N-acetyl cysteine for the conversion of atrial fibrillation into sinus rhythm after cardiac surgery: A prospective, randomized, double-blind, placebo-controlled pilot study

N-acetyl cysteine for the conversion of atrial fibrillation into sinus rhythm after
cardiac surgery: A prospective, randomized, double-blind, placebo-controlled
pilot study
Mehmet Ozaydin a,
⁎, Dogan Erdogan a
, Habil Yucel a
, Oktay Peker b
, Atilla Icli a
, Selahaddin Akcay a
,
Mustafa Etli b
, Betul M. Ceyhan c
, Recep Sutcu c
, Ercan Varol a
, Abdullah Dogan a
, Turhan Yavuz b
a Department of Cardiology, Suleyman Demirel University, Isparta, Turkey
b Department of Cardiovascular Surgery, Suleyman Demirel University, Isparta, Turkey c Department of Biochemistry, Suleyman Demirel University, Isparta, Turkey
article info
Article history:
Received 20 June 2012
Accepted 15 September 2012
Available online 3 October 2012
Keywords:
N-acetyl cysteine
Cardiac surgery
Atrial fibrillation
There are two strategies for the treatment of postoperative atrial
fibrillation (POAF): Sinus rhythm (SR) restoration and ventricular
rate control. SR restoration decreases the time to cardioversion,
maintains sinus rhythm for longer periods and decreases the length
of hospitalization [1–3]. Moreover, warfarin should be commenced in
the case of POAF lasting ≥48 h, which is a problematic condition
in this patient group [3]. Therefore, there is a trend toward SR restoration
over heart rate control in current guidelines and treatment algorithms.
However, available rhythm control agents have significant side
effects and they are not very effective [1–4]. Recent investigations
have suggested that POAF may be associated with oxidative stress
[5–9] and anti-oxidants showed conflicting results for the prevention
of atrial fibrillation (AF) in the previous studies [10–17]. However, to
the best of our knowledge, no previous study evaluated the efficacy of
anti-oxidant N-acetyl cysteine (NAC) on the conversion of POAF into
SR. Therefore, we aimed to compare the efficacy of combination of
amiodarone plus NAC and amiodarone plus saline on converting POAF
into SR in this prospective, randomized, double-blind, placebocontrolled study.
A total of 400 consecutive patients undergoing coronary by-pass
graft (CABG), valve surgery or both from February 2007 to September
2011 were screened and those with AF were detected (n=75). Patients
with the indication of urgent cardioversion, class III or IV heart failure,
pregnancy, hyperthyroidism, uncorrected QT interval N500 ms, heart
rate b50/bpm, implanted pace-makers, hepatic disease, a history of
torsades de pointes, sick sinus syndrome or second or third degree
atrioventricular block, left atrial diameter N55 mm, ejection fraction
b0.25, sepsis, inflammatory disease, reversible causes of AF, being
already on anti-arrhythmics or NAC, age b18 and an AF episode lasting
≤5 min were excluded. Thirteen patients were excluded due to an AF
episode ≤5 min (n=8), hyperthyroidism (n=2), already being on NAC
(n=2), and declining to participate (n=1) and the remaining 62
patients with POAF lasting N5 min were included (Fig. 1). Twelve-lead
ECG was taken every morning routinely and when the patients had any
symptoms suggesting dysrhythmia. AF was defined as an irregular
rhythm with the absence of discrete P-waves. Two-blinded cardiologists
reviewed the ECGs. Patients were assigned to NAC plus amiodarone
(n=29); or saline plus amiodarone (n=33) groups. Therapy was
initiated as soon as AF episode lasting N5 min was detected. Amiodarone
was given in both groups for 1 month (intravenously for the first 24 h
and then orally for the rest). It was administrated at a dose of 150 mg
bolus followed by infusion 15 mg/kg for the first 24 h, followed by
800 mg/d for the first week, 600 mg/d for the second week, 400 mg/d
for the third week and 200 mg/d for the fourth week. N-acetyl cysteine
(Asist amp, Husnu Arsan Co., Turkey) was given at a dose of 100 mg/kg
intravenous bolus infusion for 30 min and 25 mg/kg intravenous bolus
infusion for 48 h. In the control group, saline was infused on top of
amiodarone to serve as placebo. The infusion rate and duration was
similar for saline and NAC. Computer-generated randomization assignment was kept in a sealed envelope. Cardiac surgery residents not
involved in the study opened the envelope and assigned the patients.
Staff nurses not involved in the study prepared and administered