Interactions between mivacurium and atracurium

We have studied the interaction between atracurium and mivacurium.The dose—response relationships of atracurium, mivacuriumand their combination were studied in 96 ASA I or II patientsduring thiopentone—fentanyl—nitrous oxide—isoflurane(1.2% end-tidal) anaesthesia. Neuromuscular block was recordedas the evoked thenar mechanomyographic response to train-of-fourstimulation of the ulnar nerve (2 Hz at 12-s intervals). Thedose—response curves were determined by probit analysis.Isobolographic and algebraic (fractional) analyses were usedto assess quantitatively the combined effect of equipotent dosesof atracurium and mivacurium and to define the type of interactionbetween these drugs. Isobolograms were constructed by plottingsingle drug ED₅₀ points on the dose co-ordinates and a combinedED₅₀ point in the dose field. The calculated doses producing50% 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 theatracurium-mivacurium combination demonstrated zero interaction(additivism). An additional 26 patients anaesthetized with thiopentone-fentanyl-nitrousoxide—isoflurane were allocated randomly to receive eitheratracurium 0.5 mg kg^–1 (n = 13) or mivacurium 0.15 mgkg^–1 (n = 13). Additional maintenance doses of mivacurium0.1 mg kg^–1 were administered to patients in both groups,whenever the first twitch recovered to 10% of control. The durationof the first maintenance dose of mivacurium to 10% recoveryof 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 ofmivacurium after atracurium (18.3 (12.6–24) min) was similarto that of mivacurium after mivacurium (14.6 (10.6–18.6)min). We conclude that the combination of atracurium and mivacuriumis additive and that the use of mivacurium after atracurium-inducedneuromuscular block results in increased duration of the first(but not the subsequent) maintenance dose of mivacurium.