Normothermic regional perfusion (NRP) is a novel technique developed to improve organ utilization and recipient outcomes following donation after circulatory death (DCD). NRP has revolutionized DCD liver transplant by extending donor criteria and reducing the incidence of ischemic cholangiopathy (IC) and other complications in recipients. However, there is significant geographic and center-specific variation in NRP use and practices. This review collates practices from pioneering NRP centers across the globe regarding donor selection criteria, NRP techniques, organ viability monitoring, and other key areas to help guide the continued growth of NRP liver transplantation.

DCD livers recovered using NRP have consistently demonstrated excellent outcomes, with IC and patient and graft survival rates approaching those seen with grafts from donation after brain death donors. Recently, transplant centers have been working to increase the DCD donor pool by relaxing limits on donor quality, reconsidering organ viability markers, and combining NRP with ex situ machine perfusion technologies.

NRP is a powerful organ recovery technology transforming the practice of DCD liver transplantation. Current evidence suggests that organ utilization could be further expanded using NRP recovery, with excellent clinical outcomes reported by centers using less stringent donor and organ viability criteria.

Pancreas and islet transplantation face critical organ shortage challenges, with many potential grafts discarded due to concerns about consequences of ischemia-reperfusion injury, particularly from donation after circulatory death (DCD) donors. Static cold storage remains standard practice but has significant limitations. Novel preservation technologies may improve transplant outcomes, donor selection and even expand the donor pool.

Normothermic regional perfusion in DCD donors has increased pancreas utilization with promising one-year graft survival comparable to donation after brain-death (DBD) donors. Hypothermic machine perfusion maintains tissue integrity and shows promising preclinical results. Oxygenated hypothermic machine perfusion successfully restores tissue adenosine triphosphate (ATP) levels without notable tissue injury. Normothermic machine perfusion, despite challenges, offers potential for viability assessment and resuscitation.

Advanced preservation technologies provide platforms for assessment, reconditioning, and therapeutic interventions for pancreas grafts. Clinical translation requires consensus on perfusion parameters and perfusate composition optimized for pancreatic preservation. Future developments should focus on implementing sensitive and specific assessment methods, including beta-cell specific biomarkers, to confidently select and utilize marginal pancreas grafts for transplantation.

Published work evaluating machine perfusion of DCD (donation after circulatory death) liver grafts in situ and ex situ is rapidly evolving, with several landmark studies published in the last 6 months. The central question in DCD liver transplant remains; which strategies most effectively reduce cholangiopathy? This condition, which results in repeated hospital admissions, interventions, re-transplantation and death, is a major deterrent to DCD utilization. This review considers current evidence in the mitigation of transplant cholangiopathy by machine perfusion in DCD liver grafts.

Studies which directly address DCD cholangiopathy as a primary outcome are few in number, despite their critical importance. In systematic reviews, Normothermic Regional Perfusion and Hypothermic Machine Perfusion consistently and significantly reduce transplant cholangiopathy rates. By contrast, the efficacy of Normothermic Machine Perfusion performed at donor or recipient centres is less well described and cautious interpretation is required. The most recent development, namely hypothermic followed by normothermic perfusion, has only now appeared in the literature but appears to offer advantages compared to either technology alone.

To reduce DCD cholangiopathy, current data best support the use of donor centre NRP or recipient centre HMP. However, utilization is also improved when warm perfusion is involved.

Donor livers from older donation after circulatory death (DCD) donors are frequently discarded for transplantation because of the high risk of graft failure. It is unknown whether DCD livers from older donors benefit from dynamic preservation.

In a multicenter study, we retrospectively compared graft and patient outcomes after transplantation of livers from DCD donors older than 60 y, preserved with either static cold storage (SCS), ex situ sequential dual hypothermic perfusion, controlled oxygenated rewarming, and normothermic perfusion (DHOPE-COR-NMP), or in situ abdominal normothermic regional perfusion (aNRP).

