Machine Perfusion in DCD Lung Transplantation: Advances in Preservation and Donor Pool Expansion

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

Infant heart transplant following donation after circulatory death using normothermic regional perfusion and distant transport, first reported case in North America.

Assessment of Cerebral Perfusion and Activity during Normothermic Regional Perfusion in a Porcine Model of Donation after Circulatory Death

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

Strategies in Organ Preservation-A New Golden Age.

POINT: Does Normothermic Regional Perfusion Violate the Ethical Principles Underlying Organ Procurement? Yes

In donation after circulatory death (DCD) organ transplantation, normothermic regional perfusion (NRP) restores oxygenated blood flow following cardiac arrest and reverses warm ischemia. Recently, NRP has also been used to help recover DCD hearts in addition to the abdominal organs. While DCD donation has increased the number of abdominal organs and lungs pool, it has not been able to increase the number of heart transplants, despite the fact that it has the potential to increase the number of heart transplants by 15-30%. Thoracoabdominal normothermic regional perfusion makes heart transplantation feasible and permits assessing heart function before an organ procurement without affecting the preservation of abdominal organs. NRP can be used in two ways for DCD donor heart transplants: normothermic regional perfusion followed by machine perfusion (NRP-MP) and normothermic regional perfusion followed by static cold storage (NRP-SCS). Normothermic regional perfusion is an emerging technology, a cost-effective alternative in donation after circulatory death (DCD), and will increase the pool of donors in heart transplantation.

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

The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner. Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs. NRP + NMP was used in scenarios with (1) long travel distances, (2) complicated transplant recipients, or (c) the need for additional liver graft recovery in "marginal" cases. Ischemic cholangiopathy was lower in the NRP alone group (0%) and the NRP + NMP group (0%) compared with the SCS group (16.8; P < 0.001 and P = 0.04, respectively). In addition, early allograft dysfunction, number of packed red blood cells transfused, and acute kidney injury were lower in the NRP alone and NRP + NMP groups compared with the SCS group. Graft survival was higher in cases where NRP was used than in cases where SCS was used ( P = 0.016). In all the cases where lactate remained elevated at the end of NRP (mean 8.2 ± 2.0), it ultimately normalized at the end of NMP (0.92 ± 0.56). The present study demonstrates lower rates of ischemic cholangiopathy and improved graft survival with NRP alone or NRP + NMP compared with SCS when using liver grafts from DCD donors. It also demonstrates that excellent outcomes can be achieved with sequential NRP + NMP in cases with prolonged travel distances, complicated recipients, or when there is a need for additional liver recovery in "marginal" cases.

Normothermic regional perfusion (NRP) and machine perfusion (MP) are variously used in many European centers to improve the outcomes after liver transplantation from donation after circulatory death (DCD). In Italy, a combination of NRP and subsequent MP has been used since the start of the activity. While NRP is mandatory for every DCD recovery, the subsequent use of MP is left to each center. We have designed a national survey to investigate practices and policies of these techniques. The questionnaire included 46 questions and was distributed to all the 21 Italian centers using an online form between June and July 2021. The overall response rate was 100%. A local NRP program for controlled Maastricht type 3 DCD was active in 11/21 (52.4%) centers. Organization and availability of personnel were perceived as the main difficulties in starting such a program. Between 2015 and 2020, 119 DCD livers were transplanted, with an overall utilization rate of 69.2%. Pump flow and gross aspect were considered the most reliable parameters in liver selection during NRP. Eight (72.7%) centers adopted subsequent hypothermic MP, 1 (9.1%) center normothermic MP, and the remaining 2 (18.2%) used both MP types. This first snapshot survey shows that NRP with subsequent MP is the most used protocol in Italy for DCD livers, although some heterogeneity exists in the type and purpose of MP between centers. Overall, this policy ensures a high utilization rate, considering the high risk of the DCD donor population in Italy.

Heart transplantation in donation after circulatory death (DCD) relies on warm perfusion using either in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion. In this study, we explore an alternative: oxygenated hypothermic machine perfusion (HMP) using a novel clinically applicable perfusion system, which is compared to NRP with static cold storage (SCS). In a porcine model, a DCD setting was simulated, followed by either (1) NRP and SCS (2) NRP and HMP with the XVIVO Heart preservation system or (3) direct procurement (DPP) and HMP. After preservation, heart transplantation (HTX) was performed. After weaning from cardiopulmonary bypass (CPB), biventricular function was assessed by admittance and Swan-Ganz catheters. Only transplanted hearts in the HMP groups showed significantly increased biventricular contractility (end-systole elastance) 2 hour post-CPB (left ventricle absolute change: NRP HMP: +1.8 ± 0.56, p=0.047, DPP HMP: +1.5 ± 0.43, p=0.045 and NRP SCS: +0.97 ± 0.47 mmHg/ml, p=0.21; right ventricle absolute change: NRP HMP: +0.50 ± 0.12, p=0.025, DPP HMP: +0.82 ± 0.23, p=0.039 and NRP SCS: +0.28 ± 0.26, p=0.52) while receiving significantly less dobutamine to maintain a cardiac output >4l/min compared to SCS. Diastolic function was preserved in all groups. Post-HTX, both HMP groups showed significantly less increments in plasma troponin T compared to SCS. In DCD HTX, increased biventricular contractility post-HTX was only observed in hearts preserved with HMP. In addition, the need for inotropic support and signs of myocardial damage were lower in the HMP groups. DCD HTX can be successfully performed using DPP followed by preservation with HMP in a preclinical setting.

In Italy, 20minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n=1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n=9, 26.5%), or severe macroangiopathy at back-table evaluation (n=1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

Use of normothermic regional perfusion (NRP) to recover donation after circulatory death (DCD) organs demonstrates increased heart utilization with favorable outcomes. Conversely, DCD lung allograft use when NRP was employed remains controversial. This is a contemporary analysis of DCD lung recipient outcomes in which NRP was used. Utilizing the STAR-OPTN database, all adult DCD lung recipients in the United States between January 1, 2020, and June 30, 2024 were identified. NRP use was defined if the time between donor death and aortic clamp time was greater than 30min. Recipient outcomes, including 30-, 60-, and 90-day mortality, grade-3 primary graft dysfunction (PGD), and postoperative length of stay were compared using multivariable logistic regression controlling for donor and recipient covariates. Survival analysis was performed using Cox proportional hazard modeling. Of 987 DCD lung transplants, 92 (9.4%) utilized NRP. There were no differences in recipient characteristics between direct recovery and NRP cohorts. No difference in 30-, 60-, or 90-day mortality, grade-3 PGD, or length of stay was found between cohorts. 12-month survival was equivalent. Outcomes between NRP lung recipients were equivalent to DCD direct recovery recipients. Thus, donor lungs may be considered for transplantation following NRP donation procedures.

Normothermic Regional Perfusion or Normothermic Machine Perfusion in Liver Transplantation from Donation after Circulatory Death: A First Comparative Study

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