[Pharmacodynamics and clinical adverse effects of mivacurium. The effect of oral premedication with H1/H2 antagonists].

Duration of neuromuscular block may be prolonged by H1/H2 antagonists. This study was designed to determine the influence of H1/H2 antagonist treatment on onset, duration and recovery after mivacurium chloride (MIV), a new nondepolarizing neuromuscular blocking agent with a relatively short duration of action, which is metabolized by human plasma cholinesterase (PChE). METHODS. After approval from the hospital ethical committee and written informed consent, 48 ASA I-II patients of either sex (ages 18-65 years, weight 45-100 kg) were included in this double blind study and randomly allocated to four groups of 12 each: group A, 0.105 mg/kg MIV (1.5 x ED95) and H1/H2 antagonist; group B, 0.105 mg/kg MIV and placebo; group C, 0.21 mg/kg MIV (3 x ED95) and H1/H2 antagonist; Group D 0.21 mg/kg MIV and placebo. Premedication consisted of 2 mg lormetazepam p.o., 300 mg ranitidine and 0.1 mg/kg dimetindene, or placebo p.o. Anaesthesia was induced with thiopentone (5-7 mg/kg) and maintained with N2O/O2 at a 65/35 ratio, enflurane (0.8-1.5%) and supplements of fentanyl. The ulnar nerve was stimulated with supramaximal 2 Hz train-of-four (TOF) every 10 s. Neuromuscular twitch response was recorded with EMG. Onset time (time from end of injection to maximal or total block), maximal block (%), T125 (time from end of injection to 25% recovery) were recorded after each dose, and recovery index (T1 from 25% to 75% recovery) and TOF70 (time from end of injection to TOF ratio of 70%), after the last dose. RESULTS. The four groups did not differ with respect to age, weight or height. There was no difference in the pharmacodynamics of mivacurium between the groups receiving H1/H2 antagonists and those receiving placebo. Following 1.5 x ED95 the onset was at 3.7 +/- 1.2 (H1/H2) and 3.8 +/- 0.9 min (placebo), respectively. Clinical duration (T125) was 13.1 +/- 3.4 and 12.8 +/- 3.4 min. 3 x ED95 led to a significant faster onset and longer duration (P < or = 0.05). Onset was at 1.9 +/- 0.7 (H1/H2) and 2.1 +/- 0.5 min (placebo), respectively, and clinical duration 19.1 +/- 6.1 and 19.3 +/- 3.8 min. Duration of repetitive doses (10.1 +/- 5.3 min), recovery index (6.8 +/- 2.9 min) and interval from last dose to spontaneous recovery (22.4 +/- 7.0 min) did not differ between groups. Three patients in group D (placebo and 0.21 mg/kg MIV) had haemodynamic changes of over 20% from baseline. Flush and erythema were significantly less pronounced after H1/H2 premedication than after placebo (4 vs 12 pts). CONCLUSIONS. Our results suggest that time of onset and clinical duration of effects of MIV are not altered by dimetindene and ranitidine. The duration depends more heavily on the dose of MIV. The recovery of neuromuscular function, once it has begun, is prolonged neither by MIV nor by H1/H2 antagonists. As MIV is mainly broken down by PChE, it is evident that its duration of action is more prolonged by atypical PChE activity than by interaction with other drugs. Oral H1/H2 premedication may diminish haemodynamic side-effects and clinical signs of histamine release.