What is the recommended prophylaxis for seizures in traumatic brain injury (TBI)?

Seizure Prophylaxis in Traumatic Brain Injury

Routine antiepileptic drug prophylaxis is not recommended for preventing post-traumatic seizures in traumatic brain injury (TBI) patients. 1, 2

Current Recommendations

The American College of Anesthesia provides a Grade 2- recommendation with strong agreement against the routine use of antiepileptic drugs (AEDs) for primary prevention of post-traumatic seizures, both early and late 1, 2. This recommendation is based on evidence showing:

• No significant effect of AEDs in preventing the occurrence of early or delayed post-traumatic seizures
• Increased side effects with phenytoin use 1
• Potential worsening of neurological outcomes with AEDs 1, 2

Risk Assessment for Post-Traumatic Seizures

Certain factors increase seizure risk in TBI patients:

• Brain contusion
• Acute subdural hematoma
• Skull fracture
• Loss of consciousness or amnesia for more than 24 hours
• Age over 65 years
• Craniectomy 1, 2

When Seizure Prophylaxis May Be Considered

If seizure prophylaxis is deemed necessary based on risk factors, the following approach is recommended:

1. Duration: Limit prophylaxis to 7 days after injury if no seizures have occurred 2
2. Drug selection: Levetiracetam is preferred over phenytoin due to:
   • Better side effect profile
   • Fewer drug interactions 2
   • Similar efficacy to phenytoin for seizure prevention 3, 4
   • Lower total antiepileptic drug and monitoring costs 5

Phenytoin Administration (If Used)

If phenytoin is selected:

• Loading dose: 10-15 mg/kg administered intravenously
• Maximum rate: 50 mg per minute in adults (approximately 20 minutes for a 70-kg patient)
• Maintenance: 100 mg orally or intravenously every 6-8 hours 6
• Monitor serum levels to maintain therapeutic range (10-20 mcg/mL total or 1-2 mcg/mL unbound phenytoin) 6

Important Considerations

• The incidence of early clinical seizures (within 7 days after brain injury) is approximately 2.2% generally, but can reach 11.9% in the first year for severe TBI patients 1
• Recent evidence suggests levetiracetam may not reach therapeutic CSF levels as quickly as phenytoin with standard dosing regimens in acute settings 7
• Prolonged use of anticonvulsants beyond 7 days may be associated with cognitive decline and other adverse effects without providing additional seizure prevention benefit 2

Monitoring

• EEG monitoring may be beneficial in high-risk patients to detect subclinical seizure activity
• A normal EEG supports discontinuation of prophylaxis after 7 days 2

Common Pitfalls

• Continuing seizure prophylaxis beyond 7 days without evidence of seizure activity
• Failing to consider drug interactions with phenytoin (particularly relevant in polytrauma patients receiving multiple medications)
• Not adjusting phenytoin dosing based on serum levels, potentially leading to subtherapeutic or toxic levels

Despite some evidence suggesting benefits of prophylaxis in specific high-risk populations, the overall recommendation remains against routine use of AEDs for seizure prophylaxis in TBI patients.