Do intravenous N-acetylcysteine and sodium bicarbonate prevent high osmolal contrast-induced acute kidney injury? A randomized controlled trial

Abstract

Background: N-acetylcysteine (NAC) or sodium bicarbonate (NaHCO3), singly or combined, inconsistently prevent patients exposed to radiographic contrast media from developing contrast-induced acute kidney injury (CI-AKI).

Objective: We asked whether intravenous isotonic saline and either NaHCO3 in 5% dextrose or else a high dose of NAC in 5% dextrose prevent CI-AKI in outpatients exposed to high-osmolal iodinated contrast medium more than does saline alone.

Methods: This completed prospective, parallel, superiority, open-label, controlled, computer-randomized, single-center, Brazilian trial (NCT01612013) hydrated 500 adult outpatients (214 at high risk of developing CI-AKI) exposed to ioxitalamate during elective coronary angiography and ventriculography. From 1 hour before through 6 hours after exposure, 126 patients (group 1) received a high dose of NAC and saline, 125 (group 2) received NaHCO3 and saline, 124 (group 3) received both treatments, and 125 (group 4) received only saline.

Results: Groups were similar with respect to age, gender, weight, pre-existing renal dysfunction, hypertension, medication, and baseline serum creatinine and serum cystatin C, but diabetes mellitus was significantly less prevalent in group 1. CI-AKI incidence 72 hours after exposure to contrast medium was 51.4% (257/500), measured as serum creatinine > (baseline+0.3 mg/dL) and/or serum cystatin C > (1.1 · baseline), and 7.6% (38/500), measured as both serum creatinine and serum cystatin C > (baseline+0.3 mg/dL) or > (1.25 · baseline). CI-AKI incidence measured less sensitively was similar among groups. Measured more sensitively, incidence in group 1 was significantly (p<0.05) lower than in groups 2 and 3 but not group 4; adjustment for confounding by infused volume equalized incidence in groups 1 and 3.

Conclusion: We found no evidence that intravenous isotonic saline and either NaHCO3 or else a high dose of NAC prevent CI-AKI in outpatients exposed to high osmolal iodinated contrast medium more than does saline alone.

Trial registration: ClinicalTrials.gov NCT01612013.

Figure 1. Flow of 500 outpatients through a parallel trial of four treatments for preventing CI-AKI.

Practice of the trial design. Abbreviations: CI-AKI (contrast-induced acute kidney injury), IV (intravenous), NAC (N-acetylcysteine), NaHCO3 (sodium bicarbonate).

Figure 2. Change in serum creatinine and cystatin C levels of 500 outpatients exposed to ioxitalamate.

Mean of serum creatinine (panel A) and serum cystatin C (panel B) concentrations before (baseline) and after administration of ioxitalamate, according to treatment group. Treatments: NAC (N-acetylcysteine plus saline; group 1), NaHCO3 (sodium bicarbonate plus saline; group 2), NAC+NaHCO3 (N-acetylcysteine plus sodium bicarbonate plus saline; group 3), saline (group 4). Means among the treatment groups did not differ significantly. Error bars indicate 1 standard deviation about the mean.