Acute valproate poisoning - Pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy

The clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-induced changes are discussed. Central nervous system features were the predominant clinical manifestations (6/6), followed by respiratory failure (5/6) and multiorgan failure (2/6). Mechanical ventilation was required in 5 of 6 patients because of respiratory depression or deep coma. Hemodialysis was applied in 4/6 of the cases due to hyperammonemia, worsening neurologic condition, or organ dysfunction. Cerebral edema and hemorrhagic pancreatitis ensued in 2/6 of the patients and ICU mortality was 2/6. VPA peak levels ranged from 520 to 1700 mg/L with a mean of 1127 mg/L. Ammonia was elevated in all cases with a mean of 550 mu g/dL. All patients showed signs of impaired mitochondrial P-oxidation with increase of medium- and long-chain acylcarnitines in serum. Severe VPA overdose is associated with a high mortality rate requiring early medical interventions. Beside supportive intensive care, hemodialysis can be considered as an adjunctive measure.