Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis

Object. The goals of this study were to determine if the use of phenytoin t o prevent early posttraumatic seizures following head injury was associated with significant adverse side effects and also to determine if the reducti on in early posttraumatic seizures after phenytoin administration was assoc iated with a change in mortality rates in head-injured patients. Methods. The authors performed a secondary analysis of the data obtained in a prospective double-blind placebo-controlled study of 404 patients who we re randomly assigned to receive phenytoin or placebo for the prevention of early and late posttraumatic seizures. The incidence of adverse drug effect s during the first 2 weeks of treatment, however, was low and not significa ntly different between the treated and placebo groups. Hypersensitivity rea ctions occurred in 0.6% of the patients in the phenytoin-treated group comp ared with 0% in the placebo group (p = 1.0) during week I, and in 2.5% of p henytoin-treated compared with 0% of placebo-treated patients (p = 0.12) fa r the first 2 weeks of treatment. Mortality rates were also similar in both groups. Although the mortality rate was higher in patients who developed s eizures, this increase was related to the greater severity of the injuries sustained by these patients at the time of the original trauma. Conclusions. The results of this study indicate that the incidence of early posttraumatic seizure can be effectively reduced by prophylactic administr ation of phenytoin far 1 or 2 weeks without a significant increase in drug- related side effects. Reduction in posttraumatic seizure during the Ist wee k, however, was not associated with a reduction in the mortality rate.