1. Organ Donation Past, Present and Future Donation after Brain-Stem Death DBD Jerome McCann Arpan Guha 21 st May 2013 1

2. Session Objectives Present regional data for DBD Understand that DBD gives better organs than DCD Increase rate of neurological confirmation of death by increasing confidence in the Diagnosis of Death Increase quality of DBD organs – adoption of extended care bundle and compliance with the six early interventions in donor optimisation – collaboration in Scout pilot 2 Organ Donation Past, Present and Future

3. Regional Data Jerome McCann 3 NORTH WEST

4. Organ Donation Past, Present and Future Donation after Brain Death (DBD) Mechanically ventilated patient where death has been confirmed using neurological criteria. Kidneys Liver Pancreas Lungs Heart Small Intestine 74 donors -5.1% increase NORTH WEST

5. Organ Donation Past, Present and Future 5 Donations over time: North West Team 181.3% -5.1% 26.6% NORTH WEST

6. Organ Donation Past, Present and Future pancreas liver lungs kidneys heart DCDDBD intestine

7. DBD- Neurological death testing rate -------- National rate 87 82 76 74 86 78 73 76 74 76 74 ND tested (%) 0 20 40 60 80 100 Team EasternLondon Midlands North West Northern Ireland Scotland South Central South East South Wales South West Yorkshire 1 April 2012 to 31 March 2013, data as at 4 April 2013 Organ Donation Past, Present and Future 7 NORTH WEST Tied 9th with 3 others

8. ND tested (%) 0 20 40 60 80 100 Number of neurological death suspected patients 051015202530 1 10 11 12 13 14 15 16 17 18 19 2 20 21 22 23 2425 26 27 28 293 30 31 32 33 4 5 6 7 8 9 HospitalNational rate95% Lower CL 95% Upper CL99.8% Lower CL99.8% Upper CL DBD- North West Neurological death testing rate Organ Donation Past, Present and Future 8 1 April 2012 to 31 March 2013, data as at 4 April 2013 1Barrow-In-Furness, Furness General Hospital 2Douglas, Nobles I-O-M Hospital 3Chester, Countess Of Chester Hospital 4Crewe, Leighton Hospital 5Macclesfield, Macclesfield District General Hospital 6Warrington, Warrington Hospital 7Liverpool, Royal Liverpool University Hospital 8Liverpool, Alder Hey Children's Hospital 9Prescot, Whiston Hospital 10Southport, Southport District General Hospital 11Liverpool, University Hospital Aintree 12Liverpool, Walton Centre For Neurology And Neurosurgery 13Wirral, Arrowe Park Hospital 14Lancaster, Royal Lancaster Infirmary 15Blackpool, Blackpool Victoria Hospital 16Preston, Royal Preston Hospital 17Blackburn, Royal Blackburn Hospital 18Chorley, Chorley And South Ribble District General Hospital 19Bolton, Royal Bolton Hospital 20Bury, Fairfield General Hospital 21Manchester, North Manchester General Hospital 22Manchester, Manchester Royal Infirmary 23Manchester, Royal Manchester Children's Hospital 24Manchester, Wythenshawe Hospital 25Oldham, Royal Oldham Hospital(Rochdale Road) 26Salford, Salford Royal 27Stockport, Stepping Hill Hospital 28Ashton-Under-Lyne, Tameside General Hospital 29Manchester, Trafford General Hospital 30Wigan, Royal Albert Edward Infirmary 31Bodelwyddan, Glan Clwyd District General Hospital 32Wrexham, Maelor General Hospital 33Bangor, Ysbyty Gwynedd District General Hospital

9. Mean no. of organs donated per donor 1 April 2012 to 31 March 2013, data as at 4 April 2013 Tied 6’th 9 Organ Donation Past, Present and Future NORTH WEST

10. Organ Donation Past, Present and Future Diagnosis of brain-stem death 10 37 years on 19762008

11. 11 Organ Donation Past, Present and Future

12. 12 Organ Donation Past, Present and Future Harvey Cushing describes increased brain pressure provoking respiratory arrest with preserved heartbeat.

