Diagnosis of Death Masterclass Alex Manara Dale Gardiner

Diagnosis of Death Masterclass Alex Manara Dale Gardiner Paul Murphy 31 March 2010 “Improving organ donation within your hospital” Professional Development Programme for Organ Donation 1

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Diagnosis of Death Masterclass The six big wins Professional Development Programme for Organ Donation 3

Diagnosis of Death Masterclass 2. Increased diagnosis of brain stem death 3. Increased donation after cardiac death Professional Development Programme for Organ Donation 4

Incidence of Brainstem Death on ICU (< 75 years, non-cardiac ICUs) Professional Development Programme for Organ Donation

Incidence of Brainstem Death on ICU (< 75 years, non-cardiac ICUs) • 350 missed potential donors • 172 actual donors • 619 additional transplanted patients • Extra 2. 8 donors pmp Professional Development Programme for Organ Donation

Diagnosis of Brainstem Death Reasons for not testing (approx 350 / year) Professional Development Programme for Organ Donation

Diagnosis of Brainstem Death Professional Development Programme for Organ Donation

Is NHBD organ donation maximised in the UK? The Potential Donor Audit has been assessing the potential for NHBD in the UK for the last five years. The map below shows NHB donor numbers by DTC region for 2009. • Significant regional variation – Only 50% of suitable patients given the option of NHBD • Significant clinical variation – Diagnosis of death – warm ischaemic times – organ retrieval Professional Development Programme for Organ Donation 9

Aims: 1. Promote national consistency in the use of the criteria used to diagnose death. 2. You to feel confident in the criteria used to diagnose death whilst being alert to potential pitfalls. 3. For you to be aware of potential criticisms by colleagues and the literature and have thought about possible counter arguments. Professional Development Programme for Organ Donation 10

Agenda 1 Introduction 09. 30 -09. 45 2 Diagnosis of Death: A defence of the British criteria 09. 45 -10. 15 3 Quiz: Dead or not dead? 10. 15 -10. 30 Break 10. 30 -10. 40 4 The confirmation of death 10. 40 -11. 15 5 Case study activity 11. 15 -12. 15 6 Questions 12. 15 -12. 25 7 Summary & close 12. 25 -12. 30 Professional Development Programme for Organ Donation 11

A Defence of the British Criteria Dale Gardiner 12

30 years on… Professional Development Programme for Organ Donation 13

Critics Edmund Pellegrino Margaret Lock Alan Shewmon Rinaldo Bellomo UK critics David Evans David Hill Philip Keep Professional Development Programme for Organ Donation Peter Singer 14

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Criteria for Human Death = The irreversible cessation of brain -stem function => Irreversible unconsciousness + Irreversible apnoea => intra-cranial or extra-cranial cause => 5 mins absent cerebral circulation DO NOT restore Cerebral Circulation Professional Development Programme for Organ Donation 16

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Transplant Technique • Split livers • Marginal Donors Immunosuppressants • Tacrolimus • Mycophenolate Professional Development Programme for Organ Donation 19

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The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants 1 st Renal auto-Tx Brain Death 1902 Cushing (unsuccessful) Transplants Transplants Transplants Professional Development Programme for Organ Donation 21

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants Brain Death 1902 1 st xeno-Tx (unsuccessful) Transplants st Transplants 1 Renal cadaveric Tx Transplants (unsuccessful) Transplants EEG discovered ê In electric potential = Death Loss cortical potentials seen in ischaemia 1950 Professional Development Programme for Organ Donation 22

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants 1 st successful live Renal Tx Transplants Transplants Brain Death 1950 Cessation of brain blood flow = Death Cortical circulatory arrest seen in coma patients 1960 Death of the nervous system = Coma dépassé Professional Development Programme for Organ Donation 23

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants 1 st successful cadaveric Renal Tx Transplants Transplants Brain Death 1960 Irreversible cessation of the EEG = Death Professional Development Programme for Organ Donation 24

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants Brain Death 1967 -68 1 st successful Heart Tx Harvard Criteria Brain Death = DEATH Transplants Transplants Professional Development Programme for Organ Donation 25

