Effects of Mild Core Hypothermia on Pharmacokinetics, Pharmacodynamics of Vecuronium. Caldwell et al. (page 84)

Abstract

Using 12 healthy volunteers (6 male, 6 female) Caldwell et al. evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium. Anesthesia was induced with alfentanil 30 mcg/kg and propofol 3 mg/kg. Subjects were intubated and anesthesia was maintained with nitrous oxide, 60-70%, in oxygen, and isoflurane 0.7-0.9% end-tidal concentration. Three volunteers were randomly assigned to be studied at each of four core temperature ranges: 37.0 or greater; 36.0-36.9; 35.0-35.9, and less than 35 C. Core temperatures were manipulated using either forced-air warming or surface cooling, depending upon the desired target temperature.To measure neuromuscular responses, supramaximal stimuli in a train of four sequence at 2 Hz were applied every 12 seconds via surface electrodes to the ulnar nerve. When temperature was stabilized, vecuronium was infused at 5mcg*kg-1*min-1 until the first response of each TOF had decreased by 70%. For vecuronium analysis, arterial blood was sampled at pre-set intervals until the T1 recovered to at least 90% of its pre-vecuronium level. Vecuronium 20mcg*kg-1*min-1 was then infused for 10 minutes and arterial blood sampled at intervals for up to seven hours from the start of the infusion. Final blood samples and urine samples were collected when subjects emerged from anesthesia. When core temperature decreased from 38.0 to 34.0, the plasma clearance of vecuronium also decreased (11.3% per degree C). The rate of effect site equilibration also decreased, although tissue sensitivity to vecuronium did not appear to be influenced by core temperature. Reduced clearance and rate of effect site equilibration may explain vecuronium’s increased duration of action when core temperature is reduced.