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December 15, 2020; 95 (24) Article

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

Elan L. Guterman, Joseph K. Sanford, John P. Betjemann, Li Zhang, James F. Burke, Daniel H. Lowenstein, S. Andrew Josephson, Karl A. Sporer
First published September 17, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010913
Elan L. Guterman
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.
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Joseph K. Sanford
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.
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John P. Betjemann
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.
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Li Zhang
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.
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James F. Burke
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.
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Daniel H. Lowenstein
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.
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S. Andrew Josephson
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.
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Karl A. Sporer
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.
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Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus
Elan L. Guterman, Joseph K. Sanford, John P. Betjemann, Li Zhang, James F. Burke, Daniel H. Lowenstein, S. Andrew Josephson, Karl A. Sporer
Neurology Dec 2020, 95 (24) e3203-e3212; DOI: 10.1212/WNL.0000000000010913

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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.

Glossary

CI=
confidence interval;
EMS=
emergency medical services;
GCS=
Glasgow Coma Scale;
IQR=
interquartile range;
NOS=
not otherwise specified;
OR=
odds ratio

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • Received March 5, 2020.
  • Accepted in final form August 3, 2020.
  • © 2020 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Author response: Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus
    • Elan L. Guterman, Neurologist, University of California, San Francisco
    • Joseph K. Sanford, Neurologist, University of California, San Francisco
    • John P. Betjemann, Neurologist, Kaiser Permanente
    • Li Zhang, Statistics, University of California, San Francisco
    • James F. Burke, Neurologist, University of Michigan
    • Daniel H Lowenstein, Neurologist, University of California, San Francisco
    • S. Andrew Josephson, Neurologist, University of California, San Francisco
    • Karl A. Sporer, Emergency Medicine, University of California, San Francisco
    Submitted January 06, 2021
  • Reader response: Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus
    • Christoph Kellinghaus, Neurologist, Dept. of Neurology, Klinikum Osnabrück, Osnabrück, Germany
    • Andrea O. Rossetti, Neurologist, Department of Clinical Neurosciences, CHUV and University of Lausanne, Switzerland
    • Stephan Rüegg, Neurologist, Department of Neurology, University Hospital Basel, Switzerland
    • Eugen Trinka, Neurologist, Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
    • Felix Rosenow, Neurologist, 12Epilepsy Center Frankfurt Rhein-Main, Department of Neurology, University Hospital Frankfurt and Goethe University, Frankfurt,
    Submitted December 23, 2020
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