Observational Study

. 2015 Jun 9;84(23):2304-11.

doi: 10.1212/WNL.0000000000001673. Epub 2015 May 6.

Time from convulsive status epilepticus onset to anticonvulsant administration in children

Iván Sánchez Fernández¹, Nicholas S Abend¹, Satish Agadi¹, Sookee An¹, Ravindra Arya¹, James Nicholas Brenton¹, Jessica L Carpenter¹, Kevin E Chapman¹, William D Gaillard¹, Tracy A Glauser¹, Howard P Goodkin¹, Kush Kapur¹, Mohamad A Mikati¹, Katrina Peariso¹, Margie Ream¹, James Riviello Jr¹, Robert C Tasker¹, Tobias Loddenkemper²; Pediatric Status Epilepticus Research Group (pSERG)

Affiliations

¹ From the Division of Epilepsy and Clinical Neurophysiology, Department of Neurology (I.S.F., S. An, K.K., T.L.), and the Division of Critical Care, Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine (R.C.T.), Boston Children's Hospital, Harvard Medical School, MA; the Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, University of Barcelona, Spain; the Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania; the Section of Neurology and Developmental Neuroscience, Department of Pediatrics (S. Agadi), Baylor College of Medicine, Houston, TX; the Comprehensive Epilepsy Center (R.A., T.A.G.), Division of Neurology (K.P.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH; the Departments of Neurology and Pediatrics (J.N.B., H.P.G.), The University of Virginia Health System, Charlottesville; the Department of Epilepsy, Neurophysiology, and Critical Care Neurology (J.L.C., W.D.G.), Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC; the Departments of Pediatrics and Neurology (K.E.C.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora; the Division of Pediatric Neurology (M.A.M.), Duke University Medical Center, Duke University, Durham, NC; the Division of Neurocritical Care (K.P.), University of Cincinnati Medical Center, OH; the Division of Pediatric Neurology (M.R.), Nationwide Children's Hospital, The Ohio State University, Columbus; and the Division of Child Neurology (J.R.), Columbia University Medical Center, Columbia University, New York, NY.
² From the Division of Epilepsy and Clinical Neurophysiology, Department of Neurology (I.S.F., S. An, K.K., T.L.), and the Division of Critical Care, Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine (R.C.T.), Boston Children's Hospital, Harvard Medical School, MA; the Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, University of Barcelona, Spain; the Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania; the Section of Neurology and Developmental Neuroscience, Department of Pediatrics (S. Agadi), Baylor College of Medicine, Houston, TX; the Comprehensive Epilepsy Center (R.A., T.A.G.), Division of Neurology (K.P.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH; the Departments of Neurology and Pediatrics (J.N.B., H.P.G.), The University of Virginia Health System, Charlottesville; the Department of Epilepsy, Neurophysiology, and Critical Care Neurology (J.L.C., W.D.G.), Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC; the Departments of Pediatrics and Neurology (K.E.C.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora; the Division of Pediatric Neurology (M.A.M.), Duke University Medical Center, Duke University, Durham, NC; the Division of Neurocritical Care (K.P.), University of Cincinnati Medical Center, OH; the Division of Pediatric Neurology (M.R.), Nationwide Children's Hospital, The Ohio State University, Columbus; and the Division of Child Neurology (J.R.), Columbia University Medical Center, Columbia University, New York, NY. tobias.loddenkemper@childrens.harvard.edu.

PMID: 25948729
PMCID: PMC4464741
DOI: 10.1212/WNL.0000000000001673

Observational Study

Time from convulsive status epilepticus onset to anticonvulsant administration in children

Iván Sánchez Fernández et al. Neurology. 2015.

. 2015 Jun 9;84(23):2304-11.

doi: 10.1212/WNL.0000000000001673. Epub 2015 May 6.

Authors

Affiliations

¹ From the Division of Epilepsy and Clinical Neurophysiology, Department of Neurology (I.S.F., S. An, K.K., T.L.), and the Division of Critical Care, Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine (R.C.T.), Boston Children's Hospital, Harvard Medical School, MA; the Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, University of Barcelona, Spain; the Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania; the Section of Neurology and Developmental Neuroscience, Department of Pediatrics (S. Agadi), Baylor College of Medicine, Houston, TX; the Comprehensive Epilepsy Center (R.A., T.A.G.), Division of Neurology (K.P.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH; the Departments of Neurology and Pediatrics (J.N.B., H.P.G.), The University of Virginia Health System, Charlottesville; the Department of Epilepsy, Neurophysiology, and Critical Care Neurology (J.L.C., W.D.G.), Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC; the Departments of Pediatrics and Neurology (K.E.C.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora; the Division of Pediatric Neurology (M.A.M.), Duke University Medical Center, Duke University, Durham, NC; the Division of Neurocritical Care (K.P.), University of Cincinnati Medical Center, OH; the Division of Pediatric Neurology (M.R.), Nationwide Children's Hospital, The Ohio State University, Columbus; and the Division of Child Neurology (J.R.), Columbia University Medical Center, Columbia University, New York, NY.
² From the Division of Epilepsy and Clinical Neurophysiology, Department of Neurology (I.S.F., S. An, K.K., T.L.), and the Division of Critical Care, Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine (R.C.T.), Boston Children's Hospital, Harvard Medical School, MA; the Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, University of Barcelona, Spain; the Division of Neurology (N.S.A.), The Children's Hospital of Philadelphia, The Perelman School of Medicine at the University of Pennsylvania; the Section of Neurology and Developmental Neuroscience, Department of Pediatrics (S. Agadi), Baylor College of Medicine, Houston, TX; the Comprehensive Epilepsy Center (R.A., T.A.G.), Division of Neurology (K.P.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH; the Departments of Neurology and Pediatrics (J.N.B., H.P.G.), The University of Virginia Health System, Charlottesville; the Department of Epilepsy, Neurophysiology, and Critical Care Neurology (J.L.C., W.D.G.), Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC; the Departments of Pediatrics and Neurology (K.E.C.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora; the Division of Pediatric Neurology (M.A.M.), Duke University Medical Center, Duke University, Durham, NC; the Division of Neurocritical Care (K.P.), University of Cincinnati Medical Center, OH; the Division of Pediatric Neurology (M.R.), Nationwide Children's Hospital, The Ohio State University, Columbus; and the Division of Child Neurology (J.R.), Columbia University Medical Center, Columbia University, New York, NY. tobias.loddenkemper@childrens.harvard.edu.

