Higher doses of midazolam may reduce the need for rescue therapy without increasing ventilatory support requirements in patients with status epilepticus, according to study results published in Neurology suggest.

In this study, a team of researchers sought to evaluate benzodiazepine use in patients with status epilepticus, and the relationship between benzodiazepine dose and clinical outcomes.

To achieve this, they conducted a cross-sectional analysis of 2494 patients with status epilepticus (mean age, 54 years) who were treated by an emergency medical service (EMS) agency between 2013 and 2018. Study researchers obtained these patient and treatment data from EMS medical records. The primary outcome of the analysis was the need for rescue therapy, defined by treatment with a second benzodiazepine dose. Additionally, a secondary outcome included receipt of respiratory support. The only benzodiazepine used in these participants was midazolam.

The agency treatment protocol suggests either a single dose of 0.1 mg/kg up to a maximum of 6 mg or a single 5 mg dose for intranasal administration. National guidelines, however, suggest first-line treatment with midazolam should be a single 10 mg dose delivered intramuscularly.

A total of 1537 patients received midazolam at any dose, corresponding to a treatment administration rate of approximately 62 percent. None of the patients in this analysis received a dose and treatment route recommended by national guidelines. About 18 percent of patients required rescue therapy with a second midazolam dose. 99.5 percent of the 943 patients who received a midazolam dose of at least 5 mg had received a dose of 5 mg, while only 0.5 percent received a dose greater than 5 mg.

Higher doses of midazolam were associated with lower odds of requiring rescue treatment (odds ratio [OR], 0.8; 95% CI, 0.7-0.9). There was no association between receiving higher doses of midazolam and an increased respiratory support need (OR, 1.0; 95% CI, 0.9-1.0). Study researchers found evidence to support the notion that higher doses of midazolam were associated with reduced respiratory support needs in an adjusted analysis (OR, 0.9; 95% CI, 0.8-1.0).

Limitations of this study were the use of “incomplete” prehospital medical records, as well as the inability to validate whether reduced rescue therapy needs actually represented lack of seizure recurrence.

The study researchers concluded that their findings indicated “that a higher initial midazolam dose, even if the dose is below that recommended in national guidelines, is associated with increased rates of successful seizure termination.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Guterman EL, Sanford JK, Betjemann JP, et al. Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus. Neurology. 2020;95(24):3203-3212. doi:10.1212/WNL.0000000000010913

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