NRP is a disruptive innovation that improves the utilization of DCD livers. Despite higher-risk donor-recipient pairing for NRP compared with SCS, we demonstrate a decrease in IC for NRP. These data facilitate benchmarking of thoracoabdominal NRP DCD LT and support further protocol development.

TA-NRP in the United States significantly increased the utilization rate of abdominal organs from DCD donors with comparable outcomes after transplantation. Increasing use of NRP may expand the donor pool without compromising transplant outcomes.

Liver transplantation (LTX) using donors after controlled circulatory death (cDCD) is associated with poorer graft survival and increased incidence of nonanastomotic biliary strictures (NASs) compared to livers procured from brain-dead donors (DBD). The use of normothermic regional perfusion (NRP) during cDCD procurement may improve posttransplant outcomes and reduce the incidence of NAS. In Sweden, cDCD LTX was introduced through a national pilot protocol with mandatory NRP. This study aims to evaluate the outcome of cDCD LTX during the pilot period. Donor and recipient data were collected on all cDCD liver transplants during the pilot period between January 2020 to December 2022. Outcome on NAS, patient and graft survival, early allograft dysfunction, acute kidney injury, and comprehensive complication index was compared to a matched cohort of 28 patients transplanted with a DBD liver between 2018 and 2022. Eighteen patients were transplanted with a liver from a cDCD donor after using NRP. The mean functional warm ischemia time was 29 ± 6 minutes. The mean lactate reduction during NRP was 8.7 ± 2.4 mmol/L, and the end NRP perfusate alanine aminotransferase was 1.4 ± 1 µkat/L. When comparing recipients of cDCD liver transplant to DBD, no significant differences were observed in the incidence of NAS, patient and graft survival, comprehensive complication index, early allograft dysfunction, or acute kidney injury. Study protocol magnetic resonance cholangiopancreatography in cDCD patients showed no signs of subclinical biliary strictures. Evaluation of the Swedish national pilot of cDCD LTX with mandatory NRP shows comparable outcomes to a matched DBD cohort with 94.4% 1-year patient and graft survival and no incidence of NAS within the first year.

There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.

Donation after circulatory death (DCD) in Italy constitutes a relatively unique population because of the requirement of a no-touch period of 20 minutes. The first aim of this study was to compare liver transplantations from donors who were maintained on normothermic regional perfusion after circulatory death and suffered extended warm ischemia (DCD group, n = 20) with those from donors who were maintained on extracorporeal membrane oxygenation (ECMO) and succumbed to brain death (ECMO group, n = 17) and those from standard donors after brain death (donation after brain death [DBD] group, n = 52). Second, we conducted an explorative analysis on the DCD group to identify relationships between the donor characteristics and the transplant outcomes. The 1-year patient survival for the DCD group (95%) was not significantly different from that of the ECMO group (87%; P = 0.47) or the DBD group (94%; P = 0.94). Graft survival was slightly inferior in the DCD group (85%) because of a high rate of primary nonfunction (10%) and retransplantation (15%) but was not significantly different from the ECMO group (87%; P = 0.76) or the DBD group (91%; P = 0.20). Although ischemic cholangiopathy was more frequent in the DCD group (10%), this issue did not adversely impact graft survival because none of the recipients underwent retransplantation due to biliary complications. Moreover, the DCD recipients were more likely to develop posttransplant renal dysfunction with the need for renal replacement therapy. Further analysis of the DCD group showed that warm ischemia >125 minutes and an Ishak fibrosis score of 1 at liver biopsy negatively impacted serum creatinine and alanine transaminase levels in the first posttransplant week, respectively. In conclusion, our findings encourage the use of liver grafts from DCD donors maintained by regional perfusion after proper selection.

