Abstracts

Valproic acid (VPA) and its formulations have a relatively low incidence, 1/40,000 (0.0025%), of pancreatitis in routine oral use for the treatment of epilepsy. Anecdotal series of patients treated with VPA have fewer adverse effects despite increasing doses to [ge]100-mg/kg/day. We investigated the incidence of pancreatitis in patients treated with the IV formulation VPA. Our hypothesis was that IV VPA may be more toxic in causing pancreatitis in epilepsy patients treated for status epilepticus (SE) [amp] for substitution of oral doses when patients need to be NPO were highly induced [amp] required very high doses of IV VPA [gt]100-mg/kg/day.
67 patient exposures were identified from pharmacy records to have received VPA IV between 1998 and April 15, 2003 at Children[rsquo]s Hospital, St. Paul MN. Records were reviewed to identify patients who received VPA for more than 24 hours. 44 exposures in 39 patients (20 boys/19 girls, age 0.07 to 19.4 yrs, mean 8.6 years) met this criterion. Etiology of treatment, days of treatment, total daily dose [amp] dosing interval of VPA, patient weight [amp] age, max level of VPA during treatment, albumin, minimum platelet, amylase, lipase, [amp] concurrent AEDs were recorded.
3/39 patients (7.7%), total of 44 exposures, were identified as having pancreatitis by increased lipase, attributed to VPA. All 3 patients had been placed on VPA for treatment of SE with pentobarbital induced burst suppression. No patient had a prior history of pancreatitis. (Table below.) Onset of pancreatitis were 10, 11, [amp] 12 days after exposure to VPA. Patient 1 presented with new onset seizures due to encephalitis. Patients 2 [amp] 3 had a history of epilepsy, no other etiology was identified. Patient 1 was also taking PB, PHT, and LEV. Patient 2 was also taking ZNS. Patient 3 was also taking FBM, LEV [amp] TPM. Levels of VPA were within range for treatment of medically intractable epilepsy (50-150 ug/ml), however the dose of VPA needed to maintain these levels was much higher than those seen in oral dosing due to the highly induced state of the patient on pentobarbital. Amylase [amp] liver function tests were normal in all patients. Max lipase levels are listed below. All patients had a complete recovery from pancreatitis after discontinuation of VPA.[table1]41/44 (93.2%) did not develop pancreatitis. Exposure to VPA ranged from 1-29 days (mean 5.3 days). The average daily dose was 50.2 mg/kg/d with an average maximum level of 84.5 ug/ml.
In this series, 36 (92%) of pediatric patients tolerated high doses of IV VPA without adverse effects. However, if doses exceeded 130-mg/kg/day due to pentobarbital induction (3 patients [8%]) a reversable pancreatitis was observed. This implies that a maximal tolerable dose of IV valproate does exist.