Comparison of pretreatment with low-dose midazolam in combination with fentanyl and midazolam alone on the occurrence of etomidate-induced myoclonus\u2014a randomized, double-blind study

Khaise Hareed,Nisha Kachru,Rupesh Yadav

doi:10.1186/s42077-021-00173-3

Abstract

BackgroundMyoclonus is reported to occur in 50–80% of patients receiving etomidate in the absence of pretreatment. The study aimed to evaluate the efficacy of pretreatment with low-dose midazolam and fentanyl, and midazolam alone to reduce the occurrence of etomidate-induced myoclonus. Sixty patients were randomly divided into 2 groups. In group MF, patients received pretreatment with intravenous (IV) midazolam 0.015mg/kg in a volume of 5 ml normal saline, followed by IV fentanyl 1μg/kg in a volume of 5 ml normal saline. In group M, patients received pretreatment with IV midazolam 0.03mg/kg in a volume of 5 ml normal saline, followed by 5ml of IV normal saline. The test drug was injected over 30 s, and after 120 s, IV etomidate 0.3 mg/kg was injected over 30 s. The patients were observed for 120 s for myoclonus and graded as mild, moderate, or severe. Heart rate, blood pressure, and oxygen saturation were recorded immediately after test drug injection and at every minute for 5 min.ResultsThe demographic parameters and hemodynamic parameters were comparable between the two groups. In group M, the incidence of myoclonus was 36.67% (26.67% mild and 10% moderate) whereas, in the group MF, the incidence of myoclonus was 26.67% (3.33% mild, 16.67% moderate, and 6.67% severe). This incidence of myoclonus was significantly lower in group MF (p=0.030).ConclusionsThe incidence of etomidate-induced myoclonus is significantly lower in patients pretreated with midazolam and fentanyl combination as compared to midazolam alone.Trial registrationClinical Trial Registry Details: CTRI/2019/05/018920

Highlights

Myoclonus is reported to occur in 50–80% of patients receiving etomidate in the absence of pretreatment
There have been studies regarding the use of various other drugs like remifentanil, ketamine for the prevention of etomidate-induced myoclonus (EIM) (Schwarzkopf et al, 2003; Hwang et al, 2008; Wu et al, 2016)
In group M, the incidence of myoclonus was 36.67% which comprised of 26.67% mild, 10% moderate, and 0% severe myoclonus while in the group MF, the incidence of myoclonus was 26.67% which comprised 3.33% mild, 16.67% moderate, and 6.67% severe degree of myoclonus and difference between two groups was statistically significant (p=0.030) (Table 2)

Summary

Introduction

Myoclonus is reported to occur in 50–80% of patients receiving etomidate in the absence of pretreatment Very few studies (Prakash et al, 2019; Isitemiz et al, 2014) have used a combination of fentanyl and midazolam, which is important to minimize any hemodynamic changes due to the individual drugs used to prevent myoclonus associated with etomidate. Though they have reported a decreased incidence of etomidate-induced myoclonus in those patients receiving the combination, the results from these studies are not conclusive regarding the best option to prevent etomidate-induced myoclonus

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