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ORIGINAL ARTICLE
Year : 2013  |  Volume : 7  |  Issue : 2  |  Page : 151-154

N-acetylcysteine instead of theophylline in patients with COPD who are candidates for elective off-pump CABG surgery: Is it possible in cardiovascular surgery unit?


1 Department of Cardiac Surgery, Yazd Cardiovascular Researches Center, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Ali Ben Abitaleb Medical College, Islamic Azad University, Yazd, Iran
3 Medical Student and Researcher of Cardiac Surgery, Yazd Cardiovascular Researches Center, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Correspondence Address:
Sadegh Ali-Hassan-Sayegh
Shahid Sadoughi Medical University, Yazd
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-354X.114069

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Date of Web Publication26-Jun-2013
 

  Abstract 

Background: Forced expiratory volume in one second (FEV1) is a good predictor of chronic obstructive pulmonary disease (COPD). COPD is characterized by a chronic limitation of airflow. This study was designed to compare the effects and complications of theophylline alone, N-acetylcysteine (NAC) alone, and a combination of the two drugs on the rates of FEV1 in patients with COPD who were candidates for off-pump coronary artery bypass graft (CABG) surgery. Methods: This clinical trial was performed on 100 patients who had a smoking history of 27 pack years with a range of 20 to 40 pack years but were not heavy smokers and were candidates for elective off-pump CABG surgery in Afshar Cardiovascular Hospital, Yazd, Iran. The patients with a history of asthma and bronchospasm and non-COPD respiratory disorders were excluded. There were three groups, that is, the theophylline group ( n=33) that received theophylline 10 mg/kg TDS after consumption of food, NAC group ( n=33) who received NAC 10-15 mg/kg BD after consumption of food, and the combined group ( n=32) who received theophylline and NAC together. Data were analyzed by analysis of variance (ANOVA), Chi-square, and exact test for quantitative and qualitative variables. Results: One hundred patients with COPD enrolled in this study as possible candidates for CABG surgery. Average age of the patients was 60.36±10.21 years. Of the participants, 83 (83.3%) were male and 17 (17%) were female. Rate of postoperative FEV1 to basal FEV1 was 0.76±0.32, 0.66±0.22, and 0.69±0.24 in the treatments with theophylline, NAC, and the combination, respectively. Theophylline, NAC, and a combination of these drugs can decrease the rate of postoperative FEV1 compared to basal FEV1 significantly. (P=0.0001) Conclusion: Theophylline alone, NAC alone, and a combination of these drugs improve pulmonary function, and there are no significant differences between these protocols. Stomach discomfort and cardiac complications in treatment with theophylline alone is significantly higher than NAC alone and the combination.

Keywords: Chronic obstructive pulmonary disease, elective off-pump coronary artery bypass graft, N-acetylcysteine, theophylline


How to cite this article:
Mirhosseini SJ, Forouzannia SK, Nasirian M, Ali-Hassan-Sayegh S. N-acetylcysteine instead of theophylline in patients with COPD who are candidates for elective off-pump CABG surgery: Is it possible in cardiovascular surgery unit?. Saudi J Anaesth 2013;7:151-4

How to cite this URL:
Mirhosseini SJ, Forouzannia SK, Nasirian M, Ali-Hassan-Sayegh S. N-acetylcysteine instead of theophylline in patients with COPD who are candidates for elective off-pump CABG surgery: Is it possible in cardiovascular surgery unit?. Saudi J Anaesth [serial online] 2013 [cited 2020 Oct 30];7:151-4. Available from: https://www.saudija.org/text.asp?2013/7/2/151/114069


  Introduction Top


Chronic obstructive pulmonary disease (COPD) in patients who are likely candidates for open heart surgery is characterized by a limitation in airflow and decline in lung capacity. COPD is associated with a significant economic burden, including extension of hospitalization and disability. Cigarette smoking and indoor air pollution provide backgrounds for inducing COPD significantly worldwide. [1],[2] Treatment guidelines for COPD recommend theophylline as the principal line of treatment when symptoms are still persistent despite treatment with short - and long-acting inhaled bronchodilators; therefore, physicians have been administering theophylline for the improvement of outcomes of COPD for several years now. [3] Current evidence indicates that COPD is characterized by systemic inflammation, which is partially initiated by the oxidative stress that is common in COPD patients compared to healthy subjects. Considering the role of inflammation and oxidative stress in the exacerbation of clinical outcomes of pulmonary dysfunction, therefore, supplementation with N-acetylcysteine (NAC) has been shown to increase the levels of glutathione and major antioxidants. Glutathione in NAC is critically important for the removal of toxins including peroxide compounds, and free radical-generating molecules. [4],[5] This study was designed to compare the pharmacologic effects and complications of theophylline alone, NAC alone, and a combination of these drugs on the rates of forced expiratory volume in one second (FEV1) in patients with COPD, who are likely candidates for off-pump coronary artery bypass graft (CABG) surgery.


