Timing in the treatment of status epilepticus: From basics to the clinic

Objective: Describe basic science, animal models and clinical data related to timing of treatment in status epilepticus (SE). Methods: We summarized the results of 15 studies that reported time to treatment in SE, and reviewed basic and clinical literature. Results: SE is a life-threatening and time-sensitive emergency that requires immediate treatment. Current guidelines recommend escalation of anti-seizure medications (ASM) within specified time frames. Prolonged seizures may lead to changes in the composition and location of gamma-aminobutyric acid A receptors (GABA(A)R) and N-Methyl-D-aspartic acid receptors (NMDAR), leading to loss of inhibition and increased excitation. These biochemical changes are apparent in specific animal models having progressive resistance to benzodiazepines (BZD) with longer seizures. Later treatments lead to decreased response to BZD, longer seizures, greater need of continuous infusions, potential brain injury and increased in-hospital mortality. Despite mounting evidence that early treatment of SE is more effective and safer, treatment and ASM escalation is often delayed compared to protocols. Literature review of 2212 patients with SE showed an average time to treatment of 42.4 min and time to hospital arrival of 56 min. Also, only 51.8% of patients received treatment by emergency medical services and 12.8% by their families, including patients with a previous diagnosis of epilepsy or with prior SE. Conclusions: Morbidity and mortality may be avoided with rapid, effective treatment of SE. Treatment application and escalation remains delayed especially in outpatient settings, potentially leading to suboptimal outcomes. Implementation techniques and quality improvement methodologies may provide avenues for improving outcomes in SE.