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In Pediatric Status Epilepticus, Levetiracetam Is Not Superior to Phenytoin as a Second-Line Therapy

While either agent is acceptable, side effects and ease of administration may influence treatment choice.

Most seizures stop without intervention and do not progress to status epilepticus, and most cases of status epilepticus resolve with one or two adequate doses of benzodiazepines. Although many medication options exist, there is little evidence to guide the choice of a second-line agent when benzodiazepines fail. Two open-label multicenter randomized trials compared the efficacy and safety of phenytoin (20 mg/kg infused over 20 minutes) versus levetiracetam (40 mg/kg infused over 5 minutes) for the treatment of pediatric status epilepticus refractory to two doses of benzodiazepines.

The ConSEPT trial enrolled 233 children aged 3 months to 16 years in Australia and New Zealand who were not taking either study medication at baseline. Convulsions stopped within 5 minutes of completion of treatment in 60% of children treated with phenytoin and 50% treated with levetiracetam (not statistically significant). Two hours after the start of infusion roughly half the children in both groups remained seizure-free without additional medications.

The EcLiPSE trial enrolled 286 children aged 6 months to 18 years in the United Kingdom regardless of the medications they were taking at home. Levetiracetam and phenytoin terminated convulsions in 70% and 64% of children, respectively (not statistically significant).

In both trials, the median time to seizure cessation was 17 to 33 minutes after the start of drug infusion and did not differ significantly between treatment groups. Drug safety profiles were also similar.

COMMENT

Aggressive benzodiazepine dosing is essential to treating status epilepticus, and it is unclear if dosing in either study meets current U.S. guidelines (Proposed Algorithm for Convulsive Status Epilepticus; Neurocrit Care 2012; 17:3). However, these results demonstrate that levetiracetam is not superior to phenytoin as a second-line treatment. Levetiracetam does not share phenytoin's cardiovascular risks if infused very rapidly, which may influence the choice between the two. Because I don't commonly use phenytoin, my decision awaits results from future trials.

(Jason T. McMullan, MD, MS, FAEMS reviewing Dalziel SR et al. Lancet 2019 Apr 17 Lyttle MD et al. Lancet 2019 Apr 17 Silbergleit R and Elm JJ. Lancet 2019 Apr 17).