  Methods Top


Our randomized double-blind clinical trial was approved by the ethical committee in our university. After giving a written consent, the patients (n=100) participated voluntarily for an off-pump CABG surgery in Afshar Cardiovascular Hospital (Yazd, Iran) from January 2010 to June January 2012. All of the operations were conducted by a certain surgical team. Patients who had a smoking history of 27 pack years with a range of 20 to 40 pack years but were not heavy smokers and were likely candidates for elective off-pump CABG were enrolled in this study. Grading of COPD was defined as mild COPD (FEV1 between 40 and 80%), moderate COPD (FEV1 between 30 and 39%), and severe COPD (FEV1 lower than 29%). The patients were stable for at least eight weeks clinically and were not undergoing oxygen therapy. The patients with a history of asthma and bronchospasm and non-COPD respiratory disorders were excluded from this study. One hundred patients were randomly assigned to three groups, the theophylline group (n=33) that received theophylline 10 mg/kg TDS after consumption of food, the NAC group (n=33) which received NAC 10-15 mg/kg BD after consumption of food, and the combination group (n=32) which received theophylline and NAC together. These drugs were administered 72 hours before surgery. Evaluations through spirometry were done at the time of admission and discharge from hospital. Cardiac and gastrointestinal complications and impact on pulmonary function test of these drugs were recorded in the form of a questionnaire. According to definitions about benefits of drugs on the respiratory system, an improvement in respiratory parameters means an increase in the rate of FEV1 higher than 10% from the basal rate of FEV1 and fewer side effects. Our data were analyzed by SPSS15 software. We used ANOVA, Chi-square, and exact test for quantitative and qualitative variables.


  Results Top


One hundred patients with COPD enrolled in this study as possible candidates for CABG surgery. Average age of the patients was 60.36±10.21 years. Of the participants, 83 (83.3%) were male and 17 (17%) were female. The demographic characteristics of our patients have been presented in [Table 1]. In the participants, distribution of abundance in grading groups from mild to severe showed that 47 (47%), 43, and 10 cases had mild, moderate, and severe COPD, respectively [Table 2]. Frequency distribution of increase in the rate of FEV1 higher than 10% from basal rate was three cases (9.1%) in the theophylline group, one case (3.1%) in the NAC group, and two cases (6.3%) in the combined treatment group. Information about grading of COPD and increase in the rate of FEV1 higher than 10% from basal rate has been presented in [Table 3]. Average rate of basal FEV1 in the three groups was 73.4±24.9, 78.4±17.8, and 79.6±31.8 L with theophylline, NAC, and combination therapy, respectively. Therefore, there are no significant differences in the rate of basal FEV1 following treatment with a combination of NAC and theophylline versus NAC or theophylline alone (P0=0.58). Average rate of FEV1 after off-pump CABG was the same statistically in the three groups [Table 4]. Ratio of rate of postoperative FEV1 to basal FEV1 was 0.76±0.32, 0.66±0.22, and 0.69±0.24 in the treatments with theophylline, NAC, and the combination, respectively (P=0.32). Theophylline, NAC, and a combination of these drugs can decrease the rate of postoperative FEV1 compared to basal FEV1 significantly (P=0.0001 for the three protocols) [Table 5]. The incidence of nausea, vomiting, and arrhythmias after surgery in the theophylline group was significantly higher than that in the NAC and combination groups [Table 6]. In all patients, average duration of operation, intubation, and stay in the intensive care unit (ICU) and hospital were 181.95±33.2 minutes, 7.16±5.5 hours, 59.3±18.5 hours, and 5.4 8±1.47 days, respectively. Details of information about surgery, intubation time, and stay in the ICU and hospital in the three groups have been presented in [Table 7]. There were eight (24.2%), one (3%), and two cases (6.2%) of postoperative pulmonary dysfunction (pneumonia or atelectasis or aspiration) in the theophylline, NAC, and combination groups, respectively. These findings indicate that theophylline maybe more suitable compared to the NAC or combination groups for reduction in pulmonary dysfunction.
Table 1: Demographic characteristics of three groups

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Table 2: Frequency distribution of grading of COPD

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Table 3: Frequency distribution of increase in rate of FEV1 higher than 10% and grading of COPD

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Table 4: Average rate of FEV1 (L) after CABG

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Table 5: Average rates of basal and postoperative FEV1 in the three groups

