Pharmacokinetics and Dynamics of d-Tubocurarine during Hypothermia in Humans

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Abstract
To determine the influence of hypothermia on the pharmacokinetics and dynamics of d-tubocurarine (dTc), 17 patients were studied during halothane 0.5-0.7% end-tidal and 60% nitrous oxide anesthesia with controlled hyperventilation during craniotomy. Ten patients were deliberately cooled to an esophageal temperature of 31.9 .+-. 0.3.degree. C (mean .+-. SE) and a hypothenar muscle temperature of 31.8 .+-. 0.3.degree. C, while 7 patients had an esophageal temperature maintained at 35.8 .+-. 0.1.degree. C and a hypothenar muscle temperature of 36.7 .+-. 0.2.degree. C. Hypothermia did not affect the pharmacokinetics of dTc. Using 75-25% recovery times, dTc neuromuscular blockade was prolonged in the hypothermic patients by 82%, compared with the normothermic patients, as measured by twitch tension of the thumb adductors, but was unchanged as measured by the compound electromyogram (EMG). The steady state serum concentration necessary to produce 50% paralysis (Cpss(50)), was not significantly different during hypothermia (0.46 .+-. 0.07 .mu./ml) relative to normothermia (0.57 .+-. 0.07 .mu.g/ml). The half-time for equilibrium between serum dTc concentration and paralysis (t1/2 Keo) approached (P = 0.06) but was not significantly different during hypothermia (9.2 .+-. 1.2 min) vs. normothermia (5.4 .+-. 0.7 min). However 4 of the 9 patients in the hypothermic group had a marked prolongation (> 10 min) of this value. This suggests that hypothermia reduces blood flow to the neuromuscular junction, delaying onset of paralysis after administration of dTc. Other than a delayed half-time for equilibrium and differential effect on EMG vs. twitch tension, a decrease in body temperature to 31.9.degree. C does not significantly alter the pharmacokinetics and pharmacodynamics of dTc.