Normothermic Regional Perfusion
NRP involves restoring circulation after a declaration of circulatory death. Without it, the lack of perfusion of oxygenated blood to the organs damages them, making it difficult to retrieve organs after people are declared dead due to cessation of circulation. NRP’s purpose is to increase the supply of donor organs.
There are two types of NRP: One is abdominal; the other is thoracoabdominal. The concern here is primarily with the thoracoabdominal use of NRP, because it recirculates the blood through the heart. Some suggest that NRP may result in the heart resuming beating “spontaneously.” Perfusing the thoracic organs is an important distinction between the two types of NRP. (In this article, the abbreviation NRP refers to thoracoabdominal NRP after a determination of circulatory death.) There is a waiting period, generally of five minutes after circulation has stopped, prior to the start of the NRP process.
The Organ Procurement and Transplantation Network (OPTN) Ethics Committee describes the procedure:
[w]arm perfusion and circulation of oxygenated blood are initiated with an extracorporeal membrane oxygenation (ECMO) or bypass machine… Once ECMO perfusion is established, and the patient has been reintubated, the heart may resume beating inside the donor’s chest and warm oxygenated blood circulates to the lungs and abdominal organs. Perfusion to the brain is prevented by the occlusion of the brachiocephalic arteries, allowing neuronal hypoxemia and ischemia to progress. An attempt is made to wean the patient off of ECMO or bypass when cardiac function has been restored.
During the procedure, surgeons occlude arteries to try to prevent blood flow to the brain. Yet, that procedure acts as “tacit admission that the donor might not be legally dead.” And despite ligation, collateral blood flow to the brain is feasible.
The legal and ethical disposition is unsettled in the United States, despite its regular and increasing use in other countries, notably Spain, where it has been used consistently since 2012, and the UK, where its use is increasing and encouraged by the British Transplantation Society. The American College of Physicians called for a pause in this use of NRP in 2021. NYU Langone Medical Center first used the technique in January 2020, while New York – Presbyterian does not use it due to ethics concerns. Some argue that prosecutors could consider organ retrieval using NRP a cause of death because it may render the declaration of circulatory death invalid.
Dead Donor Rule
The dead donor rule requires that the patient be declared dead before procurement of vital organs for transplantation. The Uniform Determination of Death Act (Uniform Act) defines death as either
(a) irreversible cessation of circulatory and respiratory functions or
(b) irreversible cessation of all functions of the entire brain, including the brain stem.
Many researchers contend that restoring the circulation of the donor’s warm blood conflicts with the definitions of death by circulatory criteria and violates the dead donor rule. There are questions about whether subsequent restoration of circulation negates the prior determination of circulatory death. Some suggest once dead, always dead, while others see the initiation of circulating blood as an indication that the determination of death was not correct as it was not permanent. Generally, permanence legally and medically substitutes for irreversibility. This interpretation brings in intent. If the intention were to revive the person, it may be possible after the five-minute or even longer waiting period. But if the intention were to allow the person to die, that intention would justify declaring permanence, thus meeting the requirements of irreversibility (medically and legally, although technically, not literally). Some researchers do not want the definition of death to rely on intention. Others suggest intention has long been an understood part of the definition.
If circulation can be restored, the cessation of circulation was not irreversible, regardless of intention. NRP challenges the definition of circulatory death and common conceptions about death. If NRP brings a person “back to life,” then the initial declaration of death would be invalid for lack of “irreversibility.” NRP could violate the dead donor rule.
Some argue that if the vital organ has irreversibly lost its ability to function in an organized and directed manner in the person, that person is dead, regardless of whether the organ can function in a different person after transplantation. For example, Wall, et al., argue that the cessation of circulatory function is irreversible, because it cannot be reversed in a way that would return the person to life. They suggest NRP complies with the dead donor rule. Yet, their argument may stretch the definition of irreversibility to allow NRP to satisfy the dead donor rule. Their premises could also justify a definition of death outside the Uniform Act that would define irreversibility differently.
There is a distinct difference between viewpoints: Some argue NRP begins post-death and do not consider perfusion to be akin to resuscitation; others see NRP as invalidating the declaration of circulatory death.
If Not Circulatory Death, Then Possibly Brain Death?
