Guidelines for Seizure Prophylaxis in Patients with Aneurysmal Subarachnoid Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society

Background There are limited data to guide antiseizure medication (ASM) prophylaxis in patients with aneurysmal subarachnoid hemorrhage (SAH). This results in practice variation in the use and duration of ASM prophylaxis. Methods We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with aneurysmal SAH. The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM or no ASM be used in patients hospitalized for aneurysmal subarachnoid hemorrhage who have no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam or phenytoin/fosphenytoin be preferentially used? (3) If an ASM is used, should a long (> 3 days) or short (≤ 3 days) duration of prophylaxis be used? The main outcomes were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. Results The initial literature search yielded 1988 articles, of which 10 formed the basis of the recommendations: Regarding PICO 1, we did not find a significant difference in outcomes of early seizure, adverse events, mortality, or functional outcomes when comparing ASM to no ASM. In regard to PICO 2, we found fewer early seizures with phenytoin/fosphenytoin and lower risk for neurologic decline with levetiracetam; however, there was low certainty of evidence. There was no significant difference in mortality between the different treatment types. Regarding PICO 3, we found extended use of ASM may be associated with lower seizure risk, but at the same time be associated with higher risk for adverse effects. Conclusions Overall, the quality of evidence is low, precluding strong recommendations. We suggest that ASM or no ASM may be used in patients hospitalized with aneurysmal subarachnoid hemorrhage (conditional recommendation, low quality of evidence). If used, we suggest either levetiracetam or phenytoin/fosphenytoin (conditional recommendation, very low quality of evidence) for a short or long duration (conditional recommendation, moderate quality of evidence).