Time-dependent Increase in Sensitivity to d-Tubocurarine during Enflurane Anesthesia in Man

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Abstract
The pharmacokinetics of d-tubocurarine (dTc) during enflurane and during halothane anesthesia were compared in man. Seven patients received enflurane (1.3-1.4% end-tidal) with nitrous oxide (70%), while 7 other patients received an equipotent anesthetic concentration of halothane (0.5-0.7% end-tidal) with nitrous oxide (70%). Force of thumb adduction was used to assess paralysis. Using a rapid, followed by a slower infusion of dTc, relatively constant plasma concentrations were obtained within 1 h and were maintained for 1-2 h. To determine the effect of enflurane with nitrous oxide on force of thumb adduction, a control group of 4 patients did not receive dTc, while thumb adduction was monitored for 2-3 h. In the halothane-treated group, a constant plasma concentration of dTc caused a constant degree of paralysis. With enflurane a constant plasma concentration caused a time-dependent increase of paralysis, indicating an increased sensitivity of the neuromuscular junction to dTc. In the control group, enflurane alone did not decrease the force of thumb adduction. The increase in paralysis in the enflurane-treated group was linear over a 1-2 h period, with a mean increase of 9.0% per hour. Evaluating only the 1st h of enflurane anesthesia, the steady-state plasma concentration that caused 50% paralysis (Cpss(50)) was 0.52 .+-. 0.13 .mu.g/ml (mean .+-. SD), while the Cpss(50) for halothane was significantly lower, 0.36 .+-. 0.04 .mu.g/ml. During the 1st h of enflurane anesthesia, larger amounts of dTc will be needed to initiate paralysis in comparison with halothane anesthesia. As the duration of enflurane anesthesia increases, sensitivity to dTc will progressively increase, and subsequent maintenance doses of dTC needed will be smaller, relative to equipotent halothane anesthesia.