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Ten Minute Toxicology : VPA

Ten Minute Toxicology : VPA. Russell Berger, MD Co-Director of Medical Toxicology Cambridge Health Alliance. Common Presentation in Overdose. Marked Sedation (mimic of brain death) Paradoxical Seizures Ataxia Prolongation of QT Metabolic Acidosis Hemorrhagic Pancreatitis

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Ten Minute Toxicology : VPA

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  1. Ten Minute Toxicology:VPA Russell Berger, MD Co-Director of Medical Toxicology Cambridge Health Alliance

  2. Common Presentation in Overdose • 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

  3. 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

  4. 2 Pathways for metabolism • Mitochondria: Good • Cytoplasm: Bad • With cytoplasmic metabolism, get inhibition of the rate determining step in urea cycle, CPS-1>>>>hyperammonemia

  5. 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.

  6. L-carnitine: Adverse events Common: Nausea, vomiting, diarrhea Rare: hypotension/hypertension/dysrhythmia/sz

  7. 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)

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