Transplanting Lungs from Uncontrolled Donation after Circulatory Death

循环死亡后不受控制的捐赠进行肺移植

基本信息

批准号：
10661529
负责人：
ROBERT A MONTGOMERY
金额：
$ 40.54万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-08 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10661529
关键词：
Action Research Advisory Committees Aerobic Authorization documentation Autopsy Bilateral Brain Death Bronchoscopy Cessation of life Chest Chest Tubes Circulation Clinical Clinical Trials Code Communities Complex Country Cryopreservation Data Dedications Diagnostic Eligibility Determination Ethics Europe European Feedback Fiber Optics Goals Growth Hospitals Hour In Situ Interview Laboratories Lung Lung Transplantation Manuals Mediation Medical emergency Metabolism Modification Multicenter Trials National Heart, Lung, and Blood Institute Organ Organ Donations Organ Preservation Organ Procurements Outcome Patients Perfusion Persons Phase Positive-Pressure Respiration Procedures Protocols documentation Radiology Specialty Recovery Research Research Methodology Resuscitation Safety Social Workers Specific qualifier value System Teleconferences Testing Time Training Transcript Translating Transplantation Tube Warm Ischemia X-Ray Computed Tomography authority community based participatory research feasibility testing graft dysfunction improved lung preservation meetings member novel operation optical fiber participant interview performance tests preservation primary outcome prior authorization programs safety outcomes screening secondary outcome simulation supplemental oxygen

项目摘要

ABSTRACT: One way to recover more lungs for the escalating numbers of patients requiring transplants is to expand the donor pool via uncontrolled donation after circulatory death (uDCD), when organs are recovered after death occurs unexpectedly inside or outside of hospitals. European countries use uDCD lungs routinely, achieving outcomes similar to those from donation after brain death. In Europe, uDCD operates within opt-out systems that allow rapid in situ lung preservation with cold perfusion via tubes inserted into the chests of the recently deceased, a practice that would require prior authorization in the U.S. Our collaborators from Toronto developed a novel uDCD protocol that preserves lungs non-invasively for just over 3 hours after death using positive end expiratory pressure (PEEP) and supplemental oxygen. In ~3 years, five patients received lungs from uDCD donors, with four patients surviving beyond 100 days. Authorization for organ donation was required before initiating lung preservation, leading to prolonged warm ischemic times (median 166 min) and discarding 64% of lungs assessed with ex vivo lung perfusion (EVLP). Our empirical data suggest authorized persons might accept having lung preservation initiated without explicit authorization when the procedures maintain body integrity, which could dramatically reduce warm ischemic times and improve transplant yield after EVLP to >50%. Before conducting a multicenter trial of our novel uDCD protocol, garnering approval from key stakeholders and feasibility testing are essential. In Aim 1, we will refine the uDCD lung protocol using participatory action research methods. We will present the uDCD protocol iteratively in meetings with key community and clinical stakeholders for feedback. We will train readily available hospital staff (e.g., social workers, pulmonologists) to serve on dedicated preservation of organ donation (POD) teams. Comprehensive timed simulations will occur with clinical and organ recovery teams, beginning from initial presentation through lung recovery and transport to a centralized facility for EVLP. Qualitative analysis of stakeholder meeting transcripts and detailed descriptions of simulations will inform final protocol modifications and verify feasibility for lung recovery within 3 hours of termination of resuscitation. In Aim 2, we will assess program safety by continuous review of outcomes from each case activation and transplantation. We expect ~50% of lungs assessed with EVLP will be transplanted to meet sustainability targets. Safety outcomes include primary graft dysfunction grade III at 72 hours and survival tracked for 1 year. In Aim 3, we will test the ethical acceptability of requesting uDCD authorization from decision- makers. An ethics panel, convened via teleconferencing, will review case notes of conversations with decision- makers who were approached; through shared mediation, panel members will determine appropriateness (Yes, No) with expected rates >90%. Results will be corroborated with qualitative interviews of participants who were approached for uDCD lung preservation 2 weeks after the request. This research meets NHLBI's goal to identify barriers and facilitators to lung procurement via DCD.

摘要：为不断增加的需要移植的患者数量恢复更多肺部的一种方法是当器官恢复时，通过循环死亡后不受控制的捐赠（uDCD）扩大捐赠者库医院内外意外发生死亡后。欧洲国家常规使用 uDCD 肺，取得与脑死亡后捐赠相似的结果。在欧洲，uDCD 在选择退出的范围内运作通过插入胸腔的管子进行冷灌注，可实现快速原位肺保存的系统最近去世了，这种做法需要在美国事先获得授权。我们来自多伦多的合作者开发了一种新颖的 uDCD 方案，可在死亡后以非侵入性方式保存肺部 3 个多小时呼气末正压 (PEEP) 和补充氧气。在大约 3 年的时间里，五名患者接受了肺部移植来自 uDCD 捐赠者，其中 4 名患者存活超过 100 天。器官捐献需要授权在开始肺保存之前，导致热缺血时间延长（中位166分钟）并丢弃 64% 的肺部通过离体肺灌注 (EVLP) 进行评估。我们的经验数据表明授权人员可能当程序维持身体时，接受在未经明确授权的情况下启动肺保存完整性，可以显着减少热缺血时间并将 EVLP 后的移植率提高到 > 50%。在对我们的新型 uDCD 方案进行多中心试验之前，获得主要利益相关者的批准并可行性测试至关重要。在目标 1 中，我们将利用参与性行动研究完善 uDCD 肺协议方法。我们将在与主要社区和临床利益相关者的会议上迭代介绍 uDCD 协议以获得反馈。我们将培训随时可用的医院工作人员（例如社会工作者、肺科医师）来服务专门的器官捐献保存（POD）团队。全面的定时模拟将与临床一起进行和器官恢复团队，从最初的介绍开始，一直到肺部恢复和运输到 EVLP 的集中设施。对利益相关者会议记录和详细描述进行定性分析模拟将告知最终方案修改并验证肺恢复的可行性 3 小时内终止复苏。在目标 2 中，我们将通过持续审查结果来评估项目安全性每个案例的激活和移植。我们预计约 50% 接受 EVLP 评估的肺部将被移植到实现可持续发展目标。安全性结果包括 72 小时时的原发性移植物功能障碍 III 级和生存率追踪1年。在目标 3 中，我们将测试请求 uDCD 决策授权的道德可接受性：制造商。通过电话会议召集的道德小组将审查与决策者对话的案例记录接触过的制造商；通过共同调解，小组成员将确定适当性（是的，否），预期比率 >90%。结果将通过对参与者的定性访谈来证实请求后 2 周进行 uDCD 肺保存。这项研究符合 NHLBI 的目标确定通过 DCD 获取肺部的障碍和促进因素。