Fifty-six liver transplants were included in the SCS cohort, 33 in the DHOPE-COR-NMP cohort, and 27 in the aNRP cohort. Donor warm ischemia time was significantly shorter in the SCS group than in DHOPE-COR-NMP ( P  < 0.001) and aNRP ( P  < 0.001) groups. Cold ischemia times were similar. One-year incidence of nonanastomotic biliary strictures was lower after DHOPE-COR-NMP (3%, P  = 0.03) or aNRP (7%, P  = 0.13), compared with SCS alone (21%). Anastomotic strictures were less frequent in aNRP (19%) compared with DHOPE-COR-NMP (52%; P  = 0.015). One-year graft and patient survival were similar.

Dynamic preservation allows safe transplantation of livers from DCD donors aged 60 y or older. The risk of nonanastomotic strictures was significantly lower after DHOPE-COR-NMP than after SCS, despite longer donor warm ischemia times.

To overcome limitations of traditional ex vivo lung perfusion (EVLP) for controlled donation after circulatory death (cDCD) lungs, this study aimed to evaluate a novel pulmonary abdominal normothermic regional perfusion (PANRP) technique, which we uniquely designed, for in situ assessment of lungs from cDCD donors.

We modified the abdominal normothermic regional perfusion circuit for simultaneous lung and abdominal organ assessment using independent extracorporeal membrane oxygenation components. Blood was oxygenated via a membrane oxygenator and returned to the body, with pulmonary flow adjusted to maintain pressure < 25 mmHg. Femoral cannulation was performed, and the lungs were ventilated with standard settings. Organ function was assessed over 2 h using PaO2/FiO2, AST, ALT, BUN, and Cr measurements to monitor perfusion and oxygen delivery.

PANRP maintained stable lung function, with P/F ratios above 300, and preserved abdominal organ parameters, including stable AST, ALT, BUN, and Cr levels. Adequate urine output was observed, indicating normal renal function. Pulmonary artery pressure remained < 20 mmHg, and pulmonary vascular resistance was kept at 400 dyn・s/cm5, showing no signs of lung dysfunction or injury throughout the circuit.

PANRP offers a promising alternative to traditional EVLP for cDCD lung evaluation, allowing in situ assessment of multiple organs simultaneously. This approach may overcome logistical and economic challenges associated with ex vivo techniques, enabling a more efficient evaluation process. Further studies are warranted to confirm its clinical applicability and impact on long-term outcomes.

Controlled donation after the circulatory determination of death (cDCDD) has emerged as a strategy to increase the availability of organs for clinical use. Traditionally, organs from cDCDD donors have been subject to standard rapid recovery (SRR) with poor posttransplant outcomes of abdominal organs, particularly the liver, and limited organ utilization. Normothermic regional perfusion (NRP), based on the use of extracorporeal membrane oxygenation devices, consists of the in situ perfusion of organs that will be subject to transplantation with oxygenated blood under normothermic conditions after the declaration of death and before organ recovery. NRP is a potential solution to address the limitations of traditional recovery methods. It has become normal practice in several European countries and has been recently introduced in the United States. The increased use of NRP in cDCDD has occurred as a result of a growing body of evidence on its association with improved posttransplant outcomes and organ utilization compared with SRR. However, the expansion of NRP is precluded by obstacles of an organizational, legal, and ethical nature. This article details the technique of both abdominal and thoracoabdominal NRP. Based on the available evidence, it describes its benefits in terms of posttransplant outcomes of abdominal and thoracic organs and organ utilization. It addresses cost-effectiveness aspects of NRP, as well as logistical and ethical obstacles that limit the implementation of this innovative preservation strategy.

Donation after circulatory death liver transplantation (DCD LT) is underused given historical outcomes fraught with ischemic cholangiopathy (IC). We aimed to assess 6-mo IC in LT from DCD via normothermic regional perfusion (NRP) compared with DCD via static cold storage (SCS).

