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Background: Recent trials in liver machine perfusion (MP) have revealed unique challenges beyond those seen in most clinical studies. Correct trial design and interpretation of data are essential to avoid drawing conclusions that may compromise patient safety and increase costs., Methods: The International Liver Transplantation Society, through the Special Interest Group "DCD, Preservation and Machine Perfusion," established a working group to write consensus statements and guidelines on how future clinical trials in liver perfusion should be designed, with particular focus on relevant clinical endpoints and how different techniques of liver perfusion should be compared. Protocols, abstracts, and full published papers of clinical trials using liver MP were reviewed. The use of a simplified Grading of Recommendations Assessment, Development, and Evaluation working group (GRADE) system was attempted to assess the level of evidence. The working group presented its conclusions at the International Liver Transplantation Society consensus conference "DCD, Liver Preservation, and Machine Perfusion" held in Venice, Italy, on January 31, 2020., Results: Twelve recommendations were proposed with the main conclusions that clinical trials investigating the effect of MP in liver transplantation should (1) make the protocol publicly available before the start of the trial, (2) be adequately powered, and (3) carefully consider timing of randomization in function of the primary outcome., Conclusions: There are issues with using accepted primary outcomes of liver transplantation trials in the context of MP trials, and no ideal endpoint could be defined by the working group. The setup of an international registry was considered vital by the working group., Competing Interests: PF is a co-founder, Chief Medical Officer, and stock-holder in OrganOx Ltd, a spin-out company from the University of Oxford established to develop machine perfusion technology. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ischemia reperfusion injury (IRI) results in damage to local and remote organs. Remote ischemic preconditioning (RIPC) is a strategy to protect against IRI by inducing a prior brief period(s) of IRI to an organ remote from that undergoing sustained injury. RIPC has been shown to protect organs against IRI; however, the protocols and mechanisms for RIPC are unclear. For this review, a Medline/Pubmed search (January 1985 to January 2007) was conducted and all relevant articles were included. RIPC protocols are organ and species specific and both humoral and neurogenic pathways are involved in triggering intracellular signal pathways for protection.

Background: During orthotopic liver transplantation (OLT) for acute liver failure (ALF), some patients develop acute increases in intracranial pressure (ICP). The authors tested the hypothesis that increases in ICP during OLT for ALF can be prevented by moderate hypothermia., Methods: Sixteen patients with ALF undergoing OLT were studied. Depending on the measured ICP before OLT, the patients were divided into three groups as follows: group I (n=6), did not require treatment for increased ICP (ICP <15 mm Hg); group II (n=5), had episodes of increased ICP that were controlled by conventional treatment (group I and group II patients were maintained normothermic during OLT); and group III (n=5), had uncontrolled increased ICP before OLT for which they had been cooled and underwent OLT with the median core temperature of 33.4 degrees C (92.1 degrees F) (range, 31.9 degrees -33.8 degrees C [89.4 degrees -92.8 degrees F]), Results: There was a significant increase in ICP during the dissection and reperfusion phases in the patients in groups I and II (P=0.004 and P=0.006, respectively). Patients in group III had no significant increase in ICP during the OLT. The increase in ICP in groups I and II was associated with an increase in cerebral blood flow, which was not observed in group III. The increase in ICP was corrected during the anhepatic phase of the operation. There was no difference in the requirement of transfusions or incidence of postoperative infection between the groups., Conclusions: Moderate hypothermia is safe and successfully prevents increases in ICP during OLT for ALF.

Primary graft dysfunction occurs in up to 10% of liver transplant recipients and is the major reason for early mortality and retransplantation. The conventionally used markers of early graft function--i.e., correction of acidosis, glucose requirement, consumption of potassium, serum alanine transaminase (ALT), prothrombin time (PT), bile flow, resolution of encephalopathy and haemodynamic instability can be very misleading as they are dependent on numerous other factors. The aim of this study was to assess the use of indocyanine green clearance (ICG) as a measure of graft function. Peripheral ICG clearance was measured 18-24 hr after liver transplantation in twenty-three consecutive patients (24 transplants). Doppler ultrasonography confirmed normal hepatic arterial blood flow. Correlations between ICG clearance and other markers of graft function and outcome were sought. The mean ICG clearance was 406 mls/min (SD 137.5). A threshold value of 200 ml/min reliably predicted outcome. Significant correlations were found between ICG clearance and times to normalization of PT (P < 0.02) and to the correction of acidosis (P < 0.05). No correlation was found with ALT, PT, bile flow, glucose requirement, or consumption of potassium. ICG clearance measured on the day after liver transplantation accurately reflects graft function and may be used to predict graft survival and final outcome.