Phenytoin prophylaxis and functional outcomes following spontaneous intracerebral hemorrhage: A systematic review and meta-analysis

Abstract

Introduction: Seizure activity following spontaneous intracerebral hemorrhage (sICH) can worsen patients' comorbidity. However, data regarding whether seizure prophylaxis for sICH is associated with patients' poor functional outcome is inconclusive. We performed a systematic review and meta-analysis to assess the relationship between phenytoin prophylaxis and poor functional outcome after sICH.

Methods: We conducted our search on PubMed, Scopus, and EMBASE databases as of October 30, 2020 for studies that included information on seizure prophylaxis and functional outcome in patients with sICH. Primary outcome was poor functional outcome at the longest follow-up in patients receiving seizure prophylaxis. The secondary outcome was poor functional outcome at 90 days follow-up. We conducted random effects meta-analysis and moderator analyses to detect sources of heterogeneity for our outcomes.

Results: We included eleven studies in the final analysis with a total of 4268 patients. A moderator analysis further showed prospective studies had lower heterogeneity. We did not find an association between seizure prophylaxis and poor functional outcome at time of longest follow-up (OR 1.2, 95%CI 0.9-1.6, p-value = 0.22, I² = 61%), nor at 90-day follow-up (OR 1.4, 95%CI 0.8-2.4, p-value = 0.24, I² = 78%).

Conclusion: Seizure prophylaxis following sICH was not associated with worse functional outcomes at longest follow-up or at 90 days. Neither levetiracetam nor phenytoin was associated with outcome in our exploratory meta-regression, though there is a trend towards better outcomes in populations where there was a higher percentage of patients who received levetiracetam. More randomized trials are needed to confirm this observation.

Keywords: Early seizure; Functional outcome; Seizure prophylaxis; Spontaneous intracerebral hemorrhage.