Systemic inflammation and oxidative stress post-lung resection: Effect of pretreatment with N-acetylcysteine.
OBJECTIVE
N-acetylcysteine has been used to treat a variety of lung diseases, where is it thought to have an antioxidant effect. In a randomized placebo-controlled double-blind study, the effect of N-acetylcysteine on systemic inflammation and oxidative damage was examined in patients undergoing lung resection, a human model of acute lung injury.


METHODS
Eligible adults were randomized to receive preoperative infusion of N-acetylcysteine (240 mg/kg over 12 h) or placebo. Plasma thiols, interleukin-6, 8-isoprostane, ischaemia-modified albumin, red blood cell glutathione and exhaled breath condensate pH were measured pre- and post-operatively as markers of local and systemic inflammation and oxidative stress.


RESULTS
Patients undergoing lung resection and one-lung ventilation exhibited significant postoperative inflammation and oxidative damage. Postoperative plasma thiol concentration was significantly higher in the N-acetylcysteine-treated group. However, there was no significant difference in any of the measured biomarkers of inflammation or oxidative damage, or in clinical outcomes, between N-acetylcysteine and placebo groups.


CONCLUSIONS
Preoperative administration of N-acetylcysteine did not attenuate postoperative systemic or pulmonary inflammation or oxidative damage after lung resection.


BACKGROUND
NCT00655928 at ClinicalTrials.gov.
Adult Intensive Care Unit, Royal Brompton Hospital, London, UK.
Anthony J
AJ
Bastin
Liver Failure Group, UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College of London (UCL), London, UK.
Nathan
N
Davies
Academic Division of Thoracic Surgery, Royal Brompton & Harefield NHS Foundation Trust, UK National Heart and Lung Division, Imperial College, London, UK.
Eric
E
Lim
National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.|Vascular Biology, National Heart and Lung Institute, Imperial College London, London, UK.
Greg J
GJ
Quinlan
Adult Intensive Care Unit, Royal Brompton Hospital, London, UK.|National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, London, UK.|Leukocyte Biology, National Heart and Lung Institute, Imperial College London, London, UK.
Mark J
MJ
Griffiths
D000111:Acetylcysteine / Q000008:administration & dosage*; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests / Q000379:methods; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011013:Pneumonectomy / Q000009:adverse effects* / Q000379:methods; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D011183:Postoperative Complications / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D011300:Preoperative Care / Q000379:methods; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D016896:Treatment Outcome
D000975:Antioxidants; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D012709:Serum Albumin; C561522:ischemia-modified albumin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D005978:Glutathione; D000111:Acetylcysteine; D000075462:Serum Albumin, Human
critical care medicine; inflammation; lung cancer; lung injury; thoracic surgery