Perioperative N-acetylcysteine to Prevent Renal Dysfunction in High-Risk Patients Undergoing CABG Surgery: A Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association 2005-07, Vol.294 (3), p.342-350
• Main Authors: Burns, Karen E. A, Chu, Michael W. A, Novick, Richard J, Fox, Stephanie A, Gallo, Kerri, Martin, Claudio M, Stitt, Larry W, Heidenheim, A. Paul, Myers, M. Lee, Moist, Louise
• Format: Article
• Language: English
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - therapeutic use; Aged; Antioxidants; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biological and medical sciences; Cardiopulmonary Bypass; Coronary Artery Bypass - adverse effects; Creatinine - blood; Female; General aspects; Humans; Infusions, Intravenous; Kidneys; Male; Medical disorders; Medical sciences; Middle Aged; Perioperative Care; Renal Insufficiency - etiology; Renal Insufficiency - prevention & control; Risk Factors; Surgery; Vasodilator Agents - administration & dosage; Vasodilator Agents - therapeutic use
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.294.3.342

CONTEXT Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia. OBJECTIVE To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo. DESIGN, SETTING, AND PATIENTS Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgery. INTERVENTIONS Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours. MAIN OUTCOME MEASURES The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 μmol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay. RESULTS There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P = .89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1%; P = .37), total (6.1% vs 9.6%; P = .26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>.99), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 μmol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1%; P = .29). CONCLUSIONS N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications,