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：对于越来越多的需要移植的患者，恢复更多肺的一种方法是 当器官回收时，通过循环死亡后不受控制的捐献（uDCD）扩大供体库 在医院内外意外发生的死亡后。欧洲国家常规使用uDCD肺， 结果与脑死亡后捐赠的结果相似。在欧洲，uDCD在选择退出范围内运作 系统允许通过插入患者胸腔的管进行冷灌注进行快速原位肺保存， 最近去世，这将需要在美国事先授权的做法。我们的合作者从多伦多 开发了一种新的uDCD方案，使用 呼气末正压（PEEP）和补充氧气。在~3年内，5例患者接受了肺移植 来自uDCD供体，4名患者存活超过100天。器官捐赠需要授权 在开始肺保存之前，导致延长的热缺血时间（中位数166 min）和丢弃 64%的肺采用离体肺灌注（EVLP）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，接受在没有明确授权的情况下启动肺保存 完整性，这可以显著减少热缺血时间并将EVLP后的移植产量提高至> 50%。 在对我们的新型uDCD方案进行多中心试验之前，获得关键利益相关者的批准， 可行性测试至关重要。在目标1中，我们将使用参与式行动研究来完善uDCD肺方案 方法.我们将在与关键社区和临床利益相关者的会议上反复介绍uDCD方案 征求意见我们将培训随时可用的医院工作人员（例如，社会工作者，肺病学家）， 器官捐献保存（POD）将进行全面的定时模拟， 和器官恢复团队，从最初的介绍开始，通过肺恢复和运输， EVLP的集中设施。利益攸关方会议记录的定性分析和 模拟将告知最终方案修改，并验证在3小时内肺恢复的可行性 终止复苏。在目标2中，我们将通过持续审查以下结果来评估项目安全性： 每种情况下激活和移植。我们预计约50%的EVLP评估肺将被移植到 实现可持续性目标。安全性结局包括72小时时原发性移植物功能障碍III级和存活率 追踪了一年。在目标3中，我们将测试从决策中请求uDCD授权的伦理可接受性- 创客通过电话会议召集的一个道德操守小组将审查对话的案例记录，并决定- 被接触的制造商;通过共同调解，小组成员将确定适当性（是， 否），预期发生率> 90%。将通过对参与者的定性访谈证实结果， 在请求后2周接近uDCD肺保存。这项研究符合NHLBI的目标， 确定通过DCD进行肺采购的障碍和促进因素。