Transplanting Lungs from Uncontrolled Donation after Circulatory Death

点击翻译按钮获取中文摘要

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.