Forsythe Transplantation E-Book

Companion to Specialist Surgical Practice
5. Auflage 2013
ISBN: 978-0-7020-4968-2
Verlag: Elsevier HealthScience EN
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 320 Seiten

Reihe: Companion to Specialist Surgical Practice

Transplantation meets the needs of surgeons in higher training and practising consultants for a contemporary and evidence-based account of this sub-specialty that is relevant to their general surgical practice. It is a practical reference source incorporating the most current information on recent developments, management issues and operative procedures. The text is thoroughly referenced and supported by evidence-based recommendations wherever possible, distinguishing between strong evidence to support a conclusion, and evidence suggesting that a recommendation can be reached on the balance of probabilities. This is a title in the Companion to Specialist Surgical Practice series whose eight volumes are an established and highly regarded source of information for the specialist general surgeon. The Companion to Specialist Surgical Practice series provides a current and concise summary of the key topics within each major surgical sub-specialty. Each volume highlights evidence-based practice both in the text and within the extensive list of references at the end of every chapter. An expanded authorship team across the series includes additional European and World experts with an increased emphasis on global practice. The contents of the series have been extensively revised in line with recently published evidence. Modern techniques in transplantation and new forms of immunosuppression are emphasised throughout this volume. The substantial interest in new organ perfusion and in the preservation techniques in organ donation and transplantation are reflected in a new chapter written by an international expert. All the chapters reflect transplant care as a multi-disciplinary team of clinicians working in a collaborative fashion.

Autoren/Hrsg.

Forsythe, John L. R.

Inhaltsverzeichnis

1;Front Cover;1
2;Transplantation: A Companion to Specialist Surgical Practice;4
3;Copyright;5
4;Contents;6
5;Contributors;8
6;Series Editors' preface;10
7;Editor's preface;12
8;Evidence-based practice in surgery;14
9;Chapter 1: Controversies in the ethics of organ transplantation;16
9.1;Introduction;16
9.2;Key terminology;16
9.2.1;Fundamental principles of bioethics;16
9.2.2;Other terms;16
9.3;Death, organ donation, patient autonomy and the choice to donate;17
9.3.1;When does death occur?;17
9.3.2;Futility, the patient's best interests, and the decision to withdraw life-sustaining treatments;18
9.3.3;Donor pain, distress and individuals' rights after death;18
9.3.4;The conflict between donation and dignity in death;19
9.3.5;Relatives' right to veto the act of organ donation;19
9.3.6;The paradigm of uncontrolled DCD donation – still with ethical challenges;20
9.3.7;Early approach to the bereaved;20
9.3.8;Pre-consent preservation measures;20
9.3.9;Preservation measures and the potential to restore cerebral circulation;20
9.3.10;The extremes of deceased donation;21
9.4;Allocation of organs;21
9.4.1;Benefit (utility);21
9.4.2;Fairness (equity);22
9.4.3;Transparency;22
9.4.4;Legality;22
9.4.5;Societal mandate;22
9.4.6;Flexibility;22
9.4.7;The implications of variable organ quality;23
9.4.8;Balance of donor and recipient risk;23
9.4.9;Autonomy and patient choice in allocation;24
9.4.10;Practical incorporation of patient choice in an allocation system;25
9.4.11;Ethical presentation of risk: where, when and how?;25
9.5;Living donation;26
9.6;Altruistic donation;26
9.7;Implications of the living donor work-up;27
9.8;Human organs as a commodity: incentivisation and payment for organ donation;27
9.9;References;31
