
the scan is inconclusive. 

Septicaemia and septic shock. The septic compli- 
cations mentioned above may progress to septicaemia 
and septic shock in patients who are debilitated by 
disease or drug therapy such as steroids or cytotoxic 
chemotherapy. However, some organisms may be partic- 
ularly virulent from the outset. 

Remain alert after operation for all septic problems. The 
danger signs are: 

• Persistent, often swinging pyrexia with tachycardia 

• Signs of toxicity - flushed warm skin, glazed eyes, 
tachypnoea 

• Falling urinary output - less than 40 ml fr 1 

• Hypoxaemia. 



Key point 

• Treat suspected septic shock effectively to 
avoid low output septic shock with its 
associated high mortality (>50%). 

The nature of death in such patients is multiple organ 
failure, and while a patient may survive failure of a single 
organ system such as the kidneys, the more organs which 
fail the higher the mortality (Table 36.3). 

This problem is most likely to be encountered if you 
delay identifying and localizing a septic focus, and fail to 
institute adequate initial treatment. 

The principles of treatment are: 

1 . Ensure adequate circulating blood volume using a 
mixture of crystalloid and colloid fluids, aiming for a 
central venous pressure of 10-15 cmH 2 in a 
ventilated patient. 

2. Oxygen supplementation. 

3. Broad-spectrum intravenous antibiotic(s). 

4. Ventilatory support if the Pao 2 is less than 75 mmHg 
despite 40% oxygen by mask. 

5. Cardiac support with such drugs as dopamine, 
dobutamine, digitalis and catecholamines, as 
indicated. 

6. Attention to renal function with dialysis for 
established renal failure. 

7. Early recognition and treatment of any evidence of 
multiple organ failure. 

8. Collaborate closely with specialist colleagues in 
intensive care, and where required with cardiac, 
respiratory and renal physicians. 

More controversial are the methods used in some centres 
to ensure gastrointestinal decontamination. This involves 
a combination of enteral antibiotic and antiseptic agents, 
combined with a parenteral antibiotic, and this is gaining 
popularity. The value of enteral glutamine and/or a- 
ketoglutarate is considered vital in several intensive care 
units. This is yet to be proven in a controlled trial. 
However, enteral nutritional support is preferable to the 
parenteral route. 



Table 36.3 Multiple organ failure: rates of survival 



No. of organs 



1 
2 
3 



Survival (%) 

90 
40-50 

5-10 



383 



36 7 



COMPLICATIONS 



Anastomotic leakage 

Anastomotic leakage may complicate any anastomosis, 
but is seen most commonly following oesophageal and 
colorectal surgery. In the latter group, leakage results in a 
threefold increase in operative mortality. 

Colonic anastomoses below the pelvic peritoneal 
reflection are associated with an increased risk of 
leakage, both clinically and radiologically detected 
(Table 36.4). The clinical rate always underestimates the 
true incidence of leakage, as detected by Gastrografin or 
barium enema. 

Predisposing factors 

The general factors are similar to those which apply to 
wound healing in general, such as nutritional deficiencies 
(particularly protein, vitamin C and zinc), old age and 
impaired local blood flow from general conditions such as 
arteriosclerosis and cardiac disease. 

Local factors include tension at the anastomosis and 
poor surgical technique with regard to preparing the 
bowel ends, handling of tissues / excessive use of 
diathermy and the insertion and ligation of sutures. 
Contamination of the anastomosis with liquid faeces 
prejudices healing, as does an inadequate vascular supply 
to one or both sides of the anastomosis. Less important 
factors are the suture material, the number of layers 
employed, and whether a stapling or suturing technique 
is used. However, there is preliminary evidence that 
tumour recurrence is lower in experimental studies when 
stainless wire is used for the anastomosis and, in clinical 
work, if the anastomosis is stapled. 

Presentation 

Gastrointestinal contents may be identified in the wound 
or at a drain site. An intra-abdominal abscess or more 
serious septic complication may develop. There may 
be prolonged adynamic ileus, unexplained pyrexia or 



Table 36,4 Rates of clinically evident and 
radio logically detected leaks following colonic 
anastomoses performed above and below the 
pelvic peritoneal reflection 




Location of anastomoses Detected leaks {%} 



Clinical Radiological 



Above pelvic peritoneum 1.2 

Below pelvic peritoneum 16 



18.3 
33 



tachycardia, sudden collapse postoperatively or develop- 
ment of an internal fistula. 

Where there is any doubt, confirmation can often be 
obtained from a gently performed X-ray using a contrast 
medium. In this regard, Gastrografin, which is water 
soluble, is preferable to barium because leakage of barium 
has much more serious consequences if present free in the 
peritoneal cavity. 



Management 

If the patient is adversely affected by peritonitis, shock or 
infection, be prepared to intervene with: 

1 . Adequate resuscitation 

2. Antibiotic cover 

3. Operation. 

The surgical procedure depends on the operative find- 
ings, but the principles are: 

1. Thorough peritoneal lavage with cefuroxime and 
warmed saline (1.5 g l -1 ). 

2. Identification of the leak and any associated 
pathology, such as Crohn's disease. 

3. Resection of the affected area. Never try to insert a 
few extra sutures, as the tissues are very friable and 
you may cause more damage rather than achieve 
repair. 

4. Be prepared to establish a proximal stoma and a 
distal mucous fistula or carry out a Hartmann's type 
procedure of closing the distal rectal stump. 

5. Very occasionally, if contamination is slight, 
conditions are satisfactory and you are expert, you 
may elect to excise the margins and reform the 
anastomosis. 

6. As a rule, after restoring the patient's health and 
nutritional status over a minimum of 6-12 weeks, 
you may reanastomose the bowel ends. 

In the presence of a fistula, management depends on the 
state of the patient and the volume draining. When the 
volume is small (i.e. less than 500 ml per 24 h) and the 
patient is well, initially treat the patient conservatively: 

1. Restrict oral intake. 

2. Give intravenous fluids. 

3. Correct fluid, protein, electrolyte, acid-base and 
vitamin deficiencies (see Chs 9, 10). 

4. Treat associated sepsis. 

5. Institute nutritional support. 

6. Consider the somatostatin analogue octreotide to 
reduce gastrointestinal secretion and motility. If such 
treatment fails or the output is high (>500 ml day" 1 ) 
or there is associated sepsis, you must intervene 
surgically. 



384 



COMPLICATIONS: PREVENTION AND MANAGEMENT 



36 



Problems with the wound 

Failure of wound healing may result (in descending order 
of importance) in wound dehiscence, incisional hernia or 
superficial wound disruption. Wound dehiscence should 
now be less than 0.1%. Incisional hernia is more common 
but should occur in less than 10% of abdominal wounds. 

Risk factors 

General risk factors include respiratory disease, smoking, 
obesity obstructive jaundice (especially secondary to 
malignant disease), nutritional deficiencies of protein, 
zinc and vitamin C, malignant disease, steroid therapy, 
and following emergency procedures. 

Local risk factors include wound infections, impaired 
blood supply, foreign body in the wound and previous 
irradiation to the area. Clean incised wounds heal better 
than ragged traumatic wounds. The site of wound is 
important: the anterior tibial area is notorious for wound 
breakdown, as are flap wounds with inappropriate 
length-to- width ratio. Poor surgical technique is another 
important factor. 

Prevention 

As in all complications, the cornerstone of success is to 
recognize risk factors, correct those that can be corrected 
and use an appropriate surgical technique for all wounds. 
For closing the abdominal wall, the best results are 
obtained by suture with a non-absorbable material, such 
as nylon, or an absorbable suture with prolonged tensile 
strength, such as polydioxanone. The Jenkins technique of 
mass closure is now well-established: take 1 cm bites, 
1 cm apart, avoiding too much tension in the closed 
wound. 




Key point 

• To avoid wound complications, ensure that 
your surgical technique is perfect, and choose 
your materials appropriately. 

Management of superficial disruption 

• Evacuate haematoma and /or pus. 

• Excise and remove slough. 

• Remove any foreign body. 

• Irrigate with, for example, hydrogen peroxide and 
povidone-iodine. 

• Pack gently to avoid too rapid healing over of the skin, 
but avoid trauma to granulation tissue. 

• Carefully monitor healing by secondary intention. 



• Use newer materials such as Kaltostat or Sorbsan, 
which are well tolerated, highly absorbent alginates for 
wounds containing slough. 

Management of wound dehiscence 

The mortality reported following abdominal wound 
rupture varies from 24% to 46%. 

• Recognize the problem early. 

• Do not overlook premonitory serous discharge from 
the wound, a prolonged ileus, or low grade pyrexia. 

• Resuscitate the patient. 

• Re-explore the abdomen and perform adequate peri- 
toneal lavage. 

• Proceed to resuture the abdomen under general anaes- 
thetic, using an adequate length of non-absorbable 
suture without tension. 

• Use 1 cm bites about 1 cm apart. 

• Avoid pulling the suture tightly in the tissues. 

• It may be helpful to decompress the small bowel in 
retrograde fashion to reduce intra-abdominal tension. 

Recurrence is uncommon but incisional herniation com- 
plicates approximately 25% of cases. 

Management of incisional hernia 

The indications for surgical intervention are obstruction, 
pain, or increasing size that makes control difficult. First 
spend time reducing such risk factors as obesity, smoking, 
constipation and prostatism. Assess the overall prognosis. 
Not all patients require or want surgical repair. Repair is 
unrewarding in the presence of unresected neoplastic 
disease. An abdominal support will control symptoms in 
most elderly and high risk patients. 

Historically, a number of options are available as 
regards surgical technique, including Mayo or Keel 
repairs. However, except where the hernia is very small, 
a mesh repair is now the treatment of choice. Operative 
mortality should be less than 1 % and the recurrence rate 
5-10%. If a patient is morbidly obese at the time of repair 
a satisfactory result is less likely The main problem with 
mesh repair is if infection supervenes. Under those cir- 
cumstances it is most unusual that the repair will heal 
because of the presence of a foreign body. You will need 
to remove the mesh, allow the sepsis to settle completely, 
then start afresh. Meshes impregnated with antibiotics for 
high risk recurrent cases are under trial. 

Hypertrophic and keloid scarring 

Hypertrophic scars are limited to the wound area and do 
not advance after 6 months. Keloid (Greek kele — claw + 
eidos = like) scars are more extensive and continue to 



385 



36 



COMPLICATIONS 



expand beyond 6 months, but fortunately are much less 
common. Predisposing factors are pigmented skin, burn 
trauma, wounds on posterior aspects, younger age 
groups, and a past history of keloid scarring. 

There is excessive production and contraction of fibrous 
tissue. The synthesis of collagen is increased but the scar 
contains embryonic or fetal collagen. Only in hypertrophic 
scars is there an increased lysis of collagen. The main com- 
plication is joint deformity but the cosmetic problems can 
be considerable in exposed sites and with younger patients. 

Successful treatment is difficult, and should not be con- 
templated until 6 months from injury. There is no treat- 
ment for hypertrophic scars; do not attempt to treat keloid 
scars until they are mature. Re-excision with and without 
pressure or plastic procedures are as disappointing as 
radiotherapy Greater success has been claimed for injec- 
tion of steroids into the wound. The mode of action 
appears to be increased collagen lysis, with depression of 
the proliferation of fibroblasts. Injection of triamcinolone 
can be repeated at intervals of 1 or 2 weeks, depending on 
the result achieved. 



Prevention 



r 



Key points 



• Recognize patients at risk of bleeding and 
reverse the risk factors before operation. 

• Control infection. 

• Ensure your surgical technique is meticulous. 

In patients on long-term warfarin it is relatively straight- 
forward to convert the anticoagulation to intravenous 
heparin, which can be reversed more rapidly than war- 
farin by the injection of protamine. 

Cooperate with a haematologist (see Ch. 8) in managing 
patients with coagulation disorders. Infuse specific factors 
as required. Timing is vital; for example, if fresh platelets 
are required for patients undergoing splenectomy, they 
must be given after the spleen has been removed. Give 
vitamin K by the intravenous route to reverse the prob- 
lems associated with the obstructive element of jaundice. 



Haemorrhage 

Incidence 

The incidence and severity of haemorrhagic complica- 
tions are not easy to quantify. It is uncommonly necessary 
to re-explore a wound, evacuate haematoma and secure 
haemostasis. Wound haematoma and local bruising are 
sufficiently common to make it difficult to differentiate a 
complication from a normal sequel of surgery. 

Where bleeding complicates intra-abdominal surgery 
warning signs are haemodynamic instability with rising 
pulse and falling blood pressure, reduction in hourly 
urine volume to less than 40 ml h" 1 , and excessive volume 
draining from the abdominal drain. 

Predisposing factors are obesity, long-term steroid 
therapy, and jaundice. Recent transfusions of stored 
blood, coagulation diseases, platelet deficiencies and 
anticoagulant therapy may result in haemorrhage, and in 
old age there is increased capillary fragility. Severe sepsis 
may result in disseminated intravascular coagulation. 

Pathology 

It is conventional to consider primary haemorrhage as 
that occurring within 24 h of surgery This is usually a 
technical problem of haemostasis. The operative area 
appears dry but with restoration of normal blood press- 
ure or continuous infusion of intravenous fluids a vessel 
may dilate and bleed. In secondary haemorrhage, bleed- 
ing usually occurs 5-10 days after operation. It is due to 
local infection, sloughing of a clot or erosion of a ligature. 



Management 

The need for intervention is dictated by the patient's 
symptoms and vital signs. Where haemorrhage is overt it 
is usually easier to decide whether exploration of the 
wound and cavity is indicated or not. When bleeding is 
internal you cannot rely on the effectiveness of an intra- 
cavity drain. 

• Check a clotting screen to assess any established prob- 
lems and to identify any new ones. 

• Correct any deficit appropriately with vitamin K by 
injection for problems with the clotting mechanism, 
expressed as the international normalized ratio (INR). 
Use specific factors for deficiencies, fresh frozen 
plasma, and fresh platelets as indicated by the results 
of the coagulation study. 

• Do not undertake surgical exploration until you have 
corrected any deficit, at least in part. 

• It is unusual to identify a specific bleeding point at 
exploration. 

The principles of surgery are to evacuate the blood and 
clot, identify any bleeding point or points, and control 
them appropriately If a troublesome ooze persists, try the 
effect of a haemostatic agent such as Spongistan, or a col- 
lagen derivative. If you still cannot control the bleeding, 
pack the raw surface for 24^18 h. Consider leaving the 
superficial wound open. When you suspect a deeper 
source, and fear recurrent bleeding, as following a pan- 
creatic operation, consider creating a laparostomy; leave 
the main wound open, packed with sterile packs. This 
facilitates re-exploration. 



386 



COMPLICATIONS: PREVENTION AND MANAGEMENT 



36 



Summary 

• Do you realize that the combination of cor 
pulmonale and ischaemic heart disease, or 
low output septic shock, carry up to 50% 
mortality? 

• Do you appreciate the importance of 
correcting comorbidity factors before 
operation whenever possible? 

• Are you aware that there are many 
complications that are common to all 
types of operation? 

• Will you study the special risks you will 
encounter in each form of surgery? 




Further reading 

Cuschieri A, Giles GR, Moossa AR 1988 Essential surgical 

practice. Wright Bristol 
Pollock AV 1991 Postoperative complications in surgery. 

Black well Scientific, Oxford 
Smith JAR (ed.) 1984 Complications of surgery in general. 

Bailliere Tindall, London 
Tayfor I, Karran SJ (eds) 1996 Surgical principles. Edward 

Arnold, London 



387 




Intensive care 



J. Jones, R. C Leonard 






Objectives 



To identify the signs of impending critical 

illness. 

To understand the early and ICU 

management of critical illness. 

To appreciate the limitations of intensive 

care. 



Decision making 

1 . Advice on critically ill patients must be provided at 
a senior level. Never take it upon yourself to manage the 
sickest patients in the hospital without asking your con- 
sultant for support. Events proceed much more quickly in 
ICU than elsewhere, and what would be an acceptable 
delay on the wards is often not tolerated by ICU patients 
or staff. 



HYTRODUg^ 

Although it has never been proved, it is likely that very 
sick patients can be managed better and more efficiently 
in a separate area specially equipped for their needs. In 
the UK, the Department of Health has recommended that 
intensive care units (ICUs) should represent 1-2% of 
acute hospital beds. This proportion is lower than in 
almost all other Western countries, and is now manifestly 
inadequate. 

Organization 

1. Critical care is labour intensive, and properly trained 
staff represent by far its most valuable resource. There 
should be one nurse for each ventilated patient and a 
senior nurse whose sole responsibility is to manage the 
unit. 

2. There should always be at least one doctor capable 
of managing the airway on duty within the ICU and free 
from other commitments. A consultant must be immedi- 
ately available. Although in the past most intensive care 
consultants in the UK have been anaesthetists, care of the 
critically ill requires close cooperation across many disci- 
plines. The recent emergence of intensive care as a spe- 
cialty in the UK has resulted in the creation of a small 
number of specialists capable of directing this complex 
multidisciplinary process. There is now evidence that 
intensive care units controlled by intensivists have better 
outcomes and shorter patient stays than those that are not 
(Carson et al 1996, Ghorra et al 1999, Baldock et al 2001). 




Key points 

• Offer intensive care only to those who need it 
and will benefit from it. 

• Respond quickly to requests for advice or 
assistance from the ICU staff. 

2. It is often said that it is not reasonable to refuse 
admission to ICU simply on the grounds of advanced age, 
and that old people have been shown to respond to inten- 
sive care just as well as younger ones with similar dis- 
orders. While this is true, death cannot be postponed 
indefinitely, and the humane and reasonable use of inten- 
sive care over the age of 80 requires particular care in 
patient selection. Regardless of age, when the appropri- 
ateness of ICU admission is in question, an assessing 
intensivist needs the following information: 

a. Current diagnosis and its prognosis 

b. Comorbidities 

c. Functional status; often a decisive factor - exercise 
tolerance, mobility, ability to do housework, shop, and 
venture outside the home. 

3. Clearly judgements regarding the possible with- 
holding of life-sustaining treatment can be difficult. They 
should be made at a senior level, whenever possible 
involving the patient (see Chs 14, 47). If the patient is not 
competent, the role of the next of kin is to represent 
the likely wishes of the patient regarding treatment. 
However, it is inhumane and morally irresponsible to 
leave such decisions to the relatives alone. The current 
fashion of seeking written agreement from the next of kin 



388 



"^ 



INTENSIVE CARE 



37 



before making an order not to attempt resuscitation often 
leaves families feeling that they must bear ultimate 
responsibility for their relative's death. Conduct dis- 
cussions in terms of 'working together to decide what the 
patient would want us to do', not of 'asking consent to 
withdraw or withhold treatment'. Dealing explicitly with 
death can be painful and difficult but should not be 
avoided until it is too late; patients and their families are 
sometimes surprisingly grateful for the chance to discuss 
these issues openly. 

4. Intensivists often receive requests for manifestly 
inappropriate admission to ICU, justified by the words 
The family wants everything done'. Such requests repre- 
sent failures of communication during the decision- 
making process outlined above. The intensivist should 
not be asked to take on the responsibility for communi- 
cation, which lies with the referring specialist. 

5. It has been shown that some patients are admitted to 
ICU too late in the course of their disease (McQuillan 
et al 1998). Earlier treatment might improve outcome and 
perhaps even avoid ICU admission altogether. For this to 
succeed, it is necessary to detect deterioration early and 
then provide staff capable of intervening effectively. The 
concept of a medical emergency team, called in response 
to defined physiological criteria, has been suggested as a 
solution. While this is theoretically attractive, outcome 
benefits have yet to be demonstrated (Bristow et al 2000). 
It may be impossible to detect deterioration soon enough 
to affect the course of the disease. 

6. Successful management of the critically ill patient 
requires that two processes occur simultaneously: 

a. Resuscitation from the pathophysiological 
derangement 

b. Diagnosis and specific treatment of the underlying 
disease. 




Key point 

Critically ill patients need resuscitation, 
diagnosis and specific treatment. 



CORRECTING THE PHYSIOLOGY OF 
CRITICAL ILLNESS 

We shall consider the vital systems serially (in succes- 
sion); in reality they must be dealt with simultaneously - 
in parallel. Safe threshold limits for physiological values 
are given in order to provide practical guidance but there 
are some for whom these limits are too permissive or too 
stringent. If you ignore these limits without seeking 



senior advice you endanger the patient and will be called 
to account. 



Cardiovascular pathophysiology 

The function of the circulation is to transport oxygen and 
nutrients to the tissues and to remove metabolic waste 
products. There must be: 

• Enough oxygen in the blood 

• Enough blood flowing (cardiac output) 

• Enough blood pressure to let tissues regulate their own 
perfusion. 

1. The oxygen content of blood is determined by the con- 
centration and oxygen saturation of haemoglobin. 

2. Blood pressure is determined by the equation 

BP = COxTPR 

where BP = blood pressure, CO = cardiac output, and TPR 
= total peripheral resistance. Thus hypotension can be 
due either to low cardiac output or to inappropriate 
vasodilation. Treatment usually requires correction of the 
abnormal variable. 

3. Cardiac output is determined by: 

a. Rate. Too high a heart rate prevents adequate filling 
of the ventricle and reduces preload and cardiac output. 
Bradycardia reduces cardiac output as ejection simply 
does not happen often enough. 

b. Rhythm. Loss of atrial contraction in junctional 
rhythms or atrial fibrillation also reduces preload and 
hence cardiac output by up to 30%. 

c. Preload. The law of the heart described by Henry 
Starling in 1915, states that the force of contraction of a 
cardiac muscle fibre is proportional to its initial length. 
The fibre length is determined by the ventricular volume. 
However, volumes are difficult to measure clinically and 
the simplest substitute is the central venous pressure 
(CVP). The relationship between pressure and volume is 
not linear and is described by the ventricular compliance, 
which varies both between individuals and within each 
individual over time. For this reason, and because of the 
shape of the ventricular compliance curve (Fig. 37.1), it is 
usually not possible to determine the true preload or 
volume status from a single measurement of the CVP. 




Key point 

• To check the volume status, observe the 
response of the CVP to a fluid challenge. 

Give 250 ml colloid over 10 min. The response indicates 
the volume status (Gomersall & Oh 1997): 



389 



37 



COMPLICATIONS 



to 

Q. 



(A 

■ 

C 

i- 
.5 

(J 
C 

c 

3 




Low preload High preload 

Ventricular end-diastolic volume 



Fig. 37.1 The ventricular end-diastolic pressure-volume 
curve shows how, for a given pressure, the preload may 
be low or high because of the shape of the curve and 
the fact that compliance can vary between individuals 
and within individuals over time. 



- if the CVP rises by more than 7 mmHg the patient is 
hypervolaemic 

- if the CVP settles to within 3 mmHg of the original 
value, the patient is euvolaemic 

- if the CVP rises by less than 3 mmHg the patient is 
hypovolaemic. 

Serial fluid challenges may be given until the response 
suggests volume replacement is adequate. 

d. Contractility is defined as the intrinsic ability of the 
myocardium to contract, independent of loading condi- 
tions. It is impossible to measure directly even under lab- 
oratory conditions, and must be inferred clinically from 
the CVP, blood pressure and assessments or measure- 
ments of the cardiac output. If preload is adequate, and 
blood pressure remains low, with evidence of a low 
cardiac output, contractility is usually impaired. 

e. Afterload. Cardiac output is inversely related to the 
afterload, which may be defined either as the aortic input 
impedance or as the systolic ventricular wall tension. 
Afterload is reduced by: 

- vasodilation (including rewarming of hypothermic 
patients) 

- positive intrathoracic pressure 

- intra-aortic balloon counterpulsation. 
Manipulation of afterload in cardiogenic shock is 

complex and difficult, and is outside the scope of this 
introduction. 

It is not often necessary to measure cardiac output in 
clinical situations. It is debated, but with very unreliable 
evidence, whether there is an association between the use 
of pulmonary artery catheters to measure cardiac output 



and an apparent increase in mortality (Connors et al 
1996). Less invasive methods of monitoring cardiac 
output are gaining in popularity. 

4. Shock may be defined as inadequate tissue perfusion. 
It can be categorized into four types: 

a. Hypovolaemic shock is due to a reduction in circulat- 
ing volume following haemorrhage or dehydration. 
Venous return to the heart and hence ventricular preload 
are reduced, and the cardiac output and blood pressure 
fall. Reflex tachycardia and vasoconstriction partially 
compensate for the hypotension. 

b. Cardiogenic shock results from primary myocardial 
dysfunction, reducing contractility and cardiac output. 
Causes include myocardial infarction and myocarditis. 
Once again, blood pressure is low, and reflex tachycardia 
and vasoconstriction occur in an attempt to compensate, 
but CVP is raised as the heart fails to eject the venous 
return adequately. 

c. Obstructive shock occurs when an adequately filled 
heart is unable to eject its contents because of pericardial 
tamponade, tension pneumothorax or massive pul- 
monary embolism. CVP is again high because of the 
failure to eject, while cardiac output and blood pressure 
are low and the usual compensatory reflexes ensue. 

d. Distributive shock refers to a condition of patho- 
logical vasodilation and capillary leak, which result in 
hypotension with a normal or high cardiac output. The 
condition is seen in sepsis, burns, pancreatitis and ana- 
phylaxis. As the disease progresses, the capillary leak 
produces hypovolaemia. Multiple organ failure is char- 
acteristic of septic shock, and causes acute lung injury, 
renal failure and coagulopathy. Although there is a high 
cardiac output, it appears that there is a defect of tissue 
oxygen utilization. It is presently uncertain whether this 
is due to derangement of the microcirculation or of mito- 
chondrial function. 

Anaphylaxis (Greek ana = without + phylaxis - protec- 
tion) usually follows immediately after the administra- 
tion of drugs, colloids or contrast media. As in septic 
shock, there is profound vasodilation and increased ca- 
pillary permeability Urticarial rashes and bronchospasm 
are also common. 

Inadequate tissue perfusion produces the signs of 
shock listed in Table 37.1. As can be seen, the disorder 
involves several systems. 

5. Hypotension. 



Table 37,1 Signs of inadequate tissue perfusion 



Hypotension (BP < 90 mmHg) 

Tachypnoea 

Oliguria 

Agitation, confusion or coma 

Slow capillary refill (not in early sepsis) 



390 



^9*i 



INTENSIVE CARE 



37 



Ml 



Key points 

Patients with the signs of shock are critically ill 
and are liable to rapid decompensation. 
They need urgent resuscitation. 



While there may be patients for whom a slightly lower BP 
is acceptable (for instance the rule does not necessarily 
apply under anaesthesia), if you are inexperienced, do not 
take such a decision alone. Conversely if a patient has a 
systolic BP of 100 mmHg, but shows all the other signs of 
inadequate tissue perfusion, treat them with the same 
urgency as a shocked hypotensive patient. 

The early management of hypotension follows from 
the physiological principles above, and is described in 
Table 37.2. ICU admission may become necessary at any 
stage in this process, but is usually inevitable if vaso- 
active drugs are required. 

The most important point to realize is that, contrary to 
the myths instilled into all trainees at medical school, it is 
generally far safer to give fluids than to withhold them. 

It is not clear what the appropriate goals of resuscitation 
are. The past fashion for targeting supranormal values 
of oxygen delivery (the product of oxygen content and 
cardiac output) is no longer sustainable. In the absence of 
convincing evidence, aim for these endpoints: 

• Mean BP > 70 mmHg 

• Resolving tachycardia 

• Improved peripheral perfusion 

• Urine output improved above at least 0.5 and prefer- 
ably 1 ml kg 1 h 1 

• Resolving acidosis and falling lactate. 



Table 37.2 Management of hypotension 




Key points 

A non-pregnant adult with systolic blood 

pressure below 90 mmHg has dangerous 

hypotension and requires immediate 

treatment. 

It is generally far safer to give fluids than to 

withhold them. 



Respiratory pathophysiology 

The respiratory system transports oxygen to the blood 
and removes carbon dioxide from it. Success requires an 
adequate volume of gas to ventilate the alveoli and close 
matching of the degree of ventilation and perfusion of 
each lung unit. Failure results in hypoxaemia / hypercar- 
bia (raised blood carbon dioxide) or both. 



Check for airway, breathing and circulation 
Check the BP yourself 
Automatic BP machines measure the mean 
arterial pressure; the systolic and diastolic 
pressures they display are calculated and may 
therefore be inaccurate 
Give high flow oxygen 
Check for signs of shock 

Establish large-bore venous access (14 gauge or 
16 gauge) and draw blood for... 
Investigations: FBP r coagulation studies, U&E r 
amylase, cardiac enzymes, arterial blood gases, 
chest X-ray, ECG 

Examine for signs of pulmonary oedema. If a 
hypotensive patient has pulmonary oedema, he 
or she is desperatefy ill and needs expert 
assistance from the ICU immediately. If there is 
no pulmonary oedema it is safe to give fluid 
Give 500 ml of any fluid except 5% dextrose, 
and repeat as necessary 
Take a history, examine the patient, MAKE A 
DIAGNOSIS AND GIVE SPECIFIC TREATMENT 
If there is no response after between 1000 and 
2000 ml fluid, insert a central venous catheter 
and titrate filling using serial fluid challenges as 
described above 

If hypotension persists despite adequate filling, 
give vasoactive drugs: i not ropes (adrenaline 
(epinephrine)) if cardiac output is low or 
uncertain; vasoconstrictors (noradrenaline 
(norepinephrine)) if cardiac output is high. It is 
sometimes necessary to measure cardiac output 
directly in order to make this distinction 



Ventilation-perfusion (VIQ) matching 

Consider the idealized alveolar-capillary unit rep- 
resented in Fig. 37.2. If perfusion and ventilation are 
either perfectly matched or completely mismatched, then 
there are three possible situations: 

1. Perfect matching of ventilation to perfusion (V/Q = 1). 

2. Normal ventilation but no perfusion (V/Q = ~>), as 
shown in Fig. 37.3, analogous to that existing in the 
anatomical dead space, which refers to that part of the 
tidal volume which does not reach a surface where gas 
exchange can occur. 

3. Normal perfusion but no ventilation (V/Q = 0), as 
shown in Fig. 37.4, resembles what happens to the 
venous blood which is shunted anatomically past the 
lungs without participating in gas exchange because it 
passes through the thebesian or bronchial veins (in 
normal subjects) or a right-to-left intracardiac shunt (in 
patients with cyanotic congenital heart disease). These 



391 



37 \ 



COMPLICATIONS 





Fig. 37.2 Idealized alveolar-capillary unit showing 
ventilation of the alveolus and perfusion of the capillary. 



Fig. 37.4 Normal perfusion but no ventilation (V/Q = 0), 
referred to as shunt. 



situations are therefore referred to as representing the 
physiological dead space and the physiological shunt. 

Dead space ventilation decreases the proportion of each 
breath that participates in gas exchange, and hence alve- 
olar ventilation falls. Unless the respiratory rate rises to 
compensate, hypercarbia will ensue. 

The consequence of blood being shunted through the 
diseased, unventilated lung tissue without engaging in 
gas exchange is that unoxygenated venous blood is mixed 
into the blood that has been oxygenated; hence, arterial 
oxygen content falls. 




Fig. 37.3 Normal ventilation but no perfusion (V/Q = °°), 
referred to as dead space ventilation. 



In reality, there exists a spectrum of V/Q relationships 
from to oo. The vast majority of lung units of healthy 
subjects are tightly clustered around the ideal situation, 
with a few outliers, as shown in Fig. 37.5. However, when 
the lungs are diseased there is an increase in the scatter of 
the V/Q ratios, which causes an increase in physiological 
shunting and dead space ventilation. 



t/i 



en 



E 

3 








1 
V/Q relationship 



« 



Fig. 37.5 Scatter of V/Q ratios in a healthy subject 
(solid line) and in a patient with respiratory disease 
(dotted line). Note the increase in physiological shunt 
and dead space. 



392 



INTENSIVE CARE 



37 



Hypercarbia 

Caused by reduced alveolar minute ventilation, hyper- 
carbia results from: 

1 . Reduced respiratory rate (hypoventilation) 

2. Increased physiological dead space ventilation. 

Both of these can be corrected or compensated by increas- 
ing the respiratory rate. 

Hypoxaemia 

Hypoxaemia is caused by: 

1. Hypoventilation. When the rate at which fresh in- 
spiratory gas is presented to the alveoli falls, but oxygen 
consumption remains the same, the partial pressure of 
oxygen within the alveoli must also fall. As a result the 
oxygen tension within the pulmonary capillary and hence 
the systemic arteries (Pao 2 ) is reduced. Postoperative 
patients may hypoventilate because of pain from upper 
abdominal incisions, or because of opioid analgesia. 
Clearly, the hypoxaemia of hypoventilation can be cor- 
rected by increasing the respiratory rate, either pharma- 
cologically or mechanically, but also more simply by 
increasing the inspired oxygen fraction (Fio 2 ). 

2. Shunting. True anatomical shunting cannot be cor- 
rected by an increased Fio 2 , because by definition no gas 
exchange occurs. Postoperative patients may develop a 
shunt because of basal atelectasis (Greek a - not + telos = 
end + ectasis - expansion; hence, collapse) or chest infec- 
tion. However, relative physiological shunting caused by 
imperfect V/Q matching can be partially corrected by 
increasing the Fio 2 . Techniques available to reduce shunt 
involve raising the mean airway pressure in order to 
recruit collapsed lung units. 




Key point 

• Hypoxaemia is a far more dangerous and 
rapidly lethal state than hypercarbia. 

Hypoxaemia may be treated by oxygen therapy. 

Oxygen therapy. It is incorrect to withhold oxygen 
in the presence of chronic obstructive pulmonary disease 
(COPD) for fear of inducing hypercarbic narcosis. The 
false reasoning for withholding oxygen is that, although 
in healthy humans the normal source of ventilatory drive 
is the carbon dioxide response, patients with COPD have 
a blunted response to hypercarbia and are dependent on 
hypoxaemic ventilatory drive. Treatment with oxygen is 
then assumed to remove this stimulus to breathe and thus 
to cause hypoventilation, hypercarbia and coma. It is true 



that some patients with COPD do experience an increase 
in arterial carbon dioxide tension when hypoxaemia is 
treated with oxygen, but it is irresponsible to treat this 
response with a return to hypoxaemia. The increase in 
arterial carbon dioxide tension (PaC0 2 ) rarely causes prob- 
lems as long as oxygen therapy is controlled to ensure 
safe but not excessive oxygen saturations (say 90-92%). If 
hypercarbia does occur, and is causing problems, do not 
add hypoxaemia to the patient's difficulties, but instead 
refer urgently for ventilation. 

Oxygen therapy is always prescribed in the early post- 
operative period to treat hypoxaemia from the causes 
mentioned earlier. It is known that patients continue to 
experience episodic nocturnal hypoxaemia for at least 
three days after surgery. This coincides with the period of 
highest risk for perioperative myocardial infarction, and 
anaesthetists commonly prescribe oxygen for 3 days fol- 
lowing operation in patients who are at particular risk of 
this dangerous complication. Do not countermand these 
orders or you will be putting your patient at risk. 

Oxygen can be given by the following devices: 

1. Nasal cannulae deliver 2-4 1 min" 1 2 ; Hudson 
masks deliver up to 15 1 min" 1 2 . Although they deliver 
a known flow, the Fio 2 is determined by the amount of air 
entrained by the patient during inspiration. This in turn 
is determined by the peak inspiratory flow rate, which of 
course varies. 

2. Venturi masks (G. B. Venturi, 1746-1822, was an Italian 
physicist) deliver 24-60% 2 . They use Bernoulli's principle 
(as the velocity of a moving fluid increases, the pressure 
within the fluid decreases) to deliver a high enough flow of 
known Fio 2 to exceed the patient's peak inspiratory flow 
rate, thus avoiding entrainment of further air. 

3. Continuous positive airway pressure (CPAP) rep- 
resents the next level of respiratory support from oxygen 
supplementation. A tight-fitting mask connected to either 
a large reservoir or high gas flow permits an Fio 2 of up to 
1.0, while at the same time a positive pressure is applied 
continuously to the patient's upper airway. This positive 
pressure recruits alveoli which are collapsed due to lung 
disease, and results in: 

a. Reduced shunt and therefore increased Pa0 2 

b. Increased lung volume and therefore (usually) 
improved pulmonary compliance and reduced work of 
breathing. CPAP usually has little effect on Paco 2 , despite 
the reduced work of breathing. 

4. Mechanical ventilation (Latin ventus = wind) may be 
applied invasively (via a tracheal or tracheostomy tube) 
or non-invasively via a tight-fitting face mask. The latter 
technique is only suitable for conscious patients with 
adequate ventilatory drive who require a modest reduc- 
tion in their work of breathing and shunt. The indications 
for mechanical ventilation are: 



393 



37 1 



COMPLICATIONS 



a. Respiratory failure refractory to less invasive 
treatments 

b. Elective postoperative ventilation 

c. Physiological control (as for instance in raised 
intracranial pressure). 

The decision to ventilate a patient with respiratory 
failure is complex, and takes into account the following 
factors: 

• Respiratory distress 

• Respiratory drive 

• Level of consciousness 

• Natural history of underlying disease 

• Arterial blood gas results. 

Elective postoperative ventilation is often used 
in anticipation of respiratory failure in the following 
situations: 

• Major surgery (e.g. cardiac surgery, thoracoabdominal 
aneurysm repair) 

• Hypothermia 

• Massive transfusion 

• Haemodynamic instability 

• Staged procedure (e.g. following penetrating abdomi- 
nal trauma or faecal peritonitis). 

Mechanical ventilation carries a number of complications. 
Do not seek to embark upon it without proper indica- 
tions. The complications include: 

• Cardiovascular compromise 

• Fluid retention 

• Pneumothorax 

• Ventilator-associated lung injury 

• Ventilator- associated pneumonia 

• Accidental disconnection 

• Complications relating to the artificial airway (e.g. 
tracheal stenosis). 

The various modes of ventilation are confusing, and 
classifications of them are unhelpful. Essentially, other 
than the basic goal of delivering tidal volumes of 
respiratory gas to the lungs a certain number of times a 
minute, the different modes are aimed at one of the 
following: 

• Facilitating the patient's spontaneous respiratory 
efforts 

• Improving oxygenation in refractorily hypoxaemic 
patients 

• Limiting dangerously high airway pressures 

Respiratory distress 

This is one of the earliest indicators of impending critical 
illness, as well as the major determining factor of the need 



for mechanical ventilation. The signs of respiratory 
distress are: 

1. Tachypnoea (Greek tacky s = swift + pnoia = 
breathing) 

2. Use of accessory muscles of respiration - the most 
obvious being the sternocleidomastoid muscles, 
which contract during inspiration 

3. Difficulty speaking 

4. Pulse oximeter (Spo 2 = oxygen saturation from pulse 
oximeter) reading < 90% 

5. Agitation, confusion or coma. 




Key points 

• Respiratory rate > 30 or < 8 f inability to speak 
half a sentence, agitation, coma, Spo 2 < 90%, 
indicate potentially serious illness. 

• Provide immediate treatment. 

Unless a patient with these signs improves rapidly, he or 
she may require early intubation and ventilation. In the 
setting of respiratory distress, agitation or coma are par- 
ticularly worrying, as they make it very difficult to 
manage the patient without securing the airway. 

1. Spo 2 < 90% requires immediate correction, as further 
desaturation is likely to be rapid. 

2. A satisfactory Spo 2 reading does not rule out severe 
respiratory problems. Oxygen therapy can maintain a 
normal saturation until shortly before respiratory arrest 
occurs. 




Key point 



• Monitor the respiratory rate: it is a crucial 
indicator in a potentially unstable patient. 

Renal dysfunction 

Renal failure is a frequent problem in surgical wards and 
in ICU. By far the commonest cause is acute tubular 
necrosis. The cells lining the renal tubules are metaboli- 
cally very active and have a high oxygen requirement; if 
they are deprived of it, they swell, die and are shed into 
the lumen. The same effects result when toxic substances 
are excreted by the kidneys, such as gentamicin, ampho- 
tericin B and cisplatin. Fortunately, the cells can regen- 
erate. Inadequate renal perfusion is usually due to a 
combination of hypovolaemia, hypotension, sepsis, 
nephrotoxic drugs and pre-existing renal disease. 



394 



INTENSIVE CARE 



37 



In the case of sepsis, renal failure may occur as part of 
the syndrome of multiple organ dysfunction, when it 
carries a grim prognosis. However, if the patient survives 
the acute illness, renal function usually recovers. 




Key point 

• Monitor urine output hourly; if it falls below 
0.5 ml kg 1 rr\ correct it without delay. 

Early correction of underlying renal hypoperfusion may 
prevent the development of acute tubular necrosis. 
Therefore: 

1 . Correct hypovolemia, if necessary using CVP 
guidance as described above. 

2. Correct hypotension and low cardiac output, using 
vasopressors or inotropes. 

In previously hypertensive patients it may be necessary to 
raise the blood pressure to levels close to their normal 
pressure (which may be higher than the usual target mean 
arterial pressure in ICU of around 70 mmHg). Only then 
can the kidneys autoregulate their blood flow, allowing 
renal perfusion to occur. 

There is no evidence of benefit from other strategies, 
including low dose 'renal' dopamine (Bellomo et al 2000). 
Furosemide (frusemide) given to promote a diuresis is 
common; at least it has the theoretical benefit of reducing 
renal oxygen consumption and protecting the struggling 
kidney against ischaemia. However, it is essential to 
correct hypovolemia first. 




Key point 

• Do not treat oliguria with excessive early doses 
of furosemide (frusemide); hypovolaemia must 
be corrected first. 

Other causes of oliguria in a surgical patient are 
urinary obstruction, of which the commonest cause by 
far is a blocked catheter, and sodium and water retention 
due to the neuroendocrine stress response to surgical 
trauma. 

If oliguria persists despite correct treatment, it is likely 
that established renal failure will develop. A high urinary 
sodium (> 20 mmol I" 1 ) or a low urinary osmolality 
(280-320 mOsm I" 1 ) in the absence of recent diuretic 
treatment suggest renal failure. Seek the advice of an 
intensivist or nephrologist. Meanwhile: 



1 . Maintain euvolaemia, which usually involves fluid 
restriction to 20 ml Ir 1 plus the previous hour's 
output. Be particularly careful to avoid fluid 
overload in patients who are not ventilated. 

2. Monitor closely for hyperkalaemia and metabolic 
acidosis. 

3. Measure serum creatinine and urea twice daily. 

Renal replacement therapy in the form of haemofiltration 
or haemodialysis is indicated for hyperkalaemia, acidosis, 
fluid overload or an inexorably rising creatinine. Once 
dialysis is inevitable there is nothing to be gained from 
procrastination; arrange for it without delay. 



Acute neurological problems 

You will encounter many patients with an acutely 
depressed conscious level resulting from trauma, drugs, 
acute intracranial event (such as infarction or haemor- 
rhage) and encephalopathy of critical illness. 




Key points 



• Never forget to check the blood sugar level. 

• Glasgow coma score (GCS) < 8 or failure to 
localize to pain are indications for intubation, 
ventilation, investigation and specific 
treatment. 

You should only ignore this recommendation for intuba- 
tion if it has been decided that the patient should not have 
active management under any circumstances, following 
an intracranial disaster. If a CT scan shows an unrecover- 
able situation, then treatment can be withdrawn at that 
point. 

Nutrition 

1. Nutritional support is needed when the patient is 
unlikely to resume normal oral intake within 7-10 days of 
it ceasing (Klein et al 1997). If nutritional support is 
inevitable, start it as soon as the patient is stabilized (see 
Ch. 10). Discuss the timing of commencing feeding with 
the intensivists. 

2. Enteral feeding is cheaper, easier and therefore 
preferable. Evidence for a protective effect on the intesti- 
nal mucosa is weak, and complications of enteral feeding 
are underreported (Lipman 1998). It has been definitely 
indicted as an independent risk factor for ventilator- 
associated pneumonia (Drakulovic et al 1999). Thus it is 
reasonable to consider parenteral feeding in patients 
with doubtful ability to tolerate enteral feeding within 



395 



37 y 



COMPLICATIONS 



7 days (Woodcock et al 2001). Meanwhile, make strenu- 
ous efforts to establish enteral feeding. 

3. When nasogastric feeding is not tolerated despite 
giving prokinetic agents, try passing a nasojejunal tube. 
This route is now commonly used in patients with pan- 
creatitis. Traditionally, such patients were fed parenter- 
ally, but jejunal feeding is now known to be safe and 
perhaps associated with better outcomes (Pupelis et al 
2001). 

4. The optimal content of feeding solutions is uncer- 
tain. Carbohydrates, essential lipids, protein, vitamins 
and trace elements are needed, and it is clear that there 
is an upper limit to the amount of both energy and 
protein that the body can use. Excessive feeding is at 
least as dangerous as underfeeding. There is a vogue for 
using regimens containing immunologically active 
nutrients such as arginine, glutamine, RNA and 
omega-3 fatty acids; they are expensive and not well 
evaluated. 



Summary 

• Do you understand that intensive care 
depends on the availability of highly 
skilled, dedicated staff, so that selection of 
patients for admission must be justified by 
expectation of survival with acceptable 
quality of life? 

• Do you recognize that intensive care is not 
different from standard patient care, but 
performed in an exemplary fashion? 

• Are you aware of the need to adhere 
strictly and unremittingly to infection 
control measures? 

• Will you try to alleviate the stressful 
situation of the patients' families by 
maintaining good communication and 
support (see Ch. 47)? 



General considerations 

Intensive care medicine consists mainly of the vital 
process of nursing patients back to health, and requires 
meticulous attention to detail. Four areas deserve 
mention: 

1 . Nosocomial infection with resistant organisms is an 
enormous problem. You must adhere strictly to infection 
control measures: 

a. Wash hands before and after touching every 
patient. 

b. Wear gloves and a plastic apron when examining a 
patient. 

c. Use full sterile technique, as for a surgical procedure, 
when inserting a central venous catheter, both in ICU and 
on the wards. This reduces catheter-related bacteraemia 
rates sixfold. 

2. Thromboembolism prophylaxis is needed for most 
patients, usually with subcutaneous heparin. Compressive 
stockings may be useful. 

3. Stress ulcer prophylaxis is necessary, at least until 
enteral feeding is established. On current evidence give 
H 2 antagonists (Cook et al 1998). If the patient has no 
history of, or special risk factors for peptic ulceration, 
enteral feeding alone is adequate. 

4. Patients' families are under enormous stress; try to 
alleviate this with frequent, early communication and 
support (see Ch. 47). It can be one of the most rewarding 
aspects of working in the ICU. 




References 



Baldock G, Foley P, Brett S 2001 The impact of organisational 
change on outcome in an intensive care unit in the United 
Kingdom. Intensive Care Medicine 27(5): 865-872 

Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J 2000 
Low-dose dopamine in patients with early renal dysfunction: 
a placebo-controlled randomised trial. Australian and New 
Zealand Intensive Care Society (ANZICS) Clinical Trials 
Group. Lancet 356(9248): 2139-2143 

Bristow PJ, Hillman KM, Chey T et al 2000 Rates of in-hospital 
arrests, deaths and intensive care admissions: the effect of a 
medical emergency team. Medical Journal of Australia 
173(5): 236-240 

Carson SS, Stocking C, Podsadecki T et al 1996 Effects of 
organizational change in the medical intensive care unit of a 
teaching hospital: a comparison of 'open' and 'closed' 
formats. JAMA 276(4): 322-328 

Connors AF Jr, Speroff T, Dawson NV et al 1996 The effectiveness 
of right heart catheterization in the initial care of critically ill 
patients. SUPPORT investigators. JAMA 276(11): 889-897 

Cook D, Guyatt G, Marshall J et al 1998 A comparison of 
sucralfate and ranitidine for the prevention of upper 
gastrointestinal bleeding in patients requiring mechanical 
ventilation. Canadian Critical Care Trials Group. New 
England Journal of Medicine 338(12): 791-797 

Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, 
Ferrer M 1999 Supine body position as a risk factor for 
nosocomial pneumonia in mechanically ventilated patients: a 
randomised trial. Lancet 354(9193): 1851-1858 

Ghorra S, Reinert SE, Cioffi W, Buczko G, Simms HH 1999 
Analysis of the effect of conversion from open to closed 
surgical intensive care unit. Annals of Surgery 229(2): 163-171 



396 



INTENSIVE CARE 



37 



Gomersall CD, Oh TE 1997 Haemodynamic monitoring. In: Oh 
TE (ed.) Intensive care manual. Butterworth Heinemann, 
Oxford, 831-838 

Klein S, Kinney J, Jeejeebhoy K et al 1997 Nutrition support in 
clinical practice: review of published data and 
recommendations for future research directions. Summary of 
a conference sponsored by the National Institutes of Health, 
American Society for Parenteral and Enteral Nutrition, and 
American Society for Clinical Nutrition. American Journal of 
Clinical Nutrition 66(3): 683-706 

Lipman TO 1998 Grains or veins: is enteral nutrition really 
better than parenteral nutrition? A look at the evidence. 



JPEN. Journal of Parenteral and Enteral Nutrition 22(3): 

167-182 
McQuillan P, Pilkington S, Allan et al 1998. Confidential inquiry 

into quality of care before admission to intensive care. BMJ 

316: 1853-1858 
Pupelis G, Selga G, Austrums E, Kaminski A 2001 Jejunal 

feeding, even when instituted late, improves outcomes in 

patients with severe pancreatitis and peritonitis. Nutrition 

17(2): 91-94 
Woodcock NP, Zeigler D, Palmer MD, Buckley P, Mitchell CJ, 

MacFie J 2001 Enteral versus parenteral nutrition: a pragmatic 

study. Nutrition 17(1): 1-12 



397 




Dialysis 



A. Davenport 



E 



Objectives 



Be aware of the indications for dialysis. 
Understand the principles of haemodialysis 
and peritoneal dialysis. 
Recognize the limitations to artificial 
replacement of renal function. 



PRINCIPLES 



■^■k^.^-^:^^ 



INTRODUCTION 

Dialysis (Greek dia = asunder + lyein - to lose; hence 
separation of substances through a septum or partition) 
offers a method of treating patients with loss or severe 
impairment of renal function. The membrane is synthetic 
in haemodialysis but the peritoneum forms the mem- 
brane in peritoneal dialysis. 

Loss of the renal function threatens intracellular home- 
ostasis (Greek homos - like, similar + stasis = a standing; 
hence, a state of equilibrium) resulting from failure to 
maintain salt and water balance. There is an additional 
hormone disturbance. Erythropoietin (Greek erythros = 
red + poiesis = a making) is produced by peritubular cells 
in response to hypoxia. The final step in the synthesis of 
active vitamin D takes place in the kidney; vitamin D 
increases uptake of calcium in the gut and the resorption 
of bone. 

Surgical patients may present with impaired renal func- 
tion. It may develop as a complication of treatment 
following the stress of an operation there is increased 
arginine vasopressin (also known as antidiuretic 
hormone, ADH) release, resulting in water retention. 
Acute renal failure may develop secondary to hypo- 
volemia and /or septic shock. 

The increased availability of, and survival on, dialysis 
makes it likely that you will encounter patients on 
dialysis requiring surgical treatment. 



Fluid and chemical exchanges take place across a 
semipermeable membrane (Latin semi - half or partly + 
per = through + meare + to pass). On one side is natural 
fluid such as blood, on the other is dialysate, a specially 
formulated liquid. In peritoneal dialysis the peritoneal 
mesothelium is the natural membrane; in haemodialysis 
it is synthetic and the size of the pores determines what 
can cross the partial barrier. Across the membrane, inter- 
change takes place of water, electrolytes and other solutes 
under the influence of hydrostatic and osmotic forces. 
Dialysis exploits two physical principles: diffusion and 
convection. 

Diffusion 

1. Molecules within a medium are constantly moving, 
the speed determined by the temperature. As they collide, 
they bounce off each other and separate. The Scottish 
botanist, Robert Brown, observed the result of these col- 
lisions in 1827 and this movement is named after him: 
brownian movement. In an area of high concentration 
there are more collisions and an increased tendency to 
separate. This is diffusion (Latin dif, dis = asunder + 
fundere to pour out; thus, to pour out in all directions). It 
results in an even distribution of the molecules through- 
out the medium (Fig. 38.1). 

2. If blood is separated from prepared fluid - dialysate 
- by a semipermeable membrane that permits the passage 
of molecules of a substance in high concentration in the 
blood, the molecules will pass through into the dialysate 
provided the substance is absent or in lower concentra- 
tion in the dialysate. 

3. In peritoneal dialysis the membrane is the peri- 
toneum; in haemodialysis the membrane is artificial and 
has pores of predetermined size in order to control the 
size of the molecules that can or cannot pass through. 

4. In renal failure, urea, creatinine, potassium and 
other waste products accumulate in the blood. Since the 
dialysate used in peritoneal dialysis or haemodialysis 



398 



DIALYSIS 



38 




DIFFUSION OF SOLUTE 
(MEMBRANE PERMEABLE 
TO SOLUTE) 




ULTRAFILTRATION DUE TO 
HYDROSTATIC GRADIENT 



peritoneal dialysis by increasing the osmotic pressure of 
the dialysate with glucose, raising the concentration 
above plasma levels. 

Convection 

1. Convection (Latin con = together, with + tehere = to 
carry) is the transfer of substances or effects by means of 
currents. In haemodialysis, as blood is pumped through 
the haemodialyser, its hydrostatic pressure is higher than 
that of the dialysate, so that plasma water passes through 
the membrane into the dialysing fluid. Depending on the 
size of the pores in the membrane, any plasma solute that 
is small enough to pass through will be carried across 
with the plasma water. The rate of permeable solute 
removal corresponds to the solute concentration in the 
plasma water (Fig. 38.2). 

2. Convection also occurs across the peritoneal mem- 
brane but there is no significant hydrostatic pressure dif- 
ference. Therefore, the dialysate glucose concentration is 
raised to increase its osmotic pressure, creating a plasma 
water flow current into the dialysate (Fig. 38.3). 



I * • 



I 



ULTRAFILTRATION DUE TO 
OSMOTIC GRADIENT 
(MEMBRANE IMPERMEABLE 
TO SOLUTE) 

Fig. 38.1 Diffusion of a solute from a region of high 
concentration to one of low concentration. 



contains none of these substances, the accumulated sub- 
stances diffuse into it from the plasma. 

5. Conversely, by adding bicarbonate to the dialysate at 
a higher than plasma concentration, so that bicarbonate dif- 
fuses into the plasma, metabolic acidosis can be corrected. 

