Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:The science and practice of xenotransplantation is advancing more rapidly than the regulatory infrastructure that will be necessary to ensure the promise of alleviating the organ shortage can be safely and equitably met. RECENT FINDINGS/RESULTS:While countries leading the way have developed some regulatory guidance to support first in human "compassionate use" xenotransplant interventions and the first clinical trials, existing legislative, regulatory, and operational frameworks for human allotransplantation have not been explicitly extended to nonhuman animal organs. SUMMARY/CONCLUSIONS:To address safety concerns and other ethics challenges unique to xenotransplantation, existing policies must be amended and new policies must be implemented to protect patients and ensure equitable access to xenotransplantation.

This article aims to review unresolved ethical issues and raise additional questions to be answered regarding the use of intraoperative brain monitoring during thoracoabdominal normothermic regional perfusion (TA-NRP). We discuss the following ethical questions, as well as offer preliminary recommendations to advance the discourse around use of brain monitoring during TA-NRP: (1) Does brain monitoring admit violation of the dead donor rule? (2) Which monitoring techniques should be implemented during TA-NRP? (3) How should we manage positive findings? (4) How should we manage ambiguous findings on brain monitoring? (5) What procedural and institutional barriers remain to utilizing intraoperative brain monitoring for TA-NRP on a wider scale? We argue that preventing inadvertent brain reperfusion is central to ensuring TA-NRP complies with ethical standards, and that blood flow monitoring is the most direct monitor for reperfusion. We assess potential brain monitors during TA-NRP and suggest that transcranial doppler (TCD) with cerebral oximetry may be the closest existing tests to an ideal monitor for this application. We likewise review remaining questions regarding diagnostic uncertainty around these tests and the implications of this uncertainty or positive findings of brain reperfusion on the donor, their families, and public trust. To begin addressing these questions, necessary first steps include standardization of surgical protocols to include venting and consolidating data around TA-NRP.

With U.S. Food and Drug Administration (FDA) clearance of clinical trials of kidney xenotransplantation (XTx) in living humans, understanding the recipient experience is critical. Semi-structured interviews with the three living XTx recipients identified core domains of the recipient experience, including quality of life (QoL), fears about XTx, and healthcare team communication and support. Transcribed interviews were analyzed by two qualitative researchers using an inductive thematic approach and were mapped onto the Warwick Patient Experience Model, a validated framework to assess key aspects of patient satisfaction with the healthcare experience. All three recipients (53-year-old female; 66-year-old male; 54-year old male) described a restoration of hope, contrasted with their poor quality of life on dialysis. They emphasized that access to XTx and graft survival requires mutual confidence and commitment between recipients and healthcare teams. XTx recipients use dialysis as a point of reference when describing changes in their post-transplant QoL and seemed well-situated to handle the possibility of graft failure. These insights may aid in the creation of decision aids and educational materials tailored to the specific needs of XTx recipients.

Normothermic regional perfusion during controlled donation after circulatory death has emerged as a means to increase the number and viability of organs available for transplant. Because normothermic regional perfusion uses extracorporeal membrane oxygenation, an intervention used for resuscitation under other circumstances, critics have concluded that organ donation using normothermic regional perfusion violates the dead donor rule. As such, the debate about normothermic regional perfusion has been framed as a binary choice between normothermic regional perfusion and the dead donor rule. In this paper, I argue that we should resist this binary framework and instead judge the permissibility of normothermic regional perfusion based on whether it harms organ donors. The obligations owed to organ donors derive from their moral status and include the obligation to prevent harm to donors, protect futures of value and satisfy donors' critical interests. When performed correctly, normothermic regional perfusion does not violate these moral obligations. Therefore, normothermic regional perfusion does not harm organ donors during controlled donation after circulatory death, making it ethically permissible when performed in accordance with standardised protocols.

Current legislation guiding withdrawal of life-sustaining treatment and organ donation after circulatory death (DCD) leaves regulatory gaps that are not optimal for honoring the wishes of patient-donors. We describe these gaps, their consequences, and the need for revision to prevent harm to all parties.

BACKGROUND:Cardiac allotransplantation is the optimal treatment for end-stage heart failure. However, organ supply remains the principal issue impacting patients. Pediatric patients present unique challenges resulting in long wait-list times and increased mortality. Donation after circulatory death with normothermic regional perfusion represents a method to increase the number of available organs in this population. METHODS:Multi-institutional expert consultation was sought to outline extant technical, ethical, and logistical issues with regard to normothermic regional perfusion cardiac donation techniques. Specific advantages in the pediatric population are highlighted, as well as technical considerations resulting in successful organ procurement. RESULTS:Utilization of donation after circulatory death organs following normothermic regional perfusion in the United States is increasing and offers advantages to the pediatric heart failure population. Ethical reservations both nationally and abroad persist, namely pertaining to cerebral blood flow. This has led to variation in perception and utilization of normothermic regional perfusion, contributing to a discrepancy between donor and recipient locations. Procurement techniques and variations are described, with introduction into program planning and protocol development. Training in technical aspects of the procedure is paramount for both the surgeon and support staff to construct a successful program, along with transparent protocols to mitigate ethical concerns. CONCLUSIONS:Normothermic regional perfusion is relevant following donation after cardiac death in the pediatric population. Ethical and technical challenges remain in concert with substantial domestic and international variation. Standardization of technique may serve to increase future use and increase the number of available hearts for transplant, reducing pediatric mortality.

PURPOSE OF REVIEW/OBJECTIVE:Donation after circulatory death (DCD) is one of the most promising methods for expanding the organ pool for transplantation. Yet realizing the promise of DCD depends on careful coordination of end of life treatment with organ donation authorization, organ preservation, and recovery. RECENT FINDINGS/RESULTS:As organ procurement organizations (OPO) increase their DCD efforts, challenges regarding timely referral, delays in organ recovery coordination, and the requisite separation of clinical decisions from organ donation decisions are potentially preventing successful organ recovery, and having negative consequences for trust between OPOs, hospital staff, and donor families. SUMMARY/CONCLUSIONS:Recent DCD cases should be scientifically studied to understand the variables that lead to successful versus unsuccessful DCD. These variables need to be understood in order to adjust legal, logistical, and ethical approaches to DCD and thus ensure the expansion of the organ pool while preserving trust in organ transplantation.

Expanded research opportunities in deceased humans require ongoing ethical inquiry.

The standard treatment for end-stage organ failure is transplantation, but demand for organs has always vastly outstripped supply. Discussions are ongoing about the feasibility of addressing the organ shortage through measures like increasing organ donations, improving post-transplant outcomes, and xenotransplantation. This paper examines the rationale, risks, and costs of xenotransplantation, such as xenozoonoses, creating a new form of industrialized animal farming, abandoning animal ethics principles, and the opportunity costs of investing finite research dollars in xenotransplantation instead of investing in more viable strategies. Alternative strategies that can ethically and effectively address the demand for heart, kidney, and other transplants are recommended: Improving disease prevention and management to reduce demand for transplant organs, improving transplantation methods, and systemic changes to donor policies and organ recovery methods to increase overall supply. Upon careful exploration of the full landscape of organ transplantation, it is considered whether these alternative strategies that do not impose the definite harms and significant risks of xenotransplantation are the most ethical and effective means to increase life-saving options and improve clinical outcomes for patients in organ failure.