NEUROMUSCULAR EFFECTS OF ROCURONIUM BROMIDE AND MIVACURIUM CHLORIDE ADMINISTERED ALONE AND IN COMBINATION

Background: Rocuronium is a new nondepolarizing neuromuscular blocking agent with a rapid onset but with intermediate duration of action. Mi vacurium, on the other hand, is a new short-acting nondepolarizing neu romuscular 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 o f rocuronium, mivacurium, and their combination were studied in ASA ph ysical status 1 or 2 patients during thiopental-fentanyl-N2O anesthesi a. One hundred ten patients, randomly assigned to 1 of 11 groups of 10 patients each, received mivacurium 30, 50, or 70 mu g . kg(-1); rocur onium 100, 200, 250, or 300 mu g . kg(-1); or an equieffective combina tion of both drugs (1 ED(50) rocuronium + 1 ED(50) mivacurium; 1/2 ED( 50) rocuronium + 1/2 ED(50) mivacurium; 1/4 ED(50) rocuronium + 1/4 ED (50) mivacurium; or 1/8 ED(50) rocuronium + 1/8 ED(50) mivacurium, whe re ED(50) is the dose producing 50% depression of the first twitch hei ght). In the second study, 50 patients, ASA physical status 1 or 2, an esthetized with thiopental-fentanyl-N2O, were randomly allocated to 5 groups of 10 patients each to receive one of the following neuromuscul ar blocking drugs or drug combination: rocuronium 600 mu g . kg(-1) (g roup 1), mivacurium 150 mu g . kg(-1) (group 2) rocuronium 150 mu g . kg(-1) + mivacurium 37.5 mu g . kg(-1) (group 3), rocuronium 300 mu g . kg(-1) + mivacurium 75 mu g . kg(-1) ((group 4), or rocuronium 600 m u g . kg(-1) + mivacurium 150 mu g . kg(-1) (group 5). Results: The ca lculated ED(50) values and their 95% confidence intervals were 125 (12 2-129) and 37 (36-38) mu g . kg(-1) for the rocuronium and mivacurium groups, respectively. The interaction between rocuronium and mivacuriu m was found to be synergistic. The measured ED(50) of the mixture was only 62% of the predicted value assuming a purely additive interaction . In the second study, rocuronium 600 mu g . 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 mivacuri um 150 mu g . 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 (63 [63-76] and 73 [65-80] s, respectively). Clinical duration of action (recovery of T1 to 25% of baseline twitch height) was signif icantly greater in group 5 (55 [51-60] min) than with all other doses and agents, and briefest (P < 0.01) with mivacurium 150 mu g . 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 syne rgistic.