13. 13 Organ Donation Past, Present and Future Brain death: Discovered not Invented (by intensive care) 1940s Danish medical students hand ventilate polio victims Mouth to Mouth Resuscitation gains prominence & Mechanical Ventilation becomes possible 1954 1 st successful kidney transplant between identical twins

14. 14 Organ Donation Past, Present and Future 1962 1 st successful deceased donor kidney Tx 1963 1 st successful deceased donor liver & lung Tx 1966 1 st successful deceased donor pancreas Tx 1968 1 st successful deceased donor heart Tx Proposed that the EEG can demonstrate death of the Central Nervous System. 1964, Keith Simpson “there is life so long as circulation of oxygenated blood is maintained to live brainstem centres”

15. 15 Organ Donation Past, Present and Future Modern intensive care practice grows. Organ Donation from Brain Dead donors increases worldwide. 1976 (clarified 1979) UK Criteria for Diagnosing Death using Neurological Criteria Published.

16. 16 Organ Donation Past, Present and Future Growing use of ECMO and other techniques to support the circulation, establish that it is possible to be alive, without a heart-beat. 2008 UK Criteria for Circulatory Criteria published for the 1 st time. 5 minutes. Eugene Bouchut 1846 Rene´ Laennec 1819

17. UK Definition of Death 17 Organ Donation Past, Present and Future “The definition of death should be regarded as the irreversible loss of the capacity for consciousness, combined with irreversible loss of the capacity to breathe… therefore irreversible cessation of the integrative function of the brain-stem equates with the death of the individual.” All human death is anatomically located to the brain.

18. Organ Donation Past, Present and Future A medical concept of death DEATH Irreversible loss of the capacity for consciousness Irreversible loss of the capacity to breathe Neurological Criteria Circulatory CriteriaSomatic Criteria

19. Dx Death using Neurological Criteria Organ Donation Past, Present and Future 19 1.An established aetiology capable of causing structural damage to the brain which has led to the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe. Cause tells you irreversibility, based on the natural history of the disease Cause tells you how long you should observe before testing: SAH 6 hours Hypoxia 24 hours DEATH Irreversible loss of the capacity for consciousness Irreversible loss of the capacity to breathe

20. Organ Donation Past, Present and Future 20 1.An established aetiology capable of causing structural damage to the brain which has led to the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe. 2.An exclusion of reversible conditions capable of mimicking or confounding the diagnosis of death using neurological criteria. DEATH Irreversible loss of the capacity for consciousness Irreversible loss of the capacity to breathe Dx Death using Neurological Criteria

21. Organ Donation Past, Present and Future 21 2.An exclusion of reversible conditions capable of mimicking or confounding the diagnosis of death using neurological criteria. DEATH Irreversible loss of the capacity for consciousness Irreversible loss of the capacity to breathe 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 Dx Death using Neurological Criteria

22. Organ Donation Past, Present and Future 22 1.An established aetiology capable of causing structural damage to the brain which has led to the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe. 2.An exclusion of reversible conditions capable of mimicking or confounding the diagnosis of death using neurological criteria. 98.5% Death confirmed in 1220 of 1238 tests (2012 data) DEATH Irreversible loss of the capacity for consciousness Irreversible loss of the capacity to breathe Dx Death using Neurological Criteria

23. Organ Donation Past, Present and Future 23 1.An established aetiology capable of causing structural damage to the brain which has led to the irreversible loss of the capacity for consciousness combined with the irreversible loss of the capacity to breathe. 2.An exclusion of reversible conditions capable of mimicking or confounding the diagnosis of death using neurological criteria. 3.A clinical examination of the patient, which demonstrates profound coma, apnoea and absent brainstem reflexes. DEATH Irreversible loss of the capacity for consciousness Irreversible loss of the capacity to breathe Dx Death using Neurological Criteria

24. Brain-stem reflexes Organ Donation Past, Present and Future 24 Pupils (II, III) Corneal (V, VII) Pain (V, VII) Gag (IX, X) Cough (IX, X) Oculovestibular (III, VI, VIII)  Oculocephalic  Suck } Paediatric

25. Apnoea Test Organ Donation Past, Present and Future 25 5 minutes with paCO 2 > 0.5 KPa Starting paCO 2 > 6.0 KPa StartingpH<7.4 Recommended method: After pre-oxygenation, disconnect the patient from the ventilator and administer oxygen via a suction catheter in the endotracheal tube at a rate of >6 L/minute. If oxygenation is a problem, consider the use of a CPAP circuit (egMapleson B). The apnoea test is performed only twice in total.

