Article In Brief
A new approach to establishing criterial for organ donation after circulatory determination of death is raising ethical concerns because the technique requires mechanically restoring circulation in the patient who had just been declared dead by circulatory and respiratory criteria.
For decades, criteria known as donation after circulatory determination of death (DCD) has been used as a basis for setting in motion the organ donation process. The scenario typically begins when a lawful surrogate decision-maker refuses further life-sustaining therapy on behalf of a hopelessly ill, ventilator-dependent patient in the intensive care unit (ICU) and requests organ donation to follow the patient’s wishes.
ICU physicians then remove life support, which is timed to allow the transplant surgeons to be gowned and gloved in the OR and ready to operate. Once the patient’s circulation and respiration cease and five minutes elapses with no breathing or heartbeat, the patient is declared dead and taken to the OR for organ procurement.
A new approach called normothermic regional perfusion (NRP) has been added to DCD, raising ethical concerns because the technique requires mechanically restoring circulation in the patient who had just been declared dead by circulatory and respiratory criteria.
NRP uses extracorporeal membrane oxygenation (ECMO) to re-establish oxygenated blood circulating in the deceased donor to improve the health of organs before transplantation. Thoracic NRP involves surgically ligating aortic arch vessels that provide blood flow to the brain with the intent of preventing brain reperfusion and potential reanimation, but critics say there is no guarantee that some brain activity could result from collateral blow flow.
The overall goal of NRP—to increase the quality and number of organs available for transplants—is not being questioned. Instead of recovering just the kidneys and liver, for instance, restoring circulation in the deceased donor might also better keep the lungs and heart in good shape for transplant, and as many donor organs as possible are needed, given how many people are on transplant waiting lists.
Critics of the approach instead take issue with the fact that the new NRP technique seems to contradict the intent of DCD, a well-established principle that uses the cessation of circulation and respiration for a waiting period of about five minutes as the determinant of death.
Hospital neurotensivists are sometimes called in to help make that determination, whether it involves a potential donor or someone who dies separate from the organ donation process.
It is important to understand how DCD organ donors differ from brain-dead organ donors. Brain-dead organ donors are taken to the OR while their heart remains beating and they are ventilated so transplantable organs remain oxygenated and perfused. There is an urgency in DCD donation because, without any circulation or oxygenation, the organs will quickly deteriorate from warm ischemia. The use of ECMO and NRP mitigates that problem, making the donation similar to brain-dead donation.
James L. Bernat, MD, FAAN, professor of neurology, active emeritus, at Dartmouth Geisel School of Medicine, said circulatory determination of death, which is at the heart of the NRP ethical debate, is widely interpreted as meaning there is a proven permanent cessation of circulation and respiration. Because of that essential point, the restarting of circulation for the purposes of organ procurement retroactively contradicts the permanent cessation required for death determination in DCD, he said.
“Permanence is the accepted medical standard for determining death under the circulatory-respiratory criterion of death used in DCD,” said Dr. Bernat, who studies ethical issues on medicine.
In an analysis of ethical issues related to NRP, published in the November issue of Critical Care Medicine, Dr. Bernat and coauthors also noted that though major blood vessels leading to the brain are blocked when circulation and oxygenation are restored, the potential for collateral blood flow to the brain remains, which raises the possibility of restoring some degree of consciousness, and even pain perception, in the donor who had just minutes earlier been declared dead under DCD criteria.
Proponents of NRP—which may be referred to as thoraco-abdominal NRP (NRP-TA) in the literature—“state that death determination in NRP-TA is circulatory, not brain-based. Yet if brain perfusion and function continue, the patient remains alive,” the article said. “Circulatory death requires permanent cessation of circulation, irrespective of whether the circulation is spontaneous or induced and is independent of motive.”
The article cautioned that NRP should not be used until ethical, legal, and medical concerns and patient rights and informed consent issues have been fully evaluated.
“It should be the subject of vigorous debate,” said Dr. Bernat. He and other critics of NRP note, among other things, that protocols would need to be in place to monitor for collateral blood flow to the brain and activate a plan if perfusion or brain activity was detected.
The article noted that that NRP is not allowed in Canada and Australia, though Dr. Bernat said it is performed in some European countries. He said there are relatively few centers in the US that currently perform the procedure, though the number is growing. Some medical societies and organizations, including the American College of Physicians, have come out against the procedure, at least for now, saying more evaluation is needed. Some experts say the procedure should be limited to research, with protocols subject to approval by the institutional review board.
The Argument Against NPR
The journal article outlines “10 top reasons to defer normothermic perfusion at this time.” It argues that NRP may violate the so-called “dead-donor rule,” which provides the ethical foundation for organ donation and requires “that vital organs can only be donated after death and that death cannot be caused by organ donation.”
The article noted that brain flow may occur during the organ retrieval “despite the litigation of the principal arteries perfusing the brain due to collateral blood flow, anatomical variations, or technical procedures.”
