Acute Respiratory Distress Syndrome in the Perioperative Period of Cardiac Surgery: Predictors, Diagnosis, Prognosis, Management Options, and Future Directions

Acute respiratory distress syndrome (ARDS) after cardiac surgery is reported with a widely variable incidence (from 0.4%-8.1%). Cardiac surgery patients usually are affected by several comorbidities, and the development of ARDS significantly affects their prognosis. Herein, evidence regarding the current knowledge in the field of ARDS in cardiac surgery is summarized and is followed by a discussion on therapeutic strategies, with consideration of the peculiar aspects of ARDS after cardiac surgery.Prevention of lung injury during and after cardiac surgery remains pivotal. Blood product transfusions should be limited to minimize the risk, among others, of lung injury. Open lung ventilation strategy (ventilation during cardiopulmonary bypass, recruitment maneuvers, and the use of moderate positive end-expiratory pressure) has not shown clear benefits on clinical outcomes. Clinicians in the intraoperative and postoperative ventilatory settings carefully should consider the effect of mechanical ventilation on cardiac function (in particular the right ventricle). Driving pressure should be kept as low as possible, with low tidal volumes (on predicted body weight) and optimal positive end-expiratory pressure.Regarding the therapeutic options, management of ARDS after cardiac surgery challenges the common approach. For instance, prone positioning may not be easily applicable after cardiac surgery. In patients who develop ARDS after cardiac surgery, extracorporeal techniques may be a valid choice in experienced hands. The use of neuromuscular blockade and inhaled nitric oxide can be considered on a case-by-case basis, whereas the use of aggressive lung recruitment and oscillatory ventilation should be discouraged. Acute respiratory distress syndrome (ARDS) after cardiac surgery is reported with a widely variable incidence (from 0.4%-8.1%). Cardiac surgery patients usually are affected by several comorbidities, and the development of ARDS significantly affects their prognosis. Herein, evidence regarding the current knowledge in the field of ARDS in cardiac surgery is summarized and is followed by a discussion on therapeutic strategies, with consideration of the peculiar aspects of ARDS after cardiac surgery. Prevention of lung injury during and after cardiac surgery remains pivotal. Blood product transfusions should be limited to minimize the risk, among others, of lung injury. Open lung ventilation strategy (ventilation during cardiopulmonary bypass, recruitment maneuvers, and the use of moderate positive end-expiratory pressure) has not shown clear benefits on clinical outcomes. Clinicians in the intraoperative and postoperative ventilatory settings carefully should consider the effect of mechanical ventilation on cardiac function (in particular the right ventricle). Driving pressure should be kept as low as possible, with low tidal volumes (on predicted body weight) and optimal positive end-expiratory pressure. Regarding the therapeutic options, management of ARDS after cardiac surgery challenges the common approach. For instance, prone positioning may not be easily applicable after cardiac surgery. In patients who develop ARDS after cardiac surgery, extracorporeal techniques may be a valid choice in experienced hands. The use of neuromuscular blockade and inhaled nitric oxide can be considered on a case-by-case basis, whereas the use of aggressive lung recruitment and oscillatory ventilation should be discouraged. ACUTE respiratory distress syndrome (ARDS) is a cause of high morbidity and mortality. Data from the observational, international, multicenter prospective cohort study LUNG SAFE (Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE)1Bellani G Laffey JG Pham T et al.Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries.JAMA. 2016; 315: 788-800Google Scholar showed a mortality as high as 46% for the severe forms of ARDS. The current Berlin definition of ARDS2Ferguson ND Fan E Camporota L et al.The Berlin definition of ARDS: An expanded rationale, justification, and supplementary material.Intensive Care Med. 2012; 38: 1573-1580Google Scholar describes the syndrome in terms of acute onset with bilateral lung opacities not explained by cardiac failure and/or fluid overload (Table 1). However, in patients who develop ARDS after cardiac surgery, it is challenging to exclude a cardiac contribution to the deterioration in gas exchange. It is likely that ARDS after cardiac surgery potentially has a worse prognosis compared with ARDS from other causes because cardiac patients are by definition affected by a significant burden of cardiovascular (and potentially by several other) comorbidities. Moreover, the occurrence of ARDS after cardiac surgery is relatively common, and its management presents a challenge because therapeutic options used for conventional ARDS patients (eg, prone positioning) may not be easily applicable after cardiac surgery. For such reasons, ARDS in cardiac surgery deserves more characterization and clinical studies for clinicians to better understand its peculiar features and to identify the best strategies to improve patient outcomes. This review focuses on the current knowledge in the field of ARDS in cardiac surgery and gaps of knowledge and the available therapeutic options, with consideration of the peculiar aspects of ARDS in the cardiac patient in the postoperative period.Table 1ARDS Definition Task ForceBerlin Definition of Acute Respiratory Distress Syndrome According to the Task ForceDiagnostic criteria1. Onset within 1 wk of a known clinical insult or new/worsening respiratory symptoms2. Bilateral opacities (on CXR or CT scan) not fully explained by effusions, lobar/lung collapse, or nodules3. Respiratory failure not fully explained by cardiac failure or fluid overloadOxygenation impairment*A minimum level of 5 cmH2O of positive end-expiratory pressure is delivered (continuous positive airway pressure may be applied noninvasively for mild ARDS cases). Adapted from Ferguson et al.3Mild20035%, and oxygen saturation <95%. It remains challenging to identify which features are correlated with such risk because only a limited number of clinical studies have reported data in this regard.4Asimakopoulos G Taylor KM Smith PL et al.Prevalence of acute respiratory distress syndrome after cardiac surgery.J Thorac Cardiovasc Surg. 1999; 117: 620-621Google Scholar, 5Christenson JT Aeberhard JM Badel P et al.Adult respiratory distress syndrome after cardiac surgery.Cardiovasc Surg. 1996; 4: 15-21Google Scholar, 6Kaul TK Fields BL Riggins LS et al.Adult respiratory distress syndrome following cardiopulmonary bypass: Incidence, prophylaxis and management.J Cardiovasc Surg. 1998; 39: 777-781Google Scholar, 7Chen SW Chang CH Chu PH et al.Risk factor analysis of postoperative acute respiratory distress syndrome in valvular heart surgery.J Crit Care. 2016; 31: 139-143Google Scholar, 8Kogan A Preisman S Levin S et al.Adult respiratory distress syndrome following cardiac surgery.J Card Surg. 2014; 29: 41-46Google Scholar, 9Milot J Perron J Lacasse Y et al.Incidence and predictors of ARDS after cardiac surgery.Chest. 2001; 119: 884-888Google Scholar It seems that preexisting cardiorespiratory conditions are the main contributors to the risk of postoperative ARDS, together with occurrence of multiple transfusions.7Chen SW Chang CH Chu PH et al.Risk factor analysis of postoperative acute respiratory distress syndrome in valvular heart surgery.J Crit Care. 2016; 31: 139-143Google Scholar, 8Kogan A Preisman S Levin S et al.Adult respiratory distress syndrome following cardiac surgery.J Card Surg. 2014; 29: 41-46Google Scholar, 9Milot J Perron J Lacasse Y et al.Incidence and predictors of ARDS after cardiac surgery.Chest. 