Elsevier

Journal of Critical Care

Volume 28, Issue 5, October 2013, Pages 701-709
Journal of Critical Care

Acute Kidney Injury
Prevention of contrast-induced nephropathy by N-acetylcysteine in critically ill patients: Different definitions, different results

https://doi.org/10.1016/j.jcrc.2013.03.007Get rights and content

Abstract

Purpose

The use of N-acetylcysteine (NAC) for preventing contrast induced nephropathy (CIN) is debated in the intensive care unit. NAC may alter the concentration of serum creatinine and interfere with CIN diagnosis. The effectiveness of NAC was evaluated with a special attention on its specific effect on creatinine levels compared to cystatin C.

Methods

In a first period, we prospectively enrolled patients receiving saline and low osmolality contrast media for 140 exams in 2 intensive care units with opposite policies regarding the use of NAC. Renal impairment was defined by both the classical CIN and the “sensitive” Acute Kidney Injury Network (AKIN) (taking creatinine and diuresis) definitions. In a second period, we compared the evolution of serum creatinine and cystatin C after 23 additional contrast examinations under NAC.

Results

Seventy exams with and without NAC were compared in the first period. Risk factors for CIN were similar in the two intensive care unit populations. No difference in CIN incidence was found with and without NAC, using the CIN (10/70 vs 15/70) or the AKIN (24/70 vs 22/70) definition. Interestingly, NAC seemed to reduce renal impairment when the creatinine criterion of the AKIN definition was considered alone [9% vs 21%, P = .033]. Overall, the incidence of renal impairment was 18%, 33% and 15% using the CIN definition, the AKIN, or using AKIN with creatinine alone. Serum creatinine significantly decreased after exams with NAC while cystatin C remained stable.

Conclusion

The incidence of CIN does not seem to be influenced by NAC, except if small changes in creatinine only are considered.

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)

  • R.M. Lynch et al.

    Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study

    Accid Emerg Nurs

    (2004)
  • E.A. Hoste et al.

    Epidemiology of contrast-associated acute kidney injury in ICU patients: a retrospective cohort analysis

    Intensive Care Med

    (2011)
  • E.M. Levy et al.

    The effect of acute renal failure on mortality. A cohort analysis

    JAMA

    (1996)
  • J.W. Haveman et al.

    Low incidence of nephropathy in surgical ICU patients receiving intravenous contrast: a retrospective analysis

    Intensive Care Med

    (2006)
  • A. Hipp et al.

    The incidence of contrast-induced nephropathy in trauma patients

    Eur J Emerg Med

    (2008)
  • W. Huber et al.

    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

    (2001)
  • S. Ehrmann et al.

    Acute kidney injury in the critically ill: is iodinated contrast medium really harmful?

    Crit Care Med

    (2013)
  • R. Bellomo et al.

    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

    (2004)
  • R.L. Mehta et al.

    Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

    Crit Care

    (2007)
  • E. Macedo et al.

    Defining urine output criterion for acute kidney injury in critically ill patients

    Nephrol Dial Transplant

    (2010)
  • K.A. Wlodzimirow et al.

    A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ills

    Crit Care

    (2012)
  • B.J. Barrett et al.

    Clinical practice. Preventing nephropathy induced by contrast medium

    N Engl J Med

    (2006)
  • C.S. Ng et al.

    Effect of IV contrast medium on renal function in oncologic patients undergoing CT in ICU

    AJR Am J Roentgenol

    (2010)
  • M. Tepel et al.

    Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine

    N Engl J Med

    (2000)
  • S.M. Bagshaw et al.

    Acetylcysteine in the prevention of contrast-induced nephropathy: a case study of the pitfalls in the evolution of evidence

    Arch Intern Med

    (2006)
  • G.G. Biondi-Zoccai et al.

    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

    (2006)
  • U. Hoffmann et al.

    The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable

    J Am Soc Nephrol

    (2004)
  • D.A. Gonzales et al.

    A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity

    BMC Med

    (2007)
  • Cited by (19)

    • A comparison between different definitions of contrast-induced acute kidney injury for long-term mortality in patients with acute myocardial infarction

      2020, IJC Heart and Vasculature
      Citation Excerpt :

      In our cohort, the incidence of CI-AKI varied from 5.92% to 18.77% depending on the definitions. As reported by previous results, the lack of a long-established definition of CI-AKI resulted in wide variation in the incidence of CI-AKI among patients with AMI [9–11,27]. From July 2006 to June 2007, a study conducted by Jabara et al. enrolled 400 consecutive patients, the incidence of CI-AKI were 3.3% (Scr increase ≥ 0.5 mg/dl), 10.2% (Scr increase ≥ 25%), 7.6% (eGFR decrease ≥ 25%), and 10.5% (the composite), respectively [28].

    • Contrast-induced nephropathy: Basic concepts, pathophysiological implications and prevention strategies

      2017, Pharmacology and Therapeutics
      Citation Excerpt :

      The Acute Kidney Injury Network criteria can be used to define the parameters of both post-contrast AKI and CIN. However, only recently have they been employed scientifically in CIN investigation (Baumgarten & Ellis, 2008; Chousterman et al., 2013; Davenport et al., 2013; Endre & Pickering, 2010; Lakhal et al., 2011). The incidence and clinical significance of CIN definitely warrants further clarification by future investigations based on recent methodological advancements (Davenport et al., 2013; de Caestecker et al., 2015; McDonald et al., 2013, 2014), because published studies to date have been severely affected by bias and conflation (ACR Committee on Drugs and Contrast Media, 2016).

    • Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies)

      2016, Anaesthesia Critical Care and Pain Medicine
      Citation Excerpt :

      Rationale: despite a small number of studies with poor methodology, using numerous different definitions, the incidence of contrast-induced nephropathy (CIN) in non-ICUs varies from 2% in patients without any risk factor [120] to 25% in those with risk factors (chronic kidney disease, diabetes, concomitant administration of nephrotoxic agents) [121]. In the ICU, according to the definition used, this incidence varies from 16% to 31% [122–125]. Several other risk factors for kidney injury are usually concomitantly found in critically ill patients (hypotension, sepsis, nephrotoxic drugs), making it difficult to consider contrast media directly and solely responsible for AKI.

    • Drug-Induced Acute Kidney Injury: A Focus on Risk Assessment for Prevention

      2015, Critical Care Clinics
      Citation 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

    View all citing articles on Scopus
    View full text