Valproic acid toxicity

Background

• Peak concentration occurs within 4hr (12-18hr for controlled release forms)

Clinical Features

• CNS depression
• Hypotension
• Respiratory depression

Diagnosis

• Level
  • Does not correlate well w/ toxicity
  • Adverse effects increase w/ level >150
• Chemistry
  • Hypocalcemia, hypernatremia, hypophosphatemia, AG metabolic acidosis
• LFT
  • Elevated transaminases
• Hyperammonemia
  • Can be asymptomatic or cause Valproate associated Hepatic Encephalopathy(VPE)
  • Secondary to L-Carnitine and Acetyl-CoA depletion which inhibits urea cycle
  • Can be seen with therapeutic VPA levels and normal LFTs
  • Level does not correlate with severity of VPE

Treatment

• GI detox
  • Activated charcoal PO x1 or multidose (for delayed-release preparations)
• levo-carnitine
  • Increases valproate metabolism
  • Recommended for pts with:
    • Lethargy, coma, VPA assoc hyperammonemic encephalopathy, hepatic dysfunction
  • 100mg/kg IV bolus, followed by 50mg/kg Q8h or alternatively 50mg/kg/day IV in 3 divided doses
• Naloxone
  • May be effective in reversing CNS depression
• Dialysis
  • Effective

Disposition

• Consider d/c for pt with declining levels and pt is asymptomatic

Source

• Tintinalli
• Academic Life in Emergency Medicine: Valproic Acid-Induced Hyperammonemic Encephalopathy (Logan, Jill)