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Valproic acid overdose and L-carnitine therapy

H Ishikura¹, N Matsuo, M Matsubara

¹Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.

Journal of Analytical Toxicology

|January 1, 1996

Summary

A massive valproic acid (VPA) overdose in a child led to coma but was treated with enhanced excretion and L-carnitine. This intervention successfully prevented liver damage, allowing for a full recovery.

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Area of Science:

Toxicology
Pediatrics
Pharmacology

Background:

Valproic acid (VPA) is a commonly prescribed antiepileptic drug.
VPA overdose can lead to severe toxicity, including coma and potential hepatotoxicity.
Metabolic pathways of VPA, including beta-oxidation and omega-oxidation, are crucial for its clearance.

Observation:

A 16-month-old child ingested approximately 4000 mg of VPA, presenting with deep coma and hypotonia.
Elevated serum and urinary VPA levels were detected, with altered metabolite profiles (low beta-oxidation, high omega-oxidation).
Urinary 4-en-valproate, a potential hepatotoxin, was identified.

Findings:

Treatment involved gastric lavage, supportive care, intravenous fluids for diuresis, and oral L-carnitine supplementation.

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Post-treatment, urinary beta-oxidation metabolites increased, omega-oxidation metabolites decreased, and 4-en-valproate was cleared.

The child experienced a complete recovery without sequelae by the eighth hospital day.

Implications:

Enhanced drug excretion and L-carnitine supplementation may be effective in managing VPA overdose.
This approach could prevent severe hepatic dysfunction in pediatric valproic acid poisoning.
Early intervention and metabolic support are critical for favorable outcomes in acute VPA toxicity.