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Purpose: Optimal fluid management in patients with acute respiratory distress syndrome (ARDS) is challenging due to risks associated with both circulatory failure and fluid overload. The performance of dynamic indices to predict fluid responsiveness (FR) in ARDS patients is uncertain., Methods: This post hoc analysis of the HEMOPRED study compared the performance of dynamic indices in mechanically ventilated patients with shock, with and without ARDS, to predict FR, defined as an increase in aortic velocity time integral (VTI)  > 10% after passive leg raising (PLR)., Results: Among 540 patients, 117 (22%) had ARDS and were ventilated with a median tidal volume of 7.6 mL/kg [6.9-8.4] and a median positive end-expiratory pressure of 7 cmH 2 O [5-9]. FR was observed in 45 ARDS patients (39% vs 44% in non-ARDS patients, p = 0.384). Reliability of dynamic indices to predict FR remained consistent in ARDS patients, though with different thresholds. Collapsibility index of the superior vena cava (ΔSVC) showed the best predictive performance in both ARDS (area under the curve [AUC] = 0.763 [0.659-0.868]) and non-ARDS (AUC = 0.750 [0.698-0.802]) patients. A right to left ventricle end-diastolic area ratio  > 0.8 or paradoxical septal motion were strongly linked to the absence of FR (> 80% specificity). FR was not associated with intensive care unit (ICU) mortality (47% vs. 46%, p = 1). However, hypovolemia, defined as an aortic VTI increase  > 32% during PLR (median increase in patients with a partial SVC collapse) was independently associated with ICU mortality (odds ratio [OR] = 1.355 [1.077-1.705], p = 0.011), as well as pulse pressure variation (OR = 1.014 [1.001-1.026], p = 0.034)., Conclusion: Performance of dynamic indices to predict FR appears preserved in ARDS patients, albeit with distinct thresholds. Hypovolemia, indicated by a  > 32% increase in aortic VTI during PLR, rather than FR, was associated with ICU mortality in this population., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS)., Methods: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO 2 /FiO 2  < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60., Results: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups., Conclusions: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels., (© 2024. The Author(s).)

Purpose: Severe acute respiratory distress syndrome (ARDS) with PaO 2 /FiO 2  < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (V t ), moderate V t , prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS., Methods: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO 2 /FiO 2  < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence., Results: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low V t (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59-0.99, moderate certainty) and compared to moderate V t (RR 0.75, 95% CI 0.57-0.98, low certainty). Prone ventilation reduces mortality compared to moderate V t (RR 0.78, 95% CI 0.66-0.93, high certainty) and compared to low V t (RR 0.81, 95% CI 0.63-1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72-1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals., Conclusions: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate V t strategies. The impact of VV-ECMO versus prone ventilation remains uncertain., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decreased lung compliance and alveolar collapse. Lung function in ARDS could potentially be restored with surfactant replacement therapy, and synthetic surfactants with modified peptide analogues may better withstand inactivation in ARDS alveoli than natural surfactants., Methods: This study aimed to investigate the activity in vitro and the bolus effect (200 mg phospholipids/kg) of synthetic surfactant CHF5633 with analogues of SP-B and SP-C, or natural surfactant Poractant alfa (Curosurf ® , both preparations Chiesi Farmaceutici S.p.A.) in a severe ARDS model (the ratio of partial pressure arterial oxygen and fraction of inspired oxygen, P/F ratio ≤ 13.3 kPa) induced by hydrochloric acid instillation followed by injurious ventilation in adult New Zealand rabbits. The animals were ventilated for 4 h after surfactant treatment and the respiratory parameters, histological appearance of lung parenchyma and levels of inflammation, oxidative stress, surfactant dysfunction, and endothelial damage were evaluated., Results: Both surfactant preparations yielded comparable improvements in lung function parameters, reductions in lung injury score, pro-inflammatory cytokines levels, and lung edema formation compared to untreated controls., Conclusions: This study indicates that surfactant replacement therapy with CHF5633 improves lung function and lung architecture, and attenuates inflammation in severe ARDS in adult rabbits similarly to Poractant alfa. Clinical trials have so far not yielded conclusive results, but exogenous surfactant may be a valid supportive treatment for patients with ARDS given its anti-inflammatory and lung-protective effects., (© 2024. The Author(s).)

Purpose: Assessing efficacy of electrical impedance tomography (EIT) in optimizing positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) patients to enhance respiratory system mechanics and prevent ventilator-induced lung injury (VILI), compared to traditional methods., Methods: We carried out a systematic review and meta-analysis, spanning literature from January 2012 to May 2023, sourced from Scopus, PubMed, MEDLINE (Ovid), Cochrane, and LILACS, evaluated EIT-guided PEEP strategies in ARDS versus conventional methods. Thirteen studies (3 randomized, 10 non-randomized) involving 623 ARDS patients were analyzed using random-effects models for primary outcomes (respiratory mechanics and mechanical power) and secondary outcomes (PaO 2 /FiO 2 ratio, mortality, stays in intensive care unit (ICU), ventilator-free days)., Results: EIT-guided PEEP significantly improved lung compliance (n = 941 cases, mean difference (MD) = 4.33, 95% confidence interval (CI) [2.94, 5.71]), reduced mechanical power (n = 148, MD = - 1.99, 95% CI [- 3.51, - 0.47]), and lowered driving pressure (n = 903, MD = - 1.20, 95% CI [- 2.33, - 0.07]) compared to traditional methods. Sensitivity analysis showed consistent positive effect of EIT-guided PEEP on lung compliance in randomized clinical trials vs. non-randomized studies pooled (MD) = 2.43 (95% CI - 0.39 to 5.26), indicating a trend towards improvement. A reduction in mortality rate (259 patients, relative risk (RR) = 0.64, 95% CI [0.45, 0.91]) was associated with modest improvements in compliance and driving pressure in three studies., Conclusions: EIT facilitates real-time, individualized PEEP adjustments, improving respiratory system mechanics. Integration of EIT as a guiding tool in mechanical ventilation holds potential benefits in preventing ventilator-induced lung injury. Larger-scale studies are essential to validate and optimize EIT's clinical utility in ARDS management., (© 2024. The Author(s).)

