Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

Abhishek G. Sathe, Ellen Underwood, Lisa D. Coles, Jordan J. Elm, Robert Silbergleit, James M. Chamberlain, Jaideep Kapur, Hannah R. Cock, Nathan B. Fountain, Shlomo Shinnar, Daniel H. Lowenstein, Eric S. Rosenthal, Robin A. Conwit, Thomas P. Bleck, James C. Cloyd

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Objective: This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). Methods: Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second-line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline-recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second-line agent. Results: Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second-line medications in these benzodiazepine-refractory seizures. Significance: Benzodiazepines as first-line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT identifier: NCT01960075.).

Original languageEnglish (US)
Pages (from-to)795-806
Number of pages12
Issue number3
StatePublished - Mar 2021

Bibliographical note

Funding Information:
Research reported in this publication was supported by National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) under awards U01NS088034, U01NS088023, U01NS056975, U01NS059041, and R01NS099653 ( identifier NCT01960075). We would like to acknowledge the ESETT Data and Safety Monitoring Board. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS, the NIH, or the US Government.

Publisher Copyright:
© 2021 International League Against Epilepsy


  • benzodiazepine dose
  • diazepam
  • lorazepam
  • midazolam

PubMed: MeSH publication types

  • Clinical Trial
  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial'. Together they form a unique fingerprint.

Cite this