6. By similar adjustments of dialysate concentration, 
calcium can be introduced into or extracted from, the 
plasma. 

7. Because the water content of both peritoneal dialy- 
sis and haemodialysis fluid is greater than that of plasma, 
water should diffuse from the dialysate into the plasma. 
This is prevented by the relatively higher hydrostatic 
plasma pressure during haemodialysis; it is prevented in 



BLOOD 

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1 



ULTRAFILTRATE 

Fig. 38.2 During haemofiltration solute moves by 
convection, according to concentration in plasma water. 




DIALYSIS 
FLUID 



Peritoneal 
lining 



Fig. 38.3 Peritoneal dialysis. 



399 



38 



COMPLICATIONS 



Ultrafiltration 

The separation of particles by filtration under pressure or 
suction is ultrafiltration (Latin ultra - beyond + filtrum = 
felt - from the use of fabric formed from fibres that can be 
matted together without weaving, through which to 
strain liquids). Because there is very little convection 
during standard haemodialysis, the transfer effect can be 
increased by reducing the pressure in the dialysate com- 
partment. Normal kidneys ultrafiltrate 180 litres each day 
depending on the pressure difference between the renal 
glomerular arteriole and the renal tubule (Fig. 38.4). 




Key point 

• The majority of solute (dissolved substance) 
transfer during dialysis is by diffusion. 

Table 38.1 illustrates what can be accomplished by the 
different methods. 



INDICATIONS 

1. Acute dialysis may be required for: 

a. Hyperkalaemia refractory to medical treatment. A 
level above 6 mmol l l is dangerous; above 7 mmol H it 
demands urgent correction. 

b. Severe metabolic acidosis unresponsive to support- 
ive treatment. 

c. Pulmonary oedema not responding to medical 
management. 

d. Uraemia with serum urea above 30 mmol 1 _1 and /or 
creatinine above 500 fimol 1 _1 , or a rise in creatinine of 
more than 100 |mmol I" 1 in 24 h. 

2. Chronic renal dialysis replaces long-term loss of 
excretory functions. It does not, of course, replace 
endocrine functions of the kidneys. 

METHOJDJS^^ ^^^^^,^^^ mm ^ m 

1. Kolff in Holland devised the first practical 
haemodialysis machine during the Second World War. 




PUMP 



HAEMODIALYSIS 



Fig. 38.4 Ultrafiltration can occur by applying 
hydrostatic pressure during haemodialysis, or osmotic 
pressure during peritoneal dialysis. 



Scribner, in I960, described a practical method of vascu- 
lar access by uniting the cephalic vein and radial artery 
using an external shunt but this has been almost com- 
pletely superseded by the side-to-side arteriovenous 
fistula between the vein and artery described by Simeno 
and Brescia. An alternative is a venous end-to-side anas- 
tomosis into the artery. Alternative sites may be needed, 
such as basilic vein to brachial artery. Care of these fistu- 
lae demands skilled management by trained attendants. 

2. Chronic haemodialysis is increasingly performed 
using higher flux membranes than formerly, to reduce 
dialysis times. In the USA, blood flow rates have been 
increased up to 450 ml mrrr 1 . To decrease dialysis times 
still further, ultrapure dialysate may first be administered 
to maximize subsequent haemofiltration. 

3. The anaemia resulting from loss of renal production 
of erythropoietin can be corrected by administering 
recombinant human erythropoietin. 

4. Acute dialysis may be required, often on critically ill 
patients. 

5. Peritoneal dialysis became practical after the devel- 
opment of a semipermanent peritoneal catheter by 
Tenkhoff, followed by a variety of catheters and methods 
of inserting them. Peritonitis may develop, presenting 
with generalized abdominal pain, peritonism, absent 
bowel sounds, vomiting, dehydration and pyrexia. There 
is neutrophilia and cloudy peritoneal dialysate effluent. 



Ta bl e 38. 1 Comparison 


of modes of filtration. 




Peritoneal dialysis 


Solute removal 
Water removal 
Dialyser type 


Haemodialysis 


ity 


Haemofiltration 


Diffusion 
Ultrafiltration 
Low permeabil 


Convection 
Convection 
High permeability 


Diffusion 
Convection 
Peritoneal membrane 



400 



DIALYSIS 



38 



The diagnosis is confirmed by detecting in the dialysate, 
after a 4 h dwell, more than 100 leucocytes per millilitre, 
of which 90% are polymorphs. Because of changing 
trends in peritoneal dialysis, it may not be possible to 
differentiate between peritoneal dialysis peritonitis and 
an intra-abdominal catastrophe. For this reason always 
test a 4 h dwell specimen with a Gram stain. Peritoneal 
dialysis peritonitis, often resulting from coagulase- 
negative staphylococci, usually responds to intra- 
peritoneal antibiotics; an intra-abdominal catastrophe 
may demand operative intervention. 

6. Peritoneal dialysis can be employed in the manage- 
ment of acute renal failure. To minimize the changes in 
intraperitoneal pressure, which can cause cardiovascular 
instability, prefer to use small volume changes, known as 
tidal peritoneal dialysis. Reduced mesenteric blood flow 
in septic, hypotensive patients may prejudice solute 
transfer. Because of technical problems, such as leaks, 
peritoneal dialysis may not be possible following abdom- 
inal operation. 



counter the increased risks of cardiovascular disease in 
renal failure. 




Key point 

The management of patients on dialysis 
treatment demands skilled care from trained 
attendants - to maintain the system and avoid, 
anticipate, detect and treat complications. 



OUTLOOK 




Key points 

Carefully prepare patients with renal failure 

before operations by ensuring the haematocrit 

is above 30%. 

Ensure that the patients are well dialysed 

preoperativefy. 

Avoid giving low molecular weight dextrans 

prior to operation because they will have a 

prolonged half-life. 



Summary 

• Do you understand the physical principles 
on which dialysis is based? 

• Do you know the aims of dialysis therapy: 
the maintenance of patient well-being 
until acute renal failure recovers, and the 
extension of life in chronic renal failure? 

• Do you know what are the major methods 
used in a patient with renal failure? 

• Do you appreciate the deficiencies of 
dialysis compared with normal renal 
function? 



1. The effectiveness of dialysis is not more than 7% of 
that of normally functioning kidneys. 

2. Increasing the amount of dialysis increases survival. 

3. Because of decreased l,25(OH) 2 vitamin D 3 , patients 
tend to develop secondary hyperparathyroidism. Treat 
this with vitamin D analogues or patients will develop 
tertiary hyperparathyroidism with bone resorption, 
requiring operative treatment. It may be possible to 
prevent this by injecting vitamin D analogues into the 
parathyroid gland. 

4. Chronic dialysis patients may develop a form of 
amyloid disease owing to the deposition of E 2 microglobu- 
lin. Deposits in the wrist may provoke carpal tunnel syn- 
drome, in tendon sheaths causing trigger finger, in the 
palm causing Dupuytren's contracture, and elsewhere in 
the body. 

5. The native kidney shrinks and develops cysts, which 
have an increasing malignant potential. 

6. The effect of uraemia in reducing platelet function 
increases the risk of bleeding at operation. This may be 
made worse if the patient is taking prophylactic aspirin to 




Comprehensive reference 

Davison AM, Cameron JS, Grunfeld JP, Kerr DNS, Ritz E, 
Winearls CG (eds) 2002 Oxford textbook of clinical 
nephrology, 3rd edn. Oxford University Press, Oxford 




Future reading 

Davenport A, Will EJ, Davison AM 1993 Improved 
cardiovascular stability during continuous modes of renal 
replacement therapy in critically ill patients with acute 
hepatic and renal failure. Critical Care Medicine 21: 328-338 

Ronco C, Bellomo R, Kellum } A 2002 Continuous renal 
replacement therapy: opinions and evidence. Advances in 
Renal Replacement Therapy 9(4): 229-244 

Wester JP, de Koning EJ, Geers AB et al 2002 Analysis of renal 
replacement therapy in seriously ill (ARTIS) investigators. 
Catheter replacement in continuous arteriovenous 
hemodiafiltration: the balnce between infectious and 
mechanical complications. Critical Care Medicine 30(6): 
1261-1266 



401 




Chronic illness, rehabilitation 
and terminal care 

A C. Kurowska, A. Tookman 




Objectives 

Recognize the importance of effective 

communication. 

Understand the principles of pain and 

symptom control. 

Prescribe analgesics appropriately 

(especially opioids). 

Be able to manage the process of dying. 



INTRODUCTION 

In patients with chronic illness and advanced disease, 
effective symptom control forms the basis of management 
(Table 39.1). For such patients the primary aim of treat- 
ment is not necessarily to prolong life but to make it as 
comfortable and meaningful as possible. Effective palli- 



ative care enables this to happen. A significant number of 
patients experience functional limitations because of their 
disease or its treatment. Many of these can be treated by 
rehabilitation techniques that enable them to develop to 
their maximum potential. 

Patients with malignancy form a large proportion of 
the patients you see with chronic and terminal illness. 
Since such patients present with complex problems, focus 
your approach on the whole patient, rather than simply 
on the disease. An interdisciplinary team approach, 
including the patient and 'family', is essential to achieve 
these aims. 

The proportion of all deaths occurring in hospital has 
increased over the last 15 years. Patients can choose the 
most suitable place to spend their terminal illness if 
specialist palliative care support teams are used effec- 
tively. Such teams provide support and expert advice to 
the professionals and other carers involved in the 
patient's management. Make sure you are familiar with 
your local teams both within the hospital and in the 
community. 



Table 39,1 Important definitions 



• A terminally ill patient is one with a confident diagnosis that cure is impossible. Prognosis is usually months or 
less. Treatment is aimed at relief of symptoms. Most such patients have advanced cancer, but non-malignant 
disease also falls within this definition, such as the end stage of renal failure, chronic obstructive airways 
disease, multiple sclerosis, acquired immune deficiency syndrome (AIDS) and motor neuron disease. 

• A chronically iff patient {Greek chronos - time; hence lasting a long time) has a longer and less predictable 
prognosis. Many of these patients have non-malignant disease, such as inflammatory bowel disease, peripheral 
vascular disease and post-trauma. Some malignant conditions have a protracted course, such as breast and 
prostatic cancer. 

■ The palliative care approach (Latin palliare = to cloak; disguise, extenuate) aims to promote both physical and 
psychosocial well-being. It is a vital and integral part of all cltmcaf practice, whatever the illness or its stage, 
informed by palliative care principles.* 

• Specialist palliative care is provided by those with palliative care as their core speciality. It is needed by a 
significant minority whose deaths are anticipated; it may be provided directly through specialist services, or 
indirectly through advice to the patient's normal professional advisers/carers.* 



^National Council of Hospices and Palliative Care Services 1995 Specialist palliative care: a statement of 
definitions. Occasional Paper 8. 



402 



CHRONIC ILLNESS, REHABILITATION AND TERMINAL CARE 



39 



P* 



Key points 



• Address the psychological, social, sexual, 
spiritual and financial needs of the patient as 
well as the physical symptoms. 

• Provide effective symptom control. 

• Offer control, independence and choice. This 
enables the patient to participate in decisions 
about management problems. 

• In terminal illness this includes negotiating the 
most appropriate place for the patient to die - 
home, hospice or hospital. 

• Support 'the family' (i.e. all those who are 
important to the patient) as well as the patient. 

• Provide bereavement counselling for the 
terminally ill patient's 'family'. 



tation as soon as the diagnosis is made. Clinical nurse spe- 
cialists such as breast, stoma and incontinence advisors 
play a key role. 
2. Principles of good communication are to: 

a. Deal with the patient's concern before yours 

b. Fully cover each topic before proceeding to the 
next. 

c. Elicit all the problems before offering advice or 
attempting solutions 

d. Be sensitive to non-verbal clues 

e. Clarify and summarize what the patient reports and 
what is the proposed plan of action. 




Key point 



• It is not always a question of 'What should the 
patient know?' but rather 'What does the 
patient want to know?' 



COMMUNICATION 



Communication is difficult with patients who have 
advanced incurable illness. Chronic and terminal illness 
can be seen as a failure by you and so generate feelings of 
inadequacy, fear and despair. These fears lead to the use 
of certain tactics in order to keep patients at a safe 
emotional distance (see Ch. 47): 

• Premature reassurance. You reassure the patient that you 
can control physical symptoms when the real issue is 
the patient's underlying emotional fears. 

• Selective attention. You avoid addressing the emotional 
issue by selecting the physical problem for attention. 

• Changing the topic when emotional issues are raised. 

• Closed questions. 

• Physical avoidance by zvalking past the end of the patient's 
bed. 

1. Give clear explanations of the physical and func- 
tional outcome of surgery. Patients handle side-effects 
better and gain trust in you if they understand the ration- 
ale for treatment. If they are given accurate facts about 
their diagnosis and treatment they adapt better to radical 
surgery It gives them the opportunity to prepare psycho- 
logically for the major physical changes associated with 
procedures such as radical mastectomy colostomy and 
head and neck surgery, thereby facilitating postoperative 
adaptation. Explore issues surrounding 'loss', such as 
altered body image (especially when associated with 
cosmetic deformity), sexuality, social role and anxieties 
related to death and dying. Be sensitive to patients' psy- 
chological needs and educate them in order to ease their 
acceptance of their new image and readjust their goals. 
Often these issues are not discussed at all. Start rehabili- 



COMMON EMOTIONAL REACTIONS 

1. Anxiety is a normal reaction to a serious illness. One 
of the commonest emotional reactions to a life-threatening 
illness is fear. Patients with life-threatening illness com- 
monly fear: 

a. Unrelieved symptoms, especially pain 

b. Death and the process of dying 

c. Dying alone 

d. Incompleted tasks (e.g. will has not been made) 

e. Loss and separation (family, job, income, etc.) 

f. Loss of dignity (confusion, incontinence, loss of 
control) 

g. Altered body image 

h. Retribution in the afterlife. 

Find out precisely what the patient fears, as many of the 
fears on which the anxieties are based can be resolved. 
Acknowledge and accept normal levels of anxiety, but 
assess the patient for signs of clinical anxiety. Signs of 
clinical anxiety include: 

a. Persistently anxious mood, which is subjectively 
different from normal worrying 

b. Difficulty in distracting the patient from his or her 
worries 

c. Feelings of tension and restlessness 

d. Insomnia 

e. Autonomic hyperactivity (e.g. palpitations, sensa- 
tion of choking) 

f. Panic attacks. 

Offer treatment with anxiolytics (Latin angere = to press 
tightly + lyein = to loosen; release tension and anxiety) to 
these patients. 



403 



39 



COMPLICATIONS 



2. Despair or depression are normal reactions to a life- 
threatening illness. Recognize and acknowledge them. 
However, look for signs of clinical depression. The classi- 
cal somatic symptoms of depression, e.g. weight loss, 
anorexia and lethargy, carry less importance in the assess- 
ment of patients with terminal illness as they are often a 
manifestation of cancer. Important clues are: 

a. Persistently depressed mood, which is subjectively 
different from normal sadness 

b. Difficulty in distracting the patient 

c. Lowering of interest in and enjoyment of social 
activities 

d. Crying, irritability, etc. 

e. Insomnia 

f . Feelings of guilt 

g. Suicidal ideas may be present. 

Offer treatment with antidepressants to these patients. 

3. Denial. Assess whether this is causing harm, such as 
refusal of necessary medication or psychological turmoil. 
In many patients it represents a successful coping strat- 
egy, in which case breaking down the denial may cause 
unnecessary distress. 

4. Anger can be displaced on to staff and /or on to the 
relatives. It is important not to react with anger but to try 
to accept and understand. Explain to the relatives that 
the patient is not really angry with them, but is displac- 
ing the anger he or she feels towards the disease, on to 
them. 



SYMPTOM CONTROL 



^^^'^^^>?^^^<^^^-ii^^:^^^. 



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Take a positive but realistic attitude. Offer assurance that 
a considerable amount can be achieved. A problem- 
oriented individualized approach is the key to effective 
symptom control. For each symptom, undertake the 
following. 

1 . Diagnose the cause and treat appropriately. An accurate 
diagnosis is important for good symptom control. A 
careful history and examination can be more revealing 
than extensive investigations, which are often impractical 
and distressing. Investigations may be important but 
carry them out only if they alter subsequent management. 
The treatment of a symptom varies considerably, depend- 
ing on the underlying pathology. For example, in a 
patient with cancer, vomiting may be due to: 

a. Raised intracraiiial pressure 

b. Drugs 

c. Hepatomegaly 

d. Intestinal obstruction, etc. 

Each of these requires specific management. Since 
many symptoms are multifactorial in origin, recognize 
the contributory factors and tackle each as far as possible. 



Other intercurrent illnesses are common in debilitated 
patients, hence it is vital to consider non-malignant as 
well as malignant causes. Do not assume that the 
symptom is related to the primary diagnosis, as this can 
lead to inappropriate management. 

If the diagnosis is tentative but it is inappropriate to 
investigate further, give symptomatic relief. A therapeutic 
trial of drugs may be an option. For example, in a con- 
fused patient with suspected brain metastases consider a 
trial of steroids. If the patient improves, this is a thera- 
peutic test. 

2. Explain symptoms to the patient. Fear is an important 
contributory factor in the patient's interpretation of any 
symptom. The fact that you acknowledge the problem, 
understand the symptom, can explain its cause and offer 
treatment is therapeutic in itself. 

3. Discuss the treatment options. Give the patient accur- 
ate and balanced information that is appropriate to the 
stage of the illness. This allows the patient to make 
informed choices about treatment and possible options, 
thereby enhancing his or her sense of control. Treatment 
with a palliative intent need not be limited to drugs. 
Other measures, such as surgery, radiotherapy, nerve 
blocks, physiotherapy psychological therapy such as 
counselling and hypnotherapy, may be indicated. 

4. Set objectives that are realistic. It is frustrating for both 
patient and staff alike if expectations are set that will 
never be achieved. 

5. Anticipate. With advancing illness, symptoms 
(Table 39.2) may change rapidly. If such changes are 
anticipated, much distress may be avoided. For example, 
deterioration in a patient's condition with a progressive, 
advanced cancer may make it impossible for the patient 
to continue with oral medication. Such deterioration 





Table 19.2 Common symptoms in patients with 
advanced cancer 



Symptom 


Approxir 




incidenci 


Physical 




Weakness 


80 


Pain 


70 


Anorexia 


70 


Dyspnoea 


50 


Cough 


50 


Constipation 


50 


Nausea and vomiting 


40 


Psychological 




Depression 


30 


Anxiety 


30 



404 



CHRONIC ILLNESS, REHABILITATION AND TERMINAL CARE 




39 



should be anticipated and injectable preparations should 
be available. This particularly applies in the home care 
setting and can avert an unnecessary crisis. 

6. Ensure relatives remain informed and supported. It is 
important to treat the 'whole family'. 



PAIN 



$t^&?&$&&$& 



Pain is a common symptom in chronic and terminal 
illness and one that is particularly feared by cancer 
patients. Pain can be alleviated or modified in all 
patients. Proper pain assessment leads to effective man- 
agement. The principles outlined here have been devel- 
oped in the context of management of patients with 
advanced cancer, but are applicable to patients who have 
non-malignant pain secondary to chronic disease (see 
Ch. 35). 

Diagnose the cause 

The majority of patients with far advanced disease 
have pain at more than one site. Evaluate each pain 
individually. 

In order to establish the cause of any pain, take a careful 
history, particularly noting: 

• The site of pain and any radiation 

• The type and severity of pain 

• When the pain started and any subsequent changes 

• Exacerbating and alleviating factors 

• Analgesic agents already used. 

Physical examination often confirms the diagnosis. If 
appropriate, investigate the patient with X-rays, isotope 
bone scans, CT scans, etc. 




Key point 

• Pain may be due to a malignant cause but in 
up to a third of patients with advanced cancer 
the underlying cause is non-malignant. 

Always assess how significant the pain is for the indi- 
vidual patient - how does it affect and alter his or her 
life-style? 

Common causes of pain in cancer patients 

Pain in patients with advanced disease is often complex 
because it can be due to multiple pathologies. An accurate 
assessment of the cause of the pain leads to more effective 
management. 



• Bone pain from metastatic disease or local infiltration by 
adjacent tumour is characteristically a deep gnawing 
pain made worse by movement. The bone is often 
tender on percussion. 

• Visceral pain from a tumour mass in the lung or internal 
organs of the abdomen or pelvis causes pain by a 
variety of mechanisms: 

- Soft tissue infiltration causes deep-seated pain due to 
complex pathology. The tumour invades and /or 
stretches pain-sensitive structures such as parietal 
and visceral pleura, peritoneum, nerve plexuses, and 
local bony structures. 

- Stretching of a capsule of an organ is painful. The most 
common example is right hypochondrial pain due to 
stretching of the liver capsule. It can be very severe, 
and a sudden exacerbation of pain may stem from a 
bleed into a local deposit. 

- Stretching of a hollow organ, such as small and large 
intestines, bladder or ureters, can cause severe 
spasmodic colicky pain. 

• Nerve pain from irritation, infiltration and /or compres- 
sion is often a deep ache. Nerve destruction pain may 
be burning, lancinating and associated with abnormal 
sensations such as hyperesthesia. When there is 
destruction of nerve plexuses, nerve roots or peripheral 
nerves, deafferentation pain may result. This type of 
pain is not uncommon and often coexists with visceral 
and somatic pain. Deafferentation pain is characterized 
by unpleasant pain that is difficult to describe. It is 
often associated with sensory changes in the painful 
area and patients complain of allodynia (pain that is 
evoked by a non-painful stimulus, such as stroking 
skin lightly). 

• Myofascial pain. Musculoskeletal pains are common 
in chronically ill patients. They radiate in a non- 
dermatomal pattern. Typically there are localized 
hypersensitive areas of muscle known as trigger points, 
which are tender to pressure. 

• Superficial pain may develop in weak, debilitated 
patients; bedsores may be unavoidable and give rise to 
distressing pain. 

Realistic objectives 

Pain can be significantly modified in nearly all patients 
and fully relieved in many. In a few of them it can be 
intractable and unresponsive to most treatments. These 
patients provide the greatest challenge so explore all 
avenues of achieving pain relief. Invariably involve your 
local specialist palliative care team in the management of 
these patients. Pursue realistic objectives. You should 
always be able to achieve freedom from pain at night, 
usually freedom at rest. Sometimes you may not succeed 
in relieving pain on mobility. 



405 



39 1 



COMPLICATIONS 



Treat pain appropriately. 

Not all pain requires analgesia; for example, the pain of 
constipation is best treated with laxatives, not analgesics. 
However, when analgesics are indicated, prescribe them 
correctly. 



Analgesic treatment of pain 

The variety of analgesics available for use in the treatment 
of pain can be daunting. It is better to use a few drugs 
really well than many badly. The following 'three-step' 
regimen is effective in the majority of situations: 

STEP 1 Non opioid +/- adjuvant, such as paracetamol. 
If the pain is not relieved with 2 paracetamol 6-hourly 
move on to: 

STEP 2 Weak opioid +/- adjuvant, such as paracetamol/ 
dextropropoxyphene / paracetamol /codeine, tramadol. 
If the pain is not relieved with 2 co-proxamol (or equiva- 
lent) 6-hourly move on to: 

STEP 3 Strong opioid +/- adjuvant, such as morphine 
sulphate immediate release, morphine sulphate slow 
release, diamorphine subcutaneously. 



Principles of prescribing opioids 

• Give morphine orally unless the patient cannot tolerate 
oral medication. 

• Prescribe it regularly to pre-empt pain. An 'as-required' 
basis results in poor pain control, increased incidence 
of side-effects and the use of higher doses overall. 

• Give it an adequate trial at an adequate dose. 

• Coprescribe extra doses for breakthrough and incident 
pain to be used as necessary - pro re nata (Latin = 
according to the condition arising, born). 

• Side-effects should be anticipated so that they can be 
prevented. 




Prescibe p.r.n. doses of analgesic for: 

• 'Breakthrough' pain - that breaks through the 
background analgesia. Daily use of 
breakthrough analgesics implies the regular 
dose of analgesic is not adequately controlling 
the pain so increase it accordingly. 

• 'Incident' pain - that is precipitated by painful 
incidents such as dressing changes. The need 
for p.r.n. analgesics for incident pain does not 
imply that background pain is inadequately 
controlled. Therefore do not increase regular 
analgesics; this might increase side-effects. 

Strong oral opioids of choice 

1. Morphine sulphate as tablets or solution are quick- 
acting preparations. Prescribe 4-hour ly day and night. 
The short duration of action means there is rapid response 
to alterations of dose. Use them when the patient first 
starts on opioids in order to estimate the overall opioid 
requirement for that individual. 

2. Morphine sulphate controlled release is a long- 
acting preparation. Prescribe it 12-hourly. When the 
patient's pain is stable on 4-hourly morphine convert to 
the equivalent dose of morphine sulphate controlled 
release to simplify the regimen. 

3. If the pain is only moderate and urgent control is not 
necessary, you may start the patient on morphine sul- 
phate controlled release initially 

4. The above two morphine preparations are suitable 
for most patients. Other strong opioids have a role in 
pain management (Table 39.3). These drugs are generally 
used when morphine is contraindicated or when opioid- 
sensitive pain has become resistant to morphine, when 



: 




Table 393 Alternative opioids 

* Fentanyi This is available in a transdermal preparation, Change the patch every third day, It takes several days 
to reach steady state (biological haJf-JHe of 17 h). It is therefore not indicated in patients who need quick 
titration nor in the opioid naive. It is particularly useful in patients who cannot swallow, who have absorption 
problerns or who are poorly compliant with oral medication. It is metabolized in the liver to inactive 
metabolites and is therefore useful in patients with renal dysfunction. It is said to cause less constipation than 
morphine. Switching between transdermal fentanyi and other opioids can be difficult; conversion tables are 
only a guide. 

* Hydromorphone. This ts similar to morphine but 7.5 times more potent. Its metabolites are less active than 
morphine metabolites, 

* Methadone. Long acting opioid which may have a useful role in neuropathic pain. (Although opioids are said 
to be ineffective la neuropathic pain, clinical experience challenges this.) Its long half-life makes it a difficult 
drug to use because accumulation can occur, 

■ Oxycodone. A step ll/lll analgesic with inactive metabolites. 



406 



CHRONIC ILLNESS, REHABILITATION AND TERMINAL CARE 



f 39 



Table 39.4 Relative potency of opioids 




Opioid 



Relative oral potency 
(for repeated dosing) 



Typical starting dose 



Morphine 


1 


Codeine 


0.1 


Dihydrocodeine 


0.1 


Pethidine 


0,125 


Tramadol 


0.2 


Methadone 


4-5 


Hydromorphone 


7.5 


Fentanyl 


250 



10 nig 4-hourly 
30 mg 6-hourly 
30 mg 6-hourly 
50 mg 4-hourly 
50 mg B-hourly 
5 mg 8-hourly 
1,3 mg 4-houriy 
25 mg h _1 72-hourly 



Equipotent morphine dose 
(approx, - great individual variation) 



10 mg 






3 mg 






3 mg 






6.25 mg 






10 mg 






20-25 mg 






10 mg 






10-20 mg 


4-hourly 



morphine has been unexpectedly ineffective or when 
morphine is causing too many side-effects. They are 
generally second-line agents. 

5. The dose depends on previous analgesic require- 
ments: 

a. If not on any previous analgesic, start with 2.5 mg 
morphine 4-hourly or 10 mg morphine sulphate slow 
release 12-hourly 

b. If on weak opioid (e.g. co-proxamol) start with 
5-10 mg morphine 4-hourly or 30 mg morphine sulphate 
slow release 12-hourly. 

c. If on other strong opioid, use Table 39.4 to convert 
to equivalent dose of morphine 4-hourly. Titrate the dose 
as indicated by the level of pain control achieved. 




Key points 

• Treat significant pain with early, adequate, 
effective analgesics. 

• Don't waste a terminally ill patient's time using 
ineffective moderate analgesics. 

• Opioids are the most effective strong 
analgesics. 

Routes of administration 

1. If the patient is able to swallow, use the oral route. 
However, at times it may be necessary to give opioids 
transdermally or parenterally; opioids can be given 
rectally, but this route is rarely necessary. 

2. Indications for transdermal /parenteral opioids: 

a. In the last few hours/ days of life when the patient is 
unable to swallow 

b. Dysphagia 

c. Nausea and vomiting 

d. Gut obstruction 

e. Unable to tolerate taste/number of tablets. 



3. Parenteral opioids. Diamorphine hydrochloride is 
highly soluble (1 g in 1.6 ml). It is the drug of choice for 
parenteral use because of the small volume needed. 
Subcutaneous injections are effective and this is the route 
of choice. Diamorphine undergoes first-pass metabolism 
in the liver, hence the subcutaneous dose should be half 
to one-third the oral dose. 

4. If the patient is going to require more than two or 
three injections, consider a subcutaneous infusion pump. 
This is a small battery-driven device that injects the con- 
tents of a syringe over a 24 h period. It can be used in the 
home as well as in the hospital (Table 39.5). 

5. Transdermal opioids. Fentanyl patches may occa- 
sionally be used in preference to subcutaneous infusion 
(see above under alternative opioids). 

Fears of prescribing opioids 

Fears about prescribing opioids are common and may 
lead to patients having effective analgesia withheld. Both 
professionals and patients have unfounded anxieties 



Ta b I e 3 9 ■ . 5 Eq u iva lent dose of opioid s 



Equivalent doses of opioids 

(Dose of oral morphine:dose of injected 

diamorphine = 2:1 or 3:1) 
10 mg morphine sulphate orally 4-hourly 
(60 mg oral morphine in 24 h) 
is equivalent to 

30 mg slow release morphine twice a day 
(60 mg oral morphine in 24 h) 
is equivalent to 

5 mg of diamorphine s.c. 4-hourly 
(30 mg s.o diamorphine in 24 h) 
is equivalent to 
30 mg diamorphine in a 24 h sx. infusion (syringe 

driver) 



407 



39 



COMPLICATIONS 



about opioids. An understanding of these myths will lead 
to improved communication, more appropriate analgesic 
prescribing and better compliance. 

1. Fear of addiction. It has been shown in many studies 
that psychological addiction does not occur. Patients 
reduce and /or stop their opioid if their pain is controlled 
by another method (e.g. nerve block, surgical fixation). 
Since chemical dependence occurs (as is the case with 
many drugs), morphine should be gradually reduced. It 
must never be stopped abruptly. 

2. Fear of tolerance, which occurs only to a minor degree 
and for practical purposes is not relevant. If the dose of 
opioid needs to be increased, it is as a result of an increase 
in pain secondary to disease progression. 

3 . Fear of respira tory depression but with careful attention 
to dosage this does not occur. In fact opioids are used in 
palliative care to alleviate dyspnoea by reducing ventila- 
tory demand and hence the sensation of breathlessness. 

4. Fear of hastening death. Opioids do not hasten death 
when correctly prescribed. The exhaustion caused by 
unrelieved pain may do so. 

5. Fear that a morphine prescription signals that death is 
imminent. This is a common anxiety for patients, who may 
believe that a morphine prescription is given only when 
the doctor feels that death is imminent and has kept this 
information from them. 

Predictable side-effects of morphine/ 
diamorphine 

• Constipation occurs in >95% of patients. Prescribe a 
regular prophylactic laxative. 

• Nausea and vomiting occur in approximately 20% of 
patients. An antiemetic should be prescribed if nausea 
or vomiting occurs but it is not necessary to prescribe 
antiemetics prophylactically. The antiemetic of choice 
for opioid-induced nausea is haloperidol. Nausea due 
to opioids is usually self-limiting so the antiemetic can 
be withdrawn after 10-14 days. 

• Drowsiness occurs in about 30% of patients. This side- 
effect wears off after approximately 5 days on a stable 
dose. 

• Other side-effects. These include dry mouth, which is 
very common and should be treated with simple local 
measures; confusion and hallucinations are rare (<1% 
of patients) and other causes should be excluded; 
twitching can occur on high doses. 




Key points 

Morphine and its metabolites are dependent 
on the kidney for excretion. 



• Toxicity will result unless you adjust the dose 
for a patient with renal dysfunction. 

Opioid-resistant pain 

Some pains are either partially sensitive or insensitive to 
opioids. These pains will need to be managed with an 
additional or alternative drug or some other technique. 

Bone pain. Although partially sensitive to opioids, 
bone pain frequently requires the addition of a non- 
steroidal anti-inflammatory drug. Localized bone pain 
can often be treated with radiotherapy. Surgical fixation 
may be indicated if there is a pathological fracture. 
Consider prophylactic fixation if more than 75% of the 
cortex is eroded, because a spontaneous fracture is highly 
likely. Generalized bone pain in malignancy may need 
systemic therapy with bisphosphonates. Chemotherapy, 
hormone therapy and strontium-89 all have a role in the 
management of bone pain. 

Nerve pain. This is very often opioid insensitive; 
however, a trial of opioid is usually indicated. 
Methadone seems to be particularly effective. Steroids 
are useful in nerve compression. Nerve infiltration/ 
irritation /destruction pain may respond to drugs that 
alter neurotransmission (e.g. low dose tricyclic anti- 
depressants, anticonvulsants, membrane stabilizers). 
Radiotherapy and nerve blocks may also be indicated. 

Liver capsule. This pain is partially opioid sensitive. 
Steroids are very useful in this context as they may reduce 
liver swelling and relieve capsular stretching. 

Colic. If caused by constipation, this demands treat- 
ment with laxatives. Stop drugs causing hyperperistalsis. 
Colic from tumour obstruction may respond to antispas- 
modics. 

Meningeal pain/raised intracranial pressure. 

Steroids are the drug of choice. Consider using 
radiotherapy. 

Lymphoedema. Non-steroidal anti-inflammatory 
drugs and steroids can be helpful. Physical treatment 
plays an important role (massage, compression hosiery 
and manual lymphatic drainage). 

Muscle Spasm. Benzodiazepines or baclofen can be 
used. 

Infection. It may be appropriate to treat infections in 
order to relieve pain. 

Jointfmyofascial pain. Use non-steroidal anti- 
inflammatory drugs in conjunction with opioids. Local 
injections of steroid into joints and trigger points may be 
of value. Physiotherapy can also be helpful. 

Superficial pain. Patients with bedsores need to be 
kept off the pressure areas with regular turning. An effec- 
tive mattress to support the patient is essential. 

Psychological pain. If management is solely 
directed at physical factors, you may fail to control pain 



408 



CHRONIC ILLNESS, REHABILITATION AND TERMINAL CARE 



f 39 



adequately in some patients. It is important to treat co- 
existent depression or anxiety, and if appropriate offer 
counselling and diversionary activities. 

Complementary therapies 

Although scientifically unproven, these seem to benefit 
some groups of patients. If the patient perceives these thera- 
pies as adding to their overall well-being then support the 
patient, provided the treatment does no harm and does 
not interfere with their conventional management. 

Injection techniques in cancer pain 

Nerve blocks have a place in palliative care. They are 
highly effective when used in a selected group of patients 
(approximately 4% of patients with pain will benefit). 

Consider using nerve blocks for: 

• Unilateral pain 

• Localized pain 

• Pain due to involvement of one or two nerve roots 

• Abdominal pain arising from 'upper' gut 

• Rib pain. 

1. Carefully assess the cause of the pain before carry- 
ing out a block and determine the exact site at which the 
pain pathways should be interrupted. 

2. Many procedures can be performed using local 
anaesthetics and steroids. These blocks can give good pain 
relief, outlasting the effect of the anaesthetic, and they are 
safe procedures. The pain relief from a nerve block may 
be transient and repeated blocks may be necessary. 

3. Select the patient carefully and offer a nerve block 
only if there is a reasonable chance of success. 

4. In addition to neural blockade, spinal analgesics 
have an important role in selected cases. Epidural and 
intrathecal administration of opioids (and local anaes- 
thetics) by a catheter system are particularly useful in 
patients with opioid-sensitive pain who are experiencing 
unacceptable side-effects with systemic therapy. 

5. Major neurolytic procedures may carry the risk of 
serious side-effects, so first assess the patient carefully. 
For example, intraspinal neurolysis for nerve root pain 
can produce urinary and faecal incontinence. Coeliac 
plexus block for upper abdominal pain can cause postural 
hypotension. 



debility it is very difficult to treat. Exclude reversible 
causes such as cord compression and cerebral met- 
astases. Acknowledge the problem and explain to the 
patient that it is a result of the illness. This allows realis- 
tic goals to be set, which in itself can reduce the patient's 
distress. Even very sick patients need to feel a sense of 
control. Simple measures such as a wheelchair can help 
them achieve this. 

2. Steroids improve weakness in a proportion of 
patients. The response, however, is often short lived so 
take into account side-effects such as proximal myopathy 
and poor wound healing. Select patients carefully and 
assess the time at which steroids are introduced. 

3. A patient who is immobile and confined to bed loses 
muscle strength. A normal person loses 10-15% of muscle 
strength when completely rested for 1 week and it takes 
60 days to restore that strength. It is therefore not sur- 
prising that muscle weakness quickly develops in the 
immobile cancer patient, especially in the common situ- 
ation where protein catabolism is increased. If immobil- 
ity continues, contractures can develop, leading to 
impaired ability to self -care. Contractures are more likely 
when soft tissue damage is present and with improper 
positioning in bed. Good nursing care and regular 
physiotherapy are essential for these patients. 

4. When patients are debilitated and immobile, pres- 
sure sores can rapidly develop. This is aggravated by 
increased protein catabolism and negative nitrogen 
balance as well as other factors (e.g. diabetes, steroids). 
Damage can be minimized if pressure on the skin is inter- 
mittent. Limit the damage and prevent the consequent 
pain by early prophylaxis with scrupulous nursing atten- 
tion and the use of effective patient support systems (e.g. 
special mattresses, low-loss airbeds). 

5. Autonomic dysfunction and impaired peripheral cir- 
culation are the cardiovascular consequences of immo- 
bility. There is an increased likelihood of deep venous 
thrombosis and pulmonary embolism. 

6. Atelectasis results from reduced aeration of the pos- 
terior lungs and predisposes patients to chest infection. 

7. Urinary retention and urinary infection are more 
common in immobile patients. 

8. Immobility, anorexia and weakness lead to reduced 
peristalsis and constipation. 

9. Loss of proprioceptors in the skin of the feet will lead 
to an inability to balance, which can take many weeks to 
recover. 



<^^^ft^^&$$&tt# 



sreciFicre 

Weakness and immobility 

1 . Weakness is a common and distressing symptom in 
patients with advanced illness. When due to general 



Anorexia 

1. This occurs in approximately 70% of patients with 
advanced cancer. It is important to decide whose problem 
it is - the patient's or the carers'. The family need to 
understand that as death approaches it is normal to lose 



409 



39 



COMPLICATIONS 



interest in food. At this stage the goal of eating is enjoy- 
ment, not optimal nutrition. 

2. Causes of anorexia are: 

a. Tumour bulk and associated biochemical abnormal- 
ities (hypercalcaemia, uraemia, etc.) 

b. Oral problems (e.g. thrush, oral tumour) 

c. Constipation 

d. Drugs, radiotherapy 

e. Depression or anxiety. 

3. Remember that fear of vomiting may lead to avoid- 
ance of food, as opposed to true anorexia. Psychological 
factors such as anxiety and depression can manifest as 
lack of appetite. Presentation of food is important - it 
should be in small portions and well presented. 

If the above factors have been attended to and it is still 
felt to be a problem for the patient, consider progestogens 
or steroids as appetite stimulants. 

Dysphagia 

1. The site of dysphagia can be predicted from the 
symptom complex. Drooling, leaking of food and reten- 
tion of food in the mouth indicate a buccal cause; nasal 
regurgitation, gagging, choking and coughing suggest 
pharyngeal pathology; a sensation of food sticking 
behind the sternum and pain between the shoulder 
blades imply oesophageal obstruction. 

2. It is important to explain the cause (Table 39.6) to the 
patient so that any dietary adjustments are understood. If 
necessary, restrict intake to liquids or soft foods. 

3. Treat any associated pain. Mucaine is useful for the 
local pain of Candida or radiotherapy, but many patients 
require opioids for satisfactory pain relief. Actively treat 
Candida with topical or systemic antifungals. If patients 
are unable to swallow even liquids, give drugs by another 
route. A subcutaneous infusion of drugs (analgesics, etc.) 
is both effective and well tolerated. 

4. If it is appropriate to attempt to relieve the obstruc- 
tion, then possibilities include radiotherapy, endo- 



oesophageal tubes, stents, dilatation and laser therapy. 
Steroids, by reducing oedema, may palliate dysphagia for 
a significant period. They can be particularly useful in the 
management of dysphagia syndrome associated with 
head and neck tumour. Consider endo-oesophageal tubes 
and stents in patients who are relatively independent and 
active; they are not for the moribund. Percutaneous gas- 
trostomy may be an option in patients with incurable 
malignant obstruction but it does not solve the problem 
of saliva aspiration. There is a significant morbidity asso- 
ciated with percutaneous gastrostomy insertion, so select 
patients carefully. 

5. In irreversible total obstruction or terminal neuro- 
muscular dysfunction reduce secretions to a minimum 
using hyoscine. 

6. Regard dehydration as a natural process in the last 
few days of life. It can help relieve a number of symp- 
toms. Intravenous fluids may exacerbate discomfort by 
increasing bronchial secretions, gastrointestinal fluid 
(increased likelihood of vomiting), urine flow (leading to 
need for catheter), etc. However, hydration may be indi- 
cated in selected patients, for example if a patient is com- 
plaining of thirst /dryness. Usually these patients can be 
managed with subcutaneous fluids, preventing the 
repeated trauma of cannulation. 



Nausea and vomiting 

1 . These occur in approximately 40% of patients with 
far-advanced cancer. Find the cause in order that rational 
treatment can be offered (Table 39.7). 

2. If an antiemetic is needed, most nausea and vomit- 
ing in patients with advanced illness can be controlled 
using the antiemetic drugs in Table 39.8. Most antiemet- 
ics act at one of the sites shown in the table. Sometimes 
more than one antiemetic is necessary. If this is the case it 
is common sense to combine drugs that act at different 
sites, i.e. a neuroleptic with an antihistamine. 



Table 39,6 Common causes of dysphagia in patients with advanced disease 



Problem 



Sofids then liquids 

Solids and Jiquids 
simultaneously 



Painful 



Implication 



Obstruction 



Neuromuscular cause 



Mucosal causes 



— i 



Example of cause 



Tumour mass 
External compression 

Terminal neuromuscular dysfunction in very weak patients 
Perineural tumour infiltration with head and neck tumours 
which damage cranial nerves {V, IX, X) 
Bulbar palsy 

Candida (Note: only 50% of patients with oesophageal 
Candida have clinically apparent oral Candida) 
Post-radiotherapy 



410 



CHRONIC ILLNESS, REHABILITATION AND TERMINAL CARE 



39 



Table 39,7 Common causes of nausea and vomiting in advanced cancer 



Cause 



Symptomatic treatment 



Drugs 


If possible withdraw the drug 


Metabolic (hypercalcaemia, uraemia, etc.) 


Treat with centrally acting antiemetic 


Bowel obstruction 


Centrally acting antiemetic (see below) 


Squashed stomach syndrome* 


Prokinetic antiemetic, proton pump inhibitor/H- antagonist 


Gastric irritation (e.g. NSAIDs, gastric ulceration} 


Prokinetic antiemetic, proton pump inhibitor/H 2 




antagonist7misoprostol 


Constipation 


Laxatives 


Liver metastases 


Centrally acting antiemetic/sterotds 


High bulk disease 


5teroids, centrally acting antiemetic/ondansetron 


Raised intracranial pressure 


Steroids 


NSAIDs, non-steroidal anti-inflammatory drugs. 




* Squashed/small stomach syndrome is a constellation 


of alimentary symptoms seen in patients with a large 


epigastric mass/gross hepatomegaly. It is manifested 


as early satiation, epigastric fullness, flatulence, hiccoughs, 


nausea, vomiting and heartburn. 





Table 39.8 Sites of action of antiemetic drugs 








Main site of action 


Class of drug 






Example 


Central 










Chemoreceptor trigger zone 


Neuroleptic 






Haloperidol 


Vomiting centre 


Antihistamine 






Cyclizine 


5HT3 receptors 


5HT3 receptor anta 


gon 


ists 


Ondansetron 


All central sites 


Phenothiazine 






Levomepromazine 


Peripheral 


Prokinetic 






Domperidone 



3. The antiemetic must be delivered by a suitable route. 
There is little point in giving a drug orally if the patient is 
vomiting! Choose rectal or parenteral routes in these 
situations. A 24 h subcutaneous infusion by means of a 
syringe driver is a simple and effective method of drug 
delivery. (Syringe drivers are discussed in more detail 
later.) 

Bowel obstruction 

1. Gastrointestinal obstruction occurs in approxi- 
mately 4% of patients with advanced cancer, more com- 
monly in those with colonic primary (10%) and ovarian 
primary (25%). Manage these patients surgically if they 
are in good general condition, if they have low-bulk 
disease and if an easily reversible cause seems likely. Take 
into account previous laparotomy findings. Surgery 



remains the primary treatment because in selected 
patients 10% of obstructions prove to be non-malignant, 
10% represent a new primary and approximately 60% 
will not reobstruct 

2. With conservative treatment, 30% of obstructions 
resolve spontaneously. Therefore consider this manage- 
ment prior to proceeding to surgery. The medical man- 
agement of bowel obstruction is given in Table 39.9. 

3. Do not resort to either of these strategies as part of 
the primary management of irreversible obstruction in 
patients with far-advanced cancer. The majority of such 
patients have obstruction at multiple sites. Aim for 
symptom control with drugs. Intravenous fluids and 
nasogastric tubes are rarely needed. 

4. Obstruction may be proximal, in which case the pre- 
dominant symptom is vomiting, or distal, when the pre- 
dominant symptom is colicky pain. Nausea is often more 



411 



39 



COMPLICATIONS 



Table 39.9 Medical management of bowel obstruction 



Diet 

Nausea and vomiting 



Reverse obstruction 



Pain 



Colic 



No restrictions but small meals appropriate. 

Cyclizine 1 50 mg per 24 h via syringe pump. If partial/no success combine with 
haloperidol 5-10 mg per 24 h in syringe pump. Octreotide via the subcutaneous 
route has an important role in bowel obstruction, particularly in high vofume 
vomiting. 

If constipated, attempt to clear with softeners. Docusate 100-200 mg t.d.s. Consider 
dexamethasone 16 mg per 24 h by subcutaneous infusion to reduce oedema. In 
certain cases, e.g. cancer of the ovary, chemotherapy may be effective. 

Diamorphine in appropriate dose in syringe pump according to previous analgesic 
requirement and level of pain. 

If colic persists despite the above, add hyoscine butylbromide 60-120 mg per 24 h to 
pump. Octreotide is helpful by decompressing the bowel and reducing the 
distension. 



Gastrokinetic antiemetics such as metoctopramide or domperidone are contraindicated - they wilt exacerbate 
vomiting. 



distressing than vomiting. The aim is to eliminate nausea, 
reduce vomiting to a maximum of once or twice a day and 
treat associated pain. Baines et al (1985) reported on this 
form of management in 38 patients with advanced malig- 
nant disease. They found that nausea and vomiting was 
well controlled in 90% of patients, colic in 100% and pain 
relief was total in 90 %, with only mild residual pain in 
10%. The median survival was 3 months and 24% sur- 
vived >6 months. 



Syringe drivers in symptom control 

Syringe drivers delivering subcutaneous infusions of anal- 
gesics, antiemetics, anticholinergics or tranquillizers are 
commonly used in patients who require regular parenteral 
medication (Table 39.10). The subcutaneous route is 
simple, safe, effective and acceptable to most patients. 
Indications for the use of such syringe drivers have already 
been discussed above in the context of pain control. 



Constipation 

The need to treat constipation is usually a consequence of 
failing to use prophylactic laxatives (virtually all patients 
on opioids should have a regular laxative). A rectal exam- 
ination is essential on any patient complaining of consti- 
pation or diarrhoea to assess for impaction. 



TERMINAL PHASE MANAGEMENT 






1. When a patient who has advanced illness enters into 
the terminal phase, normally a day or so prior to death, 
review all medication. Stop all drugs apart from those 
aimed at symptom control. 



Reason for drug 

Analgesia 

Colic 

Antiemetic 



Bronchial secretions 



Anxiolysis 
Terminal agitation 

Other drugs 



>nly used in a continuous 24 h subcutaneous infusion 


■ r-T— _^_i. 

pump 


Drug 


Dose in 24 h 


Diamorphine 


According to need 


Hyoscine butylbromide 


30-60 mg 


Halopehdo! 


5-10 mg 


Cyclizine 


150 mg 


Levomepromazme 


12.5-25 mg 


Hyoscine hydrobromide 


1.2-1,8 mg 


Hyoscine butylbromide 


30-120 mg 


Glycopyrrolate 


0,6-1.2 mg per 24 h 


Midazolam 


5-10 mg 


Midazolam 


15-60 mg 


Levomepromazine 


100-200 mg 


Dexamethasone 


0.5-16 mg 


Octreotide 


300-1200 M .g 



412 



CHRONIC ILLNESS, REHABILITATION AND TERMINAL CARE 



39 



2. Communication is vital. Explain to the patient and 
the carers about anticipated changes in the patient's 
condition. Offer reassurance that symptoms will remain 
controlled and the patient kept comfortable. Often it 
is appropriate to use a syringe driver to administer 
medications. 

3. Continue analgesia even if the patient becomes 
unconscious. The patient may still perceive pain and, in 
addition, abrupt withdrawal of opioids can result in an 
unpleasant physical withdrawal reaction. If a patient is on 
regular opioids, these will need to be continued at an 
equivalent dose subcutaneously. If the patient will require 
more than a few injections, start a syringe driver. 

4. Agitation. Search for the causes and treat them if 
indicated; for example, retention of urine requires 
catheterization. However, it is not uncommon for 
patients to become agitated and confused shortly before 
death. If a tranquillizer is indicated, use subcutaneous 
midazolam (5-10 mg, 4-6-hourly). Midazolam (20-60 mg 
per 24 h) can be combined with diamorphine in a syringe 
driver. 

5. Bronchial secretions can be controlled using subcu- 
taneous hyoscine or glycopyrronium, as required. Either 
can also be added into the syringe driver together with 
diamorphine and midazolam. 

6. Crises. In some circumstances it may be appropriate 
to prescribe drugs for an anticipated crisis such as a 
massive haemoptysis or rupture of a major vessel. Such 
crises cause great distress to the patient and the family, so 
handle them speedily and sensitively. Prescribe midazo- 
lam with or without diamorphine as required, and give 
the nurses instructions to give it immediately should such 
an "end of life' crisis occur. 




Key points 

• Always follow the rules of symptom control 
throughout. 

• Evaluate symptoms and treat them 
appropriately. 

• Anticipate crises. 

• Communicate. 

• A peaceful death alleviates the severity of 
bereavement in the family 



Bereavement 

1. Provide support for the family both during the 
patient's illness and at the time of death. It helps them to 
cope better and also reduces the likelihood of future com- 
plications. Evidence suggests there is higher physical and 



psychiatric morbidity and possibly increased mortality in 
those recently bereaved. 

2. People avoid grieving individuals because they feel 
helpless, awkward, embarrassed, they do not wish to feel 
sad themselves and they fear releasing strong emotions. 

Bereavement counselling 

1. Identify those who are likely to have a difficult 
bereavement, as they are at risk of developing psychiatric 
illness in the bereavement period, such as psychosis, 
clinical depression or extreme anxiety states. Some indi- 
viduals may resort to alcohol, drugs, denial, idealization, 
etc. as a way of coping with loss. Refer them early to the 
appropriate agency, such as a psychiatrist or bereavement 
counsellor. 

2. Individuals at increased risk of difficult bereavement 
include those: 

a. With a close, dependent or ambivalent relationship 

b. Undergoing concurrent stress at the time of 
bereavement 

c. With memories of a 'bad' death (e.g. uncontrolled 
symptoms) 

d. Who have a perceived low level of support (the 
carer's perception is more important than the actual 
support in determining outcome) 

e. Experiencing strong feelings of guilt /reproach 

f. Unable to say goodbye, who feel there are things left 
unsaid (e.g. sudden or traumatic deaths or absence at the 
time of death). 



Summary 

• Do you recognize the essential importance 
of clear, effective communication? 

• Will you determine to treat the whole 
patient not just the disease? 

• Do you intend to assess fully each 
symptom before prescribing treatment 
and revise it as the disease progresses? 

• Do you feel confident that you can control 
or modify pain? 

• Do you recognize the value of using 
morphine sulphate as the first choice 
when a strong opioid is indicated? 

• Will you continue to control symptoms 
with analgesia, sedation and antisecretory 
drugs for excessive respiratory secretions 
during the terminal phase? 

• Will you remember to call upon the 
expertise of your local palliative care 
team/hospice? 



413 




COMPLICATIONS 




References 



Baines M, Oliver DJ, Carter RL 1985 Medical management of 
intestinal obstruction in patients with advanced malignant 
disease: a clinical and pathological study. Lancet ii: 990-993 




Further reading 

1 998 Directory of hospice and palliative care services in the 
United Kingdom and Republic of Ireland. Hospice 
Information Service, St Christopher's Hospice, London 

Buckman R 1992 How to break bad news: a guide for health 
care professionals. Papermac, London 



Doyle D, Hanks WC, Macdonald N 1998 Oxford textbook of 

palliative medicine. Oxford University Press, Oxford 
Faulkner A, Maguire P 1994 Talking to cancer patients. Oxford 

Medical Publications, Oxford 
Kaye P 1996 Breaking bad news. (Pocket Book) EPL 

Publications, Northampton 
Parkes CM 1972 Bereavement: studies of grief in adult life. 

Tavistock and Pelican, London; International Universities 

Press, New York 
Regnard C, Davies A 1986 A guide to symptom relief in 

advanced cancer. Haigh and Hochland, Manchester 
Stedeford A 1985 Facing death. Heinemann, London 
Twy cross RG 1997 Symptom management in advanced cancer. 

Radcliffe Medical Press, Abingdon, Oxfordshire 
Twy cross RG, Lack SA 1986 Control of alimentary symptoms in 

far advanced cancer. Churchill Livingstone, Edinburgh 
Twycross RG, Wilcock A, Thorp C 1998 PCF1 Palliative care 

formulary. Radcliffe Medical Press, Abingdon, Oxfordshire 



414 



SECTION 8 




415 



This page intentionally left blank 




Genetic aspects of surgery 



M. C Winslet 



W 



Objectives 



Recognize genetic disorders which may 
produce life-threatening complications 
during surgery and anaesthesia: 

- defects of haemoglobin and haemostasis 

- defects of muscle 

- defects of connective tissue 

- skeletal dysplasias. 

