Ethical Analysis of Normothermic Regional Perfusion
At a glance
This paper outlines the ethical principles relevant for review of the new medical transplant procedure, normothermic regional perfusion (NRP). NRP is a new technology that has potential to increase the number of transplantable organs, but it is important to ensure that the donation procedures are transparent and ethical.
NRP involves using a machine to pass blood through organs in a person’s body after the heart has irreversibly stopped beating. Vessels are clamped during this procedure to prevent blood flow to the brain.
As a surgical procedure NRP shows a positive impact on utility by reducing non-use of organs without negatively impacting patient outcomes. However, the fact that NRP involves recirculation after declaration of death by circulatory criteria raises concerns about compliance with the Dead Donor Rule and nonmaleficence (do no harm). To uphold the ethical principle of respect for persons, the Ethics Committee considers that informed consent procedures should be thorough and include information about the unique and relevant aspects of NRP. Uncontrolled scenarios (as explained, in detail, in the white paper) for NRP raise serious concerns for respect for persons and hastily moving from therapeutic treatment to organ recovery.
- Reviews the implications of NRP according to relevant ethical principles of organ transplant – nonmaleficence (do no harm), respect for persons (autonomy), and utility.
- What information should be given to donor families regarding the use of the NRP procedure?
- Are there any ethical arguments or additional evidence that should be taken into account in the white paper’s analysis?
- What it's expected to do
- Provide an ethical analysis of NRP
- Address and discuss concerns about compliance with the Dead Donor Rule and potential for harm
- Address and discuss the topic of informed consent in light of public trust; specifically, whether additional information is needed for donor authorization
- What it won't do
- There are no changes to policy
- There are no changes to allocation
- There are no changes to data collection
Terms to know
- White paper: A white paper considers a complex issue and develops a position.
- Ethics Committee’s Scope: The Ethics Committee makes recommendations to OPTN Board of Directors for changing, creating, or eliminating policies if warranted by ethical concerns.
- Nonmaleficence: The ethical principle of nonmaleficence, in organ transplant, refers to doing no harm to perpetuate transplant.
- Autonomy: The ethical principle of autonomy or respect for persons, in organ transplant, refers to one’s ability to be self-directing, decide what happens to oneself in the future, and the ability to be a part of decisions regarding one’s own medical treatment.
- Utility: The ethical principle of utility, in organ transplant, refers to creating the most benefit to the transplant community (i.e. promote graft survival, reduce waste, improve efficiency).
- Dead Donor Rule: A donor must be dead at the time of organ procurement and organ donation must not cause death.
Read the full proposal (PDF)
OPTN Organ Procurement Organization Committee | 09/21/2023
The OPTN Organ Procurement Organization Committee thanks the OPTN Ethics Committee for their work and for the opportunity to comment on this white paper.
A member recognized that NRP can increase transplants, and thus save lives, but question how much detail should be conveyed in conversations with donor families. The member expressed concern for limited consensus on how to discuss NRP with donor families and noted that standardization in this area would be critical for OPOs.
One member countered, expressing concern about prescribing specific talking points that OPOs must disclose to donor families, as each donor family varies on the info they want to hear. Donor coordinators must be prepared to address donor families who want to know everything regarding NRP and relevant processes as well as address donor families who may want as little detail about NRP as possible.
A member questioned how much of the discomfort surrounding disclosure comes from OPO staff perspectives or from the donor families. The member shared concerns about OPO staff transferring those concerns to donor families. The member noted that OPO staff should be mindful of this when working with donor families.
A member, who has experience with NRP, shared that they have not seen family issues, but they have noticed discomfort from hospital staff, which they believe will be the biggest challenge with NRP. They recommended a toolkit for hospital staff to help relieve discomfort.
New England Organ Bank | 09/19/2023
NEDS is appreciative of the Ethics Committee’s work on the Ethical Analysis of NRP. There are ethical and, in our view, possibly legal distinctions between abdominal NRP (A-NRP) and thoracic NRP (TA-NRP) protocols that the Paper should more fully explore. For example, the resumption of circulation of blood to the heart and the potential risk of circulation to the brain in TA- NRP has ethical implications for the permanence standard in death declaration as compared to A-NRP. For this reason, while NEDS is implementing A-NRP as an OPO-driven protocol, it is not engaging in TA-NRP until there is further understanding and resolution of these concerns specifically as they relate to fulfilling ethical and legal requirements regarding non-malfeasance and the dead donor rule. Instead, employing ex vivo technology avoids these ethical issues and enables utilization of thoracic organs from DCD cases. Because protocol specific decisions are being made regarding initiation of NRP, it would be useful for the Paper to provide a deeper analysis of the ethical distinctions between TA-NRP and A-NRP.
Resolution of the ethical concerns may be through empirical research (for example, studies confirming absence of blood flow to the brain during NRP) but also through the development of a coherent ethical paradigm for understanding the permanence standard utilizing a unified brain-based concept. The Paper should reference the international work in this area to move towards a framework where a permanent absence of circulation to the brain – as measured by the cessation of systemic circulation – serves as an ethically appropriate and clinically supported standard for determining death. See Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion, Bernat et al., Transplantation May 12, 2023.
NEDS notes that while there is not consensus on the ethical or legal issues posed by NRP, there should be strong confirmation of fundamental ethical principles that remain central to the public trust in donation including the dead donor rule. Thus, the misalignment between the legal definition of death and the practice of NRP (and we view this differently as between A-NRP and TA-NRP) should be understood as a risk that can be mitigated through an interpretation of applicable standards and, to the extent possible, by identified protocol elements. But ultimately there must be confidence both that the donor is deceased before organ donation is commenced as well as a clear articulation of on what basis death as a permanent state has been achieved (other than, because there has been a declaration). The community should acknowledge that transplant outcomes and the ethical principles of utility do not solve for these concerns.
As an aside, NEDS also notes that the Paper asserts that discussions regarding donation should occur after a decision to withdraw support has been made (p 27). In NEDS’ experience (as an OPO that coordinated 162 DCD cases last year and consistently has over 30% DCD cases for years), the number one reason families decline to authorize DCD is due to timing. By the time the family has made a withdrawal decision, many have set plans in motion around certain timing that donation would then delay. There is no ethical reason to delay the discussion about organ donation until after withdrawal decisions have been made; families should have all the information to fully understand the decisions that will come next and the process that will impact timing. Especially since in nearly half the cases, the donor him or herself has already authorized donation through a donor registry (effectively “decoupling” the donation decision from the withdrawal decision). NEDS has found that by initiating earlier discussions with families about DCD, the authorization rate improved significantly and identification by families of timing as the reason for declining authorization went down. The Paper should be revised to reflect this evolving best practice regarding when to discuss donation in DCD circumstances. This may also be a good topic for the Ethics Committee to revisit outside of the NRP White Paper.
Thomas Egan | 09/19/2023
OPTN Patient Affairs Committee | 09/19/2023
The OPTN Patient Affairs Committee would like to thank the OPTN Ethics Committee for their thoughtful work in developing this proposal. PAC members are directly impacted by the decisions made during the procurement process. This is particularly true for the donor families on the Committee who have experienced firsthand the grief of losing a loved one and deciding to pass on their lifesaving gifts to strangers so they may live longer.
The Committee’s concern regarding NRP begins with the donor families. When discussing donation with families, it is important to remember they are experiencing grief, trauma, and exhaustion. The discussion regarding NRP should be held at an appropriate time and in such a way that it does not burden the family. The families need to be reassured that everything was done to try to save the life of their loved one, and then informed on what NRP is and how it is not a lifesaving technique. Increasing the burden of information on families could increase the likelihood that authorization for donation will not be granted. There is already mistrust within certain communities when it comes to deceased organ donation, and if proper education on NRP does not occur then this process risks increasing that mistrust.
Some PAC members suggest including religious leaders in helping to develop the way this topic is introduced to donor families. The fact that it is stated that NRP “may violate the Dead Donor Rule” should make the system take pause. Risking public trust surrounding this issue could be detrimental to the transplant community. Clearer guidelines are needed to ensure that patients and families approached about organ donation know they can opt out of NRP. The conclusion to “proceed cautiously” is ambiguous and increases the ethical concerns many people will have about NRP. Will the use of NRP increase the number of utilized organs, and is there data to support this? If not, then we must seriously weigh the utility that NRP provides against the potential harm it can do to public trust in our transplant system.
Kari Esbensen | 09/19/2023
Thank you for tackling this important issue and providing a forum for public commentary.
Before addressing the ethical acceptability of NRP, we must step back to ask the fundamental ethical question that has become obscured in describing the medical minutiae of NRP. That fundamental question is: Does the laudable goal of procuring greater numbers of higher-quality organs justify the practice of inducing brain-death in non-brain-dead donor-patients? Would donor-patient consent (or, more likely, surrogate consent) be enough to condone the act of causing brain death for the purpose of harvesting a person’s organs? If so, then we should be having that larger debate in a transparent manner, in open forums, making it clear to the public that the transplant community is contemplating a dramatic shift away from the ethical norms that have placed important guardrails on the enterprise of organ transplantation since its inception – first among them, the dead donor rule (DDR). The DDR requires that the donor-patient must indeed be dead before organ procurement occurs and that the procedures undertaken to procure a donor’s organs must not cause the donor-patient’s death.
In NRP, the donor-patient is no more dead by circulatory criteria than any other patient who sustains cardiopulmonary arrest and successfully undergoes restoration of circulatory function by CPR, defibrillation, and/or initiation of ECMO and respiratory function by intubation. The only difference between the latter and the former is that, in the case of the donor-patient in NRP, the surgeons clamp the cerebral aortic arch vessels to ensure that, with restoration of circulation, no blood flow makes it to the brain to resuscitate the brain along with the heart and other organs – i.e., the surgeons induce brain death in a patient who, otherwise, would no longer be deemed dead. In fact, the patient is still not dead unless brain death has irreversibly and permanently occurred. However, if either of these were the already the case, the clamping would be unnecessary. As others have commented, further research is needed to empirically determine when such brain death actually occurs in these donor-patients. However, from an ethical standpoint, the central question is not whether the donor-patients are brain dead yet, but whether it is morally acceptable for surgeons to cause brain death solely for the purpose of procuring the patient’s organs. Thus, my initial question above, which is central to considering the moral permissibility of NRP.
Furthermore, while a person who has suffered cardiopulmonary arrest often remains dependent upon ECMO to maintain circulation, in NRP, the donor-patient (who is likely not yet brain dead in the short time-frame of NRP) is actually weaned off ECMO in order to allow assessment of the heart’s function in situ. The person’s own heart maintains circulation. Thus, the description in the Background section above, that “NRP involves using a machine to pass blood through organs in a person’s body after the heart has irreversibly stopped beating,” is misleading at best. The machine (ECMO) is temporarily needed to restart the heart, but the heart has certainly not irreversibly stopped beating, or it would not be a viable organ for transplantation. In fact, the benefit of being able to assess the heart’s function in situ (after the ischemic injury sustained during the few minutes of asystole prior to ECMO) is touted by NRP’s proponents as one of the primary advantages of NRP, as opposed to the practice of using ex vivo resuscitation and preservation of the heart (“heart-in-a-box” techniques) after typical donation after cardiac death.
Fundamental ethical norms like the DDR have not only undergirded the practices of transplant physicians; they have also sustained the public’s trust that their interests and medical care will not be compromised or sacrificed when they face critical illness, simply because their organs could be harvested to save the lives of others and they have consented to organ donation (once they are already dead). Particularly in this era of so much cynicism and erosion of the public’s trust that medical professionals will uphold patients’ interests and needs first and foremost, the acceptance of NRP – and its concomitant overturning of the moral norms that have long placed safeguards upon organ transplantation – may strike a fatal blow to the public’s trust in our organ procurement systems. Instead of increasing the supply of viable organs, it may lead, instead, to a refusal of the public to consent to organ donation, once they become aware of these important safeguards crumbling. These empirical and more fundamental ethical questions are deserving of much further scrutiny before proceeding with NRP.
Hospital of the University of Pennsylvania | 09/19/2023
This whitepaper like many others gets wrapped up in semantics. Unclear why Europe has gotten this correct (it is now mandatory in some countries) and we cannot.
