原位复苏和联合亚低温及常温机器灌注评估后高危供肝的移植：一项前瞻性临床试验。

Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial.

机构信息

Department of Surgery, Section of HPB Surgery & Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

出版信息

Ann Surg. 2019 Nov;270(5):906-914. doi: 10.1097/SLA.0000000000003540.

DOI:10.1097/SLA.0000000000003540

PMID:31633615

Abstract

OBJECTIVE

The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation.

SUMMARY BACKGROUND DATA

Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function.

METHODS

In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival.

RESULTS

Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%.

CONCLUSIONS

Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%.

TRIAL REGISTRATION

www.trialregister.nl; NTR5972.

摘要

目的

本研究旨在评估低温和常温序贯机器灌注（NMP）作为复苏和评估初始功能下降供肝活力的工具，以实现安全移植。

背景资料概要

机器灌注越来越多地用于复苏和测试供肝的功能。虽然（双）低温氧合机器灌注（[D]HOPE）可在冷保存后复苏肝脏，但 NMP 可评估肝胆功能。

方法

在一项前瞻性临床试验中，全国范围内功能下降的供肝进行离体 NMP（活力评估阶段），此前进行 1 小时 DHOPE（复苏阶段）和 1 小时控制性氧合复温（COR），使用含有血红蛋白基氧载体的灌注液。在 NMP 的前 2.5 小时内，使用预定义标准评估肝胆活力：灌流液中乳酸盐<1.7mmol/L、pH 值 7.35 至 7.45、胆汁生成量>10mL 和胆汁 pH 值>7.45。符合所有标准的肝脏可接受移植。主要终点为 3 个月移植物存活率。

结果

16 个肝脏接受了 DHOPE-COR-NMP。所有肝脏均来自循环死亡供者，中位年龄为 63 岁（范围 42-82 岁），中位欧洲器官移植协会风险指数为 2.82。在 NMP 期间，所有肝脏均清除了乳酸盐并产生了足够的胆汁量，但在 5 个肝脏中，胆汁 pH 值仍<7.45。符合所有活力标准的 11 个（69%）肝脏成功移植，3 个月和 6 个月时患者和移植物存活率均为 100%。引入 DHOPE-COR-NMP 使死亡供者肝脏移植数量增加了 20%。