Efficacy and Safety of Sodium Benzoate in The Management of Hyperammonemia in Decompensated Chronic Liver Disease of the Childhood-A Double-blind Randomized Controlled Trial.

Abstract

The objective was to evaluate the efficacy and safety of sodium benzoate in the management of hyperammonemia and hepatic encephalopathy (HE) in decompensated chronic liver disease. It was a prospective, interventional, double-blinded randomized controlled trial conducted from August 2017 to December 2018. Children with decompensated chronic liver disease and hyperammonemia were included in the study. Those with ammonia >400 μg/dL, already receiving sodium benzoate or with grade III ascites were excluded. Group A received sodium benzoate (400 mg/kg loading dose followed by 200 mg · kg · daymaintenance for 5 days) along with the standard medical therapy. Group B received standard medical therapy with placebo. A total of 108 episodes of hyperammonemia occurred in 86 patients of whom 16 were excluded. The final analysis included 46 episodes in each group. The median decrease in ammonia from baseline to day 5 was 52 μg/dL in group A versus 42 μg/dL in group B (P = 0.321). There was a significant decrease in ammonia on days 1 and 2 in group A as compared to group B, but not on subsequent days. There was no significant difference in the resolution of HE (57.1% vs 50%; P = 1), but there was higher, albeit insignificant increase in ascites in group A (15.9% vs 4.5%). Addition of sodium benzoate significantly reduced the ammonia levels on the first 2 days of therapy but the effect was not sustained till day 5. The effect of sodium benzoate would probably be more sustained, if higher dosage (400 mg · kg · day) could be used under monitoring of benzoate levels. There was no effect on resolution of HE. Sodium benzoate caused an increasing trend of adverse events with no effect on short-term survival.