A retrospective review of adult Maastricht-III DCD liver donors and recipients at the University of Colorado Hospital from January 1, 2017, to August 27, 2024, was performed. The 6-mo IC rate was compared between NRP and SCS. Secondary outcomes included biochemical assessments of accepted versus declined NRP liver allografts and allograft and patient survival for NRP and SCS groups.

One hundred sixty-two DCD LTs (SCS = 79; NRP = 97) were performed and 150 recipients (SCS = 74; NRP = 86) reached 6-mo follow-up. Six-month IC was lower for NRP compared with SCS (1.2% versus 9.5%, P = 0.03). The Donor Risk Index (2.44 [2.02-2.82] versus 2.17 [1.97-2.30], P = 0.002) and UK DCD Risk Score (4.2 ± 2.9 versus 3.2 ± 2.3, P = 0.008) were higher for NRP versus SCS. The Liver Graft assessment Following Transplantation score was less for NRP compared with SCS (-3.3 versus -3.1, P < 0.05). There were several differences in median biochemical parameters during NRP between accepted and declined livers, including higher terminal biliary bicarbonate (22.7 [20.9-29.1] versus 10.8 [7.6-13.1] mEq/L, P = 0.004). There were no significant differences in 12-mo allograft or patient survival for NRP versus SCS.

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.

The growing disparity between the demand for pancreas transplants and the availability of suitable organs underscores the urgent need for innovative donor strategies, including the utilization of donors after circulatory death (DCD). This scoping review presents a comprehensive comparative analysis of transplantation outcomes between DCD and donors after brain death (DBD), focusing on pancreatic graft survival, postoperative complications, and functional metrics such as graft performance and HbA1c levels. Although DCD grafts were suspected to be associated with higher rates of early complications, including delayed graft function and thrombosis, altogether resulting from potentially more ischemia-reperfusion injuries, their long-term outcomes are comparable to those of DBD grafts. This equivalence is likely driven by careful donor selection, a meticulous pancreas procurement, use of normothermic regional perfusion and a short ischemic time. The findings highlight the transformative potential of DCD donors in expanding the pancreas donor pool, addressing critical organ shortages, and enhancing transplant accessibility. This review advocates for the integration of DCD donors into routine clinical practice, emphasizing the need for optimized clinical protocols and organ allocation strategies. By leveraging DCD donors more effectively, the transplant community can make significant strides in improving patient outcomes and addressing the global organ shortage crisis.

Heart transplantation from donors after the circulatory determination of death is expanding worldwide. Thoraco-abdominal normothermic regional perfusion (TA-NRP) allows the validation and recovery of the donation after the circulatory determination of death (DCDD) heart, but there is limited evidence on the results of heart transplants performed with this approach. This multicenter, nationwide, prospective study describes the short-term outcomes of adult patients receiving a DCDD heart transplant obtained via TA-NRP followed by static cold storage in Spain. Recipients of hearts from donors after the neurologic determination of death were used as controls. The primary outcome was a composite of 1-year all-cause death or severe primary graft failure. During 2020-2023, 98 adult DCDD and 347 donations after the neurologic determination of death (DNDD) heart transplants were performed across 11 centers. The primary outcome was met by 21 (21.4%) and 77 (22.2%) patients, respectively (P = .87). Thirty-day and 1-year survival were 94.9% and 88.8% in the DCDD vs 93.7% and 87.3% in the DNDD group (P = .70), respectively. Severe primary graft failure was observed in 13 (13.3%) vs 52 (15.0%) patients (P = .67). By inverse probability weighting, the DCDD heart was not associated with the primary outcome (hazard ratio, 0.97; 95% confidence interval, 0.58-1.62; P = .91). In conclusion, adult DCDD heart transplantation based on TA-NRP and static cold storage provides similar short-term outcomes than DNDD heart transplants.

To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation.

Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity.

Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 μmol/L for NMP and 129.9 μmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates.

Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

In recent years, there has been resurgence in donation after circulatory death (DCD). Despite that, the number of organs transplanted from these donors remains low due to concerns about their function and a lack of an objective assessment at the time of donation. This overview examines the current DCD practices and the classification modifications to accommodate regional perspectives. Several risk factors underscore the reluctance to accept DCD organs, and we discuss the modern strategies to mitigate them. The advent of machine perfusion technology has revolutionized the field of DCD transplantation, leading to improved outcomes and better organ usage. With many strategies at our disposal, there is an urgent need for comparative trials to determine the optimal use of perfusion technologies for each donated organ type. Additional progress in defining therapeutic strategies to repair the damage sustained during the dying process should further improve DCD organ utilization and outcomes. However, there remains wide variability in access to DCD donation and transplantation, and organizational efforts should be doubled up with consensus on key ethical issues that still surround DCD donation in the era of machine perfusion.

Advancements in xenotransplantation intersecting with modern machine perfusion technology offer promising solutions to patients with liver failure providing a valuable bridge to transplantation and extending graft viability beyond current limitations. Patients facing acute or acute chronic liver failure, post-hepatectomy liver failure, or fulminant hepatic failure often require urgent liver transplants which are severely limited by organ shortage, emphasizing the importance of effective bridging approaches. Machine perfusion is now increasingly used to test and use genetically engineered porcine livers in translational studies, addressing the limitations and costs of non-human primate models. Current reports about artificial and bioartificial liver support combined with xenografts showcase the potential in ex vivo xenogeneic perfusion. Breakthroughs, such as the perfusion of genetically modified porcine liver with FDA-approved machine perfusion systems connected to human blood circulation, underscore the interest and potential feasibility of a "liver dialysis" bridge to allotransplantation or recovery. This review provides an overview of the past and current research in the field of ex vivo pig liver xenoperfusion.

The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP.

The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival.

The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P  < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P  < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P  = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P  = 0.235, respectively).

The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers.

Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020.

This single-center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records.

From 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion-facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion-facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion-facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant.

Provision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life-saving organ transplants with only modest product use, about three RBC units per organ transplant in this single-center study.

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia-reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion-NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia-reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence.

Although kidney transplantation from living donors (LD) offers better long-term results than from deceased donors (DD), elderly recipients are less likely to receive LD transplants than younger ones. We analyzed renal transplant outcomes from LD versus DD in elderly recipients with a propensity-matched score. This retrospective, observational study included the first single kidney transplants in recipients aged ≥65 years from two European registry cohorts (2013-2020, n = 4,257). Recipients of LD (n = 408), brain death donors (BDD, n = 3,072), and controlled cardiocirculatory death donors (cDCD, n = 777) were matched for donor and recipient age, sex, dialysis time and recipient diabetes. Major graft and patient outcomes were investigated. Unmatched analyses showed that LD recipients were more likely to be transplanted preemptively and had shorter dialysis times than any DD type. The propensity score matched Cox's regression analysis between LD and BDD (387-pairs) and LD and cDCD (259-pairs) revealing a higher hazard ratio for graft failure with BDD (2.19 [95% CI: 1.16-4.15], p = 0.016) and cDCD (3.38 [95% CI: 1.79-6.39], p < 0.001). One-year eGFR was higher in LD transplants than in BDD and cDCD recipients. In elderly recipients, LD transplantation offers superior graft survival and renal function compared to BDD or cDCD. This strategy should be further promoted to improve transplant outcomes.

Since 2019, the annual transplantation rate of hearts donated following circulatory death (DCD) has increased significantly in the United States. The 2 major heart procurement techniques following circulatory death are direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). Post-transplant survival for heart recipients has not been compared between these 2 techniques.

This observational study uses data on adult heart transplants from donors after circulatory death from January 1, 2019 to December 31, 2021 in the Scientific Registry of Transplant Recipients. We identified comparable transplant cases across procurement types using propensity-score matching and measured the association between procurement technique and 1-year post-transplant survival using Kaplan-Meier and Cox proportional hazards model stratefied by matching pairs.

