PROTECTIVE MECHANICAL VENTILATION IN PATIENTS WITHOUT OR WITH LUNG INJURY

The mortality of Acute Respiratory Distress Syndrome (ARDS) is still high from 27 to 45% according to Berlin definition. Even in surgical patients without lung injury, the postoperative pulmonary complications (PPCs) are frequent. Mechanisms of ARDS, ventilator associated lung injury (VALI) and PPCs are better understood. In ARDS, protective ventilation with low tidal volume 6 ml/kg PBW and higher levels of positive end-expiratory pressure (PEEP) is widely accepted as routine practice. In no ARDS patients undergoing mechanical ventilation, protective ventilation with low tidal volume 6ml/kg PBW and low to moderate levels of PEEP has become the new challenge paradigm shift of supportive care mainly in ICU and perioperative patients. Respiratory monitoring is very helpful for optimizing mechanical ventilator setting to prevent VALI and early detect PPCs during the perioperative period. Several scores have been developed to stratify the risk of ARDS, VALI and PPCs. It’s time to apply basic physiologic knowledge of respiratory function and evidence based practice to improve ARDS and PPCs outcomes.


INTRODUCTION
Using the original American-European Consensus Conference (AECC) definition of the Acute Respi-ratory Distress Syndrome (ARDS), the incidence of ARDS was vary from 5-33.8 cases per 100,000 populations (1).Several studies have shown the improvement of outcome in selected groups of ARDS and the ARDS related mortality was gradually decreased from 70% to 40% in the last decades.
According to the limitations of AECC definition of ARDS i.e. the decrease in usage of Swan-Ganz catheter to distinguish the presence of hydrostatic edema and poor sensitivity of PaO2/FiO2 ratio in different levels of positive end expiratory pressure (PEEP), the Berlin definition has been developed in order to yield better predictability for mortality than AECC definition, to be easily for clinical research implementation as well as to exclude the term acute lung injury for avoiding possible misinterpretation (2).Recent studies have demonstrated that various severities of ARDS according to Berlin definition are associated with the degree extravascular lung water index, pulmonary vascular permeability index by using transpulmonary thermodilution method (3) and the finding of diffuse alveolar damage at autopsy (4,5).The mortality of ARDS is still high from mild to severe as 27 to 45% by Berlin definition (2).
Not only ARDS but also pulmonary complications particularly during perioperative period and in intensive care unit (ICU) with previously non-injured lung became an interesting issue.A recent, large European cohort study involving 46,539 patients who un-

Mechanisms of ventilator associated lung injury and postoperative pulmonary complications 1.1 Atelectrauma, volume trauma, barotrauma
Ventilation at high lung volume has been shown yielding to alveolar rupture and barotrauma.Several experimental studies have demonstrated that the high MV pressure setting induces rupture of air space not from the absolute pressure itself, but from the degree of lung over distension.Thus, the end inspiratory plateau and tidal volume (VT) per ideal body weight are inadequate parameters to determine the real lung stress and strain.The major determinants of VALI are lung stress or distending force (depend on the applied transpulmonary pressure ŠPL¹) greater than 20-24 cm H2O during inspiration and lung strain defined by the proportion of applied tidal volume plus inflated lung volume due to PEEP application and the resting lung volume (functional residual capacity) greater than 1.5-2 (12,13).Even in healthy lung, experimental study suggested that long term high tidal volume ventilation with lung strain of 2.5 caused the animals died from respiratory failure (14).If the lungs are inhomogeneous, the applied force will mainly stress on the regions around collapsed and consolidated part which joining to those of opened part.This leads to the increase in stress and strain at wall of opening alveoli particularly in higher alveolar volume (pressure multipliers or lung stress raiser) (12).Lung inhomogeneity is associated with overall mortality and severity of ARDS (12).
During ventilation at low lung volume, repetitive tidal-cyclic opening and closing of alveoli and distal airway leads to shear stress so called atelectrauma.The surfactant dysfunction results in airway collapse hence atelectrauma by the force that generated by surface tension and consequence to an increase of stress and strain.The maneuver which aiming to decrease the lung inhomogeneity such as higher PEEP improved oxygenation and tended to decrease in mortality (15).
In addition to mechanisms associated with VALI, others mechanisms producing PPCs are: 1) general anesthesia, sedation and muscle paralysis caused a reduction of respiratory muscle tone, oxygen reabsorption lead to an increase in atelectasis as well as peripheral airway closure; 2) reduction of functional residual capacity; 3) altering of diaphragmatic position (cephalic shift of diaphragm); 4) redistribution of thoracic blood volume and 6) surfactant inactivation.

