Hemodynamic Effects and QTc Changes with Intravenous Phenytoin and Fosphenytoin during Propofol and Sevoflurane Anesthesia

Abstract

Background Phenytoin is a commonly used antiepileptic drug (AED) for postoperative seizure prophylaxis; it is associated with adverse cardiovascular effects. Fosphenytoin is considered a safer alternative but can produce prolongation of QT interval. This hypothesis generating pilot study evaluated the changes in hemodynamics and the heart rate corrected QT interval (QTc) with phenytoin and fosphenytoin during propofol and sevoflurane anesthesia. Methods Eighty American Society of Anesthesiologists I and II patients aged 20 to 60 years undergoing elective supratentorial craniotomy requiring a loading dose of the intraoperative AED for seizure prophylaxis were randomized into four groups: group PP, receiving propofol (0.2 mg/kg/min) for maintenance and phenytoin (15 mg/kg) for seizure prophylaxis; group SP, receiving sevoflurane (1 minimal alveolar concentration) for maintenance and phenytoin(15mg/kg) for seizure prophylaxis; group PF, receiving propofol for maintenance and fosphenytoin (22.5 mg/kg) for seizure prophylaxis; and group SF, receiving sevoflurane for maintenance and fosphenytoin for seizure prophylaxis. The heart rate, systolic, diastolic, mean arterial pressure, and QTc were measured at baseline before anesthesia, during maintenance of anesthesia, and during various phases of AED infusion and up to 1 hour after completion of AED administration. Appropriate statistical analysis was done and a two-tailed p-value of less than 0.05 was considered significant. Results The incidence of changes in the heart rate and hypotension was not significant among the groups. Administration of fosphenytoin significantly prolonged QTc, which was more remarkable when coadministered with sevoflurane than with phenytoin. Conclusion Fosphenytoin did not confer hemodynamic benefits over phenytoin. Fosphenytoin produces prolongation of QTc, and when coadministered with sevoflurane, the prolongation is more significant, suggesting a possible additive effect.