Lorrinda Gray-Davis | 09/19/2023
My thoughts are the understanding of DCD for donor families and when this takes place. If education does not happen in ALL “Communities” that could cause mistrust or misunderstanding of what that means.
If a donor liver goes into a box and is perfused outside of the donor I do not see and issue.
Conducting a perfusion on a donor prior to procurement may cause issues with families. Education about organ donation is not what it should be, this may cause issues and trauma for families.
There will need to be an enormous amount of education in communities.
Region 8 | 09/19/2023
Sentiment: 1 strongly support, 9 support, 8 neutral/abstain, 1 oppose, 0 strongly oppose
A member suggested that the state of the mind of the donor family at the time will be what decides whether donation occurs or not. And explained that the ability to process information or handle any information can be greatly impaired during this time and too much information/responsibility can be overwhelming. The burden should not be put on donor families to decide if they are comfortable with NRP; rather, that decision is for transplant professionals to decide before presenting it as an organ recovery option. The member was not convinced that cerebral blood flow studies on two human subjects is adequate to say that cerebral blood flow does not occur and believed that more data is needed to proceed with it. An attendee supported the paper and asked the committee to consider the delicacy of the Donor Family Care conversation. They recommended that OPOs provide Donor Families with general disclosure to the effect that the donation process will likely include the use of machine perfusion, either in-situ or ex-situ to maximize organ function for transplantation. A member commented that in addition to the ethics (and risks) of brain reperfusion, there are wide reports of NRP negatively affecting kidneys and lungs. So, while more hearts may be accepted due to NRP, the community needs to keep in mind other organs are becoming unusable. Another member said there is a need for community and clinician education and transparency. A member commented that NRP effectively increases DCD utilization of heart/lungs. A center commented that NRP is having a very positive impact at their center regarding the use of organs and organ performance. A member said they would support NRP if there are national protocols for it. An attendee pointed out that NRP is the future of transplant.
D. Joy Riley | 09/19/2023
The OPTN Ethics Committee supports the organ procurement practice of normothermic regional perfusion (NRP), and opines that it should proceed, albeit cautiously, even though
The Dead Donor Rule is not clearly being followed
The donor may not be dead prior to procurement since the heart can be restarted
The procedure may cause death because the great vessels to the brain are clamped or otherwise occluded
Public trust may be undermined if donor families become aware of difficulties (lines 593-7)
Donor families could experience psychosocial distress (line 597)
There is uncertainty over the legality of NRP, and the potential for lawsuits is of concern (lines 608-612)
There are (apparently confidential) reports of moral distress and potential moral injury of clinicians at centers where NRP is practiced (lines 614-625)
Reason demands that one ask, “Why?” Why would an ethics body support a procedure with all of these unresolved questions? The answer is perhaps found in lines 144-146 of the white paper: “It is of central importance to the Committee to consider potential recipients whose lives stand to be improved for the better as a result of NRP, and this mattered a great deal in the overall ethical analysis.” It appears that utility mattered rather too much to the OPTN Ethics Committee. Willingness to sacrifice the dead donor rule, the psychosocial wellbeing of donor families, the moral integrity of clinicians, and public trust in the transplant system should constitute too high a price to pay, even for utilitarians, not to mention those interested in the sound moral fabric of our fellow healthcare professionals, the peace of donor families, and adherence to the rule of law.
Finally, where is the patient in all of this discussion? S/he has effectively been euthanized by the medical profession, the first rule of which has been, for centuries, primum non nocere.
Brian Jackson | 09/19/2023
Thank you for the work and effort to create this much-needed ethical overview of NRP. The paper does an excellent job of summarizing arguments in support of and in opposition to NRP. There are two issues that I think would benefit from additional coverage in the white paper.
First, the paper would be improved by greater discussion of pediatric patients. Pediatric patients likely have a higher risk of autoresuscitation than adult patients increasing the risk of in vivo perfusion of vital organs. Additionally, consent issues may be different in pediatric patients who can never provide first-person consent and who may have equally qualified surrogates (parents) who disagree about whether to use NRP for the child.
Second, the paper would benefit from a discussion about whether to include NRP under a clinical/QI framework or whether to consider it a clinical research procedure. There has been significant discussion about whether IRB (or similar regulatory oversight since participants in NRP are deceased and not "persons" for the purpose of human subject regulations) oversight would make the use of NRP safer and provide a greater oversight presence than continuing to simply use it as a clinical technique.
Association of Organ Procurements Organizations | 09/19/2023
· What information should be disclosed to potential donors and next of kin regarding NRP, and how should one approach disclosure?
Our system of organ donation and transplantation is based upon the selfless act of thousands of individuals. For many families, this decision will be made at the most difficult moment in their lives, being informed of a loved ones’ passing. Every individual or family reacts and processes information at this moment in a different manner. Because of this dynamic, forcing a uniform disclosure of detailed specific information regarding NRP (see page 11) is not supported by the OPO community. This suggestion is inconsistent with current practices regarding disclosure of other aspects of the organ surgical recovery process, does not take into account the need for conversations that are appropriately family-specific and does not serve clear ethical goals (nor is it legally required).
The disclosure of information regarding NRP, to those applicable donor families and in limited circumstances potential donors themselves, should:
1) No matter the situation, or family dynamic, be facilitated by an OPO professional who is in the best position to most accurately, and fully answer the family’s questions about the organ donation recovery process.
2) Be consistent with the disclosure of information which supports authorization of the organ donation process in an informed manner.
3) Seek to provide an appropriate level of transparency as well as meeting families where they are in terms of clinical details of the organ donation process.
In cases where NRP will be considered, we recommend OPOs provide donor families with a general disclosure to the effect that the organ donation process will include the use of machines for the circulation of blood in the donor’s body for the purposes of maximizing organ function for transplantation. More detailed information about the NRP protocol being utilized in a specific case and any risks that might be pertinent thereof should be available but provided in an appropriately customized manner for families as indicated.
· Are there any additional ethical considerations or evidence that should be taken into account in the analysis?
We appreciate the thoughtful and thorough analysis which the Ethics Committee undertook on this sensitive subject. There are several areas we believe should receive additional attention:
TA-NRP vs. A-NRP – In general, the white paper discusses the differences between TA-NRP and A-NRP, however it only makes brief reference to the differing ethical concerns between the two and does not discuss these in depth. There are substantial differences in the ethical concerns based on the fact that in A-NRP the heart is not involved and there is more empirical understanding as to the absence of blood flow to the brain – all of which have ethical implications in terms of satisfying the dead donor rule and ensuring the permeance standard remains fulfilled. The paper would be strengthened by a more robust discussion of these differences.
In addition, given the risk of potential for re-circulation of blood to the brain in TA-NRP, and the legal and ethical concerns raised, we recommend the paper point out the need for programs implementing NRP to ensure their protocols take all measures necessary to preclude any recirculation of blood to the brain. Further, we support the Committee’s call for additional research confirming that protocols being deployed preclude this possibility.
Informed Decision Making (pages 15 and 27) – The Committee discusses what it terms the “informed decision making” process. However, this conversation is part of the authorization process and any discussion of “informed decision-making” with the “patient” is moot in the vast majority of cases because the donor will be deceased when these measures are discussed and implemented. In addition, on page 27, the Committee notes that “Transplant professionals should avoid evasive and paternalistic attitudes….”. However, transplant team members should never be a party to the authorization discussion which should always be conducted by appropriately trained OPO staff. In addition, at the bottom of page 27, the paper notes that “Informed decision making for ante-mortem procedures and authorization for post-mortem procedures must be obtained by the potential patient donor’s clinical care team”. It is inappropriate for hospital clinical care teams to be involved in this discussion. This conversation should be conducted by the OPO team not the clinical care team. This section of the paper should be revised for accuracy.
Withdrawal of Life Sustaining Treatment (Page 27) - The paper states: “The donation conversation, whenever possible, should not occur until after an informed decision has been made to withdraw life sustaining treatment.” However, families are indicating that a delay in timing for already formulated end of life plans is the primary reason they decline to authorize DCD. As a result, the best practices as to when to approach to discuss donation are evolving, recognizing that waiting until after the withdrawal decision is made is not ethically or legally necessary. In fact, withholding information about the possibility of organ donation, or a patient’s registered donation may diminish the informed decision-making process regarding withdrawal of care and the expectations around timing that go along with those decisions. The OPO community strongly recommends that the Committee reconsider this statement and revise the paper to reflect the fact that donation discussion may appropriately occur during the decision-making process regarding withdrawal of life sustaining treatment.
Effective Communication with Donor Hospital Staff – While discussing at length the need for communication with donor families, the paper would benefit from additional discussion on the importance of transparency with donor hospital staff. Specifically, AOPO recommends the Committee address the need for clear education and communication with donor hospital staff to ensure understanding of this emerging approach to organ recovery. A clear understanding of the procedure and its benefits by OPO staff, donor hospital staff, and transplant teams will facilitate successful implementation of NRP.
Brain-based Unified Concept of Death - The brain-based unified concept of death is being discussed national and internationally as an intellectually cohesive way to resolve much of the ethical concern in a manner that maps with the clinical understanding that the permanent absence of circulation to the brain is what defines death following the cessation of circulation. This concept would provide that death can be declared, consistent with the dead donor rule, if there has been a permanent cessation of circulation to the brain. While this is an emerging discussion, we believe a discussion of this concept should be included in the white paper as an important development in how the ethical concerns might be resolved in the future.
OPTN Transplant Administrators Committee | 09/19/2023
The OPTN Transplant Administrators Committee thanks the OPTN Ethics Committee for their dedication and work on this project. The Committee is cognizant of the difficulty of this discussion and appreciates the effort and care taken with this white paper. The Committee offers a few points for further consideration, the first being that the white paper differentiate between the different types of normothermic regional perfusion (NRP). Secondly, the Committee expresses some concern with the term “informed decision-making” as it is inconsistent with how consent for donation is approached, a term reserved for conversations with living donor candidates and patients. The Committee advises that in the event this white paper leads to policy, the Organ Procurement Organization Committee be consulted on donor family conversation language.
Region 9 | 09/19/2023
Sentiment: 4 strongly support, 4 support, 4 neutral/abstain, 1 oppose, 0 strongly oppose
A member was surprised that there is concern around NRP. An attendee appreciated the even approach taken by the paper and stated the that objection to NRP fails to respect the declaration of DCD. A member felt that information must be given to donor families, especially considering the historical distrust of the medical community by minorities. The member is concerned that that this could decrease the rate of donation among minorities, and also pointed to faith based resistance to organ donation needs to be considered as well. The member added that the idea of explaining to a donor family the need to recirculate blood after the heart has stopped would be challenging. Lastly, they wondered if the use of NRP would be standard practice nationally because if not, it could create disproportionate impacts in different regions and by proxy, patients. An attendee expressed support for NRP, as it honors the donor’s wishes and that the restoration of circulation is not intended to, nor expected to, restore life to the donor.
Region 3 | 09/19/2023
Sentiment: 1 strongly support, 10 support, 5 neutral/abstain, 0 oppose, 0 strongly oppose
One attendee commented that transplant centers need to have standard guidelines for NRP donors.
NATCO | 09/19/2023
NATCO supports both TA-NRP and A-NRP as ethical ways to increase organ donation yield. There is enough data out there demonstrating the superior outcomes, more organs placed, more lives saved. Although we understand the ethical debates surrounding NRP every day people die on the waiting list waiting for an organ that never materializes. So, the new question is, is it a risk that is worth taking? What are the harms of non-donation via NRP?
We support NRP regarding autonomy and organ donation. It can be assumed that first-person authorization donors not only want their organs to be used for donation, but they also want their recipients to do well. Therefore, it could be argued that organ procurement procedures that are associated with better recipient outcomes are not just ethically acceptable but ethically obligated.
Regarding how much information to provide to the donor families during the consent period; we want to avoid providing conflicting information during this devastating time of grief that can only be harmful. High level information to the family about the declaration of death and the use of a machine to circulate blood after death seems reasonable. However, procurement professionals should be prepared to respond to more detailed questions should the family ask. We support a standardized verbiage and dialogue to provide families in order to ensure a consistent message and prevent potential biases.
