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The Challenge of Treating Super-Refractory Status Epilepticus

Jeannette Y. Wick, RPh, MBA, FASCP
Published Online: Wednesday, August 15, 2012

The authors of a comprehensive literature review offer broad recommendations for treating super-refractory status epilepticus.

Refractory status epilepticus poses a treatment dilemma. Patients with the condition do not respond to benzodiazepines or other antiepileptic drugs (AEDs), forcing clinicians to administer anesthesia in an attempt to stop the patient’s seizure activity. If status epilepticus continues for 24 hours or more after the onset of anesthesia—or if it recurs when the clinical team tries to reduce or withdraw the anesthesia—the patient is diagnosed with super-refractory status epilepticus (SRSE). SRSE occurs in about 10% to 15% of patients hospitalized with status epilepticus, and approximately 35% of these patients die.
 
SRSE is poorly understood, making it difficult to study. No treatment guidelines exist to help clinicians choose the best treatments. In a comprehensive literature review published online on May 9, 2012, in Brain, Simon Shorvon, MD, and Monica Ferlisi, MD, of the Institute of Neurology, University College London, make broad recommendations for patients with SRSE. They categorize outcomes from SRSE into 6 possibilities:
  • Successful therapy
  • Initial failure
  • Breakthrough seizures
  • Withdrawal seizures
  • Intolerable side-effects
  • Death during treatment
The authors report that anesthesia is the best course of treatment for SRSE, but that AEDs should always be used concurrently. Despite widespread use of a large number of AEDs, no outcome analyses have been done. Shorvon and Ferlisi also discuss possible second-line therapies including hypothermia; magnesium sulfate infusion; pyridoxine infusion; immunotherapy with steroids, intravenous immunoglobulin or plasma exchange; neurosurgery; and the ketogenic diet.
 
Shorvon and Ferlisi’s recommendations are necessarily broad due to the poor quality of available outcome data. Their recommendations include the following:
  • Identify and treat the cause of the episode if possible.
  • Begin anesthesia with thiopental/pentobarbital, midazolam, or propofol.
  • Add AEDs, limiting polytherapy to at most 2 AEDS. (The authors indicate no AED has been proven superior to any other, and the choice must be driven by the patient’s history and condition.)
    • Avoid frequent AED switching.
    • Avoid GABAergic drugs.
  • If treatment with anesthetics and AEDS fails, consider second-line therapies.
Add last resort therapies if necessary (ie, electroconvulsive therapy or cerebrospinal drainage).

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.
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