Biotrauma
Lung cells have mechanisms that allow them to deal with physiological deformations during normal breathing.Nevertheless, under mechanical ventilation, such forces might be excessive and lead to cell injury.The concept of biotrauma arised in the early 1990s, when several experiments revealed the existence of a relevant biological response to mechanical forces (16,17).Biotrauma involves the local release of inflammatory mediators that reach the systemic circulation spreading the damage, an excessive activation of the immune system, as well as other numerous cellular responses triggered by mechanical forces (18).The numerous effects of these multiple biological responses greatly account for the high mortality of patients with lung injury and ARDS from multiple organ dysfunction syndrome (19).

Effects on alveolar epithelium, endothelium and extracellular matrix
The force derived from mechanical ventilation and over inflation involve a rearrangement of the cellular shape of alveolar cells, types I or II, and endothelium.In this context, cytoskeleton plays a crucial role, since it provides a physical basis for translating mechanical forces into biochemical responses (mechanotransduction).Cytoskeletal reorganization, integrins and ion channels are major players of this process, activating a complex network of intracellular pathways that eventually result in extracellular matrix remodelling, recruitment of white cells, and cytokine release (18,20).If stress and strain reach the limit of rupture of the fibre system, mechanical failure may occur with direct rupture of alveolar walls and pulmonary capillaries (19).
Toll-like receptors (TLRs) are innate immune sensors expressed by a range of immune cells, and also by epithelial cells (21).TLRs activate the transcription factor nuclear factor kappa B (NF-kappaB), which eventually results in an increased expression of inflammatory genes.The activation of NF-kappaB, which has been established in VALI (22), induces the production of inflammatory mediators like tumor necrosis factor (TNF) alpha, interleukins (IL) 6, IL-8 or IL-1â (19), which, among others, have shown to be importantly involved in the pathophysiology of VALI (23,24).Importantly, cytokines and chemokines released by epithelial cells and alveolar macrophages induce the recruitment of neutrophils to the lung via IL-8 (19), which amplify tissue inflammation.
Molecules that constitute the extracellular matrix (ECM), such as hyaluronan, biglycan, versican, heparan sulfate, fibronectin ortenascin-C are important activators of TLRs (25,26).These molecules have essential functions in many lung pathophysiological processes, as they regulate tissue hydration, macromolecular structure and function, response to inflammatory agents, and tissue repair (27).Current evidence shows that mechanical ventilation, not only at injurious but also at physiologic tidal volume, may deeply affect ECM structure and function (28,29).In this context, ECM modifications may influence the altered mechanical behavior of the lung parenchyma and also contribute to the subsequent inflammatory events, since ECM constituents are among TLR endogenous ligands (27).
Oxidative stress is another important mechanism during biotrauma.Evidence from animal models suggests that oxidative stress and redox imbalance contribute to enhance/perpetuate susceptibility to VALI (30,31).Lung alveolar and epithelial cells have showed an increase on reactive oxygen species production in response to elevated stretch (32).Elevated oxidant release in serum as well as decreased lung glutathione, the major antioxidant in the lung, were observed in rats ventilated at high tidal volume (20 mL/kg) (33).An increased superoxide production has been observed in ventilated patients (34) and, importantly, antioxidant strategies have shown beneficial effects in experimental models both at the local and systemic levels, attenu-ating VALI-associated inflammation, apoptosis and oxidative responses (35,36).
Mechanisms of inflammation, ECM disruption or oxidative stress are, to a greater or lesser extent, eventually associated with cell death.VALI has been shown to induce apoptosis of airway epithelial cells (37).Interestingly, experimental studies showed that hydrogen inhalation as a therapeutic approach provided cytoprotective effects against apoptotic and inflammatory signaling pathway activation during VALI (36,38).

