Download Ten Minute Toxicology: Valproic Acid

Ten Minute Toxicology:
VPA
Russell Berger, MD
Co-Director of Medical Toxicology
Cambridge Health Alliance
Common Presentation in Overdose
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Marked Sedation (mimic of brain death)
Paradoxical Seizures
Ataxia
Prolongation of QT
Metabolic Acidosis
Hemorrhagic Pancreatitis
Hyperammonemia
May produce pinpoint pupils and appear as
opiate overdose.
• Cerebral Edema
Management
• Airway support PRN
• Requires at least 2 measurements from the lab and
prolonged observation.
• Enterohepatic circulation so role for MDAC
• Highly protein bound, but dialzyable with levels greater
than 850 (remember dialysis corrects acidosis as well as
eliminates drug).
• L-carnitine
2 Pathways for metabolism
• Mitochondria: Good
• Cytoplasm: Bad
• With cytoplasmic metabolism, get inhibition
of the rate determining step in urea cycle,
CPS-1>>>>hyperammonemia
• The key to getting out of the cytoplasm and
into the mitochondria is L-carnitine.
• In overdose, the supply of L-carnitine is
exhausted.
• Thus, the cytoplasmic(bad) pathway is
favored.
L-carnitine: Adverse events
Common: Nausea, vomiting, diarrhea
Rare: hypotension/hypertension/dysrhythmia/sz
• Safe in pregnancy: B
• Dosing:
-Loading dose of 100mg/kg IV over 15-30
minutes
-Maintenance dosing of 50mg/kg Q 8
hours
(3 g/dose maximum)