Controversial Donor-Organ Retrieval Technology Highlighted on NPR

It's called normothermic regional perfusion ("NRP") and was the subject of a useful story on National Public Radio ("NPR") this morning.

There are two ways to be dead in this country: dead according to neurological criteria ("brain death" -- an increasingly controversial concept) and dead according to cardio-pulmonary criteria. According to the latter, death occurs when there is an irreversible cessation of all cardiac and pulmonary function. This is the standard adopted in the Uniform Determination of Death Act and adopted by statute, regulation, or judicial decision in all 50 states and the District of Columbia. Pulselessness and lack of spontaneous respiration: They have signalled death for eons. 

The development of CPR sharpened the concept of cardiopulmonary death. If CPR (or, in a clinical setting, Advanced Cardiac Life Support) fails to reëstablish a pulse, irreversibility is established and death can be declared.

A procedure known as circulatory determination of death ("DCD") allows this sequence of events to occur in an operating room. It begins when ventilator support is withdrawn from a prospective organ donor. The surgical team waits for up to 90 minutes (times may vary by institution) for the cessation of cardiac and pulmonary function. If that occurs, the clock starts clicking (typically for 5 minutes, longer at some institutions) to see if the patient experiences autoresuscitation. If not, irreversibility is deemed to be established, the patient can be declared dead, and the organ retrieval may begin.

DCD organ donations were originally controversial -- including a Cleveland prosecutor's 1997 assertion that DCD may be tantamount to killing patients for their organs (NY Times; may be behind paywall) -- and are still opposed by a minority of experts. On the other hand, DCD is actively promoted by UNOS and is supported by a majority of ethics commentators.

NRP takes DCD one step further and arguably pushes beyond the outer limits of irreversibility. There are various forms of NRP, but most appear to involve cutting off any possible blood flow to the brain and reestablishing circulation by connecting the donor to ECMO (Extra-Corporeal Membrane Oxygenation). At least one version of this process may result in restarting the donor's heart. You can see the possible conflict with the requirement of irreversibility. 

The NPR story is a good introduction to the controversy. For a deeper dive, the American Journal of Bioethics ("AJOB") devoted an entire issue to NRP. (This, too, may be behind a paywall.) If AJOB is unavailable, run this search in NIH's PubMed service. Today it pulled up 69 articles, including some that are available for free.

House & Senate Pass Bipartisan Bill to Reform Organ Procurement Transplantation Network

Last Thursday evening (7/27), in a rare bipartisan move, the Senate passed H.R. 2544 (entitled the “Securing the U.S. Organ Procurement and Transplantation Network Act”) without change, and the bill is now on President Biden's desk for his signature. The bill amends 42 U.S.C. § 274 for essentially one purpose.

Federal law currently authorizes the Secretary of HHS to contract with "a private nonprofit entity that has an expertise in organ procurement and transplantation" to operate the OPTN. Since the creation of the Network in 1984, that entity has been UNOS, a Virginia nonprofit. There has been growing unhappiness with UNOS's operation of the network, which led Congress to pass H.R. 2544. It strikes the language quoted above and replaces it with language that says the OPTN "shall . . . be operated through awards to public or private entities made by the Secretary." 

One group -- representing nephrologists and transplant professionals who have had to to work under UNOS's rules for nearly 40 years -- seem pretty happy:

"The American Society of Nephrology (ASN) is grateful for steadfast, bipartisan leadership on behalf of transplant patients demonstrated by tonight's passage of the Securing the U.S. OPTN Act," said Michelle A. Josephson, MD, FASN, ASN President. "The United States transplant system was put into place nearly 40 years ago. As the transplant field has changed over time, Congress' establishment of a modern policy infrastructure to support transplant care means that our field can continue to grow, meeting the needs of the thousands of Americans who would benefit from a kidney transplant."

Roll Call has done some interesting background reporting (7/28/2023) on the concerns that led to the passage of this bill:

 A Senate Finance Committee investigation released last year found that hundreds of people have developed diseases from transplanted organs, and 70 people died between 2008 and 2015 from those illnesses.

The committee argued that such mistakes were allowed to happen because of UNOS’s lack of oversight of organ procurement organizations

A record-high 21.3 percent of procured kidneys were not transplanted in 2020, according to the Scientific Registry of Transplant Recipients. 

