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.
Jay Khadpe MD
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