Review article Normothermic perfusion and outcomes after liver transplantation Amelia J. Hessheimer ⁎, Francisco Riquelme, Yiliam Fundora-Suárez, Rocío García Pérez, Constantino Fondevila Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic, CIBERehd, IDIBAPS, University of Bar- celona, Spain abstract article info Available online xxxx Ischemia has been a persistent and largely unavoidable element in solid organ transplantation, contributing to graft deterioration and adverse post-transplant outcomes. In liver transplantation, where available organs arise with greater frequency from marginal donors (i.e., ones that are older, obese, and/or declared dead following car- diac arrest through the donation after circulatory death process), there is increasing interest using dynamic per- fusion strategies to limit, assess, and even reverse the adverse effects of ischemia in these grafts. Normothermic perfusion, in particular, is used to restore the flow of oxygen and other metabolic substrates at physiological tem- peratures. It may be used in liver transplantation both in situ following cardiac arrest in donation after circulatory death donors or during part or all of the ex situ preservation phase. This review article addresses issues relevant to use of normothermic perfusion strategies in liver transplantation, including technical and logistical aspects as- sociated with establishing and maintaining normothermic perfusion in its different forms and clinical outcomes that have been reported to date. © 2019 Elsevier Inc. All rights reserved. Keywords: Cold storage Controlled donation after circulatory death Normothermic machine perfusion Normothermic regional perfusion Uncontrolled donation after circulatory death Warm ischemia Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2. In situ normothermic regional perfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.1. Beneficial effects of NRP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.2. Technical aspects of performing NRP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.3. Ethical and legal issues associated with the use of NRP in DCD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2.4. Clinical outcomes following the application of NRP in DCD liver transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3. Ex situ hepatic Normothermic machine perfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.1. Beneficial effects of hepatic NMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.2. Technical aspects of performing hepatic NMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.3. Perfusate during hepatic NMP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.4. Clinical outcomes following the application of NMP in liver transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4. Alternative strategies to normothermic perfusion in “high-risk” livers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 5. Summary & future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Transplantation Reviews xxx (2019) xxx Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; BO 2 , Oxygen binding capacity of hemoglobin; cDCD, Controlled donation after circulatory death; CF, Continuous flow; CiO 2 , Inflow oxygen content; CIT, Cold ischemia time; CoO 2 , Outflow oxygen content; DBD, Donation after brain death; DCD, Donation after circulatory death; DO 2 , Oxygen delivery; DWIT, Donor warm ischemia time; EAD, Early allograft dysfunction; HAF, Hepatic artery flow; HAP, Hepatic arterial pressure; [Hb], Concentration of effective hemoglobin; HOPE, Hypothermic oxygenated machine perfusion; IFLT, Ischemia-free liver transplantation; IQR, Interquartile range; ITBL, Ischemic type biliary lesions; NMP, Normothermic machine perfusion; NR, Not reported; NRP, Normothermic regional perfusion; PF, Pulsatile flow; PiO 2 , Inflow partial pressure of oxygen; PNF, Primary non-function; PoO 2 , Outflow partial pressure of oxygen; PVP, Portal venous pressure; RA, Rescue allocation; SA, Standard allocation; SCS, Static cold storage; SiO 2 , Inflow oxygen saturation; SoO 2 , Outflow oxygen saturation; SRR, Super rapid recovery; VO 2 , Oxygen extraction; uDCD, Uncontrolled donation after circulatory death. ⁎ Corresponding author at: Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Digestive & Metabolic Disease Institute (ICMDM), Hospital Clínic i Provincial, C/ Villarroel 170, 08036 Barcelona, Spain. E-mail address: ajhesshe@clinic.cat (A.J. Hessheimer). YTRRE-00504; No of Pages 9 https://doi.org/10.1016/j.trre.2019.06.001 0955-470X/© 2019 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Transplantation Reviews journal homepage: www.elsevier.com/locate/trre Please cite this article as: A.J. Hessheimer, F. Riquelme, Y. Fundora-Suárez, et al., Normothermic perfusion and outcomes after liver transplantation, Transplantation Reviews, https://doi.org/10.1016/j.trre.2019.06.001