Morning Report: Valproic Acid Toxicity

Today’s Morning Report is presented by Dr. Bart!

Valproic Acid

Background

-Used for seizure disorders, BPD, migraine prophylaxis.

-Peak concentrations at 6 hours except for enteric coated capsules.

-Complications:

-COMMON: Sedation, ataxia, weight gain, nausea, tremor, or hair loss

-SEVERE: Hepatotoxicity, thrombocytopenia, aplastic anemia, pancreatitis, hyperammonemia (>80 ug/dL or >35umol/L) and reduced L-carnitine concentrations/acetyl-CoA deficiencies → decreased B-oxidation of fatty acids → steatosis

-Therapeutic range: 50-120 mg/L or 347-833 umol/L

Overdose

-CNS depression

-Lethargy, coma (100% of patient with levels > 850 mg/L), cerebral edema

-Respiratory depression, hypotension

-Metabolic:

-Hypernatremia, hypocalcemia, AG metabolic acidosis (poor prognostic sign), and hyperammonemia

-Bone marrow suppression

-Pancreatitis, hepatotoxicity, renal insufficiency

-Can have hyperammonemia without elevated valproic acid levels

Management

-Measure level, repeat every 4-6 hours until downtrending

-Monitor electrolytes, LFTs, CBC, ammonia levels

-Supportive care

-Consider activated charcoal – especially with extended release and enteric coated tablets

-L-carnitine

-Dialysis?

-Call the poison center!

L-carnitine

-Give when evidence of hyperammonemia or hepatotoxicity

-Can be given IV or PO, but should be given IV for symptomatic patients given limited PO absorbtion.

Loading dose of 100 mg/kg up to 6 g over 30 minutes. Then, 15 mg/kg every 4 hours over 10-30 minutes.

What to watch out for after giving L-carnitine?

Most commonly nausea and vomiting. Diarhea and fishy body odor at higher doses. Toxic metabolites typically only accumulate with chronic intake in patients with poor renal function.

References

Doyon S. Chapter 47. Anticonvulsants. In: Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE. eds. Goldfrank’s Toxicologic Emergencies, 9e . New York, NY: McGraw-Hill; 2011.http://accessemergencymedicine.mhmedical.com.newproxy.downstate.edu/content.aspx?bookid=454&Sectionid=40199429.
Minns A. Chapter 109. Anticonvulsants. In: Cline DM, Ma O, Cydulka RK, Meckler GD, Handel DA, Thomas SH. eds. Tintinalli’s Emergency Medicine Manual, 7e.New York, NY: McGraw-Hill; 2012.http://accessemergencymedicine.mhmedical.com.newproxy.downstate.edu/content.aspx?bookid=521&Sectionid=41069039. Accessed September 11, 2014.