Mechanisms of repair
Membrane disruption acts as a mechanotransducer, whereby the influx of calcium after membrane injury leads to the up regulation of mediators as and NF-kappaB.Deformation-induced plasma membrane disruptions have been directly linked to the activation of pro-inflammatory signaling cascades including early stress response genes, chemokine receptors, and adhesion molecules regulation.Plasma membrane homeostasis is a dynamic process, and deformation-induced lipid trafficking is an important cytoprotective mechanism employed by the cell in the face of externally imposed shape change.The balance of these pathways may be influenced by certain conditions that shift the equilibrium towards the favoring of either a pro-injury or pro-repair state (39).
Processes of re-epithelization and collagen degradation are essential in lung repair, and inflammatory cells can modulate both ECM degradation and epithelial cell migration through different mechanisms (40): release of proteases that cleave collagen, gelatin, and elastin; modulation of inflammation toward an anti-inflammatory response; and by directly releasing growth factors that stimulate epithelial cell migration and proliferation (41).González-López et al. have demonstrated that some of these phenomena take place during the repair phase after VALI, concluding that an adequate inflammatory response and ECM remodeling are essential for recovery (42).However, ECM degradation and remodeling are complex mechanisms.If inflammation of pro-fibrotic responses are exaggerated and unbalanced, the process can lead to fibrosis and organ failure (43).
Apart from repair focused on inflammation or ECM, new approaches are emerging.In this sense, several studies have shown promising results using mesenchymal stem cells, which have shown beneficial results, reducing VALI in animal models (44,45,46).

Biomarkers for VALI
The majority of biological markers identified in plasma, serum, pulmonary edema fluid, and bronchoal-

PROTECTIVE MECHANICAL VENTILATION IN PATIENTS WITHOUT OR WITH LUNG INJURY
veolar fluid in experimental studies are cytokines and chemokines.None of them distinguishes VALI from other etiologies of lung injury.However, the temporal association between changes in levels of these proteins and changes in tidal volume or PEEP suggests a causative role (47).
The study of a panel of biomarkers has shown superior performance to single biomarkers.Abnormal levels of five biomarkers in plasma provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis, being three of them generated by lung epithelium (48).Interestingly, a recent study has found that VALI is characterized by a particular metabolic profile that suggests alterations in energy and membrane lipids (49).
Although the definition of ARDS is based on clinical criteria, altered levels of plasma biomarkers may be useful to assist in confirming the diagnosis in certain cases, to categorize them, to facilitate selection for clinical trials as well as a valuable tool for identifying patients at risk, determining prognosis and understanding pathogenesis (47).

Respiratory mechanics and Esophageal pressure measurement
Generally we can monitor patients receiving MV by observing static airway pressure, measuring respiratory system compliance and analyzing dynamic pressure-volume curve.Terragni et al assessed the accuracy of plateau pressure and stress index to identify the point associated with injurious ventilation.This study demonstrated that plateau pressure (Pplat) more than 25 cm H 2 O and stress index more than 1.05 have been shown the best performance to define the injurious ventilation (50).In terms of lung strain, the reference value computed by the ventilator is still controversial.Furthermore, the reference volume at Functional residual capacity (FRC) is the lung volume at zero PEEP level and should be at resting lung (pre-stressed condition) (12).Some studies have proposed the reference volume should be the end expiratory lung volume during PEEP application, which considered as continuous strain (12).
The proportion of airway pressure is contributed by the elastance of chest wall.Some conditions that increase chest wall elastance i.e. obesity, abdominal surgery, intra-abdominal hypertension, pleural effusion or even ARDS (H1N1 associated ARDS) make the airway pressure not representing the real stress and strain of the lungs (51,52).MV setting guided by transpulmonary pressure, not airway pressure, and intraabdo-minal pressure monitoring can promote appropriate alveolar recruitment and avoid lung hyperinflation and may prevent further pulmonary complications.In spontaneous breathing patients, during postoperative period, beside pulse oximetry (53) and capnography, esophageal pressure (Peso) can be used to monitor sedative drugs usage, patients-ventilator asynchrony and intrinsic PEEP during weaning from MV in high risk PPCs patients, i.e.COPD patients (52,54).
Talmor  (12,55).However, some authors have debated using the absolute pressure and preferred using the variation of the Peso rather than the absolute value to estimate lung stress namely elastance derived method calculating chest wall elastance (Ecw) which is the ratio of Pressure difference across chest wall (DPcw)/VT.Under static condition, P L = Paw x (E L /E RS ) in which E L = DP L /VT and E RS = DPaw/V T (52).Peso can distinguish the fraction of airway pressure that overcome lung or chest wall elastance.

