What is the role of antiepileptic medications in the treatment of status epilepticus (SE)?

Updated: Feb 13, 2018
  • Author: Julie L Roth, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Benzodiazepines are the preferred first-line agents. According to 2016 guidelines from the American Epilepsy Society (AES), any of three benzodiazepines — intramuscular (IM) midazolam, intravenous (IV) lorazepam, or IV diazepam — should be given if first-aid stabilization measures don't stop the seizure within 5 minutes. [62] Although diazepam is familiar to paramedics and emergency physicians, a consensus has evolved among neurologists and epileptologists that lorazepam may be preferred in this setting because of its long distribution half-life. 

A comparison of initial IV treatment for overt generalized convulsive SE by Treiman et al found that lorazepam was more effective than phenytoin alone. [41] Lorazepam was not more effective than phenobarbital or diazepam plus phenytoin, but it was easier to use. Not studied was fosphenytoin, which is theoretically a significant improvement over phenytoin.

A 2014 Cochrane Database review found intravenous lorazepam is better than intravenous diazepam or intravenous phenytoin alone for cessation of seizures. [69]

Intravenous valproic acid has been shown in a pilot study to be equal to or better than phenytoin in aborting generalized SE, and it has been used in some cases of focal status epilepticus. [70, 71]

The use of levetiracetam (Keppra) in treatment of refractory SE has been examined, in part due to its availability in intravenous form, although its use in treating focal SE remains investigational. [72, 73, 74] Anecdotal reports describe the beneficial use of topiramate in some cases of focal SE.

There are several intravenous formulations of antiepileptic drugs (AEDs) at different stages of development. [75] Some of these might be able to help refractory cases with SE as adjunctive therapy.

No data clearly support a best third-line drug. Controlled trials are lacking, and recommendations vary greatly. While phenobarbital has historically been among the most widely used, the list of third-line drugs also includes intravenous agents such as midazolam, propofol, pentobarbital, valproate, levetiracetam, lidocaine, [76] , ketamine [67] } and others. Lacosamide, a novel antiepileptic drug available for intravenous injection, may be used safely as adjunctive therapy for SE, but little data exist on its efficacy. [77]

A clinical practice trend seems to be for use of propofol as a third-line agent, often initiated during induction for endotracheal intubation. However, propofol infusion syndrome and increased mortality is reported when used at high doses and for prolonged periods. [66]

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