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

2. Professional Development Programme for Organ Donation 2

3. 3 Diagnosis of Death Masterclass The six big wins

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

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

6. 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

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

8. Professional Development Programme for Organ Donation Diagnosis of Brainstem Death

9. Professional Development Programme for Organ Donation Significant regional variation –Only 50% of suitable patients given the option of NHBD Significant clinical variation –Diagnosis of death –warm ischaemic times –organ retrieval Is NHBD organ donation maximised in the UK? 9 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.

10. Professional Development Programme for Organ Donation 10 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.

11. Professional Development Programme for Organ Donation Agenda 1Introduction 09.30-09.45 2Diagnosis of Death: A defence of the British criteria 09.45-10.15 3Quiz: Dead or not dead? 10.15-10.30 Break 10.30-10.40 4The confirmation of death 10.40-11.15 5Case study activity 11.15-12.15 6 Questions 12.15-12.25 7 Summary & close 12.25-12.30 11

12. A Defence of the British Criteria Dale Gardiner 12

13. Professional Development Programme for Organ Donation 13 30 years on…

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

15. Professional Development Programme for Organ Donation 15

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

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

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21. Professional Development Programme for Organ Donation 21 Brain Death Cushing1 st Renal auto-Tx (unsuccessful) Transplants 1902 The Concept of Brain Death Did Not Evolve to Benefit Organ Transplants.

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

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

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

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

26. Professional Development Programme for Organ Donation 26 3 rd December 1967

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

28. Professional Development Programme for Organ Donation 28

29. Professional Development Programme for Organ Donation 29 ‘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.’

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

31. Professional Development Programme for Organ Donation 31

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33. Professional Development Programme for Organ Donation 33 diagnosis decision

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

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

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

38. Professional Development Programme for Organ Donation 38 Brain Stem Death UK

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

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

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

42. Professional Development Programme for Organ Donation 42 Brain Stem Death UK

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44. Professional Development Programme for Organ Donation 44 NEJM 2010

45. Professional Development Programme for Organ Donation 45

46. Professional Development Programme for Organ Donation 46 ALIVE DEAD

47. Professional Development Programme for Organ Donation 47 Brain Stem Death UK

48. Professional Development Programme for Organ Donation 48 Brain Stem Death UK

49. Professional Development Programme for Organ Donation 49 Brain Stem Death UK

50. Professional Development Programme for Organ Donation 50

51. Professional Development Programme for Organ Donation 51

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

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55. Professional Development Programme for Organ Donation 55

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

57. Professional Development Programme for Organ Donation 57

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

59. Professional Development Programme for Organ Donation 59 Brain Stem Death UK

60. Professional Development Programme for Organ Donation 60 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.

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62. Professional Development Programme for Organ Donation 62

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

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

65. Professional Development Programme for Organ Donation 65 Alan Shewmon MD

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

67. Professional Development Programme for Organ Donation 67 Brain Stem Death UK

68. Professional Development Programme for Organ Donation 68

69. Professional Development Programme for Organ Donation 69 trauma unitPET scan brain no blood flowingUnited Regional Healthcare System Wichita Falls, Texas

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

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

73. Professional Development Programme for Organ Donation 73

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

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

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

80. Professional Development Programme for Organ Donation 80 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”

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82. Professional Development Programme for Organ Donation 82

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

84. Professional Development Programme for Organ Donation 84 ALIVE DEAD

85. Professional Development Programme for Organ Donation 85

86. Professional Development Programme for Organ Donation 86 Questions?

87. Quiz: Dead or not Dead? 87

88. Professional Development Programme for Organ Donation 88 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

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

90. Professional Development Programme for Organ Donation 90 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

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

92. Professional Development Programme for Organ Donation 92 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.

93. Professional Development Programme for Organ Donation 93 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!

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

95. Professional Development Programme for Organ Donation 95 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?

96. Professional Development Programme for Organ Donation 96 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.

97. Professional Development Programme for Organ Donation 97 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.

98. Professional Development Programme for Organ Donation 98 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.

99. Professional Development Programme for Organ Donation 99 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

100. The Confirmation of Death Alex Manara ICU Frenchay Hospital 100

101. Professional Development Programme for Organ Donation 101 Confirmation vs. Certification

102. Professional Development Programme for Organ Donation 102 600,000 UK deaths per annum

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

104. Professional Development Programme for Organ Donation 104 Confirming Death

105. Professional Development Programme for Organ Donation 105 Confirming Death: Most doctors.

106. Professional Development Programme for Organ Donation 106 Confirming Death: Neurosurgeons...

107. Professional Development Programme for Organ Donation 107 Confirming Death: Orthopods...

108. Professional Development Programme for Organ Donation 108 Confirming Death: What the public think...

109. Professional Development Programme for Organ Donation 109 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 and Wales. Otherwise you’re dead when a doctor says so = accepted medical practice

110. Professional Development Programme for Organ Donation 110 Variation in Practice

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

112. Professional Development Programme for Organ Donation 112 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”

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

114. Professional Development Programme for Organ Donation 114 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”

115. Professional Development Programme for Organ Donation 115 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

116. Professional Development Programme for Organ Donation 116 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

117. 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

118. Professional Development Programme for Organ Donation 118 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

119. Professional Development Programme for Organ Donation 119 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

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

121. Professional Development Programme for Organ Donation 121 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)

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

123. Professional Development Programme for Organ Donation 123

124. Professional Development Programme for Organ Donation 124 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

125. Professional Development Programme for Organ Donation 125 UK Deceased Organ Donors

126. Professional Development Programme for Organ Donation 126 Organ Donation USA

127. Professional Development Programme for Organ Donation 127 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?

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

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

130. Professional Development Programme for Organ Donation 130 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

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

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

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

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

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

136. Professional Development Programme for Organ Donation 136 Neurological Determination of Death in UK Temperature > 34 o C Na+ < 160 mmol/L K+ > 2 mmol/L Glucose > 3 mmol/L < 20mmol/L Phosphate > 0.5 mmol/L < 3 mmol/L Magnesium 3. No reversible causes / confounding factors - Metabolic Serum Na+ > 115mmol/L?

137. Professional Development Programme for Organ Donation 137 Neurological Determination of Death in UK 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 3. No reversible causes / confounding factors - Sedatives

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

139. Professional Development Programme for Organ Donation 139 Neurological Determination of Death in UK Must be done last after other reflexes absent Undertaken no more than twice Achieve CVS stability at PaCO2 > 6kPa before disconnection Disconnect for 5 minutes Return PaCO2 to normal on reconnection Apnoea Test

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

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

142. Professional Development Programme for Organ Donation 142 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

143. Case Study Activity 143

144. Professional Development Programme for Organ Donation 144 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, 15mins to discuss & answer questions and15 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

145. Professional Development Programme for Organ Donation 145 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.

146. Professional Development Programme for Organ Donation 146 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).

147. Questions??? 147