If the circulatory declaration of death were discredited, the possibility of declaring the person brain dead during the process would remain. An invalid declaration of circulatory death arguably makes ensuring that there is not blood flow to the brain crucial to the ethical permissibility of NRP. Yet, some characterize ensuring so as possibly inducing brain death. Normally, declaring brain death is complex and requires a complete lack of brain activity and brain stem reflexes, coma, and an inability to breathe without mechanical support.
Cutting off blood flow to the brain could violate the dead donor rule if the person has not met either definition of death according to the Uniform Act. So much uncertainty about the validity of the declaration of death suggests a need to confirm that donors meet the requirements of brain death as well. This presents an ethical conundrum. There would need to be such a determination only if the donor were not dead already. To clarify, the basis of circulatory death may be embedded in the concept of brain death. To avoid declaring a person with brain function dead, the declaration of death occurs after blood flow to the brain has ceased. The lack of blood flow to the brain is arguably the reason that circulatory death is considered death (unifying concept of death). Therefore, stopping blood flow to the brain is an ethical imperative for NRP.
Notably, brain death does not require the cessation of circulation. Many researchers view occlusion as a deliberate act to prevent recovery of brain function to create or maintain a state of brain death. The American College of Physicians termed NRP a “protocol more accurately described as organ retrieval after cardiopulmonary arrest and induction of brain death.” Proponents of NRP assert that occluding cerebral circulation prevents “reanimation” but that the initial declaration of circulatory death would stand regardless of any evidence of brain function.
The dead donor rule issue, while unresolved in the literature, does warrant further analysis. The viewpoint of the public, donors, and family members of donors impacts the calculus. It is not just about meeting a legal definition of death. A person making the decision to donate organs (of another or in advance) generally would not expect NRP. A donor who does not explicitly approve of NRP in an advance directive would likely not have considered or expected it.
Critiques and Alternatives to the Dead Donor Rule
In organ transplant ethics generally, some researchers have argued against the dead donor rule. They suggest that the removal of vital organs prior to death is ethically permissible. They do not view the ability to legally obtain a death certificate by meeting one of the two definitions of death set forth in the Uniform Act as necessary to the moral permissibility of donation. For example, some say that respect for autonomy and being “beyond suffering” are enough. Others suggest a lack of consciousness should be the criterion for vital organ donation, and there are mixed views on those in minimally conscious states, permanent vegetative states, comas, etc. Arguably, medical ethicists Dominic Wilkinson and Julian Savulescu take a more direct approach, suggesting euthanasia by organ removal.
Some people in minimally conscious states may have the capacity to feel pain and arguably should not be candidates for organ harvesting prior to death, even if it were permissible. The arguments against the dead donor rule tend to focus on harm, either by comparing harms of being unable to donate organs with the possible harms of death by organ retrieval, or by comparing the harm to others due to the shortage of human organs for transplant.
Another noteworthy opposition to the dead donor rule came about differently. Brain death arose to ensure donors were dead and to increase organ donation. Bioethicist David Rodríguez-Arias suggests that brain death itself led the public to become comfortable with organ donation absent declarations of death on circulatory and respiratory grounds. Brain death is based on a judgment call about what death is and should not be seen as entirely scientific. Rodríguez-Arias suggests such a declaration of death does not protect the donor.
Harm to Donor
Restoring circulation, and the resulting collateral blood flow to the brain, may be unlikely to raise the possibility of consciousness or suffering. However, some researchers, notably Harry Peled and James Bernat, are concerned with the possibility of awareness. Collateral blood flow, anatomical variations, or technical failures could feasibly allow some blood flow to the brain. The OPTN Ethics Committee also notes that the impact of recirculation on spinal cord perfusion is not well understood. Researchers continue to study the risk that minimal blood flow could reach the brain (an exclusively scientific inquiry) and what that would mean for the possibility that the process equates to retrieving organs from a live donor. The second part of the inquiry concerns the definition of death as well as the scientific information, generally from scans to show there is not consciousness. The questions of what collateral minimal blood flow would mean concern definitions of death and safeguarding trust. It is not clear that there is any likelihood that a person declared dead, then subjected to a waiting period, and then subjected to NRP, could experience any significant degree of consciousness or sentience.