10;Chapter 2: Organ donation in the UK: recent progress and future challenges;33
10.1;Introduction;33
10.2;Recent progress;33
10.2.1;Legal issues;34
10.2.2;Ethics;34
10.2.3;Disseminating donation activity data;35
10.2.4;Healthcare regulator assessments;35
10.3;Progress;39
10.4;Future challenges;40
10.4.1;Increased consent/authorisation rates;41
10.4.2;Increased diagnosis of brain stem death;42
10.4.3;Increased donation after circulatory death;43
10.4.4;Greater involvement of emergency departments;43
10.4.5;Increased referral according to minimum notification criteria;44
10.4.6;Better donor management;44
10.5;Other issues;45
10.6;Managing expectations;45
10.6.1;The potential donor pool;46
10.6.2;Donor characteristics;46
10.7;Summary/conclusions;46
10.8;Acknowledgements;47
10.9;References;47
11;Chapter 3: Immunology of graft rejection;49
11.1;Introduction;49
11.2;Basic concepts and nomenclature of immunology;49
11.2.1;Recognition of danger;49
11.2.2;Histocompatibility;49
11.2.3;Major histocompatibility complexes;50
11.2.3.1;Assembly of the MHC–peptide complex;50
11.2.4;Other histocompatibility genes in rejection;50
11.2.5;T cells;52
11.2.5.1;CD8-positive T cells;52
11.2.5.2;CD4-positive T cells;52
11.3;Early inflammatory response;52
11.3.1;Ischaemia–reperfusion injury;52
11.3.1.1;Ischaemic injury;52
11.3.1.2;Reperfusion injury;54
11.3.1.3;Sterile inflammation;54
11.3.1.4;Adaptive immune response to IRI;54
11.4;The alloimmune response;54
11.4.1;Recognition of alloantigen by T cells;54
11.4.1.1;Direct allorecognition;54
11.4.1.2;Indirect allorecognition;55
11.4.1.3;Semi-direct allorecognition;55
11.4.2;Co-stimulation;55
11.4.3;Co-inhibitory molecules;56
11.4.4;T-cell synapse;56
11.4.5;TCR signalling;56
11.4.6;T-cell differentiation: the role of cytokines;56
11.4.7;T-cell responses;57
11.4.7.1;T helper 1 (Th1) response;57
11.4.7.2;T helper 2 (Th2) response;57
11.4.7.3;T helper 17 (Th17) response;58
11.4.7.4;T regulatory (Treg) response;58
11.5;The effector arm of the immune response;58
11.5.1;Migration of activated leucocytes;58
11.5.1.1;Cell-to-cell interactions;58
11.5.1.2;Chemokines;58
11.5.2;Cellular mechanisms of injury;59
11.5.2.1;Antigen-specific cytotoxic CD8-positive T cells;59
11.5.2.2;Natural killer (NK) cells;59
11.5.2.3;Macrophages;59
11.5.2.4;B cells;59
11.5.2.5;Endothelial cells;60
11.6;Rejection of the allograft;60
11.6.1;Cell-mediated rejection;60
11.6.2;Antibody-mediated rejection (AMR);61
11.6.3;Classification of rejection;62
11.7;Future developments;63
11.7.1;Tolerance;63
11.7.2;Accommodation;63
11.7.3;Xenotransplantation;63
11.7.4;Tissue engineering;64
11.7.5;Improvements in IRI;64
11.8;Acknowledgements;65
11.9;References;65
12;Chapter 4: Testing for histocompatibility;69
12.1;Introduction;69
12.1.1;Immunity;69
12.1.2;Histocompatibility;69
12.1.3;Sensitisation;70
12.2;HLA: history of clinical application and technical development;70
12.3;HLA genes and proteins: structure and genetics relevant to transplantation;72
12.4;HLA reactive antibodies, causes of sensitisation and antibody epitopes;74
12.4.1;Antibodies and rejection;74
12.4.2;Alloimmunisation to HLA proteins;75
12.5;Establishing antibody reactivity;75
12.6;Crossmatching;76
12.7;Clinical relevance of HLA reactive antibodies;76
12.7.1;Antibodies before kidney transplantation;76
12.7.2;De novo donor-specific antibodies after kidney transplantation;77
12.7.3;HLA reactive antibodies in transplantation of other organs;77
12.7.4;Antibody removal to facilitate transplantation;77
12.7.5;Other antibodies and their clinical relevance;77
12.8;Organ allocation and histocompatibility;78
12.9;Conclusion;79
12.10;References;80
13;Chapter 5: Immunosuppression with the kidney as paradigm;82
13.1;Introduction;82
13.2;Calcineurin inhibitors;82
13.2.1;Ciclosporin;82
13.2.2;Tacrolimus;83
13.3;Antimetabolites;84
