Guidelines for Seizure Prophylaxis in Patients Hospitalized with Nontraumatic Intracerebral Hemorrhage: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society

Background: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute nontraumatic intracerebral hemorrhage (ICH).

Methods: We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute nontraumatic ICH. The following population, intervention, comparison, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? and (3) If an ASM is used, should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation methodology to generate recommendations.

Results: The initial literature search yielded 1,988 articles, and 15 formed the basis of the recommendations. PICO 1: although there was no significant impact of ASM on the outcomes of early or late seizure or mortality, meta-analyses demonstrated increased adverse events and higher relative risk of poor functional outcomes at 90 days with prophylactic ASM use. PICO 2: we did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or adverse events, although point estimates tended to favor LEV. PICO 3: based on one decision analysis, quality-adjusted life-years were increased with a shorter duration of ASM prophylaxis.

Conclusions: We suggest avoidance of prophylactic ASM in hospitalized adult patients with acute nontraumatic ICH (weak recommendation, very low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days; weak recommendation, very low quality of evidence).