In-situ v Normothermic Regional Perfusion for Abdominal Organs

Transcription

1 In-situ v Normothermic Regional Perfusion for Abdominal Organs ANGEL RUIZ M.D. DONATION AND TRANSPLNAT COORDINATION UNIT MEDICAL DIRECTION HOSPITAL CLÍNIC DE BARCELONA

2 Introduction Donation after circulatory death (cdcd or udcd) has become a significant source of organ donors Warm ischemic damage increases the risk of primary non-function and a suboptimal long-term graft function Normothermic regional perfusion (NRP) has been proposed as an alternative to super-rapid recovery (SRR) to minimize the impact of warm ischemia and improve functional restoration and organ outcome

3 Warm Ischemia and DCD

4 SUPER-RAPID RECOVERY Direct In situ Perfusion IN SITU PERFUSIÓN Doble baloon & triple lumen catheter Doble baloon & triple lumen catheter Venous Dreinage

5 REGIONAL PRESERVATION (nrp or hrp) Normothermic Recirculation 1-4h (6h) with Pump maintenance > L/m 2 Continuous gasometric and ionic control (every 30 min) Hepatic and renal biochemical Control Hemogram Control Reheparinization (1,5 mg/kg/90min)

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8 - Survival: In situ Perfusion 1year 71,8% - 5 years 50% CP Bypass 1year 87,3% - 5 years 76,1%

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11 P = 0.03 P = 0.36 P = 0.01

12 30 min CA 30 min CA + 30 min NRP

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15 Compare results of cdcd liver transplants performed in Spain with post-mortem NRP with those achieved with super rapid recovery, the current standard for cdcd. Prospective cohort study including all potential cdcd liver donors evaluated in Spain and the liver transplants that resulted between 06/2012 and 12/2016, with follow-up ending 12/2017 Recovery method determined by individual donor hospitals: NRP with pre-mortem cannulation NRP with post-mortem cannulation Super rapid recovery

16 342 potential cdcd liver donors evaluated & transplanted during study period: NRP: 152 (44%) Transplanted: 95 SRR: 190 (56%) Transplanted: 117 REASONS FOR DISCARDING cdcd LIVERS NRP (N=57/152) SRR (N=73/190) Poor macroscopic aspect at recovery 32 (21%) 51 (27%) Technical failure of NRP 6 (3,9%) -- Technical/logistical problem(s) associated with recovery 4 (2,6%) 11 (6%) Prolonged warm ischemic time 4 (2,6%) 7 (4%) Altered laboratory value(s) 4 (2,6%) 2 (1%) Anatomical problem(s) associated with the graft 2 (2,6%) 1 (0.5%) Pathological biopsy 2 (1,4%) 1 (0.5%) Previously undiagnosed cancer 2 (1,4%) 0 Active untreated infection 1 (0,7%) 0

17 DONOR- AND GRAFT-RELATED CHARACTERISTICS Raw Analysis IPTW Analysis NRP SRR P value SD* NRP SRR SD* (N=95) (N=117) Age (y) 57 [45-65] 56 [47-64] [44-65] 56 [46-64] Sex male 63 (66 3%) 77 (65 8%) (62 0%) 79 (69 0%) Cause of death CVA 42 (44 2%) 49 (41 9%) (39 7%) 48 (41 2%) Anoxic brain injury 38 (40 0%) 47 (40 2%) (48 2%) 48 (42 0%) Traumatic brain injury 8 (8 4%) 13 (11 1%) (7 4%) 13 (11 0%) Other 7 (7 4%) 8 (6 8%) (4 7%) 7 (5 7%) ICU stay (days) 7 [4-12] 7 [5-11] [5-13] 7 [5-11] Total WIT (min) 18 [13-23] 22 [19-26] < [15-30] 21 [17-25] Functional WIT (min) 12 [9-16] 15 [12-20] < [11-20] 13 [11-19] CIT (min) 315 [ ] 340 [ ] [ ] 340 [ ] Preservation UW or IGL-1 37 (38 9%) 15 (12 8%) < (23 6%) 27 (23 6%) solution HTK 1 (1 1%) 27 (23 1%) < (11 4%) 15 (13 4%) Celsior 57 (60 0%) 75 (64 1%) (65 0%) 72 (62 9%) *Bold-marked figures are greater in absolute value than 0 15.