13.4;mTOR inhibitors;85
13.5;Biological agents;87
13.6;Depleting antibodies;88
13.6.1;Equine antithymocyte globulin;88
13.6.2;Muromonab CD3;89
13.6.3;Rabbit antithymocyte globulin;89
13.6.4;Alemtuzumab;90
13.7;Non-depleting antibodies and biologicals;91
13.7.1;Daclizumab;91
13.7.2;Basiliximab;91
13.7.3;Belatacept;93
13.8;Strategies to lower toxicity;97
13.8.1;Corticosteroid-sparing regimens;97
13.8.2;CNI minimisation;99
13.9;Looking ahead;100
13.10;References;101
14;Chapter 6: Preservation and perfusion of abdominal organs for transplantation;104
14.1;Introduction;104
14.2;Development of preservation techniques;105
14.2.1;Static cold storage;105
14.2.2;University of Wisconsin solution;107
14.2.3;Histidine–tryptophan–ketoglutarate solution;107
14.2.4;Celsior solution;107
14.2.5;Institut-Georges-Lopez-1 solution;107
14.2.6;Hypothermic machine preservation;109
14.3;Kidney;109
14.3.1;State of the art;109
14.3.2;Donation after brain death;110
14.3.3;Controlled donation after circulatory death;110
14.3.4;Uncontrolled donation after circulatory death;111
14.3.5;Expanded criteria donors;111
14.3.6;New developments and the future;112
14.4;Liver;113
14.4.1;State of the art;113
14.4.2;Controlled donation after circulatory death;114
14.4.3;Uncontrolled donation after circulatory death;114
14.4.4;New developments and the future;115
14.5;Pancreas;117
14.5.1;State of the art;117
14.5.2;New developments and the future;118
14.6;Intestine;119
14.6.1;State of the art;119
14.6.2;New developments and the future;119
14.7;Evidence in the field of organ preservation and perfusion;120
14.8;Conclusion;121
14.9;References;121
15;Chapter 7: Recent trends in kidney transplantation;128
15.1;Introduction;128
15.2;Demand inflation or supply recession?;128
15.3;Innovations in living donation;129
15.4;Incompatible transplantation;130
15.4.1;ABO-incompatible transplantation;130
15.4.2;HLA-incompatible transplantation;133
15.5;Trends in deceased kidney donation;133
15.6;Optimising donor organ quality;134
15.7;Kidney allocation – new principles, same old challenges?;135
15.8;Trends in surgical technique;135
15.8.1;Donor surgery;135
15.8.2;Kidney implantation;136
15.9;Current practice and challenges in immunosuppression;136
15.10;Conclusion;137
15.11;References;138
16;Chapter 8: Liver transplantation;142
16.1;Introduction;142
16.2;Indications for liver transplantation;144
16.2.1;Acute fulminant liver failure;144
16.2.2;Budd–Chiari syndrome;145
16.2.3;Chronic liver disease;145
16.2.3.1;General considerations;145
16.2.3.2;Hepatitis C virus (HCV) infection;147
16.2.3.3;Hepatitis B virus (HBV) infection;147
16.2.3.4;Hepatocellular carcinoma (HCC);147
16.2.3.5;Alcoholic liver disease;148
16.2.3.6;Primary biliary cirrhosis (PBC);148
16.2.3.7;Primary sclerosing cholangitis (PSC);148
16.2.3.8;Non-alcoholic fatty liver disease (NAFLD);149
16.3;Liver transplant immunology;149
16.4;Technical considerations;150
16.4.1;Organ procurement;150
16.4.2;Graft implantation;150
16.5;Immunosuppressive agents;152
16.5.1;Induction agents;152
16.5.2;Primary immunosuppressants;152
16.5.3;Adjunct immunosuppressive agents;153
16.5.3.1;Azathioprine;153
16.5.3.2;Mycophenolic acid;153
16.5.3.3;mTOR Inhibitors;153
16.5.3.4;Corticosteroids;153
16.6;Post-transplant complications;153
16.6.1;Perioperative complications (first 30 days);154
16.6.1.1;Preservation/reperfusion injury;154
16.6.1.2;Primary non-function (PNF);154
16.6.1.3;Haemorrhage;154
16.6.1.4;Hepatic artery thrombosis (HAT);155
16.6.1.5;Portal vein thrombosis (PVT);155
16.6.1.6;Biliary complications: bile leaks;155
16.6.2;Early (first 6 months) complications;155
16.6.2.1;Biliary strictures;155
16.6.2.2;Acute rejection;156
16.6.2.3;Infections;156
16.6.3;Late complications ( > 6 months);158
16.6.3.1;Malignancy;158
16.6.3.2;Late surgical complications;158