Ultrasound in ICU and Perioperative period
In ARDS, the presence of pulmonary vascular dysfunction and extravascular lung water are associated with higher mortality (56).Although some methods, i.e. pulse pattern analysis and transpulmonary thermodilution technique can provide the hemodynamic goal directed therapy and respiratory variables as well as extravascular lung water (EVLW) index in either ICU or high risk surgical patients.Nevertheless, these techniques are invasive.Regarding the availability and noninvasiveness of bedside ultrasound and echocardiography, lung ultrasound can estimate EVLW index and evaluate the response of PEEP titration in ARDS (57).Jambrik et al. have demonstrated that there is significant correlation between numbers of B-lines (58) and wet to dry ratio measured by gravimetric method (r = 0.91, p < 0.001).Corradi et al. have demonstrated that quantitative lung ultrasound, based on a video gray scale analysis correlated with the amount of EVLW (59).Furthermore, the pleural effusion could be defined by the presence of anechoic or hypoechoic homogenous structure (60).In moderate to severe ARDS, the prevalence of cor-pulmonale diagnosed by trans--esophageal echocardiography is 22% despite low level of PEEP.Bedside echocardiography can be used to evaluate the right ventricular and biventricular cardiac function.During perioperative period, we can early detect atelectasis by the presence of hyper echoic hepatization suggesting the presence of consolidation.Furthermore, the measurement of air column width of larynx during endotracheal cuff deflation is the good predictor of post-extubation laryngeal edema and may predict post-operative intubation (61).

