Controlled oxygenated rewarming as novel end-ischemic therapy for cold stored liver grafts. A randomized controlled trial.
Minor, T., et alClinical and translational science 2022 [record in progress].
Aims
This study aimed to investigate whether reperfusion injury of cold stored liver grafts could be mitigated by controlled oxygenated rewarming using ex vivo machine perfusion prior to reperfusion.
Interventions
Participants were randomised to either the conventional static cold storage (SCS) group or the controlled oxygenated rewarming (COR) group.
Participants
40 liver transplant recipients.
Outcomes
The primary outcome was serum peak value of aspartate aminotransferase (AST). The secondary outcomes included maximal liver function capacity, graft survival, early allograft dysfunction (EAD), intensive care unit (ICU) stay, and post-operative surgical complications.
Follow-up
3 months
CET Conclusions
This is a single centre feasibility study, albeit conducted in a randomised controlled methodology. It was designed to provide a foundation for a large, multicentre phase II study. However, this paper presents some very interesting and noteworthy information. The study was single-blinded, and outcomes were predominately objective. Extended criteria livers were included, in order to maximise the potential benefits. Randomisation was only done after the decision to transplant an included organ, and done using an independently-run, web-based system. Livers were randomised to standard care (static cold storage) or to the intervention of Controlled Oxygenated Re-warming (COR) using the Liver Assist (Organ Assist, The Netherlands). 40 livers were included (20 in each arm), and all received the intended therapy with no cross-overs or exclusions from analysis. The primary outcome was serum peak AST in the first 3 days. This was not statistically different between the 2 arms, despite a 45% lower mean peak for COR. COR was associated with a significant improvement in day 1 LiMAx test, factor 5 and bilirubin levels. There were no significant differences in INR, early allograft dysfunction or other secondary outcomes, such as ICU stay, hospital stay or 3 month graft survival. Taking steps forward from the experimental studies that underpin this trial, the current paper makes a very good case for a larger clinical trial in liver transplantation. The use of 60-minute COR in the transplant centre is logistically much less challenging than transporting perfusion devices to the retrieval site, and the continuous monitoring of a perfused liver in transit back.
Data analysis
Strict intention-to-treat analysis
Trial registration
ISRCTN – 94691167