A randomized, double-blinded, placebo-controlled trial of phenytoin for the prevention of early posttraumatic seizures in children with moderate to severe blunt head injury

Study objective We determine the efficacy of prophylactic phenytoin in preventing early posttraumatic seizures in children with moderate to severe blunt head injury. Methods Children younger than 16 years and experiencing moderate to severe blunt head injury were randomized to receive phenytoin or placebo within 60 minutes of presentation at 3 pediatric trauma centers. The primary endpoint was posttraumatic seizures within 48 hours; secondary endpoints were survival and neurologic outcome 30 days after injury. A Bayesian decision-theoretic clinical trial design was used to determine the probability of remaining posttraumatic seizure free for each treatment group. Results One hundred two patients were enrolled, with a median age of 6.1 years. Sixty-eight percent were boys. The 2 treatment groups were well matched. During the 48-hour observation period, 3 (7%) of 46 patients given phenytoin and 3 (5%) of 56 patients given placebo experienced a posttraumatic seizure. There were no significant differences between the treatment groups in survival or neurologic outcome after 30 days. According to these results, the probability that phenytoin has the originally hypothesized effect of reducing the rate of early posttraumatic seizures by 12.5% is 0.0053. The probability that phenytoin has any prophylactic efficacy is 0.383. The median effect size in this trial was −0.015 (seizure rate increased by 1.5% in the phenytoin group), 95% probability interval −0.127 to 0.091 (12.7% higher rate of posttraumatic seizures to a 9.1% lower rate of posttraumatic seizures with phenytoin). Conclusion The rate of early posttraumatic seizures in children may be much lower than previously reported. Phenytoin did not substantially reduce that rate.