Normothermic Regional Perfusion: Ethical Issues in Thoracic Organ Donation

Abstract

Nearly 3000 heart transplants are performed annually in the United States, yet several hundred listed patients and several thousand unlisted patients die each year because of lack of an available organ.1Organ Procurement and Transplantation NetworkNational data.https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#Date accessed: October 25, 2021Google Scholar Controlled donation after circulatory-determined death (cDCD) is a potential source of additional hearts for transplantation, but is rarely used for cardiac transplantation: in 2019, no hearts were used from the 2718 cDCD donors that year.2Israni A.K. Zaun D. Rosendale J.D. Schaffhausen C. McKinney W. Snyder J.J. OPTN/SRTR 2019 annual data report: deceased organ donors.Am J Transplant. 2021; 21: 521-558PubMed Google Scholar Heart procurement efforts from cDCD donors have used 2 main techniques: direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP).3Messer S. Page A. Axell R. et al.Outcome after heart transplantation from donation after circulatory-determined death donors.J Heart Lung Transplant. 2017; 36: 1311-1318Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar,4Beaupré R.A. Morgan J.A. Donation after cardiac death: a necessary expansion for heart transplantation.Semin Thorac Cardiovasc Surg. 2019; 31: 721-725Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Although DPP is generally accepted on ethical grounds, NRP for heart procurement during thoracoabdominal NRP (TA-NRP) has generated substantial ethical concerns. NRP has also been used to procure only abdominal organs (abdominal NRP [A-NRP]), which avoids some of the ethical issues that arise in TA-NRP for procuring hearts.5Bernat J.L. The boundaries of organ donation after circulatory death.N Engl J Med. 2008; 359: 669-671Crossref PubMed Scopus (99) Google Scholar In all forms of cDCD, life-sustaining measures are withdrawn. When cardiac activity ceases, a stand-off period ensures that cardiac activity does not spontaneously resume. After this period, the patient is declared dead according to circulatory criteria and organ procurement commences. In NRP, mechanical circulation, often with extracorporeal membrane oxygenation, is initiated to limit organ damage. Blood flow to the brain is prevented in A-NRP by obstructing blood flow to the thoracic aorta, and in TA-NRP by ligating the cerebral blood vessels. The primary ethical controversy in TA-NRP has focused on the reestablishment of circulation, after which the declaration of death according to circulatory criteria would be void, according to a report from the American College of Physicians.6American College of PhysiciansEthics, determination of death, and organ transplantation in normothermic regional perfusion (NRP) with controlled donation after circulatory determination of death (cDCD): American College of Physicians statement of concern.https://www.acponline.org/acp_policy/policies/ethics_determination_of_death_and_organ_transplantation_in_nrp_2021.pdfDate accessed: October 25, 2021Google Scholar A recent international collaborative analysis, however, has shown that this process can be performed in a manner that is ethically acceptable, depending on cDCD practices in each country.7Domínguez-Gil B. Ascher N. Capron A.M. et al.Expanding controlled donation after the circulatory determination of death: statement from an international collaborative.Intensive Care Med. 2021; 47: 265-281Crossref PubMed Scopus (34) Google Scholar We first explore the ethics of NRP in the context of US standards of organ donation, then make recommendations for use of the technique in this country. A guiding principle of vital organ donation is the dead donor rule (DDR), which is an ethical principle rather than a legal doctrine. A vital organ cannot be removed until the donor is determined to be dead according to medical standards and legal criteria, and removing a vital organ cannot cause the death of the donor. Even autonomous choice cannot override the DDR: patients who do not meet the criteria for death cannot donate organs, no matter how fervent their desire to be a donor. In the United States, the Uniform Determination of Death Act (UDDA) states, “An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead. A determination of death must be made in accordance with accepted medical standards.”8National Conference of Commissioners on Uniform State LawsUniform determinatin of death act.http://www.lchc.ucsd.edu/cogn_150/Readings/death_act.pdfDate accessed: February 11, 2022Google