Abstracts

RATIONALE: Intravenous valproate (IV VPA) was approved in April 1997 as temporary substitution for oral dosing. It is recommended that it be given over one hour, at a rate not to exceed 20mg/min. Despite these recommendations optimum clinical care often requires a wider range of dosing schedules. Pediatric studies outside of approved indications are limited.
At the end of this activity, the particpants should be able to discuss safety and uses of IV VPA outside of indicated use and with a variety of dosing schedules in pediatric patients.
METHODS: Pharmacy records were reviewed to identify pediatric patients who received IV VPA from 01/1998 to 03/2002 at the Virginia Commonwealth University Health System. These patient charts were reviewed for age, gender, dosage, underlying medical condition(s) and concomitant therapies, including other anticonvulsants. Additionally, side effects, complications of infusion, obtained serum levels, and other surveillance labs were recorded. When available infusion rates were recorded. Data from a pilot study of 10 pediatric patients using rapid infusion were included in the analysis.
RESULTS: 53 patients with a total of 75 admissions were identified. The patients received 881 doses as loading and maintenance doses. Loading doses ranged from 11.2 mg/kg to 66 mg/kg. Maintenance doses ranged from 4.1 mg/kg to 25 mg/kg. One patient received 347 mg/kg/day. One patient received 108 doses. Ages ranged from 10 days to 16 years (13 less than 1 year; 35 from 1 to 5 years; 27 greater than 5 years). Indications for IV infusion were status epilepticus (SE) 16 patients (pts), acute or intermittent seizures 42 pts, substitution for oral dosing 17 pts. Two patients had transient mild decreases in blood pressure after IV VPA began. One patient had transient elevation of AST/ALT while on IV VPA. A second patient had elevated liver function tests prior to IV VPA; liver functions remained stable during IV VPA treatment. Two patients died while on IV VPA, felt to be secondary to underlying etiology (encephalitis, hypoxia/SE respectively). One patient complained of burning on infusion, not present on subsequent doses. No infusion rate or site complications, cardiac arrhythmias, respiratory failure, nor hepatic failure occurred. No infusion site tenderness, swelling or redness were noted. Levels of 34 - 183 mg/L were achieved. All patients could be maintained at target levels with dose adjusstments. When available, infusion rates of 1.5 mg/kg/min to 11 mg/kg/min were reported. One loading dose IV push was reported.
CONCLUSIONS: IV VPA may be administered safely across all age ranges in children. IV VPA can be administered across a wide range of infusion rates and dosages, including very high dosages. Pediatric patients can achieve and maintain target concentrations following IV VPA administration.