Become familiar with the disorders leading 
to a genetic susceptibility to cancer. 



RELEVANCE TO SURGERY 









In certain genetic disorders life-threatening complications 
may occur during surgery and anaesthesia. Recognize 
family history and clinical signs suggestive of these 
genetic disorders in order to plan appropriate peri- 
operative management. It is now possible to study the 
molecular basis of genetic disorders, human develop- 
ment, carcinogenesis and many other biological events. 
This stems from exciting advances in laboratory tech- 
niques for the analysis of the human genome. 

Genes involved in the control of cell proliferation and 
transcription of genetic information have been shown to 
cause increased susceptibility to cancer if their function is 
defective. Thus, genetic analysis and the development of 
new methods for clinical diagnosis, monitoring of cancer 
progression and treatment are being reported in medical 
literature and incorporated in clinical medicine. These 
advances clearly illustrate the link between basic sciences 
and clinical practice. They emphasize your need to under- 
stand basic genetic concepts in order to keep abreast of 
new developments. 

BASIC CONCEPTS AND TERMINOLOGY 



&£&&&&&?&$&?, 






1. Genes are units of genetic information which are 
passed on from generation to generation. Biochemically, 



genes are stretches of DNA (deoxyribonucleic acid) which 
direct the synthesis of a specific protein. 

2. DNA is tightly coiled and packaged in chromosomes, 
which are visible under the light microscope in the 
nucleus of dividing cells. Somatic cells (non-germline 
tissue) have 23 pairs of chromosomes (diploid number 46): 
one chromosome from each pair is inherited from each 
parent. Chromosome pairs 1-22 are called autosomes, 
while the 23rd pair are the sex chromosomes, XX in females 
and XY in males. In the ovum or sperm (germ cells or 
gonadal tissue cells) one set of autosomes and a sex chro- 
mosome are present (haploid set), so that, on fertilization, 
a diploid set of chromosomes is restored. Thus, males 
determine the sex of the offspring. 

3. When viewed under the microscope, each chromo- 
some has a visible constriction (centromere). The part of 
the chromosome above the centromere is usually shorter, 
called the short arm or p (from petite); the long arm is 
termed a. Each arm of the chromosome is further divided 
into bands for easy reference. Thus, 5q21 is the position 
of the adenomatous polyposis coli gene on the long arm 
of chromosome 5. 

4. Mutation is a change in the gene function which 
results either in activation (more protein is produced) or, 
more often, inactivation of the gene with reduction or loss 
of function. Some diseases with a gene component are 
sporadic (Greek sporadikos = scattered, from sperein - to 
sow); others, on which I shall concentrate, are familial, 
that is, characteristic of a family, because the mutation is 
passed on to subsequent generations. 

5. Single gene disorders account for many defects. A single 
base substitution results in sickle cell disease. A single 
point mutation results in some forms of p-thalassaemia. 

6. Chromosomal disorders. An extra, free-lying chromo- 
some 21 accounts for most cases of Down syndrome. 

7. Multifactorial diseases are the result of combined 
genetic and environmental factors, including some cases 
of cleft lip and palate, club foot, long segment 
Hirschsprung's disease and hypertrophic pyloric steno- 
sis. Combined genetic and environmental factors are 
implicated in insulin-dependent diabetes, ankylosing 
spondylitis, peptic ulceration and atherosclerosis. 



417 




GENERAL CONSIDERATIONS 



8. Mendelian inheritance (Gregor Mendel, 1822-1884, the 
Augustinian monk who studied the inheritance charac- 
teristics of peas) refers to the mode of transmission of 
genetic information from generation to generation. 
Dominant inheritance (autosomal or X-linked) is clinically 
expressed when a copy of the mutated gene is inherited 
from one parent but not from the other. In recessive in- 
heritance the clinical signs of the disease are evident only 
when both copies of the gene have the mutation. 

9. Proto-oncogenes (Greek protos = first + onkos = bulk, 
mass + -gene = born) are normal cellular genes which par- 
ticipate in normal proliferation. They may undergo muta- 
tion to form oncogenes, which initiate or stimulate neoplasia. 

10. Tumour suppressor genes (or antioncogenes) have the 
opposite function. 

11. Family history is essential for establishing the diag- 
nosis of genetic disorders. The drawing of a family tree 
(pedigree - French pied-de-grue = crane's foot, possibly 
from the arrowhead on the scroll) is straightforward and 
shows in graphic form the mode of genetic transmission 



(Fig. 40.1). When a complex of symptoms and signs occur 
together in a particular disorder, this is referred to as a syn- 
drome, usually named after the authors of the first report, 
for example, in 1 969, the Li-Fraumeni syndrome - the cri- 
teria for inclusion being an autosomal dominant cancer 
predisposition, a wide variety of cancer types, young onset 
and a potential for multiple primary sites. An important 
surgical familial condition is hereditary non-polyposis 
colon cancer, often referred to by the acronym HNPCC. 



PREOPERATIVE ASSESSMENT AND 
PERIOPERATIVE MANAGEMENT 




Key points 



• Concentrate on the genetic disorders with 
which you, as a trainee surgeon, should be 







BC 



1:1 



Dx58y 




BC 



BC 



H:2 



ll:3 



Dx 55y 




BC 




BC 



6 



M:4 



Dx 45y 



6 



m 



llhl 



:3 



:5 



:5 



64y 



40y 



Dx30y 
bilateral 



Dx33y 
bilateral 



35y 



Dx35y 



Fig. 40.1 A family tree for establishing a diagnosis of a genetic disorder. Roman numerals l-lll refer to generations; 
arabic numerals refer to the individual (e.g. Ill: S, fifth individual from the third generation shown on the pedigree). 
(O) female; (Q) male; shaded symbols = affected; crossed symbols = dead; BC, breast cancer; OV, ovarian cancer; 
Dx, diagnosed; y, years (present age or age at diagnosis). 



418 



GENETIC ASPECTS OF SURGERY 



40 



familiar, because they may result in serious 
complications during surgery and anaesthesia. 
• These genetic disorders can be divided into 
four groups: defects of haemoglobin and 
haemostasis; defects of muscle; connective 
tissue defects; and skeletal dysplasias. 

Haemoglobin and haemostasis 

1. Enquire about history of anaemia, bleeding ten- 
dency or recurrent venous thrombosis in the patient or 
relatives. The development of sickle cell crisis due to 
hypoxia during surgery and the need for factor VIII infu- 
sion in haemophilia A are well known. If you obtain a 
suggestive history, most rare defects of other clotting 
factors can be diagnosed on routine screening. For 
example, in Noonan syndrome, with a birth frequency of 
1 :2000, factor XI and XII deficiency and thrombocytopenia 
occur in 60% of patients. The clinical signs include short 
stature, neck webbing, congenital heart defects and 
usually subnormal intelligence. There is no chromosomal 
abnormality and both sexes are affected. 

2. Patients with thromboembolic disease due to in- 
herited protein C or S deficiency may give a history of 
superficial and deep vein thrombosis, thrombosis of the 
mesenteric, cerebral, renal and axillary veins and portal 
veins, and pulmonary embolism. 

Muscle defects 

1 . Malignant hyperthermia is the most serious genetic 
disorder of muscle presenting in the operating theatre. It 
is estimated to affect approximately 1:15000 paediatric 
patients and 1:40 000 adult patients. It is triggered by halo- 
genated anaesthetic agents, with or without depolarizing 
muscle relaxants. The inheritance is autosomal dominant 
or recessive and approximately 50% of families have a 
mutation in the calcium ion channel gene on chromosome 
19. The patient develops an acute onset of skeletal muscle 
rigidity, metabolic acidosis and malignant hyperpyrexia. 
Immediately reverse it, or it can lead to tissue damage and 
death- The mainstay of treatment is dantrolene, which acts 
directly to relax skeletal muscle. Administer 1 mg kg" 1 by 
rapid intravenous injection, repeated up to a cumulative 
maximum of 10 mg kg -1 , either prophylactically or imme- 
diately you suspect a hyperthermic episode. 

2. Hand-grip weakness and difficulty in walking are 
symptoms of myotonic dystrophy. There is usually a posi- 
tive family history. Myotonic dystrophy affects approxi- 
mately 1:10 000 individuals and the clinical expression is 
very variable. Myotonic dystrophy and the other less 
common myotonias are due to defects in the chloride and 
sodium channels of the muscle membrane. Patients show 
undue sensitivity to various anaesthetics and sedative 



agents, including opioids, barbiturates and benzodi- 
azepines. Tonic spasms during operation, prolonged recov- 
ery from anaesthetic and depression of the respiratory 
centre necessitating prolonged ventilation have been 
reported. Cold and shivering also induces myotonia. 
Myotonic dystrophy usually presents between the ages of 
15 and 35 years. The most noticeable clinical signs are facial 
and neck weakness with ptosis. Patients usually notice 
weakness of hand grip, inability to open the clenched fist 
and difficulty in walking due to weakness of foot dorsi- 
flexion. This is a multisystem disorder: heart block fre- 
quently develops in adults. Fully evaluate these patients 
prior to operation. Because anaesthetic management may 
be difficult, prefer regional anaesthesia whenever possible. 

Connective tissue defects 

1 . Is there evidence of poor wound healing, paper thin 
scar tissue, joint dislocations and possible aortic aneurysm 
in relatives? Connective tissue abnormalities may cause 
difficulty during suturing, resulting in a high incidence of 
anastomotic and wound dehiscence. In Marfan' s syn- 
drome, named for the Parisian paediatrician (1858-1942), 
the clinical signs are usually obvious: the patient is tall, 
thin, with long slim fingers, chest deformity, scoliosis and 
dislocated optic lens. Preoperative cardiac assessment is 
mandatory, as there is a high incidence of dissecting aortic 
aneurysm with aortic valve insufficiency at a young age. 

2. Ehlers-Danlos syndrome was described in 1901 by 
the Danish physician Ehlers, and by Danlos a Parisian 
dermatologist in 1908. The arterial type IV, in particular, 
is characterized by friable arteries and veins, and sponta- 
neous arterial rupture has been reported. Paper thin scars, 
joint dislocation and spontaneous colonic perforation 
may also occur. Arteriography and vascular surgery is 
particularly hazardous; if varicose vein surgery is 
absolutely necessary, perform it with the utmost care. 

Skeletal dysplasias 

1. Patients with such disorders may have odontoid 
dysplasia or C1-C2 subluxation due to ligamentous 
laxity. The patient is of short stature, with some body dis- 
proportion. The most commonly encountered conditions 
are achondroplasia and Down syndrome, described in 
1866 by John Langdon-Down of the London Hospital, 
which are easily recognized. 

2. Skeletal dysplasia due to mucopolysaccharidosis, an 
inborn metabolic storage disorder (such as Hurler syn- 
drome), is characterized by a 'coarse' looking face and 
mental retardation. Take care to limit head and neck 
manipulation during surgical operations for fear of 
causing cervical medullary compression. In certain cases, 
elective cervical vertebral fusion may be required. 



419 



40 * 



GENERAL CONSIDERATIONS 



3. Congenital malformations and genetic disorders 
may indicate the presence of unsuspected anatomical 
abnormalities of obvious importance to the surgeon. 
Patients with Sturge-Weber syndrome have a port wine 
stain on the skin, which, if present over the face or 
cranium, is associated with epilepsy or mental retarda- 
tion. Multiple arteriovenous malformations may be 
encountered during surgical manipulation of tissues 
beneath the port wine stain. 



GENETIC MECHANISM OF CANCER 
DEVELOPMENT 



Table 40,1 Features which increase the probability 
of the presence of genetic predisposition to cancer 

• The development of specific (e.g. breast/ovary) 
or uncommon (e,g. adrenal/rhabdomyosarcoma) 

tumours 

• Unusually early onset of cancer (<45 years) 
■ Multiple primary cancers in one individual 

• Relatives with cancer (maternal or paternal side) 

• Associated phenotypic or developmental 
abnormalities (rare) 



Cancer development is the result of the accumulation of 
mutations in a number of genes (4-5 in colorectal 
cancer) over time in somatic tissues. Each mutation 
results in stepwise clonal proliferation of cells, with the 
next mutation giving rise to further expansion. The 
mutations are present in two types of genes which 
regulate cell growth. There is a mutational activation of 
oncogenes and mutational inactivation of tumour sup- 
pressor genes (see Ch. 26). A genetic model for colorec- 
tal tumorigenesis has been particularly well studied, for 
example by Fearon & Vogelstein (1990). Early mutations 
in the bowel epithelium in the oncogene ras and the 
tumour suppressor genes on 5q and 18q give rise to a 
colon adenoma. Additional mutation of the tumour sup- 
pressor gene p53 (localized at 17p) result in progression 
to carcinoma. Further tumour growth results from the 
accumulated loss of suppressor genes on additional 
chromosomes. This correlates with the ability of the 
carcinomas to metastasize and cause death. 



GENETIC SUSCEPTIBILITY TO CANCER 




Key points 



• Most malignant tumours are sporadic (in one 
individual in the family) and develop in older 
age. 

• Cancer occurring in successive generations in a 
family is rare. 

1 . Features which suggest the probability of the pres- 
ence of a genetic predisposition to cancer are shown in 
Table 40.1. As molecular genetic analysis methods have 
become available, attention has focused over the last 



10 years on unusual families where a particular type of 
cancer (breast /ovary, colorectal) has developed in many 
relatives, over several generations and at a young age. 

2. Significantly the tumours are often bilateral or multi- 
focal. This clinical presentation could be explained by an 
inherited mutation of a tumour suppressor gene (which is 
present in all tissues). Subsequent mutations of further 
genes frequently result in multiple tumours at a young age 
of onset. This mechanism of genetic susceptibility to cancer 
was initially proposed by Knudson in 1986 (Knudson 
hypothesis) and has recently been confirmed. Among the 
first genes to be localized were those causing clinically 
well-characterized disorders such as familial retinoblas- 
toma, Wilms' tumour and adenomatous polyposis coli 
(APC). Table 40.2 shows the gene localization and clinical 
presentation of some of the more common cancer suscep- 
tibility genetic disorders. Adenomatous polyposis coli is 
an important surgical example of an autosomal dominant 
disorder presenting in late childhood /early teens, with 
abdominal pain or bleeding per rectum due to multiple 
large bowel polyps. At colonoscopy numerous polyps are 
visible, almost replacing the bowel mucosa. Polyps may be 
present in the rest of the gastrointestinal tract. There is a 
high frequency of progression of such polyps to the 
adenoma-carcinoma sequence. Another serious complica- 
tion in approximately 10% of patients with APC is the 
development of desmoid (Greek desmos = chain, bundle + 
eidos = like) tumours arising mainly from the peritoneum 
or abdominal wall; these are highly vascular and difficult 
to resect in their entirety. When you make the clinical diag- 
nosis of APC, you must inform the patient's close relatives 
and counsel them about their increased cancer risk. They 
need to decide whether to have regular colonoscopy, as 
some gene carriers develop the polyps later, or opt for a 
predictive genetic test or CHIRPE (congenital hypertrophy 
of retinal pigment assessment). 



420 



GENETIC ASPECTS OF SURGERY 



40 



Table 40.2 Gene localization and clinical 


presentation of disorders with a genetic susceptibility to cancer 


Disorder 


Mode of inheritance 


Gene localization 


Tumour susceptibility 


Retinoblastoma 


Autosomal dominant 


T3qU 




Retinoblastoma, 
osteogenic sarcoma 


Wilms' tumour 


Autosomal dominant 


11p13 




Nephroblastoma 


Adenomatous polyposis coli 


Autosomal dominant 


5q21 




Colorectal, 
gastrointestinal tract 


Li-Fraumeni syndrome 


Autosomal dominant 


17p12 




Rhabdomyosarcoma, 
leukaemia, glioma, 
breast cancer 


Breast and ovarian cancer 


Autosomal dominant 


SRCA1- 


17q2l 


Breast and ovarian 






BRCA2- 


-13q12 


Breast? Pancreas 


Hereditary non-polyposis colon cancer 


Autosomal dominant 


HMSH2 


-2p12 


Colorectal and 






KMLH1 


-3p21 


gastrointestinal, 






hPMS1- 


-2q31 


ureteric, endometrial, 






hPMS-7p22 


ovarian cancer 


Neurofibromatosis 1 


Autosomal dominant 


17q11 




Benign schwannoma, 
brain tumours (rare) 


Neurofibromatosis 2 


Autosomal dominant 


22q13 




Optic neuroma, 
acoustic neuroma, 
meningioma, glioma 


von Hippel-Lindau syndrome 


Autosomal dominant 


3p25 




Meningioma, renal 


Peutz-Jeghers syndrome 


Autosomal dominant 


19p 




Hamartoma, 










gastrointestinal tract 




Key point 

• Predictive tests for adenomatous polyposis coli 
may carry a social stigma or be potentially 
misused by insurance and employment agencies. 

At the same time, for the patients and their families, the 
knowledge of cancer risk and subsequent need for major 
surgery is stressful. Mutation analysis in the APC gene 
must be performed on a sample from the affected family 
member, as many different mutations from different fam- 
ilies may be found spanning the whole length of the gene. 
When the mutation is identified in a family, prenatal 
diagnosis is of course also possible, with all its associated 
problems regarding the decision to terminate pregnancy 
for late-onset disorder. 

3. The cloning of breast /ovarian cancer susceptibility 
genes (BRCA1 and BRCA2) has been accomplished (Miki 
et al 1994, Wooster et al 1995). This constitutes a major 
advance in the study of these common cancers. 
Mutations have been identified in all areas of these large 
genes. For practical clinical application, less expensive 



and less laborious methods of gene analysis need to be 
developed. 

4. Genetic susceptibility to breast and ovarian cancer is 
impossible to diagnose clinically in the absence of a con- 
vincing pedigree suggestive of autosomal dominant 
inheritance. Several mutations occur more frequently in 
the Ashkenazi Jewish population; the knowledge of the 
patient's background may facilitate mutation detection. 
The population risk for breast cancer in a woman aged 
30-39 is 4 in 1000. While the numbers of cases analysed to 
date are relatively small, and with only preliminary data 
available, the percentage of breast cancer due to BRCA1 
within that age range has been estimated at 5%. 

5. A number of cancer syndromes have been 
described, showing a characteristic combination of 
cancers (Table 40.2). As relatively small numbers of fam- 
ilies have been analysed to date; it is likely that a more 
accurate clinical spectrum will be available in the future. 

6. The study of families with a high frequency of site- 
specific colorectal cancer and colorectal cancer associated 
with malignant tumours of the genitourinary tract, uterus, 
breast cancer and other malignancies has facilitated the 
recent discovery of several new genes. These syndromes 



421 




GENERAL CONSIDERATIONS 



were initially described by Lynch et al (1988), but have sub- 
sequently been termed liereditary non-polyposis colon 
cancer' and 'cancer family syndrome'. The colorectal cancer 
is of early onset with a proclivity to the proximal colon and 
an excess of synchronous (Greek syn = together + chronos - 
time, hence simultaneous) /metachronous (Greek meta = 
after; hence occurring in sequence but separated by inter- 
vals) lesions. It is often, but not always, preceded by the 
development of colonic polyps. Colonoscopy is advocated 
every 3-5 years, with an increasing frequency in the pres- 
ence of polyps. The surveillance for the associated cancers 
is problematic because, again, clinical diagnosis is difficult. 
Genetic diagnosis is now possible, but methodological 
problems will need to be overcome for potential clinical 
application, as is the case with BRCA1/2 genes. 

7. It has been noted that tumours from these affected 
individuals contain a large number of DNA replication 
errors. The normal function of these newly discovered 
genes is to survey the fidelity of DNA replication and 
repair. Mistakes are frequently introduced during normal 
DNA replication and DNA repair has to take place, espe- 
cially when the cell is exposed to carcinogens, ionizing 
radiation or alkylating agents. The clinical expression of 
mutations in these genes is compatible with their function 
as tumour suppressor genes. The frequency of these gene 
mutations in the population is unknown, but in patients 
with colorectal cancer, genetic susceptibility has been 
estimated to account for 5-10% of cases. 

8. Advances in molecular genetics continue at an intense 
pace. With the current study of oncogene amplification to 
tumour stage and ultimately to prognosis, and the further 
development of tumour drug targeting and gene therapy, 
major practical advances in cancer prediction, detection 
and therapy should be forthcoming in the foreseeable 
future. Exciting recent developments include predictive 
genetic testing for relatives at high risk for developing 
cancer by mutation analysis. Clinical trials directed 
towards early cancer detection and chemoprevention in 
this group will provide statistically significant outcome 
data in a shorter time than other general population trials. 



Summary 

• Can you identify the genetic disorders that 
may predispose to life-threatening 
complications during surgery or 
anaesthesia? 

• Which congenital defects in 
haemoglobin, haemostasis, muscle, 
connective tissue and the skeleton should 
you note? 

• Do you understand the accumulation of 
mutations in oncogenes and in tumour 
suppressor genes that may increase 
susceptibility to cancer? 

• Do you realize that genetic mutations in 
specific tumour suppressor genes were 
identified in approximately 20% of 
individuals with early onset and family 
history of cancer? 

• While the great majority of cancers are 
sporadic, what salient features in the 
history and examination suggest a genetic 
increased susceptibility to cancer? 




References 



Fearon ER, Vogelstein B 1990 A genetic model for colorectal 

tumorigenesis. Cell 61: 759-767 
Lynch HT, Lanspa SJ, Bonan BM 7 Smyth T, Walson P, Lynch JF 

1988 Hereditary non-polyposis colorectal cancer, Lynch 

syndromes I and II. Gastroenterology Clinics of North 

America 174: 679-715 
Miki Y, Swensen J, Shattuck-Eidens D et al 1994 A strong 

candidate for the breast and ovarian susceptibility gene 

BRCA1 . Science 266: 66^-71 
Wooster R, Bignell G, Lancaster J et al 1995 Identification, of the 

breast cancer susceptibility gene BRCA2. Nature 378(6559): 

789-792 



422 




Screening for surgical disease 



T. Bates 



* 



Objectives 



• Identify essentials for justifying a 
screening programme. 

• Appreciate the practical requirements. 

• Recognize the cost-benefits, including 
mortality and quality of life. 



INTRODUCTION 

At first sight, screening the population for the common 
forms of surgical disease seems a good idea, as it should 
then be possible to cure the condition before it becomes 
symptomatic. Cancer of the lung, which is still the com- 
monest malignancy, with 22 700 male and 11 000 female 
deaths in England and Wales per year (Office of Population 
Censuses and Surveys 1994), has such a poor prognosis that 
screening the population by mass miniature chest X-ray 
failed. In contrast, prevention, by a public health pro- 
gramme to stop smoking, has reduced death rates by 
almost a third in men. Screening programmes have been set 
up for carcinoma of the colon, stomach, breast and cervix, 
and more recently the prostate and ovary. It is possible that 
screening for non-malignant conditions such as abdominal 
aortic aneurysm may reduce the number of deaths in older 
men from leaking aneurysm. To be effective, early detection 
and treatment must lead to fewer deaths from the disease, 
or have a major impact on the quality of life in the screened 
population, but in some of these conditions there are still 
doubts that this can be achieved. 



BIAS 



■^^^^■^^^'^^^^^^^^^■^"^^'^y^^ -■■>*"S 



Lead time bias 



■^;^;-':>>V!^^:^ 



The term Tead time' originated as the interval between a 
decision to begin a process and the completion of the 



project. An increased survival time from diagnosis to 
death could well be due to earlier, and therefore more 
prolonged, observation of the natural history of the 
disease, which might be unaffected by the treatment. This 
situation is known as lead time bias and in breast screen- 
ing is usually reckoned to be about 2 years. 



Length bias 

1. If the interval between screening episodes is rela- 
tively long, the test detects those cases with slowly 
growing tumours, whereas rapidly growing cancers with 
a worse prognosis tend to present in between screens. 
Both lead time and length bias increase the apparent 
benefit of screening, without necessarily improving the 
natural history of the cancer in question. 

2. The acid test for a screening programme is to 
compare a screened population with an identical non- 
screened population; this is ideally set up as a random- 
ized controlled trial (see Ch. 45), to avoid unrecognized 
systematic biases (Shapiro 1981, Hardcastle et al 1996). If 
the disease carries a relatively good prognosis when ade- 
quately treated at an early stage, it may take many years 
of observation to show a difference in the number of 
deaths between the screened and non-screened groups; 
this requires considerable resources. 

3. There are many questions which must be answered 
before considerable amounts of time, money and effort 
are committed to a screening programme. These ques- 
tions must be addressed by several disciplines: clinical 
scientists in the relevant specialty, epidemiologists with 
expertise in screening, social scientists and economists. 

4. Is the burden of the disease in the population suffi- 
cient to warrant an intervention? Is the screening test 
accurate in detecting cases in the population to be 
screened, and is the subsequent treatment effective in 
curing the disease? In trying to answer these three 
critical questions the following specific issues must be 
considered. 



423 



41 



GENERAL CONSIDERATIONS 




Key points 

If longer survival from progressive disease is 
claimed to result from improved screening: 

• Was the diagnosis being made at an earlier 
stage of the disorder than previously? 

• Were the patients suffering from a less 
rapidly aggressive form of the disease than is 
usual? 

• Will early detection alter the natural history of 
the disease? 




To be effective a screening test must 
be: 



• Sensitive - low false-negative rate 

• Specific - low false-positive rate 

• Of high negative predictive value - should 
effectively rule out the condition 

• Safe and acceptable - with a high compliance 
rate 

• Effective - treatment should reduce the 
number of deaths, the severity of treatment 
and improve the quality of life. 



REQUIREMENTS FOR A SCREENING 
TEST 

1 . Is the screening test sensitive: does it detect most of 
the cases, with few false negatives? 

2. Is the test specific: does it detect only cancer cases, 
with few false positives? 

3. Is the negative predictive value of the test high: does 
a negative test provide reassurance that the risk of the 
condition is very low? 

4. Is the test safe, relatively inexpensive and capable of 
achieving adequate compliance in the population to be 
screened? 

There are many examples of screening where these 
criteria have not been met. O-tolidine-based dyes for 
detecting occult blood increased the risk of bladder 
cancer in laboratory staff. The dose of irradiation initially 
used for breast screening mammograms is no longer 
regarded as safe. Investigation and treatment of false- 
positive cases may lead to psychological or physical 
morbidity. A few cases, only, of suicide precipitated by 
the anxiety of a positive or doubtful test negate or at 
least undermine any real survival advantage from early 
diagnosis and treatment. 

False-negative screening tests, or clerical failure to 
notify people of positive results, cause a public outcry 
when a delay in diagnosis has led to the need for more 
radical treatment or even a premature or preventable 
death. Such failures have tended to undermine public 
confidence in the cervical and breast screening pro- 
grammes in the UK. Sensitivity and specificity tend to be 
inversely related. The individual performance of screen- 
ing radiologists is monitored; a radiologist in the breast 
screening programme with a high sensitivity has a 
high recall rate with more false-positive cases, and there- 
fore a low specificity; and vice versa (Grimes & Schulz 
2002). 



POPUL^ON^T 

The at-risk population must be defined. To screen young 
people for cancer does not make sense but cancer of the 
cervix has become more common in younger women; this 
has led to a lowering in the age at which screening is 
offered. It is essential to have an accurate register of the 
population to be screened, and in city areas this must be 
frequently updated if the clients are to receive invitations 
for screening. Screening the elderly is likely to show poor 
uptake (compliance) with age, and an increasing propor- 
tion of patients will die of intercurrent disease. The 
cost:benefit ratio is therefore less favourable but there may 
be political resistance to the omission of this age group. 

Screening of high risk groups, such as those with a 
strong family history of cancer, poses special problems 
and different criteria must be used. 



COLORECTAL CANCER 

Colonoscopy is the 'gold standard' test (against which 
other tests are measured) for detecting colonic cancer or 
polyps. It has both specificity and sensitivity nearing 100%, 
but high cost and low compliance rule this out as a screen- 
ing test except for those at very high risk from, for example, 
familial adenomatous polyposis, or longstanding ulcer- 
ative colitis. Those at risk from colorectal cancer should be 
ideal candidates for screening, as many cancers are pre- 
ceded by benign adenomatous polyps. Furthermore, early 
cancer (Dukes' stage A) has a 5 year survival of 90% with 
conventional operative treatment. However, the best avail- 
able test is poor. The guaiac-based Haemoccult test of three 
samples is probably the best available test for faecal occult 
blood but it has a relatively low sensitivity, especially for 
right-sided and rectal tumours. Immunologically based 
tests are more sensitive but less specific and give rise to 
false-positive cases which require expensive and unneces- 
sary investigation. 



424 



SCREENING FOR SURGICAL DISEASE 



41 



Randomized controlled trials of faecal occult blood 
screening have shown a reduced number of deaths from 
colorectal cancer by 15-33% in the screened group 
(Hardcastle et al 1996, Kronborg et al 1996). It is intended 
to introduce systematic screening in the UK. The issues 
are well reviewed by Ransohoff & Sandler (2002). 



CANCER OF THE BREAST 

There have been four randomly allocated trials of popu- 
lation screening for breast cancer by mammography; of 
these, only the Swedish two-counties study has shown 
a significant reduction in mortality (Tabar et al 1989). 
However, an overview of these trials and other non- 
randomized studies shows that all report fewer deaths in 
the screened versus the non-screened population (Wald et 
al 1991). There has been a recent reduction in the number 
of deaths from breast cancer in many countries (Peto et al 
2000) but the trend preceded screening and may be 
principally related to the increased use of adjuvant 
therapy (Latin adjuvere = to aid; something that enhances 
the effectiveness of medical treatment). 



CARCINOMA OF THE CERVIX 










Key point 

• The incidence of cancer varies over time for 
many reasons. Do not automatically assume 
that screening programmes have generated 
observed improvements. 

There has been an unexpectedly high number of 
cancers presenting between 3-yearly screens (interval 
cancers) in the UK National Breast Screening Programme, 
which has led to the adoption of two-view instead of 
single-view mammography for the first screen (Blanks 
et al 1997), but a randomized trial of 2 versus 3 years 
showed no benefit from an increased frequency of screen- 
ing (UKCCCR 2002). The upper age limit will be 
increased from 64 to 69 years in the UK, as compliance in 
this age group seems better than was expected and there 
is evidence of benefit. Screening women under the age of 
50 achieves a relatively small reduction in the number of 
deaths and remains controversial. Recent criticism of the 
methodology used in the randomized trials of breast 
screening (Olson & Gotzsche 2001) has been countered by 
an updated overview of the Swedish randomized trials 
(Gelmon & Olivotto 2002, Nystrom et al 2002). This shows 
a 21% reduction in breast cancer deaths but the age- 
adjusted relative risk for total mortality was 0.98 
(0.96-1.00). 



Unfortunately no randomized trial of cytological screen- 
ing for carcinoma of the cervix has been carried out. 
Although death rates for this disease have fallen in many 
countries, this fall has often preceded the introduction of 
screening (Williams 1992). 

Up to 60% of women who have developed cervical 
cancer in the UK had never been screened, and the false- 
negative rate for examination of the smears is about 10%. 
Not all smears are adequate, and cytoscreening is very 
labour intensive and susceptible to problems with quality 
control (Miller 2002). This is unsatisfactory because ade- 
quate treatment of cervical intraepithelial neoplasia (CIN) 
is highly successful. An efficient mechanism has been 
developed for recalling and treating patients with posi- 
tive smears based on general practice, and compliance 
has reached 83% (Austoker 1994a). 



The incidence of cancer of the stomach seems to be falling 
as colon cancer rises but these changes may be con- 
founded (an alternative explanation for the observed 
facts) by the vagaries of death certification. 

Cancer of the stomach is much more common in Japan, 
where screening for early gastric cancer seems to be effec- 
tive (Hisamichi & Sugawara 1984) with the use of barium 
studies, gastroscopy and, more recently, serum pepsino- 
gen. In the UK the search has been less successful. It is 
suggested that screening by gastroscopy should be 
confined to symptomatic patients over the age of 55 
(Hallissey et al 1990). 



Q^RaNOMAOF™ 

Screening for carcinoma of the prostate is controversial, as 
the disease mainly affects an elderly population and 30% of 
men over the age of 50 have histological evidence of pro- 
static cancer at necropsy but in only 1% of these is there 
clinically active disease (Austoker 1994b). The available 
screening tests, apart from rectal examination, are prostatic- 
specific antigen and transrectal ultrasound. Neither the sen- 
sitivity nor the specificity of these tests is high, either alone 
or in combination, and the treatment of localized prostatic 
cancer is also controversial. Radical prostatectomy, radio- 
therapy, hormonal manipulation and a watch policy are all 
used but there is as yet no randomized trial that is suffi- 
ciently mature to indicate survival benefit. It is important 
not to cause unnecessary morbidity in elderly men with 
asymptomatic disease (Donovan et al 2001). 



425 



41 '' 



GENERAL CONSIDERATIONS 



CANCER OF THE OVARY 

Evidence for survival benefit from screening for carci- 
noma of the ovary is lacking but a large randomized con- 
trolled trial has been organized. The main screening tests 
are antigen marker CA 125 and transvaginal ultrasound, 
but other tumour markers and colour Doppler are being 
evaluated. The sensitivity of CA 125 for early ovarian 
cancer may be as low as 50%. There is, however, a strong 
case for screening a high risk group with familial ovarian 
cancer syndrome (Austoker 1994c). 



SCREENING FOR NON-MALIGNANT 

SURG^ 

Neonatal screening 

Congenital disease is increasingly diagnosed as a result 
of routine antenatal ultrasound screening but postnatal 
clinical examination must be carried out to exclude 
congenital cardiac and renal abnormalities as well as 
orthopaedic, sexual and anorectal malformations. Most 
congenital abnormalities usually present as a clinical 
problem in the first few days of life. Recognize also silent 
conditions, such as congenital dislocation of the hip, in 
which delayed diagnosis may worsen the outcome. 

Abdominal aortic aneurysm 

This accounts for 2900 male and 1040 female deaths per 
year in England and Wales. 

There are several population screening studies from 
the UK and the USA, and in men over the age of 65 ultra- 
sound screening of the aorta shows a prevalence (the 
percentage of population affected, as opposed to 
incidence, which is the rate of occurrence) of aneurysm 
of about 5%, depending on size criteria. This rate may be 
twice as high in men with hypertension or vascular 
disease, and the lifetime prevalence in first-degree male 
relatives may be as high as 50% (Collin 1994). Deaths 
from leaking abdominal aortic aneurysm can be reduced 
by screening men at age 65 years, combined with a 
policy of electively operating on fit patients with an 
aortic diameter of about 5.5 cm or more. (Multicentre 
Aneurysm Screening Study 2002). 



WHAT COMPLIANCE IS TO BE 
EXPECTED? 



screening test and the perceived effectiveness of the 
treatment. Screening for breast cancer by mammography 
achieves 80% in areas with a stable population but may 
be less than 50% in inner city areas. Compliance is also 
sensitive to media exposure in the short term. 

In screening for colorectal cancer, the acceptability of 
the faecal occult blood test is very low, leading to poor 
compliance; unless public awareness is increased at the 
time that screening is offered. There are many reasons 
why people decline screening invitations but failure to 
receive the letter is a common cause. The true refusers are 
an unusual group of people who have a poor outlook 
from both a health and a social standpoint. They neglect 
or abuse their health in many respects and cannot there- 
fore be used as a control group for comparison with those 
who accept screening; whatever comparison is made, the 
refusers will be disadvantaged. Compliance for cervical 
screening is worst in the low socioeconomic group most 
at risk from the disease (Segnan 1997). 



THE INTERVENTION TO BE USED 



&^^^^ft>^j'^fefefe^^^^ 



^i^i^y^^.^-^ 



:^^s3fr^^ 



Compliance, conforming to the advice of the screeners, 
varies with the social acceptability and public awareness 
of the disease, the inconvenience or discomfort of the 



It has already been noted that an operation for early 
bowel cancer has a high cure rate but we cannot be sure 
that this is the case for breast cancer. Screen-detected 
breast cancer has many features known to indicate a good 
prognosis (Klemi et al 1992) but ductal carcinoma in situ 
is diagnosed in up to 20% of screened cases and the best 
treatment for this condition is still in doubt. It is possible 
that fear of overtreatment by mastectomy may lead to a 
sacrifice of survival advantage by inadequate surgery. 
Severe dysplasia of the cervix (CIN III) has an extremely 
good outlook with local treatment and close surveillance. 
Node-positive carcinoma of the stomach has a 5 year sur- 
vival rate of less than 10% but in situ tumours carry a 
good prognosis with adequate surgical treatment. The 
Japanese have pioneered surgery for gastric cancer that is 
more radical than has been the norm in the West; clinical 
trials are currently in hand to try and repeat their excel- 
lent results in the UK. The place of radical prostatectomy 
in the treatment of screening-detected prostatic cancer 
remains uncertain. 

Abuse of screening 

Opportunistic screening may be offered or even adver- 
tised to give "peace of mind' where there is no evidence 
of benefit. High technology tests, such as electron-beam 
computed tomography (CT) for detecting obstructive 
coronary artery disease and low dose spiral CT for detect- 
ing early lung cancer, have been criticized in this respect, 
and it seems likely whole body CT scans will be the next 
high technology test (Lee & Brennan 2002). 



426 



SCREENING FOR SURGICAL DISEASE 



41 



o— 



Key points 



Controversies in screening 

• False negative tests cause public concern and 
fear of litigation, especially in carcinoma of the 
cervix and carcinoma of the breast. 

• There is doubt as to the actual reduction in the 
number of deaths. 

• False-positive tests lead to unnecessary 
investigations/operations. 

• The high cost of screening might be better 
spent elsewhere. 



WHAT IS THE COST? 



i:^^ ; 5^^Sv^^S : : &&^£1S + >v^>&^^ ii 



"^-^?££ftiW^^^ 



Economists wish to know the cost per case detected, per 
case treated and per life saved. Sociologists wish to know 
the psychosocial cost in those false-positive cases investi- 
gated unnecessarily and the quality of life in those 
patients who have cancer detected sooner than it other- 
wise would have been. 



Summary 

• How do you decide whether or not a 
screening test for cancer is capable of 
detecting disease at a stage when earlier 
treatment will lead to fewer deaths? 

• What are the sensitivity and specificity of a 
test, and how can your assess them? 

• What is meant by 'high negative predictive 
value'? 

• Why does the treatment of a screened 
disease need to be effective? 

• How do cost and quality of life enter into 
consideration? 




References 



Ashton HA, Buxton MJ, Day NE et al 2002 The Multicentre 
Aneurysm Screening Study (MASS) into the effect of 
abdominal aortic aneurysm screening on mortality in men: a 
randomised control trial. Lancet 360: 1531-1539 

Austoker J 1994a Screening and self-examination for breast 
cancer. BMJ 309: 168-174 

Austoker J 1994b Screening for cervical cancer. BMJ 309: 
241-248 



Austoker J 1994c Screening for ovarian, prostatic and testicular 

cancers. BMJ 309: 315-320 
Blanks RG, Moss SM, Wallis MG 1997 Use of two view 

mammography compared with one view in the detection of 

small invasive cancers: further results from the NHS breast 

screening programme. Journal of Medical Screening 4: 98-101 
Collin R 1994 Abdoiriinal aorta: epidemiology. In: Morris PJ, 

Malt RA (eds) Oxford textbook for surgery. Oxford University 

Press, New York, pp 377-378 
Donovan JL, Frankel SJ, Neal DE, Hamdy FC 2001 Screening for 

prostate cancer in the UK. BMJ 323: 763-764 
Gelmon KA, Olivotto I 2002 The mammographic screening 

debate: time to move on. Lancet 359: 904 — 905 
Grimes DA, Schulz KF 2002 Uses and abuses of screening tests. 

Lancet 359: 881-884 
Hallissey MT, Allum WH, Jewkes A], Ellis DJ, Fielding JWL 

1990 Early detection of gastric cancer. BMJ 301: 513-515 
Hardcastle JD, Chamberlain O, Robinson MH et al 1996 

Randomised controlled trial of faecal occult blood screening 

for colorectal cancer. Lancet 348: 1472-1477 
Hisamichi S, Sugawara N 1 984 Mass screening for gastric 

cancer by X-ray examination. Japanese Journal of Clinical 

Oncology 14: 211-223 
Klemi PJ, Joensuu H, Tbikkanen S et al 1992 Aggressiveness of 

breast cancers found with and without screening. BMJ 304: 

467-^69 
Kronborg O, Fenger C, Olsen J et al 1996 Randomised 

controlled study of screening for colorectal cancer with faecal 

occult blood test. Lancet 3348: 1467-1471 
Lee TH, Brennan TA 2002 Direct to consumer marketing of 

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1501-1504 



427 




Audit 



fl, Davidson, H. J. Schneider 




Objectives 

Appreciate what audit is and its vital link 

with clinical effectiveness. 

Recognize that audit is but the first step, 

not an end in itself. 

Recognize the need to change clinical 

practice in the light of audit findings. 

Use audit as a valuable educational tool. 



INTR^ 

Audit (Latin auditus - a hearing) is a critical appraisal of 
the care dispensed by clinicians. There have been many 
examples of audit activity in a number of guises over the 
last few centuries. One of the most notable surgeons to 
declare his failures as well as successes for the benefit of 
colleagues was the great 19th century German surgeon of 
Swedish origin, Theodor Billroth (1881). 

The improvement in standards of care in surgery as a 
whole and in the practices of individual surgeons has, 
until recently relied on the apprenticeship of the training 
years, and the dissemination of new learning and good 
practice through the medium of the book, the journal and 
the lecture by the 'expert'. Those who were prepared to 
listen and read were able to change practice where appro- 
priate. Even now, many surgeons rely on the annual meet- 
ings of the various 'craft' associations for education in 
current surgical practice. 

The roots of modern audit lie in the regular morbidity 
and mortality meetings held in many hospitals in the 
USA. The value of these meetings as a means of learning 
was recognized and formed the basis of broader audit 
activities. When transferred to the British Isles in the 
1950s, the American drive for change based on the find- 
ings, and the educational importance, were missing. 

In the early 1980s, microcomputers became available 
and made it possible to collect and analyse large amounts 
of information very swiftly. Most of us now have, or 
should have, access to reliable, peer-reviewed data on all 



aspects of medicine and surgery (see Ch. 12). This pro- 
vides us with a powerful tool to assist in the interpreta- 
tion of types of work done, throughput, complications, 
cost and mortality. We have the opportunity to see what 
are the best results, compare ours with them, determine 
the reason for differences and react to them. 

Possession of an audit system is not synonymous with 
the successful practice of audit. Systems are merely tools 
with which we can get a grasp and some understanding 
of the activity for which we are responsible. Moreover, 
there is great variation in acquisition, recording, 
analysing and using information. For this reason some 
people deprecate attempts to collect and compare it - 
but imperfect information is better than none at all. A 
danger of having easy access to information is that it is 
collected but never utilized. Unless it is applied in an 
effort to produce improvements, it is merely bureau- 
cratic detritus. 

Every hospital in the UK is now responsible for ensur- 
ing the development of clinical audit in which all 
doctors participate. The requirement for audit is now 
written into the job descriptions for all new medical 
staff. However, effectiveness in securing worthwhile and 
lasting improvements in the quality of care for patients 
is still very variable (Walshe & Spurgeon 1997). These 
authors have developed a clinical audit assessment and 
improvement framework designed to improve the effec- 
tiveness of audit programmes and individual audit 
projects. 

Until 1990 there was no funding or allocation of time 
for audit activity. Health authorities must now agree 
plans for audit, addressing local service and clinical prior- 
ities with trust managers and audit groups. As part of the 
audit contract with hospitals, health authorities can 
request audit of specific clinical areas. 



DEF|NITIOIK,______ 

Clinical audit is defined by the Department of Health as: 
'The systematic, critical analysis of the quality of medical 
care, including the procedures used for diagnosis and 



428 



AUDIT 




treatment, the use of resources, and the resulting outcome 
and quality of life for the patient', and states that 'an 
effective programme of medical audit will also help to 
provide reassurance to doctors, their patients, and man- 
agers that the best quality of service is being achieved, 
having regard to the resources available' (Department of 
Health 1989). The efficient and effective use of resources 
is important (Ellis et al 1990), but it is not the first prior- 
ity of clinical audit. 



improvement and to provide a mechanism for bringing 
them about. As such, it endeavours to get away from the 
'single interesting case' and look for patterns of care that 
should ideally be evaluated against research-based 
evidence or accepted best practice. Audit should initiate 
investigation into those areas of clinical care that are con- 
sidered as high risk, high cost or very common. Audit 
investigation is also suitable for resolving issues of con- 
tention or local interest. 




Key points 



• Omitted from the Department of Health's 
definition is the vital educational component 
for you as a trainee surgeon. 

• Clinical audit is not only a critical assessment of 
what has and has not been done but a 
potentially powerful and practical teaching aid. 

Clinical audit is the responsibility of clinicians and must 
be led by us. The terms 'clinical audit' and 'medical audit' 
are sometimes used interchangeably, but a consensus has 
developed whereby medical audit refers to the assessment 
by peer review of the medical care provided by the 
medical profession to the patient, and clinical audit refers 
to an assessment of the total care of the patient by nurses, 
professions allied to medicine (such as physiotherapists) 
as well as doctors. The multiprofessional team has an 
essential role in patient care and the quality of health care 
cannot be determined by doctors alone. Most hospitals 
have now focused their audit activity around clinical 
rather than medical audit. 

A revised position statement on clinical audit identifies 
future goals: 

• Clear patient focus 

• Multiprofessional working 

• Patient care managed across primary, secondary and 
continuing care 

• Closer links with education 

• Integration of effectiveness information 

• Improvement of clinical effectiveness. 



ATTrrilDE S TO AU DIT 

1. You may argue that audit is practised already; that 
ward rounds, clinical presentations, research and mor- 
bidity and mortality meetings fulfil this function. 
However, there are differences between these and clinical 
audit. Audit must be seen as a systematic approach to the 
review of clinical care to highlight opportunities for 



P 5 ! 

I I Key point 

• Discussing the rare and clinically interesting 
case is not audit. Leave it for the clinical 
conference. 



2. You may feel that the time spent on audit could be 
much better spent on other activities, such as treating 
more patients. This is not a wholly spurious argument; 
audit was introduced without any prior evaluation and, 
although there have been several subsequent evaluations, 
the results have, to date, failed to demonstrate clear value 
for money or effort expended (Walshe 1995). 

3. There is, none the less, general agreement that a 
regular review of your own practice against agreed stan- 
dards of best practice can lead to improved care of 
patients, who must be the principal beneficiaries of the 
process. 

4. Clinical audit improves patient care not only 
through direct changes in clinical practice but also 
through indirect effects such as professional education 
and team development. 

5. An effective clinical audit programme can give the 
necessary reassurance to patients, clinicians and man- 
agers that an agreed quality of service is being given 
within available resources. 

6. Clinicians and managers share audit information 
within agreed rules of confidentiality. Many deficiencies 
revealed by audit relate to the organization of care and, 
although audit must remain clinically led, support from 
National Health Service (NHS) board directors and man- 
agement is vital if it is to achieve the necessary changes 
in practice. 

7. There is a growing need to base clinical practice on 
the knowledge obtained from rigorous research into the 
effectiveness of healthcare interventions. 

8. However, your freedom to determine the treatment 
you offer individual patients must be preserved - but 
remember that you may need to justify it as accepted or 
evidence-based practice if there is an adverse outcome. 

9. An important part of the national research and 
development strategy is to make information on research 



429 



42 



GENERAL CONSIDERATIONS 



findings easily available to clinical and managerial staff, 
both in printed form, such as Effective Health Care 
bulletins, and electronic media, such as the Cochrane 
Library. 



AUDIT COMMITTEE 

UK hospital clinical audit committees draw members 
from a range of clinical backgrounds, such as nurses, 
general practitioners, educational tutors, trainee doctors, 
pharmacists and physiotherapists, together with audit 
staff. The committee reports to the unit management. The 
chairman needs to be well motivated and prepared to 
devote time on a regular basis. 
Audit committee functions are to: 

1 . Coordinate and foster clinical audit for everyone 
involved in patient care 

2. Offer reassurance that audit is valuable for patients 
and clinicians, not threatening 

3. Determine existing practice of audit 

4. Assist clinicians to implement audit methods 

5. Monitor the data, results, conclusions and reporting 
of the audit process 

6. When changes are indicated, ensure they are 
implemented and the effects monitored 

7. Promote the educational value of audit 

8. Maintain confidentiality 

9. Ensure effective liaison with general practitioners 
10. Staff requirements include an audit officer and /or 

coordinator to enable the implementation of audit, 
and to assist clinicians in the execution of the audit 
process. They help plan and prepare audit 
programmes, plans and literature searches, and 
screen case records against determined criteria. 
They give computer assistance with databases, 
graphics, forms and help with the preparation of 
reports. 

The Royal College of Surgeons of England has published 
guidance on audit, Clinical Audit in Surgical Practice 
(1995), as well as a number of clinical guidelines. 

A National Centre for Clinical Audit (NCCA) was 
established in 1995. Publications include the NCCA 
Clinical Audit Action Pack (1996), a regular newsletter and 
a series of fact sheets. The centre runs an information 
service and has its own web site on the internet. 



METHODS 

Donabedian (1966) identified three main elements in the 
delivery of health care: structure, process and outcome. 



1 . Structure includes the quantity and type of resources 
available and is generally easy to measure. It is not a good 
indicator of the quality of care but should be taken into 
account in the assessment of process and outcome. 

2. Process defines what is done to the patient. It 
includes consideration of the way an operation was per- 
formed, what medications were prescribed, the adequacy 
of notes, and compliance with consensus policies. There 
is an underlying assumption that the activities under 
review have been previously shown to produce an 
optimal medical outcome. This is the area of patient care 
that is most open to change by clinicians. 

3. Outcome is the result of clinical intervention and may 
represent the success or failure of process. For example, 
outcome could be measured by studies of surgical fatal- 
ity rates, incidence of complications, or patient satisfac- 
tion. It can be considered to be the most relevant indicator 
of patient care, but it is the most difficult to define and 
quantify. Mortality and length of stay in hospital are very 
easily measured outcome indicators, but variations in 
these outcomes are rarely related directly to the quality of 
the service being delivered. It may be more important to 
consider whether patients perceive that their problems 
have been solved, their quality of life improved and, 
where appropriate, the duration of their survival. 

A number of audit techniques have evolved and found 
a place in the regular assessment of clinical practice. 

Basic clinical audit entails analysing throughput and 
case type, and assessing complications, morbidity and 
mortality. A review of such data is undertaken by each 
clinical firm at intervals of approximately 3 months. The 
essential ingredient is to distil out of the data any notable 
deviations from an accepted 'norm' and then to investi- 
gate the reason for this observation. 

Incident review involves discussing strategies to be 
adopted under certain clinical situations. An 'incident' 
may be a leaking aortic aneurysm or using a department 
for an investigation such as emergency intravenous uro- 
graphy. The discussions should lead to clear policies for 
future actions and use, with the construction of local 
guidelines. This audit method is particularly suitable for 
multidisciplinary or interdisciplinary audit. 

Clinical record review. A member of another firm of the 
same or similar speciality reviews a random selection of 
case notes, preferably having been given criteria (Greek 
krites - judge; hence, standards) against which to assess 
them. Clinical record audit has the advantage of sim- 
plicity and requires relatively little additional time or 
other resources. However, there is a potential disadvan- 
tage in that discussion might concentrate too much on the 
quality of record keeping and not enough on patient care 
- these two are distinct facets of the clinical process, 
although related. 



430 



AUDIT 




Criterion audit is a more advanced and structured form 
of incident audit. Retrospective analysis of clinical 
records is made and judged against a number of carefully 
chosen criteria. These criteria should encapsulate the key 
elements in management of a particular topic which are 
capable of unambiguous interpretation from the medical 
record, by a non-medical audit assistant. All cases falling 
within the scope of the topic in question are screened and 
those that fail to meet any of the criteria are brought 
forward for further clinical review. The criteria may relate 
to administrative elements such as waiting time, investi- 
gations ordered, treatments given, outcome and follow- 
up strategies. Criteria for adequate management of a 
particular condition can be derived easily from clinical 
guidelines. Clinicians need to participate actively in the 
preliminary discussion, but thereafter most of the work 
can be performed by audit assistants. The method is 
applicable to a variety of circumstances and allows data 
to be compared between different hospitals (Shaw 1989). 
The criteria can be used for setting standards, with targets 
identifying the proportion of patients in whom each cri- 
terion should be met. After review, new targets can be set 
to stimulate improvement. For example, a suitable target 
is the reduction of infection rates in colorectal surgery to 
those obtained in other published studies (Hancock 
1990). 

Adverse occurrence screening is intended to identify 
events that need to be avoided, such as wound infections, 
unplanned readmissions, delayed or erroneous diag- 
noses. Occurrences are recorded and those that are 
complex or serious are reviewed by clinicians. A database 
is accumulated which can then be interrogated to identify 
trends and, for example, perform comparative analyses. 
Cases can be considered in total or as samples. This tech- 
nique can also be used for risk management (Bennett & 
Walshe 1990). 

Comparative audit implies the collection of data and its 
comparison across units, health authorities and even 
through a whole region (Gruer et al 1986, Black 
1991). Within a single hospital, comparisons may be dif- 
ficult because the number of departments undertaking 
similar work is often very small, and the case mix even 
between two general surgical firms may be disparate. The 
Royal College of Surgeons (1991) set up a comparative 
audit service in which all surgeons supply information 
under a confidential number for comparison with their 
peers at regular meetings. Techniques in data presenta- 
tion allow such sensitive information to be widely 
disseminated and discussed, while maintaining an indi- 
vidual clinician's confidentiality (Emberton et al 1991). In 
Scotland, a regional computerized audit system main- 
tained by general surgeons over 15 years, recording clini- 
cal data which is regularly reviewed in a peer group 
setting, has provided clear evidence that regional audit 



can significantly influence and improve surgical practice 
(Aitken et al 1997). 

