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Phenytoin, Levetiracetam, and Pregabalin in the Acute Management of Refractory Status Epilepticus in Patients with Brain Tumors
Study Question: Can we provide evidence for a treatment regimen for refractory status epilepticus (RSE) in patients with brain tumors that does not require intubation?
Study Description: This study used the DEDUCE (Duke enterprise data unified content explorer) database to retrospectively identify patients meeting three criteria: brain tumors, presenting with complex partial status epilepticus (SE), and receiving phenytoin (PHT), levetiracetam (LEV), and pregabalin (PGB) – also referred to as the Trifecta. A clinical response to the Trifecta was defined as complete resolution of clinical seizures and/or cessation of repetitive epileptiform discharges on EEG, if no other AEDs were added during hospitalization, and if SE did not recur during hospitalization. The electronic medical record was used to collect data on 1 year outcomes.
Results: A total of 23 patients met all three study inclusion criteria. Sixteen (70%) had a prior history of seizures and 26% had tumor progression at time of RSE diagnosis. At the time of SE onset, 21 (91%) were on an anti-convulsant with most patients being on LEV at baseline (61%). The most common tumor type was glioblastoma multiforme (52%). There was a trend towards the presence of peritumoral edema on MRI and response to the Trifecta, however, this was not significant (p=0.12). Of patients in the responder group (n=16), more were on an AED at baseline (100%) as compared to non-responders (p=0.03).
PGB was typically used as third line treatment and 16/23 (70%) had cessation of RSE after the addition of this third component of the Trifecta. Serum PHT levels were therapeutic at the time of SE cessation with an average of 18.8 mcg/mL. The mean time to response was 3.5 days and it took 2.3 days to administer the third AED in the responder group vs. 4.2 days and 2.1 days in the non-responders, respectively. In the non-responders, 5/7 had SE cessation with the addition of a fourth AED.
Conclusion(s): The use of the Trifecta (PHT, LEV, PGB) is safe and highly effective.
Perspective: The Trifecta offers an attractive alternative in managing patients with brain tumors who experience RSE. One important condition must be met for this regimen to be feasible: the patient must be able to take oral medication since PGB does not have an IV formulation. The mean doses reported in the study were acceptable, however, no information was presented regarding side effects and therefore conferring safety of this regimen. The regimen studied appears to be effective for this specific patient population, although the results must be interpreted cautiously due to the small size and retrospective nature.