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

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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)–narotic anesthesia were studied in three groups of patients. Fourteen patients received N2O-narcotic maintenance anesthesia, while seven patients received halothane, 0.5–0.7 per cent, end-tidal, with N2O, 70 per cent, and seven patients received halothane, 1.0–1.2 per cent, end-tidal, with N2O, 70 per cent. The steady-state plasma concentration necessary to cause 50 per cent paralysis (Cpss(50)) was highest in the N2O–narcotic group at 0.6 μg/ml; it was 0.36 μg/ml with halothane, 0.5–0.7 per cent, and 0.22 μg/ml with halothane, 1.0–1.2 per cent. Greater absolute and relative variability of the Cpss(50) was present in the N2O–narcotic group when compared with halothane, 0.5–0.7 per cent. The equilibration half-times t1/2Keu 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 per cent, group and 7.9 min for the halothane, 1.0–1.2 per cent, group. The greater t1/2Keu 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 to dTc.

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