Zoe Berg, Senior Photographer

A new method of procuring organs for transplant surgeries is sparking a debate over the line between life and death.  

The procedure — called normothermic regional perfusion, or NRP — can expand the pool of organ donors by keeping blood circulating to organs in the body, even after the heart has stopped. While the procedure might alleviate pressure on the organ shortage in the United States, some bioethicists are alarmed by a common practice during the perfusion process: cutting off blood flow to the brain, ensuring that donors no longer have brain function after death.

The ethicists say that it is a practice that blurs the medical and legal definitions of death for organ donors

“There are some people that are obviously dead, and there are some people that are obviously alive, and then there are some people that are in a gray zone, where different people have different opinions about whether they’re dead or alive,” said Mark Mercurio, Director of the Program of Biomedical Ethics at the School of Medicine. “Are we sure these donors are even truly dead?”  

According to the U.S. Department of Health and Human Services, 17 people die each day waiting for an organ transplant, and every 10 minutes, another person is added to the transplant waiting list. Those delays, experts say, are driven by a large organ shortage in the United States — one that prompts the need for other ways to increase the organ supply. 

The standard method of preserving the heart and lungs in donors after cardiac death — called ex-vivo perfusion — uses external machines to keep blood flowing to organs outside of the body. 

According to David Mulligan, a Yale transplant surgeon and the former President of the United Network for Organ Sharing/Organ Procurement and Transplant Network, or UNOS/OPTN, those ex-vivo machines allow surgical teams to keep donor organs healthy for hours until they can be transplanted into a patient. Otherwise, surgeons would have to perform a transplant immediately after a person dies and an organ becomes available. 

“Why do the transplant at 2 in the morning when you can do the transplant at 7 in the morning,” Mulligan said. “That way…everybody’s rested, everybody’s fresh. You can do [transplants] from morning until evening in a very scheduled way.”

But as it stands, techniques that physicians use to procure organs from deceased donors can be expensive and inaccessible. For example, those machines can range from $10,000 to $250,000, meaning that many transplant centers might not be able to justify investing in machines, Mulligan added. 

NRP, the alternative method, might address the high cost of ex-vivo machines. In the procedure, a donor’s organs are reperfused, meaning that blood is recirculated through the organs while still inside the donor body, which ensures that the organs stay transplantable during the retrieval process. NRP also does not require ex-vivo machines, instead using a more common procedure with a bypass machine to circulate blood through the body artificially. 

NRP also allows transplant centers without ex-vivo machines to harvest organs from patients who have experienced cardiac death, instead of brain death. Donors who are brain dead — whose brain activity has irreversibly ceased — often remain on life support, ensuring that their organs are supplied with blood until a transplant team can procure their organs.

For donors whose hearts have stopped after an accident, the lack of blood supply to organs can damage them before surgeons can begin harvesting them. After a patient is declared dead, oxygen depletion during the dying process can injure the organs too much for surgeons to use. 

And without an ex-vivo machine, many transplant centers across the country cannot access the organs of patients whose hearts have stopped, Mulligan said.

But by keeping organs like the heart and lungs perfused with blood in the body while the heart has stopped, NRP can keep organs in healthy shape, even after the heart has stopped. It is a technique that opens up a new pool of donors — helping to alleviate the nationwide shortage of organs, said Richard Formica, Director of Transplant Medicine at Yale.

The dead donor rule

Some physicians, however, have raised concerns about a variation of the procedure known as thoracic NRP, in which the heart and lungs, alongside the abdominal organs, are reperfused with blood.

In the process of refreshing the heart with blood, transplant physicians often use metal clamps to cut off blood flow from the heart to the brain as a safeguard to ensure that a patient’s brain function cannot be restored.

“They ligate the cerebral arteries because of the concern that when you start pumping blood flow through, there could be some neurological activity,” said Formica. “And this is where the whole controversy over NRP comes in.”

According to Formica, cutting off blood flow to make sure that brain activity does not resume creates a tricky ethical situation: if a patient has died, why should there be a concern about brain activity?

According to the Organ Procurement and Transplantation Network, a public-private partnership that facilitates the organ transplant harvesting process and waiting list, the ethical norm for organ procurement is referred to as the dead donor rule. The rule states that organ donors must be dead before their organs and harvested, and that organ procurement itself also cannot cause the death of the donor.

