Pharmacokinetics and Pharmacodynamics of d-Tubocurarine during Nitrous Oxide–Narcotic and Halothane Anesthesia in Man

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Abstract
The relative contributions of changes in pharmacokinetics and pharmacodynamics to the potentiation of d-tubocurarine (dTc)-induced paralysis by halothane in comparison with nitrous oxide (N2O)-narcotic anesthesia were studied in 3 groups of patients. Patients (14) received N2O-narcotic maintenance anesthesia; 7 received halothane, 0.5-0.7%, end-tidal, with N2O, 70%; and 7 patients received halothane, 1.0-1.2%, end-tidal, with N2O, 70%. The steady-state plasma concentration necessary to cause 50% paralysis (Cpss(50)) was highest in the N2O-narcotic group at 0.6 .mu.g/ml; it was 0.36 .mu.g/ml with halothane, 0.5-0.7%, and 0.22 .mu.g/ml with halothane, 1.0-1.2%. Greater absolute and relative variability of the Cpss(50) was present in the N2O-narcotic group when compared with halothane, 0.5-0.7%. The equilibration half-times t1/2Keo between plasma concentration and pharmacologic effect (paralysis) were 4.7 min for the N2O-narcotic group, 6.9 min for the halothane, 0.5-0.7%, group and 7.9 min for the halothane, 1.0-1.2%, group. The greater t1/2Keo with halothane anesthesia is interpreted as decreased muscle perfusion. Halothane did not alter the pharmacokinetics of dTc in comparison with N2O-narcotic anesthesia. It affected the pharmacodynamics by prolonging the equilibration between plasma concentration and pharmacologic effect and increasing the sensitivity of the neuromuscular junction of dTc.