Pharmacokinetics and Pharmacodynamics of d-Tubocurarine during Hypothermia in the Cat

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Abstract

To determine the effects of hypothermia on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc), serum, biliary, and urinary concentrations were determined and twitch tension monitored following intravenous administration of dTc, 0.7 mg/kg, at 39 (n = 5), 34 (n = 5), and 28 C (n = 6) in cats anesthetized with chloralose and urethane. Time from injection of dTc to maximum neuromuscular blockade was prolonged by hypethermia (28 C). Similarly, moderate (28 C) but not mild (34 C) hypothermia delayed recovery from paralysis. The serum half-life was prolonged 76 per cent and the serum clearance rate decreased 60 per cent by hypothermia (28 C). The combined biliary and urinary elimination of dTc was decreased 47 per cent at 28 C compared with 34 and 39 C. The serum concentration of dTc necessary for neuromuscular blockade was less at 39 C (ED50 0.87 μg/ml) than at 34 or 28 C (ED50 1.13 μg/ml). It is concluded that, in vivo, hypothermia antagonizes a dTc-induced neuromuscular blockade but decreases the elimination of dTc. At 28 C the net effect is a prolongation of neuromuscular blockade.

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