Ethical and logistical concerns for establishing NRP-cDCD heart transplantation in the United States

Abstract

Controlled heart donation after circulatory determination of death (cDCD) is well established internationally with good outcomes and could be adopted in the United States to increase heart supply if ethical and logistical challenges are comprehensively addressed. The most effective and resource-efficient method for mitigating warm ischemia after circulatory arrest is normothermic regional perfusion (NRP) in situ. This strategy requires restarting circulation after declaration of death according to circulatory criteria, which appears to challenge the legal circulatory death definition requiring irreversible cessation. Permanent cessation for life-saving efforts must be achieved to assuage this concern and ligating principal vessels maintains no blood flow to the brain, which ensures natural progression to cessation of brain function. This practice—standard in some countries—raises unique concerns about prioritizing life-saving efforts, informed authorization from decision-makers, and the clinician’s role in the patient’s death. To preserve public trust, medical integrity, and respect for the donor, the donation conversation must not take place until after an un-coerced decision to withdraw life-sustaining treatment made in accordance with the patient’s treatment goals. The decision-maker(s) must understand cDCD procedure well enough to provide genuine authorization and the preservation/procurement teams must be kept separate from the clinical care team. Controlled heart donation after circulatory determination of death (cDCD) is well established internationally with good outcomes and could be adopted in the United States to increase heart supply if ethical and logistical challenges are comprehensively addressed. The most effective and resource-efficient method for mitigating warm ischemia after circulatory arrest is normothermic regional perfusion (NRP) in situ. This strategy requires restarting circulation after declaration of death according to circulatory criteria, which appears to challenge the legal circulatory death definition requiring irreversible cessation. Permanent cessation for life-saving efforts must be achieved to assuage this concern and ligating principal vessels maintains no blood flow to the brain, which ensures natural progression to cessation of brain function. This practice—standard in some countries—raises unique concerns about prioritizing life-saving efforts, informed authorization from decision-makers, and the clinician’s role in the patient’s death. To preserve public trust, medical integrity, and respect for the donor, the donation conversation must not take place until after an un-coerced decision to withdraw life-sustaining treatment made in accordance with the patient’s treatment goals. The decision-maker(s) must understand cDCD procedure well enough to provide genuine authorization and the preservation/procurement teams must be kept separate from the clinical care team. Surgical management of end-stage heart failure generally falls into two categories: mechanical circulatory support and transplantation. Heart transplantation is limited by suitable organ availability. The majority of deceased donor hearts in the United States are obtained from patients with irreversible cessation of neurological function—donation after brain death (DBD). Recently, interest has been renewed in obtaining deceased donor hearts from controlled donation after circulatory determination of death (cDCD) donors, with irreversible cessation of cardiopulmonary function. In contrast to DBD, cDCD involves intentional withdrawal of life support measures to allow controlled circulatory death to occur. Normothermic regional perfusion (NRP) restores circulation following the declaration of circulatory death, which limits ischemic time and can allow heart recovery for transplantation. The concept of DCD heart transplantation is not new. DCD hearts were used by Barnard in his early series of heart transplants because the concept of brain death had not yet been established.1Barnard CN. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town.S Afr Med J. 1967; 41: 1271-1274PubMed Google Scholar Today, clinical cDCD heart transplant programs exist in the United Kingdom, Belgium, and Australia with Canada exploring this option. In 2012, the American Thoracic Society, the International Society for Heart and Lung Transplantation, and the United Network for Organ Sharing (among others) published an official statement in support of DCD donation.2Gries CJ White DB Truog RD et al.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.Am J Respir Crit Care Med. 2013; 188: 103-109Crossref PubMed Scopus (87) Google Scholar However, cDCD heart transplantation remains virtually nonexistent in the United States despite the potential to increase the donor pool by as much as 20%.3Jawitz OK Raman V Devore A et al.Donation after circulatory death in heart transplantation may increase the donor pool by 20% in the US.J Heart Lung Transpl. 