Finally, we support ensuring that we as a community are proactive in gathering data on NRP. This can help us track information and ensure continuous improvement in this exciting new recovery technique.
American College of Physicians | 09/19/2023
We are writing on behalf of the American College of Physicians, the largest medical specialty organization and the second-largest physician membership society in the United States. ACP members include 160,000 internal medicine physicians (internists), related subspecialists, and medical students. As an organization that has major concerns about NRP, ACP was grateful to able to present our position
(https://www.acponline.org/sites/default/files/documents/clinical_information/resources/end_of_life_care/ethics_determination_of_death_and_organ_transplantation_in_nrp_2021.pdf and https://www.acpjournals.org/doi/10.7326/M23-1361) to the OPTN Ethics Committee (although we were not invited to present to the OPTN Ethics Committee NRP Workgroup).
We appreciate the effort that has gone into the NRP white paper. It provides useful background, but it places too much weight on the role of utility—which does not displace the primary ethical principles of American bioethics of beneficence (the duty to promote the good and act in the best interest of the patient); nonmaleficence (the duty to not harm the patient); respect for patient autonomy; and justice— and is a secondary argument. The white paper misconstrues the ethical principles of beneficence and of respect for patient autonomy (which the paper seems to treat as the same as respect for persons), and is incomplete on the principles of nonmaleficence and justice. Overall, the paper fails to sufficiently consider the rights, interests, and welfare of donors, instead deflecting to an argument for utility which the paper defines as “The maximization of net benefit to the community...”
A thorough ethical analysis would have yielded a different conclusion. Even so, given the number and severity of the ethical questions and concerns you appropriately raise, your conclusion that OPTN should proceed with NRP does not follow. Calling for “assurance that NRP adheres to the Dead Donor Rule” is not possible— NRP violates the DDR. “Nonmaleficence must not be violated in the pursuit of NRP” is not possible— harm is being done to individuals. Beneficence is violated as well. And trust in health professionals and the organ transplantation system is put at further risk. Nowhere do we see a full discussion of justice considerations, either, including that NRP donors are often opioid overdose victims. NRP breaches US legal standards (https://www.amjtransplant.org/article/S1600-6135(22)08196-5/fulltext) and your call for standardized and transparent protocols will not make an unethical protocol ethical.
We believe that your focus on cerebral blood flow is misplaced and again, a secondary consideration. Recirculation of blood in situ is resuscitation of the patient. This invalidates what was the circulatory declaration of death. Ligating arteries to the brain then induces brain death. NRP violates the DDR and also the DNR orders that patients had in place. All of this can be avoided with the “heart-in-a-box” ex vivo technology.
OPTN and UNOS are under much scrutiny https://www.washingtonpost.com/health/2023/03/22/transplant-system-overhaul-unos/ and trust in the organ transplantation community by the public and health professionals is in question. Respectfully, it needs to be pointed out that your workgroup leadership previously described the “unprecedented opportunity” of NRP (https://jamanetwork.com/journals/jama/fullarticle/2805776), and other members of your workgroup seem to have an interest in promoting this protocol, including transplant surgeons who are already performing it. NRP is complex and requires an objective ethical analysis—unfortunately, this white paper is not it.
Thank you for the opportunity to comment.
Jan K. Carney, MD, MPH, MACP
Chair, Ethics, Professionalism and Human Rights Committee
American College of Physicians
Region 10 | 09/19/2023
Sentiment: 0 strongly support, 9 support, 6 neutral/abstain, 1 oppose, 0 strongly oppose
Members of the region are supportive of the white paper. Attendees noted the use of NRP as an ethical procedure to enhance donation processes, while others raised concerns about disclosing techniques to families or requiring their approval. The need for balanced education, representation, and further study was emphasized throughout the comments. Some attendees expressed their experiences and observations, pointing out the need for broader engagement beyond the transplant community. The absence of input from lawyers or laypersons was noted, and it was suggested that including individuals with diverse perspectives, such as those not directly involved in medicine or transplantation, could provide valuable insights. The thoughtful balance of the white paper was acknowledged, yet some attendees felt that it didn't delve deeply into the potential harm caused by not honoring the decision to donate organs. The harm to donor families and the potential loss of organ utilization due to not implementing NRP were raised as important considerations. Additionally, education and clear communication were emphasized as crucial aspects of engaging the public and donor families in discussions about donation and NRP. The inclusion of the American College of Physicians and donor families in the conversation was recommended to enhance transparency and understanding. Concerns were expressed about the disclosure of procurement techniques to donor families, with some attendees advocating for transparency while others were cautious about potential confusion and unintended consequences. There were calls for more study and data on this matter. Lastly, the role of declaring physicians and the difficulty they face in their role was highlighted, along with the necessity of educating families about the issues involved. The importance of distinguishing between the decision to donate and the specific techniques of recovery was stressed by some attendees, who argued against requiring families' approval of procedural details.
UC San Diego Health | 09/19/2023
As one of the leading centers performing normothermic regional perfusion recoveries in the county, the UC San Diego Health Center for Transplantation is pleased to offer feedback on the Ethics Committee White Paper on the Ethical Considerations of NRP. We appreciate the Committee’s approach to addressing this complex issue and ensuring that all sides of what is and will likely continue to be a passionate debate are heard.
Generally, we felt that the paper presented a reasonable summary of the practice and the concerns that have been raised but was not nearly comprehensive enough to arrive at many of the conclusions and recommendations on the “ethical implementation” of the practice put forward.
The data and experience demonstrate:
• NRP is not a violation of the dead donor rule by any means; Language is important but these arguments are semantics.
• Utilization of terms such as “reanimation” should be strictly avoided in discussions pertaining to NRP as this word inaccurately describes the limited restoration of circulation employed. Minimal perfusion does not equate “restoration to life or consciousness.”
• Full disclosure regarding the details of organ procurement may harm families who otherwise support donation. We agree with the recommendation of pursuing qualitative research of the public as well as donor families as this may help develop a robust understanding of what information is relevant in decision-making about organ donation and about the currently knowledge and acceptability of different procedural aspects.
• The committee may want to more thoroughly consider the ethical obligation that the transplant community has to the deceased donor and their family with regards to maximizing the number of organs utilized from the donation process. Again, qualitative research would be beneficial to inform these opinions.
Lainie Ross | 09/18/2023
Lainie Ross, MD, PhD
University of Rochester
September 18, 2023
I was part of the writing group so I mostly agree with the white paper. I believe it offers a balanced discussion. However, it may go too far in attempts to be balanced when arguments to support NRP are all overshadowed (and should all be overshadowed) by the concern that the process violates the dead donor rule.
MY MAIN OBJECTION TO THE STATEMENT as written is that the statement concludes by saying that NRP should proceed with caution when it should say that NRP should not proceed until the following issues are ethically solved.
Specifically, I object to lines 640-644:
640-644: It is with these commitments and understandings, and based on the analysis described herein, that the Committee concludes that the OPTN should proceed, but proceed cautiously regarding the practice of NRP for organ procurement.
This should be rewritten to say the Committee concludes that the OPTN should NOT proceed until the ethical considerations are addressed.
The report states: The following ethical considerations require consideration and resolution:
• Assurance that NRP adheres to the Dead Donor Rule.
If there is concern for DDR (and there is), then we must not proceed until it is determined that NRP adheres to the DDR. As written it suggests one can perform NRP (proceed) while the issue of the dead donor rule (DDR) is not resolved. The correct reading should be resolve before proceeding.
To be clear: One should not proceed unless one is certain that the procurement is consistent with the DDR for both moral and legal reasons: Organs are only procured after individuals are dead and procurement cannot be the proximate cause of death.
Thus, I must oppose the statement as written.
One minor correction:
Line 527-528: The Committee strongly recommends that local hospitals’ ethics committees review NRP practices to promote support and transparency within the surrounding community.
Revise to read
The Committee strongly recommends that local hospitals’ ethics committees review NRP practices to promote and support transparency within the surrounding community.
OPTN Kidney Transplantation Committee | 09/18/2023
The OPTN Kidney Transplantation Committee thanks the OPTN Ethics Committee for their work and for the opportunity to comment on this paper. Committee members noted that it is important for the community (both transplant professionals and the general public) to better understand the following areas relating to NRP:
• More explicit information about the NRP recovery process, including donor identification, timing of authorization, and length of anticipated perfusion.
• Statistics on matching and allocation implications, including considerations of timing and assembling transplant teams, and the mean, median, and range of NRP recovery and allocation timelines.
• Clearer information on the anticipated utility benefits, including how many additional organs per year are expected by using NRP and outcome data on NRP transplants by organ.
Without these additional pieces of information, it is difficult for the public to grasp the need for NRP. Members explained that NRP honors the donor and donor family’s wishes to donate and supports the right to autonomy. Providing clear, standardized information to donor families about NRP to avoid confusion and distress is a key component to public trust. Members also noted that there appears to be a gap between medical procedures and legal frameworks that should be closed before adoption of NRP. A standardized definition of brain death and/or a revision to the UDDA may be required to proceed with NRP.
As a subset of DCD, NRP follows the typical processes of accepted DCD donation with a few key departures. Members were divided regarding implications of ligation of the carotid artery. Some members noted that in NRP, ligation guarantees against the possibility of re-emergence of cerebral function and guarantees that the donor will not suffer as their wish to donate their organs is honored. The initial determination of death stands, and there is no chance of the donor being conscious after cardiac arrest and the hands-off period have elapsed.
However, other members explained that the argument that ligation does not violate the DDR because recirculation is regional is a weak, circular argument and appears to be done to circumvent the DDR. It is important to understand what would happen if the carotids are not ligated. This raises the question of implications of do no harm, and the possibility of autoresuscitation after the hands-off period and/or the potential of brain function or pain. More data is needed on this point, and members suggested including additional animal and human neurological studies in the analysis.
OPTN Minority Affairs Committee | 09/18/2023
The OPTN Minority Affairs Committee thanks the OPTN Ethics Committee for their work and the opportunity to comment on their white paper.
While the MAC expressed support for the Ethics white paper, they would like the Ethics Committee to consider withdrawal issues. Members of the MAC discussed the management of potential donors. Sometimes, once a patient is proclaimed brain dead, the OPO is involved in management, and the accepting team may assist with guidance. However, this is not always the case. There are also instances when the withdrawal care is done either in the PACU or the OR, and the accepting team, is not in the room and does not guide management leading up to that point. It was noted that patients do not always have a smooth withdrawal of care compared to patients who are not donors, such as using medications to help alleviate air hunger.
Additionally, the members of the MAC agreed that there should be standardization around consenting to NRP. Members expressed that NRP disclosure should be very clear, as this information is difficult to understand. If there is a misinterpretation of what NRP is, and donor families don’t understand, that could impact recipients and the efforts to expand the donor pool. Lastly, the MAC encourages continued education and transparency of this highly complex topic among vulnerable populations so that NRP is better understood and perceived favorably.
Region 7 | 09/18/2023
Sentiment: 2 strongly support, 10 support, 2 neutral/abstain, 1 oppose, 0 strongly oppose
Members of the region are supportive of the white paper and highlighted the need for careful consideration of the ethical, communication, and transparency aspects surrounding NRP as the technology becomes more prevalent in organ transplantation. Attendees emphasized the need for a well-defined strategy and path forward regarding the adoption of NRP. It was emphasized that the burden of understanding and consenting to these procedures should not fall on the grieving families at the bedside. It was recognized that clarifying the process and providing appropriate information to families is crucial. However, there were differing opinions on the extent and depth of information that should be disclosed to families during their time of grief. An attendee noted the necessity of standardized language to inform the public about the NRP process. One attendee shared there have been instances where they received organs encountered unexpected delays due to NRP, leading additional communication with the OPO. They recommended including a data field in DonorNet that provides easy access to detailed information about the procedures involved. Another attendee noted that ethical concerns regarding NRP are on the rise, and some hospitals that initially agreed to its use have changed their stance after experiencing the process. They also noted that some hospitals are instead opting for traditional DCD and ex vivo perfusion.
