Multicenter case series of valproic acid ingestion: Serum concentrations and toxicity

Background: Valproic acid exposures reported to poison centers have increased more than 4-fold over the last 5 years. There are no large case series published on valproic acid ingestion. Methods: A prospective multicenter case series of all patients reporting an ingestion of valproic acid, Data collected included: age, gender, dose ingested, concomitant medications, symptoms and vital signs, laboratory values, length of hospital stay, and medical outcome. Entrance into the study required a serum valproic acid concentration above the therapeutic threshold of 100 mug/mL, Statistical analysis was by Fisher's exact test, Results: A total of 335 patients were reported to participating centers of which 186 (55%) had serum valproic acid concentrations greater than 100 mug/mL. Of the 186 cases, 53 were multiple drug exposures leaving 133 cases of sole valproic acid ingestion for evaluation, Age ranged from 2 to 66 years with a mean of 30.1 years +/- 12, Peak serum valproic acid concentrations ranged from 110 mug/mL to 1840 mug/mL with a mean of 378.3 mug/mL +/- 310.2 mug/mL. Time from postingestion to the peak measured valproic acid concentration ranged from 1 to 18 hours, with a mean of 7.4 hours +/- 3.9. Symptoms included lethargy (n = 94), coma (n = 19), tachycardia (n = 24), aspiration (n = 8), metabolic acidosis (n = 8), and hypotension (n = 4), A peak concentration of >450 mug/mL was more likely to be associated with a moderate or major adverse outcome (p < 0.005). A peak concentration >850 mug/mL was more likely to be associated with coma (p < 0.005) and acidosis (p < 0.005). Eleven patients experienced transient thrombocytopenia (platelets < 150,000) and all had peak valproic acid concentrations >450 mug/mL. Four patients experienced transient leukopenia (WBC < 3,500), The mean hospital stay for all patients was 42 <plus/minus> 33.1 hours. A hospital stay >48 hours was more likely to be associated with a peak valproic acid concentration >450 mug/mL (p < 0.05). There were 2 fatalities. Conclusions: In this case series, patients with peak valproic acid concentrations above 450 <mu>g/mL were more likely to develop significant clinical effects and have longer hospital stays. A peak valproic acid concentration above 850 mug/mL was more likely to be associated with coma, respiratory depression, aspiration, or metabolic acidosis.