patients with cardiac issues, ES-7 and one had a general population. The CI was wide enough that a clinically unimportant difference cannot be ruled out. The SOE was low and was limited by the imprecision of the studies. The SOE was insufficient that mortality, the need for renal replacement therapy, cardiac events, and hospital length of stay did not differ between statins plus N-acetylcysteine versus Nacetylcysteine alone. Most of the studies addressing these outcomes had at least one important study limitation and were consistent but imprecise. Adenosine Antagonists The SOE was insufficient when studies compared adenosine antagonists plus IV saline versus IV saline alone because the CI was so wide that we could not rule out either a clinically important decrease or a clinically important increase in CIN (pooled risk ratio, 0.80; 95% CI, 0.01 to 44.48). The SOE was insufficient to make conclusions about the impact of adenosine antagonists on the need for renal replacement therapy, cardiac events, mortality, or length of hospitalization. Renal Replacement Therapy The pooled analysis for the three studies of hemodialysis compared with IV saline yielded a pooled risk ratio of 1.50, which is consistent with a clinically important increased risk of CIN. The corresponding 95% CI was 0.56 to 4.04, which is consistent with either an increased risk or no important difference. Although the studies on hemodialysis had high risk of bias, the results were consistent enough and precise enough to provide low SOE that hemodialysis does not reduce the risk of CIN when compared with IV saline. Two RCTs compared hemofiltration to IV saline and reported that patients with severe CKD may have a lower incidence of CIN with hemofiltration, but the SOE was insufficient to support a conclusion. The SOE was insufficient to make conclusions about the impact of using hemodialysis or hemofiltration on mortality, cardiac events, the need for subsequent renal replacement therapy, or the length of hospitalization. Ascorbic Acid From studies of the effect of ascorbic acid plus IV fluids compared with IV fluids alone, the pooled risk ratio was 0.72 (95% CI, 0.48 to 1.01), indicating a clinically important effect that was not statistically significant. The pooled estimate of the effect of ascorbic acid compared with N-acetylcysteine demonstrated a clinically unimportant reduced risk of CIN with ascorbic acid use that was associated with a wide CI (pooled risk ratio, 0.89; 95% CI, 0.34 to 2.30). The SOE was low for both comparisons. Other Comparisons Although we found many studies investigating other interventions (Table A), the evidence generally was insufficient to support conclusions regarding their comparative effectiveness. ES-8 Table A. Miscellaneous comparisons for which evidence was insufficient Intervention Comparisons N-acetylcysteine Dialysis, ascorbic acid, nebivolol, atorvastatin, aminophylline, theophylline, fenoldopam, misoprostol IV sodium bicarbonate Acetazolamide, long-term vs. short-term IV sodium bicarbonate, IV saline in 5% dextrose, oral sodium bicarbonate N-acetylcysteine plus IV sodium bicarbonate IV saline and N-acetylcysteine, furosemide plus saline plus N-acetylcysteine, placebo plus sodium bicarbonate, sodium bicarbonate Diuretics (furosemide, mannitol, and acetazolamide) IV saline Vasoactive agents (fenoldopam, calcium antagonists, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, beta-blockers) IV saline Antioxidants (probucol, pentoxifylline) Different hydration regimens Fluid administration (various) Fluid administration (various) Dopamine (or dopamine plus furosemide) Dopamine, furosemide, mannitol, IV saline Discussion Numerous interventions have been used in studies to reduce the risk of CIN. The greatest reduction in CIN was seen with N-acetylcysteine in patients receiving LOCM (Low SOE), and with statins plus N-acetylcysteine (Low SOE). All of the studies included in the statin metaanalyses were of patients receiving intra-arterial contrast media, so no evidence exists on the potential benefit of statins in patients receiving IV contrast media. In the analysis of Nacetylcysteine plus IV saline compared with IV saline alone, there is also evidence of a clinically important reduction in CIN when N-acetylcysteine plus IV saline was compared with IV saline alone in patients receiving LOCM (low SOE). One study has questioned whether Nacetylcysteine is effective at preventing CIN or if it simply reduces serum creatinine.11 This is an important finding; however, the reduction in serum creatinine reported as significant was measured at 4 hours, and it was insignificant at 48 hours, which was the timeframe for the measure of CIN in this report. IV sodium bicarbonate did not appear to be any more effective than IV saline (low SOE). However, a clinically important reduction in CIN was seen when sodium bicarbonate with IV saline was compared with IV saline in studies using LOCM. Ascorbic acid plus IV saline had a clinically important but statistically insignificant effect compared with IV saline alone (low SOE). For other interventions and comparisons included in this report, the SOE was insufficient to support a definite conclusion because, in general, the studies had important limitations, the comparators varied too much, the effects were inconsistent and imprecise, and the