Peri-operative prophylaxis with phenytoin: dosage and therapeutic plasma levels

Early postoperative epilepsy is a frequent complication of supratentorial intracranial surgery. The lack of consensus on prophylaxis of early postoperative seizures with phenytoin (PHT) may be due to the different dosages used in several studies, owing to inadequate therapeutic plasma level. The aim of this study was to evaluate which dosage of PHT can maintain the therapeutic range in the early postoperative period. Twenty patients operated on for supratentorial neoplasms were randomly allocated to receive, during the last hour of the surgical procedure, loading doses of either 10 mg/kg (group A, n = 10) or 15 mg/kg (group B, n = 10) of PHT. PHT infusion rate never exceeded 30 mg/min. Six hours after the loading dose, PHT maintenance treatment (250 mg, i.v., every 8 hours) was started in all patients. PHT plasma levels were evaluated from the end of the intra-operative loading infusion up to 24 h. During the first six hours after the loading dose, phenytoin plasma levels fell below the therapeutic range (10-20 mg/l) in 7 out of the 10 patients receiving 10 mg/kg, while in the patients treated with 15 mg/kg, PHT plasma levels were always in the therapeutic range (P < or = 0.0001). PHT maintenance dose was sufficient to keep plasma levels within the therapeutic range in 8 patients in group A, and in all the patients in group B. It is concluded that a loading dose of 15 mg/kg, followed by postoperative treatment, is necessary to guarantee therapeutic plasma levels of phenytoin in the immediate postoperative period, when seizure risk is very high.