Protective ventilation in non-injured lung
The beneficial effects of protective ventilation with lower tidal volume and higher PEEP were clearly established by ARDS Network 15 years ago (62).Protective ventilation (PV) for non-injured lung has been studied in a contest of ICU and perioperative period.
Lee et al. firstly studied the role of protective ventilations in 103 ICU patients with non-injured lungs (63).The main outcome of this study was the duration of mechanical ventilation that was lower in patients treated with protective ventilation (2.30 days vs. 3.90 days) (63).Gajic et al. evaluated the effect of PV in a cohort study on 166 patients without lung injury and admitted in ICU (64).The authors did not report significant differences in development of lung injury between the groups (64).Wolthuis et al. showed the effects of PV in lowering sedative use, as primary outcome, in non-injured lung patients (65).In this study the authors did not find significant difference between the groups (65).Yilmaz et al. performed a cohort study on 375 ICU patients to evaluate the role of PV on prevention of lung injury as primary outcome (66).The authors did not find difference between protective and conventional ventilation about the considered outcome (66).Determann et al. and Pinheiro de Oliveira et al.performed randomized controlled trials to assess the levels of cytokine in broncho-alveolar lavage (BAL) in patient treated with protective and conventional ventilation (67,68).Interestingly, Determann et al. did not show any differences in cytokine in BAL, while Pinheiro de Oliveira et al. demonstrated a higher level of Cytokine in BAL in protective than in conservative ventilation (168 pg/ml vs.72 pg/ml) (67,68).
Protective ventilation was also studied in a perioperative setting on healthy lungs.It has been reported that 5% to 10% of major abdominal and thoracic surgery developed postoperative pulmonary complications (69).Different randomized controlled trials (RCTs) have been performed in major abdominal surgery on PV with different outcomes.Determann et al. did not find any differences in BAL and plasma inflammation proteins between protective and conventional ventilation (70).Wolthuis at el. reported a reduction in BAL myeloperoxidase using PV in healthy patients underwent abdominal surgery (70).Weingarten et al. experienced a better oxygenations but no improvement of inflammatory biomarkers in a RCT on patients aged > 65 years (70).Treschan et al. evaluated the effectiveness of PV in 101 healthy lung patients (71).In this study, there was no difference in improving lung function between protective and conventional ventilation (71).Recently, Severgnini et al. performed a RCT evaluating the role of PV in major abdominal surgery (10).The authors reported an improvement in pulmonary function and modified clinical pulmonary infection score (mCPIS) and a reduction in X-ray chest findings in patients treated with PV during surgery (10).Futier et al. performed a large RCT on 400 patients submitted to major abdominal surgery with protective and conventional ventilation (9).The authors found a reduced incidence of pulmonary and extrapulmonary complications in PV group (9).Protective ventilation was also matter of study in cardiac surgeries.In coronary artery bypass surgery, three studies did not demonstrate any difference in plasma and BAL cytokine levels using PV (72,73,74).Sundar et al. performed a RCT on PV in cardiac surgery on 149 patients (75).The authors found less incidence of re-intubation and a faster weaning at 6-8 hours after surgery in patients treated with PV )75).
Protective ventilation in non-injured lung was also evaluated in different meta-analysis including ICU and perioperative studies.In meta-analysis by Serpa-Neto et al., the authors included 20 studies, but only 15 RCT, and 2833 ICU and surgical patients (76).In this meta-analysis, PV had a tidal volume of 6.5 ml/kg and PEEP of 6.4 cm H 2 O while conventional ventilation with tidal volume of 10.6 ml/kg and PEEP of 3.4 cm H 2 O.Among patients without lung injury, PV was associated with better outcomes as acute lung injury (RR 0.33; 95 %CI 0.23-0.47),pulmonary infection (RR 0.52; 95 %CI 0.33-0.82),atelectasis (RR 0.62; 95 %CI 0.41-0.95) and mortality (RR 0.64; 95 %CI 0.46-0.86)(76).In the meta-analysis by Hemmes et al., the authors included 8 studies.But 6 RCT, and 169 surgical patients without lung injury (77).PV was performed with 6.1 ml/kg mean tidal volume and 6.6 cm H 2 O PEEP while conventional ventilation with 10.4 ml/kg tidal volume and 2.7 cm H 2 O PEEP (77).In this study PV protected against postoperative complications as acute lung injury (RR 0.40; 95 % CI 0.22-0.70)pulmonary infection (RR 0.64; 95 % CI 0.43-0.97)and atelectasis (RR 0.67; 95 % CI 0.47-0.96)(77).A recent meta-analysis by Sutherasan et al. included 17 studies as RCT and 1,362 ICU and surgical patients (78).In this study PV was set with mean tidal volume of 6.1 ml/kg and PEEP of 7.6 cm H 2 O while conventional ventilation with mean tidal volume of 10.7 ml/kg and PEEP of 2.5 cm H 2 O (78).This meta-analysis suggested that among surgical and critically ill patients without lung injury, protective mechanical ventilation with use of lower VT, with or without PEEP, is associated with better clinical pulmonary outcomes in term of ARDS incidence (RR 0.27; 95 % CI 0.12-0.