“We know of no human data proving that ligation of the arch vessels completely excludes all brain blood flow; thus, it remains possible that NRP could restore enough brain blood flow to permit awareness of pain perception,” the article said. In Europe, guidelines and protocols call for brain monitoring during NRP and a plan to abort the procedure should signs of perfusion or brain activity occur, the article said.
Other concerns outlined in the article include whether the procedure may violate some donor’s religious or moral beliefs and how much information donors or their families should be given on the details of the procedure, including the possibility of brain perfusion. The article notes, for instance, that Roman Catholic Church doctrine supports organ donation from the “body of someone who is certainly dead.”
“Public trust in organ donation, which has been jeopardized by lack of transparency and the absence of truly informed discussion about NRP-TA with donor families and hospital, needs to be restored,” the article concluded.
Dr. Bernat said that as different medical groups add to the debate, he thinks it would be useful to have an organization like the prestigious National Academies of Sciences, Engineering, and Medicine weigh in. He said the Institute of Medicine was instrumental two decades ago in issuing a series of reports that provided the rationale and support for DCD that helped establish it in the organ donation process.
Given that the new approach to organ procurement challenges the notion of what it means to be declared dead, Dr. Bernat said “it’s important that there be a general understanding of what’s going on and a general agreement on what’s acceptable,” in the eyes of the many stakeholders, including doctors, potential organ recipients, organ donation organizations, patient advocates and others.
Michael Rubin, MD, FAAN, associate professor in the departments of neurology and neurological surgery and a clinical ethicist at UT Southwestern Medical Center, said the paper by Dr. Bernat and colleagues “does a great job” of outlining the debate of a difficult issue, and he urged doctors and other persons in the health care system to get informed about it. Dr. Rubin said his institution has not taken a position on NRP.
“Don’t just be for or against it until you first understand the challenging ethical issues involved,” he said. Dr. Rubin said that it is an admirable goal to try to increase the number of viable organs for transplant, and that the new technique may help ensure that not just the kidneys and liver are usable but also the heart and lungs.
At the same time, he said it’s equally important to make sure that the goal aligns with the accepted standards for determining death and the need to respect patients’ rights and wishes.
“The opponents of NRP claim that you aren’t respecting the dead donor rule,” Dr. Rubin said, noting that there are multiple aspects of the process open to debate.
Another argument against NRP noted in the paper is that the approach may arguably be “causing death by the intentional ligation of arch vessels prior to circulatory resuscitation.”
Dr. Rubin said the question of what would constitute informed consent on the procedure is another consideration, given there are complex and debatable ethical issues involved.
“Having this discussion with a family that is grieving and has limited clinical knowledge, do you think they could really understand what you are going to do during NRP? Many informed clinicians would need to read a review paper twice on the subject before being able to articulate the details of the process,” Dr. Rubin said. He said some patients or patient families who said yes to organ donation might have second thoughts if they knew the specific details of how the organ procurement would be done and were made aware of the ethical concerns that have been raised.
Flow Versus Function
Panayiotis Varelas, MD, PhD, chair and professor of neurology at Albany Medical Center, said he looked into the issues around NRP about 10 years ago when he was at another medical center and was considering it as a focus for research. The project did not get funded, but Dr. Varelas said the grant writing process enabled him to consider some of the unresolved issues.
He said whether there is some level of blood flow despite ligation is one issue, but the more important question is whether “there is enough flow to restore function.”
“If it is just low-level flow without function restoration, the patient may be still unconscious and not affected,” Dr. Varelas said. “But we don’t know if there is or isn’t enough flow to the brain to induce consciousness in general or in the specific patient due to anatomical variances,” he said.
Dr. Varelas, immediate past president of the Neurocritical Care Society, said he agreed with a point made in the article that brain monitoring should be made easily accessible in the OR and probably non-invasive—such as EEG, transcranial doppler, near-Infrared spectroscopy, CT perfusion, or a combination of those—to make sure there is no blood or brain activity as the procedure is underway. He said blood flow parameters used in critical care settings to assess the degree of brain function may be useful for comparison purposes. However, he added, “all of these monitors have limitations on what they measure in space or time.”
“You may need a neurologist or someone who is assessing these patients (organ donors) clinically at the bedside in the OR and is familiar with the interpretation of the data by these monitoring systems,” he said. “Before we get all these answers and place safety nets, I agree with the authors that NRP should not be standard of care and rather be investigational.”
Tamar Schiff, MD, who trained as an internal medicine physician and is doing post-doctoral research on medical ethics related to transplantation at NYU Langone Health, said the debate over NRP is complex and nuanced. “It is crucial to have that discourse,” she said, to make certain that protocols and policies around the use of NRP are ethical and build trust among everyone involved in the process.
“What is at stake is respecting a patient’s rights, their wishes to be a donor, and the possibility of lives saved by following their wishes,” she said.
Dr. Schiff does not see the issue of informed consent as a roadblock to adopting the procedure if done correctly. She said that donors or donor families “have the right to know necessary information without being overwhelmed with details,” noting that the legal language used for organ donation entails authorization for the procedure and not informed consent. “There is a duty to provide enough information that they are able to make an informed decision about the authorization.”