Objective: The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation. Summary Background Data: Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function. Methods: In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival. Results: Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%. Conclusions: Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%. Trial registration: www.trialregister.nl; NTR5972.

LLR can be safely performed with low overall morbidity. According to this experience and irrespective of the learning curve, resections of P-S segments were identified as an independent risk factor for conversion in LLR.

Using target-controlled infusion in healthy volunteers, the pharmacokinetics of dexmedetomidine were best described by a three-compartment allometric model. Apart from weight, no other covariates were identified.