pattern indicative of a trend by study quality. The SOE was low for all of the N-acetylcysteine versus IV saline comparisons except in the case of administration of N-acetylcysteine and LOCM, the SOE was moderate. The SOE was low that N-acetylcysteine with IV saline did not differ from IV saline with or without a placebo in the need for renal replacement therapy, cardiac events, or length of hospitalization. Most of the studies addressing these outcomes had important study limitations (frequently lacking documentation of allocation concealment or blinding of participants and personnel) and were consistent but imprecise. We found insufficient evidence to draw conclusions about the effect of N-acetylcysteine on mortality. The results of observational studies were similar to the RCTs. IV Sodium Bicarbonate Versus IV Saline Using a random-effects model for studies comparing IV sodium bicarbonate versus IV saline, the overall pooled risk ratio of CIN was 0.93 (95% CI, 0.68 to 1.27). The point estimate of the risk ratio indicated a clinically unimportant difference in the risk of CIN. The associated CI ruled out a clinically important increase in CIN but did not rule out the possibility of a clinically important decrease in CIN. However, IV sodium bicarbonate was more effective than IV saline in preventing CIN (pooled risk ratio, 0.65; 95% CI, 0.33 to 1.25), with a clinically important benefit when given for studies with LOCM only, but not when given for studies with IOCM (pooled risk ratio, 1.02; 95% CI, 0.70 to 1.48). The analysis for LOCM and IOCM subgroups was completed with the Knapp-Hartung method. The SOE was low for this conclusion because ES-6 most of the studies had important study limitations (frequently lacking documentation of allocation concealment or blinding of participants and personnel) and inconsistent results. The SOE also was low that IV sodium bicarbonate did not differ from IV saline in mortality or the need for renal replacement therapy. Most of the studies addressing these outcomes had at least one important study limitation (frequently lacking blinding of participants and personnel) and were consistent but imprecise. We found insufficient evidence to draw conclusions about how IV sodium bicarbonate compared with IV saline in the risk of cardiac events and length of hospitalization. Two observational studies reported a beneficial effect of sodium bicarbonate in reducing CIN. N-Acetylcysteine Versus Sodium Bicarbonate In the RCTs comparing IV sodium bicarbonate with the combination of N-acetylcysteine and IV normal saline, using the Knapp-Hartung method, the pooled risk ratio for CIN was 1.11, indicating no clinically important difference, and the studies were inconsistent and the 95% CI was so wide (0.51 to 2.41) that we cannot rule out the possibility of either an important decrease or important increase in risk of CIN. Therefore, the SOE was insufficient to support a conclusion about the comparative effectiveness of these two interventions. The evidence also was insufficient to draw conclusions about potential differences between the two interventions in mortality, cardiac events, need for renal replacement therapy, or length of hospitalization. Two observational studies compared N-acetylcysteine to sodium bicarbonate. One showed no difference between interventions, and the other showed a higher incidence of CIN in patients receiving sodium bicarbonate alone. Statins The SOE was low in studies that compared use of a statin plus IV fluids versus IV fluids alone, showing a clinically important reduction in CIN with statin use that was not statistically significant (pooled risk ratio, 0.68; 95% CI, 0.39 to 1.20). Because of the small number of studies, the pooled risk ratio was determined with the Knapp-Hartung method. Eight studies with a total population of 5,024 were included to reach this conclusion; five studies included only patients with CKD, three included patients with cardiac issues, three included patients with diabetes, and one study included participants from the general patient population. Half of these studies had at least one important limitation (in allocation concealment or blinding of participants and personnel) but were designed to measure CIN as the primary outcome and consistently showed a benefit in reducing CIN in favor of the statin drug, with relatively precise estimates. The number needed to treat was higher for statins than for high-dose N-acetylcysteine despite having a lower pooled risk ratio estimate because of differences between the two groups of studies in the baseline risk of CIN. 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 IV fluids versus IV fluids alone. Most of the studies addressing these outcomes had at least one important study limitation and were consistent but imprecise. One observational study showed results similar to the RCTs. The pooled estimate of the risk ratio for statins plus N-acetylcysteine versus N-acetylcysteine alone was both statistically significant and clinically important (pooled risk ratio, 0.52; 95% CI, 0.29 to 0.93), with a number needed to treat of 18 (95% CI, 13.44 to 34.72). The pooled risk ratio for statins plus N-acetylcysteine versus N-acetylcysteine was also calculated with the KnappHartung method. Three studies included CKD patients, two included