Q: Valproic Acid (VPA) overdose may cause? - select one
A) anion gap metabolic acidosis (AGA)
B) non-anion gap metabolic acidosis (NAGA)
Answer: A
VPA has seen renewed enthusiasm in US ICUs because of its efficacy in delirium. That also brings concern for VPA toxicity. Besides the dreaded complications of cerebral edema and subclinical hyperammonemia and Valproate-related hyperammonemic encephalopathy, popularly known as VHE, it can also cause significant electrolyte and metabolic abnormalities. The most common are
- hypernatremia
- hyperosmolality
- hypocalcemia, and
- elevated anion gap metabolic acidosis
- Hypernatremia occurs because VPA is administered as a sodium salt.
- Hyperosmolality occurs because VPA and its metabolites are low-molecular-weight, osmotically active acids.
- AGA may occur from mitochondrial dysfunction, carnitine deficiency, and/or overproduction of toxic VPA metabolites, which are themselves anions.
- Hypocalcemia occurs as calcium binds to anionic VPA metabolites.
#toxicity
#electrolytes
References:
1. Khoo SH, Leyland MJ. Cerebral edema following acute sodium valproate overdose. J Toxicol Clin Toxicol 1992; 30:209.
2. Sammar A, Tawfik M, Fatima F, Butler A, Aylor-Lee K. Valproate-Induced Hyperammonemic Encephalopathy Causing New-Onset Seizures. Cureus. 2023 Oct 18;15(10):e47288. doi: 10.7759/cureus.47288. PMID: 38021840; PMCID: PMC10656206.
3. Anderson, GO, Ritland, S. Life threatening intoxication with sodium valproate. Clin Toxicol 1995; 33:279.