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November 10, 2020; 95 (19) Article

First-line medication dosing in pediatric refractory status epilepticus

Alejandra Vasquez, Marina Gaínza-Lein, Nicholas S. Abend, Marta Amengual-Gual, Anne Anderson, View ORCID ProfileRavindra Arya, View ORCID ProfileJ. Nicholas Brenton, Jessica L. Carpenter, Kevin Chapman, Justice Clark, Raquel Farias-Moeller, William D. Gaillard, Tracy Glauser, Joshua L. Goldstein, Howard P. Goodkin, View ORCID ProfileRejean M. Guerriero, View ORCID ProfileKush Kapur, Yi-Chen Lai, Tiffani L. McDonough, Mohamad A. Mikati, Lindsey A. Morgan, View ORCID ProfileEdward J. Novotny, Adam P. Ostendorf, View ORCID ProfileEric T. Payne, Katrina Peariso, Juan Piantino, James J. Riviello, Kumar Sannagowdara, View ORCID ProfileRobert C. Tasker, View ORCID ProfileDmitry Tchapyjnikov, Alexis Topjian, View ORCID ProfileMark S. Wainwright, Angus Wilfong, Korwyn Williams, Tobias Loddenkemper, on behalf of the Pediatric Status Epilepticus Research Group (pSERG)
First published September 10, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010828
Alejandra Vasquez
From the Division of Epilepsy and Clinical Neurophysiology (A.V., M.G.-L., M.A.-G., J.C., T.L.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, MA; Division of Child and Adolescent Neurology (A.V., E.T.P.), Department of Neurology, Mayo Clinic, Rochester, MN; Instituto de Pediatría, Facultad de Medicina (M.G.-L.), Universidad Austral de Chile, Valdivia; Servicio de Neuropsiquiatría Infantil (M.G.-L.), Hospital Clínico San Borja Arriarán, Universidad de Chile, Santiago; Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania; Pediatric Neurology Unit (M.A.-G.), Department of Pediatrics, Hospital Universitari Son Espases, Universitat de les Illes Balears, Palma, Spain; Section of Neurology and Developmental Neuroscience (A.A., J.J.R.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Division of Neurology (R.A., T.G., K.P.), Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, OH; Department of Neurology and Pediatrics (J.N.B., H.P.G.), University of Virginia Health System, Charlottesville; Center for Neuroscience (J.L.C., W.D.G.), Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC; Departments of Pediatrics and Neurology (K.C.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora; Department of Neurology (R.F.-M., K.S.), Division of Pediatric Neurology, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee; Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program (J.L.G.), Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric Neurology (R.M.G.), Washington University Medical Center, Washington University School of Medicine, St. Louis, MO; Department of Neurology (K.K.), Boston Children's Hospital, Harvard Medical School, MA; Section of Pediatric Critical Medicine (Y.-C.L.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Division of Child Neurology (T.L.M.), Department of Neurology, Columbia University Medical Center, Columbia University, New York, NY; Division of Pediatric Neurology (T.L.M.), Ann & Robert H. Lurie Children's Hospital of Chicago, IL; Division of Pediatric Neurology (M.A.M., D.T.), Duke University Medical Center, Duke University, Durham, NC; Department of Neurology (L.A.M., E.J.N., M.S.W.), Division of Pediatric Neurology, University of Washington, Seattle; Center for Integrative Brain Research (E.J.N.), Seattle Children's Research Institute, WA; Department of Pediatrics (A.P.O.), Nationwide Children's Hospital, The Ohio State University, Columbus; Department of Pediatrics (J.P.), Division Pediatric Neurology, Neuro-Critical Care Program, Oregon Health and Science University, Portland; Division of Critical Care (R.C.T.), Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, MA; Critical Care and Pediatrics (A.T.), The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine; and Department of Child Health (A.W., K.W.), University of Arizona College of Medicine and Barrow's Neurological Institute at Phoenix Children's Hospital.
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Marina Gaínza-Lein
MD
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Nicholas S. Abend
MD, MSCE
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Marta Amengual-Gual
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Anne Anderson
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Ravindra Arya
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J. Nicholas Brenton
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Jessica L. Carpenter
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Kevin Chapman
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Justice Clark
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Raquel Farias-Moeller
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William D. Gaillard
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Tracy Glauser
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Joshua L. Goldstein
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Howard P. Goodkin
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Rejean M. Guerriero
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Kush Kapur
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Yi-Chen Lai
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Tiffani L. McDonough
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Mohamad A. Mikati
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Lindsey A. Morgan
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Edward J. Novotny
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Adam P. Ostendorf
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Eric T. Payne
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Katrina Peariso
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Juan Piantino
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James J. Riviello
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Kumar Sannagowdara
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Robert C. Tasker
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Dmitry Tchapyjnikov
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Alexis Topjian
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Mark S. Wainwright
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Angus Wilfong
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Korwyn Williams
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Tobias Loddenkemper
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Citation
First-line medication dosing in pediatric refractory status epilepticus
Alejandra Vasquez, Marina Gaínza-Lein, Nicholas S. Abend, Marta Amengual-Gual, Anne Anderson, Ravindra Arya, J. Nicholas Brenton, Jessica L. Carpenter, Kevin Chapman, Justice Clark, Raquel Farias-Moeller, William D. Gaillard, Tracy Glauser, Joshua L. Goldstein, Howard P. Goodkin, Rejean M. Guerriero, Kush Kapur, Yi-Chen Lai, Tiffani L. McDonough, Mohamad A. Mikati, Lindsey A. Morgan, Edward J. Novotny, Adam P. Ostendorf, Eric T. Payne, Katrina Peariso, Juan Piantino, James J. Riviello, Kumar Sannagowdara, Robert C. Tasker, Dmitry Tchapyjnikov, Alexis Topjian, Mark S. Wainwright, Angus Wilfong, Korwyn Williams, Tobias Loddenkemper, on behalf of the Pediatric Status Epilepticus Research Group (pSERG)
Neurology Nov 2020, 95 (19) e2683-e2696; DOI: 10.1212/WNL.0000000000010828

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Abstract

Objective To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation.

Methods This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation.

Results We included 289 patients (55.7% male) with a median age of 4.3 (1.3–9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18–3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05–1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23–3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24–3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57–0.95).

Conclusion BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation.

Classification of evidence This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.

Glossary

ASM=
antiseizure medication;
BZD=
benzodiazepine;
CI=
confidence interval;
DZP=
diazepam;
ESETT=
Established Status Epilepticus Treatment Trial;
HR=
hazard ratio;
ICU=
intensive care unit;
IM=
intramuscular;
LZP=
lorazepam;
MDZ=
midazolam;
OR=
odds ratio;
PR=
per rectum;
pSERG=
Pediatric Status Epilepticus Research Group;
p25–p75=
interquartile range;
RSE=
refractory SE;
SE=
status epilepticus

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.

  • Coinvestigators are listed at links.lww.com/WNL/B215.

  • Class of Evidence: NPub.org/coe

  • Received September 26, 2019.
  • Accepted in final form July 22, 2020.
  • © 2020 American Academy of Neurology
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  • All Epilepsy/Seizures
  • Antiepileptic drugs
  • Status epilepticus

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