Oral N-Acetylcysteine (NAC) to Prevent Contrast-Induced Nephrotoxicity: Is NAC the Answer?

The first human study assessing the effects of NAC in preventing CIN was published in 2000 by Tepel et al.14 This prospective, randomized, placebo-controlled trial assigned 83 patients with chronic kidney disease (serum creatinine > 106 pmol/L or creatinine clearance < 50 mL/min) undergoing computed tomography to receive either oral NAC or placebo twice daily plus intravenous saline. NAC was given as 600 mg orally twice daily the day before and the day of contrast administration. Half normal (0.45%) saline was given to both groups intravenously at 1 ml/kg per hour for 12 hours before and 12 hours after administration of a low osmolar non-ionic contrast medium. A modest dose (75 mL) of contrast was administered to all patients. All patients were encouraged to drink if they were thirsty. Acute CIN was defined as an increase in the serum creatinine concentration of at least 44 µmol/L within 48 hours after contrast administration. Forty-eight hours after radiocontrast exposure, there was a significant decrease in both serum creatinine and blood urea nitrogen in the NAC group (p < 0.001). Ten patients (12%) developed CIN: one patient from the NAC group (2%) and nine patients from the control group (21%) (absolute risk reduction [ARR] 19%; number needed to treat [NNT] 5; p = 0.01; 95% CI 0.02-0.9). Five of ten patients who developed CIN had diabetes mellitus. In patients with a baseline serum creatinine of greater than 221 µmol/L, none (O of 13 patients) in the NAC group and 42% (5 of 12 patients) in the control group developed CIN (ARR 42%; NNT 2.4; p = 0.02). The authors concluded that prophylactic administration of NAC twice daily the day before and on the day of contrast administration reduced the incidence of acute CIN. Most of the published studies have used NAC doses of 600 mg given twice daily for four doses (Table i).15,16,18,20-22 It has been speculated that in patients undergoing coronary procedures, where a large amount of contrast may be administered, a higher dose of NAC may be more effective than the 600 mg dose.30 The Briguori group, who were unable to demonstrate a benefit to NAC in their first study using 600 mg doses,16 recently reported the results of a head-to-head trial comparing doses of 600 mg versus 1200 mg given twice daily for four doses plus 0.45% saline hydration prior to coronary angiography and/or angioplasty.31 In this study, CIN occurred in 11% (12/109) of patients in the 600 mg group versus 3.5% (4/114) of patients in the 1200 m