16.6.3.3;Biliary strictures;159
16.6.3.4;Vascular complications;159
16.6.3.5;Chronic rejection;159
16.7;Conclusion;159
16.8;References;160
17;Chapter 9: Pancreas transplantation;164
17.1;Introduction;164
17.2;Indications for pancreas transplantation;164
17.2.1;Pancreas transplantation for type II diabetes;164
17.2.2;Pancreas transplantation from living donors;165
17.3;Patient selection for pancreas transplantation;165
17.3.1;Simultaneous pancreas–kidney transplantation (SPK);165
17.3.2;Pancreas after kidney transplantation (PAK);166
17.3.3;Pancreas transplantation alone (PTA);167
17.4;Pancreas transplantation activity worldwide;168
17.5;The pancreas donor and the organ retrieval procedure;169
17.5.1;Criteria for eligibility for pancreas donors;169
17.5.2;Pancreas retrieval operation;172
17.6;The pancreas transplant operation;173
17.6.1;General considerations;173
17.6.2;Management of exocrine secretions;174
17.6.3;Management of the venous drainage;174
17.7;Immunosuppression in pancreas transplantation;175
17.8;Acute rejection following pancreas transplantation;176
17.8.1;Diagnosis of acute rejection;176
17.8.2;Management of acute rejection;177
17.8.3;Impact of acute rejection on outcome;178
17.9;Complications of pancreas transplantation;178
17.9.1;Introduction;178
17.9.2;Vascular complications;178
17.9.2.1;Thrombosis;178
17.9.2.2;Haemorrhage;179
17.9.3;Infective complications;180
17.9.4;Allograft pancreatitis;180
17.9.5;Complications specific to bladder drainage;180
17.10;Outcome following pancreas transplantation;181
17.10.1;Introduction;181
17.10.2;Factors influencing pancreas transplantation outcome;182
17.10.2.1;Recipient age;182
17.10.2.2;Re-transplantation;182
17.10.2.3;HLA matching;182
17.10.2.4;Management of exocrine secretions: management of venous drainage;183
17.10.2.5;Immunosuppression;183
17.10.2.6;Donor factors;183
17.11;Long-term outlook following pancreas transplantation;184
17.11.1;Pancreas transplantation and life expectancy;184
17.11.2;Influence of pancreas transplantation on diabetic complications;185
17.11.2.1;Nephropathy;185
17.11.2.2;Retinopathy;185
17.11.2.3;Neuropathy;185
17.11.2.4;Cardiovascular disease;185
17.12;References;186
18;Chapter 10: Islet transplantation;190
18.1;Introduction;190
18.2;Patient selection and assessment;191
18.3;Islet isolation;192
18.4;The islet transplant;193
18.5;Immunosuppression and outcomes;194
18.6;Barriers to long-term function;195
18.7;Islets as a cell therapy;196
18.8;References;196
19;Chapter 11: Cardiothoracic transplantation;199
19.1;Introduction;199
19.2;Indications for heart transplantation;199
19.3;Aetiology of heart disease;199
19.3.1;Introduction;199
19.3.2;Ischaemic heart disease;200
19.3.3;Non-ischaemic cardiomyopathy;200
19.3.4;Congenital heart disease;200
19.4;Recipient evaluation and selection;200
19.4.1;Selection criteria;200
19.4.2;Contraindications;202
19.4.3;Other options;203
19.4.3.1;Cardiac resynchronisation treatment (CRT);203
19.4.3.2;Implantable cardio defibrillators (ICDs);203
19.4.3.3;Ventricular assist devices;203
19.5;Donor selection and matching;204
19.5.1;Donor age;204
19.5.2;Cardiac function;204
19.5.3;Donor disease;204
19.5.4;Size matching;205
19.5.5;ABO compatibility;205
19.5.6;Immunological matching;205
19.6;Donor heart procurement;205
19.7;Heart transplantation ( Figs 11.1 and 11.2);206
19.8;Special situations;207
19.8.1;Heart transplantation for congenital heart disease;207
19.8.2;Heterotopic heart transplantation;207
19.9;Perioperative management;207
19.9.1;Graft function;207
19.9.2;Immunosuppression;208
19.9.3;Infection prophylaxis and treatment;208
19.10;Survival;208
19.11;Cause of death after heart transplantation;208
19.11.1;Cardiac allograft vasculopathy;209
19.11.2;Malignancy;209
19.11.3;Hypertension;210
19.11.4;Chronic renal dysfunction;210