A distinct potential harm, and one we consider important in NRP, is “nonexperiential harm.” Some interests can survive the person, and the defeat of such interest is nonexperiential harm. If NRP conflicts with the donor’s beliefs or values, there is the risk of nonexperiential harm. When donors do not understand what NRP entails or their family members making decisions are not properly informed, there is a risk of harm to the perception of dignity the dead donor had when alive, or the family has. Clinical ethicist Walter Glannon argues the opposite: that there would be nonexperiential harm to people wishing to donate and unable to do so because hospitals refuse to use NRP. Many utilitarian arguments for organ transplant include some value for the benefit to the dead donor of having the wish to donate met or the detriment to a potential donor whose organs are not donated. However, often the dead donor’s family makes the determination, the donor’s wishes are unknown, or the degree to which the donor values organ donation is unknown. Many people opt in through driver’s licenses without being enthusiastic or even particularly interested in donating. It is not clear that there is some true detriment post-death to a would-be donor who dies in circumstances where organ retrieval cannot occur or whose organs are not appropriate for donation due to damage, ill health, etc. Certainly, some donors are especially committed to organ donation, but there is no evidence that all are or that there is measurable harm from the inability to do so.
In Defense of the Dead Donor Rule
The dead donor rule has been a cornerstone of organ transplant ethics. Technological advances including NRP have sparked more debate about the dead donor rule. The rush to retrieve organs is present in debates about death and the dead donor rule. The dead donor rule sits within organ transplant—if we were redefining death for other purposes, there would be more clear parameters. There are laws governing dead bodies arguably to the point of micromanagement. The current state of medical aid in dying may alter some of the arguments. When John Robertson defended the dead donor rule in 1999, Oregon was the only state with legal medical aid in dying. The changing landscape of medical aid in dying and the considerations about the role of physicians in active assistance alter the concept of death as natural and not to be brought about by the medical community. Yet, medical aid in dying is distinguishable from organ transplant. The dead donor rule comports with our definition of death, a definition crucial to social, legal, and medical aims. Any departure from the dead donor rule is an acknowledgement that some lives should be (or may be) cut short for the good of organ recipients.
The utilitarian defenses of allowing organ retrieval without a declaration of death make assumptions that we are unwilling to make here. If there were not organ transplants at all (as prior to the 1950s), it is unlikely that anyone would want to redefine death more broadly or place death at an earlier point in the dying process. It is the strong desire for organs that has led to utilitarian calculations that compare the value of an organ to sustain the life of another to the value of a life near, but not quite at, the end.
Arguments about life’s end often include dignity. Yet, our argument may have an element of continuing the status quo because it is both workable and important. If it isn’t broken, don’t fix it. And it truly is not broken. Organ transplant after brain death generates the vast majority of organs for transplant. Improved methods have increased organ supplies already. The dead donor rule is meant to protect organ donors, even to entice them. It absolves any fears that a plug would be pulled prematurely if they list themselves as organ donors. It is the standard for global organ donation—the World Health Organization (WHO) defends it in its Guiding Principles on Human Cell, Tissue and Organ Transplantation. WHO requires death and requires that physicians determining that the donor has died are not involved in organ retrieval. The principles are designed to prevent fraud, coercion, and crime. Eliminating the dead donor rule creates a risk of abuse in organ transplant. Carving out a new type of death or declaring death at a different point in the dying process poses similar ethical concerns. One should not be able to claim that since someone is dying anyway, the person is actually dead for all intents and purposes.
The issue of whether NRP violates the dead donor rule for various technical reasons is an open issue based on several factors. At the very least, it does seem to violate the plain language of “irreversible cessation of circulatory and respiratory functions.” There are ways around that—partly by noting a distinction between perfusion and the process of spontaneous heart-beating and circulation. But then when the heartbeat spontaneously reignites, the distinction arguably becomes moot. Continued investigation into blood leaking into the brain is necessary. If the determination of circulatory death were invalid, then testing and declaring whether the person already is brain dead would become an important precursor to organ retrieval. And if physicians cause brain death, the dead donor rule would be violated. Physicians performing NRP rely completely on the declaration of circulatory death, but have added the task of occlusion, seemingly “just in case,” or perhaps to improve public confidence that the brain will not be able to function. While there are not any cases so far, an invalid declaration of death could lead to liability or conviction for causing death by NRP.
