What is the recommended use of Keppra (levetiracetam) in patients with hemorrhagic strokes?

Levetiracetam (Keppra) Use in Hemorrhagic Strokes

Levetiracetam is preferred over phenytoin for seizure prophylaxis in hemorrhagic stroke patients due to its superior tolerability profile and better cognitive outcomes.

Seizure Risk in Hemorrhagic Stroke

Seizures are a common complication following hemorrhagic stroke:

• Seizures occur in approximately 4-43% of stroke patients, with most occurring within the first 24 hours 1
• Hemorrhagic strokes carry a higher seizure risk compared to ischemic strokes
• Status epilepticus, while uncommon, can be life-threatening when it occurs 1

Evidence for Levetiracetam Use

Research evidence strongly supports levetiracetam over traditional antiepileptic drugs:

• Levetiracetam demonstrates superior tolerability compared to phenytoin in subarachnoid hemorrhage patients 2
• Patients receiving levetiracetam have significantly better cognitive outcomes at discharge compared to those receiving phenytoin (higher Glasgow Coma Scores at dismissal: median 14 vs. 11, p=0.023) 3
• Levetiracetam is associated with lower seizure incidence (0% vs 8%, p=0.03) compared to phenytoin in ICH patients 3
• Phenytoin use is associated with more fever (p=0.03) and worse outcomes after intracerebral hemorrhage 4
• In a logistic regression model, phenytoin prophylaxis was associated with increased risk of poor outcome (OR 9.8, p=0.02) 4

Dosing Recommendations

• Initial dosing: 500mg twice daily (1000mg total daily dose)
• Optimal dosing: 1000mg twice daily (2000mg total daily dose) is associated with lower seizure incidence compared to 500mg twice daily with no increase in adverse effects 5
• Adjust dosing based on renal function as levetiracetam is primarily eliminated through the kidneys 6

Advantages of Levetiracetam

1. Better Cognitive Profile:

   • Less cognitive disruption compared to phenytoin 3
   • Higher rate of cognitive function retention (56.7% vs. 36%) 3
   • Higher rate of patients discharged home (21.7% vs. 16%, p=0.03) 3

2. Superior Tolerability:

   • Fewer adverse events compared to phenytoin 2
   • No significant issues with anemia, leukopenia, or thrombocytopenia 5
   • Lacks cytochrome P450 isoenzyme-inducing potential 6
   • Minimal drug interactions with other medications 6

3. Pharmacokinetic Advantages:

   • Rapid and complete absorption
   • High oral bioavailability
   • Minimal metabolism
   • Primarily renal elimination
   • No clinically significant drug interactions 6

Duration of Treatment

While guidelines don't specify exact duration for seizure prophylaxis in hemorrhagic stroke, clinical practice typically involves:

• Short-term prophylaxis (7-14 days) for patients without seizures
• Extended treatment (3-6 months) for patients who experience seizures
• Treatment decisions should be reassessed based on clinical recovery, EEG findings, and presence/absence of seizures

Monitoring Recommendations

• Monitor for behavioral adverse effects, which can occur in some patients 6
• Consider EEG monitoring in patients with depressed mental status 4
• Regular assessment of renal function as levetiracetam is primarily eliminated through the kidneys

Important Caveats

1. Prophylactic anticonvulsants are not routinely recommended for all stroke patients without seizures 1
2. The American Stroke Association guidelines note there are limited data about the utility of prophylactic administration of anticonvulsants after stroke 1
3. For patients who experience seizures, treatment should follow established management protocols for seizures that complicate acute neurological illness 1
4. Levetiracetam dosing >1000mg total daily dose may provide better seizure prevention 5

In summary, when seizure prophylaxis is indicated in hemorrhagic stroke patients, levetiracetam is the preferred agent due to its favorable cognitive profile, superior tolerability, and better outcomes compared to traditional agents like phenytoin.