Clinical Pharmacology of Edrophonium in Infants and Children

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Abstract
The dose-response relationship, onset, duration of action, atropine requirement, and pharmacokinetic variables of edrophonium were determined in infants and children during N2O-halothane anesthesia. The technique of steady state infusion of d-tubocurarine (dTc) was used to determine the ED50 for edrophonium (i.e., the dose producing 50% antagonism of 90% neuromuscular depression) in 14 infants (145 .mu.g/kg) and 12 children (233 .mu.g/kg). The reported values for ED50 for edrophonium (obtained under similar anesthetic conditions) in 128 .mu.g/kg for adults. These 3 dose-response curves do not differ statistically; however, there was greater variability among infants and children than adults. Time to peak antagonism was similar for all 3 age groups. Duration of antagonism was determined in 6 infants and 6 children and did not differ from the reported value for adults. The optimal dose and time of administration of atropine were established by administering edrophonium (1 mg/kg) and atropine (10-20 .mu.g/kg) to 24 infants and children. The smallest changes in heart rate and systolic blood pressure occurred when atropine (10 .mu.g/kg) was given 30 s before edrophonium. The pharmacokinetics of edrophonium (1 mg/kg) were studied in 4 infants and 4 children and were compared with published values for adults: distribution and elimination half-lives and distribution volumes were similar for the 3 groups. Total clearance (ml .cntdot. kg-1 .cntdot. min-1) was greatest for infants (17.8 .+-. 1.2) compared with children (14.2 .+-. 7.3) and adults (8.3 .+-. 2.9). The dose of edrophonium required to antagonize dTc-induced neuromuscular blockade evidently is similar or possibly greater for infants and children than for adults. Onset and duration of antagonism are similar for all 3 age groups, despite age-related differences in total clearance. Edrophonium, 1 mg/kg, appears to antagonize neuromuscular blockade effectively in infants and children; cardiovascular changes can be minimized by administering atropine (10 .mu.g/kg) 30 s before edrophonium.