3 rd December 1967 Professional Development Programme for Organ Donation 26

Ad Hoc Committee of the Harvard Medical School JAMA 5 th Aug 1968 Professional Development Programme for Organ Donation 27

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‘Our Primary purpose is to define irreversible coma as a new criterion for death… …Obsolete criteria for the definition of death can lead to controversy in obtaining organs for transplantation. ’ Professional Development Programme for Organ Donation 29

The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants Brain Death Future 1 st xeno Tx Brain Death = DEATH 1 st lab grown organ Tx Transplants Transplants Transplants Professional Development Programme for Organ Donation 30

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diagnosis Professional Development Programme for Organ Donation decision 33

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Whole Brain Death Rest of the World Brain Stem Death UK Professional Development Programme for Organ Donation Higher Brain Death Philosophers 35

Peter Singer Professional Development Programme for Organ Donation Higher Brain Death Philosophers 36

Whole Brain Death Rest of the World Professional Development Programme for Organ Donation Rinaldo Bellomo ICM 2004 37

Brain Stem Death UK Professional Development Programme for Organ Donation 38

Whole Brain Death Rest of the World Professional Development Programme for Organ Donation 39

Whole Brain Death Rest of the World Professional Development Programme for Organ Donation 40

Whole Brain Death Rest of the World Professional Development Programme for Organ Donation 41

Brain Stem Death UK Professional Development Programme for Organ Donation 42

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NEJM 2010 Professional Development Programme for Organ Donation 44

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ALIVE Professional Development Programme for Organ Donation DEAD 46

Brain Stem Death UK Professional Development Programme for Organ Donation 47

Brain Stem Death UK Professional Development Programme for Organ Donation 48

Brain Stem Death UK Professional Development Programme for Organ Donation 49

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D. Alan Shewmon, MD Professional Development Programme for Organ Donation 52

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Doctors fight to save brain-dead mom’s foetus. . . … for 3½ months Professional Development Programme for Organ Donation 56

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Whole Brain Death Rest of the World Professional Development Programme for Organ Donation 58

Brain Stem Death UK Professional Development Programme for Organ Donation 59

The inferior hypophysial artery is an artery supplying the posterior pituitary gland. It is a branch of the cavernous carotid artery (internal carotid artery) which is extradural at this point. Professional Development Programme for Organ Donation 60

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Whole Brain Death Rest of the World Professional Development Programme for Organ Donation 63

Criteria for Human Death = The irreversible cessation of brain -stem function => Irreversible unconsciousness + Irreversible apnoea Professional Development Programme for Organ Donation 64

Alan Shewmon MD Professional Development Programme for Organ Donation 65

‘Although we were unable to restore his consciousness or spontaneous breathing, the boy lived several more years. ’ (page 195) Professional Development Programme for Organ Donation 66

Brain Stem Death UK Professional Development Programme for Organ Donation 67

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trauma unit PET scan brain United Regional Healthcare System Wichita Falls, Texas Professional Development Programme for Organ Donation no blood flowing 69

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Regions only Level III Trauma Centre Professional Development Programme for Organ Donation 71

USA Trauma Center Level I - Highest to Level III - Lowest Professional Development Programme for Organ Donation 72

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Criteria for Human Death = The irreversible cessation of brain -stem function => Irreversible unconsciousness + Irreversible apnoea => intra-cranial or extra-cranial cause => 5 mins absent cerebral circulation DO NOT restore Cerebral Circulation Professional Development Programme for Organ Donation 77

75 seconds, 2 minutes, 5 minutes 2 minutes 5 minutes Professional Development Programme for Organ Donation 78

Dr Michael De. Vita University of Pittsburgh Professional Development Programme for Organ Donation 79

3. 7 days old donor Taken to the operating room Lined and given heparin Extubated & sedated Waited 75 seconds of PEA “Best interests of the recipient” Professional Development Programme for Organ Donation 80

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One Thousand One Hundred and Seven NHBD Professional Development Programme for Organ Donation 83

ALIVE Professional Development Programme for Organ Donation DEAD 84

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Questions? Professional Development Programme for Organ Donation 86

Quiz: Dead or not Dead? 87

Question 1 1. The patient flexes their arm at the elbow following imposition of a painful stimulus to the nail bed on that side? Dead - May represent a spinal reflex Professional Development Programme for Organ Donation 88

