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

Abstract

To determine the effects of hypothermia on the pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc), serum, biliary and urinary concentration were determined and twitch tension monitored following i.v. 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 hypothermia (28.degree. C). Similarly, moderate (28.degree. C) but not mild (34.degree. C) hypothermia delayed recovery from paralysis. The serum half-life was prolonged 76% and the serum clearance rate decreased 60% by hypothermia (28.degree. C). The combined biliary and urinary elimination of dTc was decreased 47% at 28.degree. C compared with 34.degree. and 39.degree. C. The serum concentration of dTc necessary for neuromuscular blockade was less at 39.degree. C (ED50 0.87 .mu.g/ml) than at 34.degree. or 28.degree. C (ED50 1.13 .mu.g/ml). Apparently, in vivo, hypothermia antagonizes a dTc-induced neuromuscular blockade but decreases the elimination of dTc. At 28.degree. C the net effect is a prolongation of neuromuscular blockade.