Could controversial technique reduce transplant organ shortage?

The field of medical ethics is grappling with use of a relatively new technique that’s expected to boost the supply of donated organs and improve the likelihood a transplanted organ will do well in its recipient.

The procedure is called normothermic regional perfusion; shorthand is NRP. In a news release , the Organ Procurement and Transplantation Network said it’s an organ-recovery procedure that’s only used if an organ donor has been declared dead by circulatory criteria, meaning the heart no longer circulates blood and respiration has stopped. After a waiting period to ensure the heart doesn’t voluntarily restart, blood vessels are clamped to ensure blood doesn’t flow to the brain, then a machine is used to restart blood flow through the potential donor’s organs.

The question at the center of the quandary, as the Pinnacle Gazette by Evrim Agaci puts it, is: “Does NRP invalidate the circulatory criteria for death, effectively resuscitating the donor?”

It’s not a simple question for many people in the health care field. The American College of Physicians in 2021 issued a statement noting strong support for organ donation and transplantation, but concern about the ethics of NRP.

Meanwhile, many health professionals see it as valid and valuable tool to boost availability and viability of organs that might otherwise not make the cut. It saves lives, they say.

There are two types of death declarations by medical professionals when it comes to organ donation. “Organ donation occurs after circulatory determination of death, defined as death confirmed by the irreversible cessation of circulatory and respiratory functions, or after determination of brain death, defined as the irreversible loss of all brain functions, including the brain stem,” the American College of Physicians wrote in its exploration of the issue.

The statement notes that organ donation after brain death has been considered generally better for transplant success because organs aren’t affected by loss of blood prior to being removed, though both forms can save lives. With circulatory death, hearts and intestines are used less often because of damage.

A Michigan Medicine article at the University of Michigan said 30% to 40% of potential donor hearts aren’t considered for transplant because they weren’t functioning well enough to be transplanted in cases where circulatory death occurred.

Some other countries have been earlier adopters of NRP, which restores limited oxygenation and blood circulation. The crux of the dilemma in the U.S.: The heart may start beating again. As the American College of Physicians noted, “Thus the determination of irreversibility — necessary for the certification of death of the patient made moments before — was apparently inaccurate since circulation is restored.”

The patient is still dead; the brain has stopped functioning and meets brain death criteria, “due to the actions taken by the physicians procuring the organs,” the statement says. “It is more accurately described as organ retrieval after cardiopulmonary arrest and the induction of brain death. The manner and declaration of death raise significant ethical questions and concerns.”

The group’s statement asks, “Is declaring a patient dead by irreversible circulatory criteria, then rendering the patient brain dead before restoring circulation honest, transparent and respectful of patient autonomy and dignity?”

Experts disagree.

Transplant by the numbers

According to the United Network for Organ Sharing , more than 16,000 deceased individuals were organ donors, which was a new annual record in the U.S. That same year, there were more than 46,000 organ transplants — also a record — including a historic 10,000 liver transplants and 3,000 lung transplants. Records were also set for kidney and heart transplants.

Many people still die as their diseased organs fail while they wait for a transplant. Organdonor.gov notes that 103,223 women, men and children are on waiting lists for a transplant at the moment and a new individual is added in the U.S. every eight minutes. Seventeen die each day. An organ donor has the potential to save eight lives and enhance dozens more through non-organ donation, including corneas and skin.

The site reports that 86% of those listed need a kidney, 10% a liver, 3% a heart and 1% each a pancreas or lung. Fewer than 1% are waiting for kidney/pancreas and allograft transplants, which include face, hands and the abdominal wall.

A University of Michigan Health team has experimented for several years with finding better ways to transport hearts so that they can be transplanted. Led by Dr. Alvaro Rojas-Pena, a research investigator in transplantation surgery, they’ve started using a “modified” normothermic perfusion system that makes transplant feasible for up to 24 hours, per the Michigan Medicine article.

“The system uses a blood-derived solution to perfuse the organs and has a hemofilter to remove toxins,” the article said. It also lets the surgical team see how well the organ functions before transplant. “This research and current data prove the concept that normothermic perfusion has the potential to increase the organ pool by considering previously discarded hearts, performing an objective assessment of heart function,” among other benefits.

In March 2023, the Alliance National Critical Issues Forum and the Gift of Life Institute co-hosted a gathering in Philadelphia for an “objective and unbiased” presentation of challenges and opportunities of NRP. Alliance News reported much of the discussion centered on legal and ethical issues.

Different deaths and transplant options

The National Institutes of Health says there are two types of NRP: “abdominal NRP (A-NRP) and thoracoabdominal NRP (TA-NRP). The former is used to support the liver, kidneys and pancreas, while the latter supports the heart, lungs and abdominal organs. The TA version can include perfusing the heart.”

