Impact of intestinal mannitol on hyperammonemia, oxidative stress and severity of hepatic encephalopathy in the ED

• Published in: The American journal of emergency medicine Vol. 36; no. 9; pp. 1570 - 1576
• Main Authors: Montes-Cortés, Daniel H., Novelo-Del Valle, José L., Olivares-Corichi, Ivonne M., Rosas-Barrientos, José V., Jara, Luis J., Cruz-Domínguez, María Pilar
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2018; Elsevier Limited
• Subjects: Adult; Alcohol; Ammonia; Ammonia - metabolism; Ammonium; Biomarkers; Biomarkers - metabolism; Blood pressure; Carbonyl compounds; Diabetes; Dilution; Discomfort; Diuretics, Osmotic - administration & dosage; Drug Administration Routes; Emergency medical care; End Stage Liver Disease - complications; Enema - methods; Female; Hepatic encephalopathy; Hepatic Encephalopathy - blood; Hepatic Encephalopathy - prevention & control; Humans; Hyperammonemia; Hyperammonemia - blood; Hyperammonemia - drug therapy; Hypertension; Intestinal; Intestinal microflora; Intestine; Ischemia; Lactulose; Liver diseases; Male; Mannitol; Mannitol - administration & dosage; Microbiota; Middle Aged; Neomycin; Neurotoxicity; Oxidative stress; Oxidative Stress - physiology; Patients; Protein metabolism; Protein turnover; Proteins; Stress concentration; Stress oxidative; Mexico; Stress oxidative; Hepatic encephalopathy; Mannitol; Hyperammonemia; Intestinal
• ISSN: 0735-6757; 1532-8171
• DOI: 10.1016/j.ajem.2018.01.032

Hyperammonemia results from hepatic inability to remove nitrogenous products generated by protein metabolism of intestinal microbiota, which leads to hepatic encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity, oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if intestinal mannitol is as effective and safe as conventional treatment for diminishing hyperammonemia, OxS, and HE in patients with CLD.
We included 30 patients with HE classified by “Haven Criteria for Hepatic Encephalopathy”. They were randomized into two groups: 1) Mannitol Group (MG) with mannitol 20% administered into the intestine by an enema, 2) conventional group (CG) with lactulose 40 g enema both substances were diluted in 800 mL of double distilled solution every 6 h; all patients received neomycin. We evaluated ammonia concentration, plasma oxidative stress, HE severity, intestinal discomfort and adverse effects.
Hyperammonemia (171 ± 104 vs 79 ± 49 μmol ammonia/L, p < 0.01), and oxidative stress (MDA 29 vs 27%, formazan 15 vs 11%, carbonyls 16 vs 9% and dityrosines 10 vs 5%) were reduced in MG and CG respectively. The HE severity decreased by two degrees compared to baseline values in both groups. Intestinal discomfort and electrolyte plasma alterations were less frequent (p < 0.05) in MG than CG.
Intestinal mannitol is as effective and safe as conventional treatment for reducing hyperammonemia, oxidative stress, and hepatic encephalopathy of CLD patients in the emergency room. Likewise, mannitol is better tolerated than conventional treatment.