Pharmacotherapy for Pediatric Convulsive Status Epilepticus

Abstract

Convulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABA_A receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration and may provide some of the pathophysiological underpinnings of established and refractory SE (RSE). Simultaneously, a practice change toward more rapid initiation of first-line benzodiazepine (BZD) treatment and faster escalation to second-line non-BZD treatment for established SE is in progress. Early administration of the recommended BZD dose is suggested. For second-line treatment, non-BZD anti-seizure medications (ASMs) include valproate, fosphenytoin, or levetiracetam, among others, and at this point there is no clear evidence that any one of these options is better than the others. If seizures continue after second-line ASMs, RSE is manifested. RSE treatment consists of bolus doses and titration of continuous infusions under continuous electro-encephalography (EEG) guidance until electrographic seizure cessation or burst-suppression. Ultimately, etiological workup and related treatment of CSE, including broad spectrum immunotherapies as clinically indicated, is crucial. A potential therapeutic approach for future studies may entail consideration of interventions that may accelerate diagnosis and treatment of SE, as well as rational and early polytherapy based on synergism between ASMs by utilizing medications targeting different mechanisms of epileptogenesis and epileptogenicity.

Fig. 1

Pediatric status epilepticus treatment algorithm combining current guidelines. This approach combines the timeline-based algorithm from current guidelines by Neurocritical Care Society [11], International League Against Epilepsy [14], the American Epilepsy Society [13], and information from institutional guidelines. See Tables 1 and 2 for further detailed dosing recommendations. Notably, the above are recommendations that should be customized for each patient based on individual case and seizure characteristics and institutional medication availability. ASM Anti-seizure medication, BZD benzodiazepine, EEG electro-encephalography, IM intramuscular, IN intranasal, IV intravenous, PE phenytoin-equivalent, POLG DNA polymerase gamma, SE status epilepticus