26. Testing for Brain-stem Death Organ Donation Past, Present and Future 26 “This form is consistent with and should be used in conjunction with, the AoMRC (2008) A Code of Practice for the Diagnosis and Confirmation of Death and has been endorsed for use by the following institutions: Faculty of Intensive Care Medicine, Intensive Care Society and the National Organ Donation Committee.” Full Abbreviated

27. Organ Donation Past, Present and Future 27

28. Organ Donation Past, Present and Future WHY TEST?

29. Organ Donation Past, Present and Future A guiding dignity consistent approach to declaring death Dying, is a process, which effects different functions and cells of the body at different rates of decay. Doctors must decide at what moment along this process there is permanence and death can be appropriately declared.

30. Organ Donation Past, Present and Future A doctors duty Diagnose the dead 1.Safe – no coming back to life after death declared 2.Timely – no unnecessary delay

31. Organ Donation Past, Present and Future WHY TEST? Where Brain Stem Death (BSD) is suspected, it is highly desirable to confirm this by Brain Stem Testing: To eliminate all possible doubt regarding survivability To confirm diagnosis for families In cases subject to medico-legal scrutiny To provide choice regarding organ donation

32. Organ Donation Past, Present and Future diagnosis decision

33. Organ Donation Past, Present and Future TWO TESTS or ONE? National professional guidance mandates two tests to be performed regardless of organ donation (Bolam&Bolithio). Same two doctors carry out the second set of tests immediately after the first set (update family and stabilise patient). Death is retrospectively confirmed at the conclusion of the second test. Until then, as a matter of law and ethics, it is necessary to treat the patient as alive.

34. Organ Donation Past, Present and Future 20081976 Lesson 1

35. Organ Donation Past, Present and Future Lesson 2

36. Organ Donation Past, Present and Future Lesson 3 Take your time Atypical presentation Hypoxic brain injury >24 hours

37. Organ Donation Past, Present and Future Lesson 4 Induced hypothermia has unpredictable consequences See Lesson 3

38. Organ Donation Past, Present and Future Lesson 5 NO EEG

39. Organ Donation Past, Present and Future Lesson 6 Start with Lesson 2 = use your brain and examine your patient 1.Clinical brain death + NO flow = Death 2.Clinical brain death + flow = Wait See Lesson 3 = take your time and ask ‘Is reversibility possible?’

40. Optimising the brainstem dead donor Organ Donation Past, Present and Future 40

43. Donor optimisation Ameliorate ‘systemic’ effects of brain stem death Why? Increase number of donors Increase number of organs per donor Increase quality of organs Who takes responsibility? ICU staff: medical and nursing SN-ODs Retrieval teams ‘Scout’ Cardio-thoracic teams Organ Donation Past, Present and Future 43

44. ‘Collateral damage’ Hormonal Diabetes insipidus Hypovolaemia Hypernatraemia T3 / T4 reduces ACTH Blood glucose Hypothermia Organ Donation Past, Present and Future 44

45. Incidence of organ involvement Hypotension81% Diabetes insipidus65% DIC28% Cardiac dysrrhythmias25% Pulmonary oedema18% Metabolic acidosis11% J Heart Lung Transplantation 2004 (suppl) Organ Donation Past, Present and Future 45

46. Organ Donation Past, Present and Future 46

47. Evidence Totsuka Transplant Proc. 2000; 32;322-326 High sodium in liver donor doubles graft loss Rosendale Transplantation 2003. 75 (4): 482-487 Protocol increased organs per donor 3.1 to 3.8. Increased probability of transplant. Snell J Heart Lung Transplant 2008;27:662-7 54% of Australian lung donations used for transplant vs. 13% in UK Organ Donation Past, Present and Future 47