For purposes of moving on to discuss consent, this article assumes that NRP will be legally permissible despite controversy over its ethical basis. Some hospitals in the US already use it.
Consent: Did the Donor Mean to Sign off on This?
Some who favor increasing organ supply using NRP build on their utilitarian foundation arguing that the increased quantity and quality of organs advances the donor’s wishes. Understanding the procedure and choosing whether to donate using NRP is crucial for transparency and informed consent. Nondisclosure undermines informed consent. Some do argue that once dead, a person is not entitled to informed consent, and many have theories on whether one should even have the right to direct the disposition of their corpse after death. Some theorists profess that the need for organs outweighs the value of control over one’s own body after death. Yet others promote the idea that people refusing to donate organs are ill-informed, provincial or religious, or ungenerous. Such arguments call for criticism and violate the premises behind a voluntary organ donation system in keeping with the WHO Guiding Principles. The discussion should include the public, as donors are the cornerstone of organ transplant. Medical voices should not sideline donors’ voices. It is noteworthy that most of the documents cited here come from within the medical community.
Potential donors can communicate their wishes to donate organs post-death through their driver’s licenses and by including them in advance directives. Although this is an expression of the donor’s consent, questions arise about whether NRP calls for special consent. Prior to expressing their wish to donate, potential donors do not receive any specific information about the donation process. It is conceivable that potential donors who consent to donation on a driver’s license or in an advance directive would object to NRP based on the relevant differences in the procedure. The issues surrounding questions about the donor’s wishes become clouded when the person has not communicated wishes, and the decision defaults to the family or surrogate.
Some suggest there is no need for specific consent for NRP and that donors, recipients, and families do not need to be informed about recirculation, reanimation, the risk of collateral blood flow to the brain, or the method of occlusion. The Organ Donation Alliance states, “Some argue that it is not necessary to discuss a technique that is utilized after death and is intended for facilitation of the stewardship of the gift, and that this information might be too overwhelming and challenging to understand for a lay and grieving family[.]” This viewpoint is objectionable for several reasons. It could be perceived as somewhat condescending. An ordinary person would not expect the NRP procedure. In fact, a New York Times article arguably brought NRP into the public discourse. People weighing in through the OPTN public comment, discussed below, suggested that the procedure is different from organ retrieval after brain death and that the public should be part of the conversation as the discussions touch on items of societal interest, including the definition of death.
Peled, et al., and others suggest that a reasonable person would want to be informed about the technique. Restarting circulation, potential cerebral perfusion, and removing organs prior to the certainty of death (or at least without consensus on the validity of the declaration of death) may contradict the donor, family, or recipient’s values and beliefs. Respect for such beliefs calls for disclosing relevant information and allowing objections on religious or moral grounds, or really on any grounds, as the decision to donate is voluntary.
The need for transparency is pressing for several reasons. First, transparency would allow the public over time to voice its opinion. OPTN held a public comment period and found the following:
- There are serious ethical concerns that NRP is not consistent with the Dead Donor Rule (DDR).
- Nonmaleficence (do no harm) must not be violated in the pursuit of NRP, even if positive utility outcomes could result.
- Consistent and transparent protocols, including adequate informed decision making with patients (pre-mortem) and of families approached about donation, are necessary pre-conditions for any ethical pursuit of NRP.
The OPTN findings note the need to protect public trust. Without a requirement of informed consent, if donors themselves in advance hear about and oppose NRP, organizations tracking registered organ donors would be able to measure any drop in registrations should there be a drop. An agreement by all institutions engaging in NRP to require a description of the process and explicit informed consent would ensure people opting in through drivers’ licenses that they are not opting in to NRP at the time they register as donors. Trust in medicine is based on transparency and truthfulness. Public trust is crucial for voluntary organ donation. Public mistrust because of non-disclosure about NRP could lead to a reduction of organs or slow the rate of growth of organ donor registrations. In addressing the possibility of euthanasia for organ retrieval, Wilkinson and Savulescu identified two public concerns related to organ donation: changes that may lead to the death of patients who would have otherwise survived and being conscious while having organs removed. While the context differs, both concerns surface in the context of NRP.
