Abstract 1797: High-dose N-acetylcysteine for Preventing Acute Renal Injury after Cardiac Surgery
BACKGROUND: Acute renal injury after cardiac surgery is associated with increased mortality and morbidity. N-acetylcysteine may prevent acute renal injury caused by ischemia, oxidative injury, and systemic inflammation. Definitive evaluation of its efficacy requires a large trial powered to measure clinical outcomes. To determine if N-acetylcysteine holds sufficient promise to warrant future study, we performed an initial trial evaluating effects on a surrogate outcome (changes in serum creatinine concentration).
METHODS: Between 2003 and 2005, 177 cardiac surgery patients with preoperative creatinine clearances below 60 mL/min were recruited in a triple-blinded placebo-controlled randomized trial. Eighty-nine were randomized to intravenous N-acetylcysteine (100 mg/kg bolus and 20 mg/kg/hr infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was percent change in estimated creatinine clearance over the first 72 postoperative hours. Secondary outcomes included mortality, renal replacement therapy, atrial fibrillation, vasoactive medications, and adverse effects. Based on an estimated standard deviation (SD) of 19%, minimum criteria for a future trial were a primary outcome that was 3.8% better (0.2 SD - small benefit) and an upper 95% confidence interval (CI) including 9.5% (0.5 SD - moderate benefit).
RESULTS: The median percent change in creatinine clearance was 5.2% better in the N-acetylcysteine arm (95% CI: 2.4% worse to 12.1% better; P = 0.46). N-acetylcysteine was associated with significantly reduced mortality (0% vs. 8%; P = 0.007) and trends toward reduced vasoactive medications, atrial fibrillation, and renal replacement therapy. N-acetylcysteine was safe: its major adverse effect was a trend towards increased nausea or vomiting.
CONCLUSIONS: The effect of N-acetylcysteine on postoperative creatinine clearance met minimum criteria to warrant further study. It was also associated with favorable trends on several important secondary outcomes. These potential benefits are biologically plausible and consistent with other perioperative studies. Given these findings, N-acetylcysteine should now be definitively evaluated in a large randomized trial.