DO THE PHARMACOKINETICS OF VECURONIUM CHANGE DURING PROLONGED ADMINISTRATION IN CRITICALLY ILL PATIENTS

Neuromuscular blocking drugs may be administered over several days to patients in the intensive care unit (ICU), but their pharmacokinetics have been studied at only one point in time, or assumed to be constant throughout the period of administration. We sought to determine if, i n individual patients, the pharmacokinetics of vecuronium changed over the course of its administration in the ICU. In six critically ill pa tients, we measured plasma vecuronium concentrations during two period s: first, during initial administration of vecuronium and second, afte r its administration continuously for 3-6 days. A pharmacokinetic mode l was fitted to these plasma concentration data, and its parameters pe rmitted to vary between the periods to determine if they had altered. Individual clearance values during the study ranged from 1.4 to 4.4 mi kg(-1) min(-1). During prolonged administration, vecuronium clearance increased in three and decreased in two patients. This change ranged from a 61% decrease to a 58% increase, and was not linked to any clini cal-factor. The steady-state volume of distribution (range 368-1765 ml kg(-1); median 494 ml kg(-1)) did not change in any patient during th e study. The change in clearance of vecuronium during its prolonged ad ministration in critically ill patients suggests that future studies o f neuromuscular blocking drugs in the ICU should take account of their changing pharmacokinetics over the course of administration.