Acute Kidney InjuryPrevention of contrast-induced nephropathy by N-acetylcysteine in critically ill patients: Different definitions, different results
Introduction
Contrast-induced nephropathy (CIN) is the third cause of hospital acquired acute kidney injury (AKI) [1]. CIN is associated with a prolonged hospitalization and adverse clinical outcomes [2], [3]. While the incidence of CIN is low (1%-6%) in general ward patients, it may be up to 50% in patients with diabetes and/or chronic renal failure [4]. CIN has been extensively studied in cardiological settings. Because they are exposed to multiple risk factors, intensive care unit (ICU) patients are usually considered at high risk for developing AKI. Only few studies are, however, available on CIN in this population [2], [5], [6], [7], [8], [9]. In addition, CIN definition does not match to recent definitions of AKI in which more sensitive criteria of renal impairment are used including a lesser threshold of absolute increase in serum creatinine (ie, 0.3 mg/dL) but a higher relative increase threshold (> 50% over the baseline serum creatinine level [Screat]) and oliguria [10], [11]. Urine output is, however, frequently omitted in studies on AKI and few of them have evaluated the performance of these new definitions using or not oliguria criterion [12], [13].
Hydration, low contrast media osmolality and N-acetylcysteine (NAC) are the three main measures proposed for CIN prevention [14], [15]. Since the first publication in 2000 showing a dramatic reduction in the incidence of CIN using oral NAC [16], a large number of randomized trials and meta-analysis have been reported with conflicting messages on NAC efficacy [17], [18]. NAC may lower the Screat independently of a change of the glomerular filtration rate (GFR) [19].This could explain the conflicting results of its efficacy in preventing CIN [20]. In ICU patients, the rise of Screat may be altered for both magnitude and delay [11], [21], [22]. The poor performance of Screat to assess renal function in a context of NAC treatment could be even a bigger issue in critically ill patients. Because of its low cost and ease of administration, oral NAC prophylaxis remains, however, widely used [2], [23], [24] and the Kidney Disease Improving Global Outcomes group still recommends the use of oral NAC for the prevention of CIN in high risk patients [15].
The aim of this study was to assess the effectiveness of NAC in preventing CIN in the ICU with a special attention on its specific effect on the evolution of Screat. We, therefore, compared the incidence of acute renal impairment after examinations needing iodinated contrast media infusion, with or without enteral NAC, using the classical definition of CIN and the more sensitive Acute Kidney Injury Network (AKIN) definition. After the completion of this first study, the evolution of Screat was compared to serum cystatin C levels, another marker of GFR, in an additional set of patients receiving NAC as preventive measure.
Section snippets
Study population
We conducted a prospective cohort study comparing the incidence of CIN in two medical ICUs having contrasted clinical practice regarding the use of enteral NAC prophylaxis. Otherwise, the policy for hydration (ie, 1 L of 0.9% saline for 12 hours before and 12 hours after examination) [25] and the use of nonionic low osmolality contrast media (Iohexol, Omnipaque, Nycomed, Oslo, Norway) were similar. In addition, these 2 ICUs, located in the similar university hospital network in Paris, were
Phase 1
Fifty four patients undergoing 70 radiological examinations with contrast in the ICU not using NAC and 62 patients undergoing 70 examinations in the ICU using NAC were included in the cohort. At ICU admission, patients had similar age 65 (50-72) vs 63 (47-73) years, P = .42, SAPS II score 38 (27-55) vs 40 (34-60) point, P = .24, need for vasopressors 40% vs 46%, P = .52, and Screat 1.30 (1.0-1.65) vs1.14 (0.86-1.63) mg/dL, P = .38, in the ICU using NAC or not respectively. Fifty three (76%)
Discussion
Our study is the first prospective evaluation of NAC in preventing CIN in the ICU. We found that the effectiveness of routine enteral NAC strongly depends on the marker of GFR used and using UO criterion increases the incidence of CIN. The discrepancy between the evolution of Screat, urine output and Scys after exams with NAC confirms the uncertain renal effect of this drug. Using Screat alone to define AKI may decrease it incidence when the rise in Screat is altered by endogenous factors such
Conclusion
The global incidence of CIN in the ICU does not seem to be influenced by NAC, except if small changes in creatinine only are considered. Until a comparative study find a reliable benefit of NAC on renal function evolution, it use in routine practice for the prevention of CIN in critically ill patients appears questionable. Including urine output in AKI definition seems suitable in the presence of endogenous and exogenous factors impairing the increase in Screat.
Acknowledgments
We thank Anaïs Charles-Nelson (Unité de Recherche Clinique, CHU Henri-Mondor, Créteil) for her help in the statistical analysis of the study.
References (56)
- et al.
Hospital-acquired renal insufficiency
Am J Kidney Dis
(2002) - et al.
A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation
J Am Coll Cardiol
(2004) - et al.
Acute Kidney Injury Network definition of contrast-induced nephropathy in the critically ill: incidence and outcome
J Crit Care
(2011) - et al.
Contemporary use and effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy among patients undergoing percutaneous coronary intervention
JACC Cardiovasc Interv
(2012) - et al.
Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial)
Am J Cardiol
(2002) - et al.
Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure
J Am Coll Cardiol
(2002) - et al.
Early detection of acute renal failure by serum cystatin C
Kidney Int
(2004) - et al.
Effect of N-acetylcysteine on cystatin C-based renal function after elective coronary angiography (ENABLE Study): a prospective, randomized trial
Int J Cardiol
(2010) - et al.
Effect of N-acetylcysteine on serum creatinine and kidney function: results of a randomized controlled trial
Am
(2010) - et al.
Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery
Br J Anaesth
(2006)
Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study
Accid Emerg Nurs
Epidemiology of contrast-associated acute kidney injury in ICU patients: a retrospective cohort analysis
Intensive Care Med
The effect of acute renal failure on mortality. A cohort analysis
JAMA
Low incidence of nephropathy in surgical ICU patients receiving intravenous contrast: a retrospective analysis
Intensive Care Med
The incidence of contrast-induced nephropathy in trauma patients
Eur J Emerg Med
Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk
Intensive Care Med
Acute kidney injury in the critically ill: is iodinated contrast medium really harmful?
Crit Care Med
Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group
Crit Care
Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury
Crit Care
Defining urine output criterion for acute kidney injury in critically ill patients
Nephrol Dial Transplant
A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ills
Crit Care
Clinical practice. Preventing nephropathy induced by contrast medium
N Engl J Med
Effect of IV contrast medium on renal function in oncologic patients undergoing CT in ICU
AJR Am J Roentgenol
Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine
N Engl J Med
Acetylcysteine in the prevention of contrast-induced nephropathy: a case study of the pitfalls in the evolution of evidence
Arch Intern Med
Compliance with QUOROM and quality of reporting of overlapping meta-analyses on the role of acetylcysteine in the prevention of contrast associated nephropathy: case study
BMJ
The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable
J Am Soc Nephrol
A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity
BMC Med
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2015, Critical Care ClinicsCitation Excerpt :The most promising approaches for the prevention of contrast-induced AKI are the use of preemptive hydration and N-acetylcysteine. Often the limitations associated with the studies surrounding which intravenous (IV) fluid to use and the use of oral versus IV N-acetylcysteine is highlighted to illustrate the need for further clarity in this area.52,53 The current KDIGO guidelines recommend the use of IV volume expansion with either isotonic sodium chloride or sodium bicarbonate rather than no IV fluid expansion in patients at risk for contrast-induced AKI.21
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