CAT
Title: Low risk of late post-traumatic seizures following severe head injury: implications for clinical trails of prophylaxis
Journal: Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:899-904
Authors: McQueen J, Blackwood DHR, Harris P, Kalbag RM, Johnson AL
Clinical Scenario:
A 12 year old boy is admitted to the PICU after a motor vehicle collision.
He lost consciousness at the scene and was intubated in the Emergency Department
for a Glasgow Coma Score of 8 and no gag reflex. The boy has no history of
seizure activity in the past or at the scene. The Traumatic Brain Injury
protocol recommends that he receive phenytoin for seizure prophylaxis. You have
recently cared for a child who nearly died from phenytoin hypersensitivity
syndrome and would like to know if there is a good indication for the drug.
Structured Clinical Question:
In a child with a traumatic brain injury [patient] does phenytoin
prophylaxis [intervention] prevent subsequent seizures and/or improve
neurological outcome? [outcome]
Search Terms:
"Craniocerebral Trauma" AND "Epilepsy, Post-traumatic"
AND "phenytoin" and filter "therapy"
Inclusion Criteria:
Patients ages 5 � 65 years, s/p head injury complicated with one of
following: dural penetration, intracranial hematoma (extradural, subdural or
intracerebral), depressed skull fracture, persistent neurological deficit or
post-traumatic amnesia for >24 hours post injury
Exclusion Criteria:
History of epilepsy (other than febrile seizures in infancy), patients who
developed seizures in first week after injury
Trial Design:
- Randomization to either phenytoin or placebo, randomization process not
described
- Double Blinded
- Patients started on phenytoin or placebo on admission, treatment continued
until 12 months post injury and follow up continued until
24 months post injury
- seizure free time calculated for each patient
- 164 patients enrolled in trial, (85% met criteria for severe head injury)
- compliance monitored
Results:
- Baseline characteristics similar
- only 50% compliance with assigned drug (phenytoin or placebo)
- Late seizure development:
Placebo:
7/80 = 8.75%
Phenytoin: 8/84 = 9.5%
Absolute
Risk Reduction: 8.75% - 9.5% = (-)0.75% (95% CI: -9.59% to 8.04%)
- Mortality:
- Rash:
Comments:
- Only 2 patients lost to follow up, and 7 deaths
- large rate of non-compliance consistent with other trials
- authors note that given low rate of seizures in both groups, future trials
would need between 1200 to 1900 patients to have adequate power "to detect
a difference of at least 5% in seizure-free rate on anti-epileptic
prophylaxis"
Conclusions:
No significant differences in the development of "late onset"
seizures, morality or rash were noted between patients treated with placebo vs.
phenytoin.