19.12;Heart and lung transplantation (HLT);210
19.12.1;Recipient selection criteria;210
19.12.1.1;Pulmonary hypertension without congenital heart disease;210
19.12.1.2;Eisenmenger's syndrome;210
19.12.2;Heart–lung operation;211
19.12.3;Survival;211
19.13;Future direction in heart transplantation;211
19.14;Lung transplantation;211
19.15;Choice of lung transplant procedure;211
19.16;Lung recipient assessment and selection;212
19.17;Lung donor criteria and selection;214
19.18;Ex vivo lung perfusion;214
19.19;Lung recipient–donor matching;214
19.20;Lung retrieval and preservation;215
19.21;Single lung implantation;216
19.22;Bilateral sequential lung implantation;216
19.23;Peri- and postoperative care for lung transplants;217
19.24;Outcomes and complications of lung transplantation;218
19.25;Recent advances and controversies;219
19.26;References;221
20;Chapter 12: Transplant infectious disease;225
20.1;Introduction and general concepts;225
20.2;Viruses: epidemiology, prophylaxis, diagnosis and treatment;229
20.2.1;Epidemiology;229
20.2.2;Prophylaxis;230
20.2.3;Diagnosis;234
20.2.4;Treatment;234
20.3;Bacteria: epidemiology, prophylaxis, diagnosis and treatment;235
20.3.1;Epidemiology;235
20.3.2;Prophylaxis;235
20.3.3;Diagnosis;235
20.3.4;Treatment;235
20.4;Fungi: epidemiology, prophylaxis, diagnosis and treatment;236
20.4.1;Epidemiology;236
20.4.2;Prophylaxis;236
20.4.3;Diagnosis;237
20.4.4;Treatment;237
20.5;Parasites: epidemiology, prophylaxis, diagnosis, and treatment;238
20.5.1;Epidemiology;238
20.5.2;Prophylaxis;238
20.5.3;Diagnosis;238
20.5.4;Treatment;239
20.6;Pre-transplant infectious disease evaluation;239
20.7;Donor-derived infections;240
20.8;Lifestyle and infection: food, pets, travel and sexuality;241
20.9;References;243
21;Chapter 13: Chronic transplant dysfunction;246
21.1;Introduction;246
21.2;Organ-specific findings;246
21.2.1;Heart;246
21.2.2;Liver;248
21.2.3;Lung;249
21.2.3.1;Management;250
21.2.4;Pancreas;250
21.2.5;Kidney;251
21.2.5.1;Why and how does IF/TA occur? Clinical insights;251
21.3;The aetiology of chronic graft injury;252
21.3.1;Peri-transplant factors: beyond our control?;253
21.3.2;Post-transplant immunity: acute rejection;253
21.3.3;Post-transplant immunity: antibody-mediated rejection;254
21.3.3.1;Diagnosis of antibody-mediated rejection: acute and chronic;254
21.3.3.2;Associations of antibody and CGI;255
21.3.4;Post-transplant factors: viral infections;256
21.3.4.1;Cytomegalovirus (CMV) infection;256
21.3.4.2;Polyomavirus infection;256
21.3.5;Post-transplant factors: immunosuppression;257
21.3.6;Post-transplant stressors;257
21.3.6.1;Hypertension;257
21.3.6.2;Dyslipidaemia;258
21.3.6.3;Post-transplant diabetes mellitus;258
21.3.6.4;Anaemia;259
21.4;Pathophysiology;259
21.4.1;What are the targets that mediate chronic injury?;260
21.4.2;What is the source of matrix?;260
21.4.3;The contributions of the innate immune response;261
21.5;The management of chronic graft injury in the kidney;263
21.5.1;Principles of management;263
21.5.2;Abrogating matrix deposition: a novel option for CGI management?;263
21.5.3;Diagnostic strategies in monitoring for CGI;264
21.5.3.1;Allograft biopsy;264
21.5.3.2;Assays of whole blood: serum antibodies;265
21.5.3.3;Assays of whole blood: proteins;265
21.5.3.4;Assays of whole blood: gene expression;265
21.5.3.5;Assays of whole blood: cellular functional analysis;266
21.5.3.6;Assays of urine: gene and proteomic approaches;266
21.5.3.7;References;267
22;Index;272

Leseproben

1 Controversies in the ethics of organ transplantation
Marc J. Clancy and Alex T. Vesey Introduction
