当前位置: X-MOL 学术Am. J. Transplant. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A North American single-center experience with liver transplantation using thoracoabdominal normothermic regional perfusion for donation after circulatory death
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
Affiliation  

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).

Details are in the caption following the image
FIGURE 1
Open in figure viewerPowerPoint
TA-NRP-DCD (A) recovery timeline, (B) contingency plans, (C) cannulation, and (D) case series. (A) Timeline of cDCD withdrawal of life sustaining treatment (WLST) and organ recovery, highlighting the involvement of patient care team and organ recovery teams: total warm ischemic time (tWIT), functional warm ischemic time (fWIT), and time from incision to initiation of NRP (iNRP). (B) Contingency plans were created for time-sensitive decision-making points that would have an impact on thoracic and abdominal organ recovery and utilization. Consensus between both thoracic and abdominal recovery teams and transplant centers in the case of such events was established prior to initiating TA-NRP-cDCD organ recoveries. (C) Schematic overlay on photograph of TA-NRP cDCD using CPB. Operative approach via midline sternotomy, division of the innominate vein, and ligation of the brachiocephalic, left carotid, and left subclavian arteries. Cannulation for TA-NRP includes (a) dual-stage venous cannula (Edwards Lifesciences TF293702) in the right atrium and (b) arterial cannula (Edwards Lifesciences Fem-Flex II 20Fr) in the ascending aorta. CPB was initiated with a sweep gas rate 10 L/min and FiO2 100%, later adjusted according to the serial blood gas analyses. The flow was targeted to maintain an SVO2 >70%. Physiologic targets were set as a systemic temperature of 35℃ and MAP >50 mm Hg. Blood from the surgical field was recaptured via (c) suction catheter. Following initiation of TA-NRP, the donor was re-intubated for mechanical volume-controlled ventilation. Arterial pressure during TA-NRP was measured directly through an aortic root needle cannula (Medtronic 20014), vasoactive medications were administered, initially, directly into the circuit and subsequently through (d) a 14Fr 9-Mac catheter directly inserted into the superior vena cava (SVC). After an initial stabilization period of 30 to 60 minutes, the donor was separated from CPB. (D) Case series of potential cDCD donors, ischemia times, and outcome of organ recovery [Color figure can be viewed at wileyonlinelibrary.com]

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。

详细信息在图片后面的标题中
图1
在图窗查看器中打开微软幻灯片软件
TA-NRP-DCD (A) 恢复时间表、(B) 应急计划、(C) 插管和 (D) 病例系列。(A) cDCD 退出生命维持治疗 (WLST) 和器官恢复的时间表,突出了患者护理团队和器官恢复团队的参与:总热缺血时间 (tWIT)、功能性热缺血时间 (fWIT) 和从切口开始的时间启动 NRP (iNRP)。(B) 为时间敏感的决策点制定了应急计划,这些决策点会对胸部和腹部器官的恢复和利用产生影响。在启动 TA-NRP-cDCD 器官恢复之前,胸腹部恢复团队和移植中心就此类事件达成了共识。(C) 使用 CPB 在 TA-NRP cDCD 照片上叠加示意图。手术方法通过正中胸骨切开术,分离无名静脉,结扎头臂动脉、左颈动脉和左锁骨下动脉。TA-NRP 的插管包括 (a) 右心房的双级静脉插管 (Edwards Lifesciences TF293702) 和 (b) 升主动脉的动脉插管 (Edwards Lifesciences Fem-Flex II 20Fr)。CPB 以 10 L/min 的扫气速率和 100% 的 FiO2 开始,随后根据系列血气分析进行调整。流量的目标是保持 SVO2 >70%。生理目标设定为全身温度35℃和MAP >50 mm Hg。通过 (c) 抽吸导管重新采集手术区域的血液。在 TA-NRP 开始后,供体被重新插管以进行机械容积控制通气。TA-NRP 期间的动脉压通过主动脉根部针插管直接测量 (Medtronic 20014),血管活性药物最初直接进入管路,随后通过 (d) 14Fr 9-Mac 导管直接插入上腔静脉 (SVC)。在 30 至 60 分钟的初始稳定期后,供体与 CPB 分离。(D) 潜在 cDCD 供体、缺血时间和器官恢复结果的病例系列 [彩色图可在 wileyonlinelibrary.com 查看]

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。

更新日期:2021-08-29
down
wechat
bug