downgraded for each domain in which a problem was identified. If the magnitude of effect was very large, the SOE could be upgraded. Observational studies were considered in grading the strength of a body of evidence if the overall results of the observational studies were not similar to the RCTs applicable to the comparison. Organization of This Report The following Results section reports on a number of comparisons. We report in detail on comparisons for which substantial evidence exists, starting with the comparisons that have received the most attention in the literature (N-acetylcysteine plus IV saline vs. IV saline, IV sodium bicarbonate vs. IV saline, N-acetylcysteine plus IV saline vs. IV sodium bicarbonate, statins plus IV saline vs. IV saline, adenosine antagonists plus IV saline vs. IV saline, renal replacement therapy vs. IV saline, and ascorbic acid plus IV saline vs. IV saline). At the end of the results section, we refer to information about other miscellaneous comparisons for which there were too few studies to draw any conclusions. Details on those comparisons appear in Appendixes H and I of the full report. Results The literature search revealed a total of 186 articles: 163 RCTs and 23 observational studies on interventions for preventing CIN, including 67 RCTs (N = 13,176) on N-acetylcysteine versus IV saline; 28 RCTs (N = 6,645) on IV sodium bicarbonate versus IV saline; 7 RCTs (N = 1,688) on N-acetylcysteine versus sodium bicarbonate; 19 RCTs (N = 10,574) on statins (8 comparing a statin to IV saline, 5 comparing a statin plus N-acetylcysteine to N-acetylcysteine, and 6 other comparisons of statin versus statin, statin by dose, or statins plus other agents); 5 RCTs (N = 3,647) on adenosine antagonists; 6 RCTs (N = 790) on use of hemodialysis or hemofiltration to prevent CIN; and 8 RCTs (N = 1,830) comparing ascorbic acid to IV saline (N = 6) or Nacetylcysteine (N = 3). We included in the meta-analyses 54 RCTs investigating N-acetylcysteine with IV saline versus IV saline with or without a placebo (46 studies using only intra-arterial contrast media, 7 studies using IV contrast media, and 1 study that did not report the route of administration); 19 RCTs investigating the use of sodium bicarbonate versus IV saline (14 studies using only intraarterial contrast media, 2 studies using only IV contrast media, and 3 studies using either intraarterial or IV contrast media); 7 RCTs investigating use of IV sodium bicarbonate versus Nacetylcysteine plus IV saline (6 studies using intra-arterial contrast media and 1 study using IV contrast media); 8 RCTs investigating use of a statin versus a placebo or IV saline (all studies using intra-arterial contrast media); 5 RCTs investigating the use of a statin plus Nacetylcysteine versus N-acetylcysteine alone (all studies using intra-arterial contrast media); 3 RCTs investigating use of hemodialysis versus IV saline alone (all studies using intra-arterial contrast media, 1 of which also included some patients receiving IV contrast media); 4 RCTs investigating use of an adenosine antagonist with IV saline versus IV saline alone (3 studies using intra-arterial contrast media and 1 study using IV contrast media); 6 studies investigating the use of ascorbic acid versus IV saline (all studies using intra-arterial contrast media); and 3 ES-5 studies investigating the use of ascorbic acid versus N-acetylcysteine (all studies using intraarterial contrast media). The results of these studies were published between 1998 and 2015. N-Acetylcysteine Versus IV Saline Using a random-effects model to pool studies comparing N-acetylcysteine with IV saline versus IV saline with or without a placebo, the pooled risk ratio for CIN was 0.78 (95% CI, 0.59 to 1.03) for high-dose N-acetylcysteine (>1,200 mg/day), indicating a small effect that is clinically unimportant and statistically insignificant (p=0.075) with low SOE, and 0.75 (95% CI, 0.63 to 0.89) for low-dose N-acetylcysteine (1,200 mg/day or less), indicating a borderline clinically important effect. Sensitivity analyses revealed imprecise estimates of the pooled risk ratio for CIN when stratified by route of administration of contrast media: 0.78 (95% CI, 0.55 to 1.12) for high-dose N-acetylcysteine when intra-arterial contrast media were used (high-dose Nacetylcysteine with intra-arterial contrast media administration pooled risk ratio was run with Knapp-Hartung method); 0.55 (95% CI, 0.12 to 2.62) for high-dose N-acetylcysteine when IV contrast media were used; 0.77 (95% CI, 0.66 to 0.91) for low-dose N-acetylcysteine when intraarterial contrast media were used; and 0.62 (95% CI, 0.18 to 2.10) for low-dose N-acetylcysteine when IV contrast media were used (low-dose N-acetylcysteine with IV contrast media administration pooled risk ratio was run with Knapp-Hartung method). The pooled risk ratio was 0.69 (95% CI, 0.58 to 0.84) for N-acetylcysteine when LOCM was used, suggesting a clinically important benefit, and 1.12 (95% CI, 0.74 to 1.69) for N-acetylcysteine when IOCM was used. When we examined how the risk ratio estimates varied according to baseline characteristics of the study population, we did not observe any meaningful difference by age, baseline renal function, presence or absence of diabetes mellitus, or proportion of female patients. When we examined how results of studies of N-acetylcysteine varied in forest plots organized by the number of study limitations, we did not see any