Faculty Bibliography

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.

Use of normothermic regional perfusion (NRP) to enable organ reconditioning and assessment in donation after circulatory determination of death (DCD) is controversial. We conducted a scoping review of peer-reviewed articles, news media, legal literature, and professional society position statements addressing ethical and/or legal issues in use of NRP in controlled DCD from January 1, 2005 to January 5, 2024. Thematic analysis, assessing the four principles of bioethics (autonomy, beneficence, non-maleficence, and justice) and sub-themes identified within each, was conducted for the 112 publications meeting inclusion criteria. More than 30 publications addressed the topic in each of 2022 and 2023, versus ≤6 per year previously. Non-maleficence was the most frequently addressed bioethical principle (111/112 publications), and most varied, with 14 subthemes. Attitudes towards NRP differed by type of NRP: Of 72 publications discussing thoracoabdominal NRP, 22 (30.6%) were 'In Favor', 39 (54.2%) 'Neutral', and 11 (15.3%) 'Against'; of 44 discussing abdominal NRP, 23 (52.3%) were 'In Favor', 20 (45.5%) 'Neutral', and 1 (2.3%) 'Against'. Attitudes differed by authors' country, degree, and affiliation, and by clinical focus of the publishing journal. Overall, our review shows the ethical and legal issues raised by NRP remain unresolved, and debate centered on non-maleficence.

Religious viewpoints have been shown to influence the ways in which many persons approach medical decision-making and have been noted as a potential barrier to xenotransplantation acceptance. This study sought to explore how attitudes toward xenotransplantation differ among various religious beliefs. A national Likert-scale survey was conducted in 2023 with a representative sample in the United States. Religious belief was self-reported. Regression analysis was used to identify associations with religious belief and hesitations about xenotransplantation. Five thousand and eight individuals across the United States responded to the survey. The two biggest concerns about xenotransplantation across religious groups were the current lack of evidence about success and the risk of xenozoonosis. Although they still expressed concerns about certain issues, Catholic and Muslim respondents were most comfortable with xenotransplantation for all. On average, the risk of xenozoonosis was a concern among 25% across all religious beliefs (p <0.0001). Orthodox Christians expressed the highest rate of negative feelings toward the recent xenotransplantation experiments on brain dead and living individuals. Those who reported no religion were most likely to have negative feelings about killing pigs for human organ transplant (OR 1.26; 95% CI: 1.08-1.46). As xenotransplantation progresses from pre-clinical studies to clinical trials, and potentially to clinical therapy, hesitations among religious groups exist. Specific studies should be designed to investigate how religious viewpoints can affect xenotransplantation acceptance.

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.

Xenotransplantation (XTx) presents a potential clinical alternative to the shortage of human organs for transplantation. Before clinical trials occur in the United States, public assessments are crucial to understand potential barriers to acceptance. The purpose of this study was to explore barriers and identify characteristics associated with attitudes toward XTx. A survey assessing demographic characteristics and attitudes toward XTx was distributed to a nationally representative sample of adults aged ≥18 years in the United States. Regression analysis was employed to identify characteristics associated with attitudes toward XTx. Between May 25 and June 14, 2023, 5008 respondents completed the survey. Importantly, half of the respondents expressed low or no knowledge of either transplantation or XTx. Approximately 40% expressed discomfort with receiving a pig organ for themselves or a loved one. Despite a lack of xenotransplant outcome data, 36% were open to experimental XTx if they needed a transplant. However, 57% rated lack of current evidence of success or fear of complications as top concerns. Regression models consistently associated being younger, female, not needing an organ, or being a member of a racial minority group with lower acceptance. This survey is the largest to date exploring public attitudes toward XTx. Despite overall acceptance, concerns persist. Increasing public acceptance is key as the field advances.