The recent New York Times article on NRP notes the lack of clarity and murky area between life and death. Trust in medicine is built on transparency leading to the donors understanding the technique. If donors’ families widely report that they did not understand NRP and felt that their relative was “brought back to life” during the process of organ retrieval the bad press would be both well-deserved and detrimental to trust in medicine. Even if they do not have concerns about the declaration of death, families and donors may have concerns about the nature of the process. Trust requires trustworthiness. The medical community should not move forward without express consent—doing so belittles the donor families, places the medical communities’ priority of obtaining more organs over the concerns of donor families, and undermines trust.
Monitoring Brain Activity
It will be crucial to ensure potential donors, their proxies, and close relatives, when relevant, that there will be some sort of monitoring of brain activity. There have been attempts to measure collateral blood flow and to discern the meaningfulness of such blood flow to consciousness, awareness, or brain function. Large hospital systems are split over the ethics of using NRP. For now, one requirement of its ethical, consensual use should be a monitoring protocol. Monitoring could become unnecessary with improved techniques.
Consent Recommendations
If NRP is permitted, consent documents for NRP should have the goal of transparency. They must include important aspects of the method:
- NRP is being offered because organs would be damaged in the aftermath of circulatory death without perfusion and NRP allows perfusion to the thoracic organs including the heart.
- Blood flow will be restarted.
- There is debate over whether the method of perfusion negates a circulatory determination of death, but without a legal declaration of death, physicians would not begin the process of organ retrieval.
- Blood flow to the brain will be cut off by occluding main arteries purposely during the process, yet some blood could reach the brain through ancillary vessels.
- To ensure there is no brain function, the organ retrieval will include monitoring of brain activity.
The OPTN Ethics Committee suggests that, “In the interest of public trust, respect for persons, and transparency, authorizations should include disclosure of recirculation through the heart (TA-NRP) and the potential restoration of cerebral perfusion (TA-NRP and A-NRP) as well as considerations of meaningful differences from other donation approaches.” Entwistle, et al., additionally suggest limiting NRP to those who were severely brain injured prior to the declaration of death and ensuring that there is not discussion of organ donation prior to the decision to withdraw life support.
Systems with Opt-out
Express consent should also be required in jurisdictions with opt-out consent systems. With opt-in systems, NRP should not be included in a blanket organ donation like that noted on a driver’s license. Opt-out systems have several ethical justifications. One is that organ donation should be based on normative consent—NRP is not likely to comport with societal norms. Normative consent makes a judgment about values that underlie social norms. It assumes that one ought not withhold consent. Such an assumption is not valid with the new technique and its ethical issues. Presumed consent relies on the idea that most people would agree. Implicit consent goes further in noting that people can opt out, so inaction is consent. None of the three noted justifications for opt-out organ donation systems should justify NRP without explicit consent. Regardless of the system for donations, NRP presents important ethical issues that are materially different from those presented by other techniques.
Conclusion
Whether NRP violates the dead donor rule is an open issue that stems from interpretations of definitions of death. NRP brings about commonsense questions about irreversibility after cessation of circulation and the meaning of resuscitation. NRP would be more clearly adherent to the legal definition of death if the irreversibility requirement had an exception or clarification. It does not have exceptions as written. The public, many of whom may become organ donors, may wish to consider some of the issues NRP presents, and to give input before changes to the definition of death or the abandonment of the dead donor rule. New technology and techniques like NRP challenge people to consider what death means, how it is determined, and whether irreversibility remains important considering current technological means to keep blood flowing yet not restore meaningful life. Most of the answers are not going to be found in science, although assessing collateral blood flow to the brain despite occlusion is an important scientific task.
The dead donor rule remains the foundation for societal acceptance of organ donation despite its critics. It is crucial to trust in organ transplant systems. Abandoning the dead donor rule could have a chilling effect on donation. If NRP continues, to satisfy the ethical imperative of explicit informed consent, donors (in advance) and their families or decision makers should be adequately informed. Information that plainly describes both the process and the relevant ethical issues without a latent motive to win their consent would comport with transparency and promote trust. It is important that donors and their decision makers and relevant family members understand both that NRP is controversial and what the process entails. Without a complete understanding, donor families are unable to provide informed consent. In such cases, hospitals should consider forgoing collecting organs this way.