Scholar The UDDA does not specify medical criteria for determining brain death, because the accepted medical standards might evolve over time.9Pope T.M. Brain death forsaken: growing conflict and new legal challenges.J Leg Med. 2017; 37: 265-324Crossref PubMed Scopus (30) Google Scholar Although some state laws codify which tests should be performed and the timing of a repeat examination if necessary, others leave the declaration of brain death up to the prevailing standards of care or national guidelines, such as those of the American Academy of Neurology.10American Academy of NeurologyUpdate: determining brain death in adults.https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwj8w7zqmIbyAhV0kmoFHTF-ANEQFjAAegQIAxAD&url=https%3A%2F%2Fwww.aan.com%2FGuidelines%2Fhome%2FGetGuidelineContent%2F432&usg=AOvVaw34kkFmt7p5mD_6yoTJ0i50Date accessed: October 25, 2021Google Scholar Although policies and laws vary, a neurological examination in the absence of confounding factors, usually including documentation of apnea, is typically required as part of the process of determining brain death.9Pope T.M. Brain death forsaken: growing conflict and new legal challenges.J Leg Med. 2017; 37: 265-324Crossref PubMed Scopus (30) Google Scholar Most determinations of death before organ procurement are made on the basis of the UDDA's second criterion, neurological status (donation after brain death [DBD]). DBD donors are the source of most abdominal organs and nearly all thoracic organs. Our main focus, however, is on the less common source of organs, cDCD. The process for recovering organs in cDCD is initiated only after a decision is made by an authorized decision-maker (usually a family member or health care agent) to remove life support from a patient who has sustained severe brain injury but does not meet the criteria for brain death (Figure 1). After that decision has been made, a request for possible organ donation can be initiated.11American Society of AnesthesiologistsStatement on controlled organ donation after circulatory death.https://www.asahq.org/standards-and-guidelines/statement-on-controlled-organ-donation-after-circulatory-deathDate accessed: October 4, 2021Google Scholar Informed consent for organ donation must be obtained after thorough explanation of the donation process, including every step of the procedure. After informed consent for organ donation, life-sustaining treatments are withdrawn, and respiratory and cardiac functions decline, slowly increasing warm ischemic time. If circulation ceases in a relatively short time after withdrawal of support, then the patient might be suitable for donation. Some medical center policies permit interventions such as the administration of heparin or preparation of the vessels for cannulation before declaration of death, whereas others prohibit premorbid interventions. After the circulation becomes undetectable (the length of time varies according to local protocol), the patient is declared dead according to circulatory criteria. The delay, termed the standoff period, is necessary because spontaneous resumption of circulation—autoresuscitation of the heart—might occur early after arrest, although it has not been shown to occur in adults after 5 minutes.12Dhanani S. Hornby L. van Beinum A. et al.Resumption of cardiac activity after withdrawal of life-sustaining measures.N Engl J Med. 2021; 384: 345-352Crossref PubMed Scopus (20) Google Scholar The appropriate standoff period has not been determined in children, to our knowledge. As circulation declines, vital organs are exposed to increasing degrees of ischemia, and complete warm ischemia occurs after circulation stops, until the organs are reperfused with blood or preservation solution. Although abdominal organs medically suitable for transplantation can be recovered from 50% to 80% of donors, hearts from cDCD donors do not do as well because of ischemic damage, and most centers have historically considered them unusable for transplantation. Two primary methods have been introduced recently to procure hearts for transplantation in cDCD.3Messer S. Page A. Axell R. et al.Outcome after heart transplantation from donation after circulatory-determined death donors.J Heart Lung Transplant. 