2001; 119: 884-888Google Scholar However, drawing conclusions from these studies is challenging because they included patients with heterogeneous clinical characteristics; reported data on small populations (12-108 patients, average 41) with a widely variable incidence of postoperative ARDS (0.4%-8.1%4Asimakopoulos G Taylor KM Smith PL et al.Prevalence of acute respiratory distress syndrome after cardiac surgery.J Thorac Cardiovasc Surg. 1999; 117: 620-621Google Scholar, 5Christenson JT Aeberhard JM Badel P et al.Adult respiratory distress syndrome after cardiac surgery.Cardiovasc Surg. 1996; 4: 15-21Google Scholar, 6Kaul TK Fields BL Riggins LS et al.Adult respiratory distress syndrome following cardiopulmonary bypass: Incidence, prophylaxis and management.J Cardiovasc Surg. 1998; 39: 777-781Google Scholar, 7Chen SW Chang CH Chu PH et al.Risk factor analysis of postoperative acute respiratory distress syndrome in valvular heart surgery.J Crit Care. 2016; 31: 139-143Google Scholar, 8Kogan A Preisman S Levin S et al.Adult respiratory distress syndrome following cardiac surgery.J Card Surg. 2014; 29: 41-46Google Scholar, 9Milot J Perron J Lacasse Y et al.Incidence and predictors of ARDS after cardiac surgery.Chest. 2001; 119: 884-888Google Scholar); adopted different diagnostic criteria; and were published over a 20-year period (1996-2016). A recent large retrospective study (3,946 patients, ARDS incidence 1.15%), in which multivariate regression analysis was performed, identified the following predictors of postoperative ARDS: prior and/or emergency and/or complex cardiac surgery (the latter defined as concomitant coronary artery grafting and valve surgery or multiple valve surgery) and transfusion of >three red blood cell (RBC) units.10Kogan A Segel MJ Ram E et al.Acute respiratory distress syndrome following cardiac surgery: Comparison of the American-European Consensus Conference definition versus the Berlin definition.Respiration. 2019; 97: 518-524Google Scholar Another recent study reported greater postoperative ARDS incidence in patients undergoing type A aortic dissection repair (15.9%), but no preoperative risk factors were identified.11Su IL Wu VC Chou AH et al.Risk factor analysis of postoperative acute respiratory distress syndrome after type A aortic dissection repair surgery.Medicine. 2019; 98: e16303Google Scholar More research is needed to characterize the risk factors for ARDS after cardiac surgery and strategies to decrease its incidence. For patients who develop ARDS after cardiac surgery, the evaluation of the origin of pulmonary edema becomes extremely challenging because of the presence of preexisting cardiopulmonary comorbidities. In most cardiac patients, the development of ARDS probably is multifactorial from its beginning, and the presence of preexisting cardiac dysfunction theoretically aggravates the degree of pulmonary edema in patients who develop ARDS; thus, it is possible that mild injuries potentially result in moderate/severe forms of ARDS. Of note, the authors of the Berlin definition2Ferguson ND Fan E Camporota L et al.The Berlin definition of ARDS: An expanded rationale, justification, and supplementary material.Intensive Care Med. 2012; 38: 1573-1580Google Scholar removed the criteria of pulmonary arterial wedge pressure (PAWP) based on the observation that a nonnegligible number of patients admitted to the general intensive care unit (ICU) with ARDS demonstrated increased PAWP. For example, in a landmark randomized controlled trial (RCT),12Wheeler AP Bernard GR et al.National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials NetworkPulmonary-artery versus central venous catheter to guide treatment of acute lung injury.N Engl J Med. 2006; 354: 2213-2224Google Scholar almost one-third of ARDS patients assigned to management according to the data from the pulmonary artery catheter had PAWP values >18 mmHg. This finding reinforced how challenging it is to determine the extent of cardiac contribution to the pulmonary edema that develops in ARDS cases, even when the diagnosis is made by experienced clinicians under the strict criteria of an RCT. Interestingly, Kogan et al.10Kogan A Segel MJ Ram E et al.Acute respiratory distress syndrome following cardiac surgery: Comparison of the American-European Consensus Conference definition versus the Berlin definition.Respiration. 