Acetylcysteine for Prevention of Acute Renal Dysfunction after Coronary Angiography
Abstract & Commentary
Synopsis: While the clinical benefit of oral N-acetylcysteine on reducing rates of contrast nephropathy for a given patient is unproven, it should be considered for all patients with abnormal renal function referred for elective coronary angiography.
Source: Kay J, et al. JAMA. 2003;289:553-558.
Contrast-induced nephropathy (CIN) is a recognized complication of any imaging procedure using intravascular contrast such as coronary angiography. Data are accumulating suggesting that this complication is associated with increased risk of other serious adverse outcomes including permanent renal dysfunction, prolonged hospitalization, and even death. Patients at particular risk for CIN include those with baseline renal dysfunction, diabetes, and poor left ventricular function, all of whom are being referred with increasing frequency to the cardiac catheterization laboratory.
Previous studies have demonstrated that preprocedural volume loading (avoidance of dehydration), the use of low-osmolality contrast, and minimization of contrast volume can reduce the risk of CIN. More recently, a randomized clinical trial demonstrated that oral administration of the anti-oxidant N-acetylcysteine (Mucomyst®) before and after contrast administration in patients with renal insufficiency undergoing contrast-enhanced CT scanning reduced the risk of postprocedural creatinine elevation.1 For patients undergoing coronary angiography or intervention, several smaller studies, abstracts, and reports from nonrandomized registries have yielded conflicting results in terms of the effect of N-acetylcysteine on rates of CIN.
Kay and colleagues from the University of Hong Kong sought to determine whether oral N-acetylcysteine reduced the rates of CIN in patients with chronic renal insufficiency (baseline creatinine [Cr] > 1.2, creatinine clearance [CrCl] < 60 mL/min) who were referred for coronary angiography. Of note, patients with overt congestive heart failure or LVEF < 0.35 were excluded from the study. Patients were randomized to receive 600-mg oral acetylcysteine or placebo twice daily for 3 doses prior to angiography and 1 dose after angiography. All patients were volume loaded with normal saline (0.5%) 1 mL/kg body weight for 12 hours before and 6 hours after the procedure. All angiography was performed using the nonionic, low-osmolality contrast agent iopamidol. Serum creatinine was measured before the procedure, and 24 hours, 48 hours, and 7 days postprocedure. Twenty-four-hour urine creatinine collections were made preprocedure and at 48 hours and 7 days postprocedure. The primary end points were acute reduction in renal function (rise in serum Cr > 25%) and change in CrCl and serum Cr. Secondary end points were pulmonary edema, need for dialysis, and length of hospitalization.
Two hundred patients were randomized, and there were no significant differences between the acetylcysteine and placebo groups with respect to baseline clinical or procedural characteristics. The median volume of contrast administered was 130 mL in the acetylcysteine group and 120 mL in the control group (P = 0.29). Twelve control patients (12%) and 4 acetylcysteine patients (4%) developed a rise in Cr > 25% at 48 hours (P = 0.03). Serum Cr was significantly lower in the acetylcysteine group. In addition, acetylcysteine administration was associated with a significant rise in CrCL, while placebo was not. The length of hospitalization was marginally, but significantly, shorter in patients receiving acetylcysteine. There were no adverse effects associated with the use of acetylcysteine.
Comment by Sarah M. Vernon, MD
Based on previously available data, many cardiac catheterization laboratories in the United States have already adopted the use of oral acetylcysteine (in this country available only as Mucomyst® solution) in hopes of preventing CIN. In our laboratory, we have been administering Mucomyst® 600 mg b.i.d. the day before and the day of/after elective coronary angiography to all patients with estimated CrCl < 50 mL/min. In addition, we have protocols in place to ensure optimal volume status pre-procedure (with a low threshold for measuring PCWP in patients with poor LV function or otherwise tenuous volume status). We perform biplane angiography with low-osmolality contrast (with an eye toward total contrast volumes less than 50 cc, which has been easily achievable) in all patients with significant renal dysfunction referred to our laboratory.
Despite its limitations, the report by Kay et al adds credence to this approach. This regimen was not completely protective against CIN and does not delineate the optimal dosing regimen or mechanism by which acetylcysteine exerts its renal-protective effects. Importantly, this study excluded patients with LVEF < 0.35, a high-risk population that we seem to encounter daily, and sometimes without prior warning, in our laboratory. However, as Curham points out in his excellent accompanying editorial,2 while the "absolute clinical benefit" of this regimen for a given patient remains unproven, it is simple, inexpensive, and safe, and, therefore, should be considered for all patients with abnormal renal function referred for elective coronary angiography (even though, as our patients tell us, it tastes pretty bad).
Dr. Vernon is Assistant Professor of Medicine Director, VAMC Cardiac Catheterization Laboratory University of New Mexico Health Sciences Center Albuquerque, NM.
References
1. Tepel M, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343:180-184.
2. Curhan GC. Prevention of contrast nephropathy. JAMA. 2003;289:606-608.
While the clinical benefit of oral N-acetylcysteine on reducing rates of contrast nephropathy for a given patient is unproven, it should be considered for all patients with abnormal renal function referred for elective coronary angiography.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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