18 RECIPIENT- AND TRANSPLANT-RELATED CHARACTERISTICS Raw Analysis IPTW Analysis NRP SRR P value SD* NRP SRR SD* (N=95) (N=117) Age (y) 56 [52-61] 59 [53-63] [52-60] 58 [52-62] Sex male 74 (77 9%) 99 (84 6%) (82 6%) 92 (79 9%) Laboratory MELD score 15 [11-19] 13 [9-18] [10-17] 14 [9-21] High-volume transplant center 4 69 (72 6%) 88 (75 2%) (74 0%) 85 (73 8%) Transplant indication Cirrhosis 53 (55 8%) 75 (64 1%) (66.9%) 72 (62 5%) Hepatocellular carcinoma 35 (36 8%) 38 (32 5%) (28 4%) 39 (33 7%) Re-transplantation or 2 (2 1%) 2 (1 7%) (1 9%) 2 (2 1%) fulminant liver failure Other 5 (5 3%) 2 (1 7%) (2 8%) 2 (1 7%) *Bold-marked figures are greater in absolute value than Defined as >50 liver transplants per year.

19 POST-TRANSPLANTATION COMPLICATIONS AND OUTCOMES NRP (N=95) SRR (N=117) Raw Analysis IPTW Analysis Risk Estimates [95% CI] P value Risk Estimates [95% CI] P value Early allograft dysfunction 21 (22%) 32 (27%) 0 75 [ ] [ ] Primary non-function 2 (2%) 3 (3%) 0 82 [ ] [ ] Hepatic artery thrombosis 4 (4%) 3 (3%) 1 67 [ ] [ ] All biliary complications 8 (8%) 36 (31%) 0 21 [ ] < [ ] <0 001 ITBL* 2 (2%) 15 (13%) 0 15 [ ] [ ] Retransplantation 5 (5%) 11 (9%) 0 54 [ ] [ ] Patient death 7 (7%) 20 (17%) 0 44 [ ] [ ] Graft loss 11 (12%) 28 (24%) 0 49 [ ] [ ] *Ischemic-type Biliary Lesions.

20 Graft Survival P = 0.008

21 RECENT SERIES DESCRIBING cdcd LIVER TRANSPLANTATION PERFORMED BY EXPERIENCED GROUPS Center, period N Donor age (y) Functional WIT (min) CIT (min) All biliary complications ITBL 1-year patient survival 1-year graft survival Washington University in St. Louis, [8-60] 12 [1-25] 318 [ ] 20% 8% 96% 94% 2014 Indiana University, [9-55] 11 [7-26] 294 [ ] 23% 0 88% 88% Toronto General Hospital & Oschner Clinic (15) 21(8) total 306 (72) 17% 4% 98% 96% Foundation, Oschner Clinic Foundation, (15) 20 (8) (92) 25% 3% 93% 92% Kings College, [range 16 (5) total 420 (12) 20% 2% >90% >90% 0-85] Mayo Clinics Florida, Rochester, & Arizona, (11) 19 (8) total 324 (120) 18% 8% 92% 86% (5) 20 (9) total 318 (84) 30% 12% 91% 87% University Hospital Birmingham, [27-52] 17 [14-21] 414 [ ] 27% 11% ~92% ~85% [64-71] 18 [14-21] 426 [ ] 33% 12% ~88% ~80% Spanish multicenter, [47-64] 15 [12-20] 340 [ ] 31% 13% 88% 83% 1 Include some of the same patients. 2 Starting from SBP <80 mmhg instead of <55-60 mmhg. 3 Using post-mortem NRP [45-65] 12 [9-16] 315 [ ] 8% 2% 93% 88%