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Table 6: Evaluation of side effects of drugs in patients with COPD

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Table 7: Operative and postoperative information

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  Discussion Top


COPD is a chronic disease of the lungs and airways that induces a socioeconomic burden. Oxidative stress has been implicated in the pathogenesis and progression of COPD. [6],[7] Anti-inflammatory actions of theophylline at low serum concentrations have an effect on pulmonary disorders, but one of the most important complications of this drug is cardiac arrhythmia. [8] NAC, a glutathione precursor, has been used in patients with COPD who are possible candidates for CABG to reduce symptoms of pulmonary dysfunction. [7] A study carried out by Tang et al. indicated that cardiac complications especially arrhythmia can be a predictor of mortality following COPD. [9] Ferrari et al. reported that atrial and ventricular arrhythmias in COPD patients were common complications in treatment with theophylline. [10] In our study, incidence of stomach discomfort and cardiac disorders was more in treatment with theophylline than NAC. A study performed by Sessler et al. reported that sinus tachycardia, supraventricular ectopic beats, and ventricular premature beats were prevalent among patients with theophylline toxicity. [11] A study conducted by Thomas et al. showed that theophylline increased the rate of FEV1 significantly. [12] Our study reports that theophylline and NAC increased postoperative rate of FEV1 compared to the basal FEV1. Fink et al. reported that cardiopulmonary procedures may exacerbate COPD in patients who are candidates for surgery; therefore, administration of theophylline improves respiratory functions. [13] In our study, the surgical procedure was CABG without cardiopulmonary bypass. A study carried out by Wang et al. indicated that theophylline could improve arterial blood gas tension and lung function, whereas the incidence of drug-related side effects was higher. [14] Zhou et al. reported that insomnia, stomach discomfort, and palpitation were common adverse effects of theophylline; however, slow-release oral theophylline may be safe and acceptable in the long-term treatment of COPD. [15] A study conducted by Ferarri et al. suggested that NAC had antioxidant, microcirculatory inhibition of aggregation of platelets and decrease in ischemic events significantly. [10] Our findings show that NAC can improve pulmonary dysfunction, but there were no significant differences compared to theophylline. A study about the mechanism of NAC carried out by Sadowska et al. indicated that NAC may induce expression of mucin by affecting oxidative stress and inflammation; therefore, NAC provided enough lung capacity in COPD patients. [16] In our study, the rate of postoperative FEV1 to basal FEV1 was 0.76±0.32, 0.66±0.22, and 0.69±0.24 in treatments with theophylline, NAC, and the combination, respectively. Theophylline, NAC, and a combination of the drugs can decrease the rate of postoperative FEV1 compared to basal FEV1 significantly. A study by Dhalla et al. indicated that NAC with anti-inflammatory effects managed pulmonary parameters effectively. [17] This finding is in line with our results. Our study suggests that the efficacy of NAC is more than theophylline for reduction in pneumonia, atelectasis, and aspiration. Finally, we conclude that theophylline alone, NAC alone, and a combination of the two improve pulmonary function, and there are no significant differences between these protocols. Stomach discomfort and cardiac complications in treatment with theophylline alone are significantly higher than NAC alone and the combination. We recommended that NAC is a safe and acceptable drug for patients with COPD who are candidates for off-pump CABG surgery.

 
  References Top

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Thomas P, Pugsley JA, Stewart JH. Theophylline and salbutamol improve pulmonary function in patients with irreversible chronic obstructive pulmonary disease. Chest 1992;101:160-5.  Back to cited text no. 12
    
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Fink G, Kaye C, Sulkes J, Gabbay U, Spitzer SA. Effect of theophylline on exercise performance in patients with severe chronic obstructive pulmonary disease. Thorax 1994;49:332-4.  Back to cited text no. 13
    
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Wang CH, Zhang Q, Li M, Fu PF, Yan ZM, Peng AM, et al. [Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease]. Zhonghua Yi Xue Za Zhi 2010;90:540-6.  Back to cited text no. 14
    
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Zhou YM, Wang XP, Zeng XY, Qiu R, Xie JF, Liu SM, et al. [Theophylline in the treatment of chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled study]. Zhonghua Jie He He Hu Xi Za Zhi 2006;29:577-82.  Back to cited text no. 15
    
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Sadowska AM. N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease. Ther Adv Respir Dis 2012;6:127-35.  Back to cited text no. 16
    
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Dhalla NS, Golfman L, Takeda S, Takeda N, Nagano M. Evidence for the role of oxidative stress in acute ischemic heart disease: A brief review. Can J Cardiol 1999;15:587-93.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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