Clinical Responses to ORG 9426 During Isoflurane Anesthesia

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Abstract
To determine average dose requirements and pharmacodynamic characteristics before general clinical use, the dose-response curve, onset time, and recovery time for the neuromuscular relaxant ORG 9426 were determined in 72 adult patients given doses of 120, 160, 200, or 240 micrograms/kg after establishment of a steady-state expired isoflurane concentration of approximately 1%. Neuromuscular blockade was continuously recorded using the ulnar evoked electromyogram. Using the log probit method, ED95 was 268 micrograms/kg, ED90 was 251 micrograms/kg, and ED50 was 144 micrograms/kg. The time until 80% blockade was 1.9 min at 240 micrograms/kg, and the average time to peak effect was 4.6 min, which did not vary with dose. The clinical duration (injection until T1 returned to 25%) was 20.5 min, and the recovery index (T1 increased from 25% to 75% of control) was 15.4 min, after a total dose of 300 micrograms/kg. The duration of 75-micrograms/kg and 100-micrograms/kg repeat (maintenance) dose was 14.6 and 17.8 min, respectively, and no cumulative effect was apparent after as many as five maintenance doses. No cardiovascular side effects were seen at doses used in the study. We conclude that ORG 9426 is a nondepolarizing muscle relaxant with a rapid onset and short duration of action that deserves further clinical evaluation.

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