2017; 36: 1311-1318Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar DPP is accomplished during a standard cDCD procedure: the aortic root is perfused with cardioplegia solution, the heart is removed, and then connected to an ex vivo apparatus (Organ Care System [OCS] for Heart; TransMedics Inc) for perfusion with warm oxygenated blood (Figure 2). Alternatively, the heart may be preserved in cold solution for transportation. In NRP, life support is withdrawn. After death is declared and extracorporeal circulation initiated, return or preservation of any degree of brain function is thought to be prevented by interrupting blood flow to the brain by occluding the descending aorta in A-NRP and occluding the arch vessels in TA-NRP.13Manara A. Shemie S.D. Large S. et al.Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal.Am J Transplant. 2020; 20: 2017-2025Crossref PubMed Scopus (39) Google Scholar Reperfusion of vital organs in situ is instituted with extracorporeal circulation, preventing further ischemic damage to vital organs and allowing some recovery from existing damage. In A-NRP, extracorporeal blood flow is thought to be limited to the abdominal organs. (Figure 3). In TA-NRP, cardiac activity resumes. After the heart has been perfused and rested, functional recovery is assessed by weaning the potential donor from extracorporeal support (Figure 4). If the heart proves functionally adequate, it can be removed and transferred to the recipient site either using cold storage or by using an ex vivo perfusion device.Figure 4Thoracic normothermic regional perfusion. (A) The aortic arch branch vessels and lower extremity vessels are occluded before initiation of thoracic and abdominal regional perfusion. The ? on electroencephalogram (EEG) indicates that minor cerebral perfusion might occur by way of spinal artery collaterals. (B) Enlarged view of thoracic cavity, showing occluded arch branches; distal divided vessels may be left open to atmospheric drainage. (C) The donor is reintubated and weaned from mechanical support, so the heart completely supports circulation to the thorax and abdomen. (D) After a suitable period of reperfusion, if assessment determines that heart function is adequate, the heart is explanted and either cooled or connected to a perfusion device for transportation. (ECG, electrocardiogram; ABP, arterial blood pressure.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) In the largest reported series of cDCD heart transplants, 100 donors were within the limits of warm ischemic times. The transplant rate was 76% for DPP (57 hearts) and 88% for TA-NRP (22 hearts). Overall heart transplant activity at the transplant center increased by 48% during the study. The survival rates (30-day and 1-year) were similar to those of DBD donors during the same time period.14Messer S. Cernic S. Page A. et al.A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors.J Heart Lung Transplant. 2020; 39: 1463-1475Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Favorable results with DPP have also been reported from Australia.15Chew H.C. Iyer A. Connellan M. et al.Outcomes of donation after circulatory death heart transplantation in Australia.J Am Coll Cardiol. 2019; 73: 1447-1459Crossref PubMed Scopus (102) Google Scholar The main advantage of DPP is that it has few of the ethical challenges related to determination of death. When ex vivo perfusion is used, it adds some complexity and cost. OCS is expensive in terms of initial cost (approximately $40,000) and personnel to manage it. A further disadvantage is the limited ability to assess the function of the heart, which is accomplished by relatively unreliable serial arterial and venous lactate measurement during ex vivo perfusion.16Page A. Messer S. Axell R. et al.Does the assessment of the donor hearts on the Organ Care System using lactate need redefining?.J Heart Lung Transplant. 2017; 36: S16-S17Abstract Full Text Full Text PDF Google Scholar This can lead to wastage of some otherwise usable hearts because no direct assessment of cardiac function is possible with this technique. An important advantage of TA-NRP is the availability of functional assessment during heart reperfusion, allowing acceptance of hearts that might have been rejected on the basis of lactate measurement. Either cold storage or OCS can be used for transport, but the ex vivo device adds substantial expense. The main concern associated with TA-NRP is the ethical question of determination of death. The idea of brain death was endorsed in publications from the President's Commission in 198117President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral ResearchDefining Death: Medical, Legal, and Ethical Issues in the Determination of Death. US Government Printing Office, 1981Google Scholar and then the President's Council in 2008.18President’s Council on BioethicsControversies in the determination of death: a white paper by the