A North American single-center experience with liver transplantation using thoracoabdominal normothermic regional perfusion for donation after circulatory death

Abstract

To the Editor: Persistent interest in controlled donation after circulatory death (cDCD) liver transplantation exists due to supply-demand discrepancy for liver allografts. In the United States, over 2000 patients die or become too sick while awaiting liver transplant annually. cDCD liver transplantation has increased the source of donor organs; however, is associated with higher risk of primary non-function (PNF) and ischemic cholangiopathy (IC). Normothermic regional perfusion (NRP) has been proposed to reduce the sequelae of ischemia-reperfusion injury observed in cDCD liver transplantation. Important contributions to this field from Spain,1Hessheimer AJ Gastaca M Miñambres E et al.Donation after circulatory death liver transplantation: consensus statements from the Spanish Liver Transplantation Society.Transpl Int. 2020; 33: 902-916Crossref PubMed Scopus (17) Google Scholar the United Kingdom,2Watson CJE Hunt F Messer S et al.In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.Am J Transplant. 2019; 19: 1745-1758Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar and France3Savier E Lim C Rayar M et al.Favorable outcomes of liver transplantation from controlled circulatory death donors using normothermic regional perfusion compared to brain death donors.Transplantation. 2020; 104 (doi:10.1097/TP.0000000000003372): 1943-1951Crossref PubMed Scopus (34) Google Scholar demonstrate promising clinical results, and provide a framework for the principles for use. A recent article evaluating the ethical considerations of NRP in cDCD organ recovery raises important considerations, timely for North American centers exploring its application.4Parent B Moazami N Wall S et al.Ethical and logistical concerns for establishing NRP-cDCD heart transplantation in the United States.Am J Transplant. 2020; 20 (doi:10.1111/ajt.15772): 1508-1512Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Concurrent with interest in cDCD liver transplantation, cDCD heart transplant has gained momentum using NRP. NRP provides in situ perfusion to both thoracic and abdominal organs (with a notable exception of brain perfusion) allowing for in situ functional assessment of the cardiac allograft before transplantation. As a collaborative multi-organ transplant center, we created a protocol in collaboration with multiple stakeholders and review by both a clinical ethicist and local IRB to establish a program of thoracoabdominal NRP (TA-NRP) for cDCD organ recovery (Figure 1A,B). Within the first 5 months of 2021, a total of 6 cDCD heart offers were provisionally accepted by our center (Figure 1D). Of these, five proceeded to circulatory death and TA-NRP was initiated using cardiopulmonary bypass (CPB, Figure 1C), with portable extracorporeal membrane oxygenation (ECMO) reserved for situations where CPB equipment was not available on site. We experienced one recoverable error due to CPB thrombus (Contingency 4). Three liver transplants were performed using organs recovered using TA-NRP. Reason for liver decline included exceeding fWIT parameters (Contingencies 1 and 5), and one situation in which a remote transplant center declined organ for quality and re-allocation was not performed. TA-NRP cDCD liver transplant recipients had a median MELD of 16, and two transplants with UK DCD Risk Score over 5 (high-risk). Expected early post-transplant outcomes were observed in liver transplant recipients, without any incidence of PNF nor early-IC. Current post-liver transplant patient and graft survival is 100%. We report to the best of our knowledge the first collaborative effort within a North America transplant center for the use of TA-NRP with the primary intention of expanding the use of cDCD heart transplant, and a secondary objective of ensuring the utility of the cDCD liver and other abdominal organs for transplantation. We believe that the increased time for NRP canulation (median 10 minutes, Figure 1D) versus that of super rapid recovery technique, is balanced or nominal to the potential benefits of normothermic oxygenated perfusion of the liver prior to cold flush and storage. As the rate of NRP cDCD heart transplantation increases in the United States, these early findings will be of interest to transplant programs performing cDCD liver transplantation. The success of an NRP cDCD program requires full disclosure to recipient centers about the use of NRP by the heart team including contingency planning to optimize real-time decision making. We advocate for transplant programs to establish guiding principles and protocols regarding TA-NRP cDCD organ recovery, which should include multi-stakeholder engagement with the thoracic and abdominal transplant teams, OPOs, donor hospitals, transplant society leaders, and clinical ethicists. Guidance from the Institute on Medicine/National Academy of Science Committee on Issues in Organ Donor Intervention Research,5National Academies of Sciences, Engineering, and MedicineOpportunities for Organ Donor Intervention Research: Saving Lives by Improving the Quality and Quantity of Organs for Transplantation. The National Academies Press, Washington, DC2017Google Scholar European consensus statements, and consultation with a clinical ethicist was central to our evaluation and approach. The authors acknowledge important contributions to this work from Live On Nebraska staff and administration and that from the Nebraska Medicine clinical perfusion team (Lance Fristo, Ryan Robertson, and Todd Stover), cardiac-anesthesiology team (Drs. Megan Chacon and Nicholas Markin), and clinical ethicist (Jacob Dahlke). The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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