American Journal of Transplantation ( IF 8.9 ) Pub Date : 2021-08-29 , DOI: 10.1111/ajt.16820 Shaheed Merani 1 , Marian Urban 2 , John Y Um 2 , Alexander Maskin 1, 3 , Luciano M Vargas 1 , Anthony W Castleberry 2 , David F Mercer 1 , Wendy Grant 1 , Alan N Langnas 1
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,1 the United Kingdom,2 and France3 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.4
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,5 European consensus statements, and consultation with a clinical ethicist was central to our evaluation and approach.
中文翻译:
循环性死亡后胸腹腔常温区域灌注供肝肝移植的北美单中心经验
由于同种异体肝移植的供需差异,人们对循环死亡 (cDCD) 肝移植后的受控捐赠一直存在兴趣。在美国,每年有超过 2000 名患者在等待肝移植期间死亡或病重。cDCD肝移植增加供体器官来源;然而,与原发性无功能 (PNF) 和缺血性胆管病 (IC) 的高风险相关。
已提出常温区域灌注 (NRP) 以减少在 cDCD 肝移植中观察到的缺血再灌注损伤的后遗症。西班牙1、英国2和法国3对该领域的重要贡献展示了有希望的临床结果,并提供了使用原则的框架。最近一篇评估 NRP 在 cDCD 器官恢复中的伦理考虑的文章提出了重要的考虑因素,对于北美中心探索其应用是及时的。4个
在对 cDCD 肝移植感兴趣的同时,cDCD 心脏移植也获得了使用 NRP 的势头。NRP 为胸腔和腹部器官提供原位灌注(脑灌注除外),允许在移植前对心脏同种异体移植物进行原位功能评估。
作为协作性多器官移植中心,我们与多个利益相关者合作制定了一项协议,并由临床伦理学家和当地 IRB 进行审查,以建立用于 cDCD 器官恢复的胸腹 NRP (TA-NRP) 计划(图 1A、B) . 在 2021 年的前 5 个月内,共有 6 个 cDCD 心脏报价被我们中心临时接受(图 1D)。其中,5 例发生循环死亡,TA-NRP 开始使用心肺旁路(CPB,图 1C),便携式体外膜氧合(ECMO)保留用于现场没有 CPB 设备的情况。由于 CPB 血栓(意外事件 4),我们遇到了一个可恢复的错误。
使用 TA-NRP 回收的器官进行了三例肝移植。肝脏下降的原因包括超过 fWIT 参数(意外事件 1 和 5),以及远程移植中心因质量下降器官而未进行重新分配的情况。TA-NRP cDCD 肝移植接受者的 MELD 中位数为 16,并且两次移植的英国 DCD 风险评分超过 5(高风险)。在肝移植受者中观察到预期的早期移植后结果,没有任何 PNF 或早期 IC 的发生率。目前肝移植后患者和移植物存活率为 100%。
据我们所知,我们报告了北美移植中心内使用 TA-NRP 的首次合作努力,主要目的是扩大 cDCD 心脏移植的使用,其次要目标是确保 cDCD 肝脏的效用和其他用于移植的腹部器官。我们认为,与超快速恢复技术相比,NRP 插管的时间增加(中位数 10 分钟,图 1D)与冷冲洗和储存前肝脏常温含氧灌注的潜在益处是平衡的或名义上的。
随着美国 NRP cDCD 心脏移植率的增加,这些早期发现将对执行 cDCD 肝移植的移植计划感兴趣。NRP cDCD 计划的成功需要向接收中心充分披露心脏团队对 NRP 的使用情况,包括应急计划以优化实时决策制定。
我们提倡移植计划建立有关 TA-NRP cDCD 器官恢复的指导原则和协议,其中应包括多方利益相关者与胸腹部移植团队、OPO、供体医院、移植学会领导人和临床伦理学家的合作。来自医学研究所/美国国家科学院委员会关于器官捐献者干预研究问题的指导、5项欧洲共识声明以及与临床伦理学家的咨询是我们评估和方法的核心。