Abstract
Purpose
N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial.
Methods
One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR ≤ 60 mL.min-1) were recruited in a blinded (patients, clinicians, data-collectors) placebo-controlled randomized trial. Eighty-nine were randomized to N-acetylcysteine (100 mg·kg-1 iv bolus, 20 mg·kg-1hr·-1 infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was the percent change in eGFR during the first 72 postoperative hours. Secondary outcomes included renal replacement therapy, mortality, atrial fibrillation, vasoactive medications, and adverse effects. A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better (small benefit), and with an upper 95% confidence interval including 9.5 (moderate benefit).
Results
The median percent change in eGFR was 5.2% better (absolute difference) in the N-acetylcysteine arm (95% confidence interval 2.4% worse to 12.1 % better; P = 0.22). With regard to secondary outcomes, all-cause mortality was lower in the N-acetylcysteine arm (0% vs 8%; P = 0.007).
Conclusion
N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study. Nonetheless, its treatment effect was consistent with a plausible small-to-moderate benefit. Given this finding, N-acetylcysteine should be definitively evaluated in a large randomized trial.
Résumé
Objectif
La N-acétylcystéine pourrait empêcher une atteinte rénale aiguë après une chirurgie cardiaque. Afin de déterminer si la N-acétylcystéine mérite une évaluation définitive menée par une étude multi-centrique étendue, nous avons évalué ses effets sur un pronostic de remplacement, le taux de filtration glomérulaire estimé (eGFR), dans une étude randomisée.
Méthode
Cent soixante-dix-sept patients de chirurgie cardiaque souffrant d’insuffisance rénale modérée préexistante (eGFR ≤ 60 mL·min-1) ont été recrutés dans le cadre d’une étude en aveugle (patients, cliniciens, collecteurs de données), randomisée et contrôlée par placebo. Quatre-vingt-neuf patients ont été randomisés à recevoir de la N-acétylcystéine (bolus 100 mg·kg-1 iv, perfusion 20 mg·kg-1 ·h-1 jusqu’à quatre heures après la circulation extracor-porelle), et 88 ont reçu un placebo. Le changement en pourcentage du eGFR durant les premières 72 h postopératoires a constitué le résultat primaire. Les résultats secondaires comptaient la dialyse, la mortalité, la fibrillation atriale, les médicaments vasomoteurs administrés, ainsi que les effets secondaires. Une étude multi-centrique ultérieure a été considérée nécessaire si la N-acétylcystéine était associée à une modification en pourcentage du eGFR qui était meilleure de 3,8 (bénéfice modeste), avec un intervalle de confiance de 95 % supérieur comprenant 9,5 (bénéfice modéré).
Résultats
Le changement en pourcentage moyen du eGFR était meilleur de 5,2 % (différence absolue) dans le groupe N-acétylcystéine (intervalle de confiance 95 % 2,4 % moins bon à 12,1 % meilleur; P = 0,22). En ce qui concerne les résultats secondaires, la mortalité — toutes causes — était plus basse dans le groupe N-acétylcystéine (0 % vs 8 %; P = 0,007).
Conclusion
La N-acétylcystéine n’a pas causé d’amélioration statistiquement significative dans l’eGFR postopératoire dans cette étude uni-centrique. Néanmoins, son effet thérapeutique pouvait correspondre à un bénéfice plausible modeste à modéré. Au vu de cette découverte, la N-acétylcystéine devrait être évaluée de manière définitive dans une étude randomisée étendue.
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Financial support: Dr. Wijeysundera is supported by a Clinician-Scientist Award, and Dr. Rao by a New Investigator Award, both from the Canadian Institutes of Health Research. Dr. Beattie is the Fraser Elliot Chair of Cardiovascular Anesthesiology at the University Health Network. Dr. Rao is the Alfredo and Teresa DeGasperis Chair in Heart Failure Surgery at the University Health Network. This study was supported by a Grant-in-Aid (NA 5231) from the Heart and Stroke Foundation of Ontario. These results were presented in part at the Annual Meeting of the Canadian Anesthesiologists’ Society in Toronto, Ontario, Canada (June 19, 2006). Conflict of interest: No authors have potential conflicts of interest pertaining to this paper. Clinical trial registration: www.ClinicalTrials.gov ID NCT00188630.
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Wijeysundera, D.N., Beattie, W.S., Rao, V. et al. N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency. Can J Anesth 54, 872–881 (2007). https://doi.org/10.1007/BF03026790
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DOI: https://doi.org/10.1007/BF03026790