Dr. Jean Botha, medical director of Intermountain Health’s abdominal transplant program and Intermountain Primary Children’s Hospital’s pediatric transplant program, said that like a growing number of transplant programs, Intermountain Health uses NRP — in its case A-NRP — but notes it’s important to understand the differences. “During A-NRP the heart is not re-started, and we also confirm that there is no blood flow to the brain. These two major differences ensure that A-NRP satisfies current accepted ethical and legal principles” of the circulatory death organ donation.

Botha said that the advantages of the NRP process include increased use of organs in cases of circulatory death, so that “more patients getting the opportunity for life-saving organ transplantation and lower risk of dying on the waitlist without that opportunity.”

And there are fewer postoperative complications, Botha said, “leading to shorter hospitalization and ICU stays, which overall drives financial efficiency and creates value for the populations that we serve.”

Dr. Emil J. N. Busch from the University of Oslo told Pinnacle Gazette’s Agaci that worries that NRP counters the declaration of death in some way is misguided, since it doesn’t restore integrated function. It restores what Agaci calls “regional blood flow. ... While certain organs may regain perfusion, the organism as a whole remains non-functional and, therefore, deceased.”

Transplant network tackles the ethics

The Organ Procurement and Transplantation Network in March released a white paper by its ethics committee that looked at ethical implications of NRP.

“The use of NRP allows more organs to be used without negatively impacting patient outcomes,” the agency said. “However, the fact that it involves recirculation after death by circulatory criteria has raised concerns about adherence to foundational principles of medical ethics.”

The committee recommended that “consistent and transparent protocols” should be used to do NRP and said potential organ donors and their families must be well-informed about it before they are asked to provide consent.

The committee said its work was based on certain principles that guide donation and transplantation, including “do no harm,” and show respect for a person. That principle “is important for maintaining public trust and requires compliance with the Dead Donor Rule, which requires that patients must be dead at the time of organ procurement (meet criteria for brain or circulatory death) and that organ donation does not cause death,” per the white paper.

Members of the ethics committee called NRP “a promising development in the field of organ transplantation, since it has the potential to substantially improve both the number and the quality of organs that are available for transplantation and in particular for the heart,” which can be hard to procure in circulatory deaths.

The committee agreed NRP could make more organs available for successful transplant, thus saving lives. But members also agreed the process somewhat muddies the question of meeting the Dead Donor Rule, in that a requirement is the permanent cessation of blood circulation, while NRP restarts circulation. “This concern implies that a person legitimately meets criteria for determining death owing to permanent cessation of circulation (at the time of death declaration), but that this criterion is violated subsequently when circulation is restored (at the time of donation),” they wrote.

Besides potentially expanding the number and viability of organs, though, another consideration speaks for the practice, however. The paper suggests families donating a loved one’s organs may “receive comfort from the knowledge that their loved one was able to save a greater number of lives with fewer complications” because of NRP. While it acknowledged that there’s little study of public attitudes about NRP, the paper said families sometimes experience psychosocial distress when a loved one has circulatory death, but not in time to donate organs.

Worried workers and public trust

The big picture is complex. Even as it appears to support the practice, the network’s paper points out potential harm to the public’s trust in the organ donation system. Also, “given the lack of consensus among leading legal scholars about the legality of NRP,” the paper notes potential legal challenges that “could further magnify the public relations challenge of sustaining public support for the mission of organ procurement and transplantation.”

Clearly, feelings are mixed within the medical profession. In the white paper, members of the group’s ethics committee said people working in transplant programs have expressed moral concerns on both sides: Some wonder about the ethics of using NRP, while others wonder if it would be ethical to oppose it, which could prevent someone from receiving a life-saving organ transplant.

Regardless, the do-no-harm principle must never be violated, even if doing so could lead to positive outcomes, the committee agreed.

Some would like modifications or different methods than NRP. The American College of Physicians noted that organs can be reperfused using machines outside the body without restarting the donor’s blood circulation or intentionally stopping blood flow to the brain. “More research is needed on these devices. There is a large and ethically significant difference between perfusing an organ versus perfusing an individual,” the group wrote.

Among those who see great potential in NRP is Dr. Aaron Ahearn, a liver transplant surgeon at Keck Medicine of University of Southern California. After restoring circulation to the liver of someone who had circulatory death, he reported that “it allowed the liver to recover before it had to go on ice,” making what might have been a questionable organ suitable for transplant.

“It’s potentially an organ pool that could be much larger than the traditional pool,” Ahearn said in a Keck news release . “Many more people die in a fashion consistent with cardiac death than with brain death.”

He added, “NRP allows us to take organs that were previously challenging and marginally unsafe to use and brings them to the safety level of our standard transplants. I think this is the future of transplant.”