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Introduction

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. The Brain Trauma Foundation updated its guidelines for the management of severe TBI in 2016; however, there remains a lack of randomized clinical trials addressing many aspects of care in TBI patient. The incidence of early post-traumatic seizures may be as high as 30 percent in patients with severe TBI

Antiseizure medications in acute management of TBI has been shown to reduce incidence of early seizures but has not been shown to prevent later development of epilepsy Prevention of early seizures is beneficial in order to prevent status epilepticus, further aggravating systemic injury. The Brain Trauma Foundation guidelines recommend phenytoin for early post-traumatic seizures for 7 days following injury, however levetiracetam is commonly used in this setting.

Key Points

  • TBI is a leading cause of death and disability, and early post-traumatic seizures may occur in up to ~30% of severe TBI.
  • Antiseizure prophylaxis reduces EARLY post-traumatic seizures but has not been shown to prevent later epilepsy.
  • Brain Trauma Foundation guidelines recommend phenytoin for 7 days after injury, though levetiracetam is commonly used in practice.
  • Recent studies show levetiracetam and lacosamide are non-inferior to phenytoin, with fewer side effects.

Clinical Detail

The Brain Trauma Foundation guidelines recommend phenytoin for early post-traumatic seizure prophylaxis for 7 days following injury; however, levetiracetam is commonly used in this setting. Valproic acid and lacosamide are additional agents that have been studied for this indication.

PropertyPhenytoinValproic AcidLevetiracetamLacosamide
DoseLoading dose: 17 to 20 mg/kg IV (max dose 2 g)
Maintenance dose: 100 mg every 8 hours or 5 mg/kg/day divided q8h (individual doses not to exceed 400 mg)
Duration not to exceed 7 days		10 – 15 mg/kg/dayLoading dose: 20 mg/kg IV infused over 5-20 min
Maintenance dose: 1 g IV over 15 min every 12 hours for 7 days (may be increased to 1.5 g q12)		50 – 100 mg IV twice daily
May give loading dose of 200 mg
AdministrationIV piggyback rate of ≤50 mg/minuteIV piggyback over 60 minutes at a rate ≤20 mg/minuteIV push or piggyback over 5-20 minBolus: May be administered undiluted at ≤80 mg/minute
Infusion: over 30 to 60 minutes

Evidence

Author, YearDesign / Sample SizeIntervention & ComparisonOutcome
Temkin, 1990Randomized, double-blind study
N = 404		Phenytoin vs PlaceboWithin the first week, 3.6% of phenytoin patients experienced seizure compared to 2% (p<0.001). Between day 8 and 1 year, 21.5% of patients in the phenytoin group experienced seizure compared to 15.7% in the placebo group. Phenytoin is effective in reducing seizures within the first 7 days after severe head injury.
Young, 2004Randomized, double-blinded, placebo-controlled trial in pediatric patients (age < 16 yo)
N = 102		Phenytoin vs Placebo for prevention of early posttraumatic seizuresDuring the 48-hour observation period, 3 of 46 (7%) patients in the phenytoin group and 3 of 56 (5%) patients in the placebo group experienced a posttraumatic seizure. No significant difference in survival or neurologic outcome between the two groups. Phenytoin did not significantly reduce the rate of posttraumatic seizures at 48 hours, neurologic outcomes, or overall survival at 30 days.

Conclusions

  • The Brain Trauma Foundation guidelines recommend phenytoin for early post-traumatic seizures for 7 days following injury, however levetiracetam is commonly used in this setting.
  • In recent studies, lacosamide and levetiracetam showed no difference compared to phenytoin in prevention of early post-traumatic seizures following TBI
  • Less side effects were associated with levetiracetam and lacosamide compared to phenytoin when used in seizure prophylaxis in TBI.

References

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Tags:traumatic brain injury seizure prophylaxis levetiracetam phenytoin

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