Amiodarone with or without N-acetylcysteine for the prevention of atrial fibrillation after thoracic surgery: A double-blind, randomized trial Journal Article


Authors: Amar, D.; Zhang, H.; Chung, M. K.; Tan, K. S.; Desiderio, D.; Park, B. J.; Pedoto, A.; Roistacher, N.; Isbell, J. M.; Molena, D.; Milne, G. L.; Meyers, B. F.; Fischer, G. W.; Rusch, V. W.; Jones, D. R.
Article Title: Amiodarone with or without N-acetylcysteine for the prevention of atrial fibrillation after thoracic surgery: A double-blind, randomized trial
Abstract: Background: Postoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation. Methods: In this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo intravenous bolus (50 mg/kg) and then continuous infusion (100 mg/kg over the course of 48 h) was administered plus intravenous amiodarone (bolus of 150 mg and then continuous infusion of 2 g over the course of 48 h). The primary outcome was sustained atrial fibrillation longer than 30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by electrocardiography within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin F2α; isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were telephoned monthly to assess the occurrence of atrial fibrillation in the first year. Results: Among 154 patients included, postoperative atrial fibrillation occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%; odds ratio, 1.24; 95.1% CI, 0.53 to 2.88; P = 0.615). The trial was stopped at the interim analysis because of futility. Of the 28 patients with postoperative atrial fibrillation, 3 (11%) were discharged in atrial fibrillation. Regardless of treatment at 1 yr, 7 of 28 patients with postoperative atrial fibrillation (25%) had recurrent episodes of atrial fibrillation. Inflammatory and oxidative stress markers were similar between groups. Conclusions: Dual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent atrial fibrillation episodes are common among patients with postoperative atrial fibrillation within 1 yr of major thoracic surgery. © 2022 Lippincott Williams and Wilkins. All rights reserved.
Keywords: controlled study; randomized controlled trial; inflammation; postoperative complication; postoperative complications; coronary artery bypass graft; coronary artery bypass; double blind procedure; double-blind method; thorax surgery; atrial fibrillation; anti-arrhythmia agents; antiarrhythmic agent; adverse event; complication; thoracic surgery; amiodarone; acetylcysteine; humans; human
Journal Title: Anesthesiology
Volume: 136
Issue: 6
ISSN: 0003-3022
Publisher: Lippincott Williams & Wilkins  
Date Published: 2022-06-01
Start Page: 916
End Page: 926
Language: English
DOI: 10.1097/aln.0000000000004201
PUBMED: 35263434
PROVIDER: scopus
PMCID: PMC9090984
DOI/URL:
Notes: Article -- Export Date: 1 June 2022 -- Source: Scopus
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MSK Authors
  1. Alessia C Pedoto
    40 Pedoto
  2. Valerie W Rusch
    869 Rusch
  3. David Amar
    138 Amar
  4. Bernard J Park
    265 Park
  5. Hao Zhang
    62 Zhang
  6. David Randolph Jones
    418 Jones
  7. Daniela   Molena
    276 Molena
  8. Kay See   Tan
    244 Tan
  9. James Michael Isbell
    128 Isbell
  10. Gregory Walter Fischer
    40 Fischer