More than 100,000 Americans are currently waiting for an organ — mainly kidneys — and an estimated 17 people die each day on the waiting list.

I'm not 100% convinced that UNOS was responsible for all of these lapses. We'll see if bringing in a new company, based on a competitive bid process, makes a difference.

UNOS's Dispute with Contractor Threatens Supply of Organs to 63 Transplant Centers

 You read that right. And the disruption could have happened as soon as today,  according to an article in the Washington Post (7/3; if you can't get past the paywall, try Newsmax). In a late-breaking development on the 4th, the corporation that runs the nationwide transplantation system extended the deadline for an agreement to end its dispute with a major player for two weeks, to July 19. Just to cut to the chase: The national organ transplantation system is too important for a couple of key players to be playing chicken.

UNOS is the United Network for Organ Sharing. It's a Virginia nonprofit corporation that runs the national organ transplantation system under an exclusive contract with the federal Health Resources and Services Administration (HRSA), an agency under the umbrella of HHS. 

It's a tough gig. Managing the supply of transplantable organs is a life-or-death proposition for the more than 104,000 people on wait lists, 19-22 of whom die each day without a match. And transplantation is big business for the hospitals that run transplant centers and obviously an important source of income for the health care professionals who provides the services. Keeping the system running smoothly is a high-stakes undertaking with lots of stakeholders.

Speaking of services, the day-to-day on-the-ground business of identifying donors, evaluating the suitability of potential donor organs, and transporting organs to waiting recipients is mostly managed by 56 Organ Procurement Organizations (OPOs), local or regional nonprofits that keep the supply chain moving. Buckeye Transplant Services competes with OPOs for basically the same set of services, which they provide to transplant centers all over the country.

In order for Buckeye to do all this, it needs access to UNOS's data. To that end, it has apparently developed a bot of some kind that scrapes UNOS's database, picking up -- according to UNOS -- data that Buckeye doesn't need to carry out its contractual duties for UNOS. UNOS is not happy and wants Buckeye to start playing by its rules. Buckeye is not happy and sued UNOS on July 3 in federal court in Richmond, home based for UNOS. 

If Buckeye loses access to the data maintained by UNOS, it's out of business until access is restored. Much if not all of the burden of screening and evaluating donations will fall to transplant centers themselves, and they are pretty busy trying to keep patients (donors, recipients) alive. It's a mess.

On March 22, HRSA announced a modernization initiative. According the WaPo article above, Congressional Republicans and Democrats seem supportive of reforms. Sen. Grassley (R-Iowa) was pretty emphatic about the need for change: "Thousands of patients are dying every year and billions of taxpayer dollars are wasted because of gross mismanagement. The system is rife with fraud, waste and abuse, corruption, even criminality.”

Cryopreservation of whole organs may be a transplantation game-changer

Human organs, once removed from their owner's body, are very fragile things. As reported in Science (News, June 21, 2023), this poses a problem for transplant medicine:

The rapid decay of organs is one of the biggest problems bedeviling organ transplants for people. From the moment a human heart or lung is disconnected from a donor, doctors have 4 to 6 hours to get it hooked up to a new patient’s blood supply before it is irretrievably damaged. For a liver, the window is 8 to 12 hours. For a kidney it’s about 1 day.

The effort to cut the warm ischemic time between organ removal and successful implantation has transformed the legal landscape for organ transplantation. 

• It was one of the reasons for the development of "brain death" in 1968 -- waiting around for a patient with no brain function to lose all cardiopulmonary function often led to the loss of organs that start to deteriorate while still in the patient's body. It may not have been "a driving force" behind the 1968 recommendation of a Harvard Ad Hoc Committee, but it surely benefited the transplant industry and certainly escaped nobody's attention at the time. The 1968 recommendation was crucial to the development of the Uniform Determination of Death Act.
• It was the reason for widespread adoption of UNOS policy and hospital protocols for "Donation After Cardiac [or "Cardiopulmonary" or "Cardiac and Circulatory" or "Controlled Cardiocirculatory"] Death" ("DCD" or "DCCD"). Careful timing and choreography of the removal of life support, determination of death, and organ retrieval can reduce warm ischemic time dramatically. No new law was needed to make this legal, but DCD provoked a vigorous debate about a practice that involved inducing death, withholding life-saving and life-supporting measures, and deeming a patient to be dead while autoresuscitation might still be possible (multiple citations are available on PubMed; here's one).

