Research Reports - Antiepileptic drugs for preventing seizures following acute traumatic brain injury

Cochrane Database Syst Rev. 2012 Jun 13;6

Schierhout G, Roberts I

BACKGROUND: Seizure activity in the early post-traumatic period following head
injury may cause secondary brain damage as a result of increased metabolic
demands, raised intracranial pressure and excess neurotransmitter release.
OBJECTIVES: To determine the effects of prophylactic anti-epileptic agents for
acute traumatic head injury.
SEARCH METHODS: We searched the Cochrane Injuries Group specialised register,
MEDLINE and the registers of the Cochrane Stroke Group and Cochrane Epilepsy
Group. We contacted pharmaceutical companies who manufacture anti-epileptic
agents, the National Institute of Neurological Disorders and Stroke, Epilepsy
Division, and the United States' National Institute of Health.
SELECTION CRITERIA: All randomised trials of anti-epileptic agents, in which
study participants had a clinically defined acute traumatic head injury of any
severity. Trials in which the intervention was started more than eight weeks
after injury were excluded.
DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and
assessed the trial quality. Relative risks and 95% confidence intervals (95%CI)
were calculated for each trial on an intention-to-treat basis, which included
pre-drug loading exclusions. As long as statistical heterogeneity did not exist,
for dichotomous data, summary relative risks and 95% confidence intervals were
calculated using a fixed effects model. Where the source of heterogeneity could
obviously be related to allocation concealment, drug type, or drug dose, we
stratified the analyses on that dimension.
MAIN RESULTS: We identified 10 eligible randomised controlled trials, including
2036 participants, but data was unavailable for four unpublished trials,
representing 631 participants and they were excluded. For the remaining six
trials, the pooled relative risk (RR) for early seizure prevention was 0.34
(95%CI 0.21, 0.54); based on this estimate, for every 100 patients treated, 10
would be kept seizure free in the first week. Seizure control in the acute phase
was not accompanied by a reduction in mortality (RR = 1.15; 95%CI 0.89, 1.51), a
reduction in death and neurological disability (RR = 1.49; 95%CI 1.06, 2.08 for
carbamazepine and RR = 0.96; 95%CI 0.72, 1.26 for phenytoin) or a reduction in
late seizures (pooled RR = 1.28; 95%CI 0.90, 1.81). The pooled relative risk for
skin rashes was 1.57 (95%CI 0.57, 39.88).
AUTHORS' CONCLUSIONS: Prophylactic anti-epileptics are effective in reducing
early seizures, but there is no evidence that treatment with prophylactic
anti-epileptics reduces the occurrence of late seizures, or has any effect on
death and neurological disability. Insufficient evidence is available to
establish the net benefit of prophylactic treatment at any time after injury.

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