National studies were first used to study perinatal mor- 
tality in obstetric units. The report of the first confiden- 
tial enquiry into perioperative deaths (CEPOD: Buck et 
al 1987) considered the factors involved in the deaths of 
patients who died within 30 days of operation within 
three regional health authorities. Much was learned, 
especially the need for doctors in the training grades to 
be given adequate support and supervision. Disaster 
was clearly associated with surgeons attempting proce- 
dures for which they possessed insufficient skill or train- 
ing. Subsequently a national review (NCEPOD) was 
launched; data is submitted on a voluntary, confidential 
basis by surgeons and anaesthetists. Reports are pub- 
lished annually (Gallimore et al 1997). The findings can 
identify remedial actions and indicate appropriate topics 
for local audit, such as out-of-hours surgery (Campling 
et al 1997). 

Outcome audit is a review of the whole process of 
healthcare delivery during a patient's hospital contact. It 
thus measures all the skills of the medical and nursing 
staff, the hospital administration and, indeed, all those 
with whom the patient comes into contact. Inevitably 
there are different perspectives of outcome by the patient, 
general practitioner and hospital clinician. Satisfactory 
measures have not yet been evolved. Outcome studies, 
especially in the surgical specialities, are likely to be 
important measures of the quality of care. 

American surgical audit practice 

Audit is used in American surgical practice for the early 
detection of poor surgical results (Kirk 2001, Singer 2001). 
There is a customer-oriented approach for cultural and 
economic reasons. It is a litigious society where the per- 
formance and outcomes of surgeons and surgical estab- 
lishments are closely scrutinized. Recent changes in the 
UK in the wake of the Bristol affair, such as the publica- 
tion of league and performance tables, suggest that some 
or all of the following audit practices, which are standard 
in the USA, will eventually become commonplace in the 
UK. 

Morbidity and mortality meetings are closed, confidential, 
and attended weekly by the full surgical faculty, residents 
and surgical medical students. The departmental chair- 
man supervises and guides the debate and, most import- 
antly, reaches a conclusion regarding each complication 
or death. It is a basic premise that complications 
inevitably occur in surgical practice. The chief resident 
from each surgical team presents surgical throughput, 
complications and deaths for the previous 1 week period. 
The methods and outcomes of every surgeon are scruti- 
nized in the light of current evidence and research, with 



431 



42 



GENERAL CONSIDERATIONS 



the acceptance that complications are an inevitable part of 
surgical practice, and from which no surgeon is immune. 
These are discussed fully, openly, with reference to con- 
temporary evidence-based literature, to define complica- 
tions or deaths that were preventable, and identify 
corrective steps. This process is termed 'closing the audit 
loop'. Passive documentation is unacceptable. The cor- 
rective action is recorded, to be effected through letters, 
guidelines and alterations in departmental policy 
intended to reduce the risk of future similar errors. 
Trainees are educated to learn vicariously (Latin vicarius 
= substitute) from the errors of others, rather than from 
their own failures. 

Tissue committee meets monthly to compare every pre- 
operative diagnosis with the histological specimen report, 
to identify discrepancies and remedy them. 

Quality assurance committee meets monthly to audit 
outcome. For a specific condition they select a sample of 
approximately 20 patients 7 case notes to compare out- 
comes with national standards. Any significant lapse in 
performance by individuals, teams, departments or 
equipment is rectified. 

Insurance companies have access, by consent of the 
insured patients, to inspect the case notes on a periodic 
basis to identify discrepancies in practice, such as pro- 
longed stay, complications and significant increase in the 
financial cost of patients' care. 

ANALYSING AND CORRECTING FAILURES 

1. For many years mortality and morbidity conferences 
and audit meetings considered isolated failures - now 
often termed 'adverse incidents'. A 'cause' was identified 
by the senior participants and the meeting passed on to 
the next incident. The atmosphere gradually changed 
with demands by the public, and therefore by the poli- 
ticians, for accountability by doctors for errors, increas- 
ingly involving litigation. This was counterproductive 
because admission that a failure had occurred inevitably 
generated a demand for exposure of the 'culprit', so that 
doctors became reluctant to report failures. 

2. Contrast this with the situation in the airline 
industry: 

a. It is accepted that we all make mistakes and the 
investigation is pursued on a 'blame-free' basis. 

b. It is mandatory (Latin manus - hand + dare - to give; 
a command given by hand, allowing no option) to report 
any failure. It is not assumed that there is a single 'cause'. 

c. The failure can be compared with other potentially 
similar failures, from the accessible, international 
database. 

d. The best and most cost-effective method of prevent- 
ing subsequent failures is determined. 



e. The correction is implemented - and monitored 
thereafter. The national and international aviation safety 
boards have the power to order changes in procedures, 
design, servicing and manning. 

f . Whenever a disaster occurs, teams of skilled investi- 
gators search for the causes, aided by flight and speech 
recorders. The findings, and corrective actions required, 
are promulgated internationally. 




Key point 

• We need to learn and apply the studies 
available within the medical profession and 
industry to avoid errors and improve safety 
and particularly the US Federal Aviation 
Administration's methods of improving civil 
aviation safety. 

3. Some of the approaches used: 

a. System analysis failures demand a clear under- 
standing of the failure or failures. This often demands 
step by step examination of each piece of evidence, with 
immediate recording of the findings. 

b. Fault tree analysis was originally developed for the 
US Air Force. After identifying the top 'undesired' event 
causing failure, the analysis continues sequentially to 
detect the subsidiary contributing causes. 

c. 'What's different?' may be a valuable question when 
an unexpected failure occurs. Changes in assessment, 
decision making, technique, equipment, monitoring and 
aftercare may have been overlooked. 

4. Corrective action may involve system changes - but 
some methods are preferable to others on grounds of 
safety, reliability or convenience: 

a. Improvement in methodology or equipment may elim- 
inate failure. The most effective measure may be physi- 
cally to prevent an error being committed. For example, 
redesign of equipment may make it 'idiot proof. If acci- 
dents have occurred because the wrong components were 
connected, the connections may be altered so the correct 
ones alone can be matched. 

b. Monitoring systems may be introduced to identify 
potential failures, such as regular, routine checking for 
premonitory signs. In some cases automatic warning 
systems can be built in to identify impending failures. In 
medical practice, intensive care unit monitors relieve 
nurses of constantly checking basal measurements, allow- 
ing them to concentrate on other problems. 

c. Replacement: components of equipment that fail may 
be exchanged for new ones after intervals that are shorter 
than the earliest recorded failure time. 



432 



AUDIT 



42 



d. Duplication and back up is an alternative to anticipat- 
ing failure by early replacement of essential components. 

e. Training methods may need to be adapted to make 
sure that the risk of error is avoided. 

f. Routines, protocols, algorithms can be changed but the 
resulting benefit depends upon the conscientiousness 
with which they are followed. 

g. Checks are often employed. A junior may need to ask 
approval from a senior to carry out a procedure. A junior 
nurse may require to have a drug chart countersigned by 
a senior before administering treatment. Routine checks 
suffer from overreliance on them; they may become 
routine and casually performed and are best reserved for 
exceptional circumstances. 

h. Warnings are an unreliable method because they are 
overused. Visual warnings may not be seen, audible 
warnings may not be heard. 




Key points 




Key point 



There are two vital steps after identifying a 
solution, or it is useless. Implement it. Evaluate 

it. 



Human factors 

1 . The human factor analysis and classification system 
(HFACS) was developed by the US military to investigate 
human causes of flying accidents, and was applied to civil 
aviation accident investigations. Errors are classified as 
skill based, decision errors, violations of safety rules, or 
perceptual errors. Other factors were adverse mental or 
physical states and supervisory or organizational defects. 

2. Acceptance that the hierarchical system of command 
has defects (pilot > copilot > cabin crew) is defective and 
has led to vital information being ignored. The emphasis 
is on the aircraft crew working as a team, with each 
member having input. 

Changes needed to reduce or prevent medical errors: 

1. We cannot totally eliminate errors. They are 
inevitable in every human activity. 

2. We need an easily accessible / national and inter- 
national database of errors, adverse incidents and near 
misses - not just the ones that have been harmful, but also 
those that were averted or were potentially harmful. This 
information can be gathered only in an atmosphere of 
trust, without the threat of blame. 

3. Errors, harmful or harmless, offer opportunities to 
study potential improvements for the future in equip- 
ment, systems, decisions and techniques. 



• Although comparison between professions is 
valuable, remember that many airline problems 
are mechanical 'black and white'; many 
biological and clinical problems are immensely 
complex and are 'shades of grey'. 

• Retrospective judgements and actions are less 
secure when analysing biological failures 
compared with mechanical and structural 
failures. 

4. In the past, out of a misplaced reluctance to 'tell 
tales', we failed to challenge or report failures, mistakes, 
lazy corner-cutting, incompetence and lack of commit- 
ment by others. As with most failures, no harm usually 
follows. Unfortunately, on occasion, other failures 
develop simultaneously and disaster occurs. To avoid 
disasters, everyone must perform to a high standard all 
the time. 



Ethics and confidentiality 

You must protect the confidentiality of individual 
patients; the same principles apply as in clinical confer- 
ences, which form part of any academic programme. 
Avoid identifying details of a patient in verbal or written 
presentations; exclude them. 

Protect the confidentiality of the professionals involved, 
although this is difficult when, for example, one consul- 
tant reviews the clinical records of another consultant's 
patient. Nevertheless, this can be successful if you foster 
an atmosphere of trust and collaboration. Obtain per- 
mission from all consultants involved beforehand. 

Anticipate and provide for what should happen if audit 
reveals deficiencies in an individual's practice (Ellis & 
Sensky 1991). The Joint Consultants Committee recom- 
mends that you develop a plan of action, which they 
suggest. If necessary, check if the Ethical Committee 
requires to give permission before interviewing patients. 



Computers 

Acquire a working knowledge of the basic uses of a com- 
puter. You can utilize word processing and graphics and 
obtain access to databases such as MEDLINE from the 
postgraduate medical centre. This is faster and more ver- 
satile than searching Index Medicus. You may download 
abstracts and papers to a personal computer. The internet 
offers extensive and rapidly expanding reference sources, 
including the Cochrane Collaboration. There are now 



433 



42_ 



GENERAL CONSIDERATIONS 



many programs available as clinical information systems, 
with outputs configured to aid audit, and also some pion- 
eering ventures into clinical decision making and artificial 
intelligence. 



3. Audit helps you to identify areas for improving and 
increasing knowledge, or suggests the need for research. 
Remember that audit itself does not lead to new clinical 
knowledge. 



Hospital information systems 

Only a few hospitals have completely integrated hospital 
information systems covering every function, such as 
clinical records, the scheduling of clinics, to the provision 
of financial and manpower reports. Other hospitals have 
a patient administration system (PAS), including the 
'master index' (patients' demographic details) and 
records of admissions and diagnostic codes. This repre- 
sents the minimum upon which a hospital manager can 
rely for information. PAS systems regularly pass aggre- 
gated patient-level data according to a national minimum 
data set to the local health authority. This, together with 
contract activity information, enables local planning of 
services. 

In hospitals with this minimum configuration some 
clinical departments have implemented their own infor- 
mation systems, and these may provide sufficient infor- 
mation on which to draw patient samples for audit 
projects and some limited clinical data. 

Current trends favour the integration of all these dis- 
parate systems so that key patient-specific information, 
once entered, is available throughout the organization. 
The surgical trainee will almost certainly be involved in 
the gathering of information for the production of a 
discharge summary to the general practitioner and for 
clinical audit. 




Key point 

• Research aims to identify 'the right thing to 
do'. Audit assesses whether 'the right thing 
has been done'. 

4. Self-evaluation and peer review, common activities 
in audit, are important components of postgraduate edu- 
cation. To realize the full educational potential of audit, 
you must learn the lessons arising from previous audit 
meetings and review the conclusions acted upon. 



IMPLEMENTING CHANGE 



^l^^^'^viy^^^ 



rv&i^-t^V;:^^ 



1. Consider audit as a cycle, the first component of 
which is the observation of existing practice to establish 
what is actually happening (Fig. 42.1). 



Adverse event? 

Poor comparison with others? 

Opportunity to improve? 



EDUCATIONAL COMPONENT 

1. Because of the manner in which audit was intro- 
duced, with the intention of improving patient treatment 
and cost-effectiveness, the educational value was a sec- 
ondary consideration. It is now seen as vital that doctors 
in training are taught the basic principles of audit. 
Equally, conclusions drawn from the audit process should 
be seen as an important feeder into education. The edu- 
cational benefits of clinical audit have been considered in 
depth by Batstone (1990). 

2. Acquire and update your knowledge by critically 
reviewing current practice and comparing it with pre- 
defined standards. The audit process also enables you to 
identify important features of clinical practice that help to 
make teaching explicit. Audit is an active process of 
review. If you are passive, and unclear whether your 
current practice is inappropriate, you are unlikely to 
respond to information through traditional channels such 
as journals or continuing medical education (Lomas 1993). 



Continuous 
improvement 



Further 
changes 
needed? 



Re-audit 
change 



Observe 



Monitor 
change 




Agree standard 
of care 



Data 
collection 



Compare and 

implement 

change 



Fig. 42.1 The audit cycle. There should be no 'closure' 
in the terminal meaning of the word, but there should 
be 'closure' in the sense that no gap can be left in the 
circle of reacting to circumstances that demand action to 
improve them. 



434 



AUDIT 




42 



2. Now set standards of practice to define what ought 
to happen and make a comparison between observed 
practice with the standard. 

3. Now implement change. 

4. Observe again to see whether what has been 
planned has been achieved. 

5. You may need to decide whether practice needs to 
change further, or whether the standards were unrealistic 
or unobtainable. 

6. This process has become known as the 'cycle of 
audit' (Royal College of Physicians 1989) and the achieve- 
ment of change has been termed "closing the audit loop'. 

7. However, 'closure' implies completion. Always con- 
tinue to observe results. 



maintained, with cooperation replacing competition. The 
quality of care is a priority for everyone. 

Chief executives of trusts will be held accountable for 
the quality of services they provide. This responsibility 
for 'clinical governance' covers quality improvement (see 
Ch. 43). The importance of clinical audit, led by clinicians, 
in improving the quality of care for patients was recog- 
nized in the previous NHS reorganization in 1989. The 
new framework signals a more directed but integrated 
role for audit within the organization. This can be seen as 
an opportunity for audit to deliver the necessary changes 
in practice which have been identified, and fulfil its 
potential in improving patient care. 




Key points 

• Never cease to monitor results. 

• Once you achieve improvement, if you relax 
attention your improvement may relapse. 

8. The provision of information on clinical activity 
without any evaluation or suggestions for improvement 
has almost no effect on clinical practice (Mitchell et al 
1990). It needs to be targeted at decision-makers who had 
already agreed to review their practice (Mugford et al 
1991), A systematic review of 160 interventions directed at 
changing clinical behaviour or health outcomes showed 
that effects were small to moderate (Davis et al 1995). 
Effective strategies were outreach visits, opinion leaders, 
patient- media ted interventions and physician reminders. 
Audit with feedback gives variable results. 

9. The most commonly used approach involves the 
publication of guidelines, which have been shown to 
change practice and affect outcomes. Guidelines are more 
likely to be effective if they have local involvement and 
take into account local circumstances, are supported by 
active educational interventions and use patient-specific 
reminders, for example, in the medical notes (Effective 
Health Care 1994). Guidelines need to be reviewed regu- 
larly to establish 'ownership' and to incorporate the latest 
research findings. 



THE NEW NHS 

The government white paper The New NHS: Modern, 
Dependable (Department of Health 1997) outlines a new 
'10 year' structuring and modernization programme. The 
internal market is replaced by a system of integrated 
care based on a partnership between health and social 
care. The split between planning and providing care is 



Summary 

• Do you recognize the two aims of audit - 
improved health care and clinical 
education - must both be addressed? 

• Do you accept that audit without 
application of the findings is a wasted 
'paper exercise'? 




References 



Aitken RJ, Nixon SJ, Ruckley CV 1997 Lothian surgical audit: a 

15-year experience of improvement in surgical practice 

through regional computerised audit. Lancet 350: 800-804 
Bats tone GF 1990 Educational aspects of medical audit. BMJ 

301:326-328 
Bennett ], Walshe K 1990 Occurrence screening as a method of 

audit. BMJ 300: 1248-1251 
Billroth TH 1881 Clinical surgery: reports of surgical practice, 

1860-1876. New Sydenham Society, London 
Black N 1991 A regional computerised surgical audit project. 

Quality Assurance in Health Care 2: 263-270 
Buck N, Devlin HB, Lunn JN 1987 Report of a confidential 

enquiry into perioperative deaths. King's Fund, London 
Campling EA, Devlin HB, Hoile RW, Ingram GS, Lunn JN 1997 

Who operates when? A report of the national confidential 

enquiry into perioperative deaths. King's Fund, London 
Davis DA, Thomson MA, Oxman AD, Haynes RB 1995 

Changing physician performance: a systematic review of the 

effect of continuing medical education strategies. JAMA 274: 

700-705 
Department of Health 1989 Working for patients (paper no. 6). 

HMSO, London 
Department of Health 1997 The new NHS: modern, dependable 

(Cmnd 3807). Stationery Office, London 
Donabedian A 1966 Evaluating the quality of medical care. 

Millbank Memorial Federation of Quality 3(2): 166-203 
Effective Health Care 1994 Implementing clinical practice 

guidelines. University of Leeds, Leeds, vol. 1 : 8 
Ellis BW, Sensky T 1991 A clinician's guide to setting up audit. 

BMJ 302: 704-707 



435 



42 




GENERAL CONSIDERATIONS 



Ellis BW, Rivett RC, Dudley HAF 1990 Extending the use of 

clinical audit data. BMJ 301: 159-162 
Emberton M, Rivett RC, Ellis BW 1991 Comparative audit: a 

new method of delivering audit. Bulletin of the Annals of the 

Royal College of Surgeons 73: 117-120 
Gallimore SC, Hoile RW, Ingram GS, Sherry KM 1997 The 

report of the national confidential enquiry into perioperative 

deaths, 1994-5. NCEPOD, London 
Gruer R, Gordon DS, Gunn AA, Ruckley CV 1986 Audit of 

surgical audit. Lancet i: 23-26 
Hancock BD 1990 Audit of major colorectal and biliary surgery 

to reduce rates of wound infection. BMJ 301: 911-912 
Kirk J 2001 American mechanisms in place for the early 

detection of poor surgical results. Bulletin of the Annals of 

the Royal College of Surgeons 83: 307 
Lomas J 1993 Diffusion dissemination, and implementation: 

who should do what? Annals of the New York Academy of 

Sciences 703: 226-235 
Mitchell MW, Fowkes FGR 1990 Audit reviewed: does feedback 

on performance change clinical behaviour? Journal of the 

Royal College of Physicians 19: 251-254 
Mugford M, Banheld P, O'Hanlon M 1991 Effects of feedback of 

information on clinical practice: a review. BMJ 303: 398-402 
National Centre for Clinical Audit 1996 NCCA clinical audit 

action pack: a practical approach. National Centre for Clinical 

Audit, London 
Royal College of Physicians 1989 Medical audit. A first report - 

what, why and how? RCP, London 
Royal College of Surgeons 1991 Royal College of Surgeons 

confidential comparative audit service. Bulletin of the Annals 

of the Royal College of Surgeons 73: 96 
Royal College of Surgeons 1995 Clinical audit in surgical 

practice. RCS, London 
Shaw CD 1989 Medical audit: a hospital handbook. King's 

Fund, London 
Singer A 2001 The Bristol affair - a view from New York. 

Bulletin of the Annals of the Royal College of Surgeons 

83: 306 



Walshe K 1995 Evaluating clinical audit: past lessons, future 
directions. Royal Society of Medicine Press, London 

Walshe K, Spurgeon P 1997 Clinical audit assessment 
framework. Handbook Series 24. HMSU, University of 
Birmingham, Birmingham 




Further reading 

National Centre for Clinical Audit 1996 NCCA criteria for 

clinical audit. NCCA, London 
Royal College of Surgeons of England 1994 Guidelines for 

clinicians on medical records and notes. RCS, London 
Royal Society of Medicine 1990 Computers in medical audit: a 

guide for hospital consultants to personal computer based 

medical audit systems. RSM Services, London 
Trent Regional Health Authority 1993 Guidelines on 

confidentiality and medical audit. Trent RHA, Sheffield 

Systems failure analysis 

Berk J, Berk S 1993 Total quality management. Sterling, 

New York 
Wiegman DA, Shappell SA, Christina E 2000 A human factors 

analysis of aviation accident data: an empirical evaluation of 

the HFACS framework. Aviation Space and Environmental 

Medicine 71: 328 

These and many more are available on the internet by searching under 
the title 'Systems failure analysis' 

Also consult: 

Reason J 1990 Human error. Cambridge University Press, 
Cambridge 

Useful links 

http://www.ahrq.gov/qual/errback.htm Medical errors: the 
scope of the problem: fact sheet. 



436 




H3 Clin 



ical governance 



B. Higgs 



F 



Objectives 



• Understand the concept of and need for 
clinical governance. 

• Outline the framework/system of clinical 
governance. 

• Understand the role of clinical governance 
in delivering quality health care. 



INTRODUCTION 






Public, political and professional pressure has been 
growing to maintain and improve standards of patient 
care throughout the National Health Service (NHS). 
Clinical governance is one aspect of a system designed to 
set, monitor and maintain standards of patient care. The 
driving force for the introduction of clinical governance 
was the perceived lowering of public confidence in the 
NHS, a desire within the medical profession for systems 
to be established that set, maintain and improve stan- 
dards, and a demand for the government to fulfil public 
expectations. 

We should all aspire to improving the quality of health 
care. Although most health professionals already provide 
excellent quality care and many keep records or data sup- 
porting their practice, there are inequalities within the 
country, instances of substandard care and isolated cases 
of abuse of the public's trust. 

Clinical governance should identify areas where 
patient care is suboptimal. However, not all of the issues 
relate directly to the quality of clinical care provided, but 
to other aspects that contribute to patient care which may 
be economic and managerial, such as underfunding, 
understaffing and lack of facilities, beds, equipment and 
support services. 

Hospital trusts, like other business activities, need to 
be well organized to address these and other issues. Any 
organization that functions as a single unit can be called 
a corporate body. The system of corporate governance 
(Greek kybernaein, Latin gubernare = control) is well 



established in NHS Trusts, just as it is in the business 
world. Within the Trust the responsibilities of those 
working within a corporate structure are defined, and 
the rules and procedures for pursuing the aims of the 
business are decided and defined. The chief executives of 
NHS Trusts are the designated accountable officers for 
corporate governance. 

Clinical governance is the clinical parallel of corporate 
governance and defines the responsibilities of all those 
who provide service for the patients, provide support for 
their activities, monitor the results and ensure that the 
quality of care provided meets the requirements of 
the patients. The chief executives of NHS Trusts are 
also the designated, accountable officers for clinical 
governance. 



CLINICAL QUALITY 

The World Health Organization defines clinical quality 
under four headings: 

1 . Professional management - quality of the technical 
aspects of care 

2. Resource use - the efficiency of the management 

3. Risk management - the risk of injury, illness or poor 
outcome resulting from the care provided 

4. Patient satisfaction. 




To achieve optimal care we need to: 

Set clear standards in each aspect of quality 

assessment 

Ensure that in each aspect the delivery of 

service is the highest attainable 

Monitor the outcome in each aspect and if 

necessary correct deficiencies. 



Audit is used to monitor clinical quality (see Ch. 42). 
Medical audit provides a means of determining the 
quality of the care by physicians and surgeons. This does 



437 



43 



GENERAL CONSIDERATIONS 



not encompass all that is included in clinical quality, and 
clinical audit incorporates the total care by nurses and 
allied health professionals in addition to doctors. 



SCOPE OF CLINICAL GOV ERNANCE 

1. For many years the majority of clinicians have 
checked results /outcomes and compared them with pub- 
lished results from highly respected centres. However, 
these have usually been restricted to survival and result- 
ing major morbidity. Clinical governance incorporates 
these results, and more, with the overall service and 
quality of patient care. 

2. A patient visiting the outpatient clinic or general 
practitioner, or one who is admitted to hospital, does not 
judge the experience on the outcome alone. Patient satis- 
faction does not depend only on your clinical skills, abil- 
ities and judgements, but on the whole episode, which 
involves medical, nursing, ancillary, technical, allied 
health professionals, managers and secretaries, as well as 
the availability of equipment and facilities. Good clinical 
care may not compensate for poor facilities or equipment. 
The process must, therefore, be a multi- and interdisci- 
plinary event. Traditional boundaries and restrictive prac- 
tices must be addressed and patient care needs to be more 
integrated, involving all staff at all levels. 



improves, there can be no doubt that useful information 
will be gained, helpful to clinicians and patients alike. 




Key points 

Professional and clinical culture needs to place 

the patient at the centre of the health care 

organization. 

The effects must extend outside any institution 

into all aspects of patient care. 



REPORTING OUTCOMES 



■£37^^;^^ 



^^0^^^^^^ 



Following American experience, there is pressure for pub- 
licly available outcome results for comparison between 
units in the health service. Access to clinical information 
in order to allow monitoring of clinical and organizational 
practice appears to be a challenge for many organizations. 
The quality of recording and classification is not uniform 
and is often unreliable because of differences in facilities, 
equipment, trained staff and commitment to accurate 
recording. Moreover, the publication in 'ranked order' of 
crude survival rates is valueless and could be harmful. 
However, comparisons between different units with com- 
parable data and informed interpretation may be useful to 
both staff and patients. As information and data collection 




Key points 



Clinical governance challenges us to identify 
and address clinical issues to improve them. 
Imperfect information is better than no 
information. 



COMPONENTS OF CLINICAL 
GOVERNANCE 

1. Clinical effectiveness is concerned with ensuring that 
the best care is provided by delivering treatments that 
work. Clinical practice should be based on objective evi- 
dence. There are several components of clinical effective- 
ness that result in the delivery of evidence-based care (see 
Ch. 12). Health workers should know what is clinically 
effective practice, and how to apply that knowledge in 
day to day practice. We should make sure that changes in 
practice work to benefit patients. 

2. Clinical audit (see Ch. 42) is a systematic and critical 
analysis of the quality of clinical care, including the pro- 
cedures for the diagnosis, treatment and care, the associ- 
ated use of resources and the resulting outcome and 
quality of life for the patient. It is used to examine current 
practice in relation to a standard. If there is a gap between 
current practice and the standard, then practice must be 
changed to close the gap. The process is then reaudited to 
make sure that the loop is closed and the audit cycle is 
completed. 

3. Risk management is clinical and non-clinical, and is 
proactive - instigating changes in anticipation of future 
developments: 

a. Clinical risk management is achieved by establish- 
ing a process of reporting by all members of the clinical 
team whenever unexpected, adverse or 'near miss' clini- 
cal incidents occur, whether or not actual harm results. 
The reports are reviewed to identify any immediate action 
that should be taken to avoid future potentially danger- 
ous incidents. The aggregated data, together with recom- 
mendations, are fed back to all members of the care team. 
This process allows immediate action on incidents when 
required and the aggregate data draw attention to risks 
that may occur seemingly in isolation. When analysed 
over time, patterns may emerge, in isolation or across the 
whole establishment, so that steps can be taken to reduce 
or eliminate the risk. 

b. Non-clinical risk management is applied to con- 
siderations such as fire and electrical safety. 



438 



CLINICAL GOVERNANCE 



43 



4. Research and development supports clinical govern- 
ance by providing the evidence base for good and effec- 
tive health care. It is a popular misconception that to be 
of any value the research has to be funded by the Medical 
Research Council, be international, multicentred and 
published in a highly rated journal. While national and 
international research collaborations help to identify 
modern and effective treatments, many improvements to 
the provision of quality health care are made at local level. 
There is an obligation on all trusts to support, train and 
develop their staff to enhance the staff's research skills 
and hence improve the quality of care delivered. 

5. Quality indicators and monitoring of quality: Trust 
boards identify quality indicators, monitor them and act 
accordingly. This is achieved by tracking all national indi- 
cators that apply to trusts (Department of Health and 
Dr Foster), the most important of which are the clinical 
indicators including mortality, other incidents and com- 
plaints. There are always problems with standardization 
and this makes comparisons difficult. It is vital that data 
relating to clinical quality are accurate. All clinicians have 
a responsibility to ensure that data about their patients are 
correct. 

6. User perspective is important: services must be centred 
on patients' needs. Strangely, this is an area that pre- 
viously was rarely addressed in a systematic, cohesive 
corporate manner. Clinical governance will not succeed 
unless the patients are involved in the initiation of trust 
strategy. There are many different mechanisms for seeking 
feedback from patients and involving patients in planning 
health care. In addition to clinical needs, it is necessary to 
address information, privacy, dignity and religious and 
cultural aspects. Feedback can be obtained by question- 
naires, surveys, audit and interviews. However, direct 
involvement of patients in 'users' groups' is essential to 
enable new ideas, concerns and help with planning new 
and existing services to be dealt with. 



7. Education, training and continuing professional develop- 
ment are essential for the provision of high quality care 
(General Medical Council 2001). There must be a balance 
between teaching and training. Support must be provided 
both for trainers and teachers. Lifelong learning should 
involve a systematic approach whereby doctors and other 
health professionals are helped to identify development 
needs that will enable them to do their jobs better and 
move toward their career goals. Postgraduate medical 
organizations are well placed to help carry this forward. 
All staff should have a personal development plan which 
balances service needs and career aspirations. 




Key points 

• All elements of clinical governance must be 
active in your trust. 

• Are you involved in all these aspects? 

8. Other systems and relationships that support or com- 
plement clinical governance: in addition to long estab- 
lished organizations within the National Health Service, 
new ones have been created (see Fig. 43.1). 'Outside' 
bodies and national principles involved in clinical 
governance in your Trust are: 

a. National Institute for Clinical Excellence (NICE). This is 
a Special Health Authority It was set up to provide a 
strong lead on clinical and cost-effectiveness by drawing 
up guidelines based on scientific evidence and to advise 
on best practice. 

b. National Service Frameworks (NSFs). These are designed 
to set national standards and define service models for a 
specific or defined service care group. They are, or put in 
place, strategies to support implementation /establish 
performance milestones. 



Patient and public 
involvement 




0> 



National Institute for Clinical Excellence 
National Service Frameworks 



~"*V~ 



I 



Professional 
self -regulation 



v 



Clinical 
governance 



>^ 



Lifelong 
learning 



I ▼ 



A^ 



^ 



Commission for Health Improvement 
National Performance Framework 
National Patient and User Survey 



^ 



> 



Clear STANDARDS of service 






Dependable local DELIVERY 



> 



MONITORED standards 



Fig. 43.1 It is important to note the central position of clinical governance. 



439 




GENERAL CONSIDERATIONS 



c. Commission for Health Improvement (CHI). Established 
to assure, monitor and improve the quality of care in the 
NHS in England and Wales. It will provide national lead- 
ership to develop and disseminate clinical governance 
principles. The Commission will visit every NHS Trust 
every 4 years and independently scrutinize local clinical 
governance arrangements to support, promote and 
deliver high quality services. By 2003 it is proposed that 
NHS performance indicators will be transferred to CHI 
and will be published. 

d. NHS Performance Framework. This will be used to 
move toward assessing performance of the NHS in the 
round, covering quality and efficiency. A set of national 
indicators will measure progress against main targets. It 
will encourage benchmarking between similar NHS 
organizations and underpin national and local perfor- 
mance and accountability arrangements. High level 
performance indicators (e.g. deaths, surgery rates, cancer 
detection, hospital stay etc.) will be used to ensure a more 
rounded assessment of NHS performance. Depending on 
their performance against the Performance Assessment 
Framework, all NHS organizations will annually and 
publicly be classified as 'green' , 'yellow' or 'red'. Red 
organizations will be those who are failing to meet a 
number of the core national targets. 

e. Professional organizations and Royal Colleges. The pro- 
fessional bodies as well as the newly established Medical 
Education Standards Board (replacing the Specialist 
Training Authority) will work together to maintain 
quality and improve training. 

The Commission for Health Improvement will join with 
the Audit Commission to form the Commission for 
Healthcare Audit and Inspection (CHAI). This body will 
lead inspections in the NHS and the private health care 
sector and be responsible for all financial and perform- 
ance audit as well for the quality of the assessment work 
which CHI has been doing. 




Key points 



(HimPs). However, hospital trusts do not work in isola- 
tion! Health authorities, hospital trusts, primary care 
trusts and social services work together to develop a 
3 year HimP. This plan should consider national and local 
priorities. The national priorities for 1999-2000 were cor- 
onary heart disease, mental health, cancer and antibiotic 
prescribing. Since then, National Service Frameworks 
(NSFs) for diabetes and care of older people have been 
introduced, and NSFs for renal services, children's ser- 
vices and long-term conditions focusing on neurological 
disorders are in preparation. 

2. Local priorities take into account the needs 
and special circumstances of the local population. If 
these priorities are to be addressed there needs to be a 
mechanism for making certain that the standards 
required are monitored and delivered. Similarly there 
needs to be evidence that the priorities are being met 
and /or pointers toward where resources are being used 
effectively. 

3. This combination of agreeing and setting priorities 
in planning, purchasing and delivering health care, 
introducing clinical governance and measuring the 
outcomes by means of the National Performance 
Assessment Programmes should result in more modern 
and effective healthcare delivery by including all the key 
partners in planning and tackling the root causes of ill 
health. 



• Do you understand the interrelationships of 
clinical governance? 

• Do you understand the role of the outside 
bodies? 



Summary 

• Do you know who is ultimately responsible 
for maintaining overall clinical standards 
in your hospital? 

• Do you know the range of people who 
come into contact with patients or provide 
a service to them? 

• Do you appreciate the range of 
experiences on which patients base their 
assessment of outcome? 

• Do you accept individual and collective 
responsibility for the reputation and 
quality of care delivered by your firm, 
unit, hospital, health service? 



HEALTH IMPROVEMENT 
PROGRAMMES AND NATIONAL 
SERVICE FRAMEWORKS 

1. Clinical governance is an integral part of developing 
and implementing Health Improvement Programmes 




References 



General Medical Council 2001 Good medical practice, 3rd edn. 
GMC, London (www.gmc-uk.org/standards/good.htm) 



440 



CLINICAL GOVERNANCE 



43 




Further reading 



Clinical governance: quality in the new NHS (HSC 1999/065). 

HMSO, London 
Bloor K, Maynard A 1998 Clinical governance: clinician heal 

thyself. Institute of Health Service Management, London 



NHS Executive 1999 Quality and performance in the NHS: high 

level performance indicators. HMSO / London 
NHS Executive 1999 Quality and performance in the NHS: 

clinical indicators. HMSO, London 
Secretary of State for Health 1997 The new NHS, modern 

dependable. HMSO, London 
Swage T 2001 Clinical governance in health care practice. 

Butterworth-Heinemann, Oxford 



441 




Economic aspects of surgery 

R. W. Hoile, 6. Douglas 



0F 



Objectives 



Understand some basic principles behind 
economic considerations in surgical practice. 
Recognize the potential conflict between 
clinical freedom, medical ethics and the 
logic of health economics. 
Examine areas of clinical practice where 
surgeons can influence the costs of surgery. 



of the disease, hospitalization and time off work. While 
we should be striving to deliver a cost-effective healthcare 
system, we should not lose sight of these personal costs. 
Measuring cost effectiveness is an unfamiliar process to 
clinicians, but it is important in evaluating and practising 
modern surgery. Before the cost effectiveness of any sur- 
gical management is understood, it is necessary to under- 
stand some of the principles, definitions and accounting 
practices that are applied to problems of health care and 
the way in which they may affect clinical decision making. 



INTRODUCTION 

This is probably a subject which, up to now in your 
surgical career, you have not needed to think about or 
understand. Before you progress much further you will 
undoubtedly be exposed to economic considerations and 
the consequences of your actions, so it is worthwhile dis- 
cussing some of the principles used when addressing this 
topic. 

The National Health Service was developed on the 
principle of fairness and that health care was free to the 
patient at the point of delivery. With rising costs of health 
care, limited resources and the heightened expectations of 
our patients, it is inevitable that questions are asked about 
cost. There is also a debate about the quality versus quan- 
tity of care and the total benefit to the community. Will the 
economic arguments take over and conflict with good 
patient care, or can good economic strategies mean better 
patient care? At all times in this debate keep central the 
outcome for your patients. 



MEASUREMENT OF COST 
EFFECTIVENESS 



COST EFFECTIVENESS: WHAT DOES IT 
MEAN? 

There are four ways of interpreting cost effectiveness in 
clinical practice. 

1. Cost savings: this can also be considered as avoided 
costs, or the estimated costs caused by the disease process 
that can be avoided by surgical intervention; for example, 
appropriate treatment of venous insufficiency in the leg 
can prevent the development of subsequent, costly (in all 
senses of the word) chronic venous ulceration. 

2. Effective improvement of health care. 

3. Cost savings with equal or better health outcome: 
this requires no compromise by accountants, financial 
directors or clinicians - it is a 'win-win' situation. 

4. Additional benefits worth the additional cost: judge- 
ment is needed to decide whether additional cost is worth 
the anticipated benefit and to select the course of action 
with the least cost at the most probable benefit. Both a high 
dependency unit (HDU) and an intensive care unit (ICU) 
give high benefit for cost. Similarly, critical care outreach 
teams effectively identify critically ill patients and advise 
on management; they are expensive but cost effective. 



The measurement of cost effectiveness can be considered, 
in simple terms, as synonymous with economic evalu- 
ation. The cost of surgery is not just monetary but also 
personal and social. For the patient, there is pain, suffer- 
ing, time spent in hospital and the economic consequences 




Key points 

Surgeons should consider both clinical benefit 
and cost effectiveness together. 



442 



ECONOMIC ASPECTS OF SURGERY 



44 



• Clinical freedom allows you to choose the best 
treatment for a patient (based on the evidence, 
clinical knowledge and understanding) but 
remember that resources are limited. 

• Unwise use of resources is poor cost 
effectiveness. 

• An unnecessarily expensive remedy for one 
patient may deprive other needy patients of 
valuable treatment. 



HOW ARE BENEFITS MEASURED? 

1. Cure. 

2. Increased life expectancy. 

3. Improved quality of life. One method of evaluating 
the value of a year of healthy life is the calculation of 
quality-adjusted life years (QALYs). One year of life 
in full health is 1 QALY. 



HOW ARE COSTS MEASURED? 

• Direct costs are those borne by the healthcare system, 
community and family. 

• Indirect costs are those borne by the individual, family, 
society and employer, such as time spent in hospital, 
loss of earnings and loss of productivity. 

• Intangible costs are those borne by the patient, such as 
pain, anxiety, grief, suffering and loss of leisure. Death 
following an operation is also often considered as an 
intangible loss. 

Hospital attendances, medical and surgical risks, mortal- 
ity, resulting disability, management of complications and 
failures, contribute to all three cost evaluations. 



HOW CAN YOU INFLUENCE HOSPITAL 
COSTS? 

1. Use resources efficiently and appropriately. The 
introduction of day surgery as a low cost /high 
throughput service reduces the cost of procedures 
without increased morbidity. Short-stay, 5 day wards, low 
dependency units and hotel use also reduce costs, are not 
detrimental and may be advantageous. Preadmission 
clinics, which may avoid last minute cancellations, are 
also proven to be cost effective. 

2. Avoid investigative and operative techniques that are 
outdated or of unproven use (see Ch. 12). 'Routine' inves- 
tigations for all admissions are valueless unless they influ- 
ence subsequent management (see Chs 6, 15). Order the 
fewest tests that will provide the speediest, most specific 



and reliable results. Tests requested out of hours cost more 
to provide so avoid them if they can be deferred. However, 
remember that sometimes a quicker diagnosis and prompt 
action may ultimately shorten hospital stay and speed 
recovery. Can you justify your requests? 

3. Critically assess the value of procedures that 
demand expensive technological back-up or instrumen- 
tation. The gains must be balanced against the costs; 
laparoscopic colonic surgery reduces hospital stay, 
recovery and back-to-work time. On the other side of the 
balance sheet there may be the costs produced by a longer 
operating time, increased risks of thromboembolism, 
ureteric injury and concerns about the adequacy of resec- 
tion. Patient preference must also be considered; for 
example, in hernia repair the cost effectiveness of the 
'open' and endoscopic techniques are roughly compar- 
able but many patients will express a preference for 
minimal access procedures. You could probably make 
considerable cost reductions and feel more at ease with 
resource implications if you and your clinical colleagues 
could agree 'best practices' for selected procedures, 
develop local protocols and adhere to them; for example, 
you might agree to perform laparoscopic procedures but 
carefully define the circumstances when it would be 
acceptable to use the more expensive disposable pieces of 
equipment. 

4. Place the patient's interests above those of academia 
or research. Patient screening (see Ch. 41) must be shown 
to be cost effective. Society must participate in the deci- 
sion to introduce screening or compliance will be poor. 

5. Keep complication rates low. Postoperative compli- 
cations are expensive and can spoil any attempt to 
improve the cost effectiveness of surgery. The manage- 
ment of complications may triple the costs of an uncom- 
plicated procedure. Avoid complications at all stages of 
assessment, decision making, preparation, active treat- 
ment, recovery, discharge and review. Audit your results. 

6. Do not be afraid to develop new ideas and think lat- 
erally if you can show a benefit. It is appropriate to seek 
funding if there is a proven or predicted benefit for the 
service or the patients. For example, an emergency ad- 
missions unit (such as that established at Eastbourne 
General and other hospitals) allows intensive preadmis- 
sion assessment and may prevent 20% of admissions. This 
saving in bed occupancy more than justifies the cost of 
such a unit. 



Key points 

• Avoid unnecessary costs. 

• Recognize that the benefit and outcome for 
the patient are the most important factors. 



443 



44 




GENERAL CONSIDERATIONS 









Choose relevant investigations. 

Assess the evidence concerning the efficacy 

and outcomes of operative interventions. 

Do not assume that you have to operate: think 

carefully about the benefits first. 

Take precautions to minimize complications. 

Only adopt new techniques after proper 

evaluation. 

Develop guidelines for 'best practice' for 

selected common procedures. 

Liaise with departmental managers in order to 

determine the service requirements for your 

local population. 



CONCLUSIONS 



^^^S&yPXui'&^'^X 



Thinking about the economics of health care raises issues 
that are sometimes uncomfortable. There are questions 
about waste, the inappropriateness of investigations and 
operations, rationing, cost containment, ethics, etc. The 
response to these questions needs to be well thought out 
and workable. It is possible to set professional standards 
and deliver appropriate care while eliminating the 
unwarranted use of medical resources. It is easy to "do 
something', particularly when faced with an individual 
patient, but perhaps we should stand back, take a broader 
view and consider whether an action for the individual 
patient is appropriate and /or cost effective. A multitude 
of tests and complex procedures do not necessarily 
produce an accurate or speedy diagnosis, a lower mor- 
bidity or mortality, or 'better' health care. Professional 
guidelines and clinical audit may sometimes help us 
when it is necessary to say 'no'. A partnership between 
clinician and manager may help rationalize the provision 
of a surgical service, with maximum benefits to all 
concerned. 

We have not found all the answers yet but you must 
begin to address these difficult issues. 



Summary 

• You should recognize that the costs of 
surgery (and health care in general) are 
rising but resources are limited. 

• Health economics provides a logical 
framework for the allocation of resources. 

• You can reduce costs without 
compromising clinical freedom and patient 
care by investigating wisely, operating 
sensibly and keeping complications low. 
'Choose well, cut well, get well.' 

• You may perceive a conflict between your 
medical ethics and the economic logic 
applied by your hospital accountants and 
trust financial director. However, having 
read this chapter, you will appreciate that 
the aim of both disciplines is to promote 
health and alleviate suffering. The surgical 
economic argument is just one more tool 
for you to use when making decisions 
about the care of your patients. 

• Consider the wider implications of your 
decisions and actions. 




Further reading 

Gray AJ, Hoile RW, Ingram GS, Sherry KM 1998 The report of 

the national confidential enquiry into perioperative deaths 

1996/97, NCEPOD, London 
Hicks NR 1994 Some observations on attempts to measure 

appropriateness of care. BMJ 309: 730-733 
Hodgson K, Hoile RW 1996 Managing health service contracts. 

WB Saunders, London 
Jefferson T, Demicheli V, Mugford M 1996 Elementary economic 

evaluation in health care. BMJ Publishing Group, London 
O'Brien B 1986 'What are my chances doctor?' A review of clinical 

risks. Health Economics Research Group, Brunei University 
Williams A, Anderson R 1985 Efficiency in the social services. 

Blackwell, London 



444 




Statistical concepts: a tool for 
evidence-based practice 



R. W. Morris 




Objectives 

• If you wish to apply up-to-date published 
research to your clinical practice, you need 
to grasp basic statistical concepts and 
common techniques that quantify the 
benefits of new interventions and 
diagnostic tests. You must be able to 
appraise critically the design of research 
studies, apart from understanding the 
handling of quantitative data in published 
research. You can then practise evidence- 
based medicine (see Ch. 12). 

• If you wish to carry out your own 
quantitative research, you must have a 
firm grasp of statistical principles. In this 
chapter I shall aim to provide a 
comprehensible outline of various 
statistical techniques employed in surgical 
research, rather than attempt a detailed 
coverage. For this reason I have 
recommended useful books for further 
reading. 



CLINICAL SCENARIO 



s ifss'^f ^k*-*; .'■$> ?%&%■■ 



Mr Dennis Gray is a 49-year-old gardener. He was 
diagnosed as having carcinoma of the rectum after 
presenting to his general practitioner with bleeding 
on defecation. A CT scan of the abdomen suggests 
that the tumour is about 3 cm in diameter and has 
not yet become locally invasive. There is no sign of 
metastatic spread. Mr Gray is scheduled for curative 
resection with preservation of anal function. You 
feel that adjuvant chemotherapy is not necessary in 
this case in view of the many favourable prognostic 
features. The consultant, however, wishes to maxi- 



mize Mr Gray's chances of complete cure by admin- 
istering an intraportal regimen of fluorouracil, 
500 mg m~ 2 , on the first day after surgery and a con- 
tinuous heparin infusion for 7 days. The patient, 
who has three young children, is keen to follow 
any regimen that improves his chances of long-term 
survival. 

Many clinical questions might arise during Mr Gray's 
encounters with both the general practitioner and the 
surgeon. These may include, in particular: 

• Diagnosis. How important is bleeding on defecation in 
establishing the presence of a rectal carcinoma? 

• Prognosis. What probability of long-term survival (e.g. 
for 10 years) does Mr Gray have? 

• Therapy. Will adjuvant therapy increase Mr Gray's 
chances of a complete cure? If so, by how much? 

All three of these questions may potentially be answered 
by appropriate studies. 



1. It is unlikely that any routine test carried out to 
establish the presence or absence of disease will be 
entirely accurate. When applying such a test however, 
knowledge of its accuracy will be helpful in interpreting 
the result gained. Traditionally this will be expressed in 
terms of two quantities, namely the sensitivity and speci- 
ficity. These can be assessed by a study in which the 
routine test has been applied to a number of subjects 
where the true presence or absence of disease has been 
established, usually by a diagnostic test seen as the 'gold 
standard' (Table 45.1). 

2. A study was carried out by Fischer et al (1991) on 
patients with new knee conditions. All subjects under- 
went arthroscopy, which was taken as the gold standard, 
as well as magnetic resonance imaging (MRI). A compar- 
ison was made for 911 patients on whether arthroscopy 



445 



45 * 



GENERAL CONSIDERATIONS 



Table 45.1 Test for presence/absence of disease 








Disease present 




Disease absent 


Totals 


Test positive 
Test negative 

Totals 


True positive 
False negative 
AH with disease 


present 


False positive 
True negative 
Ail with disease absent 


AH test positive 
AH test negative 
AH in study 



and MRI showed the presence or absence of a medial 
meniscal tear. The results were as shown in Table 45.2. 

Of 473 subjects who actually had a medial meniscal 
tear (according to the arthroscopy), 440 were correctly 
picked up by the MRI. Thus the sensitivity of the test was 
440/473 = 0.93, or 93%. The MRI missed 7% of the menis- 
cal tears. 

Of 438 subjects who did not have a medial meniscal 
tear, 367 were correctly excluded by the MRI. Thus the 
specificity of the test was 367/438 = 0.84, or 84%. 

Thus we know that if someone has a medial meniscal 
tear, there is a 93% probability that they will be picked up 
by an MRI. If they do not have a meniscal tear, there is an 
84% chance that this diagnosis will be correctly excluded 
by an MRI. 

3. As a clinician faced with an individual case, 
however, the sensitivity and specificity are of little direct 
value to you. The idea of performing an MRI is that its 
result will become available before an arthroscopy is per- 
formed. The question therefore is not 'If this patient had 
a meniscal tear, how likely is it that a positive MRI result 
would be shown?' but rather 'When given a positive MRI 
result, how likely is it that a medial meniscal tear is actu- 
ally present?' The latter question leads to consideration of 
the positive predictive value (PPV). 

From the data above, the PPV is 440/511 = 0.86, or 86%. 
In other words, 86% of all positive MRI scans indicate a 
true tear of the medial meniscus. 

By analogy, another useful statistic is the negative pre- 
dictive value (NPV). 'When given a negative test result, 
how likely is it that a medial meniscal tear is actually 
absent?' 



Table 45.2 


Presence/absence of a 


medial meniscal 


tear 










Tear present Tear absent 


Totals 


MRI scan 


440 71 




57? 


positive 








MRI scan 


33 367 




400 


negative 








Totats 


473 438 




911 



The NPV is 367/400 = 0.92, or 92%. In other words, 92% 
of all negative MRI scans indicate absence of tear in the 
medial meniscus. 

4. The PPV and NPV are of more intuitive use to you 
than the sensitivity and specificity. Unfortunately, their 
appeal may be illusory. They depend very heavily on the 
actual prevalence of the condition in the population 
under study. In the study generating the data shown in 
Table 45.2, the prevalence of a meniscal tear was just over 
50% (473/911). If a similar study was carried out on a 
population where the true prevalence was lower, then the 
PPV would be less than calculated above. The NPV 
would be even higher. For example, if the prevalence 
were 33%, the PPV would fall from 86% to 74%. The NPV 
would increase from 92% to 96%. 

5. Fagan's nomogram. A more directly useful approach 
comes through use of Bayes theorem. When applied to 
diagnostic testing, it runs as follows: 

pretest odds x likelihood ratio = post-test odds 

The pretest odds will be based on a hunch from the clini- 
cian prior to application of a diagnostic test such as MRI. 
The clinician, having taken a clinical history, may have a 
rough subjective idea of how probable it is that the patient 
has a medial meniscal tear. The probability may then be 
converted into an 'odds', but this step can be omitted by 
using Fagan's nomogram (shown and explained in detail 
below). 

The likelihood ratio (LR) will incorporate information 
given by the diagnostic test. When the test gives a posi- 
tive or negative result, the LR can take one of two poss- 
ible values. If the MRI result is positive: 



LR+ = 



sensitivity 
100 -specificity 

93 
100-84 



= 5.8 

If the MRI result is negative: 



100- sensitivity 
specificity 

100-93 
84 

= 0.08 



446 



STATISTICAL CONCEPTS: A TOOL FOR EVIDENCE-BASED PRACTICE 



45 



If you think there is a 50% probability that a meniscal tear 
is present, then the pretest odds are 50/50 = 1. 

A positive result means that post-test odds = 1 x 5.8 = 
5.8. The post- test probability is then around 85%. This 
would probably be high enough to indicate a need for 
arthroscopy, 

A negative result means that post-test odds = 1 x 0.08 
= 0.08. The post- test probability is then around 7.5%. 
This is probably low enough to render arthroscopy 
unnecessary. 

Fagan's nomogram (Fig. 45.1) allows direct mapping 
from pretest probability to post-test probability once we 
know values for the likelihood ratio for a positive and for 
a negative result. Use of a ruler will show that a pretest 
probability of 50% , combined with a likelihood ratio of 
5.8, will translate into a post-test probability in excess of 
80%. Similarly a pretest probability of 50%, combined 
with a likelihood ratio of 0.08, will translate into a post- 



0.1 



% 



0.2- 

0.5- 

1 

2- 

5- 
10- 

20- 

30 
40 H 
50 
GO 

70- 
80- 

90- 
95- 



1000 
500 

200 

100 

50 

20 

10 

5 

2 

1 



99 

Pretest 

probability 



0.5 

0,2 
0.1 
0.05 

0.02 
0.01 
0.005 

0.002 
■0.001 



Likelihood 
ratio 



99 



-95 



-90 






-60 

70 
-60 
-50 

40 
-30 

-20 

10 
-5 

-2 

-1 
0.5 

0,2 



% 



01 
Post-test 
probability 



test probability between 5 and 10%. Usually, approxi- 
mate answers will be sufficient for decisions on clinical 
management. 




Key points 



Fig. 45.1 Fagan's nomogram. 



• Studies that generate the sort of data shown in 
Table 45.2 are more useful if their methodology 
is sound. 

• Many studies are carried out on two 
independently selected groups of subjects; one 
group with confirmed disease, one healthy 
control group. 

• This ignores the spectrum of pathologies seen 
in clinical practice. It is likely to produce an 
unduly optimistic picture of the test's ability to 
discriminate between differential diagnoses. 

• A study will avoid spectrum bias if it has 
included a cohort of consecutive cases seen in a 
realistic clinical setting. 

6. It would be ideal (although perhaps difficult in prac- 
tice) if the result from the test under consideration (e.g. 
MRI) and the gold standard diagnosis (arthroscopy) are 
independently ascertained. If you already know the result 
of the MRI before undertaking the arthroscopy, your 
judgement will inevitably be influenced in marginal cases. 



Returning to the scenario of Mr Dennis Gray, the 49-year- 
old gardener, it might be asked whether there are studies 
that address the question of adjuvant therapy. The study 
by the Swiss Group for Clinical Cancer Research (1995) 
may help to resolve the question. 

Answer the following questions before deciding 
whether the Swiss study will help the decision: 

• Can the methods of the study be trusted? 

• What do the results of the study actually show? 

• Are the patients in the study like Mr Dennis Gray? 

Methods 

1. A study that evaluates the effects of a new interven- 
tion should be a randomized controlled trial (RCT). By this we 
mean that the patients entering the study should be allo- 
cated at random to one or other treatment (e.g. adjuvant 
therapy, or not). The purpose of this is that the two treat- 
ment groups should, on average, be like each other in every 
respect other than the treatment given. The two groups of 



447 



4 




GENERAL CONSIDERATIONS 



subjects should have the same average age, and the same 
ratio of males to females, and so on. Not only should there 
be a balance of known prognostic variables, there will also 
be a balance of unknown prognostic variables. 