The latest wrinkle in technology's advance to the frontiers of medicine and law was reported in a Science news report this past week (citation above). A team at the University of Minnesota took a kidney out of white lab rat, stuck it into a deep freeze (-150ºC), and then successfully transplanted the organ into a recipient rat. Within minutes, the once-frozen kidney began producing urine -- according to the young surgeon who produced this result, "First successful transplant of vitrified, nanowarmed rat kidney."

Although still a ways off, the implications of this breakthrough process are vast. Organs that cannot be used immediately -- say, after death has been declared but a donor match cannot be found -- can be frozen for future use. Stockpiling frozen organs could put a real dent in the waiting times experienced by potential recipients on the various organ waiting lists. 

The process won't be quite as straightforward with larger human organs, which take longer to freeze and are harder to squeeze water out of than tiny rat livers. But we now know that it can be done in small mammals, and you can be sure efforts are under way (or soon will be) to scale up to human organs. Stay tuned.

New study endorses harvesting hearts after declaration of cardiopulmonary death

There's an Associated Press article in this morning's Dallas Morning News describing a multicenter study involving the transplantation of hearts taken out of donors who were not brain dead but had been declared dead after irreversible cessation of cardiac and circulatory function (DCD/DCCD).

Certain solid organs have been transplanted after DCD for decades. The protocol for harvesting involves the following steps:

• moving the patient to the operating room (usually from an ICU);
• stopping all life-supporting measures;
• waiting for a fixed period of time for the heart to stop beating (usually 60-90 minutes);
• if the heart stops, waiting another period of time (usually 5 minutes) to see if the heart will autoresuscitate;
• if autoresuscitation doesn't occur, death is declared and organ harvesting (usually kidneys, liver, and pancreas).

The DCD procedure was designed to shorten the warm ischemic time from when cardiopulmonary function ceases and the harvested organ can be restored to function in the recipient's body. Even with that innovation, though, hearts were not considered for transplantation because of their extreme fragility.

As described by the AP, however, the results of a multicenter study over a number of years establishes that the six-month survival rate after DCD (94%) was slightly better that the survival rate for heart transplants after brain death (90%). So what has changed? As reported by the AP:

Now doctors can remove those hearts and put them in a machine [a "heart-in-a-box" device invented by TransMedics, the sponsor of the study] that “reanimates” them, pumping through blood and nutrients as they’re transported –- and demonstrating if they work OK before the planned transplant.

I am all for increasing the supply of donor hearts, and this is a very interesting development.  I am wondering, however, how to square the transplantation of a viable heart with the cardiopulmonary criterion of death. The statutory standard of "irreversible cessation of all cardiopulmonary function" will  now need to be understood as “irreversible in the donor’s body but not necessarily in the body of the recipient of the heart.” That begs the question, which has applied to DCD from the beginning, why has cardiopulmonary ceased (because we took away the donor’s life support) and why is the cessation irreversible (because we didn’t try to reverse it). Once we actually try to restore cardiac function (“reanimating” the heart in a “heart-in-a-box” device), some hearts are restored and do at least as well in the recipient’s body as a heart from a brain-dead patient. 

Are we comfortable with this slightly altered version of "irreversible cessation"? Should we be? The so-called "dead donor rule" (DDR) forbids killing a patient for organs or removing organs needed to sustain life from a living patient. So far, we have avoided the slippery slope of removing organs from patients who are almost dead or "as good as dead." How certain are we that this new approach to DCD heart transplantation satisfies the DDR? 

Everything You Wanted to Know About Liver and Lung Transplant Allocation Policies But Were Afraid to Ask

The Government Accountability Office has issued a detailed letter report on recent changes to the allocation policies for these two organs. Over the years, this has been a difficult subject to teach in my Bioethics & Law course. I hope this will be a good resource for anyone seeming an overview of the manner in which these scarce resources are allocated, as well as a brief summary of the responsibilities of HHS, HRSA, and UNOS in maintaining the national Oran Procurement and Transplantation Network.