Pharmacodynamic and hemodynamic effects of mivacurium in infants anesthetized with halothane and nitrous oxide

The newly developed neuromuscular blocking agent, mivacurium, has been evaluated in adults and children, but there are no data on its effects in infants. This study was designed to evaluate the neuromuscular effects of mivacurium by dose-response analysis, and its cardiovascular effects in 90 infants 2-11 months of age anesthetized with 1% halothane and nitrous oxide:oxygen.

The neuromuscular response was measured by recording the force of contraction of the adductor pollicis during train-of-four stimulation at 0.1 Hz. The infants were divided according to age into two equal groups of 45; group A infants were 2-6 months of age, and group B infants were 7-11 months of age. Each group was further subdivided into five subgroups of nine. Infants in group A received mivacurium at sequential doses of 40, 50, 55, 75, and 150 micrograms/kg, while those in group B received mivacurium at doses 40, 50, 60, 75, and 150 micrograms/kg. The first four doses in each group were used to determine dose-response relationships. The last two doses of 75 and 150 micrograms/kg were based on the observed preceding dose-response data to approximate the ED95 and 2XED95. Heart rate and blood pressure were determined every minute for a minimum of 3 min after mivacurium.

The effective doses for 50% depression of the first twitch response of the train-of-four (ED50) were 44-50 micrograms/kg (confidence limits 29-74 micrograms/kg), without any significant difference between groups A and B. In both groups, a larger dose of mivacurium, 150 micrograms/kg, caused complete ablation of the twitch response in 1.3 +/- 0.2 min (mean +/- SE) with recovery to 5, 25, and 95% of control in 7.6 +/- 0.5, 9.4 +/- 0.6, and 16.2 +/- 0.9 min, respectively. In infants, the 25-75% recovery index was 3.8 +/- 0.4 min, and the 5-95% recovery index was 8.5 +/- 0.8 min. In 28 infants, in whom surgical relaxation was required for more than 20 min, the infusion requirements to maintain 90-99% neuromuscular block in infants 2-6 and 7-11 months of age were 12.1 +/- 1 and 9.9 +/- 1 micrograms.kg-1.min-1, respectively (NS). No significant changes of heart rate of blood pressure occurred in infants, except in the subgroup of infants 7-11 months of age who received 150 micrograms/kg mivacurium. In this group, a 13-mmHg increase in mean systolic blood pressure was seen without any significant change in diastolic pressure or heart rate. In addition, in 7 of 36 patients receiving 75-150 micrograms/kg mivacurium, a greater than 29% change in systolic or diastolic pressure occurred. One infant with cholinesterase deficiency had a prolonged neuromuscular block from mivacurium.

The ED50 duration of action and infusion requirements of mivacurium in infants 2-6 months of age are comparable with those of infants 7-11 months of age.