2019; 97: 518-524Google Scholar showed that the introduction of the Berlin definition2Ferguson ND Fan E Camporota L et al.The Berlin definition of ARDS: An expanded rationale, justification, and supplementary material.Intensive Care Med. 2012; 38: 1573-1580Google Scholar produced similar figures of ARDS prevalence after cardiac surgery (1.15%) compared with the previous definition (1.14%). In summary, the postoperative period after cardiac surgery is a time of increased risk for the development of ARDS in a consistent proportion of patients. There are unique challenges in the diagnosis of ARDS after cardiac surgery because, in most patients, the contribution of cardiac dysfunction cannot be ruled out. Although patients with preoperative pulmonary disease and/or cardiac dysfunction may have a higher risk of developing ARDS, clinicians should keep in mind that these factors are not always modifiable. Pulmonary function is negatively affected by a wide spectrum of left ventricular (LV) comorbidities. Conditions such as left-sided heart valve diseases, low LV ejection fraction, and advanced LV diastolic dysfunction all cause an increase of LV end-diastolic pressures and poor LV compliance, with backwards reflection on the lungs. Conversely, there are modifiable factors in the intraoperative and postoperative periods that can be optimized to help minimize the risk of ARDS development. Direct surgical injury13Berg K Haaverstad R Astudillo R et al.Oxidative stress during coronary artery bypass operations: Importance of surgical trauma and drug treatment.Scand Cardiovasc J. 2006; 40: 291-297Google Scholar (eg, pleural opening and use of retractors and lung manipulation) and the use of cardiopulmonary bypass (CPB)14Aljure OD Fabbro 2nd, M Cardiopulmonary bypass and inflammation: The hidden enemy.J Cardiothorac Vasc Anesth. 2019; 33: 346-347Scopus (14) Google Scholar commonly are encountered as intraoperative factors that trigger inflammation at the pulmonary level. In parallel, both surgical and perfusion strategies to decrease perioperative lung damage have been developed (eg, minimally invasive surgery15Gu YJ Mariani MA Boonstra PW et al.Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass: The role of tissue injury by surgical incision.Chest. 1999; 116: 892-898Google Scholar and use of miniaturized CPB circuits16Farag M Patil NP Sabashnikov A et al.Comparison of two miniaturized cardiopulmonary bypass systems regarding inflammatory response.Artif Organs. 2017; 41: 139-145Google Scholar). From the perspectives of cardiac anesthesiologists and intensivists, there are some key aspects that may contribute to the reduction of the incidence of postoperative ARDS after cardiac surgery (Table 2).17Sundar S Novack V Jervis K et al.Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients.Anesthesiology. 2011; 114: 1102-1110Google Scholar, 18Zupancich E Paparella D Turani F et al.Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: A randomized clinical trial.J Thorac Cardiovasc Surg. 2005; 130: 378-383Google Scholar, 19Reis Miranda D Gommers D Struijs A et al.Ventilation according to the open lung concept attenuates pulmonary inflammatory response in cardiac surgery.Eur J Cardiothorac Surg. 2005; 28: 889-895Google Scholar, 20Wrigge H Uhlig U Baumgarten G et al.Mechanical ventilation strategies and inflammatory responses to cardiac surgery: A prospective randomized clinical trial.Intensive Care Med. 2005; 31: 1379-1387Google Scholar, 21Koner O Celebi S Balci H et al.Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass.Intensive Care Med. 2004; 30: 620-626Google Scholar, 22Chaney MA Nikolov MP Blakeman BP et al.Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass.J Cardiothorac Vasc Anesth. 2000; 14: 514-580Google Scholar In particular, the following are discussed:1Optimization of mechanical ventilation (MV)2Limitation of transfusions of blood products3The hemodynamic effect of MV (focusing on right ventricular [RV] function)Table 2Key Aspects to Limit the Incidence of ARDS After Cardiac Surgery: Perspectives of Cardiac Anesthesiologists and IntensivistsOptimize the MV settingsPrefer low TV (based on PBW)Determine the optimal PEEPUse the lowest possible driving pressureThe role of open lung concept remains unclearLimit transfusions of blood productsReduce hemodilution Avoid fluid overloadImplement bundles for blood product managementUse point-of-care tests for coagulopathy and bleedingConsider hemodynamic impact of MV on right ventricleSignificant strain on right ventricle may be not-well toleratedAvoid hypoxia, hypercarbia, acidosis (effects on PVR)Perform early echocardiography to evaluate RV functionEstablish timely hemodynamic support if neededAbbreviations: ARDS, acute respiratory distress syndrome; MV, mechanical ventilation; PBW, predicted body weight; PEEP, positive end-expiratory pressure; PVR, pulmonary vascular resistance; RV, right ventricular; TV, tidal volume. Open table in a new tab Abbreviations: ARDS, acute respiratory distress syndrome; MV, mechanical ventilation; PBW, predicted body weight; PEEP, positive end-expiratory pressure; PVR, pulmonary vascular resistance; RV, right ventricular; TV, tidal volume. Cardiac surgery patients often are exposed to risk factors for lung disease. History of smoking is common among these patients,23Ngaage DL Martins E Orkell E et al.The impact of the duration of mechanical ventilation on the respiratory outcome in smokers undergoing cardiac surgery.Cardiovasc Surg. 2002; 10: 345-350Google Scholar and conditions such as heart valve diseases and/or systolic or diastolic dysfunction may cause pulmonary venous congestion, thereby reducing the efficiency of the alveolar-capillary membrane. The use of small tidal volume (TV) is the “mantra” of ventilation of ARDS patients.24Brower RG Matthay MA Morris A et al.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Google Scholar A meta-analysis suggested that the use of a lung-protective ventilation strategy with low TV also is associated with improved clinical outcomes among patients without ARDS25Serpa Neto A Cardoso SO Manetta JA et al.Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: A meta-analysis.JAMA. 2012; 308: 1651-1659Google Scholar; however, the PReVENT (PRotective VENTilation in Patients Without ARDS) RCT showed that, in ICU patients without ARDS, a low TV strategy (4-6 mL/kg of predicted body weight) did not change the number of ventilator-free days compared with a high TV strategy (8-10 mL/kg).26Simonis FD Serpa Neto A Binnekade JM et al.Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial.JAMA. 2018; 320: 1872-1880Google Scholar The literature regarding the optimal combination of TV and positive end-expiratory pressure (PEEP) in patients undergoing cardiac surgery seems limited. Few good quality studies (six RCTs)17Sundar S Novack V Jervis K et al.Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients.Anesthesiology. 2011; 114: 1102-1110Google Scholar, 18Zupancich E Paparella D Turani F et al.Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: A randomized clinical trial.J Thorac Cardiovasc Surg. 2005; 130: 378-383Google Scholar, 19Reis Miranda D Gommers D Struijs A et al.Ventilation according to the open lung concept attenuates pulmonary inflammatory response in cardiac surgery.Eur J Cardiothorac Surg. 2005; 28: 889-895Google Scholar, 20Wrigge H Uhlig U Baumgarten G et al.Mechanical ventilation strategies and inflammatory responses to cardiac surgery: A prospective randomized clinical trial.Intensive Care Med. 2005; 31: 1379-1387Google Scholar, 21Koner O Celebi S Balci H et al.Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass.Intensive Care Med. 2004; 30: 620-626Google Scholar, 22Chaney MA Nikolov MP Blakeman BP et al.Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass.J Cardiothorac Vasc Anesth. 2000; 14: 514-580Google Scholar have investigated the use of different combinations of TV and PEEP in patients undergoing cardiac surgery (see Table 3), but it is difficult to draw conclusions on the best TV and PEEP combination because these studies are relatively outdated, included small populations (25-149 patients, average 61) with variable settings, and mostly were focused on soft indicators (eg, changes in cytokines). Apart from these small and heterogeneous RCTs, a large observational study published in 2012 (3,434 cardiac surgery patients)27Lellouche F Dionne S Simard S et al.High tidal volumes in mechanically ventilated patients increase organ dysfunction after cardiac surgery.Anesthesiology. 2012; 116: 1072-1082Google Scholar stratified the population into the following three groups according to the TV: <10 mL/kg, 10 to12 mL/kg, and >12 mL/kg. The authors found increased organ dysfunction and ICU length of stay in patients receiving greater TVs.Table 3Randomized Controlled Studies Addressing the Combination of Tidal Volume and/or Positive End-Expiratory Pressure in Cardiac Surgery PatientsFirst Author, yNumber of PatientsTV (mL/Kg) + PEEP (cmH2O)Advantages of More Protective Ventilation StrategiesSundar et al.,17Sundar S Novack V Jervis K et al.Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients.Anesthesiology. 2011; 114: 1102-1110Google Scholar 2011149CABG and/or valve and/or aortic surgery6 mL/kg +>5 cmH2O v10 mL/kg +>5 cmH2OHigher proportion of patients extubated within 6 h; lower reintubation rateZupancich et al.,18Zupancich E Paparella D Turani F et al.Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: A randomized clinical trial.J Thorac Cardiovasc Surg. 2005; 130: 378-383Google Scholar 200540CABG8 mL/kg +10 cmH2O v10-12 mL/kg +2-3 cmH2OLower IL-6 and IL-8 in BAL and serumReis Miranda et al.,19Reis Miranda D Gommers D Struijs A et al.Ventilation according to the open lung concept attenuates pulmonary inflammatory response in cardiac surgery.Eur J Cardiothorac Surg. 2005; 28: 889-895Google Scholar 200562CABG and/or valve4-6 mL/kg +10 cmH2O*The low tidal volume group received ventilation at respiratory frequency of 40 min−1, PEEP of 10 cmH2O, I/E ratio of 1:1, and lung recruitment maneuvers. v6-8 mL/kg +5 cmH2OSerum IL-8 and IL-10 decreased more rapidlyWrigge et al.,20Wrigge H Uhlig U Baumgarten G et al.Mechanical ventilation strategies and inflammatory responses to cardiac surgery: A prospective randomized clinical trial.Intensive Care Med. 2005; 31: 1379-1387Google Scholar 200544CABG6 mL/kg + 9 cmH2O v 12 mL/kg +7 cmH2OLower TNF-α in BALNo differences in IL-6 and IL-8 in BAL and serumKoner et al.,21Koner O Celebi S Balci H et al.Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass.Intensive Care Med. 2004; 30: 620-626Google Scholar 200444CABG6 mL/kg + 5 cmH2O v10 mL/kg + 5 cmH2O v10 mL/kg + 0 cmH2OLower shunt and improved oxygenation, no differences in proinflammatory cytokineChaney et al.,22Chaney MA Nikolov MP Blakeman BP et al.Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass.J Cardiothorac Vasc Anesth. 2000; 14: 514-580Google Scholar 200025CABG6 mL/kg + 5 cmH2O v 12 mL/kg + 5 cmH2OLess impact on lung compliance and shuntAbbreviations: BAL, bronchoalveolar lavage; CABG, coronary artery bypass grafting; I/E, Inspiratory-expiratory ratio; IL, interleukin; PEEP, positive end-expiratory pressure; TV, tidal volume. The low tidal volume group received ventilation at respiratory frequency of 40 min−1, PEEP of 10 cmH2O, I/E ratio of 1:1, and lung recruitment maneuvers. Open table in a new tab Abbreviations: BAL, bronchoalveolar lavage; CABG, coronary artery bypass grafting; I/E, Inspiratory-expiratory ratio; IL, interleukin; PEEP, positive end-expiratory pressure; TV, tidal volume. Another unique aspect in the management of MV in patients undergoing cardiac surgery is the use of an open-lung ventilation strategy, including the maintenance of MV during CPB along with recruitment maneuvers, and the use of greater PEEP levels (8 cm H2O). In this regard, the recent PROVECS (Open Lung Protective Ventilation in Cardiac Surgery) RCT (488 patients) showed that an open-lung strategy does not reduce the incidence of postoperative pulmonary complications compared with usual care.28Lagier D Fischer F Fornier W et al.Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: The PROVECS randomized clinical trial.Intensive Care Med. 2019; 45: 1401-1412Google Scholar Moreover, in a prespecified subanalysis, the authors showed that although open lung ventilation improved dorsal ventilation in the short term, this benefit was not sustained and was associated with greater plasma biomarkers of epithelial lung injury, suggesting lung overdistention.29Lagier D Velly LJ Guinard B et al.Perioperative open-lung approach, regional ventilation, and lung injury in cardiac surgery.Anesthesiology. 2020; 133: 102-145Google Scholar It is plausible that an open-lung strategy may cause lung distention under the intraoperative “open-chest” conditions and that alveolar recruitment already was maximized in the control group. Driving pressure (difference between plateau airway pressure and PEEP) represents the most important factor associated with postoperative pulmonary complications after general anesthesia, as shown by a recent meta-analysis30Neto AS Hemmes SN Barbas CS et al.Association between driving pressure