2. Random numbers are generated to produce an 
assignment to one of the treatment groups for each 
patient entering the study. This should to be done so that 
the investigators cannot predict the assignment before 
entering the subject into the study. Thus, assignment by 
whether the patient's date of birth is odd or even, or 
alternating assignments between the treatment groups, is 
unsatisfactory. Multicentre trials typically involve tele- 
phoning a central office to receive a random assignment. 

3. Once patients are assigned to a particular treatment 
group, they should stay in that group for analysis 
purposes. This principle, known as 'intention-to-treat', 
should be adhered to even if the patients or doctors are 
unable to follow the treatment protocol. 

Of course this depends on whether it has been possible 
to obtain outcome data on every patient. Sometimes 
patients drop out of a study altogether and it is not poss- 
ible to analyse all patients according to their original 
treatment group, simply because the required data have 
not been collected. Sometimes it may be possible to 
impute plausible values, but often some subjects simply 
have to be omitted from analysis. The proportion of sub- 
jects Tosf in this way, out of all those randomized, should 
not be too high. 

4. 'Blinding' is desirable to prevent subjective bias. For 
placebo-controlled drug trials, neither the patient nor the 
doctor should know what treatment the patient has 
received. Such an ideal is difficult to achieve when surgi- 
cal interventions are being assessed. In trials of coronary 
artery bypass grafting versus percutaneous angioplasty, 
neither the patient nor the surgeon may be blinded. Yet 
there may be scope for blinding study personnel who 
need to read X-rays or code death certificates to assess 
outcome in all the patients. 

Results 

1 . The first table of results in papers reporting an RCT 
should compare the baseline characteristics of the two 
groups of subjects. The process of random allocation 
should demonstrate broad similarities. However this 
balance may not occur if the study is small. If so, any dif- 
ferences in outcome later reported should be weighed 
alongside possible differences in baseline characteristics 
of the groups. 

2. You must be clear about the choice of the primary 
outcome variable, or endpoint. In the Swiss trial, there 
were two endpoints. One endpoint simply concerned 
death of the patient. The other concerned 'disease-free 
survival', which was denned when a patient did not die 



and had no evidence of relapse or a second primary 
tumour. We shall consider the simpler 'death' endpoint. 
3. It was estimated that of those who received adjuvant 
therapy, 43% died within 5 years. For those who did not 
receive adjuvant therapy, 52% died. A comparison can be 
made between these two rates, both in absolute terms and 
in relative terms. 

Absolute differences 

The absolute risk reduction (ARR) is the event rate in the 
control group minus the event rate in the intervention 
group = 52 - 43% = 9%. Thus, for every 100 patients who 
received adjuvant therapy, nine (9%) fewer subjects died 
than would have otherwise been the case. 

A popular statistic to express this idea in another way 
is the number needed to treat (NNT). This is the reciprocal 
of the ARR: NNT = 100/ARR = 100/ 9 = 11. Thus for 
every 1 1 patients treated with adjuvant therapy, one fewer 
patient will die within 5 years. 

Relative differences 

When considering the ARR, we concentrated on sub- 
tracting one death rate from the other. Another approach 
is to divide one death rate by the other: Relative risk (RR) 
= 43/52 = 0.83. In other words, use of adjuvant therapy 
reduces the probability of death within 5 years to 0.83 
(83%) of what it would have otherwise been; that is, 17% 
of the risk is removed {relative risk reduction, or RRR). 

The pie chart (Fig. 45.2) shows the effect. Suppose the 
entire circle represents the risk of death in the next 5 years 
for Mr Dennis Gray if he is not offered adjuvant therapy. 
The white slice represents the proportion by which his 
risk is reduced if adjuvant therapy is administered (17% 
of the total). The black region represents the proportion of 
his risk still remaining. 

Odds ratio 

This is another relative measure and in many circum- 
stances may be interpreted in a similar way to the relative 



17% 




83°/ 



Fig. 45.2 Pie chart showing relative risk reduction. 



448 



STATISTICAL CONCEPTS: A TOOL FOR EVIDENCE-BASED PRACTICE 




risk; however, it uses the idea of an 'odds' rather than a 
'risk'. In everyday life, the term 'odds' is most mentioned 
in the context of placing bets! When a horse is given odds 
of 4:1, it means that there is supposed to be one chance of 
it winning to four chances of it not winning. So its prob- 
ability of winning is 1 in 5, or 20%. 

The probability of death for Mr Gray if he is not treated 
with chemotherapy is 0.52 (or 52%). Therefore his odds is 
52/(100 - 52 ) = 1.08. Similarly, if he is treated with adju- 
vant therapy, his odds will be 43/(100 - 43) = 0.75. The 
odds ratio is the odds if treated with adjuvant 
therapy /odds if not treated with adjuvant therapy = 
0.75/1.08-0.69. 

When an event is uncommon (e.g. occurs less than 10% 
of the time), the odds ratio and the relative risk tend to 
converge to similar values. They are rather different in the 
present example, and the odds ratio is probably a more 
robust relative measure. However, if fewer subjects died 
when given the intervention (as here), then both the rela- 
tive risk and the odds ratio will be less than one. 



to be larger than 0.97, and it is unlikely to be below 0.57. 
At the optimistic end, the true hazard ratio may be as 
small as 0.57, suggesting that the hazard of death could 
be reduced by almost one half. At the pessimistic end, 
the true hazard ratio may be 0.97, suggesting the hazard 
would be reduced by only 3%. So the results of the study, 
which estimate a 26% reduction in the hazard, are also 
compatible with a substantial reduction on the one hand, 
or a miniscule reduction on the other. It could be argued 
that the results of the study are therefore not very 
precise. 



Application 

There is always some way in which your particular 
patient (e.g. Mr Dennis Gray) may seem unique. However 
the question 'Is my patient so different from those in the 
study that its results cannot apply?' should supply the 
right perspective. 



Confidence intervals 

1 . A group of subjects recruited to a study is a sample. 
Our true interest is not in the subjects studied but the 
underlying population from which the subjects were 
drawn. Any summary statistic (for example, a relative 
risk) calculated from a sample is an estimate. We want to 
know the true value of the relative risk, say, for the 
population. It is inevitable that if we repeated the whole 
study with a similar number of subjects included, we 
would get a slightly different estimate. We therefore 
wish to establish a confidence interval for the relative risk, 
based on the estimate from the study we have carried 
out. 

2. The mathematical theory behind the construction of 
a confidence interval cannot be covered in this chapter, 
but the idea is to provide a range within which the true 
relative risk is likely to lie. Typically a 95% confidence 
interval is quoted. 

3. In the Swiss study, the authors quote a hazard ratio 
(yet another relative measure!), which is a useful statistic 
when the data consist of differing follow-up times. The 
hazard ratio of death in those treated with adjuvant 
therapy was 0.74. This means that at any time point after 
surgery, those treated with adjuvant therapy are 0.74 
times as likely to die at that point as those not given adju- 
vant therapy (26% reduction in the 'hazard'). The authors 
also quote the 95% confidence interval as 0.57 to 0.97. 
What does this mean? 

4. Formally, there is a 95% probability that the confi- 
dence interval calculated and quoted above will contain 
the true hazard ratio for the entire population. In prac- 
tice, we may assume that the true hazard ratio is unlikely 



Sample size calculation 

If you wish to carry out an RCT you need to answer the 
question of how many subjects to study. This depends on 
answering several questions, including a specific guess 
of how much difference the new intervention might 
make. 

First, there is the need to define a primary outcome 
measure. In the Swiss trial, this was either death, or 
disease-free survival. Secondly, we should estimate how 
much difference the intervention of interest (adjuvant 
therapy) would make to this primary outcome. The 
Swiss researchers do not tell us what they expected 
before commencing the study. But let us suppose that we 
wish to replicate their study. We might expect 50% of 
subjects to die within 5 years, and that adjuvant therapy 
will cause the risk of death to be reduced by one quarter, 
to 37.5%. 

In any comparative study, there is a risk of making a 
type I error (claiming the new intervention makes a dif- 
ference, when it fact it does not) or a type II error (con- 
cluding the new intervention makes no difference, when 
in fact it does benefit to the degree initially thought). We 
would like to avoid making such errors, but the proba- 
bility of making such errors can only be diminished by 
increasing the sample size. In fact it is standard to set the 
probability of a type I error (called a) at 5%, and the prob- 
ability of a type II error (called (3) at either 10% or 20%. If 
p is 10%, the power of the study is 90%. The power is the 
probability of demonstrating a true difference of the 
specified magnitude. 

Using tables provided by Machin et al (1997), we would 
need 329 subjects in each group (658 in all) to have 90% 



449 



45 




GENERAL CONSIDERATIONS 



power to demonstrate this sort of effect as statistically 
significant at the 5% level. 



several variables on survival (e.g. age, gender, stage of 
disease). 



PROGNOSIS 

1. Studies that outline the natural history of a disease 
are useful to gauge how worthwhile the application of 
treatment is. A relative risk reduction of 30% may be 
useful for someone at high risk, but less so for someone 
who is already at low risk. 

2. Surgical studies frequently follow patients from the 
date of operation until some event such as death, or recur- 
rence of a tumour. The resulting data can then be used to 
produce a Kaplan-Meier survival curve. 

3. Not all patients will reach the endpoint within the 
time of the study. These are known as censored observa- 
tions. They contribute to construction of the survival 
curve until the time of censoring. 

4. The Swiss study shows a survival curve for each 
treatment group. However, the survival curve for the 
control group in a clinical trial may not always give a real- 
istic estimate of prognosis. Those selected for a trial may 
be selectively fitter than average members of this popu- 
lation of patients. It is sometimes asserted that many 
aspects of medical care given to patients in a trial is su- 
perior to that given to other patients. A realistic survival 
curve will be obtained using an observational rather than 
an experimental study. 

Points to consider when reading the 
literature 

1. Inclusion criteria and selection of patients should be 
carefully documented. They should be assembled at a 
common, well-defined point in the course of their disease. 
The outcome should also be well defined and established 
by a standard methodology. 

2. Assembling a cohort retrospectively is fraught with 
difficulty. Applying a clear selection criterion may be 
impossible. In addition, data may be unavailable for some 
or all of those who have died, thus producing a biased 
sample. In a prospective study, these questions may be 
tackled from the start. Prospective studies are likely to be 
expensive and take a long time to carry out if a long 
follow-up is required. 

3. Subgroups within a cohort may have different prog- 
noses (e.g. males versus females, older versus younger 
patients, stage I disease versus stage II versus stage III 
versus stage IV, etc.). Kaplan-Meier survival curves may 
be drawn for the whole group, or for a series of sub- 
groups. Comparisons of survival curves between sub- 
groups are carried out using the Tog-rank test'. Cox 
models are used to assess simultaneously the effect of 



SYSTEMATIC REVIEWS/ 
META-ANALYSIS 

1 . The last decade has seen an explosion of interest in 
formal syntheses of research studies. It was recognized 
that single studies did not in themselves provide defini- 
tive answers to clinically important questions, and that 
bringing together several results was potentially power- 
ful. Systematic reviews, however, differed crucially from 
the old-fashioned medical review, in that relevant studies 
were searched in a comprehensive and explicit manner, 
thus reducing potential charges of bias. Published sys- 
tematic reviews will outline exactly which databases were 
searched, and which key words were used, so that the 
methods could be reproduced by the interested reader. 
Inclusion and exclusion criteria will be specified. 

2. Once relevant studies have been located, they may 
be appraised by the reviewers. Those studies whose 
methodology is particularly poor may be omitted from 
further consideration. Again, explicit criteria for decisions 
made will be described. 

3. Provided the data are provided in a compatible way 
in the studies concerned, it will then be possible to pool 
their results using a technique known as 'meta-analysis'. 
The confidence intervals from a pooled analysis will be 
narrower (i.e. more precise) than from any single study 
included. 

4. The major drawback concerns the possibility of 
publication bias. Using electronic databases such as 
MEDLINE, one might reliably identify all published 
studies, but what of those studies which are never pub- 
lished? Many researchers embark on studies but never 
have them published, either because they are rejected by 
journal editors, or, more commonly, because they are 
never even submitted. It has been demonstrated empiri- 
cally that published studies are more likely than unpub- 
lished studies to contain statistically significant results. 
Thus the published studies are biased towards showing a 
new treatment in a more exciting light than is strictly true. 
A famous example concerned the use of magnesium after 
myocardial infarction; many small trials had indicated a 
possible benefit, but a large trial demonstrated that this 
treatment was in fact useless, or even slightly harmful! 

5. Publication bias, as defined above, tends to be 
particularly strong for small studies. Large studies, even 
if statistically non-significant, have a reasonable chance of 
being published, but this does not happen for small 
studies. 

For this reason, systematic reviewers often attempt to 
locate unpublished studies and include them in their 



450 



STATISTICAL CONCEPTS: A TOOL FOR EVIDENCE-BASED PRACTICE 




meta-analysis. Writing to experts in the field, and scan- 
ning abstract lists of conferences, are methods that have 
been used to some effect. 

Example: Graduated compression stockings 
in the prevention of postoperative venous 
thromboembolism 

Wells et al (1994) searched for articles on graduated com- 
pression stockings (GCS). They used MEDLINE, and also 
the bibliography of all retrieved articles. They searched 
Current Contents to find new reports that might not have 
yet appeared on MEDLINE. They found 122 articles, but 
only 35 referred to randomized trials. These articles were 
assessed by at least two authors. Some were deemed 
inadequate in their method of randomization, others did 
not contain an untreated control group, while others used 
inadequate diagnostic methods. In all, 12 studies were 
judged eligible for inclusion in a meta-analysis. Eleven of 
the studies were carried out in moderate risk, non- 
orthopaedic surgical procedures, including a total of 1752 
patients. It was estimated that the use of GCS led to a 
relative risk reduction of about two-thirds. 

This systematic review was itself later appraised by the 
Centre for Reviews and Dissemination, University of 
York. It was felt that the authors' insistence on use of 
studies with adequate forms of random allocation meant 



that the conclusions of the review were robust. However, 
it was pointed out that the authors had made no attempt 
to identify unpublished studies, thus leaving open the 
possibility of publication bias (see above). 

The Cochrane Library now contains a more up-to-date 
and thorough systematic review on this subject, last 
updated in 1999 by Amaragiri and Lees. They found 16 
randomized controlled trials, including some not identi- 
fied by Wells and coworkers. This was partly because 
some trials were published after the Wells group carried 
out their review, but these authors searched EMBASE (an 
electronic database with good access to articles not pub- 
lished in English) and the Cochrane Controlled Trials 
Register, in addition to an ever more comprehensive 
MEDLINE. They also hand-searched relevant medical 
journals. Finally, in order to address the possibility of 
publication bias, they contacted companies that manu- 
factured stockings. 

In fact, Amaragiri and Lees do not mention finding 
unpublished trials. But at least they made efforts, and the 
results of their meta-analysis revealed essentially similar 
conclusions to those of Wells and coworkers. They 
divided their 16 trials into nine where patients were not 
undergoing any other form of venous thromboprophyl- 
axis, and seven where all patients underwent another 
prophylactic intervention. The results for the former 
category are shown in a 'forest plot' (Fig. 45.3). 




Fig. 45.3 Forest plot. 



451 



45 



GENERAL CONSIDERATIONS 



A square is shown to denote the results of each individ- 
ual trial. In most forest plots, we are hoping to see squares 
(representing the estimated treatment effect) to the left- 
hand side of vertical line representing the value 1. This is 
because stockings are supposed to reduce the risk of DVT. 
If the evidence was that stockings increased the risk of 
DVT, the squares would appear to the right of the value 1 . 

The nine squares seen in the diagram are of different 
sizes. The larger the square, the more weight that study 
carries. Thus the study of Allan carries most weight. This 
is mainly because it was based on more patients than any 
of the other trials (200). By contrast, the study of Barnes 
included only 18 patients, and thus has an appropriately 
small square. 

Each square carries a horizontal line, and this represents 
the 95% confidence interval for the odds ratio. These tend 
to be wider for small studies such as that of Barnes. Those 
studies whose confidence intervals include the value 1 are 
not statistically significant (Barnes, Hui, Tsapogas, Turner, 
Turpie). Each of these studies (when taken in isolation) fails 
to demonstrate a statistically significant benefit of GCS, 
The other four studies (Allan, Holford, Kierkegaard, Scurr) 
all demonstrate the benefit of GCS in their own right. 

The diamond shape at the bottom represents the result 
of meta-analysis. The centre of the diamond demonstrates 
the overall odds ratio of 0.32. This is a weighted average 
of the nine odds ratios for the individual studies. The 
width of the diamond represents the width of the overall 
confidence interval, which is narrower than any individ- 
ual study's confidence interval. Because it is based on 
1205 patients (compared with 200 patients for the biggest 
of the individual trials), it is a good deal more precise. The 
diamond does not include the value 1, confirming the sta- 
tistical significance. Even the most conservative estimate 
suggests an odds ratio of 0.45, which still implies the odds 
of a DVT will be cut by over one-half if GCS are used. 

COMPARATIVE ANALYSIS 

You may become bewildered by the array of statistical ter- 
minology used when different analyses are carried out. 
When reading or writing a paper, descriptive data should 
be provided in such a way that the results of statistical 
techniques appear credible. The worst sort of statistical 
practice is to provide p values in the absence of descrip- 
tive data. 

Here are a few guidelines as to the use of common 
statistical techniques. 

• Quantitative variables. Calculate measures of location 
(mean, median, mode) and measures of dispersion 



(standard deviation, interquartile range), and compare 
between two (or more) groups. 

Categorical variables. Calculate proportions, or odds. 
Summary statistics to compare rates: relative risk 
reduction, absolute risk reduction, number needed to 
treat (to quantify effect of intervention). 
Comparative statistics need confidence intervals. A con- 
fidence interval (e.g. for the difference between two 
means, or the difference between proportions) puts 
limits on the likely size of the effect of intervention. 
Hypothesis tests. These test whether the comparative 
statistic calculated in a particular study is compatible 
with the 'null hypothesis'. Two sample t tests for com- 
paring means, chi-squared tests for comparing propor- 
tions. Quantitative variables not following a Normal 
distribution (e.g. pain scores) may be compared with a 
non-parametric test such as a Mann-Whitney U test. 
All tests lead to a p value; a measure of strength of 
evidence against the null hypothesis. 



Summary 

• How can knowledge of the accuracy of a 
diagnostic test help you to arrive at a firm 
diagnosis in an equivocal case? 

• What elements of a published randomized 

controlled trial are important in advising 
choice of treatment? 

• What are the potential strengths and 

weaknesses of systematic reviews? 

• How can you prepare a justifiable answer 
to: 'What is my likely outlook'? 




References 



Amaragiri SV, Lees TA 2002 Elastic compression stockings for 
prevention of deep vein thrombosis (Cochrane Review). In: 
The Cochrane Library, Issue 2. Update Software, Oxford 

Fischer SP, Fox JM, Del Pizzo W, Friedman MJ, Snyder SJ, 
Ferkel RD 1991 Accuracy of diagnoses from magnetic 
resonance imaging of the knee. Journal of Bone and Joint 
Surgery. American Volume 73-A: 2-9 

Machin D, Campbell M, Fayers P, Pinol M 1997 Sample size 
tables for clinical studies, 2nd edn. Blackwell Science, Oxford 

Swiss Group for Clinical Cancer Research 1995 Long-term 
results of single course of adjuvant portal chemotherapy for 
colorectal cancer Lancet 345: 349-352 

Wells PS, Lensing AWA, Hirsh J 1994 Graduated compression 
stockings in the prevention of postoperative venous 
thromboembolism. Archives of Internal Medicine 154: 67-72 



452 



STATISTICAL CONCEPTS: A TOOL FOR EVIDENCE-BASED PRACTICE 




45 




Further reading 

Bland M 1995 An introduction to medical statistics, 2nd edn. 

Oxford Medical Publications, Oxford 
Campbell MJ, Machin D 1999 Medical statistics. A 

commonsense approach, 3rd edn. Wiley, Chichester 
Egger M, Smith GD, Altman DG (eds) 2001 Systematic reviews 

in health care: meta-analysis in context, 2nd edn. BMJ 

Publishing Group, London 



ACKNOWLEDGEMENTS 



The clinical scenario was written by the NHS Research and 
Development Centre for Evidence-Based Medicine, Oxford 
(accessed at http://cebm.jr2.ox.ac.uk/docs/scenarios/ 
sgu.html on 9 April 2002) 



453 





Critical reading of the 
literature 



R. M. Kirk 



w 



Objectives 



Apply objective measures whenever 
possible - but do not rely only on 
measurable evidence to the exclusion of 
that which is not measurable. 
Have self-confidence. Do not accept 
received opinions - make up your own 
mind. 

Recognize that surgery does not stand still. 
Keep abreast of advances - do not become 
an expert in outdated practices. 



Absence of evidence is not evidence of absence. 

Not everything that can be counted counts, and not every- 
thing that counts can be counted. 

Sign on the wall of Albert Einstein's office at 

Princeton University 



INTRODUCTION 



$^2!^?#$$&;t&<>;&!&m 



£&$&&M&^!&$k 



The two quotations should remind you that nothing is 
settled. However hard we try to think logically, we work 
in a complex and incompletely understood subject. We 
may know the full extent of the human genome but we do 
not understand what happens to change the chemical 
formula into something that is living. Although we wish 
to apply evidence-based disease prevention and treat- 
ment, we cannot ignore factors that are not yet amenable 
to scientific understanding. 

Lord Kelvin, the distinguished physicist and mathe- 
matician, implied that only if we can describe a concept 
in numbers do we understand it. This may apply in math- 
ematics but it is not totally applicable to biological 
phenomena. The study of living organisms is not yet suf- 
ficiently advanced for it to be described in numbers. In an 
attempt to be - or appear to be - scientific, we often 
ascribe numbers to phenomena and then treat them as 
objective measurements. But they are not. The numbers 



have been allocated subjectively, in an analogue fashion. 
Different observers may allocate different numbers. 

An essential but indefinable characteristic of a good 
doctor is common sense. Beware of specious science. It is 
remarkable that if something is expressed in a formal, 
especially numerical, manner it takes on an appearance of 
authority and reliability. You need only read some of the 
commercial advertisements to appreciate the way in 
which statistics are misused. 

You must keep up to date with the literature because the 
rate of change is rapid. However, try to obtain good evi- 
dence, especially of newly introduced methods. Remember 
the statement by Voltaire, 'Use the new treatment while it 
still works/ He had identified the powerful placebo effect 
of new treatments (Latin placebo = I shall please). 

Favour evidence-based practice when it is available. 
Reports in prestigious journals are usually more reliable 
than those in which the papers are not refereed; however, 
no journals are totally reliable and you must make up your 
own mind. Remember, though, that investigation of prac- 
tice must be narrowed, with exclusion of many of the poss- 
ible variables. Your patients rarely present with exactly the 
same strictly limited features as those used in the trials. 




Key point 

Literature (Latin liters - a letter) is not 
confined to books and journals but also to 
other media. Exploit the many sources of 
information that are now available. Remember, 
though, to maintain the highest critical 
standards because much of the information 
available on, for example, the internet has not 
been subjected to strict peer review before 
being promulgated. 



LOGIC OF SCIENCE 

1. Advances in science occur in a multiplicity of ways. 
We should all feel capable of making them, or recognizing 



454 



CRITICAL READING OF THE LITERATURE 



f 46 



them if we encounter them. Do not dismiss the un- 
expected. Louis Pasteur stated, "Dans Ie champs de 
1' observation, le hasard ne favorise que les esprits 
prepares' (In the field of observation, chance favours only 
the prepared mind). 

2. Advances are often made as a result of encountered 
problems. Do not put aside problems that have so far 
resisted solution. There may be unique features that 
throw light on an individual unsolved problem. 
Consider discussing it with colleagues; we all view 
information differently, and someone may have a 
sudden idea that triggers a solution or a possible method 
of tackling it. 

3. You may develop a possible reason or explanation for 
a phenomenon. This is a hypothesis (Greek hypo = under + 
thesis = placing; a supposition) or theory (Greek theoreein = 
to view; an idea that has not yet been proven). Your natural 
instinct is to attempt to prove it. The recommendation of 
the great scientific philosopher Sir Karl Popper (1902-1994) 
is that you should, on the contrary, try to disprove your 
supposition. If you fail, you may determine to use it for the 
time being. If you disprove your initial belief, this may lead 
you to develop an alternative that may be more robust. 
Popper declared that you can never prove a theory but you 
can disprove it. He used as an example the colour of swans: 
if every swan that you see is white, you can never prove 
that all swans are white, because you can never see every 
swan that exists, has ever existed, or will in the future exist. 
However, you need to see but a single black swan to 
disprove it - and of course you can see many black swans 
on the Freemantle River in Western Australia. 




Key point 



We all pay lip service to Popper's logic. How 
many times have you seen a scientific paper 
that conforms to his teaching? 



ORGANIZING YOUR READING 



^S^K'^i-^^ 






1. There is insufficient time to read every paper on 
your subjects of interest. You must be selective. 

2. A valuable first step is to identify the journals that 
will form your core list. You should choose one or more 
general scientific journals that may have items of great 
promise in your field - Nature, Science, New Scientist. Each 
week, quickly scan the contents list. 

3. Identify the authoritative journals dealing with your 
speciality and be prepared to scan through them. 

4. You may read the titles of some articles, the 
summary of a few, the summary and selected parts of one 



or two, and occasionally the whole article. Rarely, read the 
article with obsessive critical attention. 



CRITICAL READING 

1. Some papers state a monumentally important 
advance in a short report. A classic example was the letter 
in Nature written by James Watson and Francis Crick 
announcing the construction of the DNA molecule. 

2. More frequently, the idea has a less immediate 
impact and must be presented within a conventional 
format. Take advantage of the standard presentation. 

3. The Title should clearly convey to you what the 
content is. It should convey the key words that allow it to 
be traced. Is it relevant to your interest? 

4. The Summary must encapsulate the whole article. 
When you read it, you should know in outline a simple 
answer to each of the main questions posed by and 
answered in a paper reporting, for example, an investi- 
gation stimulated by a question or a hypothesis. 

5. The Introduction answers the first question, 'Why did 
we do it?' You should be able to understand clearly what 
was the starting point, what has generated the need for an 
investigation and what is the question that was asked. Do 
you think the authors started with the correct premise? 

6. The Method section must state clearly, 'What we did/ 
It must explicitly reveal every detail of how the investi- 
gation was organized, carried out and measured. Has the 
method been fully and openly described? 

7. The Results answer, "What we found/ All the results 
must be clearly displayed. Any inconsistencies should be 
identified and explained. Do you understand them, are 
they justifiable? 

8. The Discussion states "What it means/ This is often 
the shoddiest part of scientific papers. Until now the 
authors should have provided clear, simple facts. They 
should now limit themselves to stating how their results 
fit into or alter the position from the starting point. They 
may briefly suggest possible supplementary investiga- 
tions that they or others could pursue to test the evidence. 
Are they overinterpreting their findings beyond the justi- 
fiable results of the investigation? 

9. The Conclusions should not be a mere repeat of the 
summary but clearly and briefly summarize what has 
been added to our knowledge by the investigation. 




Key point 

• Apply your most important asset to the 
conclusions - your common sense. Are you 
convinced? 



455 



46 



GENERAL CONSIDERATIONS 



WHAT DIP Y OU LEARN? 

1 . Most importantly, you practice making up your own 
mind about the 'facts' that are presented to you on the 
basis of the evidence placed before you. You are not just 
a passive acceptor of the opinion of others. This gives you 
confidence to reject evidence you consider unreliable, and 
faith in your own good sense, rather than relying 
unthinkingly on 'experts/ 

2. You may not know the fine points of statistics (see 
Ch. 45) but you can decide whether they have been 
applied correctly and with integrity. When two groups 
are compared/ we may be assured that they differ in one 
respect only, but this is never so. Biological variation is so 
great and capricious that too much cannot be read into 
small differences. 



PI 

I | Key points 

• If you are studying a prospective trial of, for 
example, two treatments, are you convinced 
that the authors had open minds beforehand - 
or were they hoping to prove one method 
superior? 

• Make sure, when comparisons are made 
between groups of patients, that 'apples' are 
not compared with 'pears'. The groups must be 
closely comparable. 

3. You may detect imperfections in the manner in 
which two populations are to be compared, that are not 
clearly stated. Sometimes aspects such as the method of 
clinical follow-up is not clear; for example, was it by 
independent assessors, by personal interview or exami- 
nation, prospective, performed blindly - when the as- 
sessor does not know the treatment or procedure to 
which the patients were subjected? Follow-up times may 
be given in a general way that does not make it clear that 
most of them were made too short, with very few long 
term follow-up times. Graphs and histograms may be 
used to avoid giving individual figures, in the same 
manner that advertisers use them to promote their 
goods. 

4. Are the claimed benefits of one treatment over 
another genuine? There are so many variables: among 
diseases, such as site, extent, involvement of vital struc- 
tures, virulence; among patients, such as age, sex, comor- 
bidity; as a result of diagnosis, early, late, confidently or 
uncertainly; institution of treatment, promptly, effec- 
tively, long enough; and any ancillary treatment. 

5. In cancer treatment, an improved method of detec- 
tion may appear to produce improved results in two 



ways. Survival times may lengthen because the new 
method allows earlier detection, lengthening the 
recurrence-free time. The apparent improvement is the 
result of the 'lead time', the interval that transpired 
between the time of pick-up with the improved method, 
compared with later detection. In addition, the improved 
method may show that the disease is more extensive than 
would be shown by previous methods so that the earlier 
likelihood of recurrence is recognized. As a result the 
'stage' is raised, whereas less effective methods may result 
in the tumour being classified as a lower grade. For 
example, when staging of breast cancer is limited to clin- 
ical assessment, a tumour may be diagnosed as stage I; 
imaging scans may demonstrate local, impalpable glands 
so that the tumour is classified in a higher stage, with a 
poorer prognosis. Chest X-ray may demonstrate, 
however, that rib metastases are present and the tumour 
must therefore be placed in stage IV - evidence of metas- 
tases. A series diagnosed by clinical examination alone 
and placed in stage I thus contains more advanced 
tumours and the results of treatment appears poor. If the 
tumours have been investigated with modern tests, these 
advanced tumours would be classified as stage II, III or IV, 
leaving only 'true' stage I tumours. Treatment of this 
smaller number produces better results than a mixture of 
early and undetected later tumours. This is often called 
the Will Roger's effect. (Will Rogers, an American homely 
sage, despised Californians. He described the often- 
despised (as mentally low grade) Oklahama farmers who 
were forced to migrate to California during the 1920s 
drought - 'thus raising the IQ in both States/) 

6. It is often accepted that authors provide only evi- 
dence that supports their hypothesis and those contra- 
dictory points that can be demolished. Seek out unstated 
weaknesses. 

7. Papers sometimes appear too perfect. Were there no 
patients lost to follow up, people who did not fully 
comply with an arduous treatment regimen, tests in some 
that were equivocal? 

8. Read other investigations in the same field of inter- 
est. You will be surprised that very often the results are 
not comparable. You may wonder how this can be: the 
populations may differ; among many other reasons, the 
expertise, case selection, and familiarity with the condi- 
tion and the treatment methods may differ. 

9. Why not just read authoritative reviews? Reviews 
are written by experts who already have a point of view. 
However honest and good intentioned they are, they 
inevitably argue for their own views — they would not 
adhere to them if they did not believe in them. If you read 
a review, seek out one that gives an opposing view. 

10. During your career you are likely to see patients with 
unusual, perhaps unique, conditions. If you retain your 
inquisitive and critical enthusiasm you may recognize 



456 



CRITICAL READING OF THE LITERATURE 




what may be an important advance. Your familiarity with 
the literature will have nourished your thinking and 
writing abilities, allowing you to report your findings to 
your colleagues. 



AVAILABILITY OF INFORMATION 



1 . We now have available a wealth of publications. In 
the past the Index Medicus - often called the greatest 
American contribution to medical science - was the 
'browser' we consulted to find articles not in the journals 
to which we had normal access. We would then write for 
reprints of important articles. 

2. Through the internet we now have available 
MEDLINE; many titles are accompanied by summaries. 
Other sources may provide access to the full text. Using 
the well-known search engines you can find an immense 
amount of information; remember, though, that you do 
not know the provenance of many reports that have not 
been subjected to independent review. However, you can 
find easily understood explanations of difficult subjects 



that give you a grasp of them, when the scientific papers 
assume you must be familiar with the terms used. 

3. A list of available sources soon becomes outdated. 
Keep abreast of the advances and of the flow of new 
discoveries. 



Summary 

• Do you acknowledge how important it is 
that you do not fall behind and practise 
outdated medicine and surgery? 

• Will you retain your critical faculties? 
However eminent the authors, or 
prestigious the journal, your common 
sense is your best protection against being 
misled by what you read. 

• Since few of us try to falsify our 
hypotheses, will you determine always to 
read opposing articles after reading a 
seemingly convincing report? 



457 




Communication skills 



R. M. Kirk, V. M. Macau lay 




Objectives 

• Good communication is essential in all 
areas of activity, not just in relation to 
patients. 

• Recognize non-verbal as well as verbal 
communication. 

• Empathize with the listener, especially 
when giving bad news. 



contrast, the tone of voice, the emphasis placed on certain 
words and the reaction to the listener's responses help to 
guide the speaker to know how to proceed and estimate 
the effect of the words. 

Telephone conversations are midway, containing vocal 
overtones but lacking the non-verbal expression and 
gestures that add a layer of meaning to the words. 

It is self-evident that if you wish to communicate with 
someone over an important or delicate matter, you should 
always choose to do so face to face. 



'Communication skills' sounds like yet another facility to 
be learned, like operating; however, most of us already 
have inbred and acquired competence, as it pervades our 
contact with all other people. 



VERBAL COMMUNICATION 



^^v&^^ 



^M^&sf&iv&'XH 



The words we use, the tone of voice, the speed with which 
we speak, the pauses that we interject, all have an effect 
on the listener. If we are giving similar information to two 
different people, we usually do not attempt to employ the 
same words to each of them. Some people adopt the word 
patterns of those to whom they are speaking; others, 
wishing to impress, may use abstruse or jargon words or 
acronyms (words formed from the initial letters of other 
words). 

The tone of voice and rhythm add a layer of meaning. 
Terse, staccato speech is sometimes commanding or 
threatening or signifies tension in the speaker. Quietly 
spoken words may be soothing or, if given in a sibilant 
(hissing) manner, may suggest potential threats. 

Face to face communication is much richer than 
writing. Words have defined meanings and the writer is 
limited to choosing the ones nearest to the intended 
meaning plus a few symbols such as exclamation and 
question marks or underlining. The writer has to guess at 
the response to the message and cannot modify it if the 
receiver reacts unexpectedly. The words do not have to be 
cast on tablets of stone to be irrevocable in their effect. In 



NON-VERBAL COMMUNICATION 

This is a very deeply ingrained way of informing others 
of our mood and intentions. Our dress may indicate that 
we are relaxed and informal, or we may wish it to 
register professionalism and formality. Posture indicates 
depression and humility or confidence and command. 
Most revealing are our facial expressions. The giving out 
of signals and the reading of them is often unconscious. 

Most of us acquire a social awareness of non-verbal 
communication. When one person is speaking and the lis- 
tener wishes to interject a remark, he or she signals the 
wish or intention, perhaps by a movement to attract the 
speaker's attention, a raising of the hand, a seeking of eye 
contact with the speaker. The speaker responds, some- 
times by returning the eye contact, by smiling and bring- 
ing the statement to a close, or resists by raising a hand 
with palm towards the person wishing to speak or raising 
the voice, to indicate resistance to stopping. The giving 
and receiving of signals can be confused and confusing. 
A smile and a sneer are not dissimilar - indeed one may 
change into the other. A gentle touch is a subtle method 
of conveying sympathy, a firm grip can convey authority 
and trust, but a push or a blow are threatening. 

Actors, salesmen and confidence tricksters have always 
recognized, sometimes instinctively, the fundamentals of 
what is often called 'body language'. In recent years, non- 
verbal communication has been studied and brought to 
notice by those claiming to advise salespeople, job appli- 
cants, interviewers and 'interviewees/ 



458 



COMMUNICATION SKILLS 



47 




Key point 

Strenuously avoid giving potentially upsetting 
news, complaining or arguing, by letter or 
telephone. You need to watch the reaction of 
your listener to what you have just said, so 
that you can, if necessary, modify what you 
will next say. 



COMf^ 

1. Remember that you are familiar with clinical sur- 
roundings but patients associate them with anxiety and 
sometimes with dread. They may be apprehensive, con- 
fused or yearning for reassurance that all is well. 

2. Because most patients are in later adult life, and 
often, therefore, more conventional, they may expect 
that doctors who dress and behave reasonably formally, 
take their responsibilities seriously. Immediate and 
casual use of first names is not welcomed by many older 
patients. Similarly, casual exposure of their bodies and 
clinical features is resented. We owe it to them to respect 
their wishes if we are to obtain their cooperation and 
trust. 

3. Note that some colleagues adopt a serious and grave 
manner, others try to appear cheerful and light-hearted. 
There is no standard pattern. Sometimes we are serious 
with one patient and jovial with another. Avoid attitudes 
and speech that denote overbearing and curt superiority, 
or the overcasual 'jokeyness' that may suggest we take the 
patient's problems light-heartedly. 

4. When you wish to discuss important information 
with a patient, ensure that the surroundings are quiet and 
that you will not be disturbed or distracted. Hand your 
'bleep' to someone who can answer it for you. In appro- 
priate circumstances suggest that a relative or friend of 
the patient is present. 

5. The information you give the patient should be 
known to your medical and nursing colleagues, and to 
other paramedical carers. In many circumstances it is 
valuable for them to be present so they can participate in 
the discussion and know what has been decided. Patients' 
confidence is eroded if different people give them con- 
flicting information. 




Key point 

Patients you see are already apprehensive. Do 
not increase their insecurity by placing them in 
undignified circumstances. 



Questioning 

1. When taking a medical history (see Ch. 3), allow 
patients time to speak. Do not make them feel that what 
they have to say is of little account. If they are stuck for 
words, allow them time to choose a suitable one; do not 
immediately feed one that fits your prejudice. However, 
you must control the interview, so your timing when inter- 
jecting a question for clarification, or asking a new question, 
must be sensitively judged. A too rapid interruption cuts off 
the patient's train of thought, but if too long delayed it may 
allow the patient to take a new, diverting, train of thought. 

2. Choose words suited to the patient before you. A 
simple person needs simple language spoken slowly, and 
repeated or rephrased without signs of impatience. For 
example, ask one person where is the pain in the belly if 
that was the term he or she employed to you. A pro- 
fessional person may resent the avoidance of the more 
formal 'abdomen'. 

3. The ability to communicate is severely tested if the 
patient is a young child, deaf, has a speech defect, a 
behavioural anomaly, or has difficulty with the language. 
When talking to a person who is hard of hearing, always 
sit face to face. It can be impossible to communicate 
rationally with those under the influence of alcohol or 
other drugs, with people who are hysterical or violent, or 
with those suffering from diminished consciousness, 
whether it is the result of injury or disease. 




Key point 



• If you have difficulty in communicating, consider 
whether you need help from a senior colleague 
or an interpreter, or should you defer action if 
the patient's cooperation is likely to return later? 

Telling and discussing 

1. First find out what is already known, what that 
information signifies to the patient, and decide how the 
additional information should be presented. As a rule it 
is best to start by asking questions such as, 'Would you 
like to talk about the [problem]? I am not sure how much 
you know.' Later, you may ask questions in order to 
evaluate the patient's appreciation of the additional 
information you have given. 

2. In most circumstances do not try to say too much all 
at once. Give the patient time to absorb what has already 
been said and wait for an indication of readiness to con- 
tinue. From time to time ask questions to check that the 
patient really understands what has passed between 
you, for example, 'Can you tell me then, how you see the 
situation?" 



459 



47 1 



GENERAL CONSIDERATIONS 



3. Especially when discussing important problems, be 
extremely sensitive to the listener's reactions and signals. 
In some cases it may be better to defer the interview to a 
later date to allow the patient to absorb and react to what 
has already been said. 

4. Patients anticipating bad news frequently demon- 
strate by their body language, or by suddenly ceasing to 
ask questions, that they do not wish to be told anything 
more at present. Do not ignore it. Allow the patient time 
to absorb what has passed between you and come back 
later. Before you restart further discussion, reassess the 
patient's comprehension of the situation; you may be sur- 
prised at the 'adjustments' made to the information so the 
patient can cope with it. 

5. Remember that distress, anxiety or despair may be 
dealt with by total rejection, blame directed at others or 
at you, threatening behaviour or aggression. Do not react 
antagonistically. 



• Do not contradict or respond to aggressive 
behaviour. Stay calm, do not interrupt, be 
willing to listen. 

Relatives 

1. Relatives deserve the same consideration that we 
give to patients. We hope that they will give encourage- 
ment, support and help to the patient throughout the 
management of the condition requiring treatment. 

2. Occasionally there is conflict between the demands 
of the patient and those of the relatives. What do you say 
if a patient demands that you do not disclose what is 
happening, while the relatives press you for information? 
Your contract is with the patient and you must honour 
that relationship. The relatives may ask you not to give 
certain information to the patient. Again, judge for your- 
self the best course, on the patient's behalf. 



Advising 

1. Discuss with patients what options are available, 
what are the advantages and disadvantages of each. This 
is not always easy to do, as not many treatment choices 
can be scientifically justified. In biology there are few 
areas that are either black or white; most are shades of 
grey. This explains the differing advice that patients 
receive when they ask for a second opinion. 

2. Surgeons have a reputation for being decisive, and 
in practice most of us are in no doubt about the advice we 
wish to give. Our advice is based on our professional 
experience - what we have encountered, read about and 
talked about. The patient needs to be encouraged to ask 
questions and, when there is no urgency, to go away, 
think about the advice, come back and discuss it again. 
However, we believe it is a rejection of professional 
responsibility merely to lay before our patients the pros 
and cons of each course of management and leave it to 
them to decide which one to follow. Patients are often not 
in a suitable state of mind to make the best decision, espe- 
cially if they have just been told that they are suffering 
from a serious condition. Therefore, we should end with, 
'So in my opinion . . .' Of course, patients are free to reject 
the suggested course of action. 



F^ 



Key points 



Anticipate aggression from an angry or 
threatening patient - but do not behave like a 
'victim'. 



COLLEAGUES 

1. A vital professional duty is to inform colleagues 
about matters of patient care. Always write up notes, 
avoiding abbreviations, jargon and opinionated remarks 
that might be misinterpreted. Sign and date them. When 
you hand over before you go off duty, inform the on-call 
doctor personally of any outstanding problems. 

2. If you have had a discussion with a patient about the 
future, or about treatment, ensure that you tell the nurses 
and your seniors. There is nothing that undermines the 
confidence of patients more than being given different 
information by different people. 

3. Your colleagues include all those with whom you 
come into professional contact: doctors of all grades, 
students, nurses, physiotherapists, technicians, managers, 
clerical staff, porters, cleaners and tradesmen. Do not 
draw a line of 'importance', below which you do not 
acknowledge people, or bolster your dignity by trying to 
diminish others. Each of us counts as just one. 

4. One of the most important qualities we have is our 
self-esteem. When we fail to carry out a task conscien- 
tiously we expect to be reprimanded. When we perform 
well, we rightly hope to be congratulated. If you expect 
to be acknowledged, remember there are others that hope 
you will acknowledge and encourage them. 



IMPARTING BAD NEWS 

1. Communicating with ill or distressed people 
requires great sensitivity. Your behaviour should 



460 



COMMUNICATION SKILLS 



47 



be influenced by your feelings of sympathy and 
compassion. Our reactions may be modified if we are 
able to enter our patient's personality in our imagination 
and think how we would feel if we were in a similar 
situation; this is termed empathy (Greek em = in + pathos 
~ feeling, suffering). Obviously we cannot always 
achieve this, but in making the effort we can identify the 
likely reactions and apprehension of the patient and 
respond sensitively. 

2. We have the duty to keep our patients and any close 
relatives informed of what is happening, and what it 
means. Of course, we must be guided by the patient's 
wishes about what we tell the relatives. This often entails 
telling them that recovery is failing, the patient has devel- 
oped a complication, or our investigations reveal severe 
and perhaps terminal disease. At times of crisis you may 
be the only doctor present and are therefore responsible 
for dealing with the problem. 

3. Prepare yourself before disclosing that the patient 
has a potential or actual terminal illness such as advanced 
cancer. Review the options by recalling or looking up the 
published results of the various choices before you go in 
to talk to the patient (see Ch. 39). 

4. Ensure that this consultation takes place in a calm 
and private area. Ask someone to take over your 'bleep', 
so you cannot be interrupted. It is usually valuable to 
have a nurse with you so that she or he can tell colleagues 
what has been said. 

5. As you approach, look at the faces of the patient and 
family, and try to judge how they are feeling. You are also 
being carefully studied in return, for hints of what you are 
about to say. 

6. You should be prepared to structure the conversa- 
tion. A suggested plan is as follows: 

a. Ask the patient and the family what they under- 
stand of the situation. 

b. Describe the situation as you see it, using terms with 
which they are familiar. 

c. Outline what can be done. 

At each stage you should allow the patient to ask 
questions so that you can explain the implications in a 
manner and speed that does not distress or confuse the 
patient. Be as optimistic as realistically feasible given the 
situation; if the outlook is poor, do not unthinkingly 
deliver the full extent in one encounter. Explain the 
reasons for recommending each aspect of the treatment, 
but if the results of trials are poor, you do not need to 
volunteer them unless the patient wishes to know them. 
Remember that the patient will be trying to come to terms 
with the diagnosis and may not be in the best frame of 
mind to absorb the consequences and make decisions 
about the practical implications. It may be necessary to 
defer making an important management decision until 



the patient has had time to assimilate information given 
during the first consultation. 

7. It is sometimes stated that information belongs to 
the patient and the doctor has no right to withhold it. 
Indeed many patients are very knowledgeable, ask direct 
questions, and may wish to be told everything that is 
known about the situation and the consequences. Be 
aware that this will not apply to every patient, and you 
should not dismiss the minority who do not wish to be 
told the whole truth, by forcing information on them 
immediately. Occasionally a very anxious patient blurts 
out the words, T want to know everything', but their eyes 
are begging for reassurance that all is well. Be sensitive 
to verbal and non-verbal cues from the patient and rela- 
tives, and be ready to defer answering questions that are 
not asked. 

8. In human relations we must retain a sense of balance 
and sensitivity. Rigid blanket rules are inappropriate. Just 
as in our personal life we try to avoid pouring out sensi- 
tive bad news, so we need to be as considerate to our 
patients and allow them to dictate the way in which we 
inform them. Our duty is to interpret the patient's often 
unspoken signals and be governed by them. 




Key point 



• The founder of the hospice movement in 
Britain, Dame Cecily Saunders, stated: 'The 
patient, not the doctor, or the nurse, or the 
relative, must retain control of information to 
suit his needs.' 

9. Provided you are sympathetic and sensitive, you are 
unlikely to make gross mistakes. Those who are told very 
serious news, and are later asked what was said, often 
give a different and more optimistic version if they are 
unable to cope with the full truth. There are some 
patients who indicate that they fully understand the cir- 
cumstances but do not wish to have them spelled out in 
concrete terms. Respect their wishes. 

10. Never leave a patient without hope or support. If 
treatment such as operation cannot be employed, it is 
possible to say, 'Operation is not appropriate but I shall 
continue to care for you/ 

11. Remember that the news may be more distressing 
for the relatives and friends than for the patient, because 
they are not only sad for the patient but they are desolate 
at the prospect of being left alone. However, the informa- 
tion belongs to the patient, not the relatives. Ensure that 
you do not disclose anything to them against the patient's 
wishes. 



461 



47 



GENERAL CONSIDERATIONS 




Key point 

Now write in the notes exactly what has passed 
between you and inform your colleagues 
including the family doctor and the nurses. 



1. The outcome of any form of medical care does not 
always reach expectations. You cannot anticipate and warn 
the patient and relatives about every possible complication. 

2. Every person makes mistakes from time to time by 
failing to notice a complicating factor, by misjudging a 
complex situation, by making the wrong decision or by 
technical error. 

3. Do not attempt to hide the fact from a patient if 
something has gone wrong. Explain it and say what 
measures you will take to put it right. Just as we detect 
evasiveness when we watch a politician being asked an 
awkward question on the television screen, so our 
patients instinctively recognize any reluctance on our part 
to explain a misadventure. 

4. One of the commonest complaints of patients is that 
when things go wrong, sympathy and openness are with- 
held. They naturally become suspicious. 




Key point 

Telling a patient that you are sorry if an 
unexpected complication occurs, is not an 
admission of guilt. 



Summary 

• Do you appreciate that there are no rigid 
or absolute rules except to be sensitive to 
the patient's signals? 

• Do you recognize that communication is 
more than mere words? 

• Will you remember to give patients time 
to absorb your remarks, and time to 
respond in their own way? 

• As you prepare to give patients 
information, will you first enquire how 
much they already know? 

• Do you accept the need to recognize and 
honour the (often non-verbal) signs that 
patients do not wish to have more 
information forced on them at this time? 

• Will you remember to keep your 
colleagues informed about the 
information passed between you and the 
patients? 

• Do you recongize the danger of trying to 
conceal complications and errors from the 
patients? 




Further reading 

Buckman R 1992 How to break bad news. Papermac, London 
Lloyd M, Bor R 1996 Communication skills for medicine. 

Churchill Livingstone, Edinburgh 
Myerscough PR 1992 Talking with patients. Oxford University 

Press, Oxford 



462 




The surgical logbook 



D. M. Baker 




Objectives 

• Understand the importance of maintaining 
a logbook. 

• Understand how and what information to 
collect in your logbook. 

• Know how to analyse the collected data. 

• Recognize the difficulties in keeping a 
logbook. 



|NTR0HDUCTION 

A surgical logbook is a record of the activity you have 
undertaken. Although important during training, it 
remains a central part of the routine throughout your 
career. Of the different parts of a surgeon's job, the easiest 
to record are: 

• Operations performed 

• Patients seen in clinic 

« Patients admitted and seen while in hospital. 

I shall concentrate on logging actual operations under- 
taken. Although this is the most commonly kept record, 
the other two records are important, as you will see and 
treat many more patients than those operated upon. The 
outcome of surgical patients treated conservatively is as 
important as the outcome of those operated on. 



WHY KEEP A LOGBOOK? 

1 . Just as airline pilots keep a log of every flight they 
make, so it is your duty and self-discipline to keep a 
record of the procedures you have performed. Although 
not yet legally demanded, you are required by the 
Surgical Colleges to keep a logbook during training. This 
is to demonstrate that you have been adequately trained 
in an operation or procedure before being considered fit 
to undertake it independently. It will soon be necessary to 



demonstrate that, as consultant surgeon, you continue to 
demonstrate your competency 

2. The logbook provides a source of self-auditing sur- 
gical practice. If, for example, it demonstrates a series of 
wound infections following a particular procedure, you 
must identify and rectify this. 

3. For you, the trainee, a logbook identifies strengths 
and weaknesses in your training. It may demonstrate sig- 
nificant experience of one procedure but show deficien- 
cies in another At the regular formal appraisal you 
should be guided to rectify the deficiency. 

4. The logbook helps your trainers assess the standards 
within the specific posts of a surgical training rotation. If 
your log shows that you have undertaken unsupervised 
major procedures at night, this can be investigated to 
establish if you are very able, or the trainer should be 
informed on the training of surgeons! 



COy-ECTINGTHE)N 

1 . Spreadsheets are ideal for recording information, or a 
grid of data divided into rows and columns. Each oper- 
ative procedure occupies a row, with each item of infor- 
mation occupying a separate column. There are a number 
of choices; the most simple is a lined school exercise book 
with vertical lines dividing the pages into rows and 
columns. The Royal Surgical Colleges have logbooks, and 
computer packages are available, at a range of prices, 
that are compatible with personal (PC) and palm-top 
computers. The data in computerized logbooks can be 
analysed quickly, presenting it clearly and neatly. More 
complex spreadsheets provide a full database. 




Key point 

It is not the logbook's complexity, type or cost 
that count but the accuracy and completeness 
with which you collect and record the data within 
it. 



463 



48 1 



GENERAL CONSIDERATIONS 



The operative information collected varies with your 
expertise and interest. This will change and develop 
throughout your career. However, some core information 
is always necessary. This includes: 

2. Patient details - record name, age or date of birth, sex 
and hospital number as a minimum, otherwise your log 
cannot be externally audited (see quality assurance later), 
and you may fail to trace the notes, or follow up the patient. 

3. Demographic details - complete the columns for 
hospital, operation, date and time, whether planned, 
emergency or 'next routine list'. 

4. Staff involvement - what was your involvement, who 
performed the operation, who assisted, who was the most 
senior surgeon present? You may record the anaesthetist 
and even the scrub nurse - although this is entered in the 
hospital records. 

5. Operation - devote at least three columns, each more 
specialized and specific than the last. Within your training 
programme you rotate, so enter the name of the speciality 
in the first column, such as orthopaedics or neurosurgery. 
In the second column name the subspecialty, for example 
within general surgery it may be colorectal or vascular. 
Record the name of the procedure in the third column. 
The Office of Population Censuses and Survey (OPCS) 
have developed specific codes for each operation to 
ensure uniformity for accurate subsequent analysis. 

6. Anaesthesia - record the type, such as local or 
general, as a minimum. 

7. Selection of procedures - you may decide what extra 
procedures you wish to record, for example, rigid sig- 
moidoscopies or central lines you insert. 

8. Complications - record details of all adverse events 
following operation. Anastomostic leaks, wound infec- 
tions and haemorrhage are obvious, but even though 
urinary tract infection and deep vein thrombosis may not 
be technical complications, record them. 

9. Mortality - a perioperative death is one occurring 
within 30 days of operation. Record all deaths even 
though they may not be related to the procedure 




Key point 



The only way to avoid complications is not to 
operate. Be honest with yourself and record all 
complications. 



PROBLEMS WITH KEEPING A LOGBOOK 



^■^^^^'/^■¥i^^^^^^;^^^:^^'/^ 



2. Develop a routine. Discipline yourself to complete 
the entries in your logbook every time - when you leave 
the operating theatre, or every night before going to bed. 
If you lag behind it is tempting to give up. 

