Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus

Neurology. 2020 Dec 15;95(24):e3203-e3212. doi: 10.1212/WNL.0000000000010913. Epub 2020 Sep 17.


Objective: To examine the use of benzodiazepines and the association between low benzodiazepine dose, breakthrough seizures, and respiratory support in patients with status epilepticus.

Methods: In this cross-sectional analysis of adult patients with status epilepticus treated by an emergency medical services agency from 2013 to 2018, the primary outcome was treatment with a second benzodiazepine dose, an indicator for breakthrough seizure. The secondary outcome was receiving respiratory support. Midazolam was the only benzodiazepine administered.

Results: Among 2,494 patients with status epilepticus, mean age was 54.0 years and 1,146 (46%) were female. There were 1,537 patients given midazolam at any dose, yielding an administration rate of 62%. No patients received a dose and route consistent with national guidelines. Rescue therapy with a second midazolam dose was required in 282 (18%) patients. Higher midazolam doses were associated with lower odds of rescue therapy (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.7-0.9) and were not associated with increased respiratory support. If anything, higher doses of midazolam were associated with decreased need for respiratory support after adjustment (OR, 0.9; 95% CI, 0.8-1.0).

Conclusions: An overwhelming majority of patients with status epilepticus did not receive evidence-based benzodiazepine treatment. Higher midazolam doses were associated with reduced use of rescue therapy and there was no evidence of respiratory harm, suggesting that benzodiazepines are withheld without clinical benefit.

Classification of evidence: This study provides Class III evidence that for patients with status epilepticus, higher doses of midazolam led to a reduced use of rescue therapy without an increased need for ventilatory support.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzodiazepines / administration & dosage*
  • Cross-Sectional Studies
  • Emergency Medical Services* / statistics & numerical data
  • Evidence-Based Medicine
  • Female
  • Guideline Adherence
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Male
  • Midazolam / administration & dosage*
  • Middle Aged
  • Outcome and Process Assessment, Health Care* / statistics & numerical data
  • Practice Guidelines as Topic*
  • Respiration, Artificial* / statistics & numerical data
  • Status Epilepticus / drug therapy
  • Status Epilepticus / therapy*


  • Hypnotics and Sedatives
  • Benzodiazepines
  • Midazolam