Abstract
We have studied the interaction between atracurium and mivacurium. The dose—response relationships of atracurium, mivacurium and their combination were studied in 96 ASA I or II patients during thiopentone—fentanyl—nitrous oxide—isoflurane (1.2% end-tidal) anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 12-s intervals). The dose—response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess quantitatively 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 ED50 points on the dose co-ordinates and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the first twitch height were 50.5 (95% confidence intervals 48.9–52.1) and 20.8 (20.3–21.3) μg kg−1 for the atracurium and mivacurium groups, respectively. Isobolographic and fractional analyses of the atracurium-mivacurium combination demonstrated zero interaction (additivism). An additional 26 patients anaesthetized with thiopentone-fentanyl-nitrous oxide—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 patients in both groups, whenever the first twitch recovered to 10% of control. The duration of the first maintenance dose of mivacurium to 10% recovery of the first twitch was greater (P < 0.0005) after atracurium (25 (21.8–28.5) min) than after mivacurium (14.2 (11.9–16.6) min). However, the duration of the second maintenance dose of mivacurium after atracurium (18.3 (12.6–24) min) was similar to that of mivacurium after mivacurium (14.6 (10.6–18.6) min). We conclude that the combination of atracurium and mivacurium is additive and that the use of mivacurium after atracurium-induced neuromuscular block results in increased duration of the first (but not the subsequent) maintenance dose of mivacurium.