Elan L Guterman1, Joseph K Sanford2, John P Betjemann2, Li Zhang2, James F Burke2, Daniel H Lowenstein2, S Andrew Josephson2, Karl A Sporer2. 1. From the Department of Neurology (E.L.G., J.K.S., J.P.B., D.H.L., S.A.J.), Weill Institute for Neurosciences (E.L.G., J.K.S., J.P.B., D.H.L., S.A.J.), Department of Epidemiology & Biostatistics (L.Z.), Department of Medicine (L.Z.), and Department of Emergency Medicine (K.A.S.), University of California, San Francisco; and Department of Neurology (J.F.B.), University of Michigan, Ann Arbor. Elan.Guterman@ucsf.edu. 2. From the Department of Neurology (E.L.G., J.K.S., J.P.B., D.H.L., S.A.J.), Weill Institute for Neurosciences (E.L.G., J.K.S., J.P.B., D.H.L., S.A.J.), Department of Epidemiology & Biostatistics (L.Z.), Department of Medicine (L.Z.), and Department of Emergency Medicine (K.A.S.), University of California, San Francisco; and Department of Neurology (J.F.B.), University of Michigan, Ann Arbor.
Abstract
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.
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.
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