What is the recommended use of Keppra (Levetiracetam) for patients with Traumatic Brain Injury (TBI)?

Levetiracetam (Keppra) for Traumatic Brain Injury

Levetiracetam is not routinely recommended for seizure prophylaxis in all TBI patients, but it may be preferred over phenytoin when seizure prophylaxis is indicated in severe TBI during the first 7 days post-injury. 1

Indications for Seizure Prophylaxis in TBI

Recommended Use:

• For severe TBI only (Glasgow Coma Scale score ≤8)
• Limited to the first 7 days after injury
• Not recommended for routine use in mild to moderate TBI (GCS >8)

Risk Factors That May Warrant Prophylaxis:

• Chronic subdural hematoma
• History of epilepsy
• Intracranial hemorrhage

Evidence and Rationale

The Brain Trauma Foundation and American Academy of Neurology recommend seizure prophylaxis only during the first seven days after severe TBI 2. This is because:

• Post-traumatic seizures occur in approximately 5-7% of hospitalized TBI patients
• Early seizures (within 7 days) may worsen secondary brain injury
• Prophylaxis beyond 7 days has not shown benefit for preventing late seizures

Levetiracetam has demonstrated comparable efficacy to phenytoin for early post-traumatic seizure prophylaxis but with fewer adverse effects and monitoring considerations 2. The 2018 Anaesthesia guidelines specifically note that "levetiracetam should be preferred to phenytoin, because of a higher degree of tolerance" 1.

Dosing Considerations

• Standard dosing: 500-1000 mg twice daily
• Recent evidence suggests that higher dosing (>1000 mg total daily dose) may be more effective than lower dosing (1000 mg total daily dose) 3
• Lower doses of 500 mg every 12 hours have shown effectiveness with a seizure rate of only 2.4% within 7 days 4

Important Caveats and Limitations

1. Efficacy concerns: A propensity score-matched analysis found that levetiracetam prophylaxis was ineffective in preventing seizures compared to no prophylaxis (1.9% vs 3.4%, p=0.50) 5

2. Overuse in non-severe TBI: Studies show inappropriate use is common in patients with mild-to-moderate TBI, with many patients continuing levetiracetam post-discharge despite lack of evidence supporting this practice 6

3. Duration: Prophylaxis should be limited to 7 days post-injury unless the patient experiences a seizure

4. Monitoring: Although levetiracetam requires less monitoring than phenytoin, patients should still be observed for:

   • Behavioral changes
   • Mood disturbances
   • Rare hematologic abnormalities

Clinical Algorithm for Levetiracetam Use in TBI

1. Assess TBI severity:

   • Severe TBI (GCS ≤8): Consider prophylaxis
   • Mild/Moderate TBI (GCS >8): Generally not indicated

2. Evaluate risk factors:

   • Presence of intracranial hemorrhage
   • History of epilepsy
   • Chronic subdural hematoma

3. If prophylaxis indicated:

   • Start levetiracetam 1000 mg twice daily
   • Continue for 7 days only
   • Discontinue after 7 days if no seizures occur

4. If seizure occurs during hospitalization:

   • Convert from prophylaxis to treatment
   • Continue levetiracetam as treatment (may require longer duration)
   • Consider neurology consultation

Remember that the overall incidence of post-traumatic seizures in severe TBI patients is relatively low (approximately 2%), which raises questions about the benefit of routine prophylactic anticonvulsant therapy in all TBI patients 5.