The influence of renal failure on the pharmacokinetics and duration of action of pipecuronium bromide in patients anesthetized with halothane and nitrous oxide

Abstract

The authors determined the pharmacokinetics and duration of action of a bolus dose of pipecuronium bromide (0.07 mg·kg-1) in 40 patients anesthetized with halothane and nitrous oxide. Twenty were patients with normal renal function, undergoing a variety of surgical procedures, and 20 were undergoing cadaver renal transplantation because of end-stage renal disease. Plasma concentrations of pipecuronium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by nonlinear regression and fit to a two-compartment or three-compartment model; in addition, the data were analyzed by a non-compartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The pharmacokinetic parameters derived by compartmental modelling were (normal vs. renal failure, respectively): volume of distribution at steady state (309±103 vs. 442±158 ml·kg-1, mean ±SD), plasma clearance, (2.4±0.6 vs. 1.6±0.6 ml·kg-1·min-1), mean residence time (140±63 vs. 329±198 min), and elimination half-life (137±68 vs. 263±168 min). The same parameters as derived by the non-compartmental method were (normal vs. renal failure, respectively): volume of distribution at steady state (307±80 vs. 426±119 ml·kg-1, mean ±SD), plasma clearance (2.4±0.6 vs. 1.6±0.6 ml·kg-1·min-1), mean residence time (134±41 vs. 323±228 min), and elimination half-life (118±35 vs. 247±168 min). All these pharmacokinetic parameters differed significantly between the patients with normal renal function and those with renal failure (P<0.05). Despite the pharmacokinetic differences, the mean duration of action (injection to 25% recovery of twitch tension) of pipecuronium was similar in both groups (98±36 min, normal, and 103±60 min, renal failure, mean ±SD). However, the duration of action of pipecuronium in patients with renal failure (range 30-267 min) was more variable than in those with normal renal function (range 55-198 min). This unpredictable response, with the possibility of prolonged blockade, suggests pipecuronium may be less suitable for use in patients with renal failure than the neuromuscular blocking drugs, vecuronium and atracurium, which have a shorter and a more predictable duration of action in these patients.