• Clinical transplantation remains a relatively young field, yet it has created considerable ethical debate. Development of clinical programmes has required the rapid parallel development of ethical frameworks to justify the steps taken in the name of patient benefit. • In many ways, the rate of technological advance has exceeded the development of the ethical, cultural and legal framework within which transplantation takes place. This has resulted in a variety of fascinating ethical debates but also represents a barrier to fully realising the potential of transplantation. • All transplant professionals have a responsibility to be aware of the many ethical issues that surround transplantation and organ donation. It is also desirable for such professionals to be familiar with the terminology used to describe and discuss the ethics of transplantation. • Good ethical practice should always be integral to efforts made to advance the science of transplantation. Interaction with stakeholders, lawmakers and those who determine public policy will be essential to the development of optimal future programmes. Key terminology
Fundamental principles of bioethics
Beneficence Doing good for the patient must be the central moral objective for all healthcare staff. Non-maleficence All effort must be made to avoid causing harm or distress to patients and their families. A central principle in organ donation is that donors are by definition ‘harmed’ in order to facilitate donation. This harm must be weighed up against the good that results from transplantation. Autonomy The patient's autonomy must be respected. The individual has a (near) absolute right to determine their own fate – including that of their organs after death. Justice Healthcare professionals should strive to seek fairness. Particularly relevant to transplantation where multiple conflicts of interest exist between various stakeholder groups. Other terms
Deontology From the Greek ‘deon’ meaning obligation or duty. The ethical position which judges the morality of an action or belief on its adherence to a rule, e.g. ‘do no harm’ or ‘always strive to save a life’. Consequentialism Contrasts with deontology; judging the morality of actions according to their consequences. Utilitarianism The ethical position that the value of a particular course of action is determined by how much ‘good’ or happiness results, the total ‘good’ usually referring to the world as a whole. Altruism In a transplant context, the voluntary wish of the individual to make the ‘gift’ of donation of their organs (or equivalent) without expectation of reward. Dignity A complex and difficult term to define but, in this context, one reflecting the unique and precious status of the human being and the ethical requirement not to treat the individual disrespectfully or harmfully in both life and death. Futility A concept that relates to a patient who has reached a point when there is no realistic prospect of a successful outcome, whatever their medical care. Equity The concept of fairness/justice often used in connection with the way organs are allocated and utilised. Also applied to access to transplant for different individuals. Death, organ donation, patient autonomy and the choice to donate
While living donation has been integral to kidney transplantation for decades, deceased donors have always constituted the majority of transplant activity. Death and its diagnosis seemed a simple and easily understandable concept until complex modern intensive methods and care of transplantation forced society to question it in more detail. If doctors are striving to save the life of a patient, and yet there exists a possibility that the patient must die and donate their organs (so that other patients may be helped), there may be a perceived conflict of interest for the responsible physician. To avoid this, a clear separation between medical care in life and the facilitation of deceased donation has been established. The pivotal component of this is the establishment of death. When does death occur?