Protective ventilation in ARDS
Protective ventilation is a supportive tool for patients with acute lung injury.In this setting, PV was extensively studied across the years.PV included low tidal volume, high PEEP and in some circumstances recruitment maneuvers.
In the 1998, Amato et al. performed a multicenter RCT to evaluate the effects of low tidal volume (6 ml/kg) on mortality, barotrauma and multiple organ failure (MOF) in a cohort of ARDS patients (79).PV, compared with conventional ventilation, was associated with improved survival at 28 days, higher rate of weaning from mechanical ventilation, and lower rate of barotrauma in patients with ARDS although it was not associated with higher rate of survival to hospital discharge (79).Brochard et al. and Brower et al. in prospective RCTs evaluated the effect of low tidal volume (7 ml/kg and 8 ml/kg) in ARDS patients in mortality, duration of mechanical ventilation and barotraumas (80,81).Both studies concluded that there were no effects of PV on considered outcomes (80,81).In the 2000, the ARDS network group performed a large RCT including 861 adult ARDS patients to assess the role of low tidal volume (6 m/kg) different outcomes as mortality, MOF, duration of mechanical ventilation, barotrauma and ventilator free days (62).In this study the authors concluded that in ARDS patients mechanical ventilation with a lower tidal volume, than is traditionally used, resulted in decreased mortality and increases the number of days without ventilator use (62).In the 2004, the ARDS network performed another study to evaluate the effect of higher versus lower PE-EP in ARDS patients on the same previous outcomes (81).In this study, PV was set high PEEP 5-25 cm H 2 O according FiO 2 while conventional ventilation with low PEEP 5 cm H 2 O (82).This study found no difference in the considered outcome when high PEEP level was compared with low PEEP (82).PV with high and low PEEP levels was matter of study in three different RCTs performed in 2008 (55,83,84).In the study by  (55,29).In these studies high PEEP did not affect mortality (55,83,84).Interestingly, while Mercat et al. found an improvement in lung function and a reduction of MOF and duration of mechanical ventilation; Meade et al. did not confirm these findings (83,84).Furthermore, the conclusion by Talmor et al, was very interesting because the authors suggested the use of mechanical ventilation guided by esophageal pressure to further improve oxygenation and compliance in ARDS patients (29).Recently a meta-analysis evaluated the effects of high versus low PE-EP in ARDS patients considering 7 RCTs and 2565 ARDS patients (15).The outcomes were mortality, oxygenation, barotrauma and length of stay in ICU (15).High PEEP did not affect mortality, barotrauma and length of stay in ICU but improved the oxygenation of ARDS patients at 1, 3 and 7 days (15).

Prone positioning
Prone position is the adjunctive treatment that can improve oxygenation in 70% of patients.The mechanisms are an increase in end-expiratory lung volume, improvement of ventilation-perfusion matching and decrease of mass effect of the heart at the lower lobes as well as an increased homogeneity of ventilation (11).
Recent randomized controlled trial has demonstrated that in patients with PaO 2 /FiO 2 less than 150 when receiving FiO 2 of 60%, patients who received prone position showed the decrease in mortality than in supine position (28-day mortality; 16% vs. 32.8%,respectively) (85).Moreover, recent meta-analysis including this RCT have demonstrated that prone position with low tidal volume ventilation in severe ARDS patients significantly decrease 60-day mortality (86).In the subgroup which the duration of prone positioning was more than 10 hours per session showed markedly reduced in overall mortality compared with the shorter duration groups (87).However, the risk of pressure ulcer and major airways problems should be considered during implementing the prone positioning protocol (87).

Extracorporeal membrane oxygenation
Extracorporeal membrane oxygenation (ECMO) have shown the increase of survival in severe ARDS (PaO 2 /FIO 2 £ 100 and PEEP ³ 5-10 cm H 2 O).To avoid further VALI in ARDS and complications from ECMO itself, another approach is bridging MV with extracorporeal membrane oxygenation.During applying EC-MO, the VT can be decreased until less than 6 ml/kg PBW ("ultra" protective MV) (85).
Strategies for prevention and management patients with ARDS and without ARDS are summarized in Table 1.

Risk factors for ARDS and ventilator associated lung injury
In severe sepsis patients present at emergency department, high lactate, lung injury prediction scores and microbiological proven infection are independent risk factors for the development of ARDS (88).Other factors i.e. hypoalbuminemia, chemotherapy, obesity and diabetic mellitus have been proposed as the risk factors of ARDS.Gajic el al have validated lung injury prediction score (LIPS) to identify the high risk patients at the time of hospital admission and can discriminate the patients who developed ARDS from those who did not with an AUC of ROC at 0.80 (95%CI; 0.78-0.82)(89).The variables that were included in calculated worksheet composed of previously mentioned factors, type of surgery and trauma.
Several factors have been proven as the predisposing factors of VALI i.e. sepsis, fluid loading, blood transfusion and age.Old animals are more susceptible to VALI with high VT and constant PEEP compared with younger animals associated with the increase amount of lung lavage protein, IL-6 concentration, and increase of lung wet to dry ratios (90).Transfusion-related acute lung injury (TRALI) is the reaction of the

Role of recent predictive scores
PPCs are associated with various risk factors namely underlying status, type of anaesthesia and surgery particularly cardiopulmonary surgery and abdominal surgery as well as smoking status.
Several investigators have developed different scores to predict the risk of PPCs.The parameters required for score calculation can be assessed preoperatively and during bedside evaluation.