Among 318 DCD heart transplants, 216 (68%) were procured via DPP, and 102 (32%) via NRP. Among 22 transplant centers that accepted circulatory-death donors, 3 used NRP exclusively, and 5 used both procurement techniques. After propensity-score matching on recipient and donor factors, there was no significant difference in 1-year post-transplant survival (93.1% for NRP vs 91.1% for DPP, p = 0.79) between procurement techniques.

NRP and DPP procurements are associated with similar 1-year post-transplant survival. If NRP is ethically permissible and improves outcomes for abdominal organs, it should be the preferred procurement technique for DCD hearts.

An adult university hospital ethics committee evaluated a proposed TA-NRP protocol in the fall of 2018. The protocol raised ethical concerns about violation of the Uniform Determination of Death Act and the prohibition known as the Dead Donor Rule, with potential resultant legal consequences. An additional concern was the potential for increased mistrust by the community of organ donation and transplantation. The ethics committee evaluated the responses to these concerns as unable to surmount the ethical and legal boundaries and the ethics committee declined to endorse the procedure. These concerns endure.

Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs. Multiple technical approaches can be used for abdominal-only NRP DCD donors and this review describes these techniques.

NRP has been associated with higher utilization of organs, particularly liver and heart grafts, from DCD donors and with better recipient outcomes. There are lower rates of delayed graft function in kidney transplant recipients and lower rates of ischemic cholangiopathy in liver transplant recipients. These benefits are driving increased interest from abdominal transplant programs in using NRP for DCD procurements.

This paper describes the technical aspects of NRP DCD that allow for maximization of its use based on different donor and policy characteristics.

Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD).

MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD.

Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P  = 0.03, I 2  = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P  = 0.04; I 2  = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts.

Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.

Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR).

To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery.

This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers.

cDCD livers were recovered by either NRP or SRR.

The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival.

A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts.

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.

The main limitation to increased rates of lung transplantation (LT) continues to be the availability of suitable donors. At present, the largest source of lung allografts is still donation after the neurologic determination of death (brain-death donors, DBD). However, only 20% of these donors provide acceptable lung allografts for transplantation. One of the proposed strategies to increase the lung donor pool is the use of donors after circulatory-determination-of-death (DCD), which has the potential to significantly alleviate the shortage of transplantable lungs. According to the Maastricht classification, there are five types of DCD donors. The first two categories are uncontrolled DCD donors (uDCD); the other three are controlled DCD donors (cDCD). Clinical experience with uncontrolled DCD donors is scarce and remains limited to small case series. Controlled DCD donation, meanwhile, is the most accepted type of DCD donation for lungs. Although the DCD donor pool has significantly increased, it is still underutilized worldwide. To achieve a high retrieval rate, experience with DCD donation, adequate management of the potential DCD donor at the intensive care unit (ICU), and expertise in combined organ procurement are critical. This review presents a concise update of lung donation after circulatory-determination-of-death and includes a step-by-step protocol of lung procurement using abdominal normothermic regional perfusion.

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

Normothermic regional perfusion (NRP) represents an innovative technology that improves the outcomes for liver and kidney recipients of donation after circulatory determination of death (DCD) organs but protocols for abdominal-only NRP (A-NRP) DCD are lacking in the US.

We describe the implementation and expansion strategies of a transplant-center-based A-NRP DCD program that has grown in volume, geographical reach, and donor acceptance parameters, presented as four eras.

In the implementation era, two donors were attempted, and one liver graft was transplanted. In the local expansion era, 33% of attempted donors resulted in transplantation and 42% of liver grafts from donors who died within the functional warm ischemic time (fWIT) limit were transplanted. In the Regional Expansion era, 25% of attempted donors resulted in transplantation and 50% of liver grafts from donors who died within the fWIT limit were transplanted. In the Donor Acceptance Expansion era, 46% of attempted donors resulted in transplantation and 72% of liver grafts from donors who died within the fWIT limit were transplanted. Eight discarded grafts demonstrated a potential opportunity for utilization.

The stepwise approach to building an A-NRP program described here can serve as a model for other transplant centers.