3. Record the data soon after the event while it is still 
fresh in your mind. Collect it little by little as you accu- 
mulate experience. If you defer it for intervals of once a 
month, you will miss patients and fail to remember the 
data accurately. 

4. Collect your data from original sources, from what 
you know to have happened in the operating theatre, not 
from the operating room logbook or the hospital com- 
puter record of admissions and discharges, as this infor- 
mation is not reliably accurate. 

5. Include all operations. Do not exclude minor proce- 
dures such as excision of sebaceous cysts because you 
have undertaken the procedure several times before. 
Avoid this temptation or your logbook will become inac- 
curate and incomplete. 

6. Record all complications, even though it may 
demand courage to admit them. 




1. Inaccurate and incompletely kept logbooks are a 
waste of time. Acquire an enthusiasm for keeping an 
accurate record of operative activities. 



Key point 

Keep your logbook up-to-date, comprehensive 
and accurate 

7. Analyse the data regularly It is a stimulus to assessing 
your progress and identifying your strengths and weak- 
nesses. It is both important and gratifying, demonstrating 
the value of keeping an accurate, complete logbook. 

8. Quality assurance checks ensure that your data col- 
lection is accurate. At intervals of approximately 3 months, 
check your list of operations against an independent 
source such as the operating room logbook. Your record 
should be more accurate and complete than any other list, 
and if it is not, then your data collection is inadequate. 

9. Keeping it legal: register your log book with the data pro- 
tection agency. Your logbook must not infringe the patient's 
personal rights. You must avoid allowing this information 
to become publicly available. Ethical and legal restrictions 
on ensuring patient confidentiality apply here, as else- 
where in medicine. To ensure this, keep minimal patient 
information, such as the initials and not the names or hos- 
pital number. This creates difficulty for future audits and 
follow-up studies. If you keep your logbook always within 
the hospital where you work, it can be registered with the 
hospital's list of patient databases. This limits your access, 
as you must register it each time you move hospitals and 
you cannot take it to your home. If you are creating a sur- 
gical log for the whole of your working career, which you 
should be, then consider registering it under the Data 



464 



THE SURGICAL LOGBOOK 



48 



Protection Act, 1988. You need to fill in a form, obtainable 
over the internet (http://www.dpr.gov.uk), and pay an 
annual nominal fee. 



ANALYSING THE DATA 

The logbook contains a vast wealth of information from 
which many facts about training and, subsequently, 
surgical practice can be drawn. Analysing what you have 
done can be an exceptionally informative and often enjoy- 
able reflection on your progress. Before starting to analyse 
your data, clearly determine what information is needed. 
For example, while in training it is important to know the 
number of operations you have done, their size, the 
degree of urgency and the level of supervision received. 
Using the above layout, this information can be extracted 
either manually or with the aid of a personal computer. 

Problems with data analysis 

Analysis takes too long 

If the logbook data is stored in a paper book, analysis is 
done manually by counting through each case. This will 
take time once there are several years of cases. If the log 
is stored on a computerized spreadsheet, analysis time is 
considerably shortened. However, a limited basic knowl- 
edge of computers and computer spreadsheet analysis is 
necessary first. This should never be considered a hurdle 
and all surgeons in training should be prepared to sacri- 
fice the single afternoon required to obtain these skills. 
The Colleges offer basic computer skill courses. 

Analysis appears incomplete 

Assuming complete data collection, a lack of uniformity 
between cases in recording similar data may result in a 
failure to detect all cases. For example, if abdominal aortic 
aneurysm repairs are sometimes recorded as 'aneurysm', at 
other times as 'AAA' and yet other times under the OPCS 
code LI 940, computer analysis looking only for 'aneurysm' 
will miss cases coded with either 'AAA' or LI 940. 

The logbook is lost 

Always keep at least one recently updated copy of your 
logbook separate from the original. 



WHAT DATA DOES YOUR HOSPITAL 
KEEP? 



as a surgeon need to undertake this. However, it is 
important at all levels of medicine. NHS trusts collect 
data about inpatients, outpatients and others on their 
patient administration systems. The data include demo- 
graphic details of the patients, dates of admitted care and 
clinic appointments, the consultants in charge of their 
care, diagnostic and operative procedure codes, and a 
variety of other such information. 

Trusts routinely send nationally specified subsets of 
these data to the NHS-wide clearing service (NWCS), 
which then electronically redistributes the information 
about patients to the appropriate commissioners of health 
care. This enables the local commissioners to monitor the 
workload of all the trusts serving large or small numbers 
of their patients. 

Each quarter, a summary of the inpatient data held by 
the NWCS is sent to the Department of Health's own 
database, the hospital episode statistics (HES) system. It 
is HES that is used for the calculation of published clini- 
cal indicators - dubbed 'league tables' by the media - and 
for high level planning of the NHS, monitoring its per- 
formance and other government purposes. 

The Department of Health is intending to add more 
detail to the data sets held at NWCS and HES, including 
the codes of surgeons and anaesthetists present in theatre 
during operations. 



CONCLUSIONS 

Keeping a record of your surgical activities is a central 
part of the discipline of being a surgeon. It requires dedi- 
cation to ensure its accuracy and completeness, but if well 
done you have a valuable record of your activities as a 
surgeon. 






^^i^:-^:^ 7 ^^ 



Data collection is very important in reviewing progress 
and planning future changes. On an individual level, you 



Summary 

• Keeping a record of all surgical activity is 
an integral part of a surgeon's job, both 
while in training and later in professional 
life. 

• On every procedure, keep information 
relating to the patient's details, the site 
and time of the operation, the procedure 
undertaken and by whom and, 
importantly, record all complications. 

• Ensure that the data are collected quickly, 
accurately and completely. 

• Analyse and review your progress 
regularly. 



465 




The MRCS examin 



D. Wilkins 




Objectives 

To explain the new format of the 

examination. 

To provide insights into the philosophy 

that underpins the examination. 

To provide advice on how to approach the 

examination. 



INTRODW 

The MRCS (Membership of the Royal Colleges of 
Surgeons) examination was devised and introduced in 
1 997 and has since been conducted by all four of the Royal 
Colleges of Surgeons of the United Kingdom and Ireland. 
Successful completion of the examination, which com- 
prises a series of assessments, is designed to mark the end 
of basic surgical training by the attainment of a 'satisfac- 
tory' standard of knowledge and clinical skills. In essence, 
the standard of performance expected is that of an ex- 
perienced, well-motivated and able senior house officer 
(SHO) who has completed a 2 year rotation through a 
series of approved basic surgical training posts. I provide 
a broad overview of the regulations for the English 
College examination appropriate from September 2002. 
Changes in format and sequence will apply to those 
taking the clinical section for the first time after May 2002. 
You must study those for your preferred College as early 
as possible. 

What of the philosophy that lies behind the MRCS? The 
aims of the examination can be expressed succinctly by 
stating that it aims to be fair and thorough. 'Fair' means 
that we shall examine to a consistent standard, explicitly 
stated as clearly as possible in the examination syllabus 
and also in the curriculum. Curriculum (Latin currere = to 
run) defines the whole breadth of knowledge and skills to 
be acquired during training; the syllabus (Greek sittuba = 
book label; programme, abstract) sets out the segments 
that will be assessed by the examination. Great care is 



taken in all modern examinations to achieve consistency. 
The expertise required to achieve this is substantial and is 
reflected by the infrastructure necessary to support the 
examination and subsequently in the cost of the exam- 
ination which, surprisingly runs at a loss! Fair also means 
that all candidates will be treated in similar manner 
without bias of any kind. 

Thoroughness' is the other, as yet unachieved, ambi- 
tion of examinations. Ideally, examinations test all areas 
of knowledge and skill outlined in the curriculum. The 
aim of basic surgical training is to train and educate aspir- 
ing young surgeons to a level of 'competence' across a 
range of skills. Clearly, an examination set outside the 
workplace cannot assess all of these competencies. 
Operating skill, attitude and values must be assessed in 
the workplace. Factual knowledge, ability to examine a 
patient properly and communicate effectively can be 
tested reliably in an artificial setting. Overall, the exam- 
ination sets a demanding agenda of quality and develop- 
ment for the examiners. 

The MRCS examination is the main hurdle for aspiring 
young surgeons and, during the 5 years since its intro- 
duction, it has come to be accepted as a well-conducted, 
fair and thorough examination. Basic science is empha- 
sized to create an adequate foundation of core scientific 
knowledge. 




Key points 

• The MRCS examination aims to be a fair and 
thorough series of assessments. 

• It will continue to develop to fulfil the 
demands of training and available reliable 
methods of assessment. 

Requirements (Table 49.1) 

1. You must have completed a minimum of 24 months 
of training in approved posts. Type 1 posts provide 
general experience, Type 2 provide specialist experience 
and training. Details are available from the examinations 



466 



THE MRCS EXAMINATION 



49 



Table 49.1 Timetable and eligibility for the sections of the MRCS (England) 




Section 


When held 


Where held 


Criteria for eligibility 


Papers 


March and September 


London and regional centres 


Any time after enrolment 


Viva 


June and December 


Royal College of Surgeons, 


A pass in MCQ papers 






London 


20 months tn approved posts 


Communication skills 


June and December 


Royal College of Surgeons, 


A pass in MCQ papers 






London 


20 months in approved posts 


Clinical examination 


January and July 


Regional centres 


22 months in approved posts 
A pass in MCQ papers 








A pass in the viva section 



departments of the respective Royal Colleges and their 
web sites. 

2. You must have satisfactorily completed an approved 
course in basic surgical skills. 

3. You may sit the multiple choice question (MCQ) 
papers at any time after enrolling with the College, You 
may attempt it an unlimited number of times. Once you 
pass the MCQs you may take the viva after a minimum 
period of 20 months in recognized training posts. 

4. Once you have taken the viva for the first time you 
must pass this plus the clinical examination within 2 years. 

5. You must attain a pass in all sections of the 
examination. 

6. The MRCS itself will not be awarded until the full 
24 months of training have been completed. 

Advice 

1. Prepare by taking every opportunity to examine 
patients thoroughly and confidently (see Ch. 3). Use your 
clinical time wisely assiduously acquire new skills, take 
every opportunity to practise what you have learned and 
be totally committed to your craft. 

2. Plan your training to mirror the philosophy of the 
examination. Choose your training post carefully to 
acquire clinical experience. Choose a committed trainer in 
preference to a prestigious one. 

3. If possible, work with friends and colleagues at the 
same stage, as it is difficult to work in isolation. It may be 
convenient to meet up once a week or in the evenings. 
Ask your senior colleagues to monitor you, question you, 
advise you, criticize you and encourge you. 

4. You will benefit from the Advanced Trauma Life 
Support (ATLS) and Care of the Critically 111 Surgical 
Patient (CCrISP) courses if possible. Progress through to 
the clinical examination will only be allowed if the viva is 
passed, but the communication skills section may be 
retaken separately if failed and will not hold up progress 
to the clinicals. 



5. On the day of each examination, you will have been 
asked to present yourself at a time and a place. Note this 
carefully, together with any documents that are required. 
Arrive on time; do not fail to allow for heavy traffic or bus 
and train delays. Examiners try to be helpful but the 
margin for error is extremely slim and if you miss your 
appointment slot you may be deferred. 

6. If you fail any section, the examiners will have made 
notes in order to provide some feedback should you fail 
the whole examination. You can obtain this information 
through the Examinations Department on request. It is 
intended to help you direct your learning towards a more 
successful outcome at your next attempt. 



ASSESSMENTS, STANDARDS AND 
MARKING 

1. Formative assessments are designed to aid you and 
your trainer. They may involve tests or assessments con- 
ducted by your trainer; your performance is then used to 
help you and your trainer decide on the requirements for 
future training. In other words, they help to 'form' sub- 
sequent teaching. 

2. Summative assessments are designed to confirm that 
a prescribed standard of skill, knowledge and /or compe- 
tence has been achieved. The driving test is an example. 
Understand that the MRCS falls firmly into the sum- 
mative category. 

3. A single isolated examination at the end of a sub- 
stantial period of training is considered unsatisfactory, as 
it is unlikely to provide the necessary range of assess- 
ments. More importantly, it is unlikely to stimulate you 
to acquire skills and knowledge systematically during 
training. 

4. A single 'exit' examination also suffers from the 
drawback that it gives you no indication of your progress 
until the end of the course. This is unhelpful and wastes 
energy and resources. 



467 



49 

i ii ■ j ■ ■ i in i n MamijiHtMiiiiMMHii^anniii 



GENERAL CONSIDERATIONS 



5. The MRCS examination addresses this by providing 
a series of assessments during, as well as at the end of, 
basic surgical training. These will be further refined and 
developed as surgical training evolves in the UK, and 
worldwide, within a society that is increasingly prescrip- 
tive and regulated. 

6. The curriculum for basic surgical training in the UK 
is being, and will be, revised, as will the pattern and 
assessment of training. The end of training will soon be 
marked by the award of a certificate of completion of 
basic surgical training (CCBST) but the MRCS examina- 
tion will remain the most important assessment to be met 
and overcome by you. 

7. The pass mark must be set at a fair and appropriate 
level, and maintained at a constant level from one 
examination to the next. When constructing the question 
papers (which incidentally are marked by optical scan- 
ning), a series of standard setting exercises is conducted 
to agree a cut-off point between pass and fail, under the 
direction of an expert. The time-consuming and demand- 
ing Angof technique combines the views of a substantial 
group of surgeons. Such methods are now a prerequisite 
for conducting professional examinations. A panel of 
external advisors was established initially and continues 
to direct the appropriate technical measures for setting 
and maintaining standards. 

8. You may wish to know the principles of marking 
methods. An aggregate of marks is used to measure per- 
formance in an MCQ paper or objective structured clini- 
cal examination (OSCE). A check list system is impractical 
and inefficient for complex tasks such as clinical exam- 
inations: examiners must make judgements. To ensure 
consistency, new examiners undergo training. Existing 
examiners undergo refresher training and regular 
appraisal of their performance during each examination. 
Furthermore, each examiner has available a set of estab- 
lished criteria to help form that judgement, and at the end 
of each interview the examiners mark independently before 
conferring, discussing details and agreeing a final mark. 
Pass /fail is decided on the combined total of marks across 
each section, with some small leeway for adjustment for 
borderline candidates resolved at the daily examiners' 
meeting. 




Key points 



• Do you match the knowledge and standards of 
a well-motivated, competent, experienced 
SHO? 

• Do you understand the difference between 
summative and formative assessment? 



Remember, in the clinical examination you may 
be able to compensate a substandard 
performance in one bay with a good 
performance in another. 



OVERVIEW OF THE E^WMN^ION 

1. Examiners must make judgements regarding the 
emphasis on particular areas of the curriculum. This is 
intended to encourage systematic learning and training 
so you develop sound insights, knowledge and skills. 
Throughout your professional life you need a grasp of the 
scientific base for surgical practice. In response to this, the 
MCQ papers have been increased to accommodate extra 
scientific content. Take every opportunity thereafter to 
refresh this knowledge beyond the examination, or it will 
decay. Be aware that basic sciences are needed for the 
Intercollegiate Board examinations sat during higher 
surgical training. 

2. The examination is divided into four sections: 

a. Multiple choice questions (MCQs) 

b. Viva voce (Latin vivere = to live + vocare = to call; oral 
testimony) 

c. Communication skills test, which takes place on the 
same day as the vivas 

d. Clinical examination (Greek kline = bed; strictly, by 
the bedside). 

The vivas, clinical examinations and communication 
skills tests are taken towards the end of basic surgical 
training and pitched at the standard expected of an ex- 
perienced SHO. Until recently, the clinical examination 
preceded the vivas. A relatively high failure rate in the 
vivas was ascribed to the fact that, following clinical 
success, candidates had only 2 weeks to prepare for the 
vivas. Clinical examination with bays taking 10 min each 
was considered too rushed and was expanded. The vivas 
are largely knowledge based. The clinical examinations 
are rightly the highest tests of skill, knowledge and deci- 
sion making. 



THE SECTIONS OF THE EXAMINATION 









Multiple choice papers 

1. There are two papers, each lasting two and a half 
hours. One is held in the morning, the other during the 
afternoon. They can be taken together or on separate occa- 
sions. The examinations are held twice a year. 

2. The papers cover two aspects: 'core' topics - a 
knowledge of the basic sciences that underpin surgical 
practice; and 'systems' topics - general surgical practice 



468 



THE MRCS EXAMINATION 



49 



itself. Both papers aim to test these two key areas. When 
the examiners set the papers they place the questions 
into one of these two categories, or a third 'mixed' 
category that combines both basic sciences and clinical 
knowledge. 

3. Each paper is divided into two sections. The first 
comprises 65 questions that are in the multiple true/ false 
format (MTF); the other comprises 60 items that are in the 
extended matching (EM) format. MTF questions test a 
very basic level of recall of factual knowledge and the 
answers are, in effect, a pure memory test. Extended 
matching questions require you to match one, more or 
none of a series of options with a series of clinical sketches 
(vignettes). This format is designed to simulate questions 
that may be encountered within genuine clinical situ- 
ations, thereby testing your ability to apply knowledge. 
This is considered to be a better, or more Valid', assess- 
ment (Table 49.2). 



Tab 




Table 49.2 Example of extended matching 
question 

Theme: postoperative complications 
Options: 

a. Tension pneumothorax 

b. Unstable angina 
c Septicaemia 

d. Acute massive pulmonary embolism 
8. Myocardial infarction 

For each of the dinical vignettes described below, 
select the single most likely postoperative 
complication from the options listed above. Each 
option may be used once, more than once or not at 
all. 

1 . A man of 75 had emergency surgery for a 
perforated diverticulum of the sigmoid colon. 
Twenty-four hours after operation he was 
peripherally warm, hypotensive (95/40 mmHg), and 
oliguric. The ECG was within normal limits. 

2. A man of 75 had a hip fracture treated by 
hemiarthroplasty. In the history it was apparent 
that he had fallen a couple of days before he 
presented. He received subcutaneous heparin from 
the time of admission. Six days after operation he 
became hypotensive (95/75 mmHg) and was blue, 
cold and clammy, with a high central venous 
pressure. He had inverted T waves in lead III. 

3. A man of 75 had a laparoscopic cholecystectomy. 
The foUowing day he was noted to be peripherally 
cold with a tachycardia. He had crackles at the lung 
bases. The ECG showed waves and ST segment 
elevation in the chest leads. 

Answers: l-c,2-d,3-e 



4. There is no negative marking for this or the extended 
matching section - marks are not deducted for incorrect 
answers. However, effective statistical techniques are 
applied to counteract the effects of overselecting choices. 
Remember that the papers are marked using optical scan- 
ning, so use only pencils of the appropriate grade/ which 
are supplied, together with erasers. Sampling is carried 
out to check the system for accuracy and the scanner 
queries uncertain pencil marks; however, be positive with 
your pencil marks and if you wish to erase a mark, do so 
thoroughly. 




Key points 



• Carefully read the glossary and instructions set 
out in the front of the papers. 

• Read the stems of the questions carefully. 

• Do not be tempted to 'random guess' the 
answers. 

Viva voce section 

1. This is a test of your ability to apply both pure and 
applied basic sciences to the practice of surgery. There are 
three sections, each of which is conducted by at least two 
examiners: 

a. Applied surgical anatomy and operative surgery. A 
specialist takes you through some anatomical questions 
that may involve photographs, sketches, a model or a 
cadaver. A colleague at the same table questions you on 
the surgical application of anatomical knowledge for 
operations and other practical procedures, and the prin- 
ciples underpinning them. Your logbook may be used as 
a guide to your experience for the purposes of framing 
questions. 

b. Clinical pathology and principles of surgery are exam- 
ined at another table. One examiner poses questions on 
knowledge of basic pathology, the other questions you on 
applied pathology. 

c. Applied physiology and critical care. At the final table 
an examiner with a specialist interest explores your 
knowledge of basic physiology; the surgeon examiner 
tests your clinical knowledge on critical care or other 
acute clinical situations, also assessing your understand- 
ing of the underlying physiological principles. 

2. Questions are constructed to provide a uniform 
approach. They usually start with a fairly straightforward 
lead into the subject so as to focus your mind on the topic. 
Subsequent questions progress to the limits of your 
knowledge before moving on. You may be taken far 
beyond the level set for a pass in order to establish that 



469 



49 




GENERAL CONSIDERATIONS 



you have attained an adequate level of knowledge across 
a range of topics. 

3. The examiners are mostly interested in eliciting what 
you know. They provide as much opportunity as possible 
for you to display it by covering a range of topics. 
Questions are framed carefully and it is vitally important 
that the candidate listens and responds to the question 
asked rather than obfuscating. Much better to admit that 
the answer to a question is not known so that the inter- 
view can move on to other, hopefully more productive / 
areas rather than leaving awkward silences or filling the 
space with irrelevant material. 




Key points 

• Listen to the questions and respond to them. 

• Admit ignorance straightforwardly so that the 
examiner can move to another subject. 

The clinical examination 

1. This tests your ability to examine a patient, elicit the 
appropriate physical signs, discuss their significance and 
formulate a plan of management. It is conducted simul- 
taneously at several centres throughout the UK and you 
are allocated as close as possible to, but not usually at, 
your own hospital. If you had not taken the clinical exam- 
ination for the first time by May 2002, the clinical section 
comprises four bays, in each of which you will spend 
15 minutes. The bays contain cases categorized as follows: 

Bay 1 - Superficial swellings and skin 
Bay 2 - Musculoskeletal and neurological conditions 
Bay 3 - Circulatory and lymphatic conditions 
Bay 4 - Trunk (including thorax). 

2. You are briefed as a group by the supervising exam- 
iner and a member of the examinations department. You 
are then shown to a holding area where the documenta- 
tion is checked. Thereafter you are addressed by number 
to provide anonymity. Following a roll call you are shep- 
herded by examination staff, ready for the bell. When this 
sounds you are introduced to a pair of examiners who 
take you to the bay for examination. 

3. Since time is limited, be prepared to move through 
topics and cases fairly rapidly. The examiners are anxious 
to test the breadth as well as the depth of your knowledge. 




Key points 

Listen closely to the instructions you are given. 
If you are uncertain, ask for clarification. 



• Do not 'short cut' the routine of inspection, 
palpation, percussion and auscultation. 

4. Be prepared to be asked to tell the examiner what 
you are doing, why, what you find and what it means, as 
you proceed. Practise doing this beforehand. The clinical 
problems tend to be straightforward, so concentrate 
initially on common conditions, not rarities. 

5. One examiner takes the lead in directing the examin- 
ation and the other listens, taking notes. 

6. Hand-cleaning facilities are available by the bed or 
nearby but avoid wasting examination time. 

7. A limited number of stations will be based on the 
Objective Structured Clinical Examinations (OSCE) 
format. These test your expertise in clinical examination 
technique. This has been introduced because some candi- 
dates are defective in the correct technique. The format 
has not yet been finalized, but it is likely to comprise a 
station, lasting 3-5 minutes, where you are required to 
perform a task under observation by the examiners. A 
typical test is the examination of a joint or another region. 
A bell rings to finish the interview. The examiners have 
2-3 minutes only to mark you independently, confer, and 
agree a final mark, so leave promptly 

8. You are ushered from the examination. The super- 
vising examiner carries out a short, collective debriefing. 
You may then leave. 

9. You may be given the option of reattending at the 
end of the day to receive your results. If you are success- 
ful, there is a short congratulatory ceremony. 

Communication skills 

1 . This section aims to assess your ability to communi- 
cate effectively with a patient or patient's relatives in a 
typical clinical situation (see Ch. 47). Until the end of 2002 
it focuses on the giving of information; for example, 
informing an anxious relative about the condition of the 
patient, or providing preoperative information to patients 
(see Ch. 14). Subsequently it is intended to pilot a test 
of the candidate's ability to extract information from a 
patient, analyse it and communicate it to fellow pro- 
fessionals. It should provide little difficulty if you have 
occupied a busy training post. 

2. You may wait in a holding room for a maximum of 
three-quarters of an hour as your group is directed, singly, 
into the examination cycle. You enter the reading room to 
be given a vignette - a short character sketch or word 
picture - to read for 5 minutes. It outlines a fairly realistic 
clinical situation in which you, as the SHO, are obliged to 
interview a relative or patient, assess the situation and com- 
municate appropriately. The vignette defines your task. 

3. You are now conducted to the interview room and 
greeted by the two examiners, who introduce you to the 



470 



THE MRCS EXAMINATION 




'patient' or 'relative' by the role-play name. You are now 
in control of the interview. The examiners observe but do 
not intervene. The actor stays in character' throughout 
and is instructed and coached to behave in a typical 
manner in that situation and given an itemized series of 
'Points of Concern' to discuss with you. You will find that 
the atmosphere rapidly ceases to be artificial. 

4. After 10 minutes the interview ends, or before this if 
you are satisfied you have covered the concerns satisfac- 
torily. The examiners then discuss the interview with you. 

5. As yet the format of the new sections is not fixed. 
Probably you will take an observed history from a simu- 
lated patient, followed by a presentation to the examiners. 
You may be asked to prepare a written communication. 
The time allotted to testing communication skills is likely 
to be at least 40 minutes, reflecting the recognition of their 
importance. 



2. At present the examinations conducted by the four 
Royal Colleges of the UK and Ireland are broadly 'equiv- 
alent'. It is hoped that an intercollegiate MRCS can be 
developed. 

3. The curriculum for basic surgical training for the 
English Royal Colleges is intended to integrate in-training 
and external assessments, including the MRCS examin- 
ation. Comprehensive assessments during basic surgical 
training should encourage those with appropriate apti- 
tudes and commitment, and discourage those without the 
essential traits. 

4. It is likely that a certificate of completion of basic 
surgical training (CCBST) will be introduced. 

5. Modern working practice, for example the European 
Working Time Directive, discourages long hours of clini- 
cal work. The required study will need to be undertaken 
out of defined working time. 




Key points 



Read the vignette carefully to determine the 
task you have been set. 
Give the simulated patient accurate 
information and behave in a professionally 
correct manner. 



FUTURE DEVELOPMENTS 

1. The MRCS examination will develop in line with 
accepted good practice in education and in response to 
changes in clinical surgery and assessment techniques. 



Summary 

• Do you appreciate that facts alone are 
insufficient unless they are organized and 
produced to the examiners at the right 
time? 

• Have you practised taking a history, 
examining a patient and interpreting your 
findings until you are confident in your 
clinical skills? 

• Is the scope of your knowledge broad 
enough and sufficiently up to date? 

• Have you fulfilled all the requirements to 
sit the examination? 



471 




The intercollegiate 
examinations in surgery 



R. E. C. Collins 



w 



Objectives 



Provide an introduction to the intentions 
of the examination. 

Display the need to obtain current details 
of your subspeciality examination. 
Outline the conduct of the examination. 



This examination is a serious hurdle. Initially it was 
considered a mere formality but the first candidates had 
received many years of prolonged intensive training. It 
demands an understanding of the syllabus, appropriate 
reading, and capability to respond to questions at con- 
sultant level. You need knowledge of and competence in 
the generality of your speciality subject that fit you to be 
on emergency call. In addition, you must be fully compe- 
tent in your subspeciality interest, in which you might be 
the sole representative in your hospital. 



INTRODUCTION 






The four Royal Colleges of the British Isles have formed 
the Intercollegiate Examinations Board. Each of the 
Specialist Advisory Committees (SAC) in the nine recog- 
nized surgical disciplines have produced their own spe- 
cialty examination. The examination has exposed areas of 
ignorance in some trainees that are a reflection of sub- 
optimal standards of training. The intention is to create a 
higher standard of rigorous annual assessment of all 
trainees, to identify their deficiencies at an earlier stage 
and take corrective action. Meanwhile, there have been 
significant changes to basic surgical training. In 2003, the 
first candidates who have not taken the Primary FRCS or 
Clinical Surgery in General (CSIG) examinations (which 
contained a significant element of basic sciences) take the 
intercollegiate examinations. Inevitably, the intercolle- 
giate examination will evolve to take these changes into 
account. 

A balance will need to be reached between all-round 
surgical competence and the recognition that surgery is 
now practised on an increasingly subspecialist basis. In 
general surgery, for example, candidates may choose to 
have a significant part of their examination devoted to the 
subspeciality they intend to pursue. In some subspecial- 
ties, such as vascular surgery, pressure exists for an exam- 
ination purely in that subject. However, this clashes with 
the need for surgeons to be capable of contributing to an 
on-call rota for emergencies in the generality of surgery. 
It is therefore in that aspect of speciality interest that the 
emphasis is placed in the examination. 



REGULATIONS RELATING TO THE 
INTERCOLLEGIATE SPECIALTY 
EXAMINATION 






These vary from specialty to specialty and also are regu- 
larly updated. You should contact the intercollegiate 
specialty examinations board for up to date details of 
the regulations in your subject. The address is: 

The Intercollegiate Examinations Board 

3 Hill Square 

Edinburgh EH8 9DR 

Tel: 0131 6629222 

Fax: 0131 6629444 

Web site: http://www.intercollegiate.org.uk 

Some regulations are common to all nine SAC subjects: 

1. You must hold a medical qualification recognized for 
qualification by the General Medical Council or the 
Medical Council of Ireland and must have been qualified 
for at least 7 years. 

2. You must satisfy the current requirements for entry 
to an approved higher surgical training programme in 
Great Britain or Ireland. 

3. You must have completed satisfactorily 4 years of 
higher training in the specialty acceptable to the relevant 
board: 

a. If you are a type I trainee, you are training with a 
view to being awarded the Certificate of Completion of 
Specialist Training (CCST) by the Specialist Training 
Authority of the United Kingdom, the Certificate of 



472 



THE INTERCOLLEGIATE EXAMINATIONS IN SURGERY 



50 



Specialist Doctor (CSD) or Specialist Registration with the 
Medical Council of Ireland. You must have enrolled with 
the relevant SAC and completed the above 4 years of 
training within a programme approved by them. You 
need to have satisfactory fourth year clinical assessment 
form(s) covering this year of training, and the appropri- 
ate declaration form signed by the Programme Director, 
b. If you are a type II trainee, you are not eligible for 
the CCST. You need to be registered with the relevant 
SAC and must have spent at least one of the above 4 years 
in a training programme in Great Britain or Ireland 
approved by the relevant SAC. This mandatory clinical 
year must offer experience equating to fourth year level 
within the specialist registrar grade and you must obtain 
written confirmation of this from your trainer. You require 
a satisfactory fourth year clinical assessment form(s) cov- 
ering this year of training and the appropriate declaration 
form signed by the Programme Director. Any other train- 
ing posts completed in Great Britain and Ireland must be 
approved by the relevant SAC in order to count towards 
the examination. If you wish training acquired outside 
Great Britain and Ireland to be taken into consideration, 
you need to present supporting documentation at the 
time of registration with the SAC. 




Key points 

• If you are a type II trainee you are not be 
eligible for the award of a CCST. 

• Passing the examination does not 
automatically entitle you to enter type I 
training. 

4. From 1 January 2003 you will be limited to three 
attempts at the examination, after which you must seek 
specific counselling, retraining where necessary, and 
written support from the Postgraduate Dean and 
Programme Director in order to resit again. Attempts 
prior to January 2003 will not be counted. 



clinical signs. You must then decide upon an appropriate 
course of management pertinent to that patient. In 
urology, on the other hand, there is very limited scope for 
spending much time on clinical examination so there is an 
understandable natural reluctance to expose patients and 
candidates to the evaluation of multiple rectal examin- 
ations. The technical skills required of a neurosurgeon 
clearly differ from those of a general surgeon with an 
interest in hepatobiliary disease. In my judgement, it is 
not only appropriate that there is a difference in exam- 
ination format between the subjects but that such differ- 
ences are actually essential. 

2. Examiners are very concerned to maintain consistent 
standards. You can be confident of having an examination 
and subject content of equal standard to the other candi- 
dates. This has produced much debate within the exam- 
inations boards; it is now common practice for all of the 
questions in oral examinations to be structured and to 
conform to a set pattern. A perceived problem in the clini- 
cal arena is the difficulty of arranging for large numbers 
of candidates to see a large number of similar patients. In 
practice, the clinical examination, particularly of short 
cases, closely mirrors the procedure in an outpatient 
clinic, where we encounter the vagaries of life and vari- 
ances of clinical presentation. The examination tests your 
ability to deal with whatever problem presents. 

3. Recognize that the examination is not an interroga- 
tion on surgical esoterica (Greek esoterikos - eso ~ within; 
revealed to an elect few), but a standard of international 
authority. However, we all encounter some rare condi- 
tions and you must demonstrate your ability to tackle an 
unusual problem sensibly. In many of the specialist sub- 
jects, particularly general surgery, the field and syllabus 
are quite colossal. It is almost impossible to go through 
the day of an examination without coming across a 
subject where one's knowledge or experience is insuffi- 
cient. You must not be unsettled. This is a fact of life in 
consultant practice. The examination is carefully 
designed to balance areas of difficulty with areas of out- 
standing competence or experience. 



THE FORMAT OF THE EXAMINATION 

1 . The format and style of the examinations differ from 
specialty to specialty. Although anxieties have been 
expressed about lack of consistency in such an approach, 
it is apparent that the nature of the different specialties, 
and particularly the clinical material involved, varies 
from subject to subject. Thus in orthopaedics the value of 
a clinical examination with long cases is considered very 
important. You need to be able to talk to an individual 
patient and outline the lifestyle problems and relevant 




Key points 

• Recognize that as a surgeon you must expect 
to encounter unfamiliar problems. 

• As a surgeon you must display common sense 
in difficult circumstances. 

To varying degrees, therefore, each of the examinations 
is composed of essentially two parts: oral examinations 
with two examiners, usually lasting half an hour; and 
clinical examinations with two examiners, again lasting 



473 



50 



GENERAL CONSIDERATIONS 



half an hour. Some of the subjects also have written exam- 
inations that are usually multiple choice. 

4. In all of the oral and clinical tests, examiners are 
instructed to treat you as if you are a consultant colleague 
asked to see an interesting or unusual case. There is room 
for debate, and you will be questioned on management 
strategies, but the examination should never become rude 
or aggressive. Almost without exception the examiners go 
out of their way to make you feel at ease within the 
understandable constraints of the circumstances. 

5. If, however, you feel you have had an unfair or dif- 
ficult experience in any part of the examination, speak to 
the chairman of the examination board, or one of the indi- 
viduals who help organize the examination. You should 
settle any matter of discontent immediately, between 
parts of the examination. You can then start the next part 
in a calm and collected frame of mind, and not carry over 
any frustrations or anxieties that might otherwise 
threaten your subsequent performance. 

6. Take the minimum baggage into the examination. 
Briefcases are not permitted. You need little instrumenta- 
tion for clinical examinations, as it is usually provided. 
Regard the clinical examination as a demonstration of 
your routine skills. Do not start with rare tests that you 
would not normally employ. Concentrate on being thor- 
ough, carrying out appropriate examinations, avoiding 
inappropriate ones. 

7. Be prepared to discuss papers from the literature. 
You may be invited to present some of your own work for 
discussion, usually of how you performed the studies, 
how they relate to previous or subsequent work and how, 
in retrospect, your study could have been improved. You 
may be asked to comment on a paper, usually taken from 
a major journal. Do not, on this account, assume it is 
without fault. The discussion concentrates on the 
strengths and weaknesses of the paper. 

8. Note that statistical method may enter into the 
format. This is not, though, an examination in statistics 
but on your understanding and use of simple statistical 
methodology in the evaluation of scientific work. 

9. The emphasis on basic sciences varies, depending on 
the speciality. Although there is a view that basic science 
teaching and examination belongs to basic surgical train- 
ing, you will be expected to apply relevant, and only 



relevant, basic sciences to your clinical subject. A candi- 
date whose main interest is in upper gastrointestinal/ 
hepatobiliary disease should understand the basic phys- 
iology of digestion and pancreatic secretion, but will not 
be asked the details of the relationships of the thalamus. 



THE END OF THE EXAMINATION 



^.^.;S ; ^£^^^^^ 



~£^^^m?&& 



1. You either fail or pass. No distinction is made 
between a bare pass and high marks. However, in some 
subjects a prize or medal is awarded for outstanding can- 
didates. As a rule you are notified of your result in an 
envelope at the end of the day's examination. If you have 
been successful you are usually invited to celebrate with 
your examiners before departing. If you are unsuccessful 
you do not discuss with the examiners why you have 
failed. This is because early experience showed that 
examiners and failed candidates can become adversarial, 
prejudicing the atmosphere at subsequent examinations 
or consultant appointment interviews. 

2. If you are unsuccessful, you will, in the following 
weeks, receive written details from the chairman on your 
weaknesses, together with advice for the future. If you are 
unsatisfied with your treatment by the examiners you 
may appeal. You can obtain details from the Examinations 
Board in Edinburgh. 

Good luck to all those who undertake the examination. 



Summary 

• Do you know whether or not you are 
eligible to sit the examination? 

• Are you aware of the standard and 
conduct of the examination? 

• Do you recognize that the Colleges owe it 
to the public to pass only those who 
demonstrate competence? 

• Will you accept that the examiners 
appreciate the stress involved and will 
treat you courteously? 



474 




Index 



Page numbers in bold refer to figures or tables. 



Abbreviated Injury Scale (AIS), 45 
ABCDE sequence, 3-8 
Abdominal incisions, 232, 232-233 

mass closure, 232-233, 385 
Abdominal pain, 50 
Abdominal surgery, 356 

postoperative complications, 379 

wound dehiscence, 385 

see also Gastrointestinal surgery 
Abdominal trauma, 25-26 

ultrasound (FAST) assessment, 60 
Abdominal wall trauma, 26 
ABO blood groups, matching, 88 
ABO incompatibility, 101, 352 
Abrasion, 242-243, 246 
Abscess, postoperative, 383 
Absolute risk reduction (ARR), 448 
Acarbose, 73 

Accident and emergency (A & E) 
department 

initial resuscitation, 3-8 

monitoring, 8-13 

secondary survey, 13-18 
Achondroplasia, 419 
Acidaemia, 119 
Acid -base balance, 119-122 

effects of surgery, 318 

interpretation of changes, 120-121 

new insights into, 121-122 

normal saline and, 117 

in resuscitation, 4-5, 10, 10-12 

terminology and definitions, 119-120 

traditional view, 119-121 

treatment of disturbances, 123 
Acid citrate dextrose, 377 
Acidosis, 10, 10, 119-120 

Bohr effect, 12 

compensatory changes, 119-120 

metabolic see Metabolic acidosis 

respiratory, 10, 10 r 119 
Acids, weak, 122 
Acromegaly, 71-72 
ACTH, 30, 315 
Activated partial thromboplastin time 

(APTT), 92, 93, 103, 103, 380 
Activated protein C, 321 
Acupuncture, 359 



Acute lung injury (AU), 34, 318 
Acute normovolaemic haemodilution 

(ANH), 94-95, 103 
Acute pain services (APS), 182, 369 
Acute-phase reactants (APRs), 31, 316, 

317 
Acute-phase response, 314, 316-317 
Acute Physiology and Chronic Health 
Evaluation (APACHE) score, 
147, 167 
Acute renal failure, 41, 378, 394-395, 401 
Acute respiratory distress syndrome 
see Adult respiratory distress 
syndrome 
Acute tubular necrosis, 394 
Addiction, 78, 366, 408 
Addisonian crisis, 15 
Addison's disease, 72 
Adenomatous polyposis coli (familial 
adenomatous polyposis, FAP), 
262, 420-421, 421 
Adenosine, 68 

ADH see Antidiuretic hormone 
Adhesions, intra-abdominal, 233 
Adjuncts to surgery, 199-205 
Adjuvant therapy, 269, 288 
Adolescents, consent issues, 158-159 
Adrenal gland disorders, 72 
Adrenaline (epinephrine) 
in arrhythmias, 69 

in local anaesthesia, 181, 181, 353, 363 
in response to injury, 30, 31-32, 314 
Adrenocortical hyperfunction, 72 
Adrenocortical insufficiency, 72, 315 
Adrenocorticotrophic hormone (ACTH), 

30, 315 
Adult respiratory distress syndrome 
(ARDS), 34, 34, 318 
in massive transfusion, 104 
postoperative, 381 
Advance directives, 160 
Advanced life support, 6-7, 7 
Advanced Trauma Life Support (ATLS), 

3,8 
Adverse incidents (occurrences) 
analysing and correcting, 432 
reporting, 183, 229, 438 



screening, 431 

see also Audit 
Advice, giving, 460 
Adynamic (paralytic) ileus, 318, 356 
Affective disorders, 78 
Afterload, 390 

Agammaglobulinaemia, primary, 85 
Aggressive behaviour, 460 
Agitation 

in respiratory distress, 394 

terminal, 413 
AIDS see HIV infection/ AIDS 
Air conditioning, 184 
Air filters, 184, 209 
Air flow systems, theatre see Ventilation 

systems, theatre 
Airway 

assessment, in primary survey, 4 

inhalational injury, 44 

management 

in initial resuscitation, 4 
postoperative, 349 

obstruction, 14, 354-355 

trauma, 22 
Albumin, 107 

plasma, 76, 76, 125 

in hypovolemia, 113-114, 114 
response to injury, 320 

solutions, 100, 115, 116 
Alcohol misuse (alcoholism), 78, 263 

head injury, 13 

hypoglycaemia, 13 
Aldosterone, 32, 315 
Aldosteronism, 72 
Algorithms, 148 
Alkalaemia, 119 
Alkalosis, 10, 10, 119-120 

compensatory changes, 119-120 

metabolic, 10, 11, 119 

respiratory, 10, 10, 119 
Alkylating agents, 287 
Allodynia, 405 
Allografts, 87-88, 249 

rejection see Rejection, graft 
Alloy implants, 203 
Alopecia, chemotherapy-induced, 291 
a-adrenergic blockers, 72, 170 



475 




INDEX 



a-fetoprotein (AFP), 88 

in germ cell tumours, 303-304, 304 

in hepatocellular carcinoma, 307 
Alveolar gas exchange, failure, 14 
American Society of Anesthesiologists 

(ASA) score, 147, 167, 168 
Amethocaine, 180, 181 
Amino acids, 319, 328 
Aminoglycoside toxicity, 376 
Amniotic membrane, 200 
Amphiarthroses, 337 
Amyloid disease, 401 
Anaemia, 74-75 

of chronic disease (ACD), 91 

classification, 91 

genetic disorders, 419 

oxygen dissociation curve and, 12 

postoperative, 105 

preoperative assessment, 91-92 
Anaesthesia, 174-182 

assessing fitness for, 54 

general see General anaesthesia 

regional, 180-181, 182, 363-365 

total intravenous (TIVA), 177 
Anaesthetic agents 

intravenous, 174, 174-175 

volatile, 176, 176-177, 178 
Anaesthetist, 174 

acute pain services, 369 

premedication, 1 72-1 74 

preoperative assessment, 172 
Analgesia 

of anaesthesia, 178 

in chronic and terminal illness, 
406-409 

pain ladder, 179 

patient-controlled (PCA), 362 

postoperative, 179, 351, 360-366 

pre-emptive, 179, 181-182, 365 

recent advances, 181-182 

in terminal phase, 413 

three-step regimen, 406 

topical, 180, 181 
Analgesics, 360-363 

premedication, 173, 173, 178 

relative efficacy, 363, 363 

sites of action, 358, 358 

see also specific agents 
Anaphylactic shock, 14, 101, 390 
Anastomotic leakage, 384 
Anastrozole, 292 

Anatomico-pathological grid, 51, 51 
Anger, 404 
Angina, 374 

unstable, 65, 66 
Angiogenesis 

tumour, 261-262 

in wound healing, 245, 324 
Angiography, intraoperative,, 196 
Anion gap, 121 
Anorexia, in cancer, 409-410 
Anterior cruciate ligament, 334, 335 
Antiandrogens, 293, 293 
Antibiotics 

adverse effects, 375-376 

antitumour, 287 



control of resistant organisms, 207-208 

preoperative, 166-167 

prophylaxis, 166-167, 212-213, 
382-383 

resistance, 207, 375 

resistant organisms, 208 
Antibodies, 83 

binding region, 83 

deficiencies, 85 

monoclonal see Monoclonal antibodies 

polyclonal, 84 

structure and synthesis, 84, 84 
Antibody-dependent cellular 

cytotoxicity (ADCC), 84 
Antibody-mediated immunity, 83-85 

deficiency, 85 
Anticholinergic drugs, 173, 173-174 
Anticholinesterase drugs, 78 
Anticoagulants, 93 

concurrent therapy, 80, 165 

thromboprophylaxis, 167, 380 

in venous thromboembolism, 380 

see also Heparin; Warfarin 
Anticonvulsant drugs, 77 
Antidiuretic hormone (ADH, 
vasopressin) 

deficiency, 72 

response to surgery, 315 

in trauma, 30, 32 
Antiemetic drugs, 410-411, 411 
Antifibrinolytic agents, 105 
Antigen-presenting cells (APCs), 85, 86 
Antigens 

recognition, 85-86 

tumour, 88 
Antiglobulin test, indirect, 94 
Antihypertensive therapy, 66 
Antilymphocytic globulin (ALG), 88, 251 
Antimetabolites, 287 
Antioestrogens, 292, 293 
Antisepsis, 183-184, 208-212 
Antiseptics, 210, 211 
Antithymocyte globulin (ATG), 88 
Antithyroid drugs, 170 
Anxiety 

in chronic and terminal illness, 
403^04 

perioperative, 78, 172, 314 
Anxiolytic drugs, 172-173, 173 
Aorta 

dissecting thoracic, 14 

traumatic injuries, 22, 26 
Aortic aneurysm, abdominal, 14, 426 
Aortic stenosis, 67-68 
APACHE score, 147, 167 
Apoptosis, 245, 259, 260 

avoidance by cancer cells, 261 

in surgical trauma, 317 
Aprotinin, 104 
Arachnoid mater, 23, 23 
ARDS see Adult respiratory distress 

syndrome 
Arginine vasopressin (AVP) see 

Antidiuretic hormone 
Argon beam coagulator, 195, 195 
Argon lasers, 188, 189 



Armed conflict, 226 
Aromatase inhibitors, 292, 293 
Arrhythmias, 68-70 

cardiac output and, 389 

in massive transfusion, 104 

risk of surgery, 374 
Arterial blood gases, 10, 121 

interpretation, 120-121, 122-123 

postoperative monitoring, 350 

in resuscitation, 4-5, 10-12 
Arterial trauma, 27-28 
Arthroscopy, 238 
ASA score, 147, 167, 168 
Ascites, 76, 77, 378 
Asepsis, 208-212 
Aspiration of gastric contents, 13, 176, 

356 
Aspirin, 360 

postoperative bleeding problems, 98, 
105 

preoperative cessation, 90, 93, 165 
Assisted ventilation, 393-394 

in myasthenia gravis, 78 

in resuscitation, 4 
Asthma, 70 
Asystole, 14 
Atelectasis, 381,409 
Atherosclerosis, 374 
Atracurium, 178 
Atrial fibrillation, 68 
Atrial flutter, 8, 68 

Atrial natriuretic peptide (ANP), 31 7 
Atrioventricular (AV) heart block, 69 
Atropine 

in heart block, 69 

for nerve gas poisoning, 17 

premedication, 173, 174 

in recovery phase, 1 79 
Audit, 142, 428-436, 437^38 

in American surgical practice, 431-433 

attitudes to, 429-430 

clinical, 428^29, 430, 438 

committee, 430 

comparative, 431 

computers, 433-434 

criterion, 431 

cycle, 434, 434-435 

definitions, 428^29 

educational component, 434 

ethics and confidentiality, 433 

implementing change, 434—435 

infection, 213 

medical, 429, 437^138 

methods, 430-434 

national, 431 

outcome, 431 
Autoclaving, 201, 211 
Autocrine actions, 325 
Autografts, 249 
Autoimmunity, 83, 87 
Autonomic neuropathy, diabetic, 73 
Autotransplantation, 87 
AVPU mnemonic, 8, 35 
Avulsion injuries, 243 
Axes, joints, 337, 337 
Axonotmesis, 40, 341 



476 



INDEX 




Axons, 27 

Azathioprine, 87, 88, 251-252, 252 



Bacteria, gut translocation, 126, 127, 318 
Bacterial infections 

in antibody deficiencies, 85 

transfusion-transmitted, 102, 102 
Bad news, imparting, 460^62 
Bag-valve-mask ventilation, 4 
Bariatric surgery, 374 
Barium imaging, 60 
Baroreflex, in trauma, 30 
Base excess (BE) (or deficit), 10, 11-12, 
120, 121 

standard (SBE), 120, 121 
Basilic vein, cutdown, 5 
Battery, 157 
Bcl-2 gene family, 261 
BCR-ABL fusion protein, 294, 295 
Beards, 209 
Beevor's sign, 39 
Benefits, measurement, 443 
Benign prostatic hypertrophy (BPH), 

306, 307 
Benzodiazepines 

induction of anaesthesia, 174, 175 

overdose, 15 

premedication, 173, 173 
Bereavement, 413 
(^-microglobulin, 308 
Beta-blockers, 65, 170, 320 
Bias 

lead time, 423, 456 

length, 423 

publication, 450-451 

spectrum, 447 
Bicarbonate 

buffer system, 10, 120 

concentration ([HC0 3 ]), 120, 121 

standard (SBC), 120, 121 

therapy see Sodium bicarbonate 
Biliary atresia, 254 
Biliary obstruction, malignant, 268 
Biliary stenting, preoperative, 169 
Biliary surgery 169-170 
Biliary tree, trauma, 25 
Bilirubin, serum, 76 
Biological anticancer therapy, 293-295, 

294 
Biomechanics, traumatic injury, 19-21 
Biopsy, 58 

image-guided, 62 

sentinel lymph node (SLNB), 267-268 

tumour, 266 
Bladder cancer, 297 
Bladder trauma, 26 
Blalock, Alfred, 112 
Blast injuries, 21, 21, 25 
Bleeding see Haemorrhage /bleeding 
Bleeding disorders, 75, 93 

postoperative assessment, 105 

preoperative assessment, 92-93 

see also Coagulation disorders 
Bleeding time, 92 
Bleomycin, pulmonary toxicity, 291-292 



Blinding, in clinical trials, 448 
Blood 

crossmatching, 94 

grouping and compatibility testing, 
94, 96-97 

intra- and postoperative salvage, 94, 
103-104, 192 

order schedules (SBOS/MBOS), 94 

postexposure measures, 219-220 

preoperative autologous deposit 
(PAD), 90, 95 

procedures with risk of contact, 218 

products for transfusion, 95-96, 96, 
118 

reducing exposure to, 219 

spillages, 212, 218 

uncrossmatched, 95 

whole, 93, 97 
Blood component therapy see Blood 

transfusion 
Blood disorders see Haematological 

disorders 
Blood gases, arterial see Arterial blood 

gases 
Blood /gas partition coefficient, 176 
Blood loss, 117-118 

quantification, 103, 118 

reducing intraoperative, 104 

see also Haemorrhage/ bleeding 
Blood pressure (BP) 

collapsed patient, 8-9 

determinants, 389 

in renal dysfunction, 395 

in shock, 5 

see also Hypertension; Hypotension 
Blood tests, 57 

Blood transfusion (blood component 
therapy), 95-100, 117-118 

autologous, 94-95, 103-104, 192 

avoiding, 94 

complications, 100-103, 101, 352, 376 

disadvantages, 91, 117-118, 118 

elective surgery, 93-94 

emergency surgery, 95 

errors, 100-101 

future directions, 105 

immune complications, 101, 377 

incompatible, 101, 352, 376-377 

indications, 97-98 

intraoperative, 103-105 

massive, 98, 104, 118, 377 

in open heart surgery, 104-105 

postoperative, 105, 352 

preoperative, 74 

preoperative arrangements, 93-95 

in prostatic surgery, 105 

refusal, 160, 161, 163 

in sickle cell disease, 92 

transmission of disease, 99, 102, 102,, 
377 
Blow-out fractures, 24 
B lymphocytes, 83-84, 86 f 87 

clonal expansion, 83 

deficiencies, 85, 87 
Body fluids 

electrolyte content, 115 



postexposure measures, 219-220 

preventing exposure to, 13, 218, 219 

procedures with risk of contact, 218 

spillages, 212, 218 

transmitting blood-borne viruses, 217 
Body temperature 

monitoring during resuscitation, 9 

oxygen dissociation curve and, 12 

postoperative changes, 317 

postoperative monitoring, 350, 355 

response to injury, 30, 314 
Bohr effect, 12 

Bomb blast injuries, 21, 21, 25 
Bone, 331, 342-348 

adult, 343-344 

blood supply, 346 

cancellous, 343 

healing, 39, 327-328, 346 
after fixation, 347 
electrical stimulation, 345 
small defects, 344 

immature, 343 

implants, 346-347 

mechanical stress, 344 

metastasis, 279, 346 

necrosis, 327 

neoplastic lesions, 345 

pain, 405, 408 

remodelling, 328, 344 

surgical procedures, 344-345 

trauma see Fractures 

woven, 327, 328 
Bone (acrylic) cement, 204, 348 
Bone marrow failure 

blood component therapy, 97-98 

cytotoxic drug-induced, 290-291 
Bone marrow transplantation, 

allogeneic, 88 
Bovine spongiform encephalopathy 

(BSE), 102 
Bowel obstruction, 169 

fluid replacement, 111 

in terminal illness, 411-412, 412 
Bowel preparation, 169, 382 
Bowel trauma, 25, 26 
Bowen's disease, 241, 244 
Bradycardia, suxamethonium-induced, 

175 
Bradykinin, 316 
Brain injury 

contra coup, 36-37 

diffuse axonal injury, 36-37 

primary, 36 

secondary, 36 

traumatic, 34-37 
Brain metastases, 279 
Brainstem herniation (coning), 23, 35 
BRCA-1 and BRCA-2 genes, 262, 421, 

421 
Breast cancer, 265 

familial, 421, 421 

molecular grading, 266 

non-surgical treatment, 292, 295-296, 
296, 297 

screening, 425, 426 

spread, 267 



477 




INDEX 



Breast cancer (cont.) 

