Cardiology Research and Practice Several trials have assessed the optimum type, amount, duration, and route of ﬂuid administration to prevent CIN [56–59]. However, much of these aspects remain unclear. Trivedi et al. found that oral ﬂuid administration alone appeared to be inferior to intravenous volume expansion with respect to the development of CIN [59]. Solomon et al. demonstrated the superiority of intravenous 0.45% Saline administration (starting 4–6 hours preprocedure and continued for 24 hours postprocedure) over IV Saline plus Furosemide and IV Saline and Mannitol in patients with mild renal insuﬃciency [56]. In a study conducted by Stevens et al., 98 participants were randomized to forced diuresis with intravenous crys- talloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55). They showed that Plain IV Fluid administration is as good as IV Fluid administration + Dopamine + Lasix + Mannitol as long as urine ﬂow rates greater than 150 mL/h in the postprocedure period were achieved [57]. Recently, Mueller et al. showed that volume expansion with isotonic saline is superior to half-isotonic saline, possi- bly explained by its enhanced ability to expand intravascular volume [60]. However, since this study was conducted on low risk patients with normal renal function, these results cannot be transferred conclusively to patients with moderate and severe chronic renal failure. The CIN Consensus Working Panel published strategies to reduced contrast nephropathy a few years ago. Adequate intravenous volume expansion with isotonic crystalloid (1.0– 1.5 mL/kg/hr) for 3–12 hours before the procedure and continued for 6 to 24 hours to prevent development of CIN in patients at risk. Caution is needed in patients with CHF. They can beneﬁt from optimal hemodynamic stabilization than excessive volume administration [61]. This was supported by two further studies [62, 63]. Merten et al. found that volume expansion with sodium bicarbonate (154 mEq/L of sodium bicarbonate in dextrose and water at a rate of 3 mL/kg/hour per 1 hour before CM exposure, followed by 1 mL/kg/hour during, and for 6 hours after the procedure) was more eﬀective than with sodium chloride for prophylaxis of contrast-induced renal failure and may provide additional renoprotection by alka- linizing renal tubular ﬂuid, which the authors hypothesized would decrease tubular damage by scavenging oxygen free radicals [64]. Over the years, a number of randomized controlled trials comparing volume administration regimens using sodium bicarbonate and sodium chloride have given conﬂicting results, [65–69] with systematic reviews and meta analyses performed on these trials inconsistently reporting superiority of sodium bicarbonate over sodium chloride [70– 72]. This may be due to heterogeneity between trials and the large number of unpublished studies. Also, Zoungas et al., in their systematic review found that smaller studies measuring outcome relatively early were prone to report superiority of sodium bicarbonate whereas larger studies provided more neutral results between the two ﬂuid administration regimens [72]. 5 Finally, Clavijo et al. conducted a retrospective analysis and demonstrated that a rapid intraarterial infusion of dex- trose 5% (1 L administered through the femoral artery sheath as a bolus >5 minutes immediately before angiography) was well tolerated and eﬀective against CIN in patients with a creatinine clearance ≤60 mL/min [73]. Although, the key is adequate volume expansion for the prevention of CIN, the prognostic implication of this strategy, however, is missing. There is also a lack in suﬃcient data to support a single best volume administration strategy (optimal timing, type, volume, and rate of ﬂuid admin- istration). Current evidence remains uncertain about any superiority of sodium bicarbonate over sodium chloride in preventing the development of CIN. Also, special emphasis is needed on patients with heart failure and preexisting renal failure as these patients are high risk for CIN and have been poorly represented in existing studies on volume administration. Also, these patients will be more challenging in subjecting to high volume expansion. 8.2. Acetylcysteine. So far, N-acetylcysteine (NAC) has been the most widely studied of all prophylaxis strategies. Several possible mechanisms exist by which this drug protects renal tissue from CM. One such mechanism is by direct vasodilation of kidney vessels, contributing to improved renal hemodynamics [74]. It may also decrease endothelial dysfunction, and, most importantly, it is able to scavenge oxygen free radicals, thus preventing direct oxidative tissue damage occurring in patients receiving CM. This property of NAC as an antioxidant gave it a popularity as a promising drug for prevention of CIN. In a landmark randomized placebo controlled trial conducted by Tepel et al., it was ﬁrst seen that prophylactic oral administration of the antioxidant acetylcysteine, along with ﬂuid administration, prevented the reduction in renal function induced by contrast agents in patients with chronic renal insuﬃciency [75]. They showed that the incidence of CIN as well as the decrease in mean serum creatinine concentration 48 hours after administration of CM was signiﬁcantly less in the acetylcysteine group. This beneﬁt was conﬁrmed by the Acetylcysteine to Prevent Angiography- Related Renal Tissue Injury (APART) trial, which showed that NAC reduced the risk of postcardiac catheterization nephropathy in patients with chronic renal insuﬃciency and decreased ejection fraction [76]. Thus, it was considered as routine prophylaxis in patients with chronic renal insuﬃ- ciency undergoing cardiac catheterization. However, recently, there has been a declining enthusiasm for the eﬃcacy of NAC as numerous studies have failed to show a signiﬁcant beneﬁt of acetylcysteine compared to controls (Table 4) [77–82]. Researchers then investigated whether increasing the standard dose of acetylcysteine (600 mg orally twice daily) resulted in better renoprotection. Hence, Briguori et al., in their single center study, found that double dose of NAC (1200 mg orally twice daily) resulted in better prevention of CIN, especially with high volumes (140 mL) of non- ionic, low-osmolality contrast agent [83]. Eﬃcacy of IV