Some bioethicists have raised questions about why cutting off circulation would be necessary for a donor who has already been declared dead. For Mark Mecurio, the Director of Yale’s Program of Biomedical Ethics, the procedure might violate the long-standing dead donor rule, since the clamping process might induce brain death. 

“My opinion, from what I understand, is that the procedure… absolutely must be abandoned,” Mercurio said. “But I think that there’s some clarity that’s needed. Everybody involved needs to know exactly what’s going on”

The procedure has also divided hospitals outside New Haven. In November, The New York Times reported that New York-Presbyterian Hospital, home of New York City’s largest organ transplant program, rejected the technique after an ethics committee reviewed the procedure.

The American College of Physicians has also opposed the procedure, claiming that by cutting off the brain’s blood flow, NRP violates the dead donor rule and raises “profound ethical questions” by, in some ways, ensuring brain death.

Mulligan, the transplant surgeon, dismissed the idea that a donor could suddenly come back to life. Mulligan said that the blood flow that is cut off to the brain is not enough to restimulate brain activity.

“There’s nobody that’s going to reanimate, [with] a brain that can think and that can be aware of something, and that all of a sudden, somebody’s going to get better,” Mulligan said.

Redefining death?

For Stephen Latham, the Director of Yale’s Interdisciplinary Center for Bioethics, the real dilemma behind NRP lies in the legal definition of death, not with the science or ethics of the method. 

Adopted by most states in 1980, the Uniform Determination of Death Act, or UDDA, defines the point of death as irreversibility, or the point when all brain function permanently ceases or when blood circulation has stopped for good. 

“The criterion that says that someone is only dead if their heart, lung function, or their brain function is completely and permanently irreversible is out of date,” Latham said. “It’s grounded in the science of the 1960s, and it’s not a great guide to ethics.” 

Methods like NRP, though, toe the line of irreversibility, Latham told the News. Technically, they restart circulation within the body to make organs like the heart and lungs viable for transplantation. 

According to Latham, restarting circulation to harvest organs essentially reverses the “irreversible” aspect of the current legal definition of circulatory death. 

“The definition of death is… not quite as obvious as we’d like to make,” said Mercurio.

Change the definition of death in the eyes of the law, Latham added, would be slow. In the United States, laws that govern medical practices are almost entirely up to states. Most states, Latham said, defer to the guidelines of a non-governmental and non-profit organization called the Uniform Law Commission, or the ULC, which recommends uniform interstate laws that have, among other things, helped define states’ definitions of death. 

As of September, Latham said, the ULC has announced that they plan to put a revision of a uniform definition of death on pause.

NRP and Yale

According to Ramesh Batra, the surgical director of the liver transplant program at Yale Transplant Center, because Yale does not perform organ procurement itself, there is no current policy or stance that the University plans to take on NRP. 

However, the Yale-New Haven Hospital system receives organs for transplantation from the nonprofit organization New England Donor Services, or NEDS, which would have to propose rules for whether they want to procure organs using NRP, Mulligan added. 

According to Mulligan, NEDS has performed NRP once before, with a kidney being used for transplantation at YNHH. He said he sees NEDS adopting NRP more readily in the near future. 

“We definitely believe in the utilization of NRP, and we love the fact that the costs are much lower,” Mulligan said. “We anticipate in the future that thoracic NRP and abdominal NRP are going to eventually come around, and everybody will be okay with that, too.” 

Batra said he believes that Yale’s use of NRP organs could pass over ethical scrutiny because, by the time YNNH receives organs, they have already been procured. By the point it reaches a surgical team, he claimed, discarding an NRP organ would be more than wasteful — it could be an ethical issue.

“If you don’t use it, actually, you’re being unethical with an organ standing in front of you,” Batra told the News. “The intent over there is to not get the patient alive, to just use the organs properly. And I think that if the intent is not at question, why are we questioning the ethics of it?”

The Yale New Haven Transplant Center is located at 800 Howard Ave.

Update, Feb. 12: This article was updated to clarify that clamping blood flow to the brain in NRP ensures that a patient’s brain activity has stopped.