Clinical Pharmacology of Mivacurium in Pediatric Patients Less Than Two Years Old During Nitrous Oxide-Halothane Anesthesia


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Abstract

We determined the dose-response relationship of mivacurium in infants 2–6 and 7–11 mo of age during nitrous oxide-halothane anesthesia. The neuromuscular and cardiovascular effects of a bolus dose of mivacurium larger than the ED95 in infants and young children from 2–23 mo of age were observed. The infusion rate of mivacurium required to maintain approximately 95% neuromuscular block was determined. There was no significant difference between the estimated dose-response relationship in infants 2–6 mo and that in infants 7–11 mo. The ED50 and ED95 were 44 μg/kg and 85 μg/kg for infants 2–11 mo (n = 70), r = 0.53. A bolus dose of 150 μg/kg mivacurium in infants (2–6 mo) produced 100% depression of the initial twitch height (T1) in 8 out of 9 infants and 85% depression in 1 infant. The time to onset of maximum block was 1.6 ± 0.3 (0.7–2.7) (mean, SEM [range]) min, and time to recovery to 25% of T1 (T25) was 7.5 ± 0.7 (5.5–11) min after 150 μg/kg in these patients. A bolus dose of 200 μg/kg mivacurium in infants and young children (7–23 mo) produced 100% depression of T1 in 14 of 17 patients, 97% depression in 2, and 90% depression in 1. The time to onset of maximum block was 1.5 ± 0.1 (0.8–3) min and T25 was 10.3 ± 1.5 (4.8–30.5) min after 200 μg/kg in these patients. Statistically significant cardiovascular changes were a small decrease in diastolic blood pressure and a small increase in heart rate in the 5-min interval after administration of 200 μg/kg mivacurium. The average infusion rate required to maintain approximately 95% depression of T1 in 20 patients (2–23 mo) during the first 15 min of infusion was 15.6 ± 1.0 (7–25.9) μg·kg−1·min−1 and 13.6 ± 1.0 (4.1–26) μg/kg−1·min−1 thereafter. After termination of the infusion, spontaneous recovery of T1 from 25% to 75% (T25–75) occurred in 3.6 ± 0.2 (2.7–5.2) min, and time to train-of-four ratio more than or equal to 0.75 (T4/T1 ≥ 0.75) was 8.0 ± 0.6 (6–11.5) min. The average plasma cholinesterase activity was 6.0 ± 0.2 (2.7–13.3) U/L. One child with plasma cholinesterase activity more than 3 SD above the mean (13.3 U/L) received an average of 32 μg·kg−1·min−1 mivacurium infusion without achieving 89% block. Mivacurium is a relatively short-acting nondepolarizing muscle relaxant that has minimal cardiovascular effects when administered in doses up to and including 200 μg/kg in infants and young children. There were no significant differences in the neuromuscular effects of a bolus or infusion of mivacurium in patients aged between 2 mo and 10 yr in pediatric patients anesthetized with halothane and nitrous oxide.

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