N-Acetylcysteine and Postoperative Atrial Fibrillation: Reply.

Abstract

We thank Dr. Kinoshita and Dr. Kawashima,1 and Dr. Wen, Dr. Huang, and Dr. Li2 for their comments and their interest in our work. In the comments from Kinoshita and Kawashima,1 they speculate that exposing our patients to a high fraction of inspired oxygen during one-lung ventilation negated the potential antioxidant effects of N-acetylcysteine during the 48 h after surgery. In our study, N-acetylcysteine was started only 1 to 2 h after the patient arrived at the postanesthesia care unit, where they had been receiving oxygen, by nasal cannula in most cases and occasionally by face mask, with varying degrees of inspired oxygen (typically in the range of 30 to 40%). In our practice, oxygen administration is usually titrated off as long as the patient is able to maintain an oxygen saturation measured by pulse oximetry greater than 94% on room air. Most lung-resection patients at our center are ambulating the day after surgery; among the patients in our study,3 some were discharged from the hospital upon completion of 48 h of N-acetylcysteine or placebo infusions. Although Dr. Kinoshita’s and Dr. Kawashima’s work in experimental animals is very interesting, it cannot be assumed that these findings apply to humans, nor is it warranted to speculate on which of the mechanisms that they identify apply to postoperative patients.Dr. Wen, Dr. Huang, and Dr. Li suggest the performance of a subgroup analysis by surgical modailty.2 However, because of the small number of patients within the groups and the lack of power to do so, we did not perform a secondary subgroup analysis of the incidence of atrial fibrillation by type of surgery, whether open or minimally invasive. We have previously shown that the extent of lung resection affects the incidence of atrial fibrillation, and it is for this reason that we included patients who underwent anatomical lung or esophageal resection.4 However, on the basis of our work—and the recommendations from the American Association for Thoracic Surgery task force on this topic—we disagree that the side of surgery affects the incidence of atrial fibrillation.5,6 We also disagree with the authors’ assertion that our finding of a lack of effect for N-acetylcysteine on inflammatory or oxidative stress markers is attributable to a lack of power. First, the number of patients in each of the randomized groups in our study was not small, and both groups were well balanced in terms of demographic and surgical characteristics. Second, all patients participated in an institutional enhanced recovery pathway and received similar intraoperative and postoperative opioid analgesics. Finally, the inflammatory and oxidative marker data were well distributed and did not require log transformation before statistical analysis. Considering that our use of N-acetylcysteine or placebo was intravenous over the course of 48 h and was started in the postanesthesia care unit long after intraoperative drugs, such as dexmedetomidine, were used, we do not believe that these pharmacologic agents influenced our findings.Support was provided solely from institutional and/or departmental sources.Dr. Jones serves as a consultant for AstraZeneca (Cambridge, United Kingdom) and on a Clinical Trial Steering Committee for Merck (Kenilworth, New Jersey). The other authors declare no competing interests.