Balancing Preservation and Maximizing Utilization: A DCD Lung Procurement Strategy During Abdominal Normothermic Regional Perfusion

The United Kingdom's experience of controlled donation after circulatory death direct procurement of lungs with concomitant abdominal normothermic regional perfusion with an analysis of short-term outcomes.

Over the decade between 2003 and 2012, the UK has seen major changes in how organ donation and transplantation is delivered. The number of deceased organ donors has increased from 709 (12.0 per million population [pmp]) to 1,164 (18.3 pmp); this increase has been predominantly a result of an increase in donors after circulatory death (DCD) (from 1.1 pmp to 7.9 pmp) while the numbers of donors after brain death (DBD) has remained broadly stable (around 10.5 pmp). The donor population has become older (from 14% 60 years or over to 35%) and heavier (from 14% with body mass index >=30 kg/m2 to 23%). Despite these changes in demographic factors, the number of organs retrieved from DBD donors has risen from a mean of 3.6 to 4.0 per donor and for DCD donors from 2.2 to 2.6. The number of transplants in adults in 2012 was 2,709 (967 DBD, 708 DCD, and 1,034 living) for kidney alone, 246 pancreas (including 172 kidney and pancreas), 792 (611 DBD, 142 DCD, 36 living, and 3 domino) for liver, 136 for heart only, and 179 (145 DBD and 34 DCD) for lung only. Median waiting times to transplant for adult patients were 1,167, 339, 141, 293, and 311 days, respectively. The proportion of adult non-urgent registrants in 2009 (2007 for kidneys) who were removed from the waiting list or died awaiting a graft within 1 year was 3% for kidneys, 6% for pancreas, 19% for liver, 27% for heart, and 24% for lung. Outcomes after solid organ transplants are improving; for adult patients grafted between 2003 and 2005, 5-year graft survival for kidney is 84% (DBD), 87% (DCD), and 92% (living donor), for simultaneous kidney and pancreas 72%, and for pancreas alone 50% (DBD). Five-year patient survival for liver is 77% (DBD) and 68% (DCD), heart 67%, and lung 52% (DBD). Although rates of organ donation and transplantation have increased in the UK, this has been almost solely because of a rise in DCD donation. Although donor age and weight is increasing, graft survival has generally improved. Despite a recent fall in the number of patients on the transplant waiting list, there remains a significant gap between the need for transplantation and the number of organs available from deceased and living donors. The implementation of a new strategy following the recommendations of the Organ Donation Task Force in 2008 has had a major impact in bringing together clinicians involved in both organ donation and transplantation, and these changes and clinical enthusiasm have been instrumental in achieving success. With an emphasis on the need to increase the family consent rate for organ donation, which has failed to show any improvement over the last 5 years, a new UK strategy for organ donation and transplantation, introduced in 2013, will further increase organ transplantation in the UK.

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.

UK National DCD Heart Transplant Program - First Year Experience

In situ abdominal normothermic regional perfusion (A-NRP) has been used for liver transplantation (LT) with donation after circulatory death (DCD) liver grafts in Europe with excellent results; however, adoption of A-NRP in the United States has been lacking. The current report describes the implementation and results of a portable, self-reliant A-NRP program in the United States. Isolated abdominal in situ perfusion with an extracorporeal circuit was achieved through cannulation in the abdomen or femoral vessels and inflation of a supraceliac aortic balloon and cross-clamp. The Quantum Transport System by Spectrum was used. The decision to use livers for LT was made through an assessment of perfusate lactate (q15min). From May to November 2022, 14 A-NRP donation after circulatory death procurements were performed by our abdominal transplant team (N = 11 LT, N = 20 kidney transplants, and 1 kidney-pancreas transplant). The median A-NRP run time was 68 minutes. None of the LT recipients had post-reperfusion syndrome, nor were there any cases of primary nonfunction. All livers were functioning well at the time of maximal follow-up with zero cases of ischemic cholangiopathy. The current report describes the feasibility of a portable A-NRP program that can be used in the United States. Excellent short-term post-transplant results were achieved with both livers and kidneys procured from A-NRP.

Direct Procurement of Thoracic Organs Along with Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death

Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study.

Direct Lung Procurement with Ongoing Abdominal Normothermic Regional Perfusion

Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation. This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique. During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function. Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.

Abdominal normothermic regional perfusion (A-NRP) allows in-situ reperfusion and recovery of abdominal organs metabolism in donors after circulatory death (DCD). Besides improving liver transplantation outcomes, liver injury and function can be assessed during A-NRP. To refine liver viability assessment during A-NRP, prospectively collected data of controlled DCD donors managed at our Institution between October 2019 and May 2022 were retrospectively analyzed. Baseline characteristics, procedural variables and A-NRP parameters of donors whose liver was successfully transplanted were compared to those of donors whose liver was discarded. Twenty-seven donors were included and in 20 (74%) the liver was accepted (positive outcome). No differences between study groups were observed concerning baseline characteristics and warm ischemia times (WIT). Initial lactate levels were positively correlated with functional WIT (r2 = 0.4, p = 0.04), whereas transaminase levels were not. Blood flow during A-NRP was comparable, whereas oxygen consumption (VO2 ) was significantly higher in the positive outcome group after 1 h. Time courses of lactate, AST and ALT were significantly different between study groups (p < 0.001). Donors whose liver was accepted showed faster lactate clearance, a difference which was amplified by normalizing lactate clearance to oxygen delivery (DO2 ) and VO2 . Lactate clearance was correlated to transaminase levels and DO2 -normalized lactate clearance was the parameter best discriminating between study groups. DO2 -normalized lactate clearance may represent an element of liver viability assessment during A-NRP.

Lung Transplantation from Controlled and Uncontrolled Donation after Circulatory Death Donors. Single Centre Experience

This study investigates whether liver grafts donated after circulatory death (DCD) that are declined by the entire Eurotransplant region can be salvaged with abdominal normothermic regional perfusion (aNRP). aNRP is increasingly used for DCD liver grafts because it prevents typical complications. However, it is unclear whether aNRP is capable to rescue pretransplant declined liver grafts by providing the opportunity to test function during donation. Donor livers from DCD donors, declined by all centers in the Eurotransplant region, were included for this study. The comparator cohort included standard DCD livers and livers donated after brain death, transplanted in the same time period. After the withdrawal of life-sustaining treatment, 28 from the 43 donors had a circulatory death within 2 hours, in which case aNRP was initiated. Of these 28 cases, in 3 cases perfusion problems occurred, 5 grafts were declined based on liver assessment, and 20 liver grafts were transplanted. The main differences during aNRP between the transplanted grafts and the assessed nontransplanted grafts were alanine transaminase levels of 53U/L (34-68U/L) versus 367U/L (318-488U/L) ( P =0.001) and bile production in 100% versus 50% of the grafts ( P =0.024). The 12-month graft and patient survival were both 95%, similar to the comparator cohort. The incidence of ischemic cholangiopathy was 11%, which was lower than in the standard DCD cohort (18%). aNRP can safely select and thus is able to rescue DCD liver grafts that were deemed unsuitable for transplantation, while preventing primary nonfunction and minimizing ischemic cholangiopathy.

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia-reperfusion autotransplant model.

Commentary: Hope on the horizon: Heart transplantation with donation after circulatory death.

Normothermic Regional Perfusion: Ethical Issues in Thoracic Organ Donation