N-acetylcysteine to prevent contrast nephropathy.

Clinical scenario A 65-year-old man with hypertension, diabetes, and chronic renal insufficiency comes to your clinic complaining of progressive angina with moderate exertion. On exercise electrocardiogram, he exercises for 2 minutes and develops 2 mm of ST-segment depression. He develops severe angina, which causes him to stop the test. You admit him for cardiac catheterization, and his baseline labs show a creatinine of 2.2 mg/dl. You wonder if there is a benefit to pretreatment with N-acetylcysteine (NAC) to limit his risk of developing contrast nephropathy. Literature search Combining heart catheterization and acetylcysteine in Medline, you find several small studies as well as the following meta-analysis: Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003;362:598-603. Question Does the addition of NAC to intravenous (IV) saline hydration limit contrast nephropathy in patients with baseline renal insufficiency who are undergoing cardiac catheterization? Design The study was a meta-analysis of 7 randomized, controlled trials. The authors of the trial attempted to ensure the validity of their meta-analysis. They exhaustively searched relevant studies and identified 13 potential reports for inclusion. Six of these were subsequently excluded because they did not meet the authors' prespecified inclusion criteria, which ensured that included studies were prospective, randomized, controlled trials of patients with chronic renal insufficiency receiving intravascular contrast media. To be included, trials had to randomize patients to NAC versus placebo and had to examine development of acute renal failure as the primary end point. Thus, 7 trials were incorporated into the meta-analysis. Patients In total, 805 patients with chronic renal insufficiency in 7 trials of coronary angiography/percutaneous transluminal coronary angioplasty and 1 trial of computed tomography (CT) scan receiving IV contrast dye were studied. The amount of dye used in the studies varied somewhat, from 75 mL per patient in 1 study (patients undergoing CT scan with a fixed dose of dye) to a mean of 187 ml per patient in a trial in which most of the patients underwent interventional procedures. Intervention The intervention studied was oral NAC versus placebo given before contrast administration. NAC dosing regimens varied slightly in the trials. Five trials prescribed 600 mg of oral NAC given twice daily for 4 doses, another administered 400 mg twice daily for 4 doses, and 1 trial gave 1200 mg once before the procedure and once after. All trials used similar methods of periprocedural IV hydration. Main outcome measures The main outcome measures were as follows: incidence of contrast nephropathy at 48 hours, as defined by a rise in serum creatinine of at least 0.5 mg/dL in 4 trials, a serum creatinine rise of >25% in 2 trials, and either of the above measures in 1 trial. Main results Because a Q statistic suggested statistical heterogeneity (P =.016), a random effects model was used to analyze the data. The authors found a 56% relative risk reduction in the incidence of contrast nephropathy in patients who received periprocedural NAC (RR 0.44, 95% Cl 0.22-0.88). Meta-regression found that neither the volume of contrast administered nor the degree of chronic renal insufficiency was associated with the relative risk of contrast nephropathy.