Post-operative respiratory failure risk index and pneumonia risk index
Based on National Surgical Quality Improvement Program (NSQIP) data, postoperative respiratory failure (PRF) index was developed by the investigators from veterans' affair in non-cardiac surgery patients.The risk factors were including the type of surgery, age, functional status and COPD.The laboratory data comprised albumin level less than 30 g/L, and blood urea nitrogen level more than 30 mg/dL in the model (92).The same group has constructed another index, postoperative pneumonia risk index that are added the data of impaired sensorium, cerebral vascular accident, transfusion, long-term steroid use, smoking, and alcohol use to previously mentioned index (93).These indexes have a limitation that the majority of populations included in the analysis are male veterans therefore these indexes may not be used generalizability.

Postoperative pulmonary complications risk score (ARISCAT score)
Canet et al. have identified the seven independent risk factors including low pre-operative arterial oxygen saturation, recent acute respiratory infection, age, anemia, upper abdominal or intra thoracic surgery, surgical duration of at least 2 h, and emergency surgery and showed that the AUCs under ROC curve of this score are 90% for the development of PPCs predictive index and 80% from the validation of this index (53).The PERISCOPE (Prospective Evaluation of a Risk Score for Postoperative Pulmonary Complications in Europe) study is completed and will show the data of external validation of this score (94).

Surgical lung injury prediction score (SLIP score)
The surgical lung injury prediction score (the SLIP score) were developed to classify the patients who at risk for postoperative ARDS in patients with high-risk surgery and require mechanical ventilation during general anaesthesia for longer than 3 hours with an AUC of 0.82 (95% CI 0.78-0.86).The score includes diabetes, COPD, GERD, alcohol abuse and type of surgery.However, this study is conducted in single centre and retrospective study (95).

Score for Prediction of Postoperative Respiratory Complications (SPORC)
Another recent score that developed to predict postoperative re-intubation is Score for Prediction of Postoperative Respiratory Complications (SPORC) within the first 3 postoperative days.Four independent predictors contribute to an American Society of Anesthesiologists (ASA) score ³ 3: emergency surgery, high-risk surgical service, history of congestive heart failure and chronic pulmonary disease (96).

1 1
-Esophageal pressure Ecw -Chest wall elastance EL -Lung elastance ERS -Respiratory system elastance PL -Transpulmonary pressure Paw -Mean airway pressure Pcw -Pressure difference across the chest wall EVLW -Extravascular lung water PV -Protective ventilation BAL -Broncho-alveolar lavage RCTs -Randomized controlled trials mCPIS -Modified clinical pulmonary infection score MOF -Multiple organ failure ECMO -Extracorporeal membrane oxygenation LIPS -Lung injury prediction score TRALI -Transfusion-related acute lung injury NSQIP -National Surgical Quality Improvement Program PRF -Postoperative respiratory failure the SLIP score -Surgical lung injury prediction score SPORC -Score for Prediction of Postoperative Respiratory Complications ASA -American Society of Anesthesiologists Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, IRCCS San Martino -IST, Genoa, Italy 2 Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 3 Department of Neuroscience and Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Italy 4 Multidisciplinary Organ Dysfunction Evaluation Research Network, Research Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain 5 Critical Patient Translational Research Group, Department of Anesthesiology, Intensive Care and Pain Management, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain et al. have demonstrated the value of Peso guiding for appropriate PEEP levels in ARDS patients to achieve better oxygenation at 72 hours compared with MV setting based on PEEP-FiO2 table according to ARDS Network.At end expiration, PEEP can be adjusted until the P L become positive and should not exceed 10 cm H 2 O to keep airway opening and avoid overstretch.At end inspiration, set tidal volume are limited to keep P L less than 25 cm H 2 O Meade et al., high PEEP level was fixed between 5-25 cm H 2 O according FiO 2 and low PEEP level at 5 cm H 2 O (83).In the study by Mercat et al. high PEEP was chosen according to Plateau pressure of 28-30 cm H 2 O and low PEEP between 5-9 cm H 2 O (84).Talmor et al. fixed the high PEEP level at 17 cm H 2 O and the low PEEP level at 10 cm H 2 O

Table 1 .
Strategies for prevention and management patients with ARDS and without ARDS