Normothermic Regional Perfusion in Organ Procurement: Do the Kidneys Benefit?

Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study.

POINT: Does Normothermic Regional Perfusion Violate the Ethical Principles Underlying Organ Procurement? Yes

Normothermic Regional Perfusion: Ethical Issues in Thoracic Organ Donation

To compare the effectiveness in U.S. practice of normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) for donation after circulatory death (DCD) liver transplantation (LT). DCD livers historically conferred inferior outcomes to donation after brain death donors, primarily due to ischemic biliary injury. NRP and NMP have emerged as promising strategies to mitigate this risk. Using UNOS data (2022-2024), we stratified DCD donors by procurement (super rapid recovery (SRR) or NRP) and preservation (static cold storage (SCS) or NMP) method. NMP cases were further stratified into on-site versus back-to-base initiation of perfusion. On-site NMP was directly captured in the UNOS dataset. NRP and back-to-base NMP were identified with surrogate markers. We then compared graft (GS) and overall (OS) survival in propensity matched cohorts. We identified 4,632 DCD LTs. The most common procurement-preservation strategy was SRR-NMP (2,637; 56.9%), followed by SRR-SCS (937; 20.2%), NRP-SCS (560; 12.1%), and NRP-NMP (498; 10.8%). SRR-NMP demonstrated superior GS (HR 0.54, 95%CI 0.32-0.92) vs. SRR-SCS. NRP-SCS similarly reduced the risk of graft loss (HR 0.42, 95%CI 0.29-0.61) versus SRR-SCS. NRP-SCS and SRR-NMP had similar GS. Similarly, adding NMP to livers procured with NRP did not lead to improved outcomes compared to NRP followed by SCS. This study provides the most comprehensive U.S. comparison of modern procurement and preservation strategies in DCD LT. Both NRP and NMP were associated with improved GS vs. the historical standard (SRR-SCS). No significant survival differences were observed between NRP and NMP, confirming that these strategies serve complementary roles in DCD liver transplantation. These findings support the adoption of both NRP and NMP as the new standard of care in DCD LT.

Normothermic regional perfusion (NRP) has emerged as a vital technique in organ procurement, particularly in donation after circulatory death (DCD) cases, offering the potential to optimize organ utilization and improve posttransplant outcomes. Recognizing its significance, the American Society of Transplant Surgeons (ASTS) convened a work group to develop standardized recommendations for abdominal NRP in the United States. The workgroup, comprising experts in NRP, DCD, and transplantation, formulated recommendations through a collaborative process involving revisions and approvals by relevant committees and the ASTS council. Four key areas were identified for standardization: Preprocedure communication, NRP procedure, Terminology and documentation, and Mentorship/credentialing. The recommendations encompass a range of considerations, including preprocedure communication protocols to facilitate informed decision-making by transplant centers and organ procurement organizations, procedural guidelines for NRP teams, uniform terminology to clarify the NRP process, and standards for mentorship and credentialing of NRP practitioners. Specific recommendations address logistical concerns, procedural nuances, documentation requirements, and the importance of ongoing quality assurance. The standardized recommendations for abdominal NRP presented in this article aim to ensure consistency, safety, and efficacy in the organ procurement process. By establishing clear protocols and guidelines, the ASTS seeks to enhance organ utilization, honor donor wishes, and uphold public trust in the donation process. Implementation of these recommendations can contribute to the advancement of NRP practices and improve outcomes for transplant recipients.

In Situ Normothermic Regional Perfusion in Controlled Donation After Circulatory Determination Death: Organ Utilization, Outcomes, and Elusiveness of a Randomized Clinical Trial.

