Treatment of Established Status Epilepticus

Abstract

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

Status epilepticus im Kindes- und Jugendalter – ein oft unterschätztes Notfallereignis

“…Die SE-Dosis liegt bei 20 mg/kg Körpergewicht, es sollen nicht mehr als 50 mg/min infundiert werden, der Zielspiegel für eine Statustherapie liegt bei 20-25 mg/l. Da aufgrund der langen Halbwertszeit Akkumulationsgefahr und damit Nebenwirkungen wie Atemdepression und Hypotonie relativ hoch sind, wird eine Statusunterbrechnung mit Phenobarbital nur unter Intensivbedingungen empfohlen [8,15].…”

Treatment outcomes after the introduction of a new seizure management protocol

“…Traditionally the evidence has supported the use of phenytoin (PHT) and diazepam, however, with the advent of the newer antiepileptic agents and novel indications for pre‐existing drugs, therapeutic options have changed. There have been several papers published assessing the efficacy of intravenous levetiracetam (LEV) and valproic acid (VPA) compared with PHT and they have been found to be at least equally efficacious and with superior side‐effect profiles . Phenobarbitone (PB), in contrast, has long been established as an effective treatment for status epilepticus .…”

Evaluation of phenytoin serum levels following a loading dose in the acute hospital setting

“…Moreover, in spite of widespread PHT/FOS use, there are no comprehensive guidelines on the timing of maintenance dosing (MD) initiation. Cranford et al (1978) state that “IV administration of a single 18 mg/kg PHT dose was safe and effective in maintaining serum PHT levels above 10 μg/mL for 24 hours in most participants after which an oral or IV maintenance PHT dose can be started when convenient, approximately 24 hours after the infusion.” Published references suggest 5 mg/kg/day dose 6 or 100 mg every six to eight hours 10 .…”