Forced Euvolemic Diuresis With Mannitol and Furosemide for Prevention of Contrast-Induced Nephropathy in Patients With CKD Undergoing Coronary Angiography: A Randomized Controlled Trial

Abstract

Contrast-induced nephropathy is common in patients with coronary angiography. Mechanistically, forced euvolemic diuresis with mannitol and furosemide ought to prevent contrast-induced nephropathy. Our objectives are to: (1) undertake a randomized trial testing this hypothesis, and (2) conduct a meta-analysis of our findings with 2 earlier studies. (1) Randomized allocation-concealed controlled trial with blinded ascertainment of outcomes, and (2) random-effects meta-analysis of 3 trials. Single-center study of consenting adults with serum creatinine level greater than 1.7 mg/dL undergoing coronary angiography; patients unable to tolerate fluid challenge or receiving dialysis were excluded. Two previous trials had randomly assigned 159 patients. Forced euvolemic diuresis with saline, mannitol, and furosemide compared with saline hydration controls. All patients were pretreated with at least 500 mL of half-normal saline before angiography; during and 8 hours after, urine output was replaced milliliter per milliliter with half-normal saline. The primary outcome was contrast-induced nephropathy within 48 hours of the procedure, defined as a 0.5-mg/dL absolute or 25% relative increase in creatinine level. Overall, 92 patients were allocated to intervention (n = 46) or control (n = 46). Mean age was 64 +/- 14 (SD) years, 23% were women, 37% had diabetes, 47% used oral furosemide, mean creatinine level was 2.8 +/- 1.6 mg/dL, and most patients (72%) underwent diagnostic catheterization. Patients had a net positive fluid balance (389 +/- 958 mL for intervention versus 655 +/- 982 mL for controls; P = 0.2). Contrast-induced nephropathy occurred in 23 (50%) intervention patients versus 13 (28%) controls (relative risk, 1.77; 95% confidence interval, 1.03 to 3.05; P = 0.03; adjusted odds ratio, 3.73; P = 0.03). Within 48 hours, creatinine level had increased by 0.8 +/- 1.1 mg/dL with intervention versus 0.2 +/- 0.6 mg/dL for controls (P = 0.002). Overall, 11 (12%) patients died or required dialysis, with no difference according to allocation status (P = 0.5). Random-effects meta-analysis of published data (3 trials; 251 patients) suggests furosemide-based interventions lead to significant harm compared with hydration: pooled relative risk, 2.15; 95% confidence interval, 1.37 to 3.37; I(2) = 0%. Small single-center study that cannot determine whether harms were related to furosemide, mannitol, or a combination. Forced euvolemic diuresis led to a significantly increased risk of contrast-induced nephropathy. This strategy should be abandoned, and our results suggest that oral furosemide therapy perhaps should be held before angiography.