Valproic acid overdose and L-carnitine therapy.
A healthy, nonepileptic 16-month-old child ingested a massive overdose (approximately 4000 mg) of valproic acid (VPA). Upon admission to the hospital, he was in a deep coma and had generalized hypotonicity and no response to pain. His serum and urinary concentrations of VPA were 1316.2 and 3289.5 micrograms/mL, respectively. Urinary concentrations of the beta-oxidation metabolites of VPA were low, whereas concentrations of omega- and omega 1-oxidation metabolites were high. Moreover, 4-en-valproate (a potential hepatotoxin) was detected in the urine. Gastric lavage and general supportive measures were undertaken, including intravenous infusion to increase urine output and oral L-carnitine to correct hypocarnitinemia. Subsequently, the beta-oxidation metabolites increased, the omega- and omega 1-oxidation metabolites decreased, and 4-en-valproate was no longer detected. The patient recovered completely and was discharged on the eighth hospital day without any sequelae. This case suggests that enhanced drug excretion and L-carnitine supplementation may prevent potentially fatal hepatic dysfunction after VPA overdose.
Ishikura
H
H
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Matsuo
N
N
Matsubara
M
M
Ishihara
T
T
Takeyama
N
N
Tanaka
T
T
D000927:Anticonvulsants / Q000506:poisoning*; D002331:Carnitine / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D002624:Chemistry, Clinical; D062787:Drug Overdose; D006801:Humans; D007223:Infant; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D013997:Time Factors; D014635:Valproic Acid / Q000097:blood / Q000506:poisoning* / Q000652:urine
D000927:Anticonvulsants; D014635:Valproic Acid; D002331:Carnitine