Abstracts

RATIONALE: Traditionally, the maximum recommended dose of valproic acid (VPA) is 60mg/kg/day and an intravenous dose is given over 60 minutes at a rate not to exceed 20mg/min.
At the end of this activity participants should be able to discuss the requirements for extremely high doses of intravenous valproic acid and continuous infusions in extraordinary clinical situations.
METHODS: Pharmacy records were reviewed at Virginia Commonwealth University Health Systems(VCUHS) for pediatric intravenous valproic acid (IV VPA)use. Two patients were identified who required high doses of IV VPA for the control of status epilepticus(SE) and both required continuous infusions.
RESULTS: Patient #1- A 3 yr 4 mo old male with a weight of 11.4 kg was transferred to VCUHS from an outlying hospital after 51 days of intractable seizures. On transfer, medications were topiramate, lamotrigine, lorazepam, valproic acid, ranitidine, L-carnitine, amoxicillin, albuterol, beclomethasone, dipropionate and ipratrapium bromide. VPA levels were [lt]25mg/L with doses of 25mg/kg every 6 hours. Additional bolus doses of IV VPA ranged from 90mg/kg/day to 263mg/kg/day with levels ranging from 26mg/L to 104mg/L and seizure activity continued. A continuous infusion of IV VPA was begun at 50/mg/hr and seizure activity ceased. VPA levels remained consistent at 71mg/L.
Patient #2- A 3 mo old male with a weight of 8.3kg was admitted via VCUHS ER in Status Epilepticus (SE). Admission medications were phenobarbital and famotidine. When IV VPA was started medications included metoclopramide, chloral hydrate, glycopyrrolate, nitrofurantoin, topiramate, tiagabine, ferrous sulfate, famotidine, and midazolam. IV VPA was started at 25mg/kg with an additional bolus given 2 hours later. VPA level was 49mg/L. Additional bolus doses of IV VPA ranging from 36mg/kg/day to 217 mg/kg/day were given. To maintain consistent therapeutic levels dosing intervals were shortened and total daily doses were increased. For patient care reasons continuous infusion was substituted when bolus dosing reached every two hours. Infusion rates of 120mg/hr (347mg/kg) which resulted in concentrations of 134mg/L to160mg/L were needed to stop the SE.
In both patients there were no significant changes in blood pressure, liver enzymes or platelet count.
CONCLUSIONS: In some cases patients high doses of IV VPA are indicated. We report 2 cases where doses up to 347mg/kg/day given by continuous infusion were needed to stop SE. These pediatric patients reinforce the need to monitor the therapeutic response in determining the most appropriate dose and rate of infusion. However appropriate surveillance labs should be followed.