Cluding dyspnea, edema, rales and jugular venous distention, with the chest Cluding dyspnea, edema, rales and jugular venous distention, with the chest X-ray demonstrating increase in vascular markings and diffuse alveolar interstitial infiltrates). Secondary clinical endpoints – include (a) intraoperative ventilation strategy related complications (e.g. de-saturation, hypotension during recruitment maneuver, need for vasoactive medication), (b) unexpected need for ICU admission or ICU readmission, (c) hospital-free days at follow-up day 90, (d) postoperative wound healing and (e) post-operative extrapulmonary complications. Extra-pulmonary complications include SIRS, sepsis, severe sepsis, septic shock (all according to consensus criteria [20]), extrapulmonary infection (wound infection or any other infection), coma (Glasgow Coma Score <8 in the absence of therapeutic coma or sedation), acute myocardial infarction (according to universal definition of myocardial infarction [21]), acute renal failure (according to the RIFLE classification system [22]), disseminated intravascular coagulation (according to ISTH diagnostic scoring system for DIC [23]), gastro-intestinal failure (defined as; gastro-intestinal bleeding or gastro-intestinal failure according to GIF-score [24])Hemmes et al. Trials 2011, 12:111 http://www.trialsjournal.com/content/12/1/Page 6 ofand hepatic failure (defined as; serum bilirubin level >2 mg/dL with elevation of the transaminase and lactic dehydrogenase levels above twice normal values).

Other study parameters – Blood samples will be collected and analyzed for systemic markers of lung injury (including but not limited to soluble Receptor for Advanced Glycation Endproducts (sRAGE), Clara Cell protein-16 (CC-16), surfactant proteins A and D and levels of proinflammatory and procoagulant/antifibrinolytic mediators (including but not limited to interleukin (IL)-6, IL-8, Fmoc-Oic-OH tumor necrosis factor (TNF)-a, and thrombin-antithrombin (TAT), protein C, and plasminogen activator 4-Bromopicolinaldehyde inhibitor (PAI)-1). The abovementioned biomarkers of lung injury, acute inflammation and coagulopathy have been shown to correlate with poor clinical outcome in patients with ALI/ARDS [25]. Notably, with short-term mechanical PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13867361 ventilation rises in systemic levels of lung injury biomarkers [26], acute inflammation [9] and procoagulant/antifibrinolytic mediators [8] have been described. Lung-protective mechanical ventilation strategies attenuated the rise in levels of some of the abovementioned mediators in patients with ALI/ARDS [27], as well as patients who underwent short-term mechanical ventilation because of surgery [8,9]. Most of these trials compared the effect of different tidal volumes. The injury induced by mechanical ventilation originates in the lung, but may also affect distal organs by release of mediators from the lung into the systemic circulation [28,29]. Therefore systemic biomarkers of distant organ injury, in particular the kidney, 3S)-2-((tert-Butoxycarbonyl)amino)-3-hydroxybutanoic acid (S)-2-Aminopent-4-ynoic acid tert-butyl 2-chloropyridin-4-ylcarbamate Molecular 4-Vinyl-1 are determined (including, but not limited to neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C).Statistical considerationstermination of the study is considered. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3081428 The third and final analysis is performed at 900 patients with a p-value of 0.045 for significance. When post-operative pulmonary complications occur significantly more frequent in the intervention group, terminating the study due to harm will be considered when p 0.022 for each interim analysis.Statistical analysisSample size calculation – the required sample size is calculated from an estimated effect size.