To the Organ Transplantation Community,
Mainstream media has once again reported on news relevant to the transplantation community but seems to have left out, perhaps unintentionally, a critical aspect of the story. Recently, NPR covered an organ retrieval procedure that remains scarcely used in the U.S. In the article and radio piece titled “Doctors Try a Controversial Technique to Reduce the Transplant Organ Shortage,” NPR discussed the use of normothermic regional perfusion (NRP) to recover a liver and two kidneys by Dr. Marty Sellers of Tennessee Donor Services. While NPR labeled the procedure as “controversial,” Dr. Sellers described it as “revolutionary.”
So, what exactly is NRP? Although it is not yet widely adopted in the U.S., NRP was first used in Spain in 2002 and is currently employed in several European countries, including France, the Netherlands, and the UK. In Italy, NRP is mandated as the only method for organ recovery following circulatory death (DCD), as it provides additional time to assess the viability of organs for transplantation. To address potential ethical concerns—dubbed “the controversy” by NPR—most countries, including the U.S., require surgeons to wait five minutes before initiating organ retrieval. The ethical question revolves around restarting circulation after the patient has been declared dead due to circulatory cessation. This raises concerns about inadvertently reactivating brain neurons and when exactly the patient is considered “officially” dead. For example, in Italy, the mandated waiting time is 20 minutes. During this waiting period, organs lose viability with every passing second without circulating blood, and much can happen in those 5 to 20 minutes of “no-touch” time.
Dr. Sellers’ use of the term “revolutionary” reflects the belief that, while NRP is still limited in the U.S., it has the potential to increase the number of available organs for transplantation, benefitting many patients on the waiting list. NRP allows more time to evaluate organ quality and provides a broader window for organ allocation. This extended time could lead to a higher utilization rate of organs, thus reducing the waitlist. The transplant community largely supports expanding the use of NRP for DCD organs over Standard Rapid Recovery (SRR), but it’s important to recognize NRP’s limitations.
During NRP, in situ perfusion is typically conducted using an Extracorporeal Membrane Oxygenation (ECMO) system. However, once the NRP procedure is complete, the organ is transported either under perfusion without oxygen (ischemic perfusion) or in Standard Cold Storage to the recipient center. Both approaches do not completely mitigate the negative effects arising from the lack of oxygen. This is where Hypothermic Oxygenated Perfusion (HOPE) comes into play.
HOPE cools the organs to temperatures between 4 and 12°C, dramatically lowering their metabolic rate to roughly 10% of normal. The system also delivers oxygenated perfusion to the dormant organ as it awaits transplantation. This oxygen-rich environment revitalizes the mitochondria—the cell’s powerhouse—priming the cells before transplantation and potentially lowering the risk of reperfusion injury, a major contributor to post transplant complications.
So, what’s the takeaway on NRP? While NRP shows great promise, it is not sufficient on its own to ensure optimal organ viability when the risk profile of the organ increases. The combination of abdominal NRP with end ischemic HOPE may provide the best chance for preserving organ quality during transport and transplantation. Together, these techniques could offer a synergistic approach to improving transplant outcomes.
Stay tuned for further research milestones, as well my perspective on organ preservation news of relevance to us all.
Looking forward to seeing you in Istanbul at TTS 2024! Meanwhile, enjoy what remains of the summer.
Again, I welcome hearing from you regarding what would be valuable in these updates moving forward. You can reach out to me at BTLBlog@b2ll.com.
Don Webber
President and Chief Executive Officer
Bridge to Life Ltd.
VitaSmart™ is CE marked and available for sale in several markets outside of the United States. VitaSmart™ is not approved for sale in the U.S. The company successfully completed its pivotal, multicenter, randomized clinical study in the US in 2023 and expects to submit for approval to FDA in Q125.
References
Pr. Corinne Antoine, et al, Direction Générale Médicale et Scientifique, Agence de la biomédecine, Saint Denis, France; Liver Transplantation from Controlled Donors after Circulatory Death using Normothermic Regional Perfusion: Initial Experience of the French Protocol; Liver Transplantation, Volume 6, Issue 11, November 2020.
Riccardo De Carlis, MD, et al, Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; How to preserve liver grafts from circulatory death with long warm ischemia? A retrospective Italian cohort study with normothermic regional perfusion and hypothermic oxygenated perfusion; Transplantation, Volume 105, Issue 11, November 2021.
Amelia J. Hessheimer, et al, General & Digestive Surgery, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain; General & Digestive Surgery Service, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain; IDIBAPS, CIBERehd, University of Barcelona, Spain; Abdominal Normothermic Regional Perfusion in DCD Transplantation: And Risk for Loss; American Journal of Transplantation, Volume 22, Issue 4, April 2022.
Xavier Muller, MD, et al, Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, University of Lyon I, Lyon, France; Hypothermic Oxygenated Perfusion Versus Normothermic Regional Perfusion in Liver Transplantation From Controlled Donation After Circulatory Death; Annals of Surgery, Volume 272, Number 5, November 2020.