Substantial ethical debate surrounds the exact definition of death and this is reflected in the variability of definition between societies.1,2 Standard clinical tests for the certification of death include the absence of circulation, respiration, any response to pain or pupillary response to light. However, these tests require a valid setting and need to be confirmed over a sufficient length of time in order to ensure no reasonable possibility of spontaneous reversal. Brain stem death3 allowed certification of death based on irreversible loss of brain stem function. This complex and intensively scrutinised mechanism for individuals to be declared legally dead has allowed organ donation even when the donor has a beating heart and viable organs maintained via mechanical ventilation. The key ethical principle is that donation should proceed only after death has been established and no prospect of spontaneous autoresuscitation exists.4 Similarly, the decision to cease attempts at life- preserving treatments should be taken in a manner independent of considerations relating to organ donation and be based purely on the concept of patient benefit. The idea of brain death remains a focus for ethical debate despite its long enshrinement in law. Initially the term ‘brain dead’ was applied, yet the demonstration of viable neuronal tissue was cited as a refutation of this as a valid state of death. This led to a change of terminology, with ‘brain stem dead’ being the currently accepted expression.5 The management of patients to facilitate organ donation either through the donation-after-brain stem-death (DBD) pathway or the alternative donation-after-circulatory-death (DCD) pathway remains one of the biggest ethical debating points of 21st century transplantation and intensive care medicine. Guidance on the determination and diagnosis of death can be found in the Academy of Royal Colleges Code of Practice for the Diagnosis and Confirmation of Death (2008);6 however, there remains no statutory definition of death in the UK and the working definition, ‘the irreversible loss of the capacity for consciousness combined with irreversible loss of the capacity to breathe’, put forward by the Department of Health, seems both practicable and socially acceptable. However, further clarification of this definition may be of benefit to all stakeholders. Futility, the patient's best interests, and the decision to withdraw life-sustaining treatments
In a situation where organ donation may be feasible, what constitutes a potential donor's best interests? Before organ donation and transplantation, it was accepted that when a stage of futility was deemed to have been reached, further life-prolonging interventions were not in a dying patient's best interests. This was observed in the early days of transplantation, when continuing intervention was seen as unethical as these interventions were not designed for the benefit of the potential donor. This debate was particularly fierce around the issue of elective ventilation, with a historical conclusion that this was not an ethically desirable course of action.7 However, the nature of futility itself may have been changed by the very existence of the possibility for organ donation. Few citizens in the developed world are unaware that donation of organs after death is a possibility. In the UK, originally through the organ donor card system and more recently through the organ donor register (ODR), the opportunity to document one's wishes relating to organ donation has become increasingly accessible. This opt-in system has donor autonomy at its heart. In states like Spain, however, opt-out is the legal norm,8 when the individual must record a wish to opt out of organ donation or it will be assumed that the wish is to go ahead with this action. Other options such as mandated choice come somewhere in between, and the desirability and likely effect on donation rates of each system are widely debated.9 What is certain, though, is that the stated, informed and autonomous wish of a competent, living person to donate their organs can be regarded as a form of mandate to advance organ donation, even if this action may include interventions traditionally considered futile and therefore unethical. In this context, what we mean by ‘best interests’ is less clear-cut. Many – including these authors – would regard it as unethical for a...