Christopher DeCock | 09/18/2023
To whom it may concern:
Thank you for the opportunity to provide feedback on normothermic regional perfusion. Though the gift of life is a laudable goal, I am afraid that some clinicians and researchers may have lost sight of why so many of us went into medicine: to take care of the patient in front of us; not to use them as a means to some end. Therefore, I must strongly oppose NRP for a number of reasons.
First, NRP causes brain death. Clamping the arteries that lead to the brain is a deliberate act to harm the patient’s brain by depriving it of necessary oxygen. Some argue that this is irrelevant since the patient has been declared dead, but that declaration was by circulatory criteria. After five minutes of asystole, the brain is damaged, but not dead. Moreover, there are data to suggest that such patients could have some awareness of what is being done to them on a phenomenal level and may even feel pain. , Causing brain death and possibly causing pain violates the principle of non-maleficence.
Second, if a patient is declared dead on the basis that circulation has ceased irreversibly and is then successfully resuscitated, the very basis for declaring death is invalidated. This represents a violation of the dead donor rule. It seems that the declaration of death is being manipulated to justify improving organ transplant outcomes. Additionally, any previous DNR order has been violated.
Third, by reversing circulatory death and inducing brain death, the patient is being objectified. NRP targets a vulnerable patient with a procedure which cannot help them but only harms them, even with the noble intention of helping other patients.
Fourth, the animal data are concerning. Truog et al., stated in a recent JAMA Viewpoint article that "recent experiments in pigs found that when ECMO was initiated after induced cardiac arrest and an 8-minute hands-off period, some pigs who did not have clamping of the brachiocephalic arteries did have restoration of cerebral circulation, in some cases with return of spontaneous ventilation and motor activity. These experiments suggest that clamping of these vessels is not merely precautionary but necessary for preventing the return of any cerebral function.” This should give the clinician pause. As the American College of Physicians states, cerebral occlusion is “a deliberate act intended to prevent the potential for recovery of brain function”.
Lastly, I am aware of situations where this procedure is being initiated without knowledge or approval of hospitals or their respective ethics committees. Moreover, families are not being educated about what this procedure entails and what will be done to their loved one. I would not be surprised that knowledge of such a procedure would put off many protentional donors
Although organ donation is a great gift, there are ethical ways to achieve this. NRP is not one of those ways.
Mid-America Transplant | 09/18/2023
Mid-America Transplant (MT) appreciates the opportunity to provide feedback to HRSA and the OPTN on the Ethical Analysis of Normothermic Regional Perfusion (NRP). As a consistently high-performing organ procurement organization (OPO), MT is committed to its mission of saving lives through excellence in organ and tissue donation.
MT supports NRP to honor organ donors and maximize donation to save more lives. MT advocates for donation opportunities that enable more organs to be transplanted, are in alignment with the desires of the potential donor and their family, and that are compliant with the legal framework governing donation and transplantation. MT receives consistent feedback from donor families emphasizing the desire to save as many lives as possible through the selfless gift of donation. The NRP process is one of these opportunities that can help to transplant more organs into individuals awaiting this lifesaving gift.
MT believes NRP is consistent with the Dead Donor Rule. NRP occurs only after an individual is declared deceased by a medical professional due to irreversible circulatory and respiratory function. This irreversibility is further confirmed when the individual does not spontaneously resuscitate for a set period after the declaration of death and before organ procurement begins, evidencing that the individual is, by all definitions and measures, deceased. The practice of NRP does not change that fact. NRP cannot resuscitate the deceased because the capacity for spontaneous function remains absent, and interventions were determined medically ineffective per accepted medical standards. Instead, NRP perfuses tissues in situ. Organ procurement pursuant to NRP, which proceeds well after death has been determined, and regardless of how it is performed, cannot induce death and is consistent with the Dead Donor Rule.
MT does not believe any additional informed consent is necessary regarding NRP. Providing families with too much detail surrounding NRP places an additional undue burden on families during an already traumatic time in their lives. Families already consent to various medical interventions to maximize organs used for transplant; MT believes NRP is another medical intervention included in this category. Furthermore, feedback from donor families indicates that most families do not want to know details on how organs are maximized and allocated; the level of information is simply too much for them to process during their time of immense grief.
We appreciate the opportunity to provide feedback on this matter.
Kevin Lee, President & CEO
Gift of Life Michigan | 09/18/2023
We echo the Committee’s focus on non-maleficence in Normothermic Regional Perfusion (NRP) and agree that several important aspects of the Uniform Determination of Death Act (UDDA) and the “dead donor rule” require the transplant community’s further consideration before implementing this technology. We also believe a distinction between Abdominal NRP (A-NRP) and Thoracoabdominal NRP (TA-NRP) is necessary because of the seeming lack of consensus as to whether postmortem circulation in Donation after Circulatory Death (DCD) restores meaningful circulation to the brain. We acknowledge that some evidence suggests better patient outcomes when this technology is used; however, the benefit of this technology cannot ignore the public’s perceptions about its potential conflict with the dead donor rule and a high ethical standard. Public trust in donation has long been recognized as the foundation of altruistic donation in the United States, and erosion of that trust would be detrimental to waiting patients.
We also recognize that this discussion in many ways is occurring after the fact. Many programs are using TA-NRP, A-NRP, or both, but without having proactively explored these topics. While those institutions and their Internal Review Boards may have explored the issues and resolved them to their satisfaction, they did not include the many stakeholders mentioned in the Committee’s white paper. Some OPOs are left scrambling to decide the matters under extreme pressure in the moment (e.g., when a recovering transplant center accepts a heart and shares their intent to use TA-NRP) without enough time to consider all the relevant variables.
We have also observed that machine perfusion technology, already widely used in the U.S., circumvents the potentially volatile discussions around reperfusion by following longstanding DCD protocols. These protocols include removing organs from the donor’s body after determination of death, and only then placing those organs on devices to optimize organ function outside the body. While not endorsing one platform over another, there does seem far less uncertainty with postmortem perfusion devices than with NRP. With much of the impetus supporting TA-NRP seemingly encouraged to increase the availability of hearts for transplant, the work of Khush et al (Circulation, DOI: 10.1161/CIRCULATIONAHA.122.063400) shows significant under-utilization of donated hearts from brain dead donors.
We support the Committee’s conclusion that several ethical considerations should be resolved, but note that some of these potentially require legal resolution as well:
- Confirmation and consensus that NRP does not violate the dead donor rule or the UDDA.
- Non-maleficence cannot be violated.
- Standardization and appropriate sharing of relevant details is required.
- NRP should not be utilized in uncontrolled situations.
The Committee asked what information should be shared with donors/donor families. Perhaps the bar for sharing can be set by confirming that nothing is being withheld from those very important people. In other words, can we confirm that we have shared enough information for a reasonable family to understand the basic intent, and have we been completely transparent in our willingness to share as much as they want to know? Families desire varying levels of detail about the donation process. It is incumbent upon the OPO to disclose general descriptions of the donation process and to expound as the family desires; however, it is unusual to go into detail about the organ preservation techniques that will be used. It seems we need to reach consensus about NRP for the donation and transplant community’s peace of mind as much as for donors and families, which we encourage. We believe, and it is our practice, that donation procedures performed antemortem require collaboration with the healthcare team to obtain informed consent.
The Committee also asked whether there are additional ethical considerations about NRP. We believe the Committee has identified the major areas of concerns, and we urge the Committee and the transplant community to address them.
We strongly support the transplant community’s vigorous exploration and resolution of all ethical matters related to NRP prior to widespread endorsement and implementation.
American Society of Transplant Surgeons | 09/18/2023
Adam Omelianchuk | 09/18/2023
"What information should be disclosed to potential donors and next of kin regarding NRP?"
That there loved one is ultimately thought to be dead on the basis of a permanent loss of brain function *after* surgery begins, not the permanent loss circulatory-respiratory functions *before* surgery begins, and that this loss of brain function will be ensured by transplant team by occluding vessels to the brain. They should also be told that the standard criteria for determining "brain death" will not be used.
"Are there any additional ethical considerations or evidence that should be taken into account in the analysis?"
Authorizing NRP will further erode the ethical norms that justify the dead donor rule. This is because NRP requires transplant surgeons to take actions on the donor's body to ensure the donor stays "dead" (ie, no revival of spontaneous breathing effort, no awareness) by causing a certain kind of death to occur via occluding blood to the brain -- unverified "brain death" -- rather than by allowing the ischemic effects secondary to the loss of circulation to occur in the whole body (what happens in standard DCDD). NRP involves medical intervention to facilitate just the right kind of death to maximize organ transplant, and therefore violates the dead donor rule.
The ethical issues at stake are those related to the justification of the “dead donor rule”: the protection of donors from homicide, the elimination of conflict of interests among physicians, and the preservation society’s trust in the transplant system. The assumption behind the rule is that no one’s life is worth less than the organs inside their body, no matter how diminished the quality of one’s life may be, and therefore one’s life cannot be sacrificed for the good of another’s. This is an ethical pillar of transplant medicine. If the reasons for the death declaration are inconsistent with the dead donor rule, the procedure risks compromising these values, and causing a drop in donation rates.
Sara Buscher | 09/17/2023
Normothermic Regional Perfusion (NPR) violates the Uniform Determination of Death Act (UDDA) which has been adopted in almost every state. The UDDA requires that circulatory death and brain death be irreversible. NPR also violates the Dead Donor Rule. Accordingly, OPTN should not be supporting NPR.
Heidi Klessig | 09/16/2023
NRP is not death by cardiorespiratory criteria under the UDDA because the cessation is manifestly not irreversible. “Irreversible” is still the letter of the law, even though the white paper employs the term “permanent”. Taking action to occlude the cerebral circulation when someone is not legally dead is assault, and results in the manner of death being homicide.
The time to decide what the public thinks of NRP is now. Full and frank disclosure of the details of NRP need to be made general knowledge BEFORE a family is stunned and confused while facing medical disaster. When people are forced to make a decision under duress, and in absence of the facts, their consent is no longer valid.
The utilitarian argument of procuring more organs does not excuse keeping donors and their surrogates in the dark about the grisly details of NRP. NRP breaks the law under the UDDA, plays fast and loose with the dead donor rule, disregards the moral requirement of truth-telling. It also leaves doctors open to a homicide charge. It needs to stop.
Region 1 | 09/15/2023
Sentiment: 1 strongly support, 5 support, 0 neutral/abstain, 0 oppose, 0 strongly oppose
Overall the region was supportive of this paper. One attendee commented that the committee has done a great job with this paper, but suggested that there is a distinction between abdominal and thoracic NRP from an ethical and potentially legal basis. They felt that exploring the differences between the two from an ethical perspective could add value to the conversation. A member spoke about the growing discussion about the unified concept of death and how cessation of circulation is meaningful so far as it stops circulation in the death. The member suggested that what is meaningful is cessation of permanent circulation to the brain. An attendee stated concern for the idea of mandating what is discussed with donor families in the moment. OPOs do not typically discuss the details of surgical procedures unless the family asks questions, it’s not a standard part of authorization. The attendee believes that the reaction of wanting to disclose things to the family is really about absolving the transplant/OPO communities own discomfort, rather than it being meaningful for the donor family. All of this comes after the donor has died, so this is disclosure. Another member said this was a very thoughtful approach, and that the important consideration is potential recirculation of blood supply to the brain. The member added that to their understanding, both Spain and the UK use additional surgical methods to prevent circulation. Another attendee stated that TA-NRP can have negative effects on the lungs. A member expressed concern about NRP potentially being misunderstood by the general public resulting in a loss of trust and a reduction in the number of donors.
Region 6 | 09/15/2023
Sentiment: 1 strongly support, 6 support, 2 neutral/abstain, 1 oppose, 0 strongly oppose
During the discussion, some attendees recommended elevating the principle of respect for persons to equal or above the principle of non-maleficence via recognition of the "last gift" justification of respect for the intention of donors/donor family to proceed with donation. One attendee commented that it is unknown how first-person authorization through a driver’s license and last directives would be affected if this information were included. Another attendee commented that families often don’t want to know this level of detail, they just want to respect their loved one’s decision to donate. One attendee recommended a distinction between abdominal NRP (A-NRP) and thoracoabdominal NRP (ta-NRP). Another attendee recommended a larger ethical discussion about how we qualify a patient as a donor, adding that there should be specific, prescribed, objective criteria. One attendee recommended that additional education be expanded to include potential recipients of NRP organs so that they understand the difference between organs recovered using NRP and those recovered using other procedures.
