Seizure Prophylaxis in Traumatic Brain Injury

• 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.

Phenytoin

Valproic Acid

Levetiracetam

Lacosamide

Dose

Loading 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/day

Loading 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

Administration

IV piggyback rate of

<=50 mg/minute

IV piggyback over

60 minutes at a rate

<=20 mg/minute

IV push or piggyback

over 5-20 min

Bolus: May be

administered undiluted

at <=80 mg/minute

Infusion: over 30 to 60

minutes

PK/PD

Author, year

Design/ sample

size

Intervention & Comparison

Outcome

Temkin, 1990

A randomized,

double-blind

study

N = 404

Phenytoin vs Placebo

Within the first week 3.6% of phenytoin

patients experienced seizure compared to

• 2% (p<0.001)

Between day 8-1 year 21.5% of patients in

phenytoin group experienced seizure

compared to 15.7% in placebo group

Phenytoin is effective in reducing seizures

within the first 7 days after severe head injury

Young, 2004

Randomized,

Double-Blinded,

Placebo-

Controlled Trial in

pediatric

patients (age <

16 yo)

N = 102

Phenytoin vs Placebo for

prevention of early

posttraumatic seizures

During 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.

●

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.

(Jordan Spurling & [email protected]

Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved October 17, 2023, from

http://www.micromedexsolutions.com/

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http://www.micromedexsolutions.com/

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