PHARMACODYNAMIC AND HEMODYNAMIC-EFFECTS OF MIVACURIUM IN INFANTS ANESTHETIZED WITH HALOTHANE AND NITROUS-OXIDE

Background: The newly developed neuromuscular blocking agent, mivacuri um, has been evaluated in adults and children, but there are no data o n its effects in infants. This study was designed to evaluate the neur omuscular effects of mivacurium by dose-response analysis, and its car diovascular effects in 90 infants 2-11 months of age anesthetized with 1% halothane and nitrous oxide:oxygen. Methods: The neuromuscular res ponse was measured by recording the force of contraction of the adduct or pollicis during train-of-four stimulation at 0.1 Hz. The infants we re divided according to age into two equal groups of 45; group A infan ts 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. Infan ts in group A received mivacurium at sequential doses of 40, 50, 55, 7 5, and 150 mug/kg, while those in group B received mivacurium at doses 40, 50, 60, 75, and 150 mug/kg. The first four doses in each group we re used to determine dose-response relationships. The last two doses o f 75 and 150 mug/kg were based on the observed preceding dose-response data to approximate the ED95 and 2XED95. Heart rate and blood pressur e were determined every minute for a minimum of 3 min after mivacurium . Results. The effective doses for 50% depression of the first twitch response of the train-of-four (ED50) were 44-50 mug/kg (confidence lim its 29-74 mug/kg), without any significant difference between groups A and B. In both groups, a larger dose of mivacurium, 150 mug/kg, cause d 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% reco very 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% neurom uscular block in infants 2-6 and 7-11 months of age were 12.1 +/- 1 an d 9.9 +/- 1 mug - kg-1 . min-1, respectively (NS). No significant chan ges of heart rate or blood pressure occurred in infants, except in the subgroup of infants 7-11 months of age who received 150 mug/kg mivacu rium. In this group, a 13-mmHg increase in mean systolic blood pressur e was seen without any significant change in diastolic pressure or hea rt rate. In addition, in 7 of 36 patients receiving 75-150 mug/kg miva curium, a greater than 29% change in systolic or diastolic pressure oc curred. One infant with cholinesterase deficiency had a prolonged neur omuscular block from mivacurium. Conclusions. The ED50 duration of act ion and infusion requirements of mivacurium in infants 2-6 months of a ge are comparable with those of infants 7-11 months of age.