PHARMACOKINETICS OF ROCURONIUM DURING THE 3 STAGES OF LIVER-TRANSPLANTATION

Background: Little is known about the influence of liver transplantati on on the pharmacokinetics of most anesthetic drugs. The authors deter mined the pharmacokinetics of rocuronium during Liver transplantation and examined whether variability in pharmacokinetics could explain var iability in recovery of neuromuscular function. Methods: Twenty patien ts undergoing liver transplantation were given rocuronium, 600 mu g/kg , after induction of anesthesia and again after perfusion of the trans planted liver, Plasma was sampled to determine rocuronium concentratio ns, Pharmacokinetic models were fit to rocuronium concentrations versu s time data using a mixed-effects population approach. Various models permitted changes in clearance (Cl) or central compartment volume to a ccount for changes in hepatic function and circulatory status during t he paleohepatic, anhepatic, and neohepatic periods, Time to initial re covery of four twitches of the orbicularis oculi was determined. Resul ts: During the paleohepatic and anhepatic periods, the typical value o f Cl was 2.47 ml.kg(-1).min(-1) and was not influenced by the magnitud e of preexisting liver disease (as evidenced by prothrombin time, bili rubin, serum albumin, alanine transaminase [ALT], and aspartate transa minase [AST]). During the neohepatic period, the typical value of Cl v aried as a function of the duration of warm ischemic of the hepatic al lograft and was 2.72 ml.kg(-1).min(-1) for a patient with an average 6 0-min period of warm ischemia; time to neuromuscular recovery varied a s a function of Cl. Conclusions: Despite prolonged hypothermic ischemi a, the newly transplanted liver eliminates rocuronium as well as the d iseased native liver (and comparably with historical control values). However, some patients had decreased rocuronium Cl during the neohepat ic period, apparently a result of prolonged graft warm ischemia. The a uthors' finding of preservation of hepatic drug elimination in the hep atic allograft is consistent with limited data for other drugs evaluat ed during anesthesia.