bicarbonate (833mEq/L) versus those who received a low dose (160 mEq/L). The study by Buhiraja et al.123 showed a significant difference in CIN in patients who received sodium bicarbonate versus those who received normal saline. We did not factor the observational studies into the strength of evidence since the outcomes were in the same direction as the RCTs. Other Outcomes Of the studies that compared the risk of CIN using IV sodium bicarbonate with the risk of CIN using IV saline, 13 included data on secondary outcomes. Of these, 11 reported participants’ needs for renal replacement therapy,46,56,70,110-112,115-117,119,130 four reported on cardiac events,56,70,114,115 three reported on hospitalization or length of stay,110,112,120 and six reported on mortality.110-112,115,117,120 (Appendix E; Evidence Table E-13). The overall strength of evidence was low that the mortality rates and the need for renal replacement therapy did not differ between IV sodium bicarbonate and IV saline (Table 4; see Appendixes F and G for study limitations). The studies addressing the need for renal replacement therapy and mortality had medium study limitations, were consistent in the direction of effect, and were imprecise, due to wide confidence intervals and small study populations. Only one study reporting on cardiac outcomes114 reported a statistically significant difference between groups in favor of IV sodium bicarbonate (p=0.03). The remainder of the studies either reported statistically insignificant differences between groups or did not report statistics. The evidence was insufficient to determine whether or not cardiac events or length of hospitalizations differed between IV sodium bicarbonate and IV saline (Table 4; Appendix E, Evidence Table E-13). Adverse events were reported in 11 studies. Data were only recorded if specific adverse events were reported or if the study reported no adverse events (Appendix E, Evidence Table E14). Adverse events were not reported in a standardized manner and were rarely analyzed in these studies. As a result, we were unable to draw any firm conclusions as to whether or not the incidence of adverse events differed between IV sodium bicarbonate and IV saline. 27 Figure 8. Meta-analysis of IV sodium bicarbonate versus IV saline for the prevention of contrast-induced nephropathy %=percent; 1/2NS=0.45% saline; CHF=congestive heart failure; CI=confidence interval; CIN=contrast induced nephropathy; CKD=chronic kidney disease; IOCM=iso-osmolar contrast media; LOCM=low-osmolar contrast media; N=sample size; NaHCO3=sodium bicarbonate; NS=normal saline (0.9%); p=p-value; RR=risk ratio 28 Table 4. Summary of the strength of evidence: IV sodium bicarbonate versus IV saline Outcome Study Design: No. Studies (N) Study Limitations Directness Consistency Precision Strength of Evidence Summary of Key Outcomes Development of CIN RCT: 19 (3303) Medium Direct Inconsistent Precise* Low Low strength of evidence that IV sodium bicarbonate did not differ from IV saline in the risk of CIN Development of CIN (in studies using LOCM) RCT: 11 (1555) Low Direct Inconsistent Imprecise Low Low strength of evidence that IV sodium bicarbonate reduced the risk of CIN compared to IV saline in patients receiving LOCM Development of CIN (in studies using IOCM) RCT: 7 (1748) Medium Direct Inconsistent Imprecise Low Low strength of evidence that IV sodium bicarbonate did not differ from IV saline in the risk of CIN in patients receiving IOCM Need for RRT RCT: 11 (1558) Medium Direct Consistent Imprecise Low Low strength of evidence that the need for RRT did not differ between IV sodium bicarbonate and IV saline Cardiac events RCT: 4 (1468) High Direct Consistent Imprecise Insufficient Insufficient strength of evidence to determine whether cardiac events differed between IV sodium bicarbonate and IV saline Mortality RCT: 6 (1237) Medium Direct Consistent Imprecise Low Low strength of evidence that mortality rates did not differ between IV sodium bicarbonate and IV saline Hospitalization, length of stay RCT: 3 (480) High Direct Consistent Imprecise Insufficient Insufficient strength of evidence to determine whether length of hospitalization differed between IV sodium bicarbonate and IV saline CIN=contrast-induced nephropathy; IV=IV; N=sample size; RCT=randomized controlled trial; RRT=renal replacement therapy *The results were precise enough to rule out a clinically important increase in CIN with IV sodium bicarbonate. 29 N-Acetylcysteine Plus IV Saline Versus IV Sodium Bicarbonate In previous sections, we briefly explained the physiologic basis for studying the use of Nacetylcysteine or IV sodium bicarbonate to prevent CIN, and we summarized the evidence on the effectiveness of each of these two interventions compared with IV saline alone. In this part of the analysis, we looked for evidence on head-to-head comparisons of these two interventions. Study Characteristics Our search identified seven RCTs36,46,56,58,70,74,132 with a total study population of 1619 that compared N-acetylcysteine plus IV saline with IV sodium bicarbonate (number analyzed=930) and two observational studies.97,133 Contrast media included iodixanol,36,58,70 ioversol,132 iohexol,46,74 and ioxaglate. 56 Contrast media were administered