Valproate-induced coma: case report and literature review

Area of Science:

• Neurology
• Clinical Pharmacology
• Toxicology

Background:

• Valproic acid (VPA) is a widely used antiepileptic drug.
• VPA can cause adverse effects, including hepatic failure and coma, often associated with elevated ammonia levels.
• However, hyperammonemic coma can occur without overt signs of hepatic dysfunction.

Observation:

• A patient on long-term phenytoin (PHT) and phenobarbital (PB) developed progressive neurological decline.
• Initiation of VPA therapy during PHT tapering led to altered consciousness, progressing to coma.
• Laboratory findings revealed isolated hyperammonemia without evidence of hepatic failure.

Findings:

• This case highlights VPA-induced hyperammonemic coma as a potential complication, even in the absence of hepatic dysfunction.
• The co-administration of PHT and PB with VPA may influence the risk or presentation of hyperammonemia.
• Distinct biochemical pathways may underlie hyperammonemia with and without hepatic failure during VPA treatment.

Implications:

• Clinicians should consider VPA-induced hyperammonemic coma in patients on concurrent PHT or PB therapy presenting with neurological symptoms.
• Early recognition and discontinuation of VPA are critical upon observing symptoms like lethargy or gastrointestinal distress.
• This case underscores the importance of vigilant clinical monitoring for VPA-related adverse events.