The clinical effect of mixing different proportions of rocuronium and mivacurium

BACKGROUND: A synergistic effect has been described when rocuronium (Roc) and mivacurium (Miv) are combined in equal (i.e. 1:1) ED95 proportions at various total doses. We have investigated the effect of Roc or Miv alone and four different ratios (1:4, 2:3, 3:2 and 4:1) of Roc and Miv mixed to a total dose of 1.33 x ED95. The primary outcome is the ratio producing the maximum enhancement of duration of clinical effect. METHODS: Sixty-eight healthy children were anaesthetized with propofol, nitrous oxide and fentanyl. They then randomly received either Roc 0.4 (mg.kg(-1)), Miv 0.133 (mg.kg(-1)) or one of four Roc + Miv combinations (mg.kg(-1)): Roc 0.32 + Miv 0.027; Roc 0.24 + Miv 0.053; Roc 0.16 + Miv 0.08; and Roc 0.08 + Miv 0.106. The mechanical response of the adductor pollicis muscle to supramaximal stimulation of the ulnar nerve at the wrist was recorded. RESULTS: Duration of effect was greater in the combination groups than that predicted from the duration of Roc or Miv used alone. Duration was maximally increased around a 1:1 ratio (2:3 and 3:2) of Roc and Miv. The likelihood of achieving 100% block was greater in combination groups compared with Roc or Miv used alone. CONCLUSIONS: Combinations of Roc and Miv show a synergistic effect, which appears maximal as the mixture approaches a 1:1 ratio of their ED95s. This combination acted as if a larger effective dose of a single (new) drug had been given, but did not offer the advantage of both rapid onset and short duration of effect.