Several medications have also been used to reduce the risk of contrast-related nephropathy. The most extensively studied of these agents is N-acetylcyste-ine, which has been evaluated in at least 20 randomized clinical trials.57 The premise behind the use of N-acetylcysteine is that it acts as a scavenger of reactive oxygen species and promotes vasodilatory effects in the renal medulla. The first of these trials was reported by Tepel and colleagues, who evaluated its use in 83 patients receiving intravenous contrast agents for computed tomography.58 They found a relative risk reduction of approximately 90% in contrast-related nephropathy with the use of acetylcys-teine, but not all studies have shown a consistent benefit. In total, the evidence suggests that there is a potential benefit with its use. It is certainly reasonable to consider its use in high-risk patients, given its good safety profile and low cost.
The most commonly studied regimen for N-acetyl-cysteine has been 600 mg orally, given twice a day starting 1 day before the procedure, but there is evidence that other routes of administration are effective and that higher doses may result in even better clinical outcomes. In one study, intravenous N-ace-tylcysteine was prepared as 150 mg/kg in 500 mL 0.9% saline and given over 30 minutes starting just before contrast agent exposure.59 This study demonstrated efficacy with the use of intravenous N-ace-tylcysteine, and this may be an effective alternate regimen if time constraints prevent its oral use. Most recently, in a provocative trial of 354 patients, the use of N-acetylcysteine routinely in all patients undergoing primary PCI for ST-elevation myocardial infarction, regardless of serum creatinine levels at baseline, also demonstrated benefit.60 Not only did it prevent the development of contrast-related nephrop-athy, but, remarkably, its use led to a reduction in in-hospital deaths. In this study, there appeared to be dose-dependent effects, with a higher dose of N-acetylcysteine (1200 mg bolus intravenously, followed by 1200 mg orally twice a day for 2 days) being superior to standard doses.
Another important medication that has been studied extensively in randomized clinical trials is fenoldapem. Fenoldapem works as a dopamine-recep-tor agonist and is believed to preserve renal blood flow despite insults from contrast agent exposure. A series of small clinical studies had suggested significant benefit in the reduction of contrast-related nephropathy, particularly in high-risk patients.61,62 However, enthusiasm for fenoldapem has fallen since publication of the large, multicenter CONTRAST trial in 2003.63 In that study, no benefit was seen with fenoldapem in 315 patients with estimated GFRs of less than 60 mL/min who underwent cardiac catheterization.
Additional agents that have been studied include ascorbic acid, captopril, theophylline (or aminophyl-line), dopamine, atrial natriuretic peptides, calcium channel blockers, and prostaglandin E1. Most of these agents have been studied in only a few trials (ascorbic acid64) or have produced conflicting results (the-ophylline65). Their routine use cannot be recommended. Medications that should be avoided unless otherwise indicated include mannitol or furosemide for forced diuresis (without hemodynamic monitoring), given their potential to result in volume depletion and to exacerbate renal dysfunction.53
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