For valproic acid overdose

Perrott J, Murphy NG, Zed PJ. L-carnitine for acute valproic acid overdose a systematic review of published cases. Ann Phar-macother 2010 44(7-8) 1287-93. 

Nuclear magnetic resonance spectroscopy was investigated as a method to screen for organic substances (and metabolites) in patients with indications of a drug overdose [17]. Urine specimens containing valproic acid were examined by H-NMR spectroscopy at 300 MHz and the results compared with GC MS. 

A patient whose death was attributed to an overdose of valproic acid had ingested 2.25 g each day for 5 days the postmortem blood concentration was 52pg/ml and therapeutic concentrations of phenobarbitone and phenytoin were also present death was thought to be due to the high initial dose of valproic acid (J. P. Tift, New Engl. J. Med., 1980,303, 394). 

After a valproate overdose a 27-year-old man developed seizures, hypernatremia, respiratory failure, metabolic acidosis, liver failure, and bone marrow depression (125). His plasma valproic acid concentration was 1414 pg/ml. Treatment with hemodialysis was effective in enhancing valproic acid clearance, while hemoperfu-sion was relatively less effective, because of saturation of the column. Overall, the half-Ufe of the drug was reduced from over 20 hours before treatment to less than 3 hours during hemodialysis/hemoperfusion drug removal was probably favored by saturation of drug binding to plasma proteins, which resulted in a low unbound fraction (32% at the start of treatment). He was comatose for 5 days but recovered fully thereafter. 

A. Specific levels. Obtain a stat serum valproic acid level. Serial valproic acid level determinations should be obtained, particularly after ingestion of divalproex-containing preparations (Depakote), owing to the potential for delayed absorption. Peak levels have been reported up to 18 hours after Depakote overdose, and could be even later after ingestion of the new formulation Depakote ER. 

Drug overdose Of 16 796 toxic exposures to antiepileptic drugs (phenytoin, valproic acid, and carbamazepine) in the USA in 2006, 12 resulted in death, as reported by the US Toxic Surveillance System [67 ]. Some specific problems determined by overdose of some old and new antiepileptic drugs have been briefly reviewed. For example, topiramate can cause a significant metabolic acidosis, lamotrigine Stevens-Johnson syndrome, oxcarbazepine hyponatremia, and levetiracetam psychosis. Possible adoption of guidelines for critical care management of overdose are discussed. 

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