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Mild Intraoperative Hypothermia Does Not Change the Pharmacodynamics (Concentration-Effect Relationship) of Vecuronium in Humans

Heier Tom MD; Caldwell, James E. MB, ChB; Sharma, Manohar L. PhD; Gruenke, Larry D. PhD; Miller, Ronald D. MD
Anesthesia & Analgesia: May 1994

To investigate the effect of mild hypothermia on the neuromuscular junction sensitivity to vecuronium, we determined the pharmacodynamics (concentration-effect relationship) of vecuronium in 10 patients (ASA physical class I or II; age range, 21–46 yr; weight range, 54–104 kg), during isoflurane-nitrous oxide-fentanyl anesthesia. Five were cooled to a mean temperature of 34.4°C and five were maintained normothermic at a mean temperature of 36.8°C. Neuromuscular function was monitored by measuring the evoked mechanical response of the adductor pollicis muscle after supra-maximal train-of-four stimulation of the ulnar nerve at the wrist. Vecuronium, 3 μg·kg−1.min−1, was infused for 10 min, venous blood sampled for 60 min, and twitch tension and plasma concentration data were used to determine pharmacodynamic variables in each patient. Results for the hypothermic and normothermic groups were compared by Mann-Whitney U-test. There were no differences in any pharmacodynamic variable between the hypothermic and normothermic patients. For the hypothermic and normothermic patients, respectively, steady-state plasma concentrations of vecuronium producing 50% neuromuscular block (CSS50) were 73 ± 13 ng/mL (mean ± SD) and 79 ± 31 ng/mL; the rate constants for equilibration of vecuronium between the plasma and the neuromuscular junction (Keo) were 0.27 ± 0.14 per min−1 and 0.26 ± 0.11 per min, and the power functions representing the slope of the concentration-effect relationship (γ) were 5.7 ± 1.9 and 4.4 ± 1.8. We conclude that the pharmacodynamics (concentration-effect relationship) of vecuronium are similar at 34.4 and 36.8°C and that pharmacodynamic factors do not explain the prolongation of action of vecuronium previously observed during mild hypothermia.

Address correspondence and reprint requests to James E. Caldwell, MB ChB, Department of Anesthesia, University of California, 521 Parnassus Avenue, San Francisco, CA 94143–0648.

© 1994 International Anesthesia Research Society