Effects of N-acetylcysteine on pulmonary function in patients undergoing coronary artery bypass surgery with cardiopulmonary bypass

Abstract

Cardiopulmonary bypass (CPB) has been implicated in causing poor pulmonary gas exchange postoperatively in patients undergoing coronary artery bypass grafting (CABG) procedures. In this prospective, randomized, double-blind, placebo-controlled study, we examined the pulmonary effects of N-acetylcysteine (NAC) in patients undergoing CABG. Twenty patients undergoing elective CABG and early tracheal extubation were randomized into two groups. Group I (ten patients) received a physiologic salt solution as a placebo in a continuous intravenous infusion for one hour before CPB and 24 hours after CPB; Group II (ten patients) received 100 mg/kg NAC intravenously for one hour before CPB and 40 mg/kg/day at 24 hours after CPB. Perioperative hemodynamic and pulmonary data were recorded. Postoperative tracheal extubation was accomplished at the earliest appropriate time. The postoperative clinical course was similar in the two groups. Both groups exhibited significant postoperative increases in A-a oxygen gradient (p<0.01), but patients in Group II exhibited significantly lower increases in postoperative A-a oxygen gradient (p<0.006). Other hemodynamic and pulmonary data (pulmonary capillary wedge pressure, pulmonary vascular resistance (PVR), cardiac index (CI), shunt flow, dynamic lung compliance and static lung compliance) exhibited no differences between the groups. There was no significant difference in terms of intubation time. The malondialdehyde (MDA) increase in Group II following CPB was found to be significantly lower than in Group I (p=0.043). This clinical study reveals that administration of NAC to patients undergoing elective CABG with CPB improves systemic oxygenation. There was no effect in other pulmonary parameters and in terms of intubation time.

Get full access to this article

View all access options for this article.

References

Royston D. The inflammatory response and extracorporeal circulation . J Cardiothorac Vasc Anesth 1997; 11: 341-354 .

Calvin SHN , Wan S , Yim APC , Arifi AA. Pulmonary dysfunction after cardiac surgery . Chest 2002; 121: 1269-1277 .

Asimakopoulos G , Smith PLC , Ratnatunga CP , Taylor KM. Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass . Ann Thorac Surg 1999; 68: 1107-1115 .

Andersen LW , Thiis J , Kharazmi A , Rygg I. The role of N -acetylcysteine administration on the oxidative response of neutrophils during cardiopulmonary bypass . Perfusion 1995; 10: 21-26 .

De Backer WA , Amsel B , Jorens PG , et al. N -Acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid . Intensive Care Med 1996; 22: 900-908 .

Wong SHY , Knight JA , Hopfer SM , Zaharia O , Leach CN , Sunderman FW. Lipoperoxides in plasma as measures by liquid-chromatographic seperation of malondialdehyde -thiobarbituric acid adduct . Clin Chem 1987; 33: 214-220 .

Fosse E , Mollnes TE , Ingvaldsen B. Complement activation during major operations with or without cardiopulmonary bypass . J Thorac Cardiovasc Surg 1987; 93: 860-866 .

Johnson D , Thomson D , Hurst T , et al. Neutrophil-mediated acute lung injury after extracorporeal perfusion . J Thorac Cardiovasc Surg 1994; 107: 1193-1202 .

Weinbroum AA , Kluger Y , Ben Abraham R , Shapira I , Karchevski E , Rudick V. Lung preconditioning with n acetyl-L -cysteine prevents reperfusion injury after liver no flow -reflow: a dose-response study . Transplantation 2001; 71: 300-306 .

10.

Liu CJ , Ueda M , Kosaka S , et al. A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model . J Thorac Cardiovasc Surg 1996; 112: 569-576 .

11.

Bernard GR , Lucht WD , Niedermeyer ME , Snapper JR , Ogletree ML , Brigham KL. Effect of N -acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function . J Clin Invest 1984; 73: 1772-1784 .

12.

Suter P , Domenighetti G , Schaller MD , Laverriege MC , Ritz R , Perret C. N -Acetylcysteine enhances recovery from acute lung injury in man . A randomized, double-blind, placebo-controlled clinical study. 1994; 105: 190-194 .

13.

Hachenberg T , Tenling A , Nystrom SO , et al. Ventilation-perfusion inequality in patients undergoing cardiac surgery . Anesthesiology 1994; 80: 509-519 .

14.

Kochamba GS , Yun KL , Pfeffer TA , Sintek CF , Khonsari S. Pulmonary abnormalities after coronary arterial bypass grafting operation: cardiopulmonary bypass versus mechanical stabilization . Ann Thorac Surg 2000; 69: 1466-1470 .

15.

Wan S , LeClerc JL , Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanism involved and possible therapeutic strategies . Chest 1997; 112: 676-692 .

16.

Quinlan GJ , Mumby S , Lamb NJ , et al. Acute respiratory distress syndrome secondary to cardiopulmonary bypass: do compromised plasma iron-binding anti-oxidant protection and thiol levels influence outcome ? Crit Care Med 2000; 28: 2271-2276 .

17.

Clark SC , Sudarsham C , Roughan J , Flecknell PA , Dark JH. Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation . J Thorac Cardiovasc Surg 1998; 115: 1335-1341 .