Question 2 2. The ventilator registers the patient as making spontaneous respirations? Dead - May represent the heart beat creating flow that is triggering ventilation Professional Development Programme for Organ Donation 89

Question 3 3. The patient has a generalised tonic clonic seizure? NOT brain stem dead – the patient must have intact neural connections to have a grand mal fit Professional Development Programme for Organ Donation 90

Question 4 4. The patient’s pulse increases from 70 bpm to 110 bpm during apnoea testing? Dead - Hypercarbia (which occurs during apnoea testing) results in endogenous adrenaline release. Professional Development Programme for Organ Donation 91

Question 5 5. There is slow drift of one eye away from the ear in which cold water is injected? NOT brain stem dead – any eye movements in response to caloric testing signifies the presence of some reflex brain stem arc function. Professional Development Programme for Organ Donation 92

Question 6 6. The patient sits up during apnoea testing (Lazarus sign)? Dead - A spinal reaction to the acidosis which follows hypercarbia. Very unsettling and disturbing! Professional Development Programme for Organ Donation 93

How are you going? These six questions were asked in the Australian JFICM exam 2008 and the pass rate was only 65%! Professional Development Programme for Organ Donation 94

Question 7 7. During an apnoea test on a mechanical ventilator after 20 seconds the patient starts to breathe and then continues to breathe at 16 breaths per minute? Dead – ventilator apnoea ventilation has kicked in. Are you convinced not to do your apnoea tests still connected to the ventilator? Professional Development Programme for Organ Donation 95

Question 8 8. Supra-orbital painful stimulus leads to movement in one of the arms? Not dead – although one primarily looks for movement in the cranial nerve distribution one must actively ensure (by repetition) that this was a coincidental spinal reflex but until proven this may represent the patient is not brain stem dead. Professional Development Programme for Organ Donation 96

Question 9 9. During the second set of brain stem testing the second clinician finds the ears full of wax and can't visualise the drum? Not dead – this finding may invalidate the first oculovestibular test and thus the patient may not be dead. Professional Development Programme for Organ Donation 97

Question 10 10. Due to left orbital trauma you can't visualise or observe the left eye? Dead – may still be dead even if one can’t carry out the full test. Some of the options we discuss in our case based discussions after morning tea. Professional Development Programme for Organ Donation 98

Question 11 10. After a complete set of brain stem tests, confirming clinical brain stem death, your colleague organises a CT angiogram which reveals persisting intracerebral blood flow? Dead – Brain Stem Death is the UK Criteria Professional Development Programme for Organ Donation 99

The Confirmation of Death Alex Manara ICU Frenchay Hospital 10

Confirmation vs. Certification Professional Development Programme for Organ Donation 101

600, 000 UK deaths per annum UK ICU deaths = 15, 000 per annum (2. 5%) 6% 0 f ICU deaths are confirmed with neuro criteria = 900 15 in 10, 000 deaths in UK are confirmed using neuro criteria Other 14, 100 confirmed using cardio-respiratory criteria Of these 300 pa become NHBDs = 2% of ICU deaths Professional Development Programme for Organ Donation 102

Confirming Death • Cessation of heart beat • Cessation of breathing • Unresponsiveness • Relatively easy to make • Reproducible • Recognizable Professional Development Programme for Organ Donation 103

Confirming Death Professional Development Programme for Organ Donation 104

Confirming Death: Most doctors. “YOU’RE DEAD WHEN YOU’VE GOT NO HEART SOUNDS, NO BREATHE SOUNDS AND FIXED DILATED PUPILS” Professional Development Programme for Organ Donation 105

Confirming Death: Neurosurgeons. . . “YOU’RE DEAD WHEN YOUR BRAIN IS DEAD” Professional Development Programme for Organ Donation 106

Confirming Death: Orthopods. . . “YOU’RE DEAD WHEN YOU’RE COLD, BLUE AND STIFF” Professional Development Programme for Organ Donation 107

Confirming Death: What the public think. . . “YOU’RE DEAD WHEN YOUR HEART STOPS” Professional Development Programme for Organ Donation 108

