Normothermic Regional Perfusion: An Introduction to a Controversial Way to Obtain Organs for Transplant

Recently there has been national publicity about a new way to procure organs for transplant called normothermic regional perfusion (“NRP”) for donation after circulatory death (“DCD”). See for example, the pieces from the New York Times, and NPR. This relatively new method not only has potential to improve transplant outcomes for more patients, but also implicates new ethical and social concerns about how organs are obtained for transplantation. 

What is NRP? NRP is a way of obtaining organs for transplant that improves the likelihood of a successful transplant by mechanically recirculating oxygenated blood through parts of a donor’s body and organs, (excluding the head and brain but potentially including the heart,) after they have been declared dead by circulatory criteria. 

Important background: Some important background information is helpful to understanding the unique ethical issues related to NRP. These issues are not related to living donor organ donation, and only concern deceased donor organ donation. 

2 ways of determining death prior to organ procurement: There are 2 ways that deceased donation can occur, depending on how the patient is determined to be dead. Currently, there are two ways that a person can be determined to be dead: by neurological criteria (brain death,) or by circulatory criteria. With some minor variations, every state has criteria that allows for the determination of death either by neurological criteria, or by circulatory criteria. Determination of death only requires meeting either circulatory or neurological criteria, not both at the same time. When a donor is determined to be dead by neurological criteria, the legally dead donor’s other organs including their heart may continue to function in some capacity with the support of life sustaining treatments like mechanical ventilation. In contrast, a donor is determined to be dead by circulatory criteria only after the heart and lungs have permanently or irreversibly stopped functioning. The requirement for irreversibility has been generally met by requiring that the circulatory and respiratory function has stopped for 5 minutes. NRP only applies to donations after circulatory death, and does not apply to donations by donors who are determined to be dead by neurological criteria. 

What death means, and why it matters: The determination of death is not only a matter of science and medicine, it is also a social issue. A dead body does not have the same rights and interests that living persons have. As a result, the duties that we have to the dead are not the same as the duties that we have to people that are living. If there is confusion or error in the determination of death, it can cause major harm when a living person is mistakenly regarded as dead and subsequently their rights and interests are violated. Furthermore, consistency in how death is defined and determined within a society is very important. Inconsistencies in the definition and process for determination of death could lead to situations where theoretically a person could be considered alive in one jurisdiction, but dead in another. 

The Dead Donor Rule: The dead donor rule is an ethical requirement that the procurement of organs from donors does not cause the donors death, and/or that the donor must be dead prior to the procurement of organs for donation. It is unethical to cause the death of a donor in the process of procuring organs for donation. There must be certainty that procurement of an organ for transplantation does not cause the death of the donor. 

The need for viable organs for transplant: Currently, the number of people who need organs is much greater than the supply of organs available for transplant. Increasing the supply of organs that can be transplanted would help save the lives of more people. One of the challenges with organ donation is optimizing the viability of an organ for transplant. When organs do not get oxygenated blood, the tissues can be damaged, which lowers the likelihood that the organ can be successfully transplanted with good outcomes for the recipient patient. 

Why NRP: A problem with DCD is that the process of determining death, which requires e.g. 5 minutes of the loss of circulatory and respiratory function, means that the organs can become damaged due to a period of time without circulation of oxygenated blood. One of the ways to improve the number of viable organs for donation is to reduce the amount of damage that occurs to organs after the donor’s heart and lungs stop working. Restoring oxygenated blood to the donor’s organs can reduce or even reverse damage to the organs. NRP is one of several ways to try and minimize damage to organs for transplant after the determination of a donor’s death by circulatory criteria. 

