Prevention of contrast-induced nephropathy: A randomized controlled trial of sodium bicarbonate and N-acetylcysteine

Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute renal failure, and has become a significant source of morbidity and mortality (1). CIN is commonly defined as an increase in serum creatinine of greater than 25% or 44.2 μmol/L (greater than 0.5 mg/dL) within three days of intravascular contrast medium administration in the absence of an alternative cause (2,3). CIN has been shown to be associated with an increased risk for a prolonged hospital stay, increased health care costs, potentially irreversible reduction in renal function and death (4). The incidence of CIN has been reported to be as high as 9% to 50% in patients with pre-existing renal impairment or certain risk factors for acute renal dysfunction following exposure to contrast media, such as diabetes, congestive heart failure, advanced age and concurrent administration of nephrotoxic drugs (4–9). The primary intervention for preventing CIN is hydration. However, the most efficacious regimen regarding the minimally effective length of time, optimal rate, and fluid composition of intravenous hydration required before and after contrast medium administration is still unclear (10). N-acetylcysteine (NAC) and sodium bicarbonate (NaHCO3) infusion are two other prophylactic strategies that have been evaluated. The proposed mechanisms of CIN prevention by NAC are antioxidation via glutathione production or as a direct free radical scavenger, prevention of apoptotic cell death mediated by the reduced generation of oxygen free radicals, and vasodilation (11,12). Several studies (11,13–18) have evaluated the effects of NAC; however, conflicting results have been reported. The postulated mechanism of CIN prevention by NaHCO3 is through the reduction of oxygen free radical formation by increasing the pH of renal flow. The Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL) (19) revealed that volume supplementation with NaHCO3 plus NAC was superior to the combination of normal saline with NAC in preventing CIN in at-risk patients. The current study was performed to further evaluate whether NaHCO3 and/or high-dose NAC provides an effective option as prophylaxis of CIN in high-risk patients when added to an aggressive hydration protocol and the use of an iso-osmolar contrast medium.