Status epilepticus - continuous seizure activity for 30 minutes or more - is a medical emergency with a high mortality rate. Prompt and effective treatment is key, but defining the best treatments is an area of intense debate. Three studies presented at the American Epilepsy Society's (AES) 69th Annual Meeting clarify the benefits and drawbacks of commonly used strategies for managing status epilepticus in pediatric patients.
The first study (abstract 1.123) offers evidence to refute the long-held notion that children experiencing status epilepticus should be given continuous intravenous infusions if they fail to respond to two antiepileptic drugs.
A multicenter team, including researchers at the University of Colorado at Denver, prospectively studied 111 children treated for drug-resistant status epilepticus at nine tertiary pediatric hospitals in the United States. During the two -year study period, the team examined clinical data from patients who experienced convulsive seizures that did not stop after administration of at least two antiepileptic drugs. All patients were admitted to the pediatric intensive care unit, and nearly half of the patients received continuous intravenous infusions.
Continuous infusions did not reduce seizure duration, according to the authors. By contrast, children who experienced status epilepticus for longer than 30 minutes fared worse if they received a continuous infusion compared with a bolus dose of antiepileptic drugs. Continuous intravenous infusions were associated with more frequent hypotension and use of vasopressors and a longer stay in the PICU, compared with on-time treatments.
"Given these variations in response and morbidity, continuous intravenous therapy may not be appropriate for all patients with drug-resistant status epilepticus," says author Kevin Chapman, M.D., an associate professor of neurology at Children's Hospital Colorado.
A second study (abstract 2.183) shows that the sedative ketamine is increasingly used for the most drug-resistant cases of status epilepticus in children. Ketamine is delivered as a continuous infusion but has fewer side effects compared with other similar medications often used for status epilepticus.
The study was led by investigators at Weill Cornell Medicine in collaboration with researchers at Boston Children's Hospital. They performed a retrospective multicenter examination of cases of pediatric status epilepticus by using the Pediatric Hospital Information System (PHIS) database. PHIS is an administrative database that contains data from over 45 not-for-profit, tertiary care pediatric hospitals in the United States. Their study shows that children with status epilepticus who were treated with ketamine required longer stays in the intensive care unit, longer EEG monitoring, more frequent use of medicines to support low blood pressure and longer ventilator use. Ketamine use for status epilepticus dramatically increased from 2010 to 2014, according to the study, both in terms of the number of hospitals that rely on the drug and the number of patients treated with it.
"These findings are consistent with our own practice to reserve ketamine for the most challenging cases. More studies are needed to understand the safety and clinical outcomes of ketamine for children with drug-resistant status epilepticus," says author Sotirios Keros, M.D., Ph.D., a clinical assistant professor of pediatrics at Weill Cornell Medicine and University of South Dakota School of Medicine.
A third study (abstract 3.177) finds that the duration of status epilepticus in children depends in part on the length of time between seizure onset and initial benzodiazepine treatment, among other factors.
The findings, reported by researchers at Boston Children's Hospital in collaboration with investigators from 10 other major children's hospitals around the nation, stem from a four-year prospective study of 190 children treated for drug-resistant, convulsive status epilepticus. Patients presented with a variety of other conditions as well, including developmental delay, epilepsy, cerebral palsy and febrile seizures.
An initial, univariate analysis revealed that the duration of status epilepticus varies according to several factors, including the length of time between seizure onset and the first dose of benzodiazepine or other antiepileptic drug, the length of time before arrival at the hospital, and whether the patient experienced continuous or intermittent status epilepticus at onset. Other variables also influenced seizure duration, including whether the patient was treated with a recommended versus non-recommended antiepileptic drug, time to EMS arrival, patient age, and whether the status epilepticus began in or out of the hospital.
After analyzing these variables and how they relate to each other, researchers determined that the most prominent factors associated with status epilepticus duration were structural etiology - whether the patient's epilepsy resulted from structural versus genetic, metabolic or unknown factors - and time to initial administration of benzodiazepine or other antiepileptic drugs.
"These findings reveal key factors underlying the duration of status epilepticus in children with a variety of medical diagnoses," says author Michele Jackson, a research assistant at Boston Children's Hospital. "Findings suggest a modifiable intervention, earlier treatment, and thereby will hopefully help us limit seizure duration in these children."