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Choice of benzodiazepine, doses given prior to administration of second\u2010line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline\u2010recommended 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\u2010line agent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, &gt;85% of midazolam and &gt;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\u2010line medications in these benzodiazepine\u2010refractory seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Benzodiazepines as first\u2010line 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 ClinicalTrials.gov identifier: NCT01960075.)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16825","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:45:06Z","timestamp":1613004306000},"page":"795-806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7348-4208","authenticated-orcid":false,"given":"Abhishek G.","family":"Sathe","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy and Center for Orphan Drug Research University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Underwood","sequence":"additional","affiliation":[{"name":"Department of Public Health Science Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-9904","authenticated-orcid":false,"given":"Lisa D.","family":"Coles","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy and Center for Orphan Drug Research University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan J.","family":"Elm","sequence":"additional","affiliation":[{"name":"Department of Public Health Science Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4101-2430","authenticated-orcid":false,"given":"Robert","family":"Silbergleit","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Chamberlain","sequence":"additional","affiliation":[{"name":"Division of Emergency Medicine Children's National Hospital and Department of Pediatrics and Emergency Medicine School of Medicine and Health Sciences George Washington University Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-1352","authenticated-orcid":false,"given":"Jaideep","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology and Department of Neuroscience, Brain Institute University of Virginia Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-0141","authenticated-orcid":false,"given":"Hannah R.","family":"Cock","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Academic Group Institute of Molecular and Clinical Sciences St. George\u2019s University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-0308","authenticated-orcid":false,"given":"Nathan B.","family":"Fountain","sequence":"additional","affiliation":[{"name":"Department of Neurology Comprehensive Epilepsy Program University of Virginia Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6714-3960","authenticated-orcid":false,"given":"Shlomo","family":"Shinnar","sequence":"additional","affiliation":[{"name":"Montefiore Medical Center Albert Einstein College of Medicine Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5869-4020","authenticated-orcid":false,"given":"Daniel H.","family":"Lowenstein","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California, San Francisco San Francisco 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