Synergism between atracurium and mivacurium compared with that between vecuronium and mivacurium

Synergism exists between some combinations of nondepolarizing muscle relaxants. To test the possibility of synergism between mivacurium and atracurium or vecuronium, 60 children anesthetized with propofol-alfentanil-N2O-O2 were randomized to one of five groups. Three groups of 10 patients each received an ED50 dose of a parent drug atracurium (A), vecuronium (V), or mivacurium (M), respectively, and two other groups of 15 patients each received a single-dose combination of atracurium with mivacurium (cAM) or vecuronium with mivacurium (cVM). Dose combinations constituted 0.5 times an ED50 dose of each drug. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG). Maximum neuromuscular block (NMB) established by a single parent drug did not differ between the groups or from 50% NMB. It averaged 5.03 +/- 0.12 probits (51.2% NMB). On the contrary, maximum NMB established by the two-dose combinations, cAM or cVM, was significantly more than NMB produced by either single parent drug of the particular combination (cAM vs A or M; P = 0.0035, and cVM vs V or M; P = 0.0004) without a statistically significant difference between groups cAM and cVM. Maximum NMB established by combinations averaged 6.15 +/- 0.21 probits (87.5% NMB). The onset of maximum NMB for mivacurium was significantly faster compared to that for atracurium or for vecuronium (2.8 +/- 0.3 vs 5.7 +/- 0.4 or 4.0 +/- 0.3 min, respectively; P = 0.0001). Our results indicate that both drug combinations are synergistic even though only vecuronium is markedly different in its molecular structure from mivacurium.