The Law • There is no statutory definition of death in the United Kingdom (Unlike USA) • The determination of death using neurological criteria has been accepted by the courts of England Wales. • Otherwise you’re dead when a doctor says so = accepted medical practice Professional Development Programme for Organ Donation 109

Variation in Practice Professional Development Programme for Organ Donation 110

What is accepted medical practice? Professional Development Programme for Organ Donation 111

Definition of death “The irreversible loss of those essential characteristics which are necessary to the existence of a living human person” = “The irreversible loss of the capacity for consciousness, combined with the irreversible loss of the capacity to breathe” Professional Development Programme for Organ Donation 112

All Death is Brain Death 1. Cardio-respiratory determination of death 2. Neurological determination of death 3. Somatic determination of death Professional Development Programme for Organ Donation 113

Cardio-respiratory criteria “The heart and lung are not important as basic prerequisites to continue life but rather because the irreversible cessation of their functions shows that the brain has ceased functioning” Professional Development Programme for Organ Donation 114

Cardio-respiratory criteria • Need to be applicable to primary care / out of hospital setting • Simultaneous and irreversible onset of apnoea, and unconsciousness in the absence of a circulation. • Irreversible cessation of brain stem function rapidly follows Professional Development Programme for Organ Donation 115

Preconditions for cardiac criteria • Decision made to abandon CPR • The individual meets the criteria for not attempting CPR (ROLE) • Active treatment is being withdrawn as declared not in the patient’s best interests • Patient has an advance directive refusing CPR Professional Development Programme for Organ Donation 116

At “asystole” • Person confirming death present and continuously observes apnoea, asystole and unresponsiveness for a minimum of 5 minutes • Absent circulation confirmed clinically or with monitors • Return of circulation or respiration prompts start of a further 5 minutes from point of next cardio-respiratory arrest • Confirm absent pupillary and corneal reflexes and no central response to pain Professional Development Programme for Organ Donation 117

At “asystole” • Person confirming death present and continuously observes apnoea, asystole and unresponsiveness for a minimum of 5 minutes • Absent circulation confirmed clinically or with monitors • Return of circulation or respiration prompts start of a further 5 minutes from point of next cardio-respiratory arrest • Confirm absent pupillary and corneal reflexes and no central response to pain Professional Development Programme for Organ Donation 118

Irreversibility • Heart will not be restarted because patient not for CPR • Cardiac activity will not resume spontaneously • Cannot be restarted even with CPR No post-mortem procedures that have the potential to restore cerebral perfusion Professional Development Programme for Organ Donation 119

Post mortem Interventions http: //www. dh. gov. uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108827. pdf Professional Development Programme for Organ Donation 120

Post Mortem Interventions Anything that places the person at risk of serious harm or distress is unlikely ever to be in the person’s best interests. (CPR, femoral cannulation, heparinisation) Professional Development Programme for Organ Donation 121

International Differences • 2 minutes Ø Pittsburgh protocol 1993 Ø ANZICS • Minimum of 2 minutes, no more than 5 minutes recommended Ø Society of Critical Care Medicine, USA • Minimum of 5 minutes: Ø Academy of Medical Royal Colleges UK Ø Intensive Care Society, UK Ø Institute of Medicine, USA Ø Canadian Council for Donation and Transplantation • Minimum of 10 minutes Ø Maastricht Conference, Holland Professional Development Programme for Organ Donation 122

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80 year old male with pancreatitis, cerebral infarction and MRSA sepsis CPR abandoned - Doctor went to shower IPPV continued ROSC noted on return at 5 minutes Patient died 2 days later Professional Development Programme for Organ Donation 124

UK Deceased Organ Donors In past 10 years there have been 1138 NHBDs Professional Development Programme for Organ Donation 125

Organ Donation USA In USA approx 3000 NHBDs (2 min – 5 min) Professional Development Programme for Organ Donation 126

Lazarus? Is auto-resuscitation a result of not having a standardised way of confirming death and also defining what can and cannot happen after death? Professional Development Programme for Organ Donation 127

Neurological Determination of Death in UK Professional Development Programme for Organ Donation 128

History • Improved ICU care of comatose patients • Coma depassé described in Paris in 1959 • Deep irreversible coma • Nearly always followed by cardiac arrest Professional Development Programme for Organ Donation 129

