Life threatening cardiac arrhythmias in massive acute valproic acid overdose

Objective: Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. Although VPA is known for its quinidine-like effects on cardiac conduction and has been described to stimulate potassium urinary excretion in experimental animals, life threatening cardiac arrhythmias following acute VPA overdose have been rarely reported. Case Report: A 72-years old man being treated with VPA for a psychiatric disorder was admitted to our emergency department with a reported self ingestion of 60 g prolonged release sodium valproate. On examination, he was miotic, apyretic and looked clinically dehydrated. His heart rate was 70 bpm, rhythmic, blood pressure 130/75 mm Hg. He showed a decreased response of deep tendon reflexes and was conscious with 15 Glasgow coma score (GCS). The total VPA plasma concentration was 2239 mg/L associated with hyperammonemia (310 mcg/dL), hypokalemia (2.7 mEq/L) and ECG QTc prolongation (528 msec). We immediately performed gastric lavage, administered multiple doses of activated charcoal and started hydration. The patient’s consciousness level worsened in two hours (GCS 6) and It became necessary to proceed with an oro-tracheal intubation and ventilation. At the same time, he suffered ventricular tachycardia runs unresponsive to antiarrhythmic drugs and junctional rhythm with hemodynamic instability contraindicating the hemodyalisis/hemoperfusion enhanced elimination of the drug. A temporary intracavitary cardiac pacing was placed and removed on the fourth day with a complete recovery of cardiac function and a concomitant return of serum valproic acid therapeutic concentration and normalization of potassium serum level. Twelve hours after the arrival we started levocarnitine administration in order to reduce hyperammonemia which normalized within 24 h. In day 4-6 the patient experienced transient thrombocytopenia (16.000) which required repeated platelets transfusion. The patient remained in hospital for 13 days due to lung comorbidity and was discharged in good health conditions. Conclusions: massive acute VPA intoxication could be complicated by complex, rarely reported and life threatening cardiac arrhythmias probably sustained by valproic acid induced quinidine-like effect and hypokalemia. Moreover, valproic acid induced hyperammonemia and thrombocytopenia must be carefully evaluated (1). References:1.Sztajnkrycer MD. Valproic Acid Toxicity: Overview and Management J Toxicol Clin Toxicol 2002;40(6):789-801.