The Influence of Mild Hypothermia on the Pharmacokinetics and Time Course of Action of Neostigmine in Anesthetized Volunteers

BACKGROUND: The pharmacokinetics, maximum effect, and time course of action of neostigmine were studied in seven human volunteers. METHODS: Each volunteer was studied twice, during both normothermia and hypothermia. Anesthesia was induced with 30 microg/kg alfentanil and 3 mg/kg propofol, and was maintained with 60-70% nitrous oxide and 0.7-0.9% isoflurane. The mechanical response of the adductor pollicis to train-of-four stimulation of the ulnar nerve was recorded, and central body temperature maintained stable at either less than 34.5 degrees C or greater than 36.5 degrees C by surface cooling or warming. Before neostigmine administration, a stable 5% twitch height was obtained by an infusion of vecuronium, and the infusion rate remained unchanged thereafter. Neostigmine, 70 microg/kg, was then infused over 2 min, and blood samples for estimation of neostigmine concentrations were collected at intervals for 240 min. RESULTS: With hypothermia, the central volume of distribution of neostigmine decreased by 38%, and onset time of maximum effect increased (4.6 vs. 5.6 min). Hypothermia did not change the clearance (696 ml/min), maximum effect, or duration of action of neostigmine. CONCLUSIONS: The efficacy of neostigmine as an antagonist of vecuronium-induced neuromuscular block is not altered by mild hypothermia.