22 Clinical Outcomes of MP in DCD LT Group Period Graft type N CIT (h) PNF (%) ITBL (%) 6-mo. graft survival (%) University Hospital Zurich cdcd (dwit ) ( ) University Medical Center Groningen 2014 cdcd (dwit ) ( ) Italian multicenter udcd (dwit ) 4 5 ( ) UK multicenter 2013 University of Cambridge Toronto General Hospital 2015 University of Alberta, Edmonton Queen Elizabeth Hospital, Birmingham ??? DBD cdcd (dwit ) DBD cdcd (dwit ) DBD cdcd (dwit ) DBD cdcd (dwit ) DBD cdcd (dwit ) * One graft lost during MP due to twisting of the portal vein NR ( ) NR 0 0 NR 3.1 ( ) * 7.0 ( )

23 90 CA + 4 h CS 90 CA + 60 NRP + 4 h NMP

24 I declare to have NO CONFLICT OF INTERESTS with any Company

25 Review of the outcome of kidney transplantation from cdcd in Hospital Clínic de Barcelona that currently employs both techniques, normothermic regional perfusion and super-rapid recovery cdcd Acceptance criteria: Age 85yr Kidney, 65yr Liver No absolute Contraindication for Donation Functional Warm Isquemia Time Liver < 30 minutes Kidneys < 90 minutes

26 Transplant characteristics NRP (24) SRR (64) p Patient age Patient gender (M/F) 14/10 40/24 NS 1 st Tx 2 nd Tx 3 rd Tx NS Donor age < Donor gender 18/6 32/ Immunosuppression: ATG + TACRO + mtori + PRED ATG + TACRO + MPA + PRED BASIL + TACRO + MPA + PRED 17 (70.8%) 7 (29.2%) 0 38 (59.4%) 21 (32.8%) 5 (7.8%) * * CNI+mTOR vs CNI+MPA

27 Transplant characteristics NRP (24) SRR (64) p Functional warm ischemia (min) p< Total warm ischemia (min) p< Cold ischemia (hr) Pulsatile perfusion machine 11/24 (45.8%) 34/64 (53.1%)

28 Renal function recovery NRP (24) SRR (64) p PNF 1/24 (4.2%) 1/64 (1.5%) 0.46 DGF (%) 8/23 (34.7%) 26/63 (41.3) DGF (days)

29 Renal function recovery 3 months creatinine 1 yr creatinine 2 years serum creatinine mg/dl 1 p= mg/dl 1 p= mg/dl 1 p= NRP SRR 0 NRP SRR 0 NRP SRR 1.58 ± 0.14 (=23) 1.78 ± 0.08 (n=63) 1.23 ± 0.08 (n=19) 1.78 ± (n=46) 1.24 ± 0.13 (n=15) 1.80 ± 0.14 (n=18)

30 Renal function recovery 3 months nadir creatinine days to nadir creatinine 2 40 mg/dl 1 p= post-transplant days p= NRP SRR 0 NRP SRR 1.53 ± 0.15 (n=23) 1.64 ± 0.08 (n=42) 19.7 ± 4.5 (n=22) 29.8 ± 3.0 (n=57)

31 Acute rejection NRP (24) SRR (64) Acute rejection 1yr 4/23 (17.4%) 8/63 (12.7%) Borderline rejection 3/23 (13.0%) 6/63 (9.5) AMR 1/4 (25%) 6/8 (75%)

32 Patient survival % survival % 86.5% 20 p=0.26 NRP (24) SRR (64) Post-transplant months

33 Death-censored graft survival Death-censored graft survival Excluding PNF % 94.0% % 95.0% % survival % survival p=0.13 SRR (64) NRP (24) p=0.12 SRR (63) NRP (23) Post-transplant months Post-transplant months

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38 Conclusions The use of post-mortem NRP appears to: In liver transplantation Reduce postoperative biliary complications, Ischemic-type biliary lesions, and graft loss. Allow for successful transplantation of livers, udcd and cdcd, even from cdcd donors of advanced age. In Kidney transplantation No differences in DGF incidence and immediate renal function recovery between NRP and SRR Comparable short-term survival rates Better mid and long-term renal function for NRP donor grafts In Pancreas and Heart transplantation Be a valid methodology to obtain valid organs Better graft survival rates

39 Thank You for your Attention