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Orphanet J Rare Dis. 2016 Sep 23;11(1):127.

Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

Author information

1
Etablissement Pharmaceutique des Hôpitaux de Paris, AGEPS, 7 rue du Fer à Moulin, Paris, 75005, France. marie-caroline.husson@aphp.fr.
2
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Robert-Debré, AP-HP, Paris, France.
3
Reference Centre for Inherited Metabolic Disorders, Hôpital Femme Mère-Enfant, Lyon, France.
4
Centre de Référence des Maladies Héréditaires du Métabolisme, CHU Timone Enfants, Marseille, France.
5
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Jeanne-de-Flandre, CHRU Lille, Lille, France.
6
Reference Centre for Inherited Metabolic Disorders (MaMEA), Hôpital Necker-Enfants Malades, Institut Imagine, Université Paris Descartes, 149 rue de Sèvres, 75743, Paris, Cedex 15, France.
7
Centre de Référence des Maladies Héréditaires du Métabolisme, CHU de Nancy, Hôpital Brabois Enfants, Vandoeuvre-les-Nancy, France.
8
URC/CIC Paris Centre, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, 75015, Paris, France.

Abstract

BACKGROUND:

The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases.

RESULTS:

Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 μmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 μmol/L (20.0-2274.0 μmol/L); it decreased to 40.0 μmol/L in patients who were alive (13.0-181.0 μmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to ≤ 100 μmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another treatment for hyperammonemia (sodium phenylacetate + sodium benzoate, haemofiltration). Eighteen side effects were reported related to the i.v. infusion (local diffusion, oedema).

CONCLUSION:

This 10-year retrospective study shows that i.v. sodium benzoate associated with an emergency regimen is an effective and safe treatment for acute episodes of UCD.

KEYWORDS:

Clinical trials; Hyperammonemia; Sodium benzoate; Systematic review; Urea cycle disorders

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