surgical management, 267 

tumour markers, 307-308 
Breast implants, silicone, 204 
Breathing 

assessment, primary survey, 4 

management, in resuscitation, 4-5 

postoperative monitoring, 349, 
367-368 
British National Formulary (BNF), 131, 

133,135 
Bronchitis, chronic, 70-71 
Bronchogenic cancer see Lung cancer 
Bronchospasm, 70, 355 
Brown-Sequard syndrome, 39 
Bruton's disease, 85 
Buffers, 120 
Bupivacaine, 180, 181, 363-364 

maximum dose, 353, 363 
Buprenorphine, 179, 362 
Burns, 20-21, 42-45, 243-244 

assessment, 244 

chemical, 43 

depth, 43 

diathermy, 187-188, 243 

electrical, 20-21, 43, 243 

full thickness, 43, 244 

metabolic response, 31 

mustard gas, 17 

partial thickness, 43, 244 

shock, 42^3 

superficial, 43 

toxic shock syndrome, 43-44 



CA 15-3, 307-308 

CA 19.9, 304 

CA 50, 304 

CA125, 305-306, 308,426 

Cachexia, cancer, 378 

Calcitonin, 308 

Calcitonin gene-related peptide, 308 

Callus, 39, 327-328, 346 

Camptothecins, 287 

Cancer, 265-270 

adjuvant therapy, 269 

advanced incurable see Terminal 
illness 

anorexia, 409-410 

biological therapy, 293-295, 294 

cachexia, 378 

chemotherapy see Chemotherapy 

communication with patients, 299 

curative (Rq) resection, 266 

evaluation of new drugs, 300, 300 

genetic susceptibility, 262, 417, 420, 
420-422 

hormone therapy, 292-293, 293 

immunology, 88 

investigations, 54 

minimal access surgery, 239 

multidisciplinary approach, 269-270, 
289 

non-surgical treatment, 295-299 

pain, 405, 409 

palliative surgery, 268 



pathogenesis, 259-264, 420 

pathological diagnosis/grading, 266 

postoperative complications, 378 

preoperative assessment, 265-266 

radiation-induced, 281-282 

radiosensitivity, 273 

radiotherapy see Radiotherapy 

reconstructive surgery, 269 

recurrence, 268 

response evaluation (RECIST) criteria, 
289-290 

secondary, 268 

second tumours after, 281-282, 292 

spread, 266-268 

staging, 54, 266 

statistics, 265 

surgical management, 266-269 

symptoms in advanced, 404, 404-405 

see also specific types 
Cancer family syndrome, 422 
Cannulae, 202 
Capecitabine, 297 
Capillary membrane, 107-110 
Capillary refill time, 9 
Carbimazole, 170 
Carbohydrate metabolism, in response 

to injury, 30, 31,319 
Carbon dioxide (CO2) 

in acid-base balance, 120 

tension (partial pressure) 
arterial see PaC0 2 
end- tidal, 10-11 

total (TC0 2 ), 120, 121 
Carbon dioxide (C0 2 ) lasers, 188-189 
Carbon fibre, 203 
Carbonic acid, 120 
Carbonic anhydrase, 120 
Carbon monoxide 

poisoning, 16, 44 

in smokers, 70 
Carboxyhaemoglobin, 44, 70 
Carcinoembryonic antigen (CEA), 88, 

268, 304-305 
Carcinogenesis, 259-264, 420 

abnormal cell cycle control, 260, 
260-261 

chemotherapy-induced, 292 

genetic damage, 262-263 

Knudson's two-hit hypothesis, 263, 
263, 420 

multi-step pathway, 263, 263 
Carcinogens, chemical, 262, 262 
Carcinoid tumours, 308 
Cardiac arrest 

acid-base balance, 11-12, 123 

resuscitation, 6-8 
Cardiac index, 113, 168 
Cardiac massage 

external chest compressions, 6 

internal, 7-8 
Cardiac output, 112, 113 

determinants, 389-390 

response to surgery, 318 
Cardiac tamponade, 22 
Cardiac transplantation, 79, 253-254, 255 
Cardiogenic shock, 14, 32, 390 



Cardiomyopathies, 68, 68 
Cardiopulmonary bypass (CPB), 104-105 
Cardiopulmonary resuscitation (CPR), 

6-8 
Cardiotoxicity, cytotoxic drugs, 291 
Cardiovascular disease, 65-70 

age-related risk, 373, 373 

fluid management, 113 

preoperative preparation, 167 

risks of surgery, 374, 374-375 
Cardiovascular risk assessment, 65 
Cardiovascular system 

effects of pain, 359 

pathophysiology in critical illness, 
389-391 ' 

response to fluid deficits/ 112-113 

response to injury, 32-33, 314, 318 

see also Circulation 
Carotid pulse, 5, 6 
Cartilage, articular, 339-340 
Catecholamines, 30, 314 

see also Adrenaline 
Catgut, 201, 202 
Catheters, 202 
Caudal epidural block, 365 
Cavitron UltraSonic Aspirator (CUSA), 

194 
CD3, 86 

CD4 T helper cells, 86, 86, 216 
CD8 cytotoxic T cells, 85, 86 
CEA see Carcinoembryonic antigen 
Celecoxib, 361 

Cell adhesion molecules (CAMs), 261 
Cell cycle control, 259-260, 260 

abnormal, 260-261 
Cell division, cytotoxic drug actions, 

285, 285 
Cell-mediated immunity, 85-87 

deficiency, 86-87 
Cell membrane, 108-109 
Cell proliferation, in wound healing, 

322, 323-324 
Cell salvage, autologous, 94, 103-104, 

192 
Censored observations, 450 
Central nervous system 

infections, 15 

wound healing, 328 
Central venous cannulation, 5-6 
Central venous pressure (CVP), 112-113, 
389-390 

monitoring during resuscitation, 9-10 
Centre for Reviews and Dissemination, 

York, 139, 451 
Centromere, 417 
Cephalosporins, 167 
Cerebellar herniation, 36 
Cerebral oedema, in head injury, 35 
Cerebral perfusion pressure (CPP), 35 
Certificate of completion of basic 

surgical training (CCBST), 468, 
471 
Certificate of Completion of Specialist 

Training (CC5T), 472-473 
Certificate of Specialist Doctor (CSD), 
472-473 



478 



INDEX 



Cervical cancer, 298, 308 

screening, 425, 426 
Cervical spine 

immobilization, 3-4, 13 

injuries, 37, 37 
Chance fracture, 19 
Change 

implementing, 140, 140-142, 434-435 

individual, 141, 141 

organizational, 141, 141 
Charnley, Sir John, 348 
Charnley exhaust gown, 200, 208 
Charnley tent, 184 

CHART (continuous hyperfractionated 
accelerated radiotherapy), 
275 
Chemical burns, 43 
Chemical weapons, 17 
Chemotherapy, 284-301 

adjuvant, 269, 288 

clinical assessment of response, 
289-290 

combination, 288 

evaluation of new drugs, 300 

highly sensitive tumours, 298-299 

immune effects, 87 

intra -arterial, 289 

intrathecal, 289 

neoadjuvant, 288 

in osteosarcoma, 270 

palliative, 288 

performance status and, 290 

principles, 284-290 

risks of surgery after, 376 

timing, 288 

toxicity, 290-292 

see also Cytotoxic drugs 
Chest 

flail, 4, 22 

incisions, 233 

trauma, 21-22 
Chest compression, external, 6 
Chest drains, 353 
Chest wall trauma, 21-22 
Chilblains, 244 
Children 

consent, 158-159 

drug prescribing, 134 

organ transplantation, 253, 254 

postoperative analgesia, 366 

preoperative preparation, 166, 170 

resuscitation, 5 

water requirements, 109-110, 110 
Child's grading of liver disease, 76, 76 
Chitosan, 200 

Chlorhexidine gluconate, 210 
Chlorpropamide, 73 
Cholangiography, intraoperative, 

195-196 
Cholangitis, acute, 169 
Cholecystectomy, laparoscopic, 239, 

378-379 
Choriocarcinoma, 299, 303 
Chromatolysis, 40, 328 
Chromosomal disorders, 417 
Chromosomes, 417 



Chronic illness, 402-414 

communication, 403 

definition, 402 

emotional reactions, 403-404 

symptom control, 404-412 
Chronic obstructive airways disease 
(COAD), 70-71, 170 

oxygen therapy, 393 

resuscitation, 5 
Ciclosporin, 87, 88, 251, 252, 376 

side-effects, 252 
Circulation 

assessment, 5 

postoperative care, 349-350 

in primary survey, 5-8 

traumatic injuries, 22 

see also Cardiovascular system 
Circulatory overload, 103 
Cirrhosis, 76-77, 170 
Cisatracurium, 178 
Cisplatin, 291 
Clean air enclosures, 199 
Clean-contaminated operations, 166, 206 

antibiotic prophylaxis, 212-213 
Cleaning, 210-211 
Clean operations, 166, 206 

antibiotic prophylaxis, 166, 212 

postoperative infections, 382 
Clinical effectiveness, 139, 438 
Clinical examination, 51-52 

intercollegiate specialty examination, 
473, 474 

MRCS examination, 467, 468, 470 

objective structured (OSCE), 468, 470 
Clinical governance, 437-441 

components, 438^140 

reporting outcomes, 438 

scope, 438 
Clinical skills, 146-147 
Clinical trials, 132, 300 

see also Randomized controlled trials 
Clips, 201-202, 234 
Clostridium difficile, 208, 376 
Closure, 246-247 

abdominal incisions, 232-233, 385 

factors complicating, 246 

no skin loss, 246 

primary, 246 

skin, 202, 234 

in skin loss, 246-247 

surgical incisions, 231-232, 246 
Clothing 

protective, 218, 218 

theatre, 184, 199, 200, 208-209 
Clotting see Coagulation 
Coagulation, 323 
Coagulation disorders, 15, 33, 75 

blood component therapy, 98, 99 

in chronic liver disease, 77 

inherited, 419 

in massive transfusion, 104 

postoperative, 320 

postoperative haemorrhage, 386 

preoperative assessment, 92-93 

preoperative management, 169 

risks of surgery, 377 



see also Bleeding disorders 
Coagulation factors 

concentrates, 100 

in fresh frozen plasma, 99 

in obstructive jaundice, 377 
Cocaine, 180, 181 
Cochrane Collaboration, 139 
Cochrane Library, 451 
Codeine, 179, 407 
Coeliac disease, 87 
Coexisting disease, 64-81 

drug therapy, 80, 80 

evaluation, 54 

management aims, 65 

preoperative preparation, 167-168 

see also specific diseases 
Cold, common, 170 
Cold injury, 243-244 
Colic, 408, 412 
Collagen, 332 

in wound healing, 245, 324 
Collapse 

causes, 14-15 

diagnosis of cause, 13-16 

initial resuscitation, 3-8 

monitoring, 8-13 
Colleagues, 460 
Collodion, 204 

Colloid osmotic pressure (COP), 107-108 
Colloid solutions, 109, 115-117, 116 

electrolyte balanced, 117 
Colonic anastomoses, leakage, 384, 384 
Colonic pseudo-obstruction, 356 
Colonic trauma, 26 
Colonoscopy, screening, 424 
Colony stimulating factors (CSFs), 294 
Colorectal cancer, 265 

adjuvant therapy, 269, 297 

genetic model for development, 420 

hereditary, 421-422 

local invasion, 267 

metastases, 267, 268 

non-surgical treatment, 297 

palliative surgery, 268 

recurrent, 268 

risks of blood transfusion, 377 

screening, 424^125, 426 

tumour markers, 304-305 
Colostomy, 169 
Coma 

causes, 35 

pupil size and responses, 8, 9 

resuscitation, 3-8 

see also Consciousness, altered level 
Commission for Healthcare Audit and 

Inspection (CHAD, 440 
Commission for Health Improvement 

(CHI), 440 
Common variable immunodeficiency 

(CVID), 85 
Communication, 458-462 

cancer patients, 299 

with colleagues, 460 

consent aspects, 160, 163 

imparting bad news, 460-462 

non-verbal, 458-459 



479 




INDEX 



Communication (cont.) 
with patients, 459— £60 
with relatives, 460 
skills, MRCS examination/ 467, 

470-471 
in terminal illness, 299, 403 
in terminal phase, 413 
verbal, 458 
Comorbidity see Coexisting disease 
Comparative statistics, 452, 456 
Compartments, limb, 28, 334, 335 

pressure monitoring, 40-41 
Compartment syndrome, 13, 40, 40-41, 
334 
pathogenesis, 40, 336 
Competence, clinical, 225 
Complaints, 229 
Complementary therapy, 409 
Complement deficiency, 83 
Complement system/ 82 
Complete response (CR), 289 
Complexity theory, 144 
Compliance, screening, 426 
Complications see Postoperative 

complications 
Compression forces, 19 
Compression stockingS/ graduated 

(GCS), 167, 451, 451-452 
Computed tomography (CT), 60-61 
interventional, 62 
intraoperative, 62 

three-dimensional reconstruction, 63 
Computers 

in clinical audit, 433-434 
for diagnosis, 49 
Concussion, 36 
Confidence intervals, 449, 452 
Confidentiality, 162-163, 433, 464 
Conflict, armed, 226 
Conflicts of interest, 228 
Conformal radiotherapy, 274, 275 
Congenital abnormalities, 373, 420 7 426 
Congenital heart disease, 66-67 
Coning, 23, 35 
Connective tissue 
genetic disorders, 419 
response to trauma and surgery, 331, 

332-337 
trauma, 331-332 
Conn's syndrome, 72 
Consciousness, 35 
altered level 
blood glucose estimation, 13 
causes, 35 

in critical illness, 395 
resuscitation, 3-8 
secondary survey, 13, 16 
in shock, 5 
in trauma, 35, 36, 37 
see also Coma; Unconscious patients 
Consent (including informed consent), 
155-164 
children, 158-159 
confidentiality and, 162-163 
implied, 157 
legal aspects, 157-159 



in mental handicap, 159 

moral aspects, 155-156 

in practice, 156, 159-161, 166 

in psychiatric illness, 159 

surgical research, 161-162 

unconscious patient, 158, 161 
Consent form, 156, 157 
Constipation, 408, 412 
Contaminated operations, 166, 206 

antibiotic prophylaxis, 167, 212-213 
Continuing professional development, 

439 
Continuous hyper fractionated 
accelerated radiotherapy 
(CHART), 275 
Continuous positive airway pressure 

(CPAP), 393 
Contra coup injury, 36-37 
Contractility, myocardial, 390 
Contractures, 234, 409 
Contrast radiology, 58, 59, 60 
Contusion, 19, 242 
Convection, 399, 399 
Coombs' test, 97 
Coronary artery disease, 65-66 

in diabetes, 73 

preoperative preparation, 170-171 
Corticospinal tract, 38, 38 
Corticosteroid (steroid) therapy, 80 

in chronic and terminal illness, 409, 
410, 412 

immune effects, 85, 87, 376 

risks of surgery, 376, 379 

side-effects, 252 

transplant recipients, 251-252 
Corticotomy, 347 
Cortisol, 30, 31-32, 315 
Cosmetic aspects, incisions, 231 
Cost effectiveness, 146, 442-443 

in clinical practice, 443-444 

measurement, 442, 443 
Costs 

drugs, 133 

investigations, 55, 443 

measurement, 443 

minimal access surgery, 239, 443 

organ transplantation, 255 

screening, 427, 443 
Counselling 

bereavement, 413 

preoperative, 359 
Craniospinal irradiation, 278 
Crash induction, 175-176 
Creatinine, serum, 400 
Creutzfeldt-Jakob disease (CJD), 211 

variant (vCJD), 95, 99, 102, 211 
Cricoid pressure, 176 
Cricothyroidotomy, 4, 355 
Criterion audit, 431 
Critical appraisal, 142, 454-457 
Critical care see Intensive care 
Crohn's disease, 87 ', 169 
Crush syndrome, 41 
Cryoprecipitate, 75, 99 
Cryosurgery (cryotherapy, cryocautery)/ 
192-194, 193, 244 



Crystalloid solutions, 110, 111, 117 

Cullen's sign, 26 

Curare, 177 

Cushing's reflex, 35 

Cushing's syndrome (adrenocortical 

hyperfunction), 72 
Cyanide poisoning, 16, 44-45 
Cyanoa cry late tissue glues, 204, 234 
Cyanosis, postoperative, 354-355 
Cyclizine, 412 
Cyclo-oxygenase, 360-361 
Cyclo-oxygenase (COX) 2 inhibitors, 1 73, 

178,179,361 
Cyclotrons, 272 
Cytochrome P450 (CYP450) enzymes, 

136 
Cytokeratins, 308 
Cytokines, 82, 86 

recombinant, cancer therapy, 293-294 

in response to injury, 314, 316 

in wound healing, 326-327 
Cytology, 58 
Cytotoxic drugs, 285-292 

administration, 289 

classification, 286, 287 

fractional cell killing, 286 

likelihood of cell killing, 288 

mechanisms of action, 285, 285, 286 

resistance mechanisms, 288 

risks of surgery and, 376 

routes of administration, 289 

toxicity, 290-292 
Cytotoxic T cells (CD8), 85 f 86 



Dacron, 203 

Dantrolene, 419 

Data analysis, surgical logbook, 465 

Data collection 

by hospitals, 465 

surgical logbook, 463-464 
Data protection, 464-465 
Daycase surgery 

postoperative analgesia, 351, 366 

postoperative care, 353-354 
D-dimer assay, 380 
Deafferentation pain, 405 
Debridement, 245-246 
Deceleration injuries, 19, 20 
Decision making, 144-151 

aids to, 146-147 

in emergencies, 146 

essentials, 145-146 

in intensive care, 388-389 

obstacles to good, 146 

patient participation/ 145-146, 460 

risk management, 147 
Decisions 

codified, 14&-149 

expected, 149-150 

types, 148-150 
Decision trees, 148, 148 
Decontamination, 210 
Deep vein thrombosis (DVT), 380-381 

complications, 380-381 

diagnosis, 380 



480 



INDEX 



in orthopaedic surgery, 379 

prophylaxis see Thromboprophylaxis 

risk factors, 167 

treatment, 380 
Defence reaction, 29, 29-30 
Defibrillation, 6-7 

internal, 8 
Degloving injuries/ 243 
Dehydration 

assessment of fluid deficit, 112-113 

fluid management, 111-112 

in terminal illness, 410 
Dendritic cells, 83, 86 
Denial, 404 
Depression, 78, 404 
Dermis, wound healing events, 324 
Dermoid cysts, implantation, 324 
Desflurane, 176 r 177 
Desmopressin (DDAVP), 104 
Despair, 404 
Dexamethasone, 412 
Dextrans, 100, 115-117, 116 
Dextrose solutions, 111 
Diabetes insipidus, 72 
Diabetes mellitus, 72-74 

chronic complications, 73 

kidney and pancreas transplantation, 
253, 254 

postoperative care, 350 

risks of surgery, 375 

surgical regimens, 73, 73-74 

vascular surgery, 171 

wound healing, 242, 245, 329, 
375 
Diabetic ketoacidosis, 375 
Diabetic nephropathy, 375 
Diabetic neuropathy, 73, 342 
Diagnosis, 51, 52 

clinical, 49-52 

computer, 49 

examination, 51-52 

gold standard test, 445^46 

history, 49-51 

investigations, 51, 52, 53-54 

not made, 52 

'pay-off/ 51 

radiological techniques, 62 

statistical analysis, 445-447, 446 
Dialysis, 76, 398^01 

indications, 400 

long-term effects, 401 

methods, 400-401 

principles, 398-400, 399 

see also Haemodialysis; Peritoneal 
dialysis 
Dia morphine 

in chronic and terminal illness, 407, 
407,412,413 

postoperative analgesia, 179 

premedication, 173 

routes of administration, 361, 362 

side-effects, 408 
Diaphragm, traumatic injury, 25 
Diaphysis, 343 

Diarrhoea, enteral feeding and, 129 
Diarthroses, 337 



Diathermy, 185-188 

bipolar, 186, 186 

burns, 187-188,243 

cutting, coagulation and blend, 186 

earth-referenced generators, 186 

isolated generators, 186-187 

in laparoscopic surgery, 188, 379 

monopolar, 186, 186 

pacemakers and, 70, 1 88 

patient plate, 186, 187 

safety, 187-188 
Diazepam, 173 

Diethyl ether (ether), 173, 176, 176 
Diets 

disease-specific, 128 

enteral, 128, 396 

polymeric, 128 

predigested or elemental, 128 
Diffuse axonal injury (DAI), 36-37 
Diffusion, 398-399, 399 
DiGeorge syndrome, 86-87 
Digoxin, 67 
Dihydrocodeine, 407 
2,3-Diphosphogly cerate (2,3-DPG), 12, 

97,377 
Diplopia, 24 
Dirty wounds, 206 
Disability, in primary survey, 8 
Disinfectants, chemical, 211 
Disinfection, 210-211 

endoscopes, 192, 203, 211 
Disposable accessories, 202 
Disposable clothing, 184, 200 
Dissection techniques, in minimal access 

surgery, 239 
Disseminated intravascular coagulation 

(DIC), 33, 99, 105 
Diving injuries, 28 
DNA,417 
DNA damage 

in cancer pathogenesis, 260, 262-263 

cytotoxic drug-induced, 285, 285 

radiation-induced, 272, 273 
DNA repair, 263, 422 
DNA synthesis, 260, 260 

cytotoxic drug actions, 285, 285 
Dominant inheritance, 418 
Domino procedure, 254 
Donabedian's structure, process and 

outcome model, 430 
Down syndrome, 419 
Doxorubicin, 286 

toxicity, 290, 291 
Drains, surgical, 202, 212, 352-353 

complications, 353 
Drapes, 184, 210, 230-231 

polyurethane incise, 231, 235 
Dressings, 200, 234-235 
Drug abuse, 78 

Drug and Therapeutics Bulletin (DTB), 133 
Drugs, 131-137 

adverse effects, 132-133, 375-376 

in cardiac arrest, 8 

in children, 134 

concurrent, 80, 80, 165, 172 

convenience and cost, 133 



development and licensing, 131 

efficacy, 132 

in elderly, 134, 373 

genetic background and, 135 

information sources, 133-134 

interactions, 136 

in kidney disease, 135 

in liver disease, 135 

metabolism, in obstructive jaundice, 
378 

poisoning, 15-16 

postmarketing surveillance, 133 

practical use, 134-136 

in pregnancy, 134-135 

in resuscitation, 6 

selection, 131-134 
Dukes' staging of colorectal cancer, 269 
Duodenal trauma, 25-26 
Dural puncture, inadvertent, 364 
Dura mater, 23, 23 

Dysphagia, in terminal illness, 410, 410 
Dysrhythmias see Arrhythmias 



E2F transcription factors, 261 
Ebb phase, response to trauma, 29-31 
ECG see Electrocardiogram 
Economics, 442-444 

see also Costs 
Ectopic pregnancy, ruptured, 14 
Edrophonium, 78, 179 
Education, 439 

Educational component, audit, 434 
Ehlers-Danlos syndrome, 332, 419 
Eisenmenger's syndrome, 67 
Elastic fibres, 332 
Elastin, 332 
Elderly, 79-80 

drug therapy, 134, 373 

intensive care unit admission, 388 

kidney transplantation, 253 

postoperative analgesia, 366 

risks of surgery, 373 
Elective lymph node dissection (ELND), 

267 
Electrical burns, 20-21, 43, 243 
Electrical stimulation, bone healing, 345 
Electrocardiogram (ECG) 

in cardiac arrest, 6 

in heart block, 69 

preoperative, 65 
Electrolyte(s) 

balance, 109-110 

effects of surgery, 318 

postoperative management, 352 

replacement, 114-115 

see also Potassium; Sodium 
EMBASE, 451 
Emergencies 

consent, 158 

decision making in, 146 

professionalism in, 226 
Emergency admissions unit, 443 
Emergency surgery 

blood transfusion, 95 

preoperative preparation, 167-168 



481 




INDEX 



EMLA, 181 

Emotion, 314 

Emotional reactions, terminal illness, 

403^04 
Empathy, 461 
Emphysema, 70-71 

subcutaneous, 24 
Endocrine action, 325 
Endocrine anticancer therapy, 292-293, 

293 
Endocrine dysfunction, 71-74 
Endocrine response to surgery, 314, 

315-316 
Endocrine surgery, 170 
Endoluminal endoscopy, 238 
Endometrial ablation, 194 
Endometrial cancer, 293 
Endoneurium, 27, 340 
^-Endorphin, 317 
Endoscopes, 190-192, 203 

care, 191-192 

cleaning and disinfection, 192, 203, 
211 

flexible Hbreoptic, 190-191, 191, 192 

rigid, 191-192 
Endoscopic retrograde 

cholangiopancreatoscopy (ERCP), 
169 
Endoscopic ultrasound (EUS), 60 
Endoscopy, 58 

endoluminal, 238 

perivisceral, 238 
Endothelial cells, vascular 

response to surgery, 314, 317 

in wound healing, 324 
Endothelins, 317 
Endotoxin, 33 

gut-derived, 126, 127 
Endotracheal intubation 

in critical illness, 395 

postoperative, 355 

in resuscitation room, 4, 13 
Endpoints see Outcomes 
Energy requirements, 127-128 
Energy transfer 

blast injuries, 21 

penetrating trauma, 20 
Enflurane, 176, 177 
Enteral nutrition, 128-129, 321 

complications, 129 

in critical illness, 395-396 

diets, 128, 396 

indications, 126, 126-127 

postoperative, 352 

route of administration, 128-129 
Enterococci, glycopeptide-resistant 

(GRE), 207 
Environmental factors, in cancer 

pathogenesis, 262 
Epidermal cells 

cultured, to aid healing, 247-248 

in wound healing, 245, 323-324 
Epidermal growth factor (EGF), 323, 326 
Epidermal growth factor receptor 
(EGFR) inhibitors, 294, 295 
Epidural abscess, 365 



Epidural anaesthesia/analgesia, 180, 181 

in cancer pain, 409 

complications, 355, 364-365 

mechanisms of action, 358, 358 

patient-controlled (PCEA), 364 

postoperative pain control, 351, 
364-365 

thromboprophylaxis and, 167, 365 
Epidural haematoma, 1 67, 364—365 
Epilepsy, 15, 77 
Epinephrine see Adrenaline 
Epineurium, 27, 341 
Epipodophylotoxins, 287 
Epstein-Barr virus (EBV), 262 
Errors, 228-229 

of judgement, 228 229 

systems, 229 

type I and type II, 449 

see also Adverse incidents 
Erythropoietin, 398 

in cancer, 294 

preoperative therapy, 90, 91, 95 

in renal failure, 400 
Escharotomy, 43 
Escherichia coli, 207 
Ether (diethyl ether), 173, 176, 176 
Ethical issues 

audit, 433 

organ transplantation, 254-255 
Ethics committees, research, 161 
Ethylene oxide (EO), 211-212 
Etomidate, 174, 175 
Eusol, 200 

Evidence-based practice (EBP), 138-143, 
454 

barriers to, 141-142 

definition, 138 

examples, 139, 140 

fears about, 139-140 

implementation, 140-142 
Examination, clinical see Clinical 

examination 
Exercise, 344 
Experience, 146, 150 
Exposure, in primary survey, 8 
External fixation, 347 
Extracellular fluid (ECF), 107, 108, 108, 
109 

expansion, 114, 115 

losses, 113-115, 114, 115 
Extradural haematoma (EDH), 23, 37, 37 
Extravasation, cytotoxic drugs, 290 
Exudate 

inflammatory, 323 

wound, 200, 235 
Eye 

mustard gas exposure, 17 

protection/ visors, 189, 190, 209 



Facial skeleton, 24 

fractures, 23-25 

middle third fractures, 24, 24 
Factor Vila, recombinant, 100 
Factor VIII preparations, 75, 100 
Factor IX preparations, 75, 100 



Faecal occult blood testing, 424-425 
Fagan's nomogram, 446-447, 447 
Falls, from a height, 19, 20 
Familial adenomatous polyposis (FAP, 
adenomatous polyposis coli, 
APC), 262, 420-421, 421 
Family see Relatives 
Family history, 418, 418 
Farnesyl transferase inhibitors, 294 
Fascia, 334 

Fasting, preoperative, 166, 166 
Fat embolism syndrome, 41-42, 42 
Fat metabolism 

after surgery, 315, 319 

response to injury, 30, 31 
Fatty acids, non-esterified (NEFA), 30, 31 
Fc receptors, 84 
Fear, 314 
FEIBA, 100 
Fentanyl, 407 

in anaesthesia, 175, 178 

in chronic and terminal illness, 406 

postoperative analgesia, 362 
Ferritin, serum, 91 
Fetal skin, wound healing, 242, 245 
FEVj/FVC ratio, 170 
Fever, postoperative, 355-356 
Fibre optics, 190-192, 191 

see also Endoscopes 
Fibrin, 323 
Fibrin glue, 204-205 
Fibrinogen, 323 

concentrate, 100 

in cryoprecipitate, 99 
Fibroblast growth factor (FGF), 244 
Fibroblasts, 204 

in malignant disease, 261 

in wound healing, 245, 324 
Fibronectin, 323, 325 
Field blocks, 180, 181 
Fight or flight response, 29-30, 314 
Filograstin, 294 
Fine needle aspiration, 58, 266 
Fire hazards, operating theatres, 187, 

190 
Flail chest, 4, 22 
Haps, 247 

fascial, 247 

free, 247 

in malignant disease, 269 

myocutaneous, 247 
Flow cytometry, 84-85 
Flow phase, response to trauma, 29, 

31-32 
Fluid 

challenge, 112, 113, 389-390 

compartments, 107-109 
water movement between, 109 

excess, 114, 115 

interstitial, 107 

losses, 111-114, 115 

requirements, postoperative, 352 

retention, postoperative, 318 

third space losses, 318 

see also Body fluids; Extracellular fluid; 
Intracellular fluid 



482 



INDEX 



Fluid balance, 109-110, 110 

charts, 111, 351 

effects of surgery, 318 

intraoperative, 118-119 

postoperative, 350, 351-352 

see also Dehydration; Hypovolemia 
Fluid management, 110-119 

assessment of deficits, 112-114 

basal regimens, 110, 111 

in burn injury, 43 

choice of fluids, 114-115 

in continuing loss, 111 

in dehydration, 111-112 

in hypotension, 391, 391 

intraoperative, 118-119 

postoperative, 350, 351-352 

in renal dysfunction, 395 

in resuscitation, 6 

in terminal illness, 410 
Flumazenil, 354 
Fluoroscopic imaging, 60, 196 
5-Fluorouracil (5FU), 291, 296, 297 
Focused abdominal sonography in 

trauma (FAST), 60 
Folic acid supplements, 90, 105 
Folinic acid, 291 
Footwear, theatre, 209 
Foreign bodies, wound healing and, 

329 
Forensic issues, A & E department, 13, 

16 
Forest plot, 451, 451-152 
Formative assessment, 467 
Fractional cell killing, 286 
Fractionation, 272 
Fractures, 39 

blood loss, 27 

bone revascularization, 346 

fat embolism syndrome, 41 

fixation, 346-347 

healing, 39, 327-328, 346 

intra-articular, 340 

limb, 27 

non-union, 328 

pathological, 39 

stress, 39 

see also specific fractures 
Fresh frozen plasma (FFP), 98-99 

indications, 99, 104, 105 

in massive transfusion, 104, 118 
Frostbite, 243-244 

Functional status, intensive care and, 388 
Furosemide (frusemide), 395 



Gait, 342, 342 

cycle, 343 

limping, causes, 342 
Gallbladder trauma, 25 
'y-irradiation 

radiotherapy, 271, 272 

sterilization, 201,212 
Gastric acid, 82 
Gastric cancer, 262, 265, 296 

screening, 425, 426 

spread, 268 



Gastric contents, aspiration, 13, 176, 356 
Gastric emptying, delayed, 356 
Gastric secretions, replacing losses, 115, 

115 
Gastritis, atrophic, 87 
Gastrografin, 60, 384 
Gastrointestinal cancer, 265 

non-surgical management, 296-207 

palliative surgery, 268 

spread, 266-267 

tumour markers, 304-305 

see also specific types 
Gastrointestinal haemorrhage, 14 
Gastrointestinal surgery 

anastomotic leakage, 384 

lasers, 189 

postoperative infections, 381-382 

upper, preoperative preparation, 169 

see also Abdominal surgery 
Gastrointestinal tract 

bacterial translocation, 126, 127, 318 

chemotherapy side-effects, 291 

decontamination, in septic shock, 383 

effects of surgery, 318 

radiation side-effects, 280, 281 
Gastrostomy, percutaneous endoscopic, 

128-129 
Gelatin solutions, 100, 116, 117 
Gelofusin, 116, 117 
Gene(s), 259, 417 

damage, in cancer pathogenesis, 
262-263 

upregulation of transcription, 317 
General anaesthesia, 174-179 

induction, 174-176 

maintenance, 176-178 

recovery, 178-179 
Gene therapy, for cancer, 295 
Genetic disorders, 417 

assessment and management, 418-420 

family history, 418, 418 
Genetics, 417-122 

basic concepts and terminology, 
417-118 

cancer susceptibility, 262, 417, 420, 
420-122 

mechanisms of cancer pathogenesis, 
262-263, 420 
Genitourinary system, trauma, 25-26 
Genomic instability, 284 
Gentamicin, 376 
Germ cells, 417 

Germ cell tumours, 299, 303-304, 304 
Gestalt, 144 
Gestational trophoblastic rumours 

(GTT), 303 
Gibbs-Donnan effect, 108 
Glasgow Coma Scale, 35, 36 
Gleevec (STI-571), 294, 295 
Gloves, 200, 209 

holes, 209, 219 
Gloving, double, 209, 219 
Glucagon, 31-32, 315-316 
Glucocorticoids 

response to injury, 30, 315, 317 

wound healing and, 329 



see also Corticosteroid (steroid) 
therapy 
Gluconeogenesis, 31 9 
Glucose 
blood 

perioperative control, 74 
response to injury, 30, 315 
in resuscitation, 13 
metabolism, in response to injury, 30, 

31, 319 
solutions, 111, 117 
Glucose-6-phosphate dehydrogenase 

(G6FD) deficiency, 92, 135 
Glues, tissue, 204-205, 205, 234 
Glue sniffing, 78 
Glutamine, 319, 321 
Glutaraldehyde, 201, 211, 212 
Glycogen, 319 
Glycopeptide-resistant enterococci 

(GRE), 207 
Glycopyrrolate, 173, 174, 179, 412 
Goitre, retrosternal, 170 
'Golden hour/ 18-19 
Gonadal damage, cancer therapy, 280, 

292 
Good surgical practice, 225-229 
Goserelin, 292, 293 
Gowns, 199, 208 

alternative materials, 200, 208 
Charnley exhaust, 200, 208 
disposable non-woven fabric, 184, 200, 
208 
Graduated compression stockings 

(GCS), 167, 451, 451-452 
Graft rejection see Rejection, graft 
Graft versus host disease (GVHD), 88, 

103 
Gram-negative bacteria, antibiotic- 
resistant, 207 
Granulation tissue, 245, 324 

in fracture healing, 327 
Granulocyte colony stimulating factor 

(G-CSF), 294 
Grey Turner's sign, 26 
Groshong catheters, 289 
Ground substance, 332 
Growth factor receptor inhibitors, 294, 

294-295 
Growth factors, 294 
in cancer pathogenesis, 260, 260-261 
cell cycle control, 259, 260 
in wound healing, 325-326, 327 
Growth hormone, 71-72, 316 
Growth plate (physis), 343 
Guedel airway 4 
Guidelines, 148, 435 
Gunshot injuries, 20, 22, 38 
Gynaecological cancer, 298 
Gynaecological surgery, 189, 379 
H 2 antagonists, 396 



Haemaccel, 116, 117 
Haemarthrosis, 336 

Haematocrit (Hct), in fluid loss/excess, 
114, 114, 115 



483 




INDEX 



Haematogenous spread, cancer, 268 
Haematological assessment 

intraoperative/ 103-105 

postoperative, 105 

preoperative, 90-93 
Haematological changes, in response to 

surgery, 320 
Haematological disorders, 74-75, 

90-106 
Haematology, 57 
Haematoma, 19, 242 

fracture, 346 

spinal epidural, 167, 364-365 

wound, 386 
Haemodialysis, 398-399, 400, 400 
Haemodilution, acute normovolaemic 

(ANH), 94-95, 103 
Haemofiltration, 399, 400 
Haemoglobin (Hb) 

C disease, 75 

concentration, 121 
postoperative, 105 
preoperative, 74-75, 91, 97-98 

fetal, 12 

oxygen binding, 12, 13 

SC disease, 75, 92 

sickle (HbS), 75, 92 
Haemoglobinopathies, 75, 92, 419 
Haemolytic transfusion reactions (HTR), 

101 
Haemophilia, 75 
Haemorrhage/bleeding 

in bone marrow failure, 290-291 

in cardiopulmonary bypass (CPB), 
105 

cardiovascular response, 32, 112 

control see Haemostasis 

fractures, 327 

intraoperative, 103-105 

metabolic response, 30 

postoperative, 386 

preoperative management, 95 

primary survey, 5 

see also Blood loss 
Haemostasis 

in minimal access surgery, 239 

postoperative bleeding, 386 

in wound healing, 322, 323 
Haemostatic agents, 202 
Haemothorax, 22 
Hair 

preoperative removal, 166, 210, 230, 
382 

tying up /covering, 209 
Haloperidol, 412 
Halothane, 176, 176-177 

hepatitis, 177 
Halsted, William, 235, 267, 332 
Handwashing, 207 

before surgery (scrubbing up), 200, 
210 
Hartmann's solution (Ringer's lactate), 

111, 117, 118 
Hazard ratio, 449 
hCG see Human chorionic 
gonadotrophin 



Head injury, 15, 22-23 

pathophysiology, 34-37 

resuscitation, 4, 13 
Health, surgeon's, 228 
Healthcare workers 

infected with blood-borne viruses, 
220-221 

risks of nosocomial virus 

transmission, 215-222 

see also Surgeons 
Health Improvement Programmes 

(HimPs), 440 
Heart 

transplantation, 79, 253-254, 255 

traumatic injury, 22 
Heart and lung transplantation, 254 
Heart block, 69 
Heart disease 

congenital, 66-67 

cytotoxic drug-induced, 291 

postoperative care, 350 

preoperative risk assessment, 167, 168 

valvular, 67^68, 374 

see also Coronary artery disease 
Heart failure, 14, 66 

congestive (CCF), 65, 66 
Heart rate, 389 

response to surgery, 318 

in trauma, 30 
Heart surgery, open, 104-105 
Heat loss, minimizing, 184 
Heat shock pToteins (HSPs), 316 
Helsinki Declaration, 161 
Henderson-Hasselbalch equation, 120, 

121 
Henry, A.K., 335 
Heparin, 93 

epidural analgesia and, 365 

-induced thrombocytopenia (HIT), 93, 
98 

low molecular weight see Low 

molecular weight heparin 

neutralization, 105 

for thromboprophylaxis, 167, 380 

in venous thromboembolism, 380 

for warfarin-treated patients, 165 
Hepatic failure, 15 
Hepatitis B virus (HBV), 215, 216, 262 

immunization, 217, 218-219, 220 

infected healthcare workers, 220-221 

occupational risk, 217 

postexposure prophylaxis, 220 

reducing occupational risk, 218-220 

sources of infection, 217 

testing, 54, 218 

transfusion-related transmission, 102, 
377 
Hepatitis C virus (HCV), 215, 216-217 

infected healthcare workers, 221 

occupational risk, 217 

postexposure prophylaxis, 220 

reducing occupational risk, 218-220 

sources of infection, 217 

testing, 54, 218 

transfusion-related transmission, 102, 
377 



Hepatocellular carcinoma (HCC), 262, 

307 
Hepatorenal syndrome, 169, 378 
Herceptin, 291, 294, 294-295 
Hereditary non-polyposis colon cancer 

(HNPCC), 418, 421,422 
Hernia, incisional, 385 
Heroin overdose, 15 
Hetastarch (hydroxyethyl starch, HES), 

100, 116, 117 
Hexachlorophane, 210 
Hextend, 117 
Hickman catheters, 289 
High dependency unit (HDU), 168 

referral algorithm, 382 

see also Intensive care 
High-risk surgery, 167-168 
Histamine, 175,317 
Histopathology, 58 
History, clinical, 49-51, 459 

general assessment, 50-51 

presenting complaint, 50 
HIV infection/ AIDS, 78-79, 87, 215-216, 
263 

in healthcare workers, 220-221 

occupational risk, 79, 217, 217 

postexposure prophylaxis, 220 

reducing occupational risk, 218-220 

sources of infection, 217 

testing, 54, 218 

transfusion-related transmission, 102, 
377 
HLA (human leucocyte antigen, MHC), 
85-86, 250 

matching, 88, 250-251 
Hodgkin's disease, 292, 298 
Hoffman elimination, 178 
Hormonal anticancer therapy, 292-293, 

293 
Hormone replacement therapy, 165 
Hospital episode statistics (HES), 465 
Hospital information systems, 434, 465 
Hospital Transfusion Committee (HTC), 

96 
Hospital transfusion laboratory, 96 
Hounsfield units (HU), 61 
Hubris, 227 
Hudson mask, 393 
Human chorionic gonadotrophin (hCG), 

303-304, 304 
Human factor analysis, 433 
Human immunodeficiency virus 

infection see HIV infection /AIDS 
Human plasma protein fraction (HPPF), 

115, 116 
Humidity, operating theatre, 184 
Hydatidiform mole, 303 
Hydrocolloid dressings, 200, 235 
Hydrocortisone, 71, 72, 80, 376 
Hydrogel dressings, 235 
Hydrogen ions (H + ), 119 

concentration, 119, 119 

production and elimination, 10, 11 
Hydromorphone, 406, 407 
Hydroxybutyrate dehydrogenase (HBD), 
303 



484 



INDEX 



Hydroxyethyl starch (HES), 100, 116, 117 
5-Hydroxyindoleacetic acid (5HIAA), 

308 
5-Hydroxytryptamine (5HT), 316 
Hyoscine 

premedication, 173, 174 

in terminal illness, 412, 413 
Hypercapnia (hypercarbia), 314, 393 

intracranial pressure effects, 35 

management in resuscitation, 4 
Hyper fractionation, 275 
Hyperglycaemia, 15, 30, 319 
Hyperkalemia, 110 

in crush syndrome, 41 

dialysis, 400 

suxamethonium-induced, 175 
Hypermetabolic state, 31-32 

after surgery, 318-319 

energy and nitrogen requirements, 
127-128 
Hyperparathyroidism, secondary, 401 
Hypersensitivity reactions 

antibiotics, 375 

blood transfusion, 101 
Hypertension, 66 

in phaeochromocytoma, 72 

postoperative, 355 

in renal disease, 76 

risks of surgery, 374 
Hyperthermia, malignant, 175, 419 
Hyperthyroidism (thyrotoxicosis), 71, 

170 
Hypertrophic scars, 234, 245, 329, 

385-386 
Hyperventilation, 10, 120 
Hypnosis, during anaesthesia, 174, 176 
Hypocalcaemia, 15 
Hypofibrinogenaemia, 99 
Hypoglycaemia, 13, 15, 314 
Hyponatremia, 15, 318 
Hypopituitarism, 71 
Hypotension, 391 

epidural analgesia-associated, 355, 
364 

in hypovolemia, 112 

management, 391, 391 

postoperative, 355 

in shock, 5, 390 
Hypothalamic-piruitary-adrenal (HPA) 
axis, response to surgery, 314, 315, 
317 
Hypothermia 

in massive transfusion, 104 

resuscitation, 9, 15 
Hypothesis, 455 

testing, 452 
Hypothetico-deductive approach, 49 
Hypothyroidism, 71 
Hypoventilation, 4, 5, 393 
Hypovolemia, 109 

assessment, 5, 112-113 

cardiovascular response, 32 

management, 114-117 

monitoring, 8-10 

postoperative, 352 

renal dysfunction, 395 



response to surgery and, 314, 321 

resuscitation, 5-6 

water and electrolyte replacement, 
114-115 
Hypovolemic shock, 14, 390 

in burn injury, 42-43 

pathophysiology, 32 
Hypoxia /hypoxaemia, 314, 393-394 

head injury and, 35 

postoperative, 318, 349, 367 
risk factors, 374, 375 

spinal cord injury and, 38 
Hypoxic ventilatory drive, 5, 393 



IgA, 84, 85 

IgD, 84 

IgE, 84 

IgG,84 

IgM,84 

Ileostomy, 169 

Ilizarov, Gavril, 348 

Image-guided surgery, 62, 62-63 

Image intensifiers, 196 

Imaging (radiology), 58, 59-63 

cancer staging, 266 

interventional techniques, 62, 196 

role in surgery, 61-63 

safety, 60, 60 

techniques, 59-61 
Immobility, in terminal illness, 409 
Immobilization 

joint, 335 

muscles, 333 
Immunity, 82-89 

adaptive, 83-87 

antibody-mediated, 83-85 

cancer, 88 

cell-mediated, 85-87 

effects of surgery, 320 

innate, 82-83 

transfusion-induced suppression, 103, 
377 

transplantation, 87-88, 250 
Immunodeficiencies 

acquired, 83, 85, 87 

B cell, 85 

combined T and B cell, 87 

iatrogenic, 83, 85 

primary, 83 
Immunoglobulin, 83 

gene rearrangements, 83 

intravenous, 100 

isotypes, 84 

preparations for infusion, 100 

structure, 84, 84 

see also Antibodies 
Immunohistochemistry, 266 
Immunosuppressive therapy, 79, 87 

cancer risk, 88 

side-effects, 252 

transplant recipients, 88, 251-252 
Immunotherapy, cancer, 88 
Implant materials, 203-204 

infection risk, 203 

tissue response, 204 



Implants, orthopaedic, 346-347 
Incident review, 430 

Incidents, adverse see Adverse incidents 
Incisional hernia, 385 
Incisions, 230-233 
chest, 233 
closure see Closure 
internervous planes, 342 
laparotomy, 232, 232-233 
in muscle, 332-333 
preoperative marking, 166 
principles, 231 
Index Medicus, 457 
Induction of anaesthesia, 1 74-1 76 
crash, 175-176 
relaxation at, 175 
Infections 

in antibody deficiencies, 85 
audit, 213 
burn injuries, 43 
endogenous transfer, 210 
epidural analgesia-associated, 364 
hospital acquired (nosocomial), 206, 

207 
in immunodeficiencies, 83 
overwhelming postsplenectomy, 85 
postoperative, 355-356, 381-383 
in diabetes, 375 

in obstructive jaundice, 377-378 
risk factors, 381-382 
treatment, 382 
see also Wound infections 
prevention, 206-214, 382-383 
asepsis and antisepsis, 208-212 
control of resistant organisms, 

207-208 
feedback, 213 
in intensive care, 396 
in orthopaedic surgery, 184, 199-200 
prophylactic antibiotics, 212-213 
surgical technique, 212 
prosthetic surgery risk, 203 
response to surgery and, 313-314 
surgical access and, 231 
surveillance, 213 
in T cell deficiency, 86-87 
testing for, 54 
transfusion-transmitted, 99, 102, 102, 

377 
wound see Wound infections 
wound healing and, 329 
see also Sepsis 
Inferior vena cava, traumatic injury, 26 
Infertility, in cancer patients, 280, 292 
Inflammatory joint disease, 336-337 
Inflammatory response, 244-245, 322, 
323-324 
fractures, 39, 327 
implant materials, 204 
Information 
availability, 457 
breaking bad news, 460—462 
confidentiality, 162-163 
in decision making, 145 
for evidence-based practice, 142 
for informed consent, 156, 157-158 



485 




INDEX 



Information (cont.) 

for postoperative patients, 354 

for surgical logbook, 463-464 

withholding, 461 
Information systems, hospital, 434, 465 
Inhalational injury, 4, 44 
Inheritance, Mendelian, 418 
Inhibitor of kappa B kinase/ nuclear 

factor kappa B (IKK/NF kappa B) 
proteins, 317 
Injury Severity Score (ISS), 45 
Innate immunity, 82-83 

deficiencies, 83 
Inoculation (needlestick) injuries 

management, 219-220 

prevention, 209, 218, 219 
Inotropes, 391 
Instruments, 201 

cleaning and disinfection, 210-211 

precautions against loss, 233-234 

sets, 201 

sharp see Sharp instruments 

sterilization, 201, 211 

transmissible spongiform 

encephalopathy (TSE)- 
contaminated, 211 
Insulin 

Actrapid, 74 

resistance, in trauma, 30, 31 

response to surgery, 315, 319 

therapy, 73, 74 
Insulin analogues, 73 
Insulin-like growth factor (IGF), 244, 

245 
Insurance companies, 432 
Integrin receptors, 323 
Integrins, 261 
Integrity, 228 
Intensive care, 388-397 

acute neurological problems, 395 

cardiovascular pathophysiology, 
389-391 

decision making, 388-389 

general aspects, 396 

nutrition, 395-396 

organization, 388 

referral algorithm, 382 

renal dysfunction, 394^395 

respiratory pathophysiology, 391-394 
Intensive care unit (ICU), 168, 388 
'Intention-to-treat' analysis, 448 
Intercollegiate Examinations Board, 472 
Intercollegiate specialty examinations, 
472-^74 

format, 473-474 

outcome, 474 
Interferon-a (IFNa), 220, 294, 298 
Interferon-7, 316 
Interferons, 316 

Interleukin 1 (IL-1), 316, 317, 326, 327 
Interleukin 2 (IL-2), 294, 316 
Interleukin 6 (IL-6), 30, 33, 316, 317 
Interleukin 10 (IL-10), 30 
Interleukins, 86 
Intermittent pneumatic calf 
compression, 167, 380 



Intermittent positive pressure 

ventilation, in asthma, 70 
Internal jugular vein, cannulation, 5-6 
International normalized ratio (INR), 93 
Internervous planes, 342 
Interstitial fluid, 107 
Interventional radiology, 62, 196 
Intestinal transplantation, 254 
Intracellular fluid (ICF), 107, 108, 109 

in fluid loss/ excess, 114, 115 
Intracellular pathogens, 86-87 
Intracerebral haematoma (ICH), 37 
Intracranial haematoma 

acute traumatic, 23, 37 

posterior fossa, 36 
Intracranial pressure (ICP), 35 

raised, 35, 408 
Intradural haematoma (IDH), acute, 37 
Intramedullary nails, 347 
Intramucosal pH (pHi), gut, 113 
Intraoperative assessment, 

haematological, 103-105 
Intraosseous infusion, 5 
Intraventricular conduction defects, 69 
Invasive diagnostic procedures, 58 
Investigations, 51, 52, 53-58 

acceptability, 55 

aims, 53-54 

availability, 55 

complications, 56 

cost, 55, 443 

limitations, 55-56 

in practice, 57-58 

preoperative, 166 

protocols, 57 

routine, 55 

safety, 55 

selection, 54-55 

sensitivity, 54-55 

sequence and timing, 56-57 

simplicity, 55 

specificity, 54-55 

urgency, 56-57 
Iodine-131 therapy, 280 
Iressa, 294, 295 
Iron 

deficiency, 91, 92, 98 

overload, 103 

supplements, 90, 91, 98, 105 

toxicity, 16 
Ischaemia 

muscle, 333 

tourniquet, 342 
Ischaemic heart disease see Coronary 

artery disease 
Isoflurane, 176,177 
Isolation, 'wound and enteric'/ 'source,' 

208 
Isoprenaline, 69 
Isotype switching, 84 



Jaundice, 169 

obstructive, 377-378 
Jehovah's Witnesses, 160, 161, 163 
Jejunostomy, needle catheter, 128-129 



Joint(s), 337-340 

articular cartilage, 338-339 

axes, 337, 337 

classification, 338 

immobilization, 335 

inflammatory disease, 336-337 

intra-articular surgery, 238 

menisci, 338-339 

pain, 408 

synovial see Synovial joints 
Joint replacement surgery, 171, 203 

bone cement, 204, 348 

infectious complications, 203, 379 

tissue response to foreign materials, 
204 
Journals, 454, 455 



Kallikreins, 316 

Kaplan-Meier survival curves, 450 

Karaya gum, 204 

Keloids, 234, 245, 329, 385-386 

Keratinocyte growth factor (KGF), 244, 
323 

Keratinocytes, in wound healing, 323 

Ketamine, 174, 175 

Kidneys 
in acid-base balance, 120 
transplantation, 249, 252-253, 255, 

377 
trauma, 26 

Killer inhibitory receptors (KIRs), 83 

Kinins, 316 

Knife wounds, 20 

Knowledge, tacit, 150 

Knudson's two-hit hypothesis, 263, 263, 
420 



Lacerations, 243 

Lactate dehydrogenase (LDH), 303, 304 

Lamivudine, 220 

Langerhans cells, 83 

Langer's lines, 231, 234, 242 

Laparoscopic surgery, 237 

cholecystectomy, 239, 378-379 

diathermy, 188, 379 

economic aspects, 239, 443 

hand-assisted, 379 

limitations, 239 

preoperative preparation, 169 

vs open surgery, 238 

see also Minimal access surgery 
Laparoscopic ultrasound, 239 
Laparoscopy diagnostic, 58 
Laparotomy 

diagnostic, 58 

incisions, 232, 232-233 

vs laparoscopic surgery, 238 
Large bowel 

surgery, preoperative preparation, 
169 

trauma, 26 
Lasers, 188-190 

classification, 189 

clinical applications, 189 



486 



INDEX 



r : -™^ :aj i"' 



hazards, 189-190 

safety measures, 190 

types, 188-189 
Latex allergy, 171,209 
Law of Tension Stress, 348 
Lead time bias, 423, 456 
Learning, lifelong, 439 
Le Fort fractures, 24, 24 
Left bundle branch block, 69 
Left ventricular function, assessment 

112-113 
Leg ulcers, chronic, 329 
Length bias, screening, 423 
Leucocytosis, postoperative, 320 
Leucodepletion of blood products, 