President’s Council on Bioethics. President’s Council on Bioethics, Washington, DC2008Google Scholar The main conclusions of these groups were that brain death is ethically equivalent to biological death, because without the brain to perform the fundamental vital work of integrating the organism's functioning, the person as an organism could no longer function as a whole. They concluded that loss of function of the whole brain, including the brain stem, had to be irreversible, and this conclusion became the basis of the UDDA. Death according to circulatory criteria requires “irreversible cessation of circulatory and respiratory functions.” Some critics of cDCD have argued that such donors are not dead at the time of organ recovery because the circulation is capable of being restored after 5 minutes of circulatory arrest, so it is not irreversible. A counterargument posits that if there is no intention to restore circulation, then the circulatory arrest is permanent (even if potentially reversible), so the patient is dead.19Bernat J.L. How the distinction between “irreversible” and “permanent” illuminates circulatory-respiratory death determination.J Med Philos. 2010; 35: 242-255Crossref PubMed Scopus (80) Google Scholar The “unifying concept of death” proposes that the loss of all brain function is the common thread joining death according to neurological criteria and death according to circulatory criteria.20Gardiner D. McGee A. Bernat J.L. Permanent brain arrest as the sole criterion of death in systemic circulatory arrest.Anaesthesia. 2020; 75: 1223-1228Crossref PubMed Scopus (5) Google Scholar,21Dalle Ave A.L. Bernat J.L. Donation after brain circulation determination of death.BMC Med Ethics. 2017; 18: 15-20Crossref PubMed Scopus (17) Google Scholar In death according to circulatory and neurological criteria, the brain is completely and permanently destroyed. In circulatory death, the loss of circulation is a surrogate for destruction of the whole brain, and destruction of the whole brain is permanent.7Domínguez-Gil B. Ascher N. Capron A.M. et al.Expanding controlled donation after the circulatory determination of death: statement from an international collaborative.Intensive Care Med. 2021; 47: 265-281Crossref PubMed Scopus (34) Google Scholar,19Bernat J.L. How the distinction between “irreversible” and “permanent” illuminates circulatory-respiratory death determination.J Med Philos. 2010; 35: 242-255Crossref PubMed Scopus (80) Google Scholar The complete loss of neurological function is common to all death; if there is no blood perfusion to the entire brain, then the patient is dead whether or not there is circulation to other vital organs. TA-NRP has been used successfully in a few European countries for several years, and has recently been adopted by a few transplant centers in the United States. Those engaged in the use of this procedure clearly believe that the DDR has not been violated, but others argue that the procedure violates the DDR and should be considered unacceptable. We now consider conflicting views on both sides of this issue. The conflict turns on the question of whether, for the diagnosis of death to be valid, cessation of organ or brain function must be irreversible or can be permanent. For TA-NRP to respect the DDR, the patient must be demonstrably dead, not merely presumed dead. Circulatory death, by definition, occurs when there is irreversible cessation of circulation, meaning that there is no perfusion to the vital organs (including the heart and brain). If this process is reversed spontaneously, by resuscitative efforts, or through the use of extracorporeal circulation, then, from this viewpoint, death did not occur.22Veatch R.M. Killing by organ procurement: brain-based death and legal fictions.J Med Philos. 2015; 40: 289-311Crossref PubMed Scopus (24) Google Scholar Although death is irreversible, “dying” is reversible. Dying is the state between life and death in which resuscitation is possible.23Truog R.D. Miller F.G. Counterpoint: are donors after circulatory death really dead, and does it matter? No and not really.Chest. 2010; 138: 16-18Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar In TA-NRP, the dying process has been interrupted, and the patient might be alive. Because oxygenated blood flows to some vital organs, the declaration of death according to circulatory criteria might no longer be valid; restoration of circulation in a cDCD donor nullifies the declaration of death according to circulatory criteria. If this is correct, then to avoid violation of the DDR, death must be determined on neurological grounds, yet no brain death examinations on TA-NRP donors have been reported, and such an examination is necessary to determine brain death according to the American Academy of Neurology Guidelines.24Wijdicks E.F.M. Varelas P.N. Gronseth G.S. Greer D.M. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.Neurology. 2010; 74: 1911-1918Crossref PubMed Scopus (661) Google Scholar Those who support TA-NRP argue that the patient remains dead after circulatory arrest because there is no blood flow to the brain, even if circulation has been restored. Absence of brain perfusion has never been proven, however, and there is reason to believe that it might persist. The brain stem can be perfused by vessels other than the aortic arch branches that are ligated in current TA-NRP protocols; for example, the anterior spinal artery supplies some blood flow to the medulla.25Er U. Fraser K. Lanzino G. The anterior spinal artery origin: a microanatomical study.Spinal Cord. 2008; 46: 45-49Crossref PubMed Scopus (11) Google Scholar That artery arises from branches of the descending aorta, and they will not be occluded using NRP protocols, so whether the brain stem is completely and irreversibly ischemic in NRP cases is not known. Some supporters of TA-NRP acknowledge that some residual flow to the brain might continue through collateral circulation, as their own experiences “raise the theoretical possibility that there could be a degree of vertebrobasilar flow into the brain stem and the circle of Willis.”13Manara A. Shemie S.D. Large S. et al.Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal.Am J Transplant. 2020; 20: 2017-2025Crossref PubMed Scopus (39) Google Scholar This becomes critically important in the United States, where any residual brain stem function might negate the declaration of death. One technique intended to completely eliminate flow to the brain is open drainage of the distal end of the aortic arch vessels, but this has not been proven to prevent all blood flow to the entire brain.13Manara A. Shemie S.D. Large S. et al.Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal.Am J Transplant. 2020; 20: 2017-2025Crossref PubMed Scopus (39) Google Scholar It will be difficult to prove absence of blood flow to the brain stem. Some authors have discussed the use of ancillary tests such as transcranial Doppler to demonstrate the absence of blood flow to the brain, but data on transcranial Doppler in extracorporeal membrane oxygenation to diagnose death of the entire brain are limited, and have not been rigorously validated.26Cestari M. Gobatto A.L.N. Hoshino M. Role and limitations of transcranial Doppler and brain death of patients on veno-arterial extracorporeal membrane oxygenation.ASAIO J. 2018; 64: e78Crossref PubMed Scopus (5) Google Scholar Beyond the question of blood flow to the entire brain, the act of ligating the cerebral vessels is also ethically controversial. From the viewpoint we have been discussing, the purpose of ligating the cerebral vessels is to create or maintain the state of death when circulation has been reestablished, because this act occurs when the patient might not be actually dead and restoration of circulation at that time has potential to restore some brain function. Because death according to circulatory criteria might be no longer valid when the heart is beating and able to support the circulation of the potential donor, proponents of this technique in essence are creating a state of brain death in order to avoid violating the DDR. According to the principle of double effect, an action such as, for example, withdrawal of life-sustaining treatment is ethically acceptable if the purpose is to respect the patient's autonomy and relieve suffering, even if the withdrawal is likely to result in the death of the patient, as long as death is not the intent of the action. However, any action that is designed to create or accelerate death during withdrawal of life-sustaining treatment is akin to euthanasia and is ethically unacceptable.27Stanford Encyclopedia of PhilosophyDoctrine of double effect.https://plato.stanford.edu/entries/double-effect/Date accessed: October 25, 2021Google Scholar In TA-NRP, the intention of occluding the cerebral vessels is not to relieve suffering—the patient no longer suffers—but, according to this viewpoint, is an attempt to create the state of brain death to avoid violation of the DDR. If this were the case, then, according to the principle of double effect, the positive act of interrupting blood flow to the brain would be morally wrong. Even if this action were considered permissible out of respect for the wishes of the donor, causing death by obstructing brain perfusion would be, like euthanasia, morally unacceptable.23Truog R.D. Miller F.G. Counterpoint: are donors after circulatory death really dead, and does it matter? No and not really.Chest. 