Organ procurement procedures have evolved significantly over the past decade, resulting in new moral uncertainties. The dead donor rule (DDR), a foundational principle, mandates that organ procurement occurs only after death is confirmed. However, developments such as donation after circulatory death (DCD) and normothermic regional perfusion (NRP) have raised ethical issues, creating moral distress and moral injury among anesthesiologists. This review highlights the recent changes in the organ procurement processes and the potential impact on anesthesiologists and also discusses the strategies to prevent and manage moral distress. A narrative review was conducted using a structured search strategy across Ovid MEDLINE, Embase, and Web of Science. The search included the terms "anesthesiology", "moral distress", "dead donor rule", "brain death", and "normothermic regional perfusion". Of the 77 identified articles, 18 met inclusion criteria focusing on the ethical, psychological, and educational aspects of the anesthesiologist’s role in organ procurement. The increasing use of novel organ procurement techniques such as NRP after DCD may result in moral distress among anesthesiologists. While the literature on moral distress continues to expand in the healthcare field, more needs to be written on this topic with anesthesiologists involved in organ procurement. Anesthesiologists are participating in novel organ procurement techniques with minimal control of decision-making. As a result, moral distress may occur with negative consequences. Solutions to the identification and prevention of moral distress with organ procurement include expanded ethics education, peer and mentor support, and institutional support. Addressing these issues can empower anesthesiologists to navigate complex scenarios, mitigating moral distress and increasing wellness and patient safety.

Despite the unmet need for donor organs, organ use from donation after circulatory determination of death (DCD) donors has been limited by inferior transplant outcomes. Normothermic regional perfusion (NRP) improves recipient outcomes and organ utilization from DCD donors. There is variability in NRP policies and experience among US organ procurement organizations (OPOs). To determine OPO experience, identify operational inconsistencies, and explore needs related to NRP. This survey study included 55 OPOs in the US that had recovered DCD organs and completed a survey on operational, administrative, and educational components related to NRP in November to December 2023. Data analysis was performed from February to April 2024. The primary outcome was the number of OPOs participating in and/or anticipating NRP participation. Secondary outcomes were NRP implementation barriers, OPO education practices, and future needs regarding consensus NRP recommendations and standards. Of 55 respondents, 11 (20%) were chief executive officers, 8 (15%) were chief operating officers, and 36 (65%) were medical directors or chief clinical officers. Forty-nine OPOs facilitated NRP cases: 26 OPOs (53%) facilitated both thoracoabdominal NRP (TA-NRP) and abdominal NRP (A-NRP) cases, 16 OPOs (33%) facilitated only TA-NRP, and 7 OPOs (14%) facilitated only A-NRP. OPOs reported 606 NRP cases (421 TA-NRP [69%], 185 A-NRP [31%]); median (range) case experience was 8 (1-52). Fifty-two of 55 OPOs (95%) thought standardized guidance documents would be helpful. All 49 OPOs facilitated NRP at a transplant center's request; 39 (80%) had NRP initiated by a nonlocal transplant center. Twenty-three of 49 OPOs (47%) participated in NRP without a policy and without a policy pending approval. Positive donor hospital feedback was received by 29 OPOs (59%), primarily focused on increased organs transplanted and prerecovery communication. Allocation challenges were experienced by 21 OPOs (43%); their median (range) case volume was higher than those with no reported allocation challenges (11 [3-52] vs 6.5 [1-29]; P = .03). Eleven OPOs (22%) had incorporated NRP into general donor hospital education. In this survey study of US OPOs, wide variation existed with respect to NRP experience and practice. Allocation challenges occurred more frequently with increased NRP experience. NRP guidelines and standardization were desired by most OPOs to decrease allocation challenges and maximize the gift of organ donation.

Assessment of Cerebral Perfusion and Activity during Normothermic Regional Perfusion in a Porcine Model of Donation after Circulatory Death

In donation after circulatory death (DCD) organ transplantation, normothermic regional perfusion (NRP) restores oxygenated blood flow following cardiac arrest and reverses warm ischemia. Recently, NRP has also been used to help recover DCD hearts in addition to the abdominal organs. While DCD donation has increased the number of abdominal organs and lungs pool, it has not been able to increase the number of heart transplants, despite the fact that it has the potential to increase the number of heart transplants by 15-30%. Thoracoabdominal normothermic regional perfusion makes heart transplantation feasible and permits assessing heart function before an organ procurement without affecting the preservation of abdominal organs. NRP can be used in two ways for DCD donor heart transplants: normothermic regional perfusion followed by machine perfusion (NRP-MP) and normothermic regional perfusion followed by static cold storage (NRP-SCS). Normothermic regional perfusion is an emerging technology, a cost-effective alternative in donation after circulatory death (DCD), and will increase the pool of donors in heart transplantation.

Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion.

We thank Ayorinde et al1 for their interest in our article2 and the editor for giving us the opportunity to clarify concerns. In our manuscript,2 we reported our initial experience with 46 consecutive controlled donors after circulatory death (cDCD) liver transplants (LTs) preserved with normothermic regional perfusion (NRP), presenting an 80% organ recovery rate and an outstanding low rate of complications (no cases of primary nonfunction or ischemic cholangiopathy [IC]). As the authors mentioned,1 it can be argued that the positive results could be partly justified by the short functional warm ischemia time due to premortem interventions or by a highly selected cohort. However, in the UK experience,3 they also presented excellent results with postmortem cannulation, despite a significantly longer functional warm ischemia time. Moreover, our donors cannot be considered highly selected, because our median donor age was 58 years (higher than that reported in other studies)2–4 and almost 30% were over 65 years of age. It is accepted that NRP allows a better evaluation of the graft according to liver function tests and macroscopic aspect. The authors suggest a randomized controlled trial between the rapid recovery (RR) and NRP to achieve evidence. Although it is not completely clear why NRP is beneficial, several experimental studies have demonstrated a replenishment of intracellular ATP that may help organs tolerate the subsequent cold ischemia.2,3 Moreover, RR and NRP have been recently retrospectively compared in 2 studies3,4 that demonstrate an evident benefit of NRP and even present NRP as an independent factor preventing IC. In addition, the use of NRP in Spain has significantly increased during the past years, currently being almost the only preservation system in cDCD. NRP also offers the advantage of being a relatively inexpensive technique that allows the perfusion of not only the liver but also the kidneys and pancreas and even combining with intrathoracic organ retrieval.5 Given the excellent results that we have experienced with NRP, it seems unlikely that any center would abandon NRP to perform RR and expose its recipients to a higher IC rate and graft loss. Therefore, the authors propose1 another trial comparing NRP and RR followed by ex situ machine perfusion (MP). Because NRP has shown superb results from its initial experiences,2 we do not consider NRP cDCD as marginal donors “per se,” rather donors that allow for a safe expansion of the donor pool. So, it seems to have no sense to associate MP. In our opinion, MP must still find its role in LT, although it seems to be useful in discard grafts. Our more extended experience with 83 NRP cDCD LTs has been recently presented in the International Liver Transplantation Society meeting in Toronto; primary nonfunction and IC rates remain 0% with a median follow-up of 24 months. In our opinion, although large trials would be advisable in the interest of evidence-based medicine, the results show that the benefits of NRP are so overwhelming that the adoption of the technique by worldwide active groups involved in cDCD LT is only a matter of time.

The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner. Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs. NRP + NMP was used in scenarios with (1) long travel distances, (2) complicated transplant recipients, or (c) the need for additional liver graft recovery in "marginal" cases. Ischemic cholangiopathy was lower in the NRP alone group (0%) and the NRP + NMP group (0%) compared with the SCS group (16.8; P < 0.001 and P = 0.04, respectively). In addition, early allograft dysfunction, number of packed red blood cells transfused, and acute kidney injury were lower in the NRP alone and NRP + NMP groups compared with the SCS group. Graft survival was higher in cases where NRP was used than in cases where SCS was used ( P = 0.016). In all the cases where lactate remained elevated at the end of NRP (mean 8.2 ± 2.0), it ultimately normalized at the end of NMP (0.92 ± 0.56). The present study demonstrates lower rates of ischemic cholangiopathy and improved graft survival with NRP alone or NRP + NMP compared with SCS when using liver grafts from DCD donors. It also demonstrates that excellent outcomes can be achieved with sequential NRP + NMP in cases with prolonged travel distances, complicated recipients, or when there is a need for additional liver recovery in "marginal" cases.

Regarding normothermic regional perfusion: Arguing by insistence is not a strong argument

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.