Background: Donation after circulatory death (DCD) can increase the pool of available organs for transplantation. We hereby present the 1 year results from 18 controlled DCD (cDCD) using abdominal normo-thermic regional perfusion (NRP). Methods: Patients aged 16 -70 years in coma with devastating brain injury, with a high probability of attaining cardiac arrest within 90 minutes after extubation, were eligible for cDCD evaluation. With the acceptance from the next of kin and their wish for organ donation, Heparin® was given at withdrawal of life-sustaining treatment (WLST) and cardiac arrest observed. After a 5 minute “no-touch” period, extracorporeal membrane oxygenation cannula were introduced by Seldinger´s technique via pre-identified femoral vessels to establish NRP. Cerebral and cardiac reperfusion was prevented by an aortic occlusion catheter. Post transplant kidney graft function was evaluated by measured glomerular filtration rates (mGFR, iohexol plasma clearance) at eight weeks and one year comparing cDCD grafts with DBD grafts matched for recipient and donor age, immunosuppression and era. Mann-Whitney U test was used for comparison and two-tailed p-values < 0.05 were considered statistically significant. Descriptive data from all liver transplant recipients receiving cDCD livers in Oslo are also presented. Results: Eighteen cDCD were performed from 2014-2017. Diagnosis in the cDCD group: traumatic brain injury (n=6), cerebrovascular accident (n=5), hypoxic-anoxic brain injury (n=7). Organs from 2 donors were not used (preoperative cancer/misplaced aortic catheter). There was no significant difference in mGFR between the recipients of 32 cDCD and 163 DBD kidney grafts (P=0.43). The increased rate of delayed graft function in the cDCD group compared to the DBD group (22 vs 5%) did not affect the one-year graft survival (P=0.61). Eight liver transplantations after cDCD were observed for median (range) 26 (16-40) months. There were no delayed graft function and all patients are alive with normalized liver function. No patient has ischemic type biliary lesions associated with cDCD. At ISODP19, we also plan to present two- years data on organ function and graft survival. Conclusions: Excellent graft- and patient outcomes in addition to content next of kin and ICU staff has encouraged us to continue this line of work. The first 32 cDCD kidney transplants have clinical graft function in line with results from our DBD transplantations. The results after liver transplantation using NRP cDCD liver are excellent. The cDCD protocol is now under assessment for national implementation.

While there is increasing interest in its use, definitive evidence demonstrating superiority of normothermic regional perfusion in controlled donation after circulatory death liver transplantation has not been presented. Unlike the rest of the Western world, where use of NRP has been anecdotal, 25% of all cDCD donors that have been performed in Spain since 2012 have included post-mortem NRP. Aim Analyze the first years of the Spanish experience with cDCD liver transplantation, in particular regarding the impact post-mortem NRP has had on organ utilization rates and transplant outcomes. Methods Data was collected regarding potential cDCD liver donors and transplants that resulted between 2012 and 2016. All transplants had at least 6 mos of follow-up. Each donor hospital determined the process by which organs were recovered: NRP with pre-mortem cannulation, NRP with post-mortem cannulation, or super rapid recovery. Results From 2012 to 2016, 370 potential cDCD liver donors were evaluated: 152 with NRP and 218 with SRR. Ultimately, rates of liver transplantation were 64% NRP and 57% SRR (P=0.102). Among livers that were transplanted, median donor age was 57 (46-65 IQR). While there were no differences in terms of relevant donor or recipient characteristics when analyzed according to recovery method, the functional warm ischemia time was shorter when NRP was applied – 12 (10-16) NRP vs. 15 (11-20) SRR – given that in most cases femoral cannulae were placed prior to withdrawal of care. While rates of early allograft dysfunction (22% NRP vs. 29% SRR) and PNF (2% NRP vs. 4% SRR) did not vary, rates of overall biliary complications (9% NRP vs. 24% SRR, P=0.006) and ITBL (2% NRP vs. 12% SRR, P=0.01) were significantly improved among recipients of livers recovered with NRP. One-year graft survival was 87% NRP vs. 78% SRR (P=0.110). On multivariate analysis analyzing risk factors for ITBL (including fWIT), the only significant factor was the organ recovery method used. Conclusions This is the first large series describing the application of NRP in cDCD liver transplantation. While results with SRR were acceptable, results using NRP were superior and comparable to those achieved using standard-quality livers, even in spite of advanced donor age.

