Plasma Ammonia Level In Patients Receiving Valproic Acid At Srinagarind Hospital: A Case Series

Abstract

Introduction: Valproic acid, a widely used antiepileptic drug and antipsychotic drug, has a high efficacy. However, its side effects can occur in many organs, especially in the central nervous system and valproate-induced hyperammonemic encephalopathy (VHE) has been reported. This study aimed to examine plasma ammonia level and any information which might associate with factors affecting plasma ammonia level in patients with valproic acid therapy. Methods: A retrospective descriptive study was conducted in patients who received valproic acid therapy and had at least one plasma ammonia level in Srinagarind Hospital between 1^st January and 31^st December 2020. Patient demographic data, drug profile, underlying diseases, and side effects were collected. Results: The mean age of 13 patients (8 females, 5 males) was 40.08±28.45 years old with an average BMI 19.50±3.81 kg/m². Hyperammonemia was defined by using a cut point of plasma ammonia level higher than 50 μmol/L. The average plasma ammonia level was 81.87±56.05 μmol/L (33.6-222.3 μmol/L). Nine (69.24%) patients had hyperammonemia (6 females, 3 males). Total valproic acid level was reported in 6 (46.15%) patients with an average level of 94.08 mg/L. Free valproic acid level was reported in 2 (15.38%) patients (15.97 and 38.79 mg/L) and both were above the therapeutic range. The median valproic acid dose in patients was 1000 mg/day (120-2400 mg/day) or 20.78 mg/kg/day (4.41-44.44 mg/kg/day). The total valproic acid dose was above 20 mg/kg/day in most of the hyperammonemic patients. Conclusion: This study revealed that the information which might associate with factors affecting plasma ammonia level in patients were the total daily dose of valproic acid and combination treatment with antiepileptic drugs and antipsychotic drugs. Monitoring plasma ammonia level may be useful for active surveillance in valproic acid safety in the patients at risk.