3 anticonvulsants compared in refractory status epilepticus


By Michael Woodhead

28 Nov 2019

There is no difference in effectiveness and safety between three medications commonly used to treat benzodiazepine-refractory status epilepticus, a US randomised controlled trial has found.

Fosphenytoin, valproate, and levetiracetam were all effective in about half the patients who had status epilepticus that was unresponsive to treatment with benzodiazepines, according to findings published in the NEJM.

The drugs did not differ significantly with regard to safety, the study showed.

In the prospective study carried out in 57 emergency departments in the US, 384 adults and children (age >2 years) with benzodiazepine refractory status epilepticus were randomised to intravenous infusion of either levetiracetam, fosphenytoin or valproate.

The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 47% of patients assigned to levetiracetam 45% of patients assigned to fosphenytoin and 46% of patients assigned to valpropate.

Time to seizure termination was 10.5 minutes for levetiracetam, 11.7 minutes for fosphenytoin and 7.0 in the valproate group, but the numbers were too small to make valid comparisons, the study authors said.

There was also no significant difference in rates of seizure cessation within 20 minutes after trial-drug initiation or in the percentage of patients with acute seizure recurrence (10.7%, 11.2%, and 11.2%, respectively).

More episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.

The study authors said clinical guidelines emphasise the need for rapid control of benzodiazepine-refractory status epilepticus but there has been little research in this area, and so guidelines do not provide guidance regarding the choice of medication on the basis of either efficacy or safety.

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