Successful Management of Valproate Overdose by a Combination of Extracorporeal Therapies

Valproic acid toxicity is not infrequent and is difficult to treat, as there is no specific antidote. In the past, this drug was considered unremovable by extracorporeal methods because of the highly protein bound state (90–95%). However, recent reports suggest that the toxicokinetics of valproate vary considerably from the pharmacokinetics at therapeutic levels, and at higher concentrations protein‐binding sites become saturated. The drug's relatively low molecular weight (144 Da), small volume of distribution (0.13–0.23 L/kg), and saturable protein binding render it potentially amenable to extracorporeal removal, but published experience is scant and there are only a few reported instances in which patients were successfully treated with extracorporeal methods. Here we report the case of a patient with serious valproate toxicity treated with simultaneous “in series” hemodialysis and hemoperfusion followed by continuous veno‐venous hemodiafiltration. A 35‐year‐old homeless male presented to the emergency department after ingesting 120 pills of valproic acid. Initial valproic acid level was 59 µg/mL. Urine drug screen was negative and serum chemistries including LFTs were normal. He was treated with activated charcoal and admitted to the intensive care unit. 4 h later, he developed respiratory failure and became hemodynamically unstable. He was intubated and successfully resuscitated. Subsequently, the valproic acid level was found to be 553 µg/mL and a decision was made to employ extracorporeal methods for drug removal. “In series” hemodialysis and hemoperfusion were done for 4 h and simultaneous blood samples for measurement of valproic acid levels were obtained as blood entered the hemoperfusion column (arterial) and as it exited the hemodialysis membrane (venous). Extraction ratio, whole blood, and plasma clearances were calculated and they compared substantially with the published data. The above measures decreased valproate levels from 572.6 (pre‐dialysis level) to 203.2 µg/mL. This was followed by continuous veno‐venous hemodiafiltration for 18 h, which sustained the drug removal and prevented significant post‐dialytic rebound. This is the first reported instance in which these three methods were administered together successfully in the management of valproic acid toxicity.