Chicago, IL - N-acetylcysteine, an antioxidant shown to prevent kidney complications in patients undergoing contrast imaging, did not show any benefit vs placebo in preventing renal complications in patients undergoing CABG surgery, a new trial shows [1].

"In this study, perioperative, intravenous intermittent-dose N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, or complications compared with placebo in high-risk patients undergoing on-pump CABG surgery," Dr Karen EA Burns (University of Toronto, St Michael's Hospital, ON) and colleagues conclude. "Before additional prophylaxis trials are initiated to investigate alternative N-acetylcysteine dosing regimens, further research is required to identify CABG patients at risk for postoperative renal events [and] valid markers of renal dysfunction and to establish renal thresholds associated with important clinical outcomes."

Their report appears in the July 20, 2005 issue of the Journal of the American Medical Association.

Renal dysfunction is an important complication after CABG using cardiopulmonary bypass, the authors write; acute renal failure requiring renal-replacement therapy is estimated to occur in up to 3.7% of patients. N-acetylcysteine has been shown to reduce ischemic renal failure through its action as a nitric-oxide-dependent vasodilator and an antioxidant, they note. Several studies have now demonstrated that N-acetylcysteine treatment can reduce decline in renal function associated with the use of contrast during imaging, Burns et al write.

The drug is inexpensive and associated with low toxicity, and doctors now have extensive experience with it, they write. "If N-acetylcysteine was demonstrated to be beneficial in reducing morbidity in CABG patients exposed to [cardiopulmonary bypass], it may represent a cost-saving preventive strategy."

To find out, the researchers randomized 295 patients undergoing elective CABG at two Ontario tertiary-care centers to receive two intraoperative and two postoperative doses of N-acetylcysteine (600 mg) or placebo over a 24-hour period.

However, they found no significant difference in the primary end point of postoperative renal dysfunction between the groups, defined as an increase in serum creatinine level greater than 0.5 mg/dL (44 µmol/L) or a 25% increase from baseline within the first five postop days.

There were some differences in postoperative interventions and complications, but none reached statistical significance.

A post hoc subgroup analysis of patients with baseline creatinine levels of 1.4 mg/dL (120 µmol/L) or greater showed a nonsignificant trend toward a reduction in the numbers of patients experiencing renal dysfunction in the treated group, although they point out this finding is "underpowered, exploratory in nature, and potentially confounded by other factors influencing postoperative renal function."

The authors speculate on the reasons for this negative finding, including the possibility that it is simply "ineffective" in this setting. It's possible, for example, that the dose they used, while well studied in preventing contrast-induced renal problems, might not apply in this indication. Another possibility is that not enough time was given for the drug to work, they add. "We administered the initial dose of N-acetylcysteine at induction of anesthesia, leaving marginal time" for the drug to exert its effects.