Why partial heart transplantation could be regulated as organ transplantation.

Partial heart transplant (PHT) is a recent clinical innovation involving the transplantation of a segment of the heart (valves) directly from the deceased donor into the recipient patient. This procedure holds out the possibility of significant benefit, especially for pediatric patients because these grafts show growth potential after transplant, reducing or eliminating the current need for repeat procedures. The clinical process for donation and transplant of partial heart (PH) grafts generally follows an organ clinical pathway; however, the Food and Drug Administration has recently stated its intent to regulate PH as tissues, raising a host of regulatory considerations. PHT requires donor testing and eligibility determinations within a short, clinically viable timeframe and, similar to organ transplant, involves donor-recipient matching. Waitlist allocation policies that are a regulatory focus of the Organ Procurement and Transplantation Network including equity and efficiency may become relevant. Oversight of PHT by the Organ Procurement and Transplantation Network could be accomplished through interpretation of the vascular composite allograft definition or through designation by the US Department of Health and Human Services of PH grafts as organs. While some clinical questions remain unanswered, it is important to carefully address these regulatory considerations to support the emergence of this innovation and ensure the continued trust of the donating public and the patients who may benefit from PHT.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

Measuring Critical Care Providers' Attitudes About Controlled Donation After Circulatory Death.

INTRODUCTION: Unfavorable attitudes and insufficient knowledge about donation after cardiac death among critical care providers can have important consequences for the appropriate identification of potential donors, consistent implementation of donation after cardiac death policies, and relative strength of support for this type of donation. The lack of reliable and valid assessment measures has hampered research to capture providers' attitudes. Design and Research Aims: Using stakeholder engagement and an iterative process, we developed a questionnaire to measure attitudes of donation after cardiac death in critical care providers (n = 112) and examined its psychometric properties. Exploratory factor analysis, internal consistency, and validity analyses were conducted to examine the measure. RESULTS: A 34-item questionnaire consisting of 4 factors (Personal Comfort, Process Satisfaction, Family Comfort, and System Trust) provided the most parsimonious fit. Internal consistency was acceptable for each of the subscales and the total questionnaire (Cronbach α > .70). A strong association between more favorable attitudes overall and knowledge ( r = .43, P < .001) provides evidence of convergent validity. Multivariable regression analyses showed that white race ( P = .002) and more experience with donation after cardiac death ( P < .001) were significant predictors of more favorable attitudes. CONCLUSION: Study findings support the utility, reliability, and validity of a questionnaire for measuring attitudes in critical care providers and for isolating targets for additional education on donation after cardiac death.

Regulatory oversight in the United States of vascularized composite allografts.

Vascularized composite allograft (VCA) transplantation is a medically acceptable treatment for the reconstruction of major tissue loss. The advent of VCA transplantation has spurred regulatory and policy development in the United States to address the multiple clinical, ethical and legal issues that must be considered for the practice of VCA donation and transplantation to develop within the existing framework of public trust and transparency vital to the success of donation and transplantation.

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement.

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Circulatory death determination in uncontrolled organ donors: a panel viewpoint.

One barrier for implementing programs of uncontrolled organ donation after the circulatory determination of death is the lack of consensus on the precise moment of death. Our panel was convened to study this question after we performed a similar analysis on the moment of death in controlled organ donation after the circulatory determination of death. We concluded that death could be determined by showing the permanent or irreversible cessation of circulation and respiration. Circulatory irreversibility may be presumed when optimal cardiopulmonary resuscitation efforts have failed to restore circulation and at least a 7-minute period has elapsed thereafter during which autoresuscitation to restored circulation could occur. We advise against the use of postmortem organ support technologies that reestablish circulation of warm oxygenated blood because of their risk of retroactively invalidating the required conditions on which death was declared.

An official American Thoracic Society/International Society for Heart and Lung Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of Organ Sharing Statement: ethical and policy considerations in organ donation after circulatory determination of death.

RATIONALE: Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues. OBJECTIVES: To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders. METHODS: A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders. RESULTS: A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD. CONCLUSIONS: The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.

Knowledge gaps in heart and lung donation after the circulatory determination of death: Report of a workshop of the National Heart, Lung, and Blood Institute.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.

Organ and Tissue Donation Consent Model and Intent to Donate Registries: Recommendations From an International Consensus Forum.

Consent model and intent to donate registries are often the most public facing aspects of an organ and tissue donation and transplantation (OTDT) system. This article describes the output of an international consensus forum designed to give guidance to stakeholders considering reform of these aspects of their system. Methods: This Forum was initiated by Transplant Québec and cohosted by the Canadian Donation and Transplantation Program partnered with multiple national and international donation and transplantation organizations. This article describes the output of the consent and registries domain working group, which is 1 of 7 domains from this Forum. The domain working group members included administrative, clinical, and academic experts in deceased donation consent models in addition to 2 patient, family, and donor partners. Topic identification and recommendation consensus was completed over a series of virtual meetings from March to September 2021. Consensus was achieved by applying the nominal group technique informed by literature reviews performed by working group members. Results: Eleven recommendations were generated and divided into 3 topic groupings: consent model, intent to donate registry structure, and consent model change management. The recommendations emphasized the need to adapt all 3 elements to the legal, societal, and economic realities of the jurisdiction of the OTDT system. The recommendations stress the importance of consistency within the system to ensure that societal values such as autonomy and social cohesion are applied through all levels of the consent process. Conclusions: We did not recommend one consent model as universally superior to others, although considerations of factors that contribute to the successful deployment of consent models were discussed in detail. We also include recommendations on how to navigate changes in the consent model in a way that preserves an OTDT system's most valuable resource: public trust.

The principles of gift law and the regulation of organ donation.

The principles of gift law establish a consistent international legal understanding of consent to donation under a range of regulatory systems. Gift law as the primary legal principle is important to both the foundation of systems that prevent organ sales and the consideration of strategies to increase organ donation for transplantation.

Expanding controlled donation after the circulatory determination of death: statement from an international collaborative.

A decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death.