Donor hearts procured after circulatory death (DCD) may significantly increase the number of hearts available for transplantation. The purpose of this study was to analyze current DCD and brain-dead donor (DBD) heart transplantation rates and characterize organ refusal using the most up-to-date United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network data.

We analyzed UNOS and Organ Procurement and Transplantation Network DBD and DCD candidate, transplantation, and demographic data from 2020 through 2022 and 2022 refusal code data to characterize DCD heart use and refusal. Subanalyses were performed to characterize DCD donor demographics and regional transplantation rate variance.

DCD hearts were declined 3.37 times more often than DBD hearts. The most frequently used code for DCD refusal was neurologic function, related to concerns of a prolonged dying process and organ preservation. In 2022, 92% (1329/1452) of all DCD refusals were attributed to neurologic function. When compared with DBD, DCD donor hearts were more frequently declined as the result of prolonged warm ischemic time (odds ratio, 5.65; 95% confidence interval, 4.07-7.86) and other concerns over organ preservation (odds ratio, 4.06; 95% confidence interval, 3.33-4.94). Transplantation rate variation was observed between demographic groups and UNOS regions. DCD transplantation rates are currently experiencing second order polynomial growth.

DCD donor hearts are declined more frequently than DBD. DCD heart refusals result from concerns over a prolonged dying process and organ preservation. Heart transplantation rates may be substantially improved by ex situ hemodynamic assessment, adoption of normothermic regional perfusion guidelines, and quality initiatives.

Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data.

We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe.

All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045).

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.

Since the advent of University of Wisconsin preservation solution in the 1980s, clinicians have learned to work within its confines. While affording improved outcomes, considerable limitations still exist and contribute to the large number of livers that go unused each year, often for fear they may never work. The last 10 years have seen the widespread availability of new perfusion modalities which provide an opportunity for assessing organ viability and prolonged organ storage. This review will discuss the role of in situ normothermic regional perfusion for livers donated after circulatory death. It will also describe the different modalities of ex situ perfusion, both normothermic and hypothermic, and discuss how they are thought to work and the opportunities afforded by them.

Given the current severe shortage of available livers for transplantation, there is an urgent need to maximize the utilization of donor organs. One of the strategies to increase the number of available livers for transplantation is to improve organ utilization through the use of elderly, overweight, or organs donated after circulatory death. However, the utilization of these "marginal" organs was associated with an increased risk of early allograft dysfunction, primary nonfunction, ischemic biliary complications, or even re-transplantation. Ischemia-reperfusion injury is a key mechanism in the pathogenesis of these complications.

Orthotopic liver transplantation remains the definitive treatment for patients with end-stage liver disease. Unfortunately, the increasing demand for donor livers and the limited supply of viable organs have both led to a critical need for innovative strategies to expand the pool of transplantable organs. The mitochondrion, central to hepatic cellular function, plays a pivotal role in hepatic ischemic injury, with impaired mitochondrial function and oxidative stress leading to cell death. Mitochondrial protection strategies have shown promise in mitigating IRI and resuscitating marginal organs for transplant. Machine perfusion (MP) has been proven a valuable tool for reviving marginal organs with very promising results. Evaluation of liver viability during perfusion traditionally relies on parameters including lactate clearance, bile production, and transaminase levels. Nevertheless, the quest for more comprehensive and universally applicable viability markers persists. Normothermic regional perfusion has gained robust attention, offering extended recovery time for organs from donation after cardiac death donors. This approach has shown remarkable success in improving organ quality and reducing ischemic injury using the body's physiological conditions. The current challenge lies in the absence of a reliable assessment tool for predicting graft viability and post-transplant outcomes. To address this, exploring insights from mitochondrial function in the context of ischemia-reperfusion injury could offer a promising path toward better patient outcomes and graft longevity. Indeed, hypoxia-induced mitochondrial injury may serve as a surrogate marker of organ viability following oxygenated resuscitation techniques in the future.

