Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation

Highlights

• In cDCD livers, postmortem NRP reduces biliary complications, in particular ITBL.

• Postmortem NRP helps improve cDCD liver graft survival.

• Use of postmortem NRP facilitates successful transplantation of older cDCD livers.

Background & Aims

Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD.

Methods

This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes.

Results

During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45–65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06–0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02–0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20–0.78; p = 0.008).

Conclusions

The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age.

Lay summary

This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors.

Introduction

Donation after circulatory death (DCD) donors, who are declared dead following cardiorespiratory arrest, are an increasingly common source of organs. The period of donor warm ischaemia surrounding arrest can damage the quality of organs in general and the liver in particular, because biliary cells are exquisitely susceptible to warm ischaemia.¹ Thus, initial experiences with DCD liver transplantation described high rates of graft dysfunction and non-function and ischaemic type biliary lesions (ITBL). Although complication rates have improved with experience, the rate of post-transplant ITBL remains higher among recipients of DCD grafts vs. those receiving donation after brain death (DBD) grafts (16% vs. 3%, according to 2 meta-analyses[2], [3]). Development of ITBL leads to repeat biliary procedures and hospitalisations; up to 70% of patients with ITBL either require retransplantation or die.⁴

Although DCD donors are typically classified among 4 categories depending on conditions surrounding cardiac arrest,⁵ category III controlled DCD (cDCD) donors are the most frequent source of DCD organs for transplantation globally. These are ventilated patients with a devastating brain injury that does not meet the criteria for brain death; the decision is made to withdraw life-sustaining therapy because it is no longer beneficial. Experience gained over the years has allowed for better donor and graft selection to the point that outcomes are comparable to those achieved with livers arising through donation after brain death.[6], [7] However, achieving these results has come at the cost of high liver discard rates.⁸

In contrast to most of the Western world, the initial Spanish experience with DCD was with donors suffering sudden out-of-hospital cardiac arrest who were unable to be resuscitated after repeated attempts. Category II uncontrolled DCD (uDCD) donors are declared dead in the hospital, and femoral vasculature is cannulated to establish normothermic regional perfusion (NRP) to reperfuse and reoxygenate abdominal organs while donor evaluation and preparations for organ recovery are undertaken.[9], [10] Using NRP, even livers with extensive prerecovery warm ischaemic periods of up to 2.5 h have been successfully transplanted, with biliary complication and graft survival rates comparable to those seen using cDCD livers exposed to considerably shorter periods of warm ischaemia.[9], [10], [11], [12], [13]

In 2009, cDCD was piloted in Spain, and a legal and ethical framework for its widespread practice was established in 2012.[14], [15] Unlike the rest of the world, where reports of the use of NRP in cDCD have been anecdotal,[16], [17] approximately 25% of all cDCD transplants and 50% of all cDCD liver transplants performed in Spain have included postmortem NRP. Here, we report an analysis of the first years of the Spanish experience with cDCD liver transplantation, in particular regarding the hypothesis that the use of postmortem NRP improves organ utilisation rates and post-transplantation outcomes.