OPTN Lung Transplantation Committee | 09/15/2023
The OPTN Lung Transplantation Committee thanks the OPTN Ethics Committee for their white paper and is generally supportive. The Committee encourages the OPTN Ethics Committee to examine the differences between abdominal and thoracic NRP and any potential negative effects on other organs, particularly the lungs.
American Society of Transplantation | 09/15/2023
The American Society of Transplantation (AST) generally supports the proposal, “Ethical Analysis of Normothermic Regional Perfusion (NRP)” as it aligns with our position statement on NRP: https://www.myast.org/sites/default/files/AST%20KEY%20POSITION%20STATEMENT%20ON%20NORMOTHERMIC%20REGIONAL%20PERFUSION_final.pdf. The AST offers the following comments for consideration:
• The white paper could better differentiate between A-NRP and TA-NRP and the differences in ethical considerations between the two. For example, the committee may wish to include a comment to the effect of “it is important to note the procedural and thus potential ethical differences between A-NRP and TA-NRP” with some further elucidation of what those ethical differences are.
• Did the committee consider including discussion of the unified brain-based concept of death? This is the idea that the permanent absence of circulation to the brain is what ultimately defines death as an irreversible state. Using this definition as a principle could resolve much of the ethical concern related to NRP in terms of ensuring the dead donor rule is respected (it does not resolve remaining potential legal misalignments with the Uniform Determination of Death Act). Referencing this concept and the published papers supporting brain-based concept of declaring death based on circulatory criteria might be a useful addition to the white paper.
• The committee may wish to clarify the initial description in the background section that NRP is “aimed at improving organ quality by reducing cold ischemic time.” NRP is not focused on reducing cold ischemic time. NRP allows for warm perfusion of the organs shortly after the declaration of death. This process leads to a more rapid recovery from warm ischemic damage and allows the recovery team to assess the function and viability of the organs for transplant. After a period of assessment and dissection, the organs are then flushed with cold preservation solution and removed in a standard fashion. Cold ischemic time ensues until implantation into the recipients.
• The committee used the following terminology to describe NRP: recirculation, restoration of circulatory blood flow, and circulatory restoration. Utilization of these terms interchangeably can be confusing to the reader. The committee may wish to edit the document for more clarity in definition and consistent use of terminology.
• The committee may wish to clarify the comparison of TA- and A-NRP in the table on page 18. For TA-NRP it says that warm perfusion and circulation of oxygenated blood are initiated with an ECMO or bypass machine. In A-NRP, it says normothermic perfusion to the abdominal organs is initiated. However, in both cases, oxygenated blood perfuses the organs with the assistance of an ECMO or bypass machine. In TA-NRP, the donor is reintubated and the lungs are ventilated for gas exchange. Reintubation and ventilation are also used with all rapid recovery lung procedures. It is not, however, used in abdominal-only NRP donor procedures.
• In the table on page 18 under A-NRP the committee may wish to consider the following modification: “A laparotomy and sternotomy are performed, the iliac artery and vein and the suprahepatic abdominal aorta and the inferior vena cava are occluded (preventing blood flow through the thoracic aorta), the aorta is cannulated, normothermic perfusion to the abdominal organs is initiated.” (replace “or” with “and” after “iliac artery and vein”).
• On page 20, the authors note that “spontaneous reversal of asystole has been observed in TA-NRP when cardio-pulmonary bypass was used.” Seeing that asystole is reversed with the intervention of cardio-pulmonary bypass, this reversal is not ‘spontaneous.’ Therefore, we recommend removing ‘spontaneous’ from this sentence.
• On page 29, the paper notes that donors may be moved to an OPO recovery center. Unless the donor care unit is within a licensed hospital, at the current time this is not possible with DCD donation as only deceased individuals can be transferred to recovery centers, and DCD donors are not dead at the time of withdrawal of life-sustaining treatments. For clarity around this point, the AST recommends adding language that moving DCD donors to an OPO recovery center can only happen when the donor care unit is within a licensed hospital.
• In response to the questions included in the proposal:
What information should be disclosed to potential donors and next of kin regarding NRP, and how should one approach disclosure?
• The committee may wish to reference or incorporate key recommendations from the AST guidelines on this topic: Guidelines Regarding Communication to Donor Families in Cases Where Normothermic Regional Perfusion (NRP) is Planned - https://www.myast.org/sites/default/files/DTO%20COP_NRP%20Guidance_final%20%281%29.pdf
• This question would also benefit from input outside of the transplant community. Qualitative research of the public as well as donor families may help develop a robust understanding of what information is relevant in decision-making about organ donation and about the acceptability of different procedural aspects.
• When authorization for donation occurs, the OPO may not know if NRP is going to be used so we recommend that authorization for all DCD donation include information about the possibility of using NRP as well as that of using ex-situ machine perfusion (which may also pose ethical concerns particularly with heart donation) so that the family is not approached multiple times for additional authorizations.
Are there any additional ethical considerations or evidence that should be taken into account in the analysis?
• The committee may want to consider the ethical obligation that we have to the deceased donor and their family with regards to maximizing the number of organs utilized from the DCD process. While the implementation of new technology or organ recovery strategies should always remain within ethical boundaries, it is also an ethical obligation of the transplant community to explore all options that can lead to increased numbers of patients transplanted with better outcomes than the current standard of care.
OPTN Heart Transplantation Committee | 09/15/2023
The OPTN Heart Transplantation Committee thanks the OPTN Ethics Committee for their work on the white paper, and for the opportunity to comment. Heart Committee members who were familiar with the white paper’s ethical analysis and/or the debate surrounding NRP expressed gratitude to the Ethics Committee for tackling the subject and producing a neutral analysis that at the same time raises important questions that need consideration.
Some Committee members questioned whether the Uniform Declaration of Death Act (UDDA) is still appropriate given the advances in biological understanding that have occurred in the 42 years since the UDDA was released. They also asked if NRP violates the UDDA?
A Heart Committee member pointed out that the white paper recommends that the transplant community “proceed cautiously” with regard to NRP. The members suggested that the Ethics Committee might want to consider clarifying what is meant by “proceed cautiously” and/or how the transplant community might interpret the phrase.
Heart Committee members asked whether the decision to use NRP should be up to the individual transplant programs, rather than addressed nationally? A member commented that what the analyses describes gets “in between” the patient-doctor relationship, and that can have negative consequences. It was suggested that perhaps the ethical analyses should be less prescriptive, and would be better framed as a societal question. Another member said that how the discussions about NRP are handled between the donor families and caregivers and the transplant program staff is also critical. The discussions need to be specific and clear about the purposes, and associated benefits and risks that come with the procedure. Another member suggested the examining how the organ recipients are informed and involved with the whole process might also be beneficial.
Anonymous | 09/15/2023
Confusion, in my opinion, revolves around the ambiguity of the
use of the terms circulation and resuscitation. Generally, when we
use extracorporeal membrane oxygenation (ECMO) to supply the
human body with systemic circulation, it is for the purpose of resuscitation
and sustaining life. In the circumstances of use of ECMO for
NRP, are these two practices suddenly completely distinct?
The crux of the argument is that the person has been declared
dead, and, therefore, the re-establishment
of systemic circulation
is only to preserve the organs and save them from warm ischemic
injury. Yet part of the procedure is to add the unique intervention of occlusion
of cerebral circulation to prevent the possibility of neuronal activity
in the brain, which would obviously create questions around the circulatory determination of death. The dead donor rule (DDR) states that a patient cannot be killed
by, or for, organ procurement. To justify this added procedure of
clamping circulation to the brain itself. People writing on behalf of NRP has said, “The brain remains a ‘black box’ and the degree or extent of
neuronal death cannot be ascertained.” The clamping of circulation
is obviously to ensure brain death, yet the authors repeatedly state
the DDR is not violated because the patient has been declared dead.
Because brain death is, by definition, the cessation of all brain activity,
is not this “circulatory” logic? A tautology?
Is the re-establishment
of circulation a violation of the donor's
DNR order? Indeed, one could argue that with systemic circulation
and a question of ongoing neuronal activity, the donor could at that point even be sent
back to the ICU to determine brain activity over the next 24 to
48 h, as is common practice when we are attempting to establish
Do we believe that a procedure to clamp cerebral
circulation to cut-off
flow to a human brain is worthy of a great
deal more consideration before we update the legal definition of
Neeraj Sinha | 09/15/2023
I am supportive of the white paper. However, we should not deny NRP to the cases where therapeutic ECMO, when donor was alive, had been deemed futile. In terms of technique, therapeutic ECMO and NRP may look similar, but they are different as indications are different. And we can end up denying many potential donors if we adopt white paper's proposed line of thinking on this aspect.
Anonymous | 09/14/2023
-The Committee analyzes NRP through the ethical lenses of nonmaleficence or do no harm, respect for persons, and utility.
- I believe they do acknowledge and honor all 3 in the donation process.
-What information should be disclosed to potential donors and next of kin regarding NRP, and how should one approach disclosure?
-OPO's should approach donor family once pt is deemed unsalvageable but doesn't meet brain death criteria. the basics of the NRP process should be disclosed to the pt and it should be expressed that it is not until their loved one passes, and is clinically dead, prior to starting the NRP process for cDCD donors.
-Are there any additional ethical considerations or evidence that should be taken into account in the analysis?
-I do not believe so. i believe it covered the topic very well and supports nonmaleficence, respect for persons, and utility.
Kevin Daly | 09/14/2023
I appreciate the efforts of the UNOS Ethics Committee to carefully gather various perspectives on Normothermic Regional Perfusion (NRP) and incorporate them into a formal ethical analysis. It is only through this type of engagement with key stakeholders, and members of American society, that we can develop a societal understanding of the ethics of NRP.
The document briefly discusses utility considerations regarding NRP (Lines 135-143) and references how ex vivo machine perfusion has had positive impact on organ utilization while avoiding the ethical controversy created by in situ reperfusion. However the document falls short of providing full context regarding the types of organs for which ex vivo perfusion is available, and the size of such organs that can be perfused ex vivo. For example in DCD heart procurement, ex vivo perfusion technology is available for donors who are > 40 kg. However, no currently available ex vivo machine perfusion device exists for donors less than 40 kg. This means that TA-NRP is the only way to perform DCD procurements for most pediatric donors. There is a clear utility benefit to safely expanding the donor pool for pediatric heart transplant candidates where waitlist mortality exceeds that of adult candidates and median waitlist times at the highest urgency status can exceed 3-4 months. I recommend that the Ethics Committee provide additional context in this regard.
In addition to highlighting differences by organ type/size, I believe that the paper would be strengthened by clarifying that the primary means for declaration of death in the United States is via circulatory criteria. In several places the white paper discusses how neurological criteria for death are not assessed after circulatory death has been declared (See: In Table 1: Uniqueness of NRP (Lines 55-56)). However, Lines 372-381 (under the heading, “Argument that NRP does violated the Dead Donor Rule and may cause harm:”) discuss whether brain death has occurred at the time that circulatory death is declared. However in this section of the document, there is no clarification that brain death criteria are not part of the circulatory death paradigm. While there is an implicit understanding that brain function will cease if no circulation is present, this is never assessed in any formal way when death is declared by circulatory criteria. I recommend that this distinction be clarified.
The authors also discuss neurological activity and NRP in the context of the ethical requirement of non-maleficence (Lines 118-123). The white paper intends to draw a connection between being insensate and neurological activity being absent as a way to demonstrate that non-maleficence is being followed. However, these two things are not equivalent. While a person with no neurological function is always expected to be insensate, there are scenarios where neurological function persists and the person is insensate such as deep anesthesia. I feel that discussion about the correlation between lack of neurological activity and being insensate is confusing and requires clarification.
