Delayed peak serum valproic acid in massive divalproex overdose - Treatment with charcoal hemoperfusion

Background: increased clearance and apparent clinical improvement in valproic acid overdose has been reported following in-series hemodialysis/hemoperfusion therapy. We report a case of divalproex sodium and chlorpheniramine overdose treated with charcoal hemoperfusion and multiple-dose activated charcoal. Case Report: A 32-year-old female presented alert three hours postingestion of her own medication. Serum valproic acid was 105 mu g/mL. No anticholinergic toxicity was seen. Despite three doses of activated charcoal over 14 hours, serum valproic acid continued to rise. Whole bowel irrigation and multiple-dose activated charcoal were commenced 17 h postingestion when serum valproic acid was 1380 mu g/mL. Charcoal hemoperfusion was instituted three hours later when serum valproic acid had not fallen and the patient remained obtunded. Results: Initial extraction ratio of the hemoperfusion cartridge was 0.54 with plasma clearance of 54.5 mL/min. Valproic acid elimination half-life was 3 h during the 190 min hemoperfusion cycle. Posthemoperfusion elimination half-life was 4.8 h with continued multiple-dose activated charcoal dosing. The clinical condition improved during hemoperfusion. Conclusion: Enteric coated valproic acid preparations may cause delayed toxicity in overdose, particularly with coingested anticholinergic medications. In our case, charcoal hemoperfusion appeared to increase valproic acid clearance.