#EMConf: Valproic Acid Toxicity

Pathophysiology: Increased GABA therefore CNS depression and in higher doses leads to mitochondrial toxicity by depleting L-carnitine. 


  • CNS depression - sedation, coma, ataxia, tremor; can lead to cerebral edema which is what can kill these patients.
  • Cardiac - can lead to cardiac arrest
  • GI - nausea and vomiting.
  • Levels can peak at 18 hours so this is not your usual observe for 6-8 hour ingestion; can also have delayed presentation from ER preps or bezoar formation.


  • Hypernatremia - secondary to the sodium load in "sodium valproate"
  • Hypoglycemia, hypocalcemia
  • Transaminitis and Hyperammonemia which can worsen the encephalopathy. 
  • Metabolic acidosis


  • EKG and continous monitoring given overdose
  • Labs:
    • CBC, Chem7, VBG, Lactate 
    • Valproic Acid Level
    • LFTs and NH4
    • Acetaminophen and Salicylates
  • Imaging: consider CTH for the undifferentiated altered mental status and/or to monitor for cerebral edema. 


  • Symptomatic and supportive care is the mainstay. 
  • Toxicology or Poison Center Consult 
    • May recommend GI decontamination such as Activated Charcoal (beware of airway protection) or Whole Bowel Irrigation
  • L-carnitine - mixed data 
  • Naloxone - case reports that helps improve mentation transiently. 
  • Hemodialysis - usually at level > 800; nephrology consult. 
  • Carbapenems - ask your toxicologist about using Carbapenem as it can increase hepatic metabolism and increase distribution of Valproate in erythrocytes.