Abstract: We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046 (a thromboxane A2 synthetase inhibitor)). All trials had high risk of bias. There were no significant differences between the groups in mortality, liver failure, or perioperative morbidity. The trimetazidine group had a significantly shorter hospital stay than control (MD -3.00 days; 95% CI -3.57 to -2.43). There were no significant differences in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared with controls. However, there is a high risk of type I and type II errors because of the few trials included, the small sample size in each trial, and the risk of bias. Trimetazidine, methylprednisolone, and dextrose may protect against ischaemia reperfusion injury in elective liver resections performed under vascular occlusion, but this is shown in trials with small sample sizes and high risk of bias. The use of these drugs should be restricted to well-designed randomised clinical trials before implementing them in clinical practice.

Plain-language summary: In experimental studies many drugs have shown some promise in decreasing liver damage caused by the occluded blood supply. We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046). All trials had risk of bias ('systematic errors') and risk of play of chance ('random errors'). There was no significant difference between the groups in mortality, liver failure, or post-operative complications. The trimetazidine group had a significantly shorter hospital stay, and the vitamin E group had a significantly shorter intensive therapy unit stay than the respective controls. There was no significant difference in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared to controls. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the risks of bias. Three pharmacological drugs - trimetazidine, methylprednisolone, and dextrose - have potential for a protective role against liver injury in elective liver surgery involving blood supply occlusion. However, based on the current evidence it is recommended that the use of these agents should be restricted to well-designed trials in patients undergoing resection.