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 tran splantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia -reperfusion injury and improve postoperative outcome. Design: Prospective, randomised, placebo controlled trial, Setting: Univers ity hospital. Patients: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). Interventions: Patients in the tirilazad group (n = 10) received four intra venous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/ kg) after the induction of anaesthesia, The ether patients (n = 10) served as controls. Measurements and results: Plasma levels of malonaldehyde (MDA) were determi ned after the induction of anaesthesia prior to the infusion of tirilazad ( baseline), during the anhepatic period, and 5 min and 24 h after reperfusio n. Postoperatively, alanine aminotransferase, aspartate aminotransferase, p rothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change durin g the anhepatic period and after reperfusion and they did not differ betwee n groups. postoperative liver enzymes and prothrombin time did not differ b etween groups, but on the first (p = 0.03) and second (p = 0.01) postoperat ive day cholinesterase levels were significantly higher in tirilazad-treate d patients than in control patients. For neither length of Stay in the inte nsive care unit nor hospital stay were any differences observed between gro ups. Conclusions: In patients undergoing liver transplantation, tirilazad does n ot improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earl ier recovery of liver function remains to be tested.