American Society for Histocompatibility and Immunogenetics | 09/14/2023
This proposal is not pertinent to ASHI or its members.
Region 5 | 09/13/2023
Sentiment: 8 strongly support, 10 support, 6 neutral/abstain, 0 oppose, 1 strongly oppose
The vast majority of region 5 supported this analysis. An attendee commented that explaining the NRP procedure to some donor families could be overwhelming to the family. They explained the donor conversation is a delicate conversation and is not just one conversation, it’s multiple conversations, over various time periods. They don’t ever rule anything out, so if the consensus is they need to give them information of NRP, it will necessitate another conversation. They said it would be very awkward to change their process and not in line with what we’ve been doing for 30-40 years. A member suggested to consider the negative effect on donor family feelings if we limit the options for their loved ones to have their wish to donate after death fulfilled. An attendee said that asking for a level of informed consent is unnecessary. Another attendee pointed out that the transplant community is familiar with first person consent - Families have no say because their loved one agreed to donate, and families can’t do anything about it. He explained that the donor family discussions can be painful and he would never want to have a discussion about NRP when a patient had decided to donate, and then the family aggressively disagrees. He believed that explaining the NRP procedure to donor families may make the community hesitant to donate. He believed the community should seek donor management and not NRP.
·An attendee was distressed by some of the assumptions in the paper, especially with the word “reanimation”. In support of the paper an attendee commented that technical issues are important to think about, but would separate that from ethical and legal issues. They explained that the alternative to this is DCD, respect for this is important for patient autonomy. The fact that we are discussing reanimating the heart or reperfusing organs, we have to go back to the original intent that this patient was expected to pass. For that attendee, NRP is a legal issue not an ethical issue. It is important to go back and think about death means. For abdominal perfusion should not be an ethical concern at all nor a legal concern. I would urge all to think of this as a legal issue not ethical. An attendee commented that a key message is the donor wishes. TANRP and how we manage all of that. They suggested that the white paper have a separate section between TANRP vs. ANRP. They also recommended to be in control of the messaging and having trained personnel in media communication is important. Another attendee said that this is more of a legal issue than an ethical issue. The alternative to NRP is DCD - which has the same result of the donor passing. There should be work done to clarify the definition of death to enable NRP. And that abdominal NRP should be whole heartedly endorsed.
·In opposition of NRP, an attendee pointed out that he has lost lungs to NRP, which he believed shouldn’t be allowed to happen. He pointed out, that there are devices available where we can take the heart out of the body and put them into machines to see if they can work and we can still use the lungs. He opined, why are we all going after a method that is moving in a gray zone treating life and death, why don’t we have to tie off the neck vessels if we’re totally sure that the patient is dead. Then he explained that it is because of autoresuscitation which we’ve known about from DCD donors.
·A member suggested that the Ethics Committee re-evaluate NRP in light of recent publication regarding the absence of brain reperfusion in NRP. In opposition of the paper, an attendee commented that the paper’s ethical analysis does not consider the donation process, will increase distrust in the community, and that donation opportunities will be lost. Another attendee commented that parts of the paper were more than a white paper and a policy recommendation.
OPTN Pediatric Transplantation Committee Meeting | 09/13/2023
The OPTN Pediatric Transplantation Committee thanks the OPTN Ethics Committee for their work on this white paper and for the opportunity to provide feedback. In general, members were supportive of the analysis, especially because of the potential for NRP to reduce waitlist time, morbidity, and mortality for pediatric candidates, but offer the following suggestions for additional items to consider in the analysis.
The Pediatric Transplantation Committee asks the Ethics Committee to consider that there may be additional ethical concerns with restoring perfusion in a child versus in an adult. Typically, resuscitation efforts are much more successful in pediatric patients than in adults. It is important to consider the pediatric population specifically when doing any studies on brain perfusion related to NRP, and the Committee cautions against simply extrapolating from adult data. Also, the Committee asks the Ethics Committee to keep in mind that there are different procedures for determination of neurological death in children, and this is important to consider in the analysis. Members noted that the pediatric ICU and critical care communities may be good resources for additional data on concerns specific to restoration of perfusion in pediatric donors. The Committee agrees with the Ethics Committee’s determination that uncontrolled scenarios of NRP cannot be ethically supported at this time.
On the topic of authorization and disclosure, members noted that families of pediatric donors typically undergo a much longer decision and pre-recovery process, and that it is important that NRP should not interfere with this. While the Committee agrees that families may not want explicit details about the process of NRP recovery, clarity on the expected timeline of NRP would be especially important for a family of a pediatric donor. The Committee also asks the Ethics Committee to consider if it would be appropriate to inform potential recipients of the possibility of receiving NRP organs, because of the potential of moral concern about the NRP process on the recipient end.
Region 11 | 09/12/2023
Sentiment: 4 strongly support, 2 support, 5 neutral/abstain, 3 oppose, 1 strongly oppose
Several members commented that after death is declared, NRP perfuses organs, but does not reverse death. They commented that it leads to increased utilization and improved graft function. There were multiple recommendations for the Ethics Committee to separate their recommendations for Thoracoabdominal versus Abdominal only NRP. As the ethical concerns are different and by combining them, the committee adds to the confusing information shared with people who do not understand the differences. Members commented that there is an obligation to give the family details of NRP, but balance this with their loved one’s/their decision to donate. A member commented that donation is governed by gift law and requires authorization, either next of kin or first person, but not informed consent and questions why the recovery process would change that. They also questioned if donation is first person authorized, who would be responsible for consent, particularly if the family has chosen to not participate in the process. A member commented that they support ongoing data collection and ethical analysis and at this time their center is not participating in NRP.
OPTN Operations and Safety Committee | 09/11/2023
The OPTN Operations and Safety Committee thanks the OPTN Ethics Committee for their work and for the opportunity to comment on this proposal.
Committee members provided the following feedback:
•There was concern about the white paper addressing NRP broadly and not providing specific information about the ethical concerns related to thoracoabdominal NRP (TA-NRP) and the reperfusion of the brain.
•There was a question about the general process for white papers and how the OPTN Board of Directors approves them. For example, if the Board approves a white paper, does that mean the OPTN approves the conclusion reached by the Ethics Committee or should white papers be used as a framework for thought and discussion on specific topics?
International Society for Heart and Lung Transplantation | 09/11/2023
The International Society for Heart and Lung Transplantation (ISHLT) appreciates the opportunity to provide feedback on the “Ethical Analysis of Normothermic Regional Perfusion (NRP)” OPTN Public Comment proposal. Feedback was solicited from the ISHLT Advocacy Committee, the ISHLT Ethics Committee, the ISHLT Advanced Lung Failure and Transplant Interdisciplinary Network Steering Committee and the ISHLT Advanced Heart Failure and Transplant Interdisciplinary Network Steering Committee
ISHLT understands that the OPTN White paper is not meant to be a referendum on the topic of NRP, and not meant to solicit agreement on a single unified policy or position.
As you know, ISHLT represents many countries, in some of which the practice of NRP is considered illegal, therefore much of the paper may pertain only to the US and North America. However, ISHLT feels that the following were ethical issues that also have broader implications.
Overall, the document addresses the utilitarian arguments well, but these could be more closely linked to the respect for persons argument, with more emphasis on accomplishing the donor’s final autonomous wish.
1) The fundamental question is whether one accepts the declaration of death in the donor. For the majority of DCD donation (Maastrict III), a protocol is followed – a decision is made to withdraw life sustaining treatment based on accepted medical standards and shared decision making between the family and the donor’s clinical team that continued efforts to save the donor’s life will not be effective. Once that decision is made, then it is ethical to proceed with DCD donation. For TA-NRP, this protocol is no different: the patient is declared dead in the same manner as all DCD. The ethical challenge arises when organ perfusion in situ with care not to restore neurologic circulation is interpreted as resuscitation. Once death has been declared, such efforts may be perceived as attempts to resuscitate the donor which would be an ethical violation of self-determination. Moreover, if the determination of death is conditional on avoiding resuscitative efforts, A-NRP and TA-NRP could risk undermining the practice of cDCD even without NRP.
This question is at the core of the debate about NRP. It is possible to separate out the therapeutic intent for the patient as patient, vs the intent for the donor as recently dead patient.
More discussion of the definition of death, particularly because the interpretation of the language of the law is such an important aspect. There is some reference to this with the distinction between “cardiac” and “circulatory” but more discussion about this, particularly as it relates to the lawwould be helpful. In addition, recognition that the definitions of death with respect to permanent were made in a setting of very different life sustaining treatment technologies.
This would also have added value as we consider the other regulatory frameworks (legally and ethically) on the international stage.
2) The discussion of what information should be discussed with the surrogate stems from the question: are the surrogates providing authorization or informed consent?
TA-NP started in the UK in 2015 and all donor families gave specific informed consent for NRP, and no family was recorded as declining NRP. This document argues for a similar approach. Certainly, good practice would be transparency with families and surrogates which should be documented, and it is not much further to achieve informed consent.
A more comprehensive discussion of the difference, and the ramifications of this difference would help clarify some of the questions raised in this paper.
It is difficult to determine what the reasonable person standard is for organ procurement of all manners. Having specific suggestions about what this might comprise, and how to achieve this would be important as the paper leans more towards informed consent rather than authorization.
More research needs to be performed to understand donor family understanding of DCD TA-NRP when consenting for this process.
3) Although this OPTN white paper is focused on US activities, some discussion of the international differences should be acknowledged and discussed. This would also lend to more deliberation on the difference between TA-NRP and abdominal only NRP as they do have different ethical considerations.
A-NRP is much more widely practiced worldwide than TA-NRP, frequently in the context of pre-mortem vessel cannulation. It does make lung procurement more challenging, and indeed heart procurement where direct thoracic organ procurement is to be performed alongside A-NRP. Although A-NRP is accepted to carry a lesser risk of cerebral perfusion than TA-NRP, the act of clamping the supra-celiac aorta is no different from the act of clamping the supra-aortic vessels. These issues should be addressed to avoid the situation where A-NRP becomes accepted and not TA-NRP.
4) In the context of DCD donation for thoracic organs, there is an alternative to TA-NRP which the paper mentions briefly, namely, the ex-vivo perfusion systems. ISHLT suggests that as this is an alternative procedure to TA-NRP, at least for donors weighing more than 40kg, that this should be further expanded upon in this paper,
More concretely the OPTN might wish to consider whether ex vivo perfusion systems are uniformly accessible. While ex vivo may not have the ethical concern of death definition, the availability of these systems does squarely fall into ethics of justice and equity.
5) Finally, it is important to note that although there is good evidence pointing to better outcomes with NRP for liver and kidney transplantation, the evidence for improved outcomes with NRP in cDCD heart transplantation is currently weak and the data for data for lung transplant outcomes is unclear at best. In terms of beneficence and organ utilization in DCD TA-NRP, current experience with lung transplantation from TA-NRP is promising within the United States. As centers have gained experience with DCD TA-NRP, lung allograft utilization and function has been similar to standard DBD donors. The DCD TA-NRP system not only has allowed for good quality lung allografts, but has an advantage over ex-vivo perfusion systems as it allows for en-bloc heart-lung allograft usage as well. Though some people argue TA-NRP may have detrimental effects on lung allografts, the data arguing worse lung quality comes from porcine data recently presented at the AATS Mechanical Support and Thoracic Transplantation Summit – this model did not involve venting the left atrium which is likely cause of worse lung function and is not consistent with current procurement techniques. Further standardization of technique is necessary for more centers to reliably procure lung allografts utilizing DCD TA-NRP.
In addition, the ability to perform a functional assessment of the heart and lungs in situ is likely to push the acceptance of extended criteria donors in this setting over ex-vivo perfusion systems which are less effective in this regard. Whether pursuing A-NRP or TA-NRP to improve outcomes of abdominal organs may come at the risk of poorer outcomes for thoracic organs remains to be fully elucidated.
In summary, TA-NRP remains a promising technique to increase available lung allografts with good clinical outcomes. It also can best fulfill the wishes of the donor and donor family by increasing organ utilization and ensuring the best possible outcomes for organ recipients.
