Controlled hypothermic storage may extend ischemic time for donor lungs

Key takeaways:

• Among 13 donor lungs in controlled hypothermic storage, the average total ischemic time was 17.3 hours.
• No recipients had grade 3 primary graft dysfunction at 72 hours after the procedure.

Storing donor lungs in a controlled hypothermic storage device with a total ischemic time of more than 15 hours “appears to be safe” in adult recipients, according to results published in Journal of Heart and Lung Transplantation.

“By safely extending the donor lung preservation window, we open a wide range of new possibilities for transplant professionals and increase the potential of reaching a broader spectrum of patients,” Laurens J. Ceulemans, MD, PhD, assistant professor of surgery and deputy head of the clinic in the department of thoracic surgery at University Hospitals Leuven in Belgium, told Healio. “By extending the out of body time for these sensitive organs, the potential to transplant more patients increases drastically.”

In a retrospective multicenter cohort analysis, Ceulemans and colleagues analyzed 13 adults (median age, 59 years; 8 men) who underwent bilateral lung transplantation with lungs preserved through an FDA-cleared controlled hypothermic storage device (LUNGguard, Paragonix Technologies) with a total ischemic time greater than 15 hours of the second lung to assess feasibility and safety of this type of device.

Lisa Anderson

“The Paragonix LUNGguard Donor Lung Preservation System creates a sterile and temperature-controlled environment for organs during transit between donor and recipient,” Lisa Anderson, PhD, CEO and cofounder of Paragonix Technologies, told Healio. “Using Bluetooth, temperatures are monitored throughout the journey via the Paragonix app and web portal, ensuring secure transport with predictable and measurable results, even in high-pressure clinical settings.”

According to Ceulemans, previous studies have established that higher ischemic times — more than 6 to 8 hours — for donor lungs are a risk factor for transplant outcomes.

“With increasing ischemic time, the risk of primary graft dysfunction, a serious complication that can occur after lung transplantation, also increases,” Ceulemans said. “However, this is based on practice where donor lungs are preserved in unregulated coolers of ice, where the temperature is closer to 0ºC, causing cellular freezing injury.”

Findings

Within the controlled hypothermic storage device, the average temperature was 7ºC, and the average total ischemic time of the second lung was 17.3 hours. The lowest total ischemic time was 15.07 hours (904 minutes), whereas the highest time was 22.03 hours (1,322 minutes).

During transplantation, eight patients received extracorporeal membrane oxygenation. The main reason for ECMO use was routine protocol (n = 5), followed by one patient each needing ECMO due to pulmonary arterial hypertension, hemodynamic collapse and first-lung syndrome.

After transplantation, four patients required ECMO either for lung edema (n = 2) or non-hypoxic cardiac reasons (n = 2).

Within 72 hours after transplantation, researchers observed four patients with grade 3 primary graft dysfunction (the most severe form of the condition), but this went down to zero at 72 hours after the operation.

“This is remarkable, given that the average ischemic time in this study was 17.3 hours, almost three times higher than what has historically been a risk factor,” Ceulemans said.

“Also encouraging is that the longest case in our analysis, which had an ischemic time of 22 hours, had excellent outcomes,” he added. “This is a game changer, as we are talking about almost a full day of preserving lungs using this new device, which opens a lot of new opportunities in the field of transplant.”

The average length of mechanical ventilation use following the procedure was 29 hours. Additionally, the average ICU stay was shorter than the average hospital stay (9 days vs. 30 days).

Researchers reassessed patients at 1 month using transbronchial biopsies (n = 11) and found two patients with grade A2 acute cellular rejection and one patient with grade B1R airway inflammation.

Of the total cohort, one patient died during the average follow-up period of 48 days. This death occurred on day 7 after malpositioning of an ECMO cannula, according to researchers.

Implications, future studies

Findings from this study open up new possibilities for both patients in need of a lung transplant and clinicians carrying out the operation, Ceulemans told Healio.

“For our patients, this means that donor lungs that previously would not have been evaluated due to their anticipated ischemic time given their geographic location, are now new opportunities to get transplanted sooner,” Ceulemans said.

“For clinicians, this also adds flexibility into our clinical practices, in the form of optimizing the time of transplant procedures based on staff availability and volume of other surgical procedures,” he continued. “This is important as it also has the potential to reduce the rates of burnout in the field of transplant, which is a growing area of focus professionally.”

Future studies will continue to evaluate the impact of controlled hypothermic storage, but Ceulemans said they will include more patients and transplant centers.

“From a basic science perspective, we are also investigating the underlying biological mechanisms that play a key role in controlled hypothermic preservation and its ability to safely extend ischemic times,” he added.

Ceulemans also said he is interested in identifying what the overall impact of adding flexibility could have on the team and logistics involved in the lung transplantation process.

Reference:

• New international study reports extension of the donor lung transplantation window. https://www.paragonixtechnologies.com/news/new-international-study-reports-extension-of-the-donor-lung-transplantation-window. Published March 12, 2024. Accessed March 14, 2024.