How does NRP work: Generally, the steps for NRP are: 

1. A patient independently decides to be an organ donor.
2. The patient also has a terminal condition, is imminently dying, and is on life sustaining treatment that usually involves mechanical respiratory support.
3. The patient makes an independent and informed decision to refuse and withdraw life sustaining treatment because ongoing life sustaining treatment would be inconsistent with their goals and values. This decision is separate from any decisions regarding donation.
4. At a chosen time, life sustaining treatment is withdrawn from the patient based on the obligation to honor a patient’s refusal of unwanted treatment. The withdrawal of life sustaining treatment is done by the patient’s care team, which is separate from the team that procures organs for transplant.
5. After life sustaining treatment is withdrawn, the patient may or may not continue to live in that their heart and lungs may or may not continue to function. If the patient’s heart and lungs do not stop functioning, then organ procurement cannot proceed.
6. If the patient’s heart stops, death is declared when it stops.
7. A stand off period of 5 minutes must elapse after the heart stops as a way of ensuring irreversibility of death, and no autoresuscitation.
8. After the stand off period, the donor’s body begins to be operated on by a separate organ procurement team.
9. The first step is to clamp off the blood vessels from the heart that lead to the donor’s brain.
10. The second step is that lines are inserted into the donor’s body that allow oxygenated blood to be pumped through parts of the donor’s body and organs.
11. After lines are placed, oxygenated blood is pumped through the organs and parts of the body that have not been blocked off from circulation.
12. After a period of time during which the organs are being oxygenated inside the donor’s body, the organs needed for donation are assessed, then removed for transplantation.

The ethics issues: There are ethical considerations that have led clinicians and scholars to different positions regarding the ethical defensibility or appropriateness of NRP. Some argue that NRP is not ethically appropriate; some argue that NRP is ethically appropriate as long as certain unique conditions or procedures are met; some argue that NRP is ethically appropriate in the same way that existing DCD practice is ethically defensible and can be practiced like standard DCD without significant changes to existing procedures. 

Areas of agreement:

• There is broad agreement that increasing the number of viable organs for transplant is an ethical and valuable goal.
• There is also broad agreement that the dead donor rule should remain as an ethical norm and requirement. 

Areas of disagreement: 

• Whether replacing or restarting circulation in part of the donor’s body including the heart, but not the head or brain, invalidates a prior determination of death. If the replacement or restarting of circulation means that the donor has been resuscitated and is no longer dead, even though the blood vessels to the brain are blocked, then procurement of organs may violate the dead donor rule.
• Whether there is harm caused to the donor due to the possibility of incidental circulation to the brain even after main vessels have been blocked, through other minor kinds of circulation, which results in concern that the donor may not be completely without consciousness or sensation. This could result in serious harm to a donor. There are ongoing studies about this concern.
• Whether the act of blocking of the blood vessels to a donor’s head is morally significant, and depending on why, when, and who is doing the blocking of the blood vessels
• Whether the NRP-DCD can be defended if there is an equally effective (but more expensive) way of preserving organs. This is specifically technology that oxygenates and preserves organs for donation outside the donor’s body.
• The kinds of consent or authorization that should be involved for NRP, if it is ethically defensible. It’s worth noting that if NRP is not ethical because for example it necessarily violates the dead donor rule, then even appropriate consent or authorization cannot fix the ethical problem. If NRP is ethically defensible, then there may also need to be special procedures to be ethical, including appropriate consents or authorizations. 
• Whether the laws that govern the definition and determination of death need to be revised to improve consistency and clarity for NRP. 

Currently there remains significant variation in practice and policy both nationally and regionally. Some institutions continue to employ NRP, some institutions have suspended or decided not to participate in NRP procurements. Minnesota is in the same situation.

The University of Minnesota Medical Center Ethics Committee and faculty at the University of Minnesota Center for Bioethics has been involved in discussion about the ethics of NRP since early 2022, when transplant program leaders brought their questions and concerns to our attention. 

On May 18, 2022, the UMMC Ethics Committee met to discuss NRP. The committee came to a consensus agreement that NRP was ethically defensible in the same ways that standard DCD is ethically defensible, but that the differences in the process would require special procedures for informed consent and authorization, and also require  new efforts for community engagement and professional education. The committee recommended that NRP-DCD not proceed until specialized policies for informed consent and authorization are implemented, and until after special community and professional outreach and education has been implemented. The opinions of the ethics committee were presented to the Organ Procurement and Transplant Network Ethics Committee on August 4, 2022, and referenced in a white paper on NRP published by the Ethics Committee of the OPTN. Presently, NRP is not occurring at UMMC, pending further policy and practice developments. 

*Professor Joel Wu is also a current member of the OPTN ethics committee. However, he did not contribute to the white paper on NRP ethics from the OPTN ethics committee, since his term began after the completion of the NRP document.