Pharmacodynamics and pharmacokinetics of rocuronium in intensive care patients.

Abstract

We have studied dose requirements, recovery times and pharmacokinetics of rocuronium in 32 intensive care patients. After an initial dose of 50 mg, rocuronium was administered as maintenance doses of 25 mg whenever two responses to train-of-four (TOF) stimulation reappeared (bolus group; n = 27) or by continuous infusion to maintain one response in the TOF (infusion group; n = 5). Median requirements for rocuronium were 27.4 (range 14.5-68.3) mg h-1 and 43.7 (30.9-50.3) mg h-1 in patients in the bolus and infusion groups, respectively. Median total duration of rocuronium administration was 29.0 (12.4-95.5) h and 63.4 (24.0-140.3) h, respectively. Median time from administration of the last bolus dose and end of infusion to recovery of the fourth twitch in the TOF was 100 (45-300) min and 60 (15-155) min, respectively. Arterial blood samples were obtained for up to 10 h after cessation of rocuronium administration, and concentrations of the parent compound and its putative metabolites were measured using high pressure liquid chromatography (HPLC). The plasma concentration profile (n = 12) was described adequately by a two-compartment model. Mean plasma clearance (Cl), steady-state distribution volume (Vss), mean residence time (MRT) and elimination half-life (T1/2 beta) were 3.16 (SD 1.15) ml kg-1 min-1, 769 (334) ml kg-1, 262 (120) min and 337 (163) min, respectively. Recovery times, Vss, MRT, and T1/2 beta differed from previously published data obtained after rocuronium infusion of moderate duration in surgical patients.