Pharmacokinetics of Muscle Relaxants in Patients with Liver Disease

Abstract

Summary Patients with cirrhosis often exhibit a resistance to muscle relaxants. This phenomenon can be explained by an increase in the initial volume of distribution of the relaxant. Increased plasma protein binding, which was thought to be the main explanation of resistance to curare in cirrhotics, appears to be unlikely since muscle relaxants do not bind to a significant extent to plasma proteins in either normal patients or patients with cirrhosis. This increase in the volume of distribution is probably caused by the increase in the extracellular fluid space in cirrhotics. Thus, the dose requirement is increased in patients with cirrhosis, this being especially true in the presence of ascites or oedema. However, this phenomenon was not observed with vecuronium. Cirrhosis and cholestasis caused a prolongation of the elimination half-life of pancuronium and vecuronium; in the former this change was caused by an increased volume of distribution and in the latter by a decreased clearance. Among the muscle relaxants available in clinical practice, vecuronium is the only one whose elimination appears predominantly dependent on the liver. The duration of the neuromuscular blockade caused by vecuronium is significantly prolonged in patients with cirrhosis but its effect remains shorter than that of pancuronium in healthy patients. The elimination kinetics of gallamine and atracurium, whose elimination is independent of liver function, are not modified in patients with liver dysfunction.