Second-Line Treatment of Pediatric Status Epilepticus: Levetiracetam vs Phenytoin

Results suggest that levetiracetam could be considered as an alternative treatment to phenytoin for second-line management of pediatric convulsive status epilepticus.

Levetiracetam is just as effective and safe as phenytoin when used as a first-choice, second-line anticonvulsant for pediatric convulsive status epilepticus, according to findings from an open-label randomized trial published in The Lancet.

Individuals age 6 months to 18 years who presented to 1 of 30 emergency departments in the United Kingdom with convulsive status epilepticus requiring second-line treatment were enrolled. Researchers randomly assigned patients to either 40 mg/kg levetiracetam over 5 minutes (n=152) or 20 mg/kg phenytoin over ≥20 minutes (n=134). The Advanced Pediatric Life Support algorithm was used to guide clinicians in the treatment of subsequent ongoing convulsive status epilepticus. The time from treatment allocation to cessation of convulsive status epilepticus was the primary outcome.

Related Articles

Approximately 70% of children in the levetiracetam group and 64% of children in the phenytoin group experienced cessation of convulsive status epilepticus. The median time from treatment allocation to convulsive status epilepticus cessation was similar between the levetiracetam and phenytoin groups (35 min [interquartile range, 20 to not assessable] vs 45 min [interquartile range, 24 to not assessable], respectively; hazard ratio, 1.20; 95% CI, 0.91-1.60; P =.20).

Death occurred in 1 patient who was treated with levetiracetam followed by phenytoin; however, this death was a result of catastrophic cerebral edema and was considered unrelated to therapy. Immediately life-threatening hypotension and increased focal seizures as well as decreased consciousness was observed in 1 patient who received phenytoin.

Approximately 38% and 37% of participants in the levetiracetam and phenytoin groups, respectively, were treated with additional anticonvulsants (relative risk, 1.01; 95% CI, 0.74-1.36; P =.97).

Limitations of the study include its open-label design as well as the relatively small sample size.

The researchers concluded that their results indicate that levetiracetam “could be an appropriate alternative to phenytoin as the first-choice anticonvulsant for second-line treatment of paediatric convulsive status epilepticus.”


Lyttle MD, Rainford NEA, Gamble C, et al; Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI) collaborative. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial [published online April 17, 2019]. Lancet. doi:10.1016/S0140-6736(19)30724-X