2019; 38: S26Abstract Full Text Full Text PDF PubMed Google Scholar Increasing heart cDCD should not detract from DBD as these populations are distinct, and the need for organs is so great. Of the more than 41 000 adult heart transplants performed in the United States in the past 20 years, only 4 have been from cDCD donors.4Organ Procurement Transplantation Network. Advanced Data report, specifying DCD and heart. https://optn.transplant.hrsa.gov/data/view-data-reports/build-advanced/.Google Scholar Logistical and ethical issues must be addressed prior to widespread acceptance and implementation of cDCD heart transplantation. Even with international success in heart procurement and transplant in both cDCD and uncontrolled donation after circulatory determination of death (uDCD) contexts, there remains some hesitancy in using hearts that have recently undergone complete circulatory arrest and warm ischemia. There are also differing opinions as to which procurement and transport strategy is best for organ assessment and preservation. From an ethical standpoint, we must prevent the potential conflict of interest when life-sustaining measures are withdrawn prior to organ donation. Furthermore, the use of NRP to restore systemic circulation can be viewed as discordant with the definition of circulatory death as the “irreversible cessation of circulatory and respiratory functions.” Several methods have been proposed for procurement and evaluation of cDCD donor hearts. The original method was direct procurement (rapid recovery) and transplantation. The donor and the recipient were co-located in order to minimize time between withdrawal of donor life support and implantation and reperfusion in the recipient. This method does not permit a thorough functional reassessment following circulatory death prior to implantation. An alternative method involves direct procurement after circulatory death followed by ex situ normothermic reperfusion using a specialized perfusion device, for example TransMedics Organ Care System (OCS) or other machine perfusion methodologies. Although the OCS allows for continued reperfusion of the donor heart while en route to the recipient, there are challenges to its widespread use. The use of OCS requires significant capital cost and per-use disposables (~$40 000 per heart) and familiarity with the system. Furthermore, this approach precludes in situ hemodynamic and functional evaluation of the potential donor heart under physiologic conditions and limits graft viability assessment to measuring venous and arterial lactate levels. A recent study using a porcine heart model demonstrated that ex situ perfusion might actually contribute to a decline in myocardial function.5Hatami S White CW Shan S et al.Myocardial functional decline during prolonged ex situ heart perfusion.Ann Thorac Surg. 2019; 108: 499-507Abstract Full Text Full Text PDF PubMed Google Scholar Unfortunately, there is still no way to prevent all damage from occurring during the initial warm ischemia period after circulatory arrest. However, if in situ circulatory support could be instituted quickly following circulatory death, initial ischemic impact might be mitigated for all donor organs while allowing more time for evaluation prior to acceptance. This can best be accomplished using thoracoabdominal NRP, in which extracorporeal membrane oxygenation (ECMO) technology or cardiopulmonary bypass is used to reperfuse the heart and other organs in situ after isolating and ligating the internal carotid and vertebral vessels. Once flow through the coronaries is reestablished, in situ heart resuscitation with full hemodynamic and echocardiographic assessment can be performed prior to final acceptance for transplantation, without risk of ongoing warm ischemia. Rapid resumption of thoracoabdominal circulation should also minimize ischemic insult to other organs being considered for procurement and potentially lead to improved functionality of all recovered organs by limiting warm ischemia and providing a reperfusion period. NRP use in the DCD setting is not novel. In Spain, NRP has been used since 1989 to aid in DCD organ recovery.6Sánchez-Fructuoso AI Prats D Torrente J et al.Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool.J Am Soc Nephrol. 2000; 11: 350-358Crossref PubMed Google Scholar Beyond the cardiac benefits of NRP, it limits warm ischemic time for other organs, allows for a period of reperfusion, and permits organ assessment under nonischemic conditions. NRP use might reduce the incidence of ischemic hepatic cholangiopathy in DCD livers.7Watson CJE Hunt F Messer S et al.In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.Am J Transpl. 2019; 19: 1745-1758Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar DCD kidneys placed on NRP have demonstrated graft survival equivalent to DBD and had earlier recovery of graft function when compared to standard DCD in situ cold perfusion preservation.8Antoine C, Savoye E, Gaudez F, et al. Kidney transplant from uncontrolled donation after circulatory death: contribution of normothermic regional perfusion. Transplantation. 2019. https://doi.org/10.1097/TP.0000000000002753.Google Scholar NRP-facilitated multiorgan procurements have already been performed in the United Kingdom demonstrating higher recovery rates compared to standard cDCD.9Oniscu GC Randle LV Muiesan P et al.In situ normothermic regional perfusion for controlled donation after circulatory death – the United Kingdom experience.Am J Transplant. 2014; 14: 2846-2854Crossref PubMed Scopus (0) Google Scholar A retrospective review of DCD organ transplants (liver, kidney, and pancreas) from 2000 to 2013 demonstrated that results (rate of delayed graft function and primary nonfunction) from DCD organs reperfused with extracorporeal support were comparable to those from brain dead donors and better than those procured by rapid recovery.10Rojas-Pena A Sall LE Gravel MT et al.Donation after circulatory determination of death: the University of Michigan experience with extracorporeal support.Transplantation. 