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N-acetylcysteine to reduce renal failure after cardiac surgery: a systematic review and meta-analysis |
Naughton F, Wijeysundera D, Karkouti K, Tait G, Beattie W S |
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CRD summary This review concluded that N-acetylcysteine did not confer renal protection in patients undergoing cardiac surgery. Overall, the authors' conclusions appear to be supported by the data presented, but some caution is advised given the risk of publication bias and the limited size and number of trials included in the review. Authors' objectives To determine the effects of N-acetylcysteine on acute kidney injury and other important clinical outcomes, after cardiac surgery involving cardiopulmonary bypass. Searching PubMed and EMBASE were searched from inception to May 2008. Search terms were reported. Study selection Randomised controlled trials (RCTs) comparing N-acetylcysteine with placebo for cardiac surgery involving cardiopulmonary bypass were eligible for inclusion in the review. Eligible outcomes included death, stroke, atrial fibrillation, myocardial infarction and acute renal failure; a 25% increase in serum creatinine from baseline was eligible as a surrogate measure of acute kidney injury. Angiographic and vascular surgery trials were excluded, as were trials which examined cardio-protection or anti-inflammatory markers and did not include renal outcomes. Trials included in the review assessed various dose regimens of N-acetylcysteine ranging from 100 to 1000 mg per hour. In just under half of the studies N-acetylcysteine was given as an intravenous bolus; in the remaining studies N-acetylcysteine was given as an intravenous infusion or orally. Patients included in the review were mainly at a moderate to high risk of developing renal injury postoperatively. The age range of participants was specified in just over half of the trials; all of these studies included only adult patients, half of which specifically included only elderly patients. Forty-three percent of patients used aprotinin. The authors did not state how papers were selected for review or how many reviewers performed the selection. Assessment of study quality Study validity was assessed by two reviewers according to the following criteria: randomisation, blinding of outcome assessment, allocation concealment, and loss to follow-up. The authors also reported the treatment effect size used for calculating sample size. Data extraction Dichotomous data including the incidence of death, stroke, MI, atrial fibrillation, re-operation, low output state, acute kidney injury and renal replacement therapy/dialysis, were extracted and used to calculate relative risks with 95% confidence intervals (CIs). Continuous data including postoperative blood loss and baseline creatinine levels were extracted as mean values. Two reviewers extracted the study data. Methods of synthesis Studies were grouped by outcome and data combined to calculate pooled relative risks (RRs) with 95% confidence intervals (CIs) or weighted mean differences (WMDs) with 95% confidence intervals. The authors stated that all data were combined using a random- effects analysis, but one analysis was reported as using a fixed-effect method. Statistical heterogeneity was assessed using the I2 statistic. Meta-regression was used to investigate the effects of baseline creatinine levels and N-acetylcysteine dose. Publication bias was assessed using funnel plots. Results of the review Seven RCTs (1,000 patients) were included in the review. Six out of seven trials used blinded outcome assessment and all of the trials used intention-to-treat data. Overall, the authors described the trials as been well-designed. Sample sizes were not reported. No statistically significant differences between N-acetylcysteine and placebo were reported for mortality (seven RCTs), renal replacement therapy (seven RCTs), baseline creatinine (seven RCTs, significant statistical heterogeneity reported), >25% increase in creatinine from baseline (surrogate measure for acute kidney injury, seven RCTs), use of aprotinin (six RCTs, significant statistical heterogeneity reported), reoperation rate (six RCTs), low output state (six RCTs) and stroke (four RCTs). There was a slight but statistically significant increase in postoperative blood loss (WMD 119 mL, 95% CI: 51 to 187) in favour of placebo in comparison with N-acetylcysteine. Meta-regression showed that baseline creatinine level and N-acetylcysteine dose did not affect either postoperative creatinine levels or the need for renal replacement therapy. Funnel plots suggested that there was no evidence of publication bias. Authors' conclusions This review found that N-acetylcysteine did not confer renal protection in patients undergoing cardiac surgery. CRD commentary This review answered a clearly defined research question. Two databases were searched but no specific attempts were made to locate unpublished information. It was unclear whether language restrictions were applied. Therefore there may be a risk of publication bias and/or language bias. Publication bias was assessed using funnel plots, but given the small number of included trials, this assessment may not be reliable. The authors did not report how trials were selected for inclusion in the review, but two authors extracted the study data and assessed the quality of the trials using standard criteria. This suggested that the risk of reviewer error and bias was reduced. Overall, the sample sizes were described as relatively small, although the data were not reported. The methodological quality of the trials was described as good, so the data are likely to be reliable. Statistical heterogeneity was assessed and found to be low in the majority of cases. The trials were also described as been clinically similar, but there was some variation in surrogate measures of outcome, definitions and local practice. Overall, the authors' conclusions appear to be supported by the data presented, but some caution is advised given the risk of publication bias and the limited size and number of trials included in the review. Implications of the review for practice and research Practice: The authors did not state any implications for practice. Research: The authors stated that an individual patient meta-analysis may determine how outcomes are affected by the interrelationship between N-acetylcysteine dosage, aprotinin usage and baseline renal function. Further trials, if conducted, should also address this issue and include large sample populations, with a similar baseline renal function, who receive the same N-acetylcysteine dose regimen. Funding R. Fraser Elliot endowment. Bibliographic details Naughton F, Wijeysundera D, Karkouti K, Tait G, Beattie W S. N-acetylcysteine to reduce renal failure after cardiac surgery: a systematic review and meta-analysis. Canadian Journal of Anesthesia 2008; 55(12): 827-835 Indexing Status Subject indexing assigned by NLM MeSH Acetylcysteine /therapeutic use; Acute Disease; Cardiac Surgical Procedures /adverse effects; Cardiopulmonary Bypass /adverse effects; Free Radical Scavengers /therapeutic use; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency /etiology /prevention & Risk; Treatment Outcome; control AccessionNumber 12009102115 Date bibliographic record published 10/06/2009 Date abstract record published 14/10/2009 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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