Comparative assessment of different doses of midazolam to prevent etomidate-induced myoclonus – A randomized, double-blind, placebo-controlled trial

Background: Etomidate is a popular induction agent, due to its several advantages for example, an extremely stable hemodynamic profile with no effects on sympathetic nervous system and baroreceptors, minimal effect on respiration and also prevents histamine release in healthy patients or in those with reactive airway disease. It, however, may be associated with myoclonus whose incidence has been reported as 50%–80% in nonpremedicated patients. Ideally, a pretreatment drug for preventing myoclonic movements should be short acting, not have significant effects on respiration and hemodynamics, and not prolong recovery from anesthesia. Midazolam has been used as a pretreatment to attenuate myoclonus in different doses with varied results, but the optimal dose has not been established. The present study was planned to compare the effect of three doses of midazolam, i.e., 0.015 mg/kg, 0.03 mg/kg, and 0.05 mg/kg in preventing etomidate-induced myoclonus. Materials and Methods: This study comprised 164 American Society of Anesthesiologists I/II consenting patients between 18 and 60 years. They were randomly divided into four groups after which pretreatment with normal saline in group M0, midazolam 0.015 mg/kg in group M0.015, 0.03 mg/kg in group M0.03, and 0.05 mg/kg in group M0.05 was administered. The primary outcome was the incidence of myoclonus after etomidate. The secondary outcome measures included severity of myoclonus and changes in hemodynamic parameters. One-way analysis of variance with Bonferroni's correction was used to compare quantitative data. Chi-square test was applied for qualitative data. Further, as there were four groups with multiple comparisons, Bonferroni's correction was applied and P < 0.01 was considered statistically significant. Results: We observed a significant reduction in the incidence of myoclonus of group M0.015 as compared to group M0 (P < 0.001). A significant reduction in severity of myoclonus was observed in all the three midazolam groups compared to the control group (P < 0.001) without any significance among the patients receiving different doses of midazolam. Conclusion: We recommend using midazolam pretreatment in a dose of 0.015 mg/kg for prevention of etomidate-induced myoclonus.