32 nd Spanish Co-ordination Congress

Transcription

1 32 nd Spanish Co-ordination Congress Santander 19 th October 2017 Stephen Large ma ms mrcp frcs(cth) frcs mba pae(rcp)

2 conflicts of interest 1. TransMedics: halved cost of disposables in one of our experiments 2. Novatis: advisor for annual transplant conference Aims: 1. describe the reasons for and 2. development of DCD heart transplantation 3. results of DCD heart transplantation to date

3 So what is the fuss all about? In

4 Adult Heart Transplants Kaplan-Meier Survival by Era (Transplants: January 1982 June 2014) Median survival (years): =8.5; =10.4; =11.9; /2014=NA All pair-wise comparisons were significant at p < Survival with best medical Rx 2016 JHLT Oct; 35(10):

5 Adult Heart Transplants Kaplan-Meier Survival by Era (Transplants: January 1982 June 2014) Median survival (years): =8.5; =10.4; =11.9; /2014=NA All pair-wise comparisons were significant at p < Prognos;c Value added 2016 JHLT Oct; 35(10):

6 100% 80% 60% 40% 20% Adult Heart Transplants Func;onal Status of Surviving Recipients by Karnofsky Score (Follow-ups: January 2009 June 2015) 10% 20% 30% 40% 50% 60% 70% 80% 90% 0% 1 Year (N=11,431) 3 Years (N=9,766) 5 Years (N=8,242) 2016 JHLT Oct; 35(10): %

7 UK Heart Transplant Activity Figure 7.1 Deceased donor heart programme in the UK, 1 April March 2014, Number of donors, transplants and patients on the active transplant list at 31 March Donors 200 Transplants Transplant list Num ber Year NHSBT Annual Report on Cardiothoracic Transplanta8on 2013/2014. Available at hbp// organ_specific_report_cardiothoracic_2014.pdf

8 1. Tracking 147 patients on the routine list for 3 years Available at http// organ_specific_report_cardiothoracic_2014.pdf

9 1. Tracking 147 patients on the routine list for 3 years 2. Tracking patients on the urgent list for same period = 46% tx Available at http// organ_specific_report_cardiothoracic_2014.pdf

10 What to do? In

11 Ayyaz A. Ali et al Eur J Cardiothorac Surg (2007) 31 (5): /566 donors

12 1400 DBD, living and DCD donation NHSBT 2016 report DBD donors 1200 Living donors DCD donors NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http// organ_specific_report_cardiothoracic_2014.pdf

13 1400 DBD, living and DCD donation NHSBT 2016 report DBD donors 1200 Living donors DCD donors NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http// organ_specific_report_cardiothoracic_2014.pdf

14 Is DCD heart transplantation possible? Recent NHSBT update: probably 135 more donor /year British Journal of Anaesthesia 108 (S1): i108 i121 (2012) Donation after circulatory death A. R. Manara 1*, P. G. Murphy 2 and G. O Callaghan 3

15 Is it needed? NHSBT (3 year period)

16 Papworth Hospital NHS Founda;on Trust NHS So can we use DCD donor hearts clinically? DCD results in profoundly ischaemic organs: but how ischaemic?

17 Method for modelling DCD (rat and pig) Am J Transplant (8) Ali A et al.

18 Energy stores in the porcine DCD model Ayyaz Ali PhD

19 Contractile reserve in isolated cardio-myocytes after isoproterenol administration: BSD vs. 15 min NHBD heart Am J Transplant (8) Ali A et al.

20 Hearts from DCD donors display acceptable biventricular function after heart transplatation. Am J Transplant (8) Ali A et al.

21 DCD heart transplantation: How tolerant the heart to normothermic ischaemia? 1. Ayyaz Ali PhD 2. Int Rev Cell Mol Biol ; 298: and so for all organs

22 Tolerance to duration of ischaemia (canine): Ganote et al AJP 80(3)

23 Orthotopic porcine heart transplant model DCD heart Tx BSD heart Tx Hearts from DCD donors display acceptable biventricular function after heart transplantation. Am J Transplant (8) Ali A et al. Left ventricle Right ventricle Ayyaz Ali PhD

24 DCD v DBD donation: Problem: DCD DBD Heart beating: X Brain damage Catecholamine storm

25 So what about clinically? In

26 Left and right ventricular pressure-volume loops from normal human heart. Left and right P/V loops after resuscitation following 23 min normothermic arrest in the human J Heart Lung Transplant Mar;28(3): Ali A et al,

27 Papworth Hospital The Code Of Practice For The Diagnosis & Confirmation Of Death NHS Founda;on Trust NHS After 5 minutes of continued cardiorespiratory arrest, the absence of pupillary responses to light, of corneal reflexes, and of motor response to supra-orbital pressure is confirmed Diagnosing death in this situation requires confirmation that there has been irreversible damage to the vital centres in the brain-stem due to the length of time in which the circulation to the brain has been absent. Cerebral perfusion should not be restored after death has been confirmed

28 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST)

29 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST) FuncXonal warm ischaemia (FWIT)

30 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST) Loss of pulse = asystole FuncXonal warm ischaemia (FWIT)