93-94, 97, 102 
Leucotrienes, 316 

Leucovorin, calcium (folinic acid), 291 
Leukaemia 

biological therapy, 294, 295 

cytotoxic drug-induced, 292 

radiation-induced, 281-282 
Levobupivacaine, 180, 181, 364 
Levodopa, 80 
Levomepromazine, 412 
Lidocaine (lignocaine), 180, 181 

maximum dose, 353, 363 

overdose, 16 
Li-Fraumeni syndrome, 421 
Ligaments, 334-335 
Ligatures, 201-202 
Likelihood ratio (LR), 44^-447 
Limbs 

compartments, 28, 334, 335 

incisions, 231 

trauma, 27-28 
Limp, causes, 342 
Linear accelerators, 271, 271 
Lipid metabolism see Fat metabolism 
Literature, critical reading, 454^457 
Liver 

capsule pain, 408 

glucose production, 31 

injury, 25 

metastases, 268 

surgery, preoperative preparation, 
169-170 

transplantation, 254, 255 
Liver disease, 15, 76-77 

cancer chemotherapy, 289 

drug prescribing, 135 

haematological assessment, 105 
Living wills, 160 
Local anaesthesia, 180-181 

daycase surgery, 353-354 
Local anaesthetic (LA) agents, 180, 181 

epidural analgesia, 364 

maximum doses, 353, 363 

postoperative analgesia, 363-365, 366 

sites of action, 358, 358 

toxicity, 353-354, 363 
Logbook, surgical, 463-465 

data analysis, 465 

information required, 463-464 

problems, 464-465 

rationale, 463 



Logic, scientific, 454-455 
Log-roll, 8 
Lorazepam, 173 
Low molecular weight heparin 
(LMWH), 93 

epidural analgesia and, 365 

thromboprophylaxis, 167, 380 

in venous thromboembolism, 380 
Lung(s) 

in acid-base balance, 120 

inhalational injury, 44 

resection, 170 

response to surgery, 318 

toxicity of chemotherapy, 291-292 

trauma, 21-22 
Lung cancer, 265, 279, 296 
Lung function tests, 170 
Luteinizing hormone releasing hormone 

(LHRH) analogues, 292, 293, 293 
Lyell's syndrome, 242 
Lymphatic drainage 

cancer, 267 

radiation side-effects, 281 
Lymph nodes 

elective dissection (ELND), 267 

enlarged, 51 

irradiation, 278 

metastases, 267, 268 

sentinel, 267-268 
Lymphocyte count, 125 
Lymphoedema, 281, 408 
Lymphoma, 298 
Lysozyme, 82 



Macrophages, 82-83, 86 

in fracture healing, 327 

in wound healing, 244-245, 324, 326 
Magnetic resonance imaging (MRI), 61 

interventional, 62 

intraoperative, 62-63 
Maintenance of anaesthesia, 176-178 
Major histocompatibility complex 
(MHC), 85-86, 250 

class I, 85-86 

class II, 86 

see also HLA 
Malaria, 15, 102 
Malignant disease see Cancer 
Malignant hyperthermia, 175, 419 
Malnutrition, 314 

detection, 125 

immune effects, 87 

protein-energy (PEM), 125 

wound healing, 328 

see also Nutritional support 
Mammography, screening, 425 
Mandibular fractures, 24-25, 25 
Manometry, 58 
Marfan's syndrome, 332, 419 
Masks, face, 184, 208-209 
Mastectomy, 267, 269 
Matrix metalloproteinases (MMPs), 261 
Maxillofacial fractures, 23-25 
Mean arterial pressure (MAP), 35 
Mean cell haemoglobin (MCH), 91, 92 



Mean cell volume (MCV), 91, 92 
Mechanical ventilation see Assisted 

ventilation 
Medawar, Sir Peter, 49 
Mediastinal trauma, 22 
Medical Education Standards Board, 440 
MEDLINE, 450, 451, 457 
Medroxyprogesterone acetate, 292, 293 
Megestrol acetate, 292 
Melanoma, malignant, 267-268, 298 

biological therapy, 294 

tumour markers, 308 
Mendelian inheritance, 418 
Meninges, 23, 23 
Menisci, 338-339 
Mental handicap, consent in, 159 
6-Mercaptopurine, 251 
Mesenteric embolism, 14 
Mesorectal excision, total, 267 
Meta-analysis, 138, 450-452, 451 
Metabolic acidosis, 10, 11, 119 

dialysis, 400 

postoperative, 318 

secondary or compensatory, 119 

treatment, 123 
Metabolic alkalosis, 10, 11, 119 
Metabolic rate, 31, 318-319, 319 
Metabolic response to injury, 29, 29-32, 
125 

in diabetic patients, 375 

ebb phase, 29-31 

flow phase, 31-32 

necrobiotic phase, 29, 30-31 

in surgical patients, 315, 318-320 
Metaphyseal arteries, 346 
Metaphysis, 343 

Metastasis, tumour, 261, 261-262 
Metformin, 73 
Methadone, 406, 407 
Methicillin-resistant Staphylococcus 

aureus (MRSA), 54, 207-208, 375 
Methionine, 328 
Methods, study, 447-448 
Methotrexate, 291 
Methylprednisolone, 72 
Microbiology, 57-58 
Micrometastases, 284 
Microscopes, operating, 196-197 
Microsurgical instruments, 197 
Microwave ablation techniques, 194 
Midazolam, 173, 173, 174, 175 

daycase surgery, 354 

in terminal illness, 412, 413 
Minimal access surgery, 237-240 

boundaries, 237-238 

cost effectiveness, 239, 443 

future, 240 

limitations, 238-239 

postoperative complications, 378-379, 
380 

training, 239-240 

see also Laparoscopic surgery 
Minimal Access Therapy Training Unit 

(MATTU), 239 
Minimum alveolar concentration 
(MAC), 176 



487 




INDEX 



Missile injuries, 20 

Mitral stenosis, 67 

Mobility, wound healing and, 329 

Mobilization, pain and, 359 

Mobitz type 1 (Wenckebach) heart block, 

69 
Mobitz type 2 heart block, 69 
Monitoring 

after initial resuscitation, 8-13 

postoperative analgesia, 366-368 

recovery phase, 349-350 
Monoamine oxidase inhibitors, 78, 80 
Monoclonal antibodies, 84-85 

radiolabeled, 88 

therapeutic use, 88 
Monocyte chemoattractant protein 1, 

323 
Monocytes, 326 
Moral rights, 155 
Morbidity and mortality meetings, 

431^32 
Morphine 

in chronic and terminal illness, 
406-107 

postoperative analgesia, 179 

premedication, 173 

routes of administration, 361, 362 

side-effects, 408 
Mortality, personal records, 464 
Motor vehicle accidents see Road traffic 

accidents 
Moynihan, Lord, 235 
MRCS examination, 466-471 

assessments, standards and marking, 
467-468 

future developments, 471 

overview, 468 

requirements, 466—167, 467 

sections, 468-471 
MRSA (methicillin-resistant 

Staphylococcus aureus), 54, 
207-208, 375 
Mucopolysaccharidoses, 419 
Multidrug resistance (MDR) gene, 288 
Multifactorial diseases, 417 
Multiple choice question (MCQ) papers, 
MRCS examination, 467, 468^69, 
469 
Multiple organ failure (MOF), 19, 33-34, 
320, 390 

pathophysiology, 33, 126, 127 

postoperative, 383 

renal failure, 395 

survival rates, 383 
Multiple sclerosis, 77 
Muscle 

denervation, 333 

genetic disorders, 419 

healing, 332, 333 

immobilization, 333 

incisions, 332-333 

ischaemia, 333 

response to trauma, 31, 319-320, 
332-333 

spasm, 408 

weakness, in terminal illness, 409 



Muscle relaxants, 175, 176, 177 

depolarizing, 175, 177 

non-depolarizing, 177, 178 
Muscle relaxation, reversal, 178-179 
Muscle wasting, 31 
Mustard gas, 17 
Mutations, 259, 284, 417 

in cancer pathogenesis, 263, 263, 420 
Myasthenia gravis, 77-78 
Myelin, 340 

Myeloma, multiple, 84, 298, 308 
Myelosuppression see Bone marrow 

failure 
Myocardial contractility, 390 
Myocardial infarction 

in diabetes, 73 

perioperative, 66 

prior, 170-171, 374, 374 

risk factors, 374-375 
Myocardial ischaemia, perioperative, 65, 

66 
Myofascial pain, 405, 408 
Myofibroblasts, 42, 245, 324, 325 
Myoglobinuria, 13, 41 
Myotonic dystrophy, 419 
Myxoedema, 15 



Nails, intramedullary, 347 
Naloxone, 8, 361, 364 
Nasal cannulae, 393 
Nasoethmoidal-orbital fractures, 23-24 
Nasogastric tube feeding, 128 
Nasogastric tubes, 8, 352-353 
Nasojejunal tube feeding, 396 
Nasopharyngeal airway, 4 
National Blood Authority (NBA), 95 
National Centre for Clinical Audit 

(NCCA), 430 
National Confidential Enquiry into 

Perioperative Deaths (NCEPOD), 

64, 168, 431 
National Institute for Clinical Excellence 

(NICE), 133, 148, 439 
National Performance Assessment 

Programme, 440 
National Prescribing Centre (NPC), 133 
National Service Frameworks (NSFs), 

439, 440 
Natural killer (NK) cells, 83 
Nausea and vomiting 

chemotherapy-induced, 291 
in chronic and terminal illness, 

410-411, 411, 412, 412 
opioid -induced, 408 
postoperative (PONV), 368, 368 
Near misses see Adverse incidents 
Necrobiosis, in trauma, 29, 30-31 
Needles, suture, 202 
Needles tick injuries see Inoculation 

injuries 
Negative predictive value (NPV), 424, 

446 
Negative pressure, topical, 200 
Negligence, 157-158 
claims, 229 



Neianavir, 220 

Neoadjuvant therapy, 269, 288 

Neodymium, yttrium, aluminium garnet 

(NdYAG) laser, 188, 189 
Neonates 

risks of surgery, 373 
screening, 426 
Neostigmine, 179 
Nephrotic syndrome, 76 
Nerve, peripheral see Peripheral nerve 
Nerve blocks, 180, 181, 409 
Nerve fibres, types, 180, 180 
Nerve gases, 17 
Nerve injuries, 27 
classification, 340, 341 
healing, 39-41, 328 
surgical patients, 185, 340-342 
surgical repair, 342 
Nerve pain, 405, 408 
Nervous tissue, 340-342 

healing, 328 
Neurapraxia, 40, 341 
Neuroblastoma, 308 
Neurofibromatosis, 421 
Neurogenic shock, 14, 32-33 
Neurological assessment, 8 
Neurological disease, 77-78 
Neurological problems, acute, 395 
Neuroma, 40, 328 
Neuromuscular blockade, reversal, 

178-179 
Neuromuscular blockers see Muscle 

relaxants 
Neuron-specific enolase, 308 
Neuropathy see Peripheral neuropathy 
Neurosurgery, 185, 350 
Neuro tmesis, 341 
Neutropenia, 83, 290 
Neutrophils (polymorph leucocytes), 

82-83 
in wound healing, 244-245, 323 
New chemical entities (NCE), 131 
New Injury Severity Score (NISS), 45 
The New NHS: Modem, Dependable (1997), 

435 
New York Heart Association (NYHA) 

classification, 167, 168 
NHS Performance Framework, 440 
NHS- wide clearing service (NWCS), 

465 
Nicotine, 70-71 
Nitric oxide, 317 
Nitrogen balance, 128 

in response to injury, 31, 319 
Nitrogen requirements, 127-128 
Nitrous oxide, 176, 178 
Non-haemolytic febrile transfusion 

reaction (NHFTR), 101 
Non-Hod gkin's lymphoma (NHL), 

298 
Non-seminomatous germ cell tumours 

(NSGCT), 303-304 
Non-steroidal anti-inflammatory drugs 

(NSAIDs), 360-361 
adverse effects, 178, 360 
mechanisms of action, 358, 358 



488 



INDEX 




postoperative analgesia/ 178, 179, 351 , 
366 

preoperative medication, 90, 93, 173 
Non-union, 328 
Noonan syndrome, 419 
Noradrenaline (norepinephrine), 314 
Nosocomial infections, 206, 207 
NSAIDs see Non-steroidal anti- 
inflammatory drugs 
Nuclear medicine, 61 
Number needed to treat (NNT), 132, 448 
Nuremburg Code, 161 
Nutrient artery, long bones, 346 
Nutrition 

postoperative management, 352 

wound healing and, 328-329 
Nutritional assessment, 125, 165 
Nutritional support, 125-130 

in critical illness, 395-396 

energy and nitrogen requirements, 
127-128 

monitoring, 128 

postoperative, 127, 352 

preoperative, 127, 165-166 

response to surgery and, 320-321 

selection of route, 126 

in septic shock /septicaemia, 383 

see also Enteral nutrition; Parenteral 
nutrition 
Nutritional support team, 130 



Obesity, 74 

morbid, 74, 374 

risks of surgery, 373-374 
Objective structured clinical examination 

(OSCE), 468, 470 
Octreotide, 170, 384, 412 
Odds ratio (OR), 448^49 
Oedema, in tissue injury, 323, 329 
Oesophageal cancer, 265, 268, 269, 296 
Oestrogen receptors (ER), 266, 292, 293, 

295 
Oliguria, 352, 395 
Oncogenes, 259, 260, 418, 420 
Oncogenesis, 263 
Oncotic pressure, 107-108 
Operating suit, 184 
Operating tables, 184-185 
Operating tent, 184 
Operating theatres, 183-198 

airflow, 183-184,199,209 

clothing see Clothing, theatre 

design and environment, 183-184 

equipment, 184-197 

management, 199-200 

technique, 200 

zones, 183 
Ophthalmology, laser therapy, 189 
Opioid receptors, 361 
Opioids /opiates, 361-363 

addiction, 78, 366, 408 

anaesthetic supplementation, 178 

in chronic and terminal illness, 406, 
406-108 

in elderly patients, 366 



endogenous, 317 

epidural, 364 

equivalent doses, 407 

fears of prescribing, 407-408 

induction of anaesthesia, 175 

mechanisms of action, 358, 358 

poisoning, 8, 15 

postoperative analgesia, 179, 366 

premedication, 173, 173, 178 

relative potency, 407 

routes of administration, 361-362, 407 

side-effects, 361, 367, 408 

spinal (intrathecal), 365 

tolerance, 366, 408 
Opsonization, 82 
Oral contraceptives, 80, 165 
Oral hypoglycaemic drugs, 73 
Orbit, blow-out fractures, 24 
Orchiectomy, 267 
Organ donors 

availability, 254 

cadaveric, 250, 251, 252 

living related, 249, 250 

living unrelated, 255 
Organophosphate poisoning, 16, 17 
Organ transplantation see 

Transplantation 
Oropharyngeal (Guedel) airway, 4 
Orthopaedic surgery, 199 

bone cement, 348 

implant materials, 203 

implants, 346-347 

operating tables, 185 

postoperative care, 350 

postoperative complications, 379 

preoperative preparation, 171 

prevention of infection, 184, 199-200 

in steroid-treated patients, 376 

theatre clothing, 200, 208, 209 

theatre management, 199-200 

theatre ventilation systems, 199, 209 

see also Joint replacement surgery; 
Osteotomy 
Osmolality, 108-109 

plasma, 72 
Osmotic pressure, colloid (COP), 

107-108 
Ossification 

centres, 343 

in fracture healing, 328 

heterotopic, 333 
Osteoarthritis, 171, 340, 344, 346 
Osteoblasts, 327, 328, 343 
Osteoclasts, 327, 344 
Osteomalacia, 345 
Osteoporosis, 72, 343, 345 
Osteosarcoma, 269-270, 298 
Osteotomy, 345, 346, 347-348 

distraction, 347-348 

healing after, 347 
Otolaryngology, 189, 197 
Outcomes (endpoints) 

health care delivery, 430 

randomized controlled trials, 448 

reporting, 438 

surrogate, 132 



Ovarian cancer, 298 

familial, 421, 421 

impaired wound healing, 378 

screening, 426 

tumour markers, 305-306 
Overseas, working, 226 
Oxycel, 202 
Oxycodone, 406 

Oxygen, inspired (Fi0 2 ), 121, 393 
Oxygen consumption (TO 2 ), 30 

goals in high-risk surgery, 113, 168 

in multiple organ failure, 34 
Oxygen content of blood, 389 
Oxygen delivery (D0 2 ), 30 

goals in high-risk surgery, 113, 168 

in multiple organ failure, 34 

in shock, 32 
Oxygen dissociation curve, 12, 13 
Oxygen extraction ratio (OER), 30 
Oxygen flux, 12 
Oxygen saturation (0 2 sat.), 12, 
120-121 

in critical care, 394 

postoperative monitoring, 350 
Oxygen tension (partial pressure) see 

Pa0 2 ; P0 2 
Oxygen therapy, 393-394 

methods of delivery, 393-394 

postoperative, 349, 381, 393 

in resuscitation, 4, 5 



p53 suppressor gene, 261 
Pacemakers, 69-70, 374 

diathermy and, 70, 188 
Packs, 202 
PaC0 2 (PC0 2 ), 10, 10-11, 120, 121 

in acid-base balance, 120, 122 

correction, 123 

postoperative monitoring, 350 

in resuscitation, 4, 5 

see also Hypercapnia 
Paediatric formulary, 134 
Paediatric patients see Children; 

Neonates 
Paget' s disease, 346 
Pain 

assessment, 367, 367 

bone, 405, 408 

breakthrough, 406 

cancer, 405, 409 

definition, 357 

diagnosis of cause, 405 

different operations, 359 

incident, 406 

mechanisms, 357 

myofascial, 405, 408 

nerve, 405, 408 

opioid-resistant, 408-409 

perception threshold, 357 

postoperative, 357-369 

psychological, 408-409 

response to surgery and, 313 

services, acute (APS), 182, 369 

tolerance threshold, 357 

visceral, 405 



489 




INDEX 



Pain management 

in chronic and terminal illness, 
405-409 

injection techniques, 409 

postoperative,, 351, 357-369 

see also Analgesia 
Palliative care, 402 

approach, 402 

chemotherapy, 288 

radiotherapy, 278-280 

specialist, 402, 402 

surgery, 268 

symptom control, 404-412 
Pancreas 

endocrine disorders, 72-74 

surgery, preoperative preparation, 
169-170 

transplantation, 253, 254 

trauma, 25-26 
Pancreatic cancer, 265, 268, 296, 378 
Pancreatitis, 14 
Pancuronium, 178 
Pannus, 336-337 
Pa0 2 , 12, 121 

postoperative, 318, 350 

in resuscitation, 4, 5 
PA0 2 , 121 

PA0 2 -Pa0 2 gradient, 121 
Papaveretum, 173 
Paracetamol, 179, 360 

overdose, 15 
Paracrine actions, 325 
Paralytic (adynamic) ileus, 318, 356 
Paramedian incisions, 232, 233 
Paraproteins, 84, 308 
Parasites, causing cancer, 263 
Paratenon, 334 

Paravertebral anaesthesia, 180, 181 
Parenteral nutrition, 129-130 

access, 129-130 

central venous, 126, 129-130 

complications, 130 

in critical illness, 395-396 

home, 130 

indications, 126-127 

monitoring, 130 

nutrients, 130 

peripheral (PPN), 126, 130 

postoperative, 352 
Partial response (PR), 290 
Patient administration system (PAS), 

434 
Patient-controlled analgesia (PCA), 

362 
Patient-controlled epidural analgesia 

(PCEA), 364 
Patients 

breaking bad news, 460-462 

clinical governance perspective, 439 

communication with, 459-460 

participation in decision making, 
145-146, 460 

preparation for surgery see 

Preoperative preparation 

trust, 226 
Patslide, 185 



Pattern recognition, 52 

PC0 2 see PaC0 2 

Pedigree, 418 

Pelvic fractures, 27, 27 

Pelvic injuries, 26 

Pelvic surgery, 378, 379 

Penicillin allergy, 167 

Penis, trauma to, 26 

Peptic ulceration, prophylaxis, 396 

Percutaneous transhepatic 

cholangiography (PTC), 169 
Perineal trauma, 26 
Perineurium, 27 
Periosteal arterioles, 346 
Periosteum, 327, 345-346 
Peripheral nerve, 340 

injuries see Nerve injuries 

mobilization, 340 

structure and function, 27 
Peripheral neuropathy 

chemotherapy-induced, 291 

in diabetes, 73, 342 
Peripheral vascular disease, in diabetes, 

375 
Peritoneal cavity 

cancer spread, 268 

trauma, 25 
Peritoneal dialysis, 400-401 

principles, 398-399, 400 
Peritonitis 

peritoneal dialysis, 400^401 

post-traumatic, 25 
Perivisceral endoscopy, 238 
Pethidine, 361, 362, 407 
Peutz-Jeghers syndrome, 421 
P-glycoprotein, 288 
pH, 119, 119 

arterial blood, 10, 10, 121 

oxy haemoglobin dissociation and, 
12,13 

gut intramucosal (pHi), 113 
Phaeochromocytoma, 72, 170 
Phagocytes, 82-83, 244-245 
Pharmacodynamic interactions, 136 
Pharmacodynamics, 134 
Pharmacokinetic interactions, 136 
Pharmacokinetics, 134 
Pharmacology, 131-137 
Pharyngitis, bacterial, 210 
Phenothiazines 

overdose, 16 

premedication, 173, 173 
Phenoxybenzamine, 72, 170 
Physiological assessment, 58 
Physiotherapy, respiratory, 381 
Pia mater, 23, 23 
Pituitary gland disorders, 71-72 
Placebo effect, 132, 454 
Placental alkaline phosphatase (PLAP), 

303 
Plasma, 107 

fresh frozen see Fresh frozen plasma 

products, 99-100 

virally inactivated, 99 
Plasma osmolality, 72 
Plasma volume, 109 



expansion, 109, 117 

quantification of loss, 113-114, 
114 

replacement/ substitutes, 100, 115-117, 
116 
Plastic surgery, 189 
Plate fixation, bone, 346-347 
Platelet-activating factor (PAF), 317 
Platelet count, 92, 93, 103 
Platelet-derived growth factor (PDGF), 

244, 245, 323, 325 
Platelet disorders, 75, 93, 93, 98 
Platelets, in wound healing, 244, 

323 
Platelet transfusion, 98 

indications, 98, 104, 105 
Pleural effusion, 381 
Pneumocystis carinii, 58 
Pneumonia, postoperative, 318 
Pneumothorax 

complicating central venous 
cannulation, 5, 6 

postoperative, 355, 381 

tension, 4, 14, 22 

traumatic, 21-22 
POi, 121 

alveolar (PA0 2 ), 121 

arterial blood see Pa0 2 
Poiseuille, Jean, 5 
Poisons, common, 15-16 
Polyethylene, high density, 203 
Polymethylmethacrylate (PMMA, acrylic 

cement), 204, 348 
Polypharmacy, 134 
Polypropylene, 201, 204 
Polytetrafluoroethylene (PTFE), 201, 203 
Popper, Karl, 49, 455 
Population, 449 
Porphyria, 135 
Portal hypertension, 170 
Positioning, patient, 185, 230 
Positive predictive value (PPV), 446 

tumour markers, 302, 302 
Positron emission tomography (PET), 

61 
POSSUM, 147 
Posterior fossa intracranial haematoma, 

36 
Postoperative analgesia, 179, 351, 
360-366 

children, 366 

day surgical patients, 366 

elderly, 366 

monitoring, 366-368 
Postoperative assessment, 
haematological, 105 
Postoperative care, 349-356 

after hospital discharge, 354 

daycase surgery, 353-354 

immediate (recovery phase), 349-350 

on ward, 350-353 
Postoperative complications, 354-356, 
373-387 

anastomotic leakage, 384 

economic aspects, 443 

haemorrhage, 386 



490 



INDEX 



■ 



infective, 381-383 

respiratory, 318, 354-355, 381 

risk factors, 373-380 
blood transfusion, 376-377 
drug therapy, 375-376 
type of pathology, 377-378 
type of surgery, 378-380 

surgical logbook, 464 

venous thromboembolism, 380-381 

wound problems, 385-386 
Postoperative nausea and vomiting 

(PONV), 368, 368 
Postoperative pain, 351, 357-369 

mechanisms, 357 

non-pharmacological management, 
359-360 

pharmacological management see 
Postoperative analgesia 

reasons for treating, 359 
Postphlebitic limb, 381 
Postural hypotension, 5 
Potassium (K + ), 108 

effects of surgery, 318 

in fluid regimens, 110, 111 

postoperative replacement, 119, 352 

requirements, 110 
Potassium chloride (KC1), 74, 110, 111 
Povidone-iodine, 210, 230 
Power, study, 449-450 
P-POSSUM, 147 
Predictive value 

negative (NPV), 424, 446 

positive (PPV), 302, 302, 446 
Prednisolone, 252 
Pregnancy 

causes of collapse, 14 

drug prescribing, 134-135 

uterine trauma, 26 
Prejudices, 145 
Preload, 389-390, 390 
Premedication, 172-174 
Preoperative assessment 

anaesthetic, 172 

cancer, 265-266 

genetic disorders, 418-420 

haematological, 90-93 

risk assessment, 167, 168 
Preoperative preparation, 165-171 

antibiotic therapy, 166-167 

high risk patients, 167-168 

infection control aspects, 210 

routine, 165-166 

in specific patient groups, 168-171 

thromboprophylaxis, 167 
Presenting complaint, 50 
Pressure sores, 244, 409 
Prilocaine, 180, 181, 353 
Primary survey, 3-8 
Prions, 102, 201 
Prisoners, 226 

Probability, pre- and post-test, 447 
Process, health care delivery, 430 
Prochlorperazine, 173, 173 
Procuren, 200 
Professionalism, 226 
Professional organizations, 440 



Progesterone receptors (PR), 292 
Progestins (progestogens), 292, 293 
Prognosis, statistics, 450 
Prognostic risk scores, 147 
Programmed cell death see Apoptosis 
Progressive disease (PD), 290 
Prolonged operations, 379-380 
Promethazine, 173, 173 
Promoters, tumour, 263 
Propacetamol, 360 
Propofol, 174, 175 
Propoxyphene, 179 
Propranolol, 71, 170 
Propylthiouracil, 71 
Prostaglandins, 316, 317 
Prostate cancer, 265, 279 

non-surgical treatment, 292-293, 297 

screening, 425 

tumour markers, 306-307 
Prostate-specific antigen (PSA), 306-307 
Prostatic hypertrophy, benign (BPH), 

306, 307 
Prostatic surgery, 1 05 
Prosthetic surgery, 203-204 

see also Joint replacement surgery 
Protamine, 105 
Protein C, activated, 321 
Protein-energy malnutrition (PEM), 

125 
Proteins 

catabolism, in response to injury, 31, 
319 

osmotic effect, 107-108 

pH changes and, 10 

plasma, in fluid loss /excess, 113-114, 
114, 115 
Prothrombin complex concentrate, 

100 
Prothrombin time (PT), 76, 92, 103, 103, 

165 
Protocols, 57, 148,199 

preoperative, 166 
Proto-oncogene, 259, 263, 418 
PRX-2 gene, 245 

Pseudomembranous colitis, 208, 376 
Pseudomonas aeruginosa, antibiotic- 
resistant, 207 
Psychiatric disease, 78, 159 
Publication bias, 450-451 
Pulmonary capillary wedge pressure 

(PCWP), 112-113 
Pulmonary embolism, 355, 380-381 

prophylaxis see Thromboprophylaxis 
Pulmonary metastases, 268, 298 
Pulmonary oedema 

dialysis, 400 

hypotension with, 391 

in smoke inhalational injury, 44 
Pulse, 8 

Pulseless electrical activity, 6, 14 
Pulse oximetry, 350, 367-368 
Pulse pressure, 9 
Pupil size and responses, 8, 9 
Pus swabs, 57 

Pyrexia, postoperative, 355-356 
Pyridostigmine, 17 



Quality 

clinical, 437-438 

indicators, 439 

monitoring, 439 
Quality-adjusted life years (QALYs), 148, 

443 
Quality assurance committee, 432 
Questioning, 459 



Radiation 

biological actions, 272-273 

in cancer pathogenesis, 262, 262, 
281-282 

sources, 271-272 
Radiation dose 

distribution, linear accelerator, 271, 
271-272 

fractionation, 272 

hyperfractionation, 275 

late radiation complications and, 281, 
281 

radiological investigations, 60 

tolerance of different tissues, 273 
Radioactive isotopes, 271, 280 
Radiographs, plain film (X-rays), 58, 
59-60, 195-196 

fluoroscopy, 60 

intraoperative, 1 95-1 96 

legal aspects, 196 

operating theatre equipment, 
196 

preoperative, 195 

safety, 60, 60, 196 
Radiology see Imaging 
Radiosensitivity, tumour, 273 
Radiosurgery, stereotactic, 275 
Radiotherapy, 271-283 

accelerated, 275 

adjuvant, 269, 277, 277-278 

complications, 280-282 

conformal, 274, 275 

continuous hyperfrac donated 
accelerated (CHART), 
275 

haemoglobin concentrations and, 
97-98 

immune effects, 87 

new techniques, 275 

palliative, 278-280 

planning, 273-275, 274 

postoperative, 278 

preoperative, 278 

to prevent graft rejection, 251 

primary (curative), 276, 276-277 

radiation sources, 272-273 

role, 275-280 

systemic disease, 280 

treatment volume, 273-274 

tumour size and, 272-273 
Random allocation, 448 
Randomized controlled trials (RCTs), 
138 

methods, 447-448 

results, 448 

sample size calculation, 449^450 



491 




INDEX 



Raynaud's disease, 244 

Reaming / intramedullary, 347 

Reassurance, premature, 403 

Recessive inheritance, 418 

RECIST (response evaluation criteria in 

solid tumours), 289-290 
Records, 227 

clinical diagnosis, 51-52 

informed consent, 160 

resuscitation, 16 

review of clinical, 430 

see also Logbook, surgical 
Recovery 

from anaesthesia, 178-179 

phase, management, 349-350 
Rectal trauma, 26 
Red cell concentrates, 93, 96, 97-98 

effects of storage, 97, 377 

transfusion see Red cell transfusion 
Red cell indices, in anaemia, 91-92 
Red cells 

antibodies, 96-97 

inherited disorders, 92 
Red cell transfusion, 97-98 

indications, 97-98 

massive, 98, 104 
Re-epithelialization, 245, 323-324 
Reflection coefficient, 108 
Refusal of treatment, 159, 160, 161 
Regional anaesthesia, 180-181, 182, 

363-365 
Rehabilitation, in chronic and terminal 

illness, 403 
Rejection, graft, 88, 250 

acute, 250 

chronic, 250 

hyperacute, 250 

prevention, 88, 250-252 
Relative risk (RR), 448 
Relative risk reduction (RRR), 448, 448 
Relatives 

bereavement, 413 

breaking bad news, 461 

communication with, 460 

consent by, 158 

end-of-life decisions, 388-389 

intensive care patients, 396 

organ donation, 249, 250 

terminally ill patient, 299 
Remifentanil, 178 
Renal cell cancer, 294, 297 
Renal disease, 75-76 

cancer chemotherapy, 289 

in diabetes, 375 

drug prescribing, 135 

kidney transplantation and, 253 
Renal failure, 15, 398 

acute, 41, 378, 394-395, 401 

chronic, 75-76, 253 

in diabetes, 73 

dialysis, 400 
Renal function 

in elderly, 373 

in obstructive jaundice, 378 
Renal replacement therapy, 395 

see also Dialysis 



Renal system trauma, 26 
Renin-angiotensin system, 32, 315 
Research 

consent to participation, 161-162 

and development, 439 
Respiration 

accessory muscles, 394 

effects of pain, 359 

postoperative monitoring, 349, 
367-368 
Respiratory acidosis, 10, 10, 119 
Respiratory alkalosis, 10, 10, 119 
Respiratory complications, 

postoperative, 318, 354-355, 
381 
Respiratory depression, 349, 364, 367, 

408 
Respiratory disease, 70-71 

age-related risk, 373 

heart and lung transplantation, 254 

risks of surgery, 375 
Respiratory distress, 394 
Respiratory failure, 14 

mechanical ventilation, 394 

in myasthenia gravis, 78 

in spinal injury, 38, 38 
Respiratory rate, 4, 8, 367, 394 
Respiratory support, 393-394 
Respiratory system 

inhalational injury, 4, 44 

pathophysiology in critical illness, 
391-394 

response to surgery, 318 
Respiratory tract infection, upper, 1 70 
Resuscitation, 3-17 

cardiopulmonary (CPR), 6-8 

critically ill patients, 390-396 

goals, 391 

initial, and primary survey, 3-8 

monitoring after, 8-13 

secondary survey, 3, 13-16 

withholding, 388-389 
Retinoblastoma, 421 

protein (Rb), 261 
Retraction, skin edges, 243 
Retroperitoneal haematoma, 26 
Retroperitoneal trauma, 25-26 
Revised Trauma Score (RTS), 45 
Rhabdomyolysis, 13 
Rheumatic heart disease, 67 
Rheumatoid arthritis, 336-337, 379 
Rib fractures, 21-22 
Right bundle branch block, 69 
Ringer's lactate see Hartmann's 

solution 
Risk 

preoperative assessment, 167, 168 

relative (RR), 448 
Risk management, 147, 438 

clinical, 147, 438 

non-clinical, 438 

organizational, 147 
Risk reduction 

absolute (ARR), 448 

relative (RRR), 448, 448 
Rituximab, 85 



Road traffic accidents (RTA) 
biomechanics of injury, 19, 19 
prevention of injury, 18, 18 
spinal injuries, 28 

Rocuronium, 176, 178 

Roentgen, W.K., 59 

Rofecoxib, 361 

Ropivacaine, 180, 181, 364 

Royal Colleges, 440 

Royal Colleges of Surgeons 

intercollegiate examinations, 472-474 
membership (MRCS) examination, 
466-171 

Rugby football, spinal trauma, 28 



S-100, serum, 308 
SAG-M blood, 97 
Salicylate overdose, 15 
Saline 

hypertonic, 109, 111 

normal, 109, 111, 117 
Saliva, 115 
Sample, 449 

Sample size calculation, 449-450 
Saphenous vein cutdown, 5 
Sarcomas, 298 
Sarin, 17 
Scalds, 20, 243 
Scalp injuries, 22-23 
Scars 

formation, 245, 324 

hypertrophic, 234, 245, 329, 385-386 

incisions near, 231 
Scientific logic, 454-455 
Scintigraphy, 61 
Scoline apnoea, 175 
Scoline rash, 175 
Screening, 423-427 

abuse, 426 

bias, 423^24 

cancer, 424— i26 

compliance, 426 

controversies, 427 

costs, 427, 443 

neonatal, 426 

non-malignant disease, 426 

population at risk, 424 

radiological techniques, 62 

test, requirements, 424 

treatment of detected disease, 426 
Scrubbing up, 200, 210 
Scurvy, 328 
Seat belt injuries, 26 
Secondary survey, 3, 13-16 
Sedation, 173, 174 

daycase surgery, 354 

monitoring, 367 

opioid-induced, 408 
Seizures, epileptic, 77 
Seminomas, 299, 304 
Semmelweiss, Ignaz, 206 
Sensitivity 

diagnostic test, 54-55, 446 

screening test, 424 

tumour markers, 302, 302 



492 



INDEX 



■ 



Sentinel lymph node biopsy (SLNB), 

267-268 
Sepsis 

acid-base balance, 123 

drug therapy, 321 

neutropenic, 290 

postoperative, 383 

see also Infections 
Sepsis syndrome, 19 
Septicaemia, postoperative, 383 
Septic shock, 14, 19, 33, 390 

postoperative, 383 
Serotonin (5-hydroxytiyptamine, 5HT), 

316 
Severe combined immune deficiency 

(SCID), 87 
Sevoflurane, 176, 177 
Sharp instruments (sharps) 

disposal, 212, 218 

injuries see Inoculation (needlestick) 
injuries 

precautions, 218, 219 
Shaving, operation site, 166, 210, 230, 

382 
Shearing forces, 19 
Shock, 14, 32-33, 390-391 

anaphylactic, 14, 101, 390 

assessment, 5 

in burn injury, 42-43 

cardiogenic, 14, 32, 390 

causes, 32-33 

distributive, 390 

hypovolemic see Hypovolaemic 
shock 

neurogenic, 14, 32-33 

obstructive, 390 

preoperative management, 95 

resuscitation, 5-6 

septic see Septic shock 

signs, 390 

spinal, 39 
Shoemaker's goals, 113, 168 
SHOT (Serious Hazards of Transfusion), 

96,101 
Showering, preoperative, 210 
Shunting, 391-392, 392, 393 
Sickle cell crisis, 15 
Sickle cell disease, 12, 75, 92, 344 
Sidaway case, 157, 158 
Signs, clinical, 51 
Silicone 

joint prostheses, 203 

mammary prostheses, 204 

tissue response, 204 
Single gene disorders, 417 
Single photon emission computed 

tomography (SPECT), 61 
Skeletal dysplasias, 419^120 
Skin 

characteristics, 241-242 

cleansing (scrubbing up), 200 

closure, 202, 234 

cover, 241-248 

functions, 241 

healing see Wound healing 

infections, surgical staff, 210 



loss 
closure, 246-247 
mechanisms, 242-244 

preparation, 184, 210, 230, 382 

radiation side-effects, 280 

substitutes, 247-248 

tension (Langer's) lines, 231, 234, 
242 

trauma, 29, 242-243 

wounds see Wound(s) 
Skin grafts, 246-247, 249 

donor sites, 235, 247 

full thickness, 247 

split thickness, 247 
Skull fractures, 22-23, 36 
Small bowel 

immunity, 85 

trauma, 25 
Small cell lung cancer (SCLC), 296, 308 
Small stomach syndrome, 411 
Smoke inhalation, 4, 44 
Smoking, 70-71, 171, 375 
Sodium (Na + ), 108, 109 

effects of surgery, 318 

in fluid regimens, 111 

loss, 114, 115 

postoperative replacement, 119, 352 

requirements, 110 

retention, postoperative, 318 
Sodium bicarbonate, 111, 123 

hazards of therapy, 12, 123 

in resuscitation, 11-12 
Solvent abuse, 78 
Somatic hypermutation, 83 
Specialist Advisory Committees (SAC), 

472, 473 
Specificity 

diagnostic test, 54-55, 446 

screening test, 424 

tumour markers, 302 302 
Spillages, 212, 218 
Spinal anaesthesia/analgesia, 180, 181, 

365 
Spinal cord, 28, 38 

compression, in cancer, 279 
Spinal cord injuries, 38-39 

neurogenic shock, 32-33 

partial, 38-39 

primary damage, 38 

secondary damage, 38 
Spinal epidural haematoma, 1 67, 

364-365 
Spinal injuries, 28 , 37, 37-39 
Spinal shock, 39 
Spinothalamic tract, 38, 38-39 
Spironolactone, 72 
Splenectomy, 85, 1 70 
Splenic trauma, 25 
Sports, spinal trauma, 28 
Spreadsheets, 463 
Squamous cell carcinoma antigen (SCO, 

308 
Squashed stomach syndrome, 411 
Stable disease (SD), 290 
Stab wounds, 20, 22 
Stainless steel implants, 203 



Staphylococcus aureus 

methicillin-resistant (MRSA), 54, 
207-208, 375 

vancomycin intermediate (VISA), 207 
Staples, 201-202 
Starling forces, 108 
Starling's law, 389 
Starvation, 314 
Statistics, 445-453 

comparative, 452, 456 

critical appraisal, 456 

diagnostic studies, 445-447, 446 

prognostic studies, 450 

systematic reviews /meta-analysis, 
450-452 

therapeutic studies, 447-450 
Steam sterilization, 211 
Steel's rule of three, 28 
Stem cells, radiation damage, 280 
Stents, 202 

Stereotactic radiosurgery, 275 
Sterilants, 211-212 
Sterilization, 211-212 

instruments, 201, 211 
Sterispon, 202 
Steri-strips, 234 
Sternotomy, median, 233 
Steroid hormones, wound healing and, 

329 
Steroid therapy see Corticosteroid 

(steroid) therapy 
Stoma appliances, 202 
Stomach 

cancer see Gastric cancer 

trauma, 25 
Stress response to surgery, 313-317, 359 

in steroid-treated patients, 376 

see also Surgery, body's response to 
Stress ulcer, prophylaxis, 396 
Stroke volume, 112, 113 
Strong ion difference (SID), 122 
Structure, health care delivery, 430 
Sturge-Weber syndrome, 420 
Subarachnoid haemorrhage (SAH), 15, 

23,37 
Subclavian vein, cannulation, 6 
Subdural haematoma (SDH), 23, 37 
Sugar, blood see Glucose, blood 
Sulphonylureas, 73 
Sulphur mustard, 17 
Summative assessment, 467 
Superior vena cava, obstruction (SVCO), 

279 
Supine hypotension, 14 
Supraventricular tachycardia, 8 
Surgeons 

good practice, 225-229 

logbook, 463-465 

preparation for surgery, 210 

risks of nosocomial virus 

transmission, 215-222 
Surgery, body's response to, 313-321 

acute-phase response, 314, 316-317 

clinically apparent systemic, 317-320 

connective tissue and bone, 331-348 

endocrine changes, 314, 315-316 



493 




INDEX 



Surgery, body's response to (cont.) 

initiation, 313-314 

intracellular signalling processes, 317 

manipulation, 313-321 

in open vs laparoscopic surgery, 238 

regulation, 314-317 

sympathetic activation, 314-315 

vascular endothelial response, 314, 317 
Surgical access, 230-233 
Surgical technique 

infection prevention, 212, 381, 382 

reducing exposure to blood, 219 
Surgicel, 202 

Surveillance of infections, 213 
Survival curves, 450 
Sutures, 201-202, 232 

abdominal closure, 232-233 

removal, 234 
Suxamethonium, 175, 176, 177 
Swabs, 202 

precautions against loss, 233-234 

pus, 57 
Swan-Ganz catheter, 112-113 
Sweat, replacing losses, 115, 115 
SWOT analysis, 147 
Sympathetic nervous system, 30, 32, 

314-315 
Symptom control, 404-412 
Symptoms, 50 
Synarthroses, 337 
Syndrome, 418 
Synovial fluid, 336 
Synovial joints, 338 

lubrication, 337-338, 339 
Synovial membrane, 335-337 
Syringe drivers, in terminal illness, 412, 

412 
Systematic reviews, 139, 450-452, 451 
Systemic inflammatory response 
syndrome (SIRS), 33, 320 



Tabun, 17 

Tachycardia, 318, 352 

Tachypnoea, 32, 394 

Tacrolimus, 87, 88 

Tamoxifen, 292, 295, 296, 297 

Tamponade, cardiac, 22 

Tape closure, 234 

Taxanes, 287 

T cell receptors (TCR), 85, 86 

T cells, 85-87 
antigen recognition, 85-86 
cytotoxic (CD8), 85, 86 
deficiency, 86-87 
function, 86 
selection, 86 

Teaching, 226, 228 

Team membership, 227-228 

Technetium-99m ( 99m Tc), 61 

Temazepam, 173 

Temperature 
body see Body temperature 
correction, blood gases, 121 
operating theatre, 184 

Tendons, 333-334 



Tendon sheath, 334 
Tensile strength, wounds, 324 
Tension forces, 19 
Tentorial herniation, 23, 35 
Teratomas, 299 
Terminal illness, 402^14 

breaking bad news, 460-462 

communication, 299, 403 

definition, 402 

emotional reactions, 403-404 

symptom control, 404-412 

terminal phase, 412-413 
Terrorist attacks, chemical weapons, 1 7 
Testicular trauma, 26 
Testicular tumours, 299 

adjuvant therapy, 269 

spread, 267 

tumour markers, 303-304 
Tetracaine (amethocaine), 180, 181 
Thalassaemia, 75, 92 
Thalidomide, 134-135 
T helper cells (CD4), 86, 86 
Theory, 455 

Therapeutic index, narrow, 136 
Thermal injuries, 243-244 

see also Burns 
Thiazolidinediones, 73 
Thiopental, 174, 174-175 
Third space fluid losses, 318 
Thoracic surgery, 1 70, 233, 379 
Thoracic trauma, 21-22 
Thoracoabdominal incision, 233 
Thoracoscopy, 238 
Thoracotomy, 233 

emergency, 8 
Three-dimensional preoperative 

modelling, 63 
Thrombin, 323 
Thrombin time (TT), 92, 103 
Thrombocytopenia, 75 

heparin-induced (HIT), 93, 98 

platelet transfusion, 98 
Thrombocytopenic purpura 

immune, 98 

thrombotic, 98, 99 
Thromboelastogram (TEG), 95, 103 
Thrombophlebitis migrans, superficial, 

378 
Thromboprophylaxis, 167, 380 

epidural analgesia and, 167, 365 

in intensive care, 396 

systematic reviews, 451, 451-452 
Thromboxanes, 317 
Thymectomy, 77-78, 87 
Thymus, 85, 86, 86 

agenesis, 86-87 
Thyroid cancer, 280, 308 
Thyroid disorders, 71 
Thyroid surgery, 170 
Thyrotoxicosis (hyperthyroidism), 71, 

170 
Thyroxine (T 4 ), 71, 316 
Time management, 227 
Tinel's sign, 40 

TIPPS on the vowels mnemonic, 35 
Tissue committee, 432 



Tissue expansion, 247, 269 
Tissue glues, 204-205, 205, 234 
Tissue injury, in surgery, 313 
Tissue perfusion, signs of inadequate, 

390 
Tissue planes, 231 
Tissue transfer, 249, 249, 269 

see also Transplantation 
Tissue typing, 250-251 
TNM staging system, 266 
Tomography, 61 
Topical analgesia, 180, 181 
Topoisomerases, 285, 286 
Total body irradiation, 280 
Total body water (TBW), 107, 108 
Total intravenous anaesthesia (TIVA), 

177 
Tourniquets, 185, 342, 379 
Toxic epidermal necrolysis (TEN), 242 
Toxic shock syndrome, 43^44, 243 
Tracheal tube, drug administration via, 6 
Training, 228, 439 

minimal access surgery, 239-240 

see also Intercollegiate specialty 
examinations; MRCS 
examination 
Tramadol, 179, 362-363, 407 
Tranexamic acid, 105 
Transcellular water, 107, 108 
Transcoelomic spread, cancer, 268 
Transcutaneous electrical nerve 

stimulation (TENS), 358, 359 
TransCyte, 200 
Transferrin, 125 
Transfers, patient, 185 
Transforming growth factor a (TGFa), 

323, 326 
Transforming growth factor p (TGFp), 

245, 260-261, 323, 325, 326 
Transmissible spongiform 

encephalopathy (TSE), 211 
Transplantation, 249-255 

ethical issues, 254-255 

historical development, 249 

immunity, 87-88, 249 

non-transplant surgery after, 79 

specific organs, 252-254 

tissue typing, 250-251 

see also Organ donors; Rejection, graft 
Transportation, resuscitated patients, 16 
Trastuzumab (Herceptin), 291, 294, 

294-295 
Trauma, 18-46, 331-332 

abdomen, 25-26 

airway, 22 

anatomical sites, 21-29 

biomechanics of injury, 19-21 

blast injuries, 21 

blunt, 19-20 

bony pelvis, 27 

burns see Burns 

circulation, 22 

connective tissue and bone responses, 
331-348 

energy transfer, 20 

genitourinary system, 25-26 



494 



INDEX 



head see Head injury 

limbs, 27-28 

maxillofacial skeleton, 23-25 

metabolic response, 29-32 

pathophysiological response, 29, 29-45 

penetrating, 20 

severity scoring, 45 

skin, 29, 242-243 

skull, 22-23 

spinal column see Spinal injuries 

surgical, 313,332 
response to see Surgery, body's 
response to 

thorax, 21-22 

trimodal mortality pattern, 18-19 
Treatment 

futile, 160-161 

life-saving, 158, 160 

refusal, 159, 160, 161 

statistical analysis, 447-450 

withholding, 388-389 
Tremor, in microscopic surgery, 197 
Tricyclic antidepressants, 15, 78 
Tri-iodothyronine (T 3 ), 316 
TRISS, 45 
Troglitazone, 73 
Trophoblastic tumours, 299, 303 
Trust, patient, 226 
D-Tubocurarine, 177 
Tumour(s) 

antigens, 88 

growth, 284 

malignant see Cancer 

metastasis, 261, 261-262 

promoters, 263 

radiosensitivity, 273 

spread, 266-268 
Tumour markers, 266, 302-309 

clinical applications, 302-303 

definitions, 302, 302 

in specific tumours, 303-308 
Tumour necrosis factor a (TNFa), 30, 33, 

316, 326-327 
Tumour suppressor genes, 259, 260, 418, 

420 
Type I error, 449 
Type II error, 449 
Tyrosinase, 308 
Tyrosine phosphorylation, 259 



Ulceration, 244, 329 
Ultrafiltration, 400, 400 
Ultrasonic harmonic scalpel, 194-195 
Ultrasonic surgical aspirator (CUSA), 

194 
Ultrasound imaging, 60, 194-195 

in deep vein thrombosis, 380 

endoscopic (EUS), 60 

interventional, 62 

intracavitary, 60 

intraoperative, 62, 194 

laparoscopic, 239 
Unconscious patients 

consent issues, 158, 161 

see also Coma; Consciousness 



Universal precautions, 218 
Uraemia, 400 
Urea, urinary, 128 
Ureteric injury, 26 
Urethral trauma, 26 
Urinary catheterization, 8 
Urinary output, 9, 395 
Urinary system trauma, 26 
Urogastrone, 326 
Urological tumours, 297 
Urology, 189, 350 
Uterine trauma, 26 
Utility 148, 149 
expected, 148, 149 



Valvular heart disease, 67-68, 374 
Vancomycin intermediate Staphylococcus 

aureus (VISA), 207 
Vascular damage, radiation, 281 
Vascular endothelial growth factor 

(VEGF), 244, 245, 262 
Vascular supply, wound healing and, 

231, 329 
Vascular surgery 

implant materials, 203 

interventional radiology, 62 

laser therapy, 189 

postoperative care, 350 

preoperative preparation, 170-171 
Vascular trauma, 26, 27-28 
Vasoactive drugs, 391 
Vasopressin see Antidiuretic hormone 
Vecuronium, 178 
Veins, trauma, 28 
Venography, 380 
Venous access 

long term, 289 

for resuscitation, 5 
Venous cutdown, 5 
Venous drainage, wound healing and, 

329 
Venous thromboembolism, 380-381 

in cancer, 378 

complications, 380-381 

diagnosis, 380 

incidence, 380 

inherited causes, 419 

in orthopaedic surgery, 379 

prophylaxis see Thromboprophylaxis 

risk factors, 167, 380 

treatment, 380 
Ventilation 

dead space, 392, 392 

mechanical see Assisted ventilation 
Ventilation-perfusion (V/Q) matching, 

391-392, 392 
Ventilation systems, theatre, 183-184, 
199, 209 

positive pressure (plenum), 209 

ultraclean, 209 
Ventilatory failure see Respiratory 

failure 
Ventricular fibrillation, 6-7, 14 
Ventricular septal defect, 67 
Venturi masks, 393 



Vertebral column, Steel's rule of three, 

28 
Vertebral fractures 
Chance, 19 
traumatic, 28 
Vinca alkaloids, 287 

toxicity, 290, 291 
Virchow, Rudolf, 324 
Viruses 

blood-borne, 215-222 

infected healthcare workers, 

220-221 
reducing infection risk, 218-220 
risks to healthcare workers, 217 
sources of infection, 217 
nosocomial infections, 215 
oncogenic, 262, 262-263 
surgical staff infections, 210 
in T cell deficiency, 86-87 
in tissue glues, 205 
transfusion-related transmission, 99, 
102, 102 
Viscera, response to surgery, 315 
Visceral pain, 405 
Vitamin A, 328 
Vitamin C, 328 
Vitamin D, 398, 401 
Vitamin K, 93, 99, 105, 169, 386 
Vitronectin, 323 
Viva voce, MRCS examination, 467, 468, 

469-470 
Volkmann's contracture, 333 
Vomiting see Nausea and vomiting 
Von Hippel-Lindau syndrome, 421 
Von Willebrand's disease, 99 



Walking see Gait 
Wallerian degeneration, 40 
Ward round, postoperative, 351 
Warfarin 

preoperative therapy, 90, 93, 165 

reversal, 99 

thromboprophylaxis, 380 

in venous thromboembolism, 380 
Waste disposal, 212 
Water 

deprivation test, 72 

requirements, 109-110, 110 

total body (TBW), 107, 108 

see also Fluid 
Weak acids, 122 

Weakness, in terminal illness, 409 
Weight reduction, before surgery, 374 
Wenckebach phenomenon (Mobitz type 

1 heart block), 69 
Wernicke's encephalopathy, 13 
Whiplash phenomenon, 28 
White cell count (WCC), raised, 57 
Wide local excision, breast cancer, 267 
Will Rogers' effect, 456 
Wilms' tumour, 421 
Wolff's law, 344 
World Health Organization (WHO) 

analgesic ladder, 1 79 

clinical quality, 437 



495 




INDEX 



Wound(s), 241 
assessment 242 
chronic, 200 
classification, 381-382 
clean (class I), 166, 166, 206 
clean-contaminated (class II), 166, 206 
closure see Closure 
complications, 385-386 
contaminated (class III), 166, 167, 206 
contraction, 245, 325 
contracture, 42, 245 
debridement, 245-246 
dehiscence, 232-233, 385 
dirty (class IV), 206 
dressings, 200, 234-235 
exuding, 200, 235 
haematoma, 386 
incised, 322-324 
malignant transformation, 241 
open, 200, 235 

principles of management, 235 
retraction of skin edges, 243 



skin cover, 241-248 

tensile strength, 324 
Wound healing, 42, 320, 322-330 

biology, 244-245 

in bone, 39, 327-328 

in cancer, 378 

complications, 329 

corticosteroid therapy and, 376 

in diabetes, 242, 245, 329, 375 

factors affecting, 328-329, 385 

fundamental requirements, 322 

nervous tissue, 328 

in obstructive jaundice, 377 

by primary intention, 246, 322-324 

problems, 385-386 

by secondary intention, 246, 322, 
324-327 

skin substitutes, 247-248 

superficial disruption, 385 

vascular supply and, 23 1 
Wound infections 

classification of risk, 166, 206 



dressings, 200 
in orthopaedic surgery, 379 
prevention, 206-214, 382-383 
risk factors, 381-382 
surveillance and audit, 213 
treatment, 383 



Xenografts, 249, 250 
Xenon, 176, 177 
X-rays 

diagnostic see Radiographs, plain 
film 

radiotherapy, 271-272 



Yellow Card Scheme, 133 



Zidovudine (AZT), 220 

Zinc, 328-329 

Zygomatic complex fractures, 24 



496 



Also available... 



ShCQMB&mON 



The New Aird's 

COMPANION 

IN SURGICAL 

STUDIES 



Edited by 
Kevin G. Burnand 

Anthony E. Young 



CLINICAL 
CASES AND 



•EW 



IN SURGERY 



Manoj Ramachandran 
Adam Poole 



CHURCHILL LIVINGSTONE 






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