INTERACTIONS BETWEEN MIVACURIUM AND ATRACURIUM

We have studied the interaction between atracurium and mivacurium. The dose-response relationships of atracurium, mivacurium and their combi nation were studied in 96 ASA I or II patients during thiopentone-fent anyl-nitrous oxide-isoflurane (1.2% end-tidal) anaesthesia. Neuromuscu lar block was recorded as the evoked thenar mechano-myographic respons e to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s interv als). The dose-response curves were determined by probit analysis. Iso bolographic and algebraic (fractional) analyses were used to assess qu antitatively the combined effect of equipotent doses of atracurium and mivacurium and to define the type of interaction between these drugs. Isobolograms were constructed by plotting single drug ED(50) points o n the dose co-ordinates and a combined ED(50) point in the dose field. The calculated doses producing 50% depression (ED(50)) of the first t witch height were 50.5 (95% confidence intervals 48.9-52.1) and 20.8 ( 20.3-21.3) mu g kg(-1) for the atracurium and mivacurium groups, respe ctively. Isobolographic and fractional analyses of the atracurium-miva curium combination demonstrated zero interaction (additivism). An addi tional 26 patients anaesthetized with thiopentone-fentanyl-nitrous oxi de-isoflurane were allocated randomly to receive either atracurium 0.5 mg kg(-1) (n = 13) or mivacurium 0.15 mg kg(-1) (n = 13). Additional maintenance doses of mivacurium 0.1 mg kg(-1) were administered to pat ients in both groups, whenever the first twitch recovered to 10% of co ntrol. The duration of the first maintenance dose of mivacurium to 10% recovery of the first twitch was greater (P < 0.0005) after atracuriu m (25 (21.8-28.5) min) than after mivacurium (14.2 (11.9-16.6) min). H owever, the duration of the second maintenance dose of mivacurium afte r atracurium (18.3 (12.6-24) min) was similar to that of mivacurium af ter mivacurium (14.6 (10.6-18.6) min). We conclude that the combinatio n of atracurium and mivacurium is additive and that the use of mivacur ium after atracurium-induced neuromuscular block results in increased duration of the first (but not the subsequent) maintenance dose of miv acurium.