2010; 138: 16-18Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The arguments that TA-NRP violates the DDR assumes a literal interpretation of the UDDA, namely, that cessation of circulatory and respiratory functions must be irreversible. Yet permanence rather than irreversibility has been widely accepted and practiced for decades. The stand-off period of 5 minutes from circulatory arrest to declaration of death does not guarantee irreversibility; successful circulatory resuscitation after more than 5 minutes after cardiac arrest is commonplace. The de facto standard for circulatory determination of death has for many years been permanence rather than irreversibility of circulatory cessation. As long as no intention to perfuse any part of the brain exists and perfusion is prevented, total destruction of the brain is inevitable. In all forms of cDCD, there is no intention to reperfuse the brain, so in all forms of cDCD, after determination of death according to circulatory criteria, the patient remains dead, even if corporeal circulation is restored. Under the unifying concept of death, determination of brain death is not necessary, because the patient's death according to circulatory criteria entails brain ischemia and infarction; preventing perfusion of the brain ensures that the already permanently ischemic brain will not recover function. The International Collaborative puts it this way: “Following systemic circulatory cessation, when there is no intent to attempt resuscitation (such as in patients who have a do-not-attempt-resuscitation order or as occurs in cDCD), and the possibility of auto-resuscitation has been excluded, death is defined as the permanent loss of capacity for consciousness and loss of all brainstem functions, determined by the permanent cessation of circulation to the brain.”7Domínguez-Gil B. Ascher N. Capron A.M. et al.Expanding controlled donation after the circulatory determination of death: statement from an international collaborative.Intensive Care Med. 2021; 47: 265-281Crossref PubMed Scopus (34) Google Scholar The unifying concept of death claims to ensure conformance with the DDR, and this applies to all cases of donation after circulatory death, including standard cDCD, DPP, and NRP (abdominal and thoracic). In all forms of cDCD, biological death (irreversible loss of function of the entire brain) has likely not occurred at the time that death is declared because parts of the brain survive after 5 minutes of ischemia, yet it is broadly accepted that death has occurred when circulation has ceased for 5 minutes. Under the unifying concept of death, all forms of cDCD, including the standard cDCD that has been widely used for decades, assume that permanent lack of circulation to the brain results in destruction of the brain. TA-NRP protocols require prevention of cerebral circulation to ensure permanent absence of brain function. Although it is relatively easy to prevent major vessel perfusion of the brain using ligation or balloon occlusion, collateral sources of blood flow might provide some degree of brain perfusion. Several methods have been advocated to ensure complete loss of brain circulation during TA-NRP procedures, including free drainage of aortic arch vessels to atmospheric or negative pressure, thus allowing collateral vessels, such as vertebral or spinal arteries, to drain to atmospheric pressure.13Manara A. Shemie S.D. Large S. et al.Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal.Am J Transplant. 2020; 20: 2017-2025Crossref PubMed Scopus (39) Google Scholar Total absence of brain perfusion has not yet been proven definitively, but in the study from Manara and colleagues13Manara A. Shemie S.D. Large S. et al.Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal.Am J Transplant. 2020; 20: 2017-2025Crossref PubMed Scopus (39) Google Scholar of 3 patients, persisting drainage of blood from the open ends of the arch vessels provides support for the presumption that ischemia is complete. Several possible means to substantiate absence of brain perfusion exist, but have not yet been systematically investigated in TA-NRP.28Parent B. Moazami N. Wall S. et al.Ethical and logistical concerns for establishing NRP heart transplantation in the United States.Am J Transplant. 