Evaluation of a protease inhibitor in the prevention of ischemia and reperfusion injury in hepatectomy under intermittent Pringle maneuver

Background The severity of ischemia and reperfusion (I/R) injury is an important determinant of patient outcome in hepatic surgery. The aim of this study was to investigate the efficacy of a protease inhibitor in alleviating I/R injury to human liver in the setting of hepatectomy under intermittent Pringle maneuver. Methods Sixty patients who underwent liver resection under conditions of intermittent inflow occlusion were randomly assigned to 2 groups (n = 30 each) according to the use of a synthetic protease inhibitor (gabexate mesilate or GM). GM was administered intravenously at a dosage of 2.0 mg/kg/h starting 12 hours before surgery until postoperative day 2. Preoperative and intraoperative clinical variables and postoperative outcomes were evaluated. The plasma levels of a cytokine, interleukin (IL)-6, as well as laboratory biochemical liver function parameters were analyzed to evaluate hepatic I/R injury. Results The 2 groups of patients were comparable with regard to hepatic inflow occlusion time, extent of liver resection, and background liver histology. The preoperative administration of GM (GM group) substantially alleviated hepatic I/R injury compared with the untreated control group; postoperative serum transaminase levels were significantly decreased in association with marked suppression of IL-6 levels in blood circulation during surgery. This was accompanied by a lower incidence of postoperative complications. The patients without postoperative complications had significantly lower activities of plasma IL-6 at 24 hours after surgery. Conclusions This prospective randomized study demonstrated the hepatoprotective effect of a synthetic protease inhibitor in the setting of hepatectomy under the intermittent Pringle maneuver.