IV Fluid Prophylaxis Against Contrast-Induced Nephropathy?
The Article: Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial. Nijssen, Estelle C et al. The Lancet, Volume 389, Issue 10076
The Idea: Contrast-induced nephropathy (CIN) has historically been considered the 3rd most common cause of acute kidney injury (AKI) in patients admitted to the hospital. It is thought to increase in-hospital morbidity and mortality, although it usually resolves and leaves no lasting effects. The mechanism behind the AKI is unclear, and there are strategies to try prevent it, including prophylactic hydration. Most of these hydration protocols are directed towards patients with reduced renal function, advanced age, diabetes, and cardiac disease. There is a significant cost associated with the protocols and complications of volume overload in certain populations, so the AMACING trial (A MAstricht Contrast-Induced Nephropathy Guideline) was designed to decide if giving no prophylaxis is non-inferior to hydration prophylaxis.
The Study: Prospective non-inferiority trial with 1:1 computer-generated randomization Study completed in the Netherlands from June 2014 to July 2016 Blinding of laboratory staff processing creatinine samples but not of patients or clinicians administering the treatment Pre-specified subgroups were analyzed: Diabetes, eGFR<45 vs eGFR>45, route (IA vs IV), procedure type (interventional vs diagnostic) Inclusion: Age 18+, elective IV contrast procedure, eGFR 45–60 + diabetes OR 2 of >75 years; anemia; cardiac disease; NSAIDs; diuretics OR eGFR 30–45 OR multiple myeloma OR Waldenstrom’s macroglobulinaemia with small chain proteinuria Exclusion: ICU patients, eGFR < 30, hemodialysis, emergency procedures 328 allocated to hydration group, 332 to no prophylactic group Hydration protocols were 4 or 12 hours of hydration before and after the procedure
There was no difference in the incidence of CIN in the hydration vs no-hydration group but there was a significant cost difference. Primary outcomes: 1. Incidence of contrast-induced nephropathy (increase in serum creatinine by more than 25% or 44 µmol/L within 2–6 days of contrast exposure) 2.7% (8/296 in hydration group) vs 2.6% (8/307 in no hydration group). Difference -0.1% (95% CI -2.25% to 2.06%; p=0.47) 2. Cost-effectiveness of hydration vs no hydration. Mean total cost €1455 vs €792. Difference -€663 (95% CI -€1234 to -€191) Secondary outcomes: 1. Mean change in creatinine from baseline at 2–6 days and 26–35 days. Mean 2–6 day change in Cr was 0.31 µmol/L in the hydration group and 1.3 µmol/L in the no hydration group (p=0.40). Mean 26–35 day change in Cr was 1.44 µmol/L in the hydration group and 1.39 µmol/L in the no hydration group 2. Major adverse events: mortality, RRT, ICU admission, sequelae of fluid administration… all non-significant differences except that 4% of the hydration group developed heart failure vs 0% in the no hydration group P=0.0001 Subgroups: no different in CIN in any of the prespecified subgroups
The Takeaway: The study did what it set out to do in demonstrating that no hydration was non-inferior to hydration in the prevention of contrast-induced nephropathy. Hydration is more expensive and can cause problems in and of itself. As far as applicability to the ED, it is limited. Most of the instances where we need a contrast study in the emergency department, it is to evaluate for a life-threatening entity, and we will be obtaining the study regardless of renal function. Furthermore, the design of this study was not focused on patient-centered outcomes. The secondary outcomes (major adverse events, mortality, RRT, ICU admission, sequelae of fluid administration) are more pertinent for our practice and stress that if we do give our own prophylactic doses of IV fluids prior to a contrast study, to be careful not to be volume-overload patients.