Intravenous acetylcysteine for indications other than acetaminophen overdose

Abstract

The use of intravenous acetylcysteine for off-label indications, specifically non-acetaminophen-induced acute liver failure (NAI-ALF), severe alcoholic hepatitis, and contrast-induced nephropathy (CIN), is reviewed. I.V. acetylcysteine is most often used as an antidote for acetaminophen overdose due to its ability to increase levels of glutathione; however, it is also used to treat NAI-ALF and severe alcoholic hepatitis and to prevent CIN. Although the i.v. and oral formulations of acetylcysteine have been evaluated for these indications, most studies have examined the i.v. form. I.V. acetylcysteine is used in the treatment of NAI-ALF to improve oxygenation to the liver. One large randomized trial of 173 adults with NAI-ALF from any etiology and of any grade encephalopathy demonstrated overall improvement in transplant-free survival, particularly for patients with low-grade encephalopathy, though overall survival was not improved. When used to treat severe alcoholic hepatitis, i.v. acetylcysteine serves as an antioxidant and glutathione source. A trial of 174 patients with severe alcoholic hepatitis revealed that patients had 28-day survival benefit when treated with acetylcysteine; improvement in patients with hepatorenal syndrome was also noted. When used for the prevention of CIN, i.v. acetylcysteine provides antioxidants and vasodilation. The benefit for this indication is limited to surrogate markers such as serum creatinine and in patients with multiple risk factors for the development of CIN. Data regarding the use of i.v. acetylcysteine for the treatment of NAI-ALF and severe alcoholic hepatitis and in the prevention of CIN are inconclusive, though some evidence supports its use in certain populations.