2014; 98: 328-334Crossref PubMed Scopus (82) Google Scholar Further optimizing all recoverable organs including lungs, and ensuring a source of blood oxygenation and ventilation during cardiac assessment must involve restarting lung mechanical ventilation. Although NRP effectively limits initial ischemic time following DCD, a remaining question is how best to manage the second ischemia period that occurs after procurement. The initial NRP-DCD heart transplants in the United Kingdom were performed with OCS for transport. As previously mentioned, mechanical perfusion for transport might not be superior to static cold storage, despite being vastly more expensive. Another possible solution is to co-locate recipient and donor to decrease travel distance as Barnard did in the earliest days of heart transplant. However, deliberately moving a patient to a recipient hospital for organ donation remains controversial. This may change as demonstrated by the growing number of donors being transferred to dedicated procurement facilities built by some organ procurement organizations (OPOs). Although cDCD has proven successful for procuring and transplanting more organs, there remain ethical and legal concerns about ensuring that the goal of organ transplantation does not negatively affect medical care for, or inappropriately hasten the death of, the potential donor. Adequate authorization is essential for any organ donation, but proximity of donation to withdrawal of life-sustaining treatment (WLST) and unique preservation/procurement process in cDCD cases (regardless of preservation method) creates complexity. Ideally, the donor will have registered explicit wishes via an organ donation registry and will either have the capacity to request WLST after continued care has become inconsistent with treatment goals or will have advance directives dictating withdrawal under these circumstances. Confirmation from a person authorized to make organ donation decisions—often next of kin—can then be obtained and the cDCD preservation process can begin. Short of this, an authorized decision-maker must be more involved in both the WLST decision, and the donation decision. To reduce the appearance or reality of organ donation goals influencing quality of medical care or hastening death, someone other than a member of the care team (almost always an OPO representative) must facilitate the donation conversation.11Bernat JL. Controversies in defining and determining death in critical care.Nat Rev Neurol. 2013; 9: 164-173Crossref PubMed Scopus (56) Google Scholar In cases of donation after brain death, this conversation must happen only after the individual has been declared dead. In cDCD cases, because preservation must be initiated quickly after declaration of death to prevent organ degradation, the donation conversation must take place before the death declaration. To be consistent with the goal of prioritizing medical care, the donation conversation should take place only after the medical team initiates a WLST conversation, and after an expressed and uncoerced decision to withdraw by the authorized decision-maker. The conversation needs to adequately explain the cDCD process in addition to describing the benefits of donation.12Overby K Weinstein MS Fiester A. Addressing consent issues in donation after circulatory determination of death.Am J Bioeth. 2015; 15: 3-9Crossref PubMed Scopus (0) Google Scholar Preservation efforts and their timing relative to the death declaration must be explained. This includes emphasizing the separation of the clinical care team from the organ preservation/transplant team, as well as decisions to administer heparin and relocate the patient to the facility where procurement and transplant might take place prior to WLST. Although these premortem preservation methods are not used in all DCD protocols,13Bastami S Krones T Biller-Andorno N. Whose consent matters? Controlled donation after cardiac death and premortem organ-preserving measures.Transplantation. 2012; 93: 965-969Crossref PubMed Scopus (13) Google Scholar with adequate consent they can be ethically implemented to improve heart transplant outcomes as seen with liver transplant.14Cao Y Shahrestani S Chew HC et al.Donation after circulatory death for liver transplantation: a meta-analysis on the location of life support withdrawal affecting outcomes.Transplantation. 2016; 100: 1513-1524Crossref PubMed Scopus (37) Google Scholar Postmortem preservation efforts, including NRP use and vessel ligation, should be described with enough detail that the decision-maker can give informed authorization, but without overburdening the individual during a stressful time. The purposes of these processes—keeping organs the of these efforts to patient recovery should be explained. should also be that the procurement process will not until after circulatory death has been in accordance with medical the individual to facilitate the donation conversation must be on after the WLST decision, and the of donation must be and of the informed obtaining authorization, preservation and procurement must still be with the legal definition of death and the dead donor The requires that death is declared prior to organ transplantation, patient death by organ The dead donor PubMed Google Scholar To with the dead donor it is to understand when a person is actually dead. The legal definition of death in some but the and of adopted the of of on to brain death determination of death Scholar which individual has irreversible cessation of circulatory and respiratory or irreversible cessation of all of the brain, including the brain is dead. 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