Naples, Italy - Volume supplementation by sodium bicarbonate plus N-acetylcysteine (NAC) is superior to other common strategies for preventing renal insufficiency following contrast media infusion, a new randomized clinical trial suggests [1]. Reporting the results of the Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL) online February 19, 2007 in Circulation, Dr Carlo Briguori (Clinica Mediterranea, Naples, Italy) and colleagues hypothesize that sodium bicarbonate likely has additive effects to NAC beyond its antioxidant properties.

Current guidelines for preventing renal toxicity following use of contrast dye recommend intravenous volume expansion using saline and a low or iso-osmolality contrast agent and advise that the amount of contrast agent used should be as little as possible. As Briguori et al note, NAC is a "potent antioxidant" that scavenges oxygen-derived free radicals believed to cause contrast-induced nephropathy; recent studies have suggested that other antioxidants—such as sodium bicarbonate or ascorbic acid—may also help prevent renal side effects of contrast infusion.

For their study, the Italian investigators randomized more than 300 patients undergoing interventional procedures to either saline plus NAC, sodium bicarbonate plus NAC, or saline plus ascorbic acid and NAC, in a double-blind fashion. All of the study participants also received iodixanol, an iso-osmolar, nonionic contrast agent, and all were at medium to high risk of contrast nephropathy, based on their serum creatinine levels or glomerular filtration rate at baseline.

Compared with the NAC/sodium-bicarbonate group, patients randomized to the saline/NAC group and to the saline/ascorbic acid/NAC group experienced significantly higher rates of contrast-induced nephropathy, with no significant differences between these two groups. Roughly one in 10 of the patients treated with either of these two strategies developed contrast-induced nephropathy; by contrast, less than 2% of patients in the bicarbonate group did.

"The results of the present trial suggest that in patients at medium to high risk, the combined administration of NAC plus sodium bicarbonate seems to be more effective in preventing contrast-induced nephropathy," Briguori told heartwire. "This strategy should be utilized in all patients at risk."

However, additional studies are needed to know whether this strategy is also superior in high- to very high-risk patients, he noted.

Further research may also help illuminate the protective properties of different antioxidants, Briguori told heartwire.

"The lack of a favorable protective effect of the combination of ascorbic acid plus NAC as compared with NAC alone suggests additional and/or alternative mechanisms—other than antioxidant effects—which require further investigation. We may hypothesize that NAC and ascorbic acid work through similar pathways while the protective action of bicarbonate may be different [from that of] NAC and therefore additive."

Commenting on the REMEDIAL study for heartwire, Dr Roxana Mehran (Columbia University, New York, NY) expressed some concern about the size of the trial, which she suggested was not powered to show a true difference between the different strategies.

"This is not a definitive trial, but a good study that does show that hydration with bicarb and NAC may be beneficial," Mehran stated. "I think we still have a way to go in finding ways to prevent contrast nephropathy, but by just paying attention to it and hydrating the patients, we have made some improvements and increased awareness for this very troubling complication."