The impact of temperature ranges on liver machine perfusion and development of combined perfusion protocols

Abstract

Liver machine perfusion is being rapidly adopted in many parts of the world to improve transplant outcomes and increase the pool of donor grafts. Machine perfusion appears to be particularly effective in expanding the use of extended criteria donor grafts by reducing and/or assessing the impact of ischemia-reperfusion injury on post-transplant graft function. There are 3 main temperature categories for liver machine perfusion: normothermic (37 °C), hypothermic (2–10 °C), and subnormothermic (20–25 °C). Each mode has advantages, disadvantages, and distinct beneficial effects on liver graft function. It is currently unknown which temperature range of perfusion is most effective with respect to improving extended criteria donor graft performance. Because periods of static cold storage (0–4 °C) may still be required, it is also unclear how to transition liver grafts through these perfusion temperature zones in a way that minimizes ischemia-reperfusion injury related to abrupt shifts in temperature. Moreover, perfusate requirements differ for each perfusion modality and temperature range. In this review, we discuss evidence that gradual temperature transitions that combine perfusion approaches may further improve outcomes for extended criteria liver grafts. We highlight unique considerations at each temperature range, approaches to transition between temperature zones, and temperature-dependent perfusate constraints. We propose that as liver machine perfusion gains widespread clinical implementation, the next phase of machine perfusion development will entail the optimization of combined perfusion protocols that efficiently traverse temperature ranges.