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 μg 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 μg 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 μg mL to 1840 μg mL with a mean of 378.3 μg mL ± 310.2 μg 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 μg mL was more likely to be associated with a moderate or major adverse outcome (p < 0.005). A peak concentration >850 μg 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 μg mL. Four patients experienced transient leukopenia (WBC < 3,500). The mean hospital stay for all patients was 42 ± 33.1 hours. A hospital stay >48 hours was more likely to be associated with a peak valproic acid concentration >450 μg mL (p < 0.05). There were 2 fatalities. Conclusions: In this case series, patients with peak valproic acid concentrations above 450 μg mL were more likely to develop significant clinical effects and have longer hospital stays. A peak valproic acid concentration above 850 μg mL was more likely to be associated with coma, respiratory depression, aspiration, or metabolic acidosis.