48. Principles Ameliorate ‘systemic’ effects of brain stem death Why? Increase number of donors Increase number of organs per donor Increase quality of organs Who takes responsibility? ICU staff: medical and nursing SN-ODs Retrieval teams ‘Scout’: who are they attached to? Cardio-thoracic teams Abdominal teams Free standing Organ Donation Past, Present and Future 48

49. What do we aim for ? General stability Examples of target values MAP: 60 – 80 mm Hg Heart rate: 60 – 100 / min SR CI: > 2.1 l/min/m 2 Guidelines Australian Canadian Map of Medicine ICS NHSBT Organ Donation Past, Present and Future 49

50. Cardiovascular management Summary of cardio vascular target values MAP: 60 – 80 mm Hg CVP: 4 – 10 mm Hg Heart rate: 60 – 100/min SR CI: > 2.1 l/min/m 2 (can be higher, be aware of myocardial stunning) Filling targets: no good evidence for any specific targets, depends on device SvO 2 > 60% SVRI target Secondary target Dehydration  temptation to maintain MAP with vasopressors rather than filling Organ Donation Past, Present and Future 50

51. Respiratory management Recruitment manoeuvre Post BSD testing: apnoea test resulting in atelectasis After suctioning / disconnection When SpO 2 drops / FiO 2 increases Lung protective ventilation: 4 – 8 ml/kg ideal body weight Permissive hypercapnia with pH > 7.25 Optimum PEEP (5 – 10 cm H 2 O) and FiO 2 (aim for < 0.4 as able) Head–up positioning (30 - 45°) Suctioning, physiotherapy as required Antibiotics for purulent secretions: local microbiology surveillance Avoid over-hydration Organ Donation Past, Present and Future 51

52. Managing Diabetes insipidus Very common occurrence Pathophysiology Posterior pituitary failure Polyuria: output > 4ml/kg/h Dehydration with  Na + Usually at least partially addressed with stabilisation for BSD testing Treatment: Fluids Vasopressin DDAVP Aim for u-output 0.5 – 2.0 ml / kg / h Organ Donation Past, Present and Future 52

53. Hormonal treatment Vasopressin Reduction in other vaso-active drugs Dose: 1 – 4 units/h (can start with boluses of 1 unit at a time) Liothyronine (T3) No clear evidence yet for either use or not May add haemodynamic stability in very unstable donor Dose: 3 units/h, sometimes bolus of 4 units asked for by retrieval team Methylprednisolone in all cases Dose: 15 mg/kg up to 1g Insulin At least 1 unit/h (Occasionally may need to add glucose infusion) ‘Tight’ glycaemic control (4 - 10 mmol/l) Organ Donation Past, Present and Future 53

54. Haematological management DIC seen occasionally as direct consequence of BSD May require correcting prior to BSD testing if bleeding Hb> 8 g/dl (~ 10 g/dl traditionally advocated) (even > 7g/dl ?) No evidence on harm with lower Hb, but some evidence of harm with blood transfusions and organ function post transplant Where Hb borderline, ensure blood available for retrieval procedure: local protocols and antibodies will determine whether G&S only, or units to be cross matched Use of clotting factors Only where bleeding is an issue Monitor clotting status Use local hospital protocol Retrieval procedure may require additional products Organ Donation Past, Present and Future 54

55. General measures Maintain normothermia (active warming may be required) Thrombo-embolism prophylaxis Stockings Sequential compression devices LMWH Positioning Head-up Side to side Attention to cuff pressures and leaks to prevent aspiration Continue NG feeding (may be reduced/ stopped for bowel transplant) Antibiotics according to sensitivities or empirical according to Trust guidelines Organ Donation Past, Present and Future 55

56. Monitoring optimisation Implementation: use of care bundle Adherence easy to monitor Audit first 5 priorities Results of optimisation evaluated Number of organs retrieved Increase in cardiothoracic organs retrieved Quality of organs: organ function in recipients Delayed graft function Quality: biomarkers Duration of graft function: long term project Organ Donation Past, Present and Future 56