Association of Time to Treatment With Short-term Outcomes for Pediatric Patients With Refractory Convulsive Status Epilepticus

Abstract

; for the Pediatric Status Epilepticus Research Group IMPORTANCE 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 ϱ; 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.

Long‐term outcomes of status epilepticus: A critical assessment

“…Delays in time to treatment are independently associated with worse outcomes in the short term (higher mortality, higher need for continuous infusions, longer convulsive duration, and more frequent hypotension). [1][2][3]33,82,83 Families and caregivers play a crucial role, as timely treatment is often possible if families and caregivers administer a rescue medication at home and quickly call emergency services. [84][85][86] However, a survey of 100 families of patients with epilepsy showed that 87% had a rescue medication prescription, but only 61% of them reported receiving training on how to use it.…”

Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population‐based study on German health insurance data

“…23,24,26 Despite an increased incidence rate in children, reduced mortality rates have been observed compared to adult populations. [24][25][26] There have been few studies on the outcome of pediatric SE, 6,27,28 and much less is known about pediatric SRSE.…”

The ADAN scale: a proposed scale for pre‐hospital use to identify status epilepticus

“…It is well recognized that prolonged duration of SE is an important factor related to prognosis. The time lapse from onset to diagnosis and treatment have been related to a poorer functional outcome in SE.…”

“…One of the main modifiable prognostic factors in SE is the duration of the episode , which is influenced by how quickly the various lines of treatment are applied (among other factors) . Depending on the type of SE, treatment should be initiated between 5 and 15 min after the onset of the episode ; hence, it is important to detect and treat patients with SE in the out‐of‐hospital setting .…”