Normothermic organ preservation may be a boon for transplant graft survival

Paul Basilio, MDLinx | April 21, 2017

Physicians at the University of Alabama at Birmingham (UAB) Department of Surgery have successfully transplanted a cadaver liver that was preserved at body temperature following donation. This technique allows surgeons to watch the liver produce bile before the transplantation surgery.

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The technique has been successful in Europe, and it appears to offer a marked improvement in the quality of the transplanted organ. Image courtesy of UAB News.

The surgery was part of a clinical trial that evaluated a normothermic machine perfusion technique developed by OrganOx.

During the procedure, the donated liver is placed in the normothermic machine, where it is pumped with warm, oxygenated blood and nutrition. It is kept at, or just below, body temperature for up to 24 hours prior to transplantation.

Devin Eckhoff, MD, Director of the UAB Division of Transplantation, noted that the technique has been successful in Europe, and it appears to offer a marked improvement in the quality of the transplanted organ.

“Because there is a large shortage of livers available for transplantation, the transplant community is continuing to push the boundaries to increase the availability of organs,” Dr. Eckhoff said. “These normothermic machines enable us to preserve the liver under near perfect physiological conditions, as opposed to the usual hypothermic conditions in which the organ is typically transplanted. With the normothermic preservation, the liver maintains all aspects of graft function throughout the preservation process; it allows for pre-transplant assessment of organ function and thereby viability to predict suitability for implantation and the delivery of potential agents such as stem cells to further improve the tissue damage caused when blood supply returns to the tissue after a lack of oxygen.”

In addition to the UAB School of Medicine and UAB Hospital, 14 other transplant centers in the US are involved in the study. Similar efforts have focused on overcoming the limitations of cold storage, the current standard for organ preservation.

“I’m doing fantastic, just wonderful, and I’m already back home doing everything I did before my transplant,” said Lana Wiggins, the 63-year-old recipient and long-time advocate for organ donation. “It’s ironic that I would be the one in need after all of the years of talking about organ donation with patients or patient families. Even before I was a donor coordinator, I believed in organ donation. I signed up when I was in my early 20s. I’m beyond grateful to have received this gift now.”

Normothermic advantages

Cold storage of donor organs offers simplicity, portability, and affordability, even though the process has a limited duration of preservation. However, marginal organs have been increasingly used in recent years due to the limited number of livers available for transplantation. The limitations of static cold storage have been a major factor that influence patient and graft survival rates.

The normothermic machine is the first completely automated liver perfusion device of its kind. It functions in a similar manner as a greenhouse, and it is constructed from the basic components of conventional cardiopulmonary machines, such as basic roller pumps, oxygenators, and heat exchangers.

“This machine can really help in a number of ways,” said Stephen Gray, MD, liver transplant surgeon and Director of UAB’s Abdominal Transplant Fellowship. “The fact that the machine can perfuse the organ with oxygenated red blood cells at normal body temperature—just as it would be inside the body—and that we can observe it making bile before transplant is just an extraordinary feat, and a significant benefit to us as surgeons and our patients. With these normothermic machine-perfused livers, we can assess whether it is going to work before we transplant it into the patient, whereas we typically do not know if the liver will work until the transplant takes place.”

The advent of normothermic organ preservation could potentially mean that livers could be shipped from coast to coast in the US, which would eliminate geographic limitations of transplantation for those in need. Overnight transplantations would also decrease if the donor organ can be kept viable for up to 24 hours.

“You can use a liver for transplant that was placed in cold storage for up to 12 hours; but cooling the organ to ice temperature to slow down its metabolism does not stop it from deteriorating, usually within the first six to eight hours,” said Dr. Gray. “And if the organ is damaged in some way, perhaps by being deprived of oxygen, the combined effect can be catastrophic for the organ. The perfused machine would allow us to extend the storage time and only enhance the viability of the liver.”

Dr. Eckhoff added that preliminary evidence in Europe has shown normothermic organ preservation is superior to static cold storage.

“If this is as successful as it appears it can be, it will be a significant benefit to those in need of liver transplantation,” he said. “About 60,000 patients die of liver disease annually in the United States, and many of them could theoretically have been treated with a liver transplant. This device has the potential to change that radically by enabling us to transplant many organs that are simply unusable with current techniques.”

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