Timing is everything: Where status epilepticus treatment fails

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While “time is brain” has traditionally described the pathophysiology of stroke, our present‐day understanding of status epilepticus reaffirms this mantra. Status epilepticus, prolonged seizures or multiple seizures with incomplete return to baseline, is an emergency that requires prompt treatment.1 On the cellular level, changes in receptor trafficking and neuropeptide expression occur within minutes to encourage a hyperexcitable state.1 Clinically, seizure cessation becomes less likely as time to therapy lengthens.5 Yet despite its importance, timely treatment is not achieved for the majority of patients presenting with status epilepticus.
Status epilepticus has an incidence of 10 to 40 per 100,000 population, and the impact is considerable.4 Mortality is estimated at 20% to 30%,2 and up to 23% of patients will deteriorate in neurological function.6 Additionally, its estimated annual direct inpatient costs in the United Status are >$4 billion.4 While age and etiology are critical determinants of prognosis,7 prolonged seizure duration is associated with higher mortality and morbidity,8 worse functional outcome,10 and increased risk of subsequent epilepsy.11 Furthermore, seizure duration is the only modifiable prognostic factor7 and can be improved by expeditiously administering antiepileptic medication.
Expert opinion supports utilizing a protocol to facilitate urgent treatment.12 The initial first‐line agent should be administered within 5 to 10 minutes of seizure onset, a second‐line agent within 20 to 40 minutes, and a third‐line agent within 60 minutes.14 Class I evidence supports using a benzodiazepine as the first‐line agent, but weaker evidence guides choice of a second‐line agent and beyond.13 The 2016 Guideline Committee of the American Epilepsy Society proposed fosphenytoin, valproic acid, and levetiracetam as second‐line options,15 and the ESETT (Established Status Epilepticus Treatment Trial) is currently underway to compare effectiveness of these three second‐line therapies.17 Given that prompt therapy is a critical component of effective therapy, delivery of care warrants similarly rigorous examination.
We performed a review of the literature to characterize observed divergences from recommended guidelines, consider their clinical significance, and explore initiatives to improve adherence to treatment protocols. We aim to identify opportunities and approaches to optimize antiepileptic drug delivery to patients presenting with status epilepticus.
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