This study demonstrates that ultra-high dose intravenous NAC does not prevent contrast-induced nephropathy in patients with impaired renal function undergoing emergency contrast CT-Scan, whatever the definition used for the condition and independently of the use of creatinine or cystatin C as markers of renal function.
In this work, we used both the classical definition of contrast nephropathy (25% increase in serum creatinine or absolute increase of 44 umo/l of creatinine), as well as cystatin C and AKIN criteria. AKIN critera have been recently demonstrated to be predictive of hospital mortality contrast nephropathy in ICU patients . The use of different definition did not modify the fact that iv NAC did not protect against contrast nephropathy, but altered the prevalence of events in our population as it could range from 16 to 24.5% depending on the definition used. More studies are needed to determine which definition best predicts mortality in ER patients after contrast injection.
This study focuses on a poorly studied and fragile population, namely patients from the ER with elevated creatinine levels undergoing emergency CT-Scan. This population is important since it is a large population in which standard preparation before contrast injection is impossible due to time constraints. In addition these patients usually require rapid and often multiple radiologic examinations. Furthermore, appreciation of the basal renal function of these patients is difficult given a usually unique measurement of creatinine level available. In this study, we observe that approximately one out of four patients presenting to the ER with an elevated creatinine undergoing contrast CT-Scan level will develop contrast nephropathy. This high incidence differs from the incidence described post angiography or post elective CT , demonstrating that emergency CT in a high risk population is still an important cause of AKI. It is however probable that a significant percentage of these observed AKI are multifactorial. Indeed, according to the severity of the medical conditions and the emergency setting, associated ischemic AKI might contribute to this high incidence. The study was not designed for this purpose but each patient was treated according to the medical illness necessitating the emergency CT SCAN, which includes treatments to prevent or minimize AKI. This is illustrated by the decrease in mean creatinine at Day 10 as compared to baseline creatinine. Nevertheless, we do not think that it does change the conclusion of the study regarding the role of NAC in this setting as our results demonstrate than NAC administration does not alter this renal evolution. The search for efficient and rapid means of prevention of contrast nephropathy in patients with decreased renal function undergoing emergency CT is therefore of paramount importance and should take into account the risk of multifactorial AKI.
NAC possesses potential anti-oxidant and hemodynamic properties that have been hypothesized to protect against contrast nephropathy. Since 2000 and the princeps study from Tepel , it has been used extensively for renal protection together with hydration before contrast medium use. However, data in the literature are variable and even meta-analysis are conflicting due to variation of protocols used, heterogeneicity of studies and to publication bias toward positive studies in either oral or intravenous NAC administration [15, 24–27]. Moreover the largest trial on oral NAC to date observed no effect of this drug in preventing contrast nephropathy post angiography . However Marenzi and collegues describe a dose dependent protection of NAC, potentially contributing to the variability of results . High doses (6000 mg over 48 h, the first 1200 mg iv before contrast media, 4800 mg orally after contrast media) seems indeed to give a better protection than low doses (3000 mg over 48 h). This may be related to a lower antioxidant effect due to a lower first pass liver generation than in the oral route. This study is the first one focusing on ultra high dose intravenous NAC in the ER population in prevention of contrast nephropathy. Our observation does not substantiate a beneficial role of even ultra high doses of intravenous NAC, administrated within 1 hour before CT, for preventing CN as this treatment was unable to decrease the rate of contrast-induced nephropathy after emergency CT. Although this therapy may appear interesting given its low price and few secondary effects, its administration may result in a false security for the team in charge. This may also lead to under consideration of alternative imagery method or delaying contrast injection in this population. Proper hydration stays the main therapy also in the emergency setting. A 0.9% saline infusion is generally recommended for the hydration of patients with renal failure prior and after injection of contrast media . However, in an emergency setting, when large quantity of fluids have to be administrated in a short period of time, in patients with uncertain cardiac function, we consider that the use of a 0.45% solution  is more appropriated to avoid acute pulmonary edema.
A role of NAC on creatinine secretion independently of kidney filtration has been reported by Hoffman and collegues . To correct for this, we also measured cystatin C at all time points of our study. We observed no effect of NAC on AKI based on creatinine or cystatin C level. Furthermore, cystatin C and creatinine levels showed a good correlation at all time points, arguing against a major role of intravenous NAC on creatinine secretion.
Our study is limited by some aspects. First our population is relatively small and we cannot exclude a minor effect of NAC that might have been detectable in a larger cohort. However, such a small effect would probably not be relevant in clinical practice. Second our selection criteria were based on a single creatinine level measurement in the ER. We may therefore have mixed acute and chronic cases of renal impairment, rendering our population less homogenous than in previous studies but closer to everyday practice in the ER. The high rate of CN demonstrates that this population was in any cases vulnerable. Finally, the contrast medium dose used for CT-Scan is generally lower than for cardiac angiography which has been the situation mostly studied regarding NAC effect. Despite these limitations, the follow up of patients with two renal markers, the very high dose of NAC and different definitions of AKI used are strong arguments against an effect of IV NAC on AKI prevention in patients presenting on the ER with a decreased estimated clearance and undergoing contrast CT-Scan.