31 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST) Loss of pulse = asystole FuncXonal warm ischaemia (FWIT) + 5mins confirmaxon of DCD death

32 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST) Loss of pulse = asystole Method of organ protecxon following insults FuncXonal warm ischaemia (FWIT) + 5mins confirmaxon of DCD death

33 Establishing blood supply for this ischaemic heart: 1. DPP direct procurement to perfusion Langandorff blood perfusion 2. NRP Normo-thermic reperfusion neck vessels ligated to prevent brain perfusion - limited perfusion with ECMO

34 1. Direct procurement and perfusion - DPP: Withdrawal of life support (WLST) 1 Loss of pulse = asystole Method of organ protecxon following insults FuncXonal warm ischaemia (FWIT) + 5mins confirmaxon of DCD death

35 Establishing blood supply for this ischaemic heart: 1. DPP direct procurement to perfusion Langandorff blood perfusion 2. NRP Normo-thermic reperfusion neck vessels ligated to prevent brain perfusion - limited perfusion with ECMO

36 Thoraco-abdominal normothermic reperfusion TA-NRP: Withdrawal of life support (WLST) Loss of pulse = asystole Method of organ protecxon following insults FuncXonal warm ischaemia (FWIT) + 5mins confirmaxon of DCD death

37 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST) Loss of pulse = asystole Method of organ protecxon following insults FuncXonal warm ischaemia (FWIT) + 5mins confirmaxon of DCD death TransportaXon of organ to recipient hospital

38 Timings following identification of futile treatment & consent for DCD organ donation: Withdrawal of life support (WLST) Loss of pulse = asystole Method of organ protecxon following insults TransplantaXon FuncXonal warm ischaemia (FWIT) + 5mins confirmaxon of DCD death TransportaXon of organ to recipient hospital

39 Method for modelling DCD (rat and pig) WLST REPERFUSION ANOXIA FWIT DEATH ASYSTOLE

40 Serum lactate levels in the blood based perfusate of the DCD donor heart on donor NRP and OCS or ECMS (extra corporeal machine perfusion) (Messer S 2016 by kind permission) TA-NRP ECMP

41 Timings DPP (15) NRP (13) withdraw asystole 33±53 25±39 asystole blood perf. 21.6± ±2.4 (ischaemia) Death to Reperfusion 16 8

42 Ejection Fraction 65 Functional Assessment Donor Technique (Cardiac Index (L/min/m 2 ) NRP 13 (DPP 15) 3.4 CO (L/min) 6.7 Heart Rate (bpm) 114 CVP (mmhg) 5 PCWP (mmhg) 9 MAP (mmhg) 78

43 Transplant DPP 15 NRP 13 OCS time 275±76 197±89 implant 37.4± ±5.9

44 Outcomes DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 VenXlaXon DuraXon (days) 0.6 ( ) 2.1 ( ) ( ) 0.6( ) ns CVVH n (%) 5 (24) 6 (29) ns 3 (25) 2 (22) ns ITU DuraXon (days) 5 (3-5) 7 (6-9) (4-5) 3 (3-7) ns Hospital DuraXon (days) 19 (17-26) 27 (19-34) ns 20 (18-27) 19(16-23) ns RejecXon n (%) 9 (43) 13 (62) ns 4 (33) 5 (56) ns

45 Outcomes DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 VenXlaXon DuraXon (days) 0.6 ( ) 2.1 ( ) ( ) 0.6( ) ns CVVH n (%) 5 (24) 6 (29) ns 3 (25) 2 (22) ns ITU DuraXon (days) 5 (3-5) 7 (6-9) (4-5) 3 (3-7) ns Hospital DuraXon (days) 19 (17-26) 27 (19-34) ns 20 (18-27) 19(16-23) ns RejecXon n (%) 9 (43) 13 (62) ns 4 (33) 5 (56) ns

46 Results Other solid organ usage with DCD heart Tx:

47 Results Retrieval Technique NRP vs DPP

48 Incidence of Cause-Specific Deaths 20% 16% 12% 8% 4% Adult Heart Transplants Cumulative Incidence of Leading Causes of Death (Transplants: January 1994 June 2014) CAV Malignancy (non-lymph/ptld) Grae Failure Renal Failure Acute Rejec;on Infec;on (non-cmv) Mul;ple Organ Failure 0% Years 2016 JHLT Oct; 35(10):

49 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion

50 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion

51 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion

52 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion

53 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion

54 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion

55 ! Take home messages: of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion 7. Perhaps some increased use of other organs

56 ! Musing? 1. Can we make this a National programme? 2. Can we make the DCD heart more tolerant of normo- thermic ischameia? 3. What I/R damage there is around death: can this be reversed/prevented? 4. Can these be expanded to the abdominal organs?

57 Heart transplantation & DCD provision Manchester Papworth Harefield

58 ! Musings: 1. Can we make this a National programme? 2. Can this extend to other centres? 3. Can we make the DCD heart more tolerant of normo- thermic ischameia?

59 ! Musings: 1. Can we make this a National programme? 2. Can this extend to other centres? 3. Can we make the DCD heart more tolerant of normo- thermic ischameia?

60 Is this so very far off?

61