Abstracts

Epileptic patients are at great risk of self poisoning. Safety in overdose is important when choosing and antiepileptic drug. Several conditions are known to be associated with an increased risk for valproate (VPA)-induced liver toxicity. Rare cases of fatal liver injury due to overdose with VPA were reported. A group of 12 patients, children and adolescents, aged 12-18 years (mean 16.4) was treated for VPA-overdose with suicidal intent. Sustained-release VPA formulation was orally administered in 9 patients with idiopathic epilepsy and normal intelligence. Prescribed doses ranged between 24-38 mg/kg/daily for 8 to 52 months of continuous antiepileptic treatment. Serum concentrations were in therapeutic range (64-112 ug/ml). Regular monitoring of liver tests showed no significant abnormalities. Transient increase in serum-transaminase activity was seen in 4 patients during the first year of treatment. In remaining three non-epileptic patients, no previous VPA use was noted. The VPA overdoses ranged from 12.5 to 34 g (mean 18.2 g). No concomitant administration of cytochrome P-450-inducing drugs was noted. Acute intervention (gastric lavage) was taken in 7 of 12 patients. When admitted, their VPA serum levels ranged from 108 to 174 ug/ml. Remaining five patients were managed 2-5.5 hours after VPA overdosage. Their VPA serum levels ranged from 246 to 682 ug/ml. CNS toxicity presenting with lethargy, malaise, nausea, vomiting and seizure aggravation was observed in 7 patients. Cerebellar dysfunction including nystagmus, incoordination, dysarthria and ataxia was initial feature in half of patients. Impaired respiration and coma developed in three of them. L-carnitine was started. Serum aminotransferase, alkaline phosphatase and gama-glutamyl-transferase activity were moderately increased in 6/12 patients. The protrombin time was prolonged in one patient with no bleeding tendency. Serum ammonia levels were elevated in 8/12. Transient hypoglycemia occurred in two children. Mild jaundice developed in one girl taking 14 g of VPA with alcohol. Her liver biopsy showed drug-induced hepatitis. Serial electrocardiograms showed no abnormality through their hospital stay. Complete clinical recovery was achieved in all patients for two to five days after the ingestion of VPA overdose. Specific psychiatric intervention in epileptics with suicidal behavior was strongly recommended. No significant liver lesions occurred in patients with suicidal ingestion of VPA overdoses. Excessive VPA amount ingested, without other risk-factors for liver toxicity, seemed to be associated rather with CNS toxicity than with liver injury.