Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia

Abstract

Purpose: To compare the pharmacokinetics, pharmacodynamics and the concentration-effect relationship of rocuronium in patients under stable propofol or isoflurane anesthesia. Methods: Ten patients were randomized to receive fentanyl, propofol and nitrous oxide (60%) or fentanyl, thiopental, isoflurane (1.2% end-tidal concentration) and nitrous oxide (60%). To obtain good intubation conditions and maintain adequate muscle relaxation during surgery, patients received two bolus doses of rocuronium: 0.5 mg·kg-1 (1.7 × ED95) at induction followed one hour later by 0.3 mg·kg-1 (1 × ED95). Arterial blood samples were obtained over six hours after the second bolus dose. Plasma concentrations of rocuronium were measured using high pressure liquid chromatography. Muscle twitch tension was monitored by mechanomyography for the two doses. Pharmacokinetic and pharmacodynamic parameters were determined. Results: No differences in rocuronium pharmacokinetic parameters were observed between both groups. After the second bolus, clinical duration was 20 ± 6 min in the propofol group vs 39 ± 8 min in the isoflurane group (P < 0.05). The effect compartment concentration corresponding to 50% block, EC50 was higher under propofol anesthesia: 1008 vs 592 μg·L-1 (P < 0.05). Conclusion: Rocuronium body disposition is similar under stable propofol or isoflurane anesthesia. In contrast to isoflurane, propofol does not prolong the neuromuscular block. Therefore, the potentiating effect of isoflurane is of pharmacodynamic origin only, as explained by an increased sensitivity at the neuromuscular junction. In contrast with isoflurane anesthesia where the dose of rocuronium has to be decreased under stable conditions, no dose adjustment is required under propofol anesthesia.