Minor specific issues with the text
1) Table 1: box 2
The comment that “NRP is the only [technique] that perfuses the organs while they are in the body” is potentially misleading to the lay person. Every deceased donor organ procurement whether DBD or DCD currently involves a period of perfusion of the organs while they are in the body, prior to organ procurement. Perhaps the phrase could be that “NRP is the only technique that recirculates blood through the organs of a DCD donor following declaration of death and prior to organ procurement”. The distinction between circulation and perfusion is referred to in footnote 48 but then not really adhered to in Table 1. or line 71 of the text.
2) Line 169, a second Table, Box 1
The last sentence where consent for NRP is mentioned is inappropriate in the same box as the decision to withdraw life support. It is better moved to the end of Box 2.”
Margie Hodges Shaw | 09/10/2023
I support the conclusion of the OPTN Ethics Committee white paper, specifically to “proceed cautiously” with the practice of NRP for organ procurement. As the paper documents and the commentary reinforces, NRP is controversial and the OPTN has much work to do to earn the trust of the public, which is necessary to achieve the potential of transplantation.
With respect to the first question, colleagues and I have previously have observed the “…it is critical to avoid past mistakes and to genuinely engage the public in conversations about transplant decisions, including the decisions about the meaning of life and death.” (The American Journal of Bioethics 23(2): 33-35.) This is in addition to encouraging full transparency about all procurement processes with donors and next of kin regarding NRP. There is vigorous academic debate about the ethical implications of transplantation practices, including NRP, and it would behoove the transplant community to engage the public in these discussions. As others in the commentary have observed, the religious community needs to be included. Beliefs about the what constitutes death differ, and in a democratic society, policies and laws can acknowledge and accommodate different belief systems. New Jersey provides an example.
With respect to the specific question about how one should approach the disclosures, there is ample literature about how to approach difficult conversations in clinical care which can inform discussions in the setting of organ transplantation, including the importance of asking the patient how much information they would like and how they would like it delivered. As discussed in the white paper, the separation between discussions about treatment for the patient and decisions about what happens to the body after death, including organ transplantation, is critical. Discussions about organ transplantation must only occur once the patient or surrogate decision maker request withdrawal of life sustaining treatment so that the patient may be allowed to die.
With respect to the second question, the Ethics Committee white paper summarizes the various positions on the ethical implications of NRP, identifies weaknesses in clinical knowledge, and recommends additional research. In addition, when there is uncertainty or imprecision, my colleagues and I have suggested it is important to consider the “patient and family’s willingness to tolerate some diagnostic imprecision….” The way to respect the right of self-determination is to listen to the individuals whose life (and death) are on the line and address their needs.
Anonymous | 09/08/2023
Overall, I greatly appreciate the lengths in which a large number of professionals of varying backgrounds have come together to discuss the ethical impact of NRP. In review of the presentation and white paper, I have only one concern regarding this topic. It was mentioned that research has been conducted using animals and two human donors to determine if there is a return of blood circulation to the brain even when cerebral vessels are clamped. The results of this research showed that there was NO blood flow, which is encouraging with the process of NRP and some ethical questions surrounding it. However, my concern is that there are only TWO human donors in this research, which is not an adequate sample size to draw conclusions from. I believe this needs to continue to be monitored if NRP is going to be become an accepted practice.
Region 2 | 09/05/2023
Sentiment: 4 strongly support, 12 support, 4 neutral/abstain, 0 oppose, 0 strongly oppose
Members of the region are supportive of the white paper and are supportive of disclosing information about the NRP process to donor families while also acknowledging the need for thoughtful consideration of the extent of information provided. An attendee noted concern with the extensive information proposed to be disclosed to families prior to NRP. The potential restoration of cerebral circulation was deemed not fully justified by current data, potentially impacting donor family willingness to participate. It was suggested that more nuanced information should be included if the proposal persists. Another attendee stated that NRP could be defined as a perfusion technique after death pronouncement similar to in situ kidney perfusion. Currently, in situ kidney perfusion does not require additional donor family consent, so requiring NRP consent could lead to additional consent requirements on all procedures. Another attendee stated that informing family members about ligation and the possibility of circulation as part of informed consent was necessary. The intention behind the act of ligation was considered important, with the notion that fulfilling the deceased donor's wishes and allowing a peaceful passing might take precedence over the dead donor rule. Another attendee noted there needs to be transparency around which hospitals are willing to allow NRP recovery. Additionally, donor families should be allowed to opt out of NRP recovery due to the principle of respect for persons. Lastly, standardization of protocols for donor and donor family conversations and adherence to the dead donor rule during NRP were emphasized. The importance of feedback from donor families and clarification on the utilization of the analysis were noted.
Region 4 | 08/30/2023
Sentiment: 7 strongly support, 7 support, 9 neutral/abstain, 1 oppose, 0 strongly oppose
Region 4 generally supported the white paper. One attendee commented that it seemed like the white paper is taking a certain position instead of analyzing the issue. They added that the issue of whether normothermic regional perfusion (NRP) violates dead donor rule or not hinges on the definition of death in each jurisdiction. They went on to comment that not every state has adopted the definition, and the committee needs to define circulation versus perfusion. Another attendee commented that they supported NRP to increase organ transplantation and agree that the ethics of the process needs to be evaluated as well as the analysis of the Dead Donor Rule. One attendee commented that they appreciated the committee taking on this complex and polarizing topic, however the paper’s conclusion strongly highlights the need to create policy/standardized protocols surrounding NRP. They added that efforts should be made to expedite this work as the white paper may unintentionally place centers performing NRP at risk in the absence of policy/standardized protocols. Other attendees commented that this paper does not separate the issues of abdominal NRP (A-NRP) and thoracoabdominal NRP (ta-NRP) effectively and by not doing so, creates public perception rules that are not necessarily applicable to all protocols. One attendee added that the validity of the analysis may depend on whether the heart is involved. Another attendee added that an analysis of questions to be answered for each method, which again are very different, will be useful if the committee starts to make recommendations on practice. Several attendees commented that there is a need for education so that diverse communities of patients can understand the process. One attendee commented that if this white paper is endorsed it will be considered the OPTN position and they recommend additional work by the committee before moving forward. Another attendee commented that while the conclusions in the paper are reasonable, the content of the paper needs clarification. They added that to state that NRP is recirculation is misleading as it is artificial without intent to revive the patient but rather to support the organs of the pronounced donor. They went on to comment that NRP is not providing blood flow to the person-that ended at declaration of death; it is providing flow to the donor. One attendee commented that this paper is a critically important contribution to the US and global donation and transplantation community that helps clarify the various ethical and clinical approaches to carefully evaluating the risks and benefits of evolving NRP organ recovery approaches. It is balanced, well researched and referenced and provides a pragmatic framework for organizations already performing this technique to review as well as for those considering. It is an extremely valuable and timely resource for all stakeholders, including the community at large, most importantly, potential donors and donor families.
OPTN Transplant Coordinators Committee | 08/28/2023
The OPTN Transplant Coordinators Committee thanks the OPTN Ethics Committee for their work and for the opportunity to comment on this proposal.
A member noted that each transplant center handles NRP differently and thus there is no clear standard. Another member stated that NRP has had a positive impact on organ utilization and urged the Ethics Committee to keep science at the forefront of the recommendations being made.
Several members commented about what NRP information should be disclosed to potential donors and next of kin, with one member recommending that OPOs and transplant programs provide as much information as the family wants to know while also using caution about providing too much detail that might impact the decision to donate organs. A member recommended having standard language explaining NRP while allowing the opportunity for donor families to ask additional questions. They also advised considering information for donor hospitals, since many donor hospitals are not familiar with the NRP process and need to be engaged as the practice evolves.
A member recommended involving transplant programs when determining what information about NRP should be shared with donor families, because having such a partnership will promote providing accurate information to families. Additionally, OPOs should also be included to understand the transplant center’s NRP process so they are able to share the information with operating room staff and other important stakeholders.
Anonymous | 08/28/2023
I was to thank the Ethics Committee for their consideration in this matter. After serious consideration, I do not think enough data was shared on this topic for the donor family to consider. Medical innovations are developed daily to help advance procedures to their fullest potential, but reading this has caused me great concern from a humanitarian standpoint.
As a deceased donor recipient, I wouldn’t be living today if someone hadn’t died for me. But the manner of recirculating the blood after the heart has stopped is a challenge for me. Though I volunteer on an OPTN committee, I am also a Patient Advocate and a Pastor. I don’t believe during the emotional duress of death; a family would be under the explanation regarding this procedure. I don’t recall reading any data supporting the increase in the number of organs transplanted into individuals and the survival rate.
I believe that more data needs to be provided for a clear decision to be made at this time.
Donor Network West | 08/25/2023
I'd like to address that I am an ICU physician, OPO associate medical director, and heart transplant recipient. I'm also very close with my organ donor's family. NRP is a topic that is very near & dear to my heart in several ways.
Overall, I support NRP as a medical innovation. It can bring a lot to the world of donation + transplantation. It's potentially a cheaper alternative to using ex situ perfusion devices, although no direct comparisons have been made on the outcomes (that I know of).
Now, keep in mind the following: that the perception of what is going on is frequently more important than what is actually going on. Even if there are absolutely no ethical concerns with NRP, this doesn't mean that perceptions of ethical concerns won't exist. As a physician-- even outside of the OPO world-- I deal with this daily. There is already so much public mistrust in the system solely based on rumors and wrong information. What can do we do about this?
What should be talked about with donor families?
- I don't know the exact answer to this, but there needs to be some sort of standardized procedure. I know donor families who DO NOT WANT to know anything about the specifics, and I know donor families who would scrub into a procurement if they could. We also need to be careful about the wording that we use. In countries or regions where TA-NRP is done regularly & has been successful, we need to see how they are informing their own donor families about the process.
Are there any additional ethical considerations or evidence that should be taken into account in the analysis?
- Dr. Frontera's case series was published in JHLT **this month** in which cranial dopplers showed NO restoration of brain flow in these donors. Please see "Thoracoabdominal NRP in donation after circulatory death does not restore brain blood flow" for the specifics.
John Entwistle | 08/25/2023
I thank the Ethics Committee for the time and effort to address this area of debate. While some of the proponents of NRP consider the ethical issues in this area "settled", this paper makes it clear that there is still significant debate about the appropriateness of NRP in thoracic organ donation.
One area that was not addressed in detail by this paper is the ethical issue of the ligation of the cerebral vessels. If the patient is not dead by circulatory criteria (the cessation of circulation is no longer permanent once ECMO has been initiated), isn't the procurement team causing death by ligating the cerebral vessels? If circulation has been restored and we are now assuming that the patient is dead by neurologic criteria, then the only way that it can be true is because of the actions of the procurement team.
One reason that I believe that this needs to be addressed separately is that many of the other questions in thoracic NRP can be answered by additional scientific study, yet this cannot. We can design studies to look at the degree of collateral flow to the brain stem, or the period of time before autoresuscitation is no longer possible, but this question will require ethical debate and discussion, which should be happening in parallel with the scientific discovery. My personal belief is that NRP for thoracic organs should not proceed outside of carefully controlled clinical trials that help answer the scientific questions while the ethical questions are being addressed at the same time.
Jondavid Menteer | 08/24/2023
I am writing as an individual and I strongly support this white paper for its thoughtful and thorough analysis of a complex subject.
I recognize that this is an ethical paper, and my comments are not meant to criticize the paper but comment on the context of the subject of NRP in the United States.
1) Public sentiment is CRITICAL to the success of organ donation in the US. We are opt-in, not opt-out, as a society - and we need potential donors to FEEL that the transplant allocation system is respectful and ethical. The process of TA-NRP is under scrutiny because is lies in a grey zone ethically and requires a great deal of knowledge to understand. When misunderstood, which it has plenty of potential for, it has the potential to substantially erode public trust. We need a large benefit to justify continued pursuit of TA-NRP.
