PHARMACOKINETICS AND PHARMACODYNAMICS OF D-TUBOCURARINE DURING NITROUS OXIDE NARCOTIC AND HALOTHANE ANESTHESIA IN MAN

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 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%, and seven patients received halothane, 1.0-1.2%, end-tidal, with N2O, 70 per cent. The steady-state plasma concentration necessary to cause 50% 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%, and 0.22 μg/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 per cent, 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 to dTc.