The British Transplantation Society (BTS) 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated and this manuscript summarises the relevant recommendations in abdominal organ transplantation from Donation after Circulatory Death (DCD) donors, encompassing the chapters on liver, kidney, pancreas and islet cell transplantation.

Heart failure imposes a significant burden on all health care systems and has a 5-year mortality of 50%. Heart transplantation and ventricular assist device (VAD) implantation are the definitive therapies for end stage heart disease, although transplantation appears to offer superior long-term survival and quality of life over VAD implantation. Transplantation is limited by a shortage in donor hearts, resulting in considerable waiting list mortality. Donation after circulatory determination of death (DCD) offers a significant uplift in the number of donors for heart transplantation. The outcomes both from the UK and internationally have been exciting, with outcomes at least as good as conventional donation after brain death (DBD) transplantation. Currently, DCD hearts are reperfused using ex-situ machine perfusion (ESMP). Whilst ESMP has enabled the development of DCD transplantation, it comes at significant cost, with the per run cost of approximately GBP £90,000. In-situ perfusion of the heart, otherwise known as thoraco-abdominal normothermic regional perfusion (taNRP) is cheaper, but there are ethical concerns regarding the potential to restore cerebral perfusion in the donor. We must determine whether there is any cerebral circulation during in-situ perfusion of the heart to ensure that it does not invalidate the diagnosis of death and potentially violate the dead donor rule. Besides this, there is a need for a randomised controlled trial to definitively determine whether taNRP offers any clinical advantages over ex-situ machine perfusion. This viewpoint article explores these issues in more detail.

United States transplant centers have low rates of liver allograft utilization from donation after circulatory death (DCD) donors. Prolonged functional donor warm ischemic time (f-DWIT) is associated with worse outcomes; however, center practices regarding f-DWIT are unclear. As emerging technologies are changing the landscape of DCD liver transplantation, this study aims to gain insights into the practices of US centers around DCD liver allograft utilization.

An electronic survey was distributed to transplant surgeons at US transplant centers from May to July 2022.

Responses were received from 108 transplant surgeons, of which, 44.4% reported their center's annual DCD liver transplant volume as <10%, and 40.7% reported volumes of 10% to 30%. Warm ischemic time (WIT) was the principal donor variable considered by accepting surgeons (72.2%). Center definition of f-DWIT varied widely, with at least 14 definitions being used. Nearly half of the surgeons (48.6%) defined f-DWIT as time from systolic blood pressure (SBP) <80 mm Hg or oxygen saturation (Sp02) <80% to flush; 21.5% defined f-DWIT as ≤30 minutes from withdrawal of life-sustaining therapy to flush. Nearly 13% of centers use normothermic machine perfusion for most of their DCD liver allografts. More than half of surgeons transplanted at least 1 DCD liver allograft recovered after normothermic regional perfusion.

Differences in the definition of f-DWIT and acceptance patterns of DCD liver allografts limit the ability to evaluate patient and allograft outcomes. As the DCD landscape is evolving, consensus definitions and granular databases can improve the transplant community's ability to evaluate outcome data and utilization from DCD liver allografts.

Organ transplantation with donation after circulatory death can potentially increase the donor pool. Here, we report the rare case of triple-organ (heart/liver/kidney) transplantation from a donor after circulatory death using thoraco-abdominal normothermic regional perfusion. The recipient was a 61-year-old man with end-stage heart failure, liver failure, and kidney failure secondary to arrhythmogenic right ventricular dysplasia. He received a heart/liver/kidney transplantation from a donor after circulatory death. The course was complicated with primary graft dysfunction of the heart that resolved on postoperative day 3. The patient was discharged on postoperative day 39. He has no evidence for rejection on heart biopsy, and all 3 organs exhibit stable function. The use of donation after cardiac death donors greatly increases the donor pool and should be considered for patients requiring multiorgan transplantation. The use of thoraco-abdominal normothermic reperfusion is not only a feasible method for multiorgan procurement but also provides enhanced protection for all transplanted organs.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.