The clinical effect of mixing different proportions of rocuronium and mivacurium.

Summary 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 × 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.