Temperature-dependent Pharmacokinetics and Pharmacodynamics of Vecuronium

Background: The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia 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 >= 37.0[degrees]C. With temperature stabilized, vecuronium was infused at 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 [mu]g [middle dot] kg-1 [middle dot] min-1, was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics 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 constant for drug equilibration between plasma and effect site (0.023 min-1 per [degrees]C), and increases the slope of the concentration-response relationship (0.43 per [degrees]C).