The use of the antioxidant tirilazad mesylate in human liver transplantation: is there a therapeutic benefit?

Objectives: To test the hypothesis whether in patients undergoing liver transplantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia-reperfusion injury and improve postoperative outcome. Design: Prospective, randomised, placebo controlled trial. Setting: University hospital. Patients: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). Interventions: Patients in the tirilazad group (n = 10) received four intravenous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/kg) after the induction of anaesthesia. The other patients (n = 10) served as controls. Measurements and results: Plasma levels of malonaldehyde (MDA) were determined after the induction of anaesthesia prior to the infusion of tirilazad (baseline), during the anhepatic period, and 5 min and 24 h after reperfusion. Postoperatively, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change during the anhepatic period and after reperfusion and they did not differ between groups. Postoperative liver enzymes and prothrombin time did not differ between groups, but on the first (p = 0.03) and second (p = 0.01) postoperative day cholinesterase levels were significantly higher in tirilazad-treated patients than in control patients. For neither length of stay in the intensive care unit nor hospital stay were any differences observed between groups. Conclusions: In patients undergoing liver transplantation, tirilazad does not improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earlier recovery of liver function remains to be tested.