2020; 20: 1508-1512Crossref PubMed Scopus (18) Google Scholar For that reason, TA-NRP in the United States should be done under research protocols that include verification that perfusion of the brain stem is absent. The validity and public acceptability of these factors is suggested by the fact that standard cDCD has been practiced openly for decades without widespread objection. Further support for the ethical acceptability of NRP can be found in 2 clinical trials of the use of an ex vivo apparatus in cDCD donors, at Stanford University School of Medicine29Shudo Y. Benjamin-Addy R. Koyano T.K. Hiesinger W. MacArthur J.W. Woo Y.J. Donors after circulatory death heart trial.Future Cardiol. 2021; 17: 11-17Crossref PubMed Scopus (16) Google Scholar and at New York University Langone Medical Center.30Smith DE, Kon ZN, Carillo JA, et al. Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States. J Thorac Cardiovasc Surg. Published online September 14, 2021. https://doi.org/10.1016/j.jtcvs.2021.07.059.Google Scholar Both studies were approved by their respective institutions. Some critics believe A-NRP to be acceptable while rejecting TA-NRP on grounds of continuing perfusion of the brain through spinal artery connections with brain stem arteries. However, some perfusion of the brain might persist in A-NRP through spinal–vertebral artery anastomoses even after isolation of the thoracic aorta because of extensive anastomoses among all of the spinal arteries, thoracic and abdominal31Santillan A. Nacarino V. Greenberg E. Riina H.A. Gobin Y.P. Patsalides A. Vascular anatomy of the spinal cord.J Neurointerv Surg. 2012; 4: 67-74Crossref PubMed Scopus (67) Google Scholar; minor flow into the brain stem is possible unless perfusion of the entire aorta is interrupted. Thus, persistent minor brain perfusion links TA-NRP and A-NRP—they are acceptable or unacceptable together. Concerns about potential loss of public trust if TA-NRP is publicly criticized might be overstated, because some evidence suggests widespread support of organ donation, even in the face of scandals and mistrust. For example, many were outraged when Mickey Mantle, the former New York Yankees slugger, received a liver ahead of others who had been on the transplant list much longer, yet there was no perceivable effect on organ donation.32Kolata GThe Nation: transplants, morality and Mickey. June 11, 1995. The New York Times.https://www.nytimes.com/1995/06/11/weekinreview/the-nation-transplants-morality-and-mickey.htmlDate accessed: February 11, 2022Google Scholar The same can be said when an undocumented immigrant received multiple heart–lung transplants at Duke University Hospital because of an error in blood typing.33Sade R. Why illegal aliens get a place in line. Duke case involved a serious medical error, not a transplant policy violation.Mod Healthc. 2003; 33: 16PubMed Google Scholar In fact, most Americans have been reported to support taking organs for transplantation even if removal of organs from an imminently dying donor causes death.34Nair-Collins M. Green S.R. Sutin A.R. Abandoning the dead donor rule? A national survey of public views on death and organ donation.J Med Ethics. 2015; 41: 297-302Crossref PubMed Scopus (47) Google Scholar In the event that TA-NRP were to be publicly criticized, loss of trust in organ donation seems unlikely. The debate over the ethical and legal status of NRP is likely to continue, as have many debates over various aspects of vital organ donation and transplantation. For example, reasonable questions persist about whether cDCD donors are biologically alive or dead,35Miller F.G. Truog R.D. Brock D.W. The dead donor rule: can it withstand critical scrutiny?.J Med Philos. 2010; 35: 299-312Crossref PubMed Scopus (60) Google Scholar yet despite publicly aired doubts, cDCD has been supported by nearly every commentator on the subject. Several European transplant centers are actively using TA-NRP, and it is currently used clinically in a few US transplant centers. It has the potential to increase the number of hearts available for transplantation,14Messer S. Cernic S. Page A. et al.A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors.J Heart Lung Transplant. 2020; 39: 1463-1475Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar and thus to decrease the suffering and death of those waiting on transplant lists. Several hundred heart failure patients will die this year for lack of an organ, so it is understandable that transplant surgeons will want to use every ethically and legally acceptable source of organs to save lives.