Cardiac Prognosis After NDD Pallis 1987: 1300 patients all developed cardiorespiratory arrest even with full support Hung et al 1995: • 73 adults and children • Full and continued CVS support • All became asystolic; within 10 days Professional Development Programme for Organ Donation 130

Rationale for New Guidelines • Variable practice when guidelines not specific • Guidelines not always followed even when specific Professional Development Programme for Organ Donation 131

New Guidelines • Published 2008 • Attempts further standardisation • Primarily a clinical diagnosis • Clinical judgement still required Professional Development Programme for Organ Donation 132

Neurological Determination of Death in UK 1. Patient in deep apnoeic coma Professional Development Programme for Organ Donation 133

Neurological Determination of Death in UK 2. Known cause capable of causing ND Professional Development Programme for Organ Donation 134

Neurological Determination of Death in UK 3. No reversible causes / confounding factors • Primary hypothermia • Metabolic disturbances • Alcohol • Depressant drugs • Muscle relaxants Professional Development Programme for Organ Donation 135

Neurological Determination of Death in UK 3. No reversible causes / confounding factors - Metabolic • Temperature > 34 o C • Na+ < 160 mmol/L • K+ > 2 mmol/L • Glucose > 3 mmol/L < 20 mmol/L • Phosphate > 0. 5 mmol/L < 3 mmol/L • Magnesium Serum Na+ > 115 mmol/L? Professional Development Programme for Organ Donation 136

Neurological Determination of Death in UK 3. No reversible causes / confounding factors - Sedatives • Clinical judgement essential • Impossible to create rules covering every situation • Difficulties mainly with thiopentone and midazolam • Plasma concentrations not good predictors of effect • Use of antagonists may help • Ideally use non cumulative drugs – propofol, remifentanil Professional Development Programme for Organ Donation 137

Neurological Determination of Death in UK 4. Absent brainstem reflexes Professional Development Programme for Organ Donation 138

Neurological Determination of Death in UK Apnoea Test • Must be done last after other reflexes absent • Undertaken no more than twice • Achieve CVS stability at Pa. CO 2 > 6 k. Pa before disconnection • Disconnect for 5 minutes • Return Pa. CO 2 to normal on reconnection Professional Development Programme for Organ Donation 139

Neurological Determination of Death in UK 5. Ancillary Tests • 4 vessel cerebral angiography • CT angiography • MRI angiography • EEG • TCD • SPECT • Brain stem evoked potentials • Response to 2 mg atropine • ICP > MAP Professional Development Programme for Organ Donation 140

Whole Brain Death ? http: //video. bloodservices. ca/Streaming/nddvideo/ Professional Development Programme for Organ Donation 141

Reducing Variability in Practice • Guidelines – Helpful but limited value • CLODs – Professional Development Programme • Development of international approach to confirmation • Prospective observational studies on onset of asystole Professional Development Programme for Organ Donation 142

Case Study Activity 143

Case Study Exercise • We have 2 case studies which we would like you to discuss and respond to in your table groups • You each have a handout of the 2 case studies which provide a case context and a series of questions • We will spend 30 mins total on each case study, 15 mins to discuss & answer questions and 15 mins to feedback as a wider group • This part of the session will take an hour to complete and will be followed by a more general Q&A Professional Development Programme for Organ Donation 144

Case Study 1 A middle-aged woman presents to your Emergency Department at 1600 after collapsing at home. She has fixed pupils and is intubated without drugs. CT head reveals catastrophic subarachnoid haemorrhage. Neurosurgical opinion is that this is an unsurvivable situation and withdrawal of life sustaining treatment is advised. The family approach the ED staff suggesting their relative would wish to be an organ donor. Brain death is suspected. Professional Development Programme for Organ Donation 145

Case Study 2 A young man is admitted to your neuro-critical care unit with severe traumatic brain injury. Despite aggressive treatment his pupils fix after four days and irreversible cessation of brain stem function (brain stem death) is suspected. He has received substantial doses of sedatives (midazolam, alfentanil and propofol). Professional Development Programme for Organ Donation 146

Questions? ? ? 147