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Reference - AMACING study (Lancet 2017 Feb 20 early online) (level 3 [lacking direct] evidence)
- IV saline is often recommended to reduce the risk of contrast-induced nephropathy in high-risk adults, but evidence directly assessing its efficacy is limited.
- The AMACING study randomized 660 adults at high risk for nephropathy to no IV hydration vs. prophylactic hydration with 0.9% saline IV before elective procedures with iopromide contrast administration. Only 8.6% of the procedures required inpatient management.
- Contrast-induced nephropathy, assessed by serum creatinine levels 2-6 days post-procedure, occurred in 2.6% of patients who did not have IV hydration vs. 2.7% of patients who had prophylactic 0.9% saline IV.
Iodinated contrast agents may aid visualization in imaging procedures, but they are associated with transient nephropathy within a few days of the procedure in about 2% of the general population, with higher rates in patients who are older or with impaired renal function, diabetes, heart failure, or other conditions (KDIGO 2012, NICE 2013). Extracellular volume expansion with IV saline is often recommended to reduce the risk of nephropathy in high-risk patients (KDIGO 2012, NICE 2013). However, there is little evidence directly assessing its efficacy, and IV saline itself may be accompanied by complications (J Zhejiang Univ Sci B 2016 Mar;17(3):181, Med J Aust 2008 Nov 3;189(9):509). The recent AMACING study investigated the effectiveness of prophylactic IV saline in 660 adults (mean age 72 years, 62% men) before an elective procedure requiring iodinated contrast administration with iopromide 300 mg iodine/mL. Only 8.6% of the procedures required inpatient management. All patients had a high risk of nephropathy, defined as estimated glomerular filtration rate (eGFR) 30-44 mL/minute/1.73 m2; eGFR 45-59 mL/minute/1.73 m2 plus diabetes or multiple other risk factors; or multiple myeloma or lymphoplasmacytic lymphoma with small chain proteinuria (only 3 patients fell under the latter category). The patients were randomized to no IV hydration vs. prophylactic hydration with 0.9% saline IV at 3-4 mL/kg per hour for 4 or 12 hours before and after the procedure. The primary outcome was occurrence of contrast-induced nephropathy, defined as serum creatinine increase of ≥ 25% from baseline or an absolute increase of ≥ 44 micromolar/L (0.5 mg/dL) at 2-6 days post-procedure (depending on patient availability). Noninferiority of no IV hydration was established if the rate of nephropathy with no IV hydration minus the rate with prophylactic 0.9% saline IV had a 95% confidence interval with an upper limit < 2.1%.
In 603 patients (91% of randomized patients) who had serum creatinine levels assessed at 2-6 days post-procedure, contrast-induced nephropathy occurred in 2.6% of patients who did not have IV hydration vs. 2.7% of patients who had prophylactic 0.9% saline IV, with an absolute risk difference of -0.1% (95% CI -2.25% to 2.06%), establishing noninferiority of no IV hydration. In subgroup analyses based on diabetes status, eGFR levels, contrast administration route, and type of procedure, absolute differences in nephropathy rates were small and usually favored no IV hydration, but noninferiority was not met in most cases, likely due to smaller sample sizes and the resulting wider confidence intervals. In 520 patients who had serum creatinine levels assessed about 1 month after the procedure, eGFR < 30 mL/minute/1.73 m2 occurred in 2.3% of patients who did not have IV hydration vs. 2.7% of patients who had prophylactic saline IV (not significant). No patients required dialysis or intensive care within 1 month of the procedure.
This trial showed that prophylactic 0.9% saline IV hydration may not reduce the risk of contrast-induced nephropathy in high-risk adults with eGFR 30-59 mL/minute/1.73 m2 having iodinated contrast administration with iopromide for outpatient procedures. However, there are two sources of potential missing nephropathy cases in this trial. First, 9% of the randomized patients were not assessed for contrast-induced nephropathy. Second, serum creatinine was assessed once at 2-6 days post-procedure, but creatinine levels are thought to peak within 3 days post-procedure in most patients before returning to baseline (KDIGO 2012, NICE 2013). Given that the risk difference almost exceeded the 2.1% noninferiority margin, even a small difference in nephropathy rates among missing cases may alter the overall conclusion. Finally, the results of this study cannot be generalized to patients with eGFR < 30 mL/minute/1.73 m2, those requiring inpatient management, or who otherwise have more severe clinical conditions. For adults having iodinated contrast administration for elective outpatient procedures, however, prophylactic IV saline may not materially reduce the risk of contrast-induced nephropathy.
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