Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium

Background: The authors evaluated the influence of temperature on the pharm acokinetics and pharmacodynamics of vecuronium because mild core hypothermi a doubles its duration of action. Methods: Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35 .0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and greater than or equal to 37.0 degrees C. With temperature stabilized, vecuronium was infus ed at 5 mu g . kg(-1) . min(-1) until the first response of each train-of-f our had decreased by 70%. Arterial blood (for vecuronium analysis) was samp led at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 mu g . kg(-1) . min(-1), was then infus ed for 10 min, and arterial blood was sampled at intervals for up to 7 h. p opulation-based nonlinear mixed-effects modeling was used to examine the ef fect of physical characteristics and core temperature on vecuronium pharmac okinetics and pharmacodynamics. Results: Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate c onstant for drug equilibration between plasma and effect site (0.023 min(-1 ) per degrees C), and increases the slope of the concentration-response rel ationship (0.43 per degrees C). Conclusions: Our results show that reduced clearance and rate of effect sit e equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influen ced by core temperature.