PMID: 25948729
PMCID: PMC4464741
DOI: 10.1212/WNL.0000000000001673

Abstract

Objective: To describe the time elapsed from onset of pediatric convulsive status epilepticus (SE) to administration of antiepileptic drug (AED).

Methods: This was a prospective observational cohort study performed from June 2011 to June 2013. Pediatric patients (1 month-21 years) with convulsive SE were enrolled. In order to study timing of AED administration during all stages of SE, we restricted our study population to patients who failed 2 or more AED classes or needed continuous infusions to terminate convulsive SE.

Results: We enrolled 81 patients (44 male) with a median age of 3.6 years. The first, second, and third AED doses were administered at a median (p25-p75) time of 28 (6-67) minutes, 40 (20-85) minutes, and 59 (30-120) minutes after SE onset. Considering AED classes, the initial AED was a benzodiazepine in 78 (96.3%) patients and 2 (2-3) doses of benzodiazepines were administered before switching to nonbenzodiazepine AEDs. The first and second doses of nonbenzodiazepine AEDs were administered at 69 (40-120) minutes and 120 (75-296) minutes. In the 64 patients with out-of-hospital SE onset, 40 (62.5%) patients did not receive any AED before hospital arrival. In the hospital setting, the first and second in-hospital AED doses were given at 8 (5-15) minutes and 16 (10-40) minutes after SE onset (for patients with in-hospital SE onset) or after hospital arrival (for patients with out-of-hospital SE onset).

Conclusions: The time elapsed from SE onset to AED administration and escalation from one class of AED to another is delayed, both in the prehospital and in-hospital settings.

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Figures

**Figure 1. Kaplan-Meier curves representing time from seizure onset to administration of the first AED (green), second AED (blue), and third AED (red)**
Time axis is truncated at 100 minutes. As an illustration of the delays in antiepileptic drug (AED) administration, 40 minutes after seizure onset, approximately 60% of patients had received their first AED, approximately 45% of patients had received a second AED, and approximately 25% of patients had received their third AED.

**Figure 2. Kaplan-Meier curves representing time to benzodiazepine and non-benzodiazepine antiepileptic drug administration**
(A) Time from status epilepticus (SE) onset to benzodiazepine (BZD) administration. Time axis truncated at 100 minutes. Time to administration of first BZD (green) and second BZD (blue). As an illustration of the delays in BZD administration, 20 minutes after seizure onset, approximately 40% of patients had received their first BZD and approximately 25% of patients had received a second BZD. (B) Time from SE onset to non-BZD antiepileptic drug (AED) administration. Time axis truncated at 100 minutes. Time to administration of first non-BZD AED (green) and second non-BZD AED (blue). As an illustration of the delays in non-BZD AED administration, 40 minutes after seizure onset, approximately 25% of patients had received their first non-BZD AED and approximately 10% of patients had received a second non-BZD AED.

**Figure 3. Kaplan-Meier curves representing time to antiepileptic drug administration in the prehospital and in-hospital settings**
(A) Time from status epilepticus (SE) onset to out-of-hospital antiepileptic drug (AED) administration for patients with out-of-hospital SE onset (times were censored on hospital arrival). Time axis truncated at 100 minutes. Time to administration of first out-of-hospital AED (green) and second out-of-hospital AED (blue). As an illustration of the delays in the prehospital administration of AEDs, 20 minutes after seizure onset, approximately 25% of patients had received their first AED and approximately 10% of patients had received a second AED. (B) Time from hospital management (time 0 was time of SE onset for patients with in-hospital SE onset; time 0 was time of hospital arrival for patients with out-of-hospital SE onset) to in-hospital AED administration. Time axis truncated at 60 minutes. Time to administration of first in-hospital AED (green) and second in-hospital AED (blue). As an illustration of the delays in in-hospital administration of AEDs, 20 minutes after initiation of hospital management, approximately 75% of patients had received their first in-hospital AED and approximately 50% of patients had received a second in-hospital AED.

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Comment in

Status epilepticus: For what are we waiting?
Thio LL, Wainwright MS. Thio LL, et al. Neurology. 2015 Jun 9;84(23):2296-7. doi: 10.1212/WNL.0000000000001670. Epub 2015 May 6. Neurology. 2015. PMID: 25948730 No abstract available.

References

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1. Chin RF, Neville BG, Peckham C, Bedford H, Wade A, Scott RC. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet 2006;368:222–229. - PubMed
1. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996;46:1029–1035. - PubMed
1. Loddenkemper T, Syed TU, Ramgopal S, et al. Risk factors associated with death in in-hospital pediatric convulsive status epilepticus. PLoS One 2012;7:e47474. - PMC - PubMed
1. Maytal J, Shinnar S, Moshe SL, Alvarez LA. Low morbidity and mortality of status epilepticus in children. Pediatrics 1989;83:323–331. - PubMed

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Time from convulsive status epilepticus onset to anticonvulsant administration in children

Affiliations

Time from convulsive status epilepticus onset to anticonvulsant administration in children

Authors

Affiliations

Abstract

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials