POINT: Does Normothermic Regional Perfusion Violate the Ethical Principles Underlying Organ Procurement? Yes

Abstract

Normothermic regional perfusion (NRP) uses extracorporeal technologies (such as cardiopulmonary bypass and extracorporeal membrane oxygenation) to preserve organs for transplantation, particularly hearts.1Smith D.E. Kon Z.N. Carillo J.A. et al.Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States.J Thorac Cardiovasc Surg. 2022; 164: 557-568.e1Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar,2Hoffman J.R.H. McMaster W.G. Rali A.S. et al.Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.J Heart Lung Transplant. 2021; 40: 1408-1418Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Notably, this is done by restarting circulation of the donor’s own warm blood after irreversible circulatory death was declared. NRP is performed in a few countries and prohibited in others (eg, Australia). Sometimes called thoraco-abdominal NRP in controlled donation after circulatory determination of death (cDCD), NRP is used in much of the literature and therefore, used here. Increasingly, ethical and legal concerns are being raised about NRP.3D’Alessandro D. Pierson 3rd, R.N. Commentary: a long road back to the beginning.J Thorac Cardiovasc Surg. 2022; 164: 569-570Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 4Jawitz O.K. Milano C. Commentary: An innovative strategy for expanding the donor pool.J Thorac Cardiovasc Surg. 2022; 164: 571-572Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 5Pagani F.D. Heart transplantation using organs from donors following circulatory death: the journey continues.J Am Coll Cardiol. 2022; 79: 163-165Crossref PubMed Scopus (2) Google Scholar, 6Ethics, 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. April 17, 2021. Accessed February 1, 2022. https://www.acponline.org/acp_policy/policies/ethics_determination_of_death_and_organ_transplantation_in_nrp_2021.pdfGoogle Scholar, 7Bernat J.L. Bleck T.P. Blosser S.A. et al.Circulatory death determination in uncontrolled organ donors: a panel viewpoint.Ann Emerg Med. 2014; 63: 384-390Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 8Dalle Ave A.L. Shaw D.M. Bernat J.L. Ethical issues in the use of extracorporeal membrane oxygenation in controlled donation after circulatory determination of death.Am J Transplant. 2016; 16: 2293-2299Crossref PubMed Scopus (47) Google Scholar Use of the technology gets ahead of ethics and US law. In considering NRP, one must keep in mind that a declaration of death does not mean an individual is dead if the declaration is invalidated by subsequent action. This is an issue only in the last of the following procurement circumstances:•In cadaveric donation (eg, corneas, which may be procured hours after death), status of the donor is not ambiguous.•In donation after brain death, cardiopulmonary support is continued to maintain solid organ viability because brain death is irreversible.•In standard donation after circulatory death, life-sustaining therapies are withdrawn and not restarted; organs are procured once circulation has ceased irreversibly.•In NRP, a patient is declared dead because circulation has ceased irreversibly, but then, in the interest of solid organ viability, circulation is restarted, which is a manifest contradiction. Moreover, along with reinitiating donor circulation, NRP protocols call for the deliberate interruption of blood flow to the brain. NRP is thus distinct from other types of procurement and is distinctly ethically problematic. The dead donor rule, a fundamental norm that governs organ procurement, states that organ procurement cannot cause death and that a patient’s death cannot be caused in organ procurement.9Robertson J.A. The dead donor rule.Hastings Cent Rep. 1999; 29: 6-14Crossref PubMed Scopus (197) Google Scholar Based in ethical principles of respect and nonmaleficence, it remains foundational to maintaining trust in voluntary organ donation. It assures patients and families of medicine’s commitment to not harm patients and to not use one patient merely to serve the needs or goals of another. NRP is used in cDCD when a patient does not meet criteria for brain death and is receiving cardiorespiratory support. Life-sustaining therapies are withdrawn consistent with patient and/or family wishes, resulting in the cessation of cardiorespiratory functions. But because the intention from the outset is to restart circulation, and recognizing the possibility of brain viability, active steps to prevent recirculation to the brain (eg, ligation or balloon occlusion of the carotid arteries) are taken. This violates the US standards for determining death. The Uniform Determination of Death Act (UDDA) defines standards for determining death as the irreversible cessation of circulatory and respiratory functions or of all brain functions, including the brainstem. Restarting circulation reverses what was just declared to be the irreversible cessation of circulatory and respiratory function. It is no defense to suggest the patient was already dead when the action negates the conditions upon which that determination was made. Although there has been debate about whether permanence is a better description than irreversible, resuscitation was intentional, and circulation is restored; the loss of circulation was neither irreversible nor permanent. UDDA drafters defined the standard for determining death as either the irreversible cessation of circulatory and respiratory function or the irreversible cessation of the functions of the entire brain after apparently rejecting the idea of death defined only as the death of the brain, declared in either of these two ways.7Bernat J.L. Bleck T.P. Blosser S.A. et al.Circulatory death determination in uncontrolled organ donors: a panel viewpoint.Ann Emerg Med. 2014; 63: 384-390Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar Some proponents who support NRP, however, appear to adopt this rejected definition of death;2Hoffman J.R.H. McMaster W.G. Rali A.S. et al.Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.J Heart Lung Transplant. 2021; 40: 1408-1418Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar for example, defining death as the “cessation of circulation to the brain.”10Domínguez-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 (Erratum in: Intensive Care Med. 2021;47(9):1059-1060): 265-281Crossref PubMed Scopus (42) Google Scholar Others seem to suggest circulatory/respiratory death is death only because it leads, eventually, to brain death. However, linking the two types of death determination contravenes the intent of the UDDA. Moreover, given the timeline of NRP and organ procurement, whole brain death criteria could not have been evaluated or met. The transplantation community, limited expert panels, nor others have the authority or the requisite objectivity to change the definition of death, even for a noble cause. Sometimes construed as a technical problem to be overcome in NRP,11Manara 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 (47) Google Scholar the prevention of brain recirculation is anything but a technicality. Such actions reflect recognition that brain death has not occurred. Restarting circulation while preventing blood flow to the brain cannot be justified by saying the actions are not intended to resuscitate or benefit the donor.12Parent B. Moazami N. Wall S. et al.Ethical and logistical concerns for establishing NRP-cDCD heart transplantation in the United States.Am J Transplant. 2020; 20: 1508-1512Crossref PubMed Scopus (21) Google Scholar Intended or not, the actions do in fact resuscitate the patient. Similar concerns that were voiced years ago regarding NRP-like techniques7Bernat J.L. Bleck T.P. Blosser S.A. et al.Circulatory death determination in uncontrolled organ donors: a panel viewpoint.Ann Emerg Med. 2014; 63: 384-390Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar,8Dalle Ave A.L. Shaw D.M. Bernat J.L. Ethical issues in the use of extracorporeal membrane oxygenation in controlled donation after circulatory determination of death.Am J Transplant. 2016; 16: 2293-2299Crossref PubMed Scopus (47) Google Scholar remain unaddressed. Some say the disruption of brain circulation is to “maintain” brain death.4Jawitz O.K. Milano C. Commentary: An innovative strategy for expanding the donor pool.J Thorac Cardiovasc Surg. 2022; 164: 571-572Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar This makes no sense; if brain death had occurred, active steps would not be necessary; if it had not, those active steps caused it. Likewise, some say cutting off circulation to the brain ensures “natural” progression to brain death,12Parent B. Moazami N. Wall S. et al.Ethical and logistical concerns for establishing NRP-cDCD heart transplantation in the United States.Am J Transplant. 2020; 20: 1508-1512Crossref PubMed Scopus (21) Google Scholar but this is not natural. Equally troubling is the argument that, if the patient were unintentionally resuscitated or experienced autoresuscitation, it would not result in “meaningful” recovery. This is not about death, but a value judgment about quality of life. Using this or similar language would be very confusing to family members approached for consent; however, it is unclear whether any meaningful attempt at all is made to explain NRP. More importantly, even if completely and understandably explained to both the recipient and the donor’s family, consent alone cannot justify NRP nor override medicine’s obligations to help and not do harm. Also, respecting a person’s wish to be a donor does not itself justify NRP. It is possible to fulfill the laudable wish to donate under usual cDCD procedures. Some proponents say NRP saves money, but it is an empiric question whether organs so procured result in lower overall costs. Moreover, avoiding cost is not a justification for pursuing an ethically problematic course of action. Use of ex vivo devices instead of in situ NRP shows promise. And after all, any cost is relative to the $1.7 million dollar cost of a heart transplantation operation. More fundamentally, “Reperfusion devices can be applied after organs are procured via cDCD without restarting the donor’s circulation or intentionally occluding brain perfusion to render an individual brain dead. There is a large and ethically significant difference between perfusing an organ versus perfusing an individual.”6Ethics, 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. April 17, 2021. Accessed February 1, 2022. https://www.acponline.org/acp_policy/policies/ethics_determination_of_death_and_organ_transplantation_in_nrp_2021.pdfGoogle Scholar The burden of proof in this debate is with proponents of NRP. They have not met this burden. Their use of obfuscating language is unhelpful, as is their misapplication of both ethical principles and the law.