2) TA-NRP, in contrast to A-NRP, potentially adds utility of hearts but not likely lungs, and may in fact be deleterious to lung utility. Reannimation of the heart after DCD creates an additional ischemic period to the recovery of the organ that ex-vivo perfusion does not. To take on ethical and political risk with TA-NRP when ex-vivo perfusion exists in 2023 really makes no sense to me. Ex vivo perfusion provides longer term perfusion support for the reanimated organ, and does no damage to the lungs.
In summary, I support this white paper. And I support A-NRP, but the ethical dilemma and political risks associated with TA-NRP, however well-intentioned, counter the utility benefits of this procedure in my opinion, especially in the age of ex-vivo perfusion.
Garrett Erdle | 08/24/2023
As a patient and a member of the general public, I was spooked about what I read in the NRP white paper. I believe this procedure is currently in use but is the risk worth it? One bad outcome, highlighted in the NY Times or Washington Post, and I can see a reduction in the donor pool.
Reading and learning that the medical team must clamp an artery to prevent the flow of blood to the brain has me questioning if the patient is truly dead. I interpret this action to mean we are “pushing” the patient into the death category, and this disturbs me. Are we taking away the slightest chance a patient may recover? Are we taking hope away from grieving parents? Does a donor family truly understand what NRP means? This procedure risks straining the public trust, which itself is its own utility consideration.
As this procedure is currently in use, how many additional organs have been recovered with the aid of NRP that would not have been if the patient was allowed to pass away without the use of NRP? Presenting this data is critical to evaluating the benefits of NRP. If I am informed, with data, that we may recover thousands of additional organs with an OPTN approved and vetted NRP procedure, my response may be different.
We currently throw away 4,000 recovered organs a year. There is zero risk of damage to the transplant system in this country, and the public trust, if we find a way to utilize these organs. In fact, reducing discards is a result which the Contract holder should highlight to the country. It says, “your gift of life is important to us, and we are finding ways to save more lives.” I do not imagine the Contract holder will highlight the use of NRP in its marketing materials.
I view the role of the Ethics Committee to be the safe space where procedures, like NRP, and policies are discussed with an eye towards making certain we not only sustain, but increase, organ donation and transplantation in an ethical manner. I appreciate those who volunteered on the Workgroup to discuss a difficult topic.
Personally, I believe we should not advance the use of NRP until we capture the data on utility since the risks appear to me to greatly outweigh the benefits.
Living Kidney Donor
Chairman, OPTN Patient Affairs Committee
Anonymous | 08/23/2023
I believe that NRP appears to be the best option to increase utilization of DCD specific organs, that otherwise might not be recovered. As long as there are strict regulations in terms of ensuring that blood flow cannot and will not reach the brain, then I fully support NRP. I believe that it is not an ethical concern, but rather a modality used to save lives. If there was confusion or concern about the brain being reprofused then it would be necessary to fully inform families. Having worked with donor families for 7 years I see the OPO's strive to give families a lot of information, and in their time of grief, it is oftentimes too much information and can overload the family. NRP seems to be the future of donation and transplantation and I think we have an ethical obligation to ensure that we do what we can to further implement and advocate for this process in order to get more recipients off the waitlist.
OPTN Liver & Intestinal Organ Transplantation Committee | 08/23/2023
The Liver and Intestinal Organ Transplantation Committee thanks the OPTN Ethics Committee for their efforts on the Ethical Analysis of Normothermic Regional Perfusion proposal.
The Committee suggested for the Ethics Committee to consider the “last gift” concept when analyzing the respect for persons principle, as they believed it should be heavily weighted in comparison to the other ethical principles in the analysis. The Committee recognizes that utility and the “last gift” concept is important, however they also recognize the importance of not violating the Dead Donor Rule (DDR).
The Committee cautions the Ethics Committee about overwhelming donor families with details about normothermic regional perfusion (NRP), therefore balancing disclosure while respecting the level of detail families want to receive is important with NRP. Regarding the proposal’s recommendation to disclose details about NRP to donor families, the Committee suggests that the Ethics Committee let donor families guide how much information they want to receive.
The Committee agrees that there is a difference between brain function and perfusion.
Harry Peled | 08/21/2023
We thank the OPTN ethics committee for their excellent work though we do not believe NRP is ethical or should be done at this time. In order to assist ethics committees and IRBs to perform a proper review we have attached a table with a list of the factual differences between NRP and conventional DCD. We fully agree with the ethical analysis that recommends ensuring informed decision making given the key factual differences which have moral and practical impact between NRP and DCD. Because of the absence of consensus that NRP is ethical, it is essential that that neither patients nor clinicians should be coerced into accepting or performing NRP. Patients must be offered procurement without NRP; direct procurement and ex vivo machine perfusion should be performed as clinically appropriate and available. Similarly, OPO’s should not require procurement teams to perform NRP. Though we believe performing NRP is not appropriate at this time, we hope that at a minimum there will be greater transparency and oversight by local ethics committees
Aaron Wightman | 08/18/2023
Congratulations to the OPTN ethics committee for a thorough description of the ethical issues raised by the introduction of normothermic regional perfusion. I would like to raise a few additional questions for the committee to consider.
1. The committee has recommended additional education or counseling be provided to potential DCD donors or their families about NRP. This recommendation seems to suggest, at least implicitly, that some potential donors or their families may view NRP as morally different than other forms of DCD organ donation and as a result may refuse for NRP to be used for their organ procurement. If that is correct, wouldn’t it also like be correct that potential transplant recipients or their families may feel there is a moral difference between organs procured using NRP and those procured using other procedures? It would seem to follow that potential recipients also be counseled about NRP and potentially given the option to refuse an organ recovered using an NRP procedure. Would the committee support requiring education for potential recipients and their families about NRP as well?
2. The ethics committee has identified that “non-maleficence requires demonstrating that the performance of NRP occurs when a donor is insensate and that this state is maintained.” The committee provides a list of potential tools such as transcranial dopplers, angiograms, or tissue oxygenation to demonstrate no blood flow reaches the brain. Such testing and demonstration of a lack of cerebral blood flow is not required when declaring death by neurologic criteria. Further, if the donor receives anesthesia during NRP, as is often done in organ procurement following a declaration of death by neurologic criteria (see Balogh et al. Transplantation Reports 2022), why shouldn’t anesthesia be provided to ensure a donor does not have the possibility of becoming sensate? Would that lessen concerns of maleficence toward organ donors.
Anonymous | 08/17/2023
The following comments apply to NRP with respect to all forms of "cardiac donation after cardiac death," and not intended to address donation of non-cardiac organs after cardiac death; I also agree that clergy are underrepresented stakeholders.
It is my earnest and sincerely-held belief that, with respect to heart transplantation, all forms of donation after cardiac death and donation after induction of cardiac death and with facilitated completion of brain death are manifestly self-contradictory, jeopardize the entire system of organ transplantation, and render the US transplant system no better morally or ethically than selected systems in authoritarian countries where transplant ethics are inherently questioned. As a transplant professional, it is important that these voices be heard. Yet, given the risk, I have opted to remain anonymous for the purpose of this commentary, as the field is already far down the slippery slope across the ethical Rubricon.
If one attempts to declare death via irreversible cessation of cardiovascular function and then demonstrates reversibility, the very restoration of cardiac function disproves the initial declaration of cardiac death, regardless of whether NRP or any other means of perfusion is utilized. The only way to faithfully declare cardiac death is when cardiac function is not restored. The movement of a heart from a donor into a recipient, by any means, with restoration of cardiovascular function or viable cardiac function manifestly disproves cardiac death.
I agree with the concerns expressed in the ACP (American College of Physicians) statement of concern ( https://www.acponline.org/sites/default/files/documents/clinical_information/resources/end_of_life_care/ethics_determination_of_death_and_organ_transplantation_in_nrp_2021.pdf ) that NRP-cDCD is more accurately "organ retrieval after cardiopulmonary arrest and the induction of brain death."
Yet cardiac donation should inexorably requires formal brain death declaration,
Put another way, when cardiac function is ultimately restored (whether internal or external to the corpus), it should limit the definition of death to that of brain death. Yet when brain death, rather than cardiac death is declared, it is typically an affirmation and confirmation far after the event. Brain death declarations are usually merely confirmation that death has already occurred, and the discrete time specified is merely a post-hoc documentary time, long after the completion of actual brain death. Brain death is usually a process, and the only case where physiologic brain death truly occurs at a definable moment in time is when there exists traumatic and instantaneous catastrophic physical destruction of the brain. It is our desire and legalistic process requirements to place a "time" of death that further propagates the misconception that brain death occurs at a moment, rather than as a continuum. That time scale is inconsistent with the process of NRP when used to facilitate cardiac retrieval.
It is my belief that the only organs that are ethically retrievable after cardiac death are non-cardiac organs, and the need to declare brain death for retrieval of a heart is inherently inconsistent with viable and ethical cardiac transplantation after declaration of cardiac death. Active action to secure irreversibility of brain death in a "DCD cardiac donor" (who is manifestly not dead by cardiac means given that irreversible cardiac cessation will be manifestly disproven) by preventing recirculation to the brain (re-animation) is, (with full respect to the term) homicide and violates the bedrock principle of non-maleficence.
The term of cardiac donation of cardiac transplantation after cardiac death is self-contradictory. Its existence is attempting to rationalize the irrational, driven by both altruistic but misguided understanding by some, and by financial incentives by others. To continue such actions jeopardizes all forms of transplantation and trust of the community.
The ends do not justify the means.
DonorLink LLC | 08/10/2023
The debate cannot be between NRP or machine perfusion. It is a DCD discussion only. Either the pt is dead or not dead and what is the acceptable standoff period and most definitive way to pronounce. Discussing this with a family different than any other dcd will cause confusion and mistrust. A standard way to pronounce is needed. Mandatory A-line? PEA vs asystole? Minimum standoff period. If a brain is dead restoring blood flow does not bring it back. The bigger question is how long does it take for all brain activity to cease post cardiac arrest and this is the same question for all dcd donors.
W. Graham Carlos | 08/04/2023
If the patient is dead - why worry about clamping the cerebral vessels to do NRP?
This does not seem to be out of concern that brain may "steal" blood from other organs but more about concern about brain function and any perception patient may experience as one does not know what portions of their brain are "active" at this time.
In addition, the move many hospitals are making from 5 min to 2 min pause after time of death before retrieval to decrease ischemia time heightens my concern that insufficient time is lapsing for brain function to cease in DCD cases.
The 2021 NEJM article "resumption of cardiac activity after withdrawal of life-sustaining measures" demonstrates some cases of "autoresuscitation" even after several minutes of pulselessness. While all of these patients eventually died, the concern is that potential NRP patients will not be completely dead (esp. if using 2 min after TOD) and may have resumption of flow to brain before or in spite of clamping vessels (posterior circulation).
In my opinion, if we are confident the patient is dead, there is no reason to clamp cerebral vessels. If we are not confident, or if we worry that patient may not die (may be auto-resuscitated) than cross-clamping is serving to hasten brain death which is wrong. Importantly, even if vessels are clamped and it hastens death, this occurs after their chest opened. This seems ethically and morally wrong.
Anonymous | 07/31/2023
I appreciate the depth of this analysis and the degree to which the committee went to analyze as many perspectives as possible.
I do not feel NRP violates the Dead Donor Rule, as circulation is re-established artificially after natural death and with the sole purpose to perfuse the organs, not to restore life to a person otherwise considered deceased.
I do worry about the possibility of brain reperfusion posteriorly and agree that something must be done to ensure this not a possibility in the name of non-maleficence.
Overall I strongly support NRP and look forward to future guidance on this topic.
Anonymous | 07/28/2023
I was surprised in viewing the presentation that ethicists were included as stakeholders, but clergy were not included. I can't imagine why? It seems like clergy should have been included. In many communities, they will be the ones providing both support and guidance to potential donor families. This is especially true for African American, Latino, and non-Caucasian families. Perhaps the slide wasn't careful in its listing of stakeholders? In any case, if you want to build trust, in these processes, inclusion of marginalized populations is essential.
Additionally, this does seem like a violation of the Dead Donor Rule. What percent of transplants go to marginalized populations? Who benefits from these additional organs? People who can't afford transplants won't get them. So, this proposal suggests we skirt the Dead Donor Rule to benefit people and the transplant hospitals with more means.