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients' outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty-seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty-seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1-year death-censored kidney survival was 91%, and delayed graft function rate was 27%. The 1-year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.

A total of 132 and 93 liver grafts were transplanted after NRP and HOPE, respectively. NRP grafts were procured from younger donors (50 vs 61 years, P < 0.001), with shorter functional donor warm ischemia (22 vs 31 minutes, P < 0.001) and a lower overall predicted risk for graft loss (UK-DCD-risk score 6 vs 9 points, P < 0.001). One-year tumor-death censored graft and patient survival was 93% versus 86% (P = 0.125) and 95% versus 93% (P = 0.482) after NRP and HOPE, respectively. No differences in non-anastomotic biliary strictures, primary nonfunction and hepatic artery thrombosis were observed in the total cohort and in 32 vs. 32 propensity score-matched recipients CONCLUSION:: NRP and HOPE in cDCD achieved similar post-transplant recipient and graft survival rates exceeding 85% and comparable to the benchmark values observed in standard DBD liver transplantation. Grafts in the HOPE cohort were procured from older donors and had longer warm ischemia times, and consequently achieved higher utilization rates. Therefore, randomized controlled trials with intention-to-treat analysis are needed to further compare both preservation strategies, especially for high-risk donor-recipient combinations.

. The use of NRP during DCD organ recovery leads to increased organ utilization and improved transplant outcomes compared with conventional organ recovery.

Prolonged warm ischemia time (WIT) has a negative prognostic value in liver transplantation (LT) using grafts procured after circulatory death (DCD). To assess the value of abdominal normothermic regional perfusion (A-NRP) associated with dual hypothermic oxygenated machine perfusion (D-HOPE) in controlled DCD LT, prospectively collected data on LTs performed between January 2016 and July 2021 were analyzed. Outcome of controlled DCD LTs performed using A-NRP + D-HOPE (<i>n</i> = 20) were compared to those performed with grafts procured after brain death (DBD) (<i>n</i> = 40), selected using propensity-score matching. DCD utilization rate was 59.5%. In the DCD group, median functional WIT, A-NRP and D-HOPE time was 43, 246, and 205 min, respectively. Early outcomes of DCD grafts recipients were comparable to those of matched DBD LTs. In DCD and DBD group, incidence of anastomotic biliary complications and ischemic cholangiopathy was 15% versus 22% (<i>p</i> = 0.73) and 5% versus 2% (<i>p</i> = 1), respectively. One-year patient and graft survival was 100% versus 95% (<i>p</i> = 0.18) and 90% versus 95% (<i>p</i> = 0.82). In conclusion, the association of A-NRP + D-HOPE in DCD LT with prolonged WIT allows achieving comparable outcomes to DBD LT.

Although good results have been reported with the use of normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation (LT), there is a lack of evidence to demonstrate similar results to donation after brain death (DBD). We present a single-center retrospective case-matched (1:2) study including 100 NRP cDCD LTs and 200 DBD LTs and a median follow-up of 36 months. Matching was done according to donor age, recipient Model for End-Stage Liver Disease score, and cold ischemia time. The following perioperative results were similar in both groups: alanine transaminase peaks of 909 U/L in the DBD group and 836 U/L in the cDCD group and early allograft disfunction percentages of 21% and 19.2%, respectively. The 1-year and 3-year overall graft survival for cDCD was 99% and 93%, respectively, versus 92% and 87%, respectively, for DBD (P = 0.04). Of note, no cases of primary nonfunction or ischemic-type biliary lesion were observed among the cDCD grafts. Our results confirm that NRP cDCD LT meets the same outcomes as those obtained with DBD LT and provides evidence to support the idea that cDCD donors per se should no longer be considered as "marginal donors" when recovered with NRP.

This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.

aNRP can safely select and thus is able to rescue DCD liver grafts that were deemed unsuitable for transplantation, while preventing primary nonfunction and minimizing ischemic cholangiopathy.

cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.