Clinical utility of a continuous intravenous infusion of valproic acid in pediatric patients

Study Objective. To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used. Design. Retrospective and concurrent chart review. Setting. Tertiary care, 473-bed, academic medical center with a 120-bed, dedicated children's hospital. Patients. Twenty-six pediatric patients (< 18 yrs old) who received VPA according to the protocol for continuous intravenous infusions between January 1, 2004, and March 31, 2006, identified by using a pharmacy order-entry system. Measurements and Main Results. Patient demographics, VPA treatment regimens, clinical responses, and safety data were recorded and analyzed. Median patient age was 8.5 years (range 1.4-16 yrs). Approximately two thirds received VPA for seizures, and one third for migraines. Patients were given a mean ± SD VPA loading dose of 28.5 ± 5.2 mg/kg followed by a continuous infusion rate of 1 ± 0.2 mg/kg/hour. Mean ± SD serum concentration measured 4.5 ± 1.6 hours after the loading dose was 83.3 ± 22.8 μg/ml. Steady-state concentration at 23.3 ± 3.0 hours after the start of the continuous infusion was 80.0 ± 26.0 μg/ml. Postload and steady-state serum concentrations were within the target concentration of 50-100 μg/ml in 77% and 69% of patients, respectively. On further analysis, when the target range was expanded to 50-125 μg/ml (125 μg/ml was deemed acceptable if no adverse effects were noted), 89% and 92% of patients, respectively, had postload and steady-state VPA serum concentrations within this range. The response rate was excellent, with nearly 85% of patients achieving a complete or partial response to therapy. Adverse effects were generally mild and uncommon. Conclusions. The continuous-infusion protocol permitted rapid intravenous loading of VPA in pediatric patients while minimizing adverse events and achieving concentrations in the upper region of the therapeutic range.