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

• 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
• 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

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：用于恢复更多肺部增加肺部的一种方法，需要移植的患者数量 循环死亡后通过不受控制的捐赠（UDCD）扩展供体池，恢复器官时 死亡之后出乎意料地发生在医院内部或外部。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在退出中运行 可以通过插入的管子插入的管子的冷灌注来快速原位肺部保存的系统 最近去世，这种做法需要在美国事先授权，我们来自多伦多的合作者 开发了一种新型的UDCD方案，该方案可在死后3小时内无创地保存肺部 正末端呼气压力（PEEP）和补充氧气。在〜3年内，五名患者接受了肺 来自UDCD捐赠者，四名患者存活超过100天。需要进行器官捐赠的授权 在启动肺部保存之前，导致长时间温暖的缺血时代（中位166分钟）并丢弃 用体内肺灌注（EVLP）评估的肺中有64％。我们的经验数据表明，授权的人可能 当该程序保持身体时，接受无明确授权的肺部保存开始 完整性可以大大降低温暖的缺血时代，并在EVLP后提高移植产量至> 50％。 在进行我们新颖的UDCD协议的多中心试验之前，获得了主要利益相关者的批准和 可行性测试至关重要。在AIM 1中，我们将使用参与式行动研究完善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地介绍UDCD协议 用于反馈。我们将培训随时可用的医院工作人员（例如社会工作者，肺科医生） 专门保护器官捐赠（POD）团队。临床将发生全面的定时模拟 和器官恢复团队，从初始演示开始，一直到肺恢复和运输到 EVLP的集中设施。对利益相关者会议成绩单的定性分析和详细描述 仿真将为最终协议修改提供信息，并在3小时内验证肺恢复的可行性 复苏的终止。在AIM 2中，我们将通过对结果的持续审查来评估计划安全 每个情况激活和移植。我们预计用EVLP评估的肺中约有50％将被移植到 满足可持续性目标。安全结果包括72小时的初级移植功能障碍III级和生存 跟踪1年。在AIM 3中，我们将测试要求根据决策要求UDCD授权的道德可接受性 - 制造商。通过电视会议召集的道德小组将审查与决策的对话的案例笔记 - 接近的制造商；通过共享调解，小组成员将确定适当性（是的， 否）预期率> 90％。结果将通过对参与者的定性访谈来证实 请求后2周，与UDCD肺部保存联系。这项研究实现了NHLBI的目标 通过DCD确定肺癌采购的障碍和促进因子。