Effects of Bolus Administration of ORG-9426 in Children during Nitrous Oxide–Halothane Anesthesia


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Abstract

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose–response relationship of ORG-9426 in 62 children (aged 1–5 yr) during nitrous oxide–halothane anesthesia by means of log-probit transformation and leastsquares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 μg/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose–response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) μg/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 μg/kg, respectively. Time from administration of 600 μg/kg to onset of 90% and 100% neuromuscular block was 0.8 ± 0.1 (0.5–1.3) and 1.3 ± 0.2 (0.7–2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 ± 1.9 (17.2–39.0) min. The recovery index (T25–75) was 11.0 ± 1.6 (6.0–22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) ≥ 0.75 was 41.9 ± 3.2 (26.5–57.7) min. The heart rate transiently increased from 90 ± 4 (68–108) to 106 ± 4 (76–122) beats/min (P < 0.01) within 1 min after ORG-9426 (2 X ED95) administration. The relatively rapid onset of action of a bolus of ORG-9426 that can produce paralysis and the minimal change in heart rate make this neuromuscular blocking drug useful in children in situations where rapid tracheal intubation is desired.

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