Toxin-Related Benzodiazepine-Refractory Status Epilepticus Causes, Management

Cocaine/opioid use and alcohol withdrawal were the most frequent causes of seizure in patients with status epilepticus who presented a toxin-related seizure, according to study findings published in the Annals of Emergency Medicine.

Status epilepticus, defined as the inability of a seizure-abortive mechanism to stop a seizure or prevent prolonged seizures and the possibility of additional long-term consequences, requires immediate treatment with sufficient doses of benzodiazepines, anticonvulsants, and supportive care. The study authors investigated the safety and efficacy of second-line medications in patients with toxin-related seizures.

They conducted a post hoc analysis of the Established Status Epilepticus Treatment Trial (ESETT; ClinicalTrials.gov Identifier: NCT01960075), a double-blind, prospective trial evaluating second-line medications in benzodiazepine-refractory status epilepticus in adults and children. The primary outcome was improvement in the level of consciousness 1 hour following medication and the absence of subsequent seizures.

Of the 478 patients (adults, n=249; children, n=229), 29 adult patients (men, 25; women, 4) and 1 pediatric patient experienced toxin-related seizures. Of the 30 participants, alcohol withdrawal (n=11) and use of cocaine (n=11) were identified as the most common toxic precipitants of status epilepticus.

Overall, 7 of the 11 patients with alcohol withdrawal-related status epilepticus met the primary outcome compared with 2 of the 11 patients with cocaine-related status epilepticus. Effective treatment for alcohol withdrawal-related seizures included levetiracetam (n=3/3), valproate (n=3/6), and fosphenytoin (n=1/2). Effective treatment for cocaine-related seizures included levetiracetam (n=1/7), valproate (n=0/1), and fosphenytoin (n=1/3).

In the ESETT, where 1 in 10 adults with status epilepticus developed a toxin-related seizure, cocaine/opioid use and alcohol withdrawal were found to be the most frequent seizure triggers.

The study authors acknowledged several limitations. Among these included underpowered samples of specific toxins in ESETT, higher doses of benzodiazepines than those administered (which may have been more beneficial), and history of epilepsy in more than half of the study group. Moreover, they said duration of status epilepticus prior to medication had an undetermined effect on the primary outcome, and patients were not screened for additional unanticipated drug abuse, which could have led to some toxins being misclassified. Lastly, the study outcomes may have been disrupted to an unknown degree by additional known coingestants.

“Toxin-related benzodiazepine-refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of the patients,” and more effective for patients with alcohol withdrawal seizures than those with seizures related to cocaine, the study authors concluded.

Reference

Coralic Z, Kapur J, Olson KR, Chamberlain JM, Overbeek D, Silbergleit R. Treatment of toxin-related status epilepticus with levetiracetam, fosphenytoin, or valproate in patients enrolled in the Established Status Epilepticus Treatment Trial. Ann Emerg Med. Published online June 16, 2022. doi:10.1016/j.annemergmed.2022.04.020