Neuromuscular effects of rocuronium bromide and mivacurium chloride administered alone and in combination

Abstract

Background: Rocuronium is a new nondepolarizing neuromuscular blocking agent with a rapid onset but with intermediate duration of action. Mivacurium, on the other hand, is a new short-acting nondepolarizing neuromuscular relaxant, but of slower onset of action. The current study was undertaken to characterize the interaction between rocuronium and mivacurium. Methods: In the first study, the dose-response relations of rocuronium, mivacurium, and their combination were studied in ASA physical status 1 or 2 patients during thiopental-fentanyl-N2O anesthesia. One hundred ten patients, randomly assigned to 1 of 11 groups of 10 patients each, received mivacurium 30, 50, or 70 μg · kg-1; rocuronium 100, 200, 250, or 300 μg · kg-1; or an equieffective combination of both drugs (1 ED50 rocuronium + 1 ED50 mivacurium; 1/2 ED50 rocuronium + 1/2 ED50 mivacurium; or 1/4 ED50 rocuronium + 1/4 ED50 mivacurium, or 1/8 ED50 rocuronium + 1/8 ED50 mivacurium, where ED50 is the dose producing 50% depression of the first twitch height). In the second study, 50 patients, ASA physical status 1 or 2, anesthetized with thiopental-fentanyl-N2O, were randomly allocated to 5 groups of 10 patients each to receive one of the following neuromuscular blocking drugs or drug combination: rocuronium 600 μg · kg-1 (group 1), mivacurium 150 μg · kg-1 (group 2) rocuronium 150 μg · kg-1 + mivacurium 37.5 μg · kg-1 (group 3), rocuronium 300 μg · kg-1 + mivacurium 75 μg · kg-1 ((group 4), or rocuronium 600 μg · kg-1 + mivacurium 150 μg · kg-1 (group 5). Results: The calculated ED50 values and their 95% confidence intervals were 125 (122-129) and 37 (36-38) μg · kg-1 for the rocuronium and mivacurium groups, respectively. The interaction between rocuronium and mivacurium was found to be synergistic. The measured ED50 of the mixture was only 62% of the predicted value assuming a purely additive interaction. In the second study, rocuronium 600 μg · kg-1 group and group 3 had similar onset times (99 [74-123] and 114 [100-128] s, respectively), which were significantly shorter than that observed in the mivacurium 150 μg · kg-1 group (178 [149-206] s). Onset times in groups 4 and 5 were significantly shorter than that in each of the other study groups (69 [63-76] and 73 [65-80] s, respectively). Clinical duration of action (recovery of T1 to 25% of baseline twitch height) was significantly greater in group 5 (55 [51-60] min) than with all other doses and agents, and briefest (P < 0.01) with mivacurium 150 μg · kg-1 (14.5 [12.6-16.5] min) and group 3 (14.7 [13.4-16] min). Conclusions: The interaction between rocuronium and mivacurium was found to be synergistic.