Pharmacokinetics of Rocuronium during the Three Stages of Liver Transplantation

Background: Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The authors determined the pharmacokinetics of rocuronium during liver transplantation and examined whether variability in pharmacokinetics could explain variability in recovery of neuromuscular function.

Methods: Twenty patients undergoing liver transplantation were given rocuronium, 600 micro gram/kg, after induction of anesthesia and again after perfusion of the transplanted liver. Plasma was sampled to determine rocuronium concentrations. Pharmacokinetic models were fit to rocuronium concentrations versus time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to account for changes in hepatic function and circulatory status during the paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four twitches of the orbicularis oculi was determined.

Results: During the paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml [center dot] kg sup -1 [center dot] min sup -1 and was not influenced by the magnitude of preexisting liver disease (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase [ALT], and aspartate transaminase [AST]). During the neohepatic period, the typical value of Cl varied as a function of the duration of warm ischemia of the hepatic allograft and was 2.72 ml [center dot] kg sup -1 [center dot] min sup -1 for a patient with an average 60-min period of warm ischemia; time to neuromuscular recovery varied as a function of Cl.