Sodium valproate-induced hyperammonemia without clinical hepatic dysfunction

Area of Science:

• Neurology
• Clinical Pharmacology
• Toxicology

Background:

• Valproic acid (VPA) is a widely used antiepileptic drug.
• Hyperammonemia is a known, albeit uncommon, side effect of VPA.
• The relationship between VPA, protein intake, and hyperammonemia in adults requires further elucidation.

Purpose of the Study:

• To investigate the occurrence and characteristics of hyperammonemia in adult patients receiving VPA.
• To explore the correlation between VPA dosage, serum VPA concentrations, and arterial ammonium levels.
• To assess the impact of VPA-induced hyperammonemia on neurological and gastrointestinal symptoms.

Main Methods:

• Case series of three adult patients on unrestricted protein diets receiving VPA.
• Monitoring of gastrointestinal symptoms, encephalopathy, and seizure control.
• Measurement of arterial ammonium levels, serum VPA concentrations, and liver function tests.
• Evaluation of phenobarbital concentrations in relevant patients.

Main Results:

• Three adult patients developed gastrointestinal symptoms and/or encephalopathy with hyperammonemia while on VPA.
• Symptoms and hyperammonemia did not directly correlate with VPA dosage or serum VPA levels.
• Neurologic and gastrointestinal symptom remission was linked to VPA concentration reduction.
• One patient experienced recurrent hyperammonemia upon VPA rechallenge.

Conclusions:

• Valproic acid can induce significant hyperammonemia and associated neurological complications in adults, independent of liver function.
• The clinical presentation and severity of hyperammonemia may not correlate with VPA dosage or serum levels.
• Management strategies should include monitoring for hyperammonemia and considering VPA dose reduction for symptom resolution.