Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus
Sánchez Fernández, Iván
Abend, Nicholas S.
Brenton, J. Nicholas
Carpenter, Jessica L.
Chapman, Kevin E.
Gaillard, William D.
Glauser, Tracy A.
Goldstein, Joshua L.
Goodkin, Howard P.
Mikati, Mohamad A.
Tasker, Robert C.
Topjian, Alexis A.
Wainwright, Mark S.
AffiliationUniv Arizona, Sch Med, Dept Pediat, Barrows Neurol Inst,Phoenix Childrens Hosp, Phoenix, AZ USA
MetadataShow full item record
PublisherAMER MEDICAL ASSOC
CitationGaínza-Lein M, Sánchez Fernández I, Jackson M, et al. Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus. JAMA Neurol. 2018;75(4):410–418. doi:10.1001/jamaneurol.2017.4382
Rights© 2018 American Medical Association. All rights reserved.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractIMPORTANCE Treatment delay for seizures can lead to longer seizure duration. Whether treatment delay is associated with major adverse outcomes, such as death, remains unknown. OBJECTIVE To evaluate whether untimely first-line benzodiazepine treatment is associated with unfavorable short-term outcomes. DESIGN, SETTING, AND PARTICIPANTS This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in the United States within the Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1 month to 21 years, with refractory convulsive status epilepticus (RCSE) that did not stop after the administration of at least 2 antiseizure medications were included. Patients were divided into 2 cohorts: those who received the first-line benzodiazepine treatment in less than 10 minutes and those who received it 10 or more minutes after seizure onset (untimely). Data were collected and analyzed from June 1, 2011, to July 7, 2016. MAIN OUTCOMES AND MEASURES The primary outcome was death during the related hospital admission. The secondary outcome was the need for continuous infusion for seizure termination. Multivariate analysis of mortality controlled for structural cause, febrile RCSE, age, and previous neurological history (including previous RCSE events). Use of continuous infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5 or more administrations of antiseizure medication. RESULTS A total of 218 patients were included, among whom 116 (53.2%) were male and the median (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%) received their first-line benzodiazepine treatment in less than 10 minutes, and 144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate analysis showed that patients who received untimely first-line benzodiazepine treatment had higher odds of death (adjusted odds ratio [AOR], 11.0; 95% CI, 1.43 to infinity; P = .02), had greater odds of receiving continuous infusion (AOR, 1.8; 95% CI, 1.01-3.36; P = .047), had longer convulsive seizure duration (AOR, 2.6; 95% CI, 1.38-4.88; P = .003), and had more frequent hypotension (AOR 2.3; 95% CI, 1.16-4.63; P = .02). In addition, the timing of the first-line benzodiazepine treatment was correlated with the timing of the second-line (95% CI, 0.64-0.95; P < .001) and third-line antiseizure medications (95% CI, 0.25-0.78; P < .001). CONCLUSIONS AND RELEVANCE Among pediatric patients with RCSE, an untimely first-line benzodiazepine treatment is independently associated with a higher frequency of death, use of continuous infusions, longer convulsion duration, and more frequent hypotension. Results of this study raise the question as to whether poor outcomes could, in part, be prevented by earlier administration of treatment.
Note12 month embargo, April 2018
VersionFinal published version
SponsorsEpilepsy Research Fund; Pediatric Epilepsy Research Foundation; Epilepsy Foundation of America [EF-213583]; American Epilepsy Society/Epilepsy Foundation of America Infrastructure Awards
- Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.
- Authors: Tasker RC, Goodkin HP, Sánchez Fernández I, Chapman KE, Abend NS, Arya R, Brenton JN, Carpenter JL, Gaillard WD, Glauser TA, Goldstein J, Helseth AR, Jackson MC, Kapur K, Mikati MA, Peariso K, Wainwright MS, Wilfong AA, Williams K, Loddenkemper T, Pediatric Status Epilepticus Research Group.
- Issue date: 2016 Oct
- Admissions to paediatric intensive care units (PICU) with refractory convulsive status epilepticus (RCSE): A two-year multi-centre study.
- Authors: Tully I, Draper ES, Lamming CR, Mattison D, Thomas C, Martland T, Appleton R
- Issue date: 2015 Jul
- Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.
- Authors: McTague A, Martland T, Appleton R
- Issue date: 2018 Jan 10
- Treatment of Convulsive Status Epilepticus.
- Authors: Grover EH, Nazzal Y, Hirsch LJ
- Issue date: 2016 Mar
- Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation.
- Authors: Kowalski RG, Ziai WC, Rees RN, Werner JK Jr, Kim G, Goodwin H, Geocadin RG
- Issue date: 2012 Sep