Although the acute respiratory distress syndrome (ARDS) is well defined by the development of acute hypoxemia, bilateral infiltrates and non-cardiogenic pulmonary edema, ARDS is heterogeneous in terms of clinical risk factors, physiology of lung injury, microbiology, and biology, potentially explaining why pharmacologic therapies have been mostly unsuccessful in treating ARDS. Identifying phenotypes of ARDS and integrating this information into patient selection for clinical trials may increase the chance for efficacy with new treatments. In this review, we focus on classifying ARDS by the associated clinical disorders, physiological data, and radiographic imaging. We consider biologic phenotypes, including plasma protein biomarkers, gene expression, and common causative microbiologic pathogens. We will also discuss the issue of focusing clinical trials on the patient's phase of lung injury, including prevention, administration of therapy during early acute lung injury, and treatment of established ARDS. A more in depth understanding of the interplay of these variables in ARDS should provide more success in designing and conducting clinical trials and achieving the goal of personalized medicine.

Obesity is an important risk factor for major complications, morbidity and mortality related to intubation procedures and ventilation in the intensive care unit (ICU). The fall in functional residual capacity promotes airway closure and atelectasis formation. This narrative review presents the impact of obesity on the respiratory system and the key points to optimize airway management, noninvasive and invasive mechanical ventilation in ICU patients with obesity. Non-invasive strategies should first optimize body position with reverse Trendelenburg position or sitting position. Noninvasive ventilation (NIV) is considered as the first-line therapy in patients with obesity having a postoperative acute respiratory failure. Positive pressure pre-oxygenation before the intubation procedure is the method of reference. The use of videolaryngoscopy has to be considered by adequately trained intensivists, especially in patients with several risk factors. Regarding mechanical ventilation in patients with and without acute respiratory distress syndrome (ARDS), low tidal volume (6 ml/kg of predicted body weight) and moderate to high positive end-expiratory pressure (PEEP), with careful recruitment maneuver in selected patients, are advised. Prone positioning is a therapeutic choice in severe ARDS patients with obesity. Prophylactic NIV should be considered after extubation to prevent re-intubation. If obesity increases mortality and risk of ICU admission in the overall population, the impact of obesity on ICU mortality is less clear and several confounding factors have to be taken into account regarding the "obesity ICU paradox".

Purpose: The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV)., Methods: This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients., Results: A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH 2 O. Values of respiratory system compliance 35 (27-45) ml/cmH 2 O, plateau pressure 25 (22-29) cmH 2 O, and driving pressure 12 (10-16) cmH 2 O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93), p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97), p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients., Conclusions: In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards - treatments that have a solid evidence base and are well established as targets for usual care - and also evolving standards - treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

In ARDS patients, the change from supine to prone position generates a more even distribution of the gas-tissue ratios along the dependent-nondependent axis and a more homogeneous distribution of lung stress and strain. The change to prone position is generally accompanied by a marked improvement in arterial blood gases, which is mainly due to a better overall ventilation/perfusion matching. Improvement in oxygenation and reduction in mortality are the main reasons to implement prone position in patients with ARDS. The main reason explaining a decreased mortality is less overdistension in non-dependent lung regions and less cyclical opening and closing in dependent lung regions. The only absolute contraindication for implementing prone position is an unstable spinal fracture. The maneuver to change from supine to prone and vice versa requires a skilled team of 4-5 caregivers. The most frequent adverse events are pressure sores and facial edema. Recently, the use of prone position has been extended to non-intubated spontaneously breathing patients affected with COVID-19 ARDS. The effects of this intervention on outcomes are still uncertain.

Purpose: To investigate whether COVID-19-ARDS differs from all-cause ARDS., Methods: Thirty-two consecutive, mechanically ventilated COVID-19-ARDS patients were compared to two historical ARDS sub-populations 1:1 matched for PaO 2 /FiO 2 or for compliance of the respiratory system. Gas exchange, hemodynamics and respiratory mechanics were recorded at 5 and 15 cmH 2 O PEEP. CT scan variables were measured at 5 cmH 2 O PEEP., Results: Anthropometric characteristics were similar in COVID-19-ARDS, PaO 2 /FiO 2 -matched-ARDS and Compliance-matched-ARDS. The PaO 2 /FiO 2 -matched-ARDS and COVID-19-ARDS populations (both with PaO 2 /FiO 2 106 ± 59 mmHg) had different respiratory system compliances (Crs) (39 ± 11 vs 49.9 ± 15.4 ml/cmH 2 O, p = 0.03). The Compliance-matched-ARDS and COVID-19-ARDS had similar Crs (50.1 ± 15.7 and 49.9 ± 15.4 ml/cmH 2 O, respectively) but significantly lower PaO 2 /FiO 2 for the same Crs (160 ± 62 vs 106.5 ± 59.6 mmHg, p < 0.001). The three populations had similar lung weights but COVID-19-ARDS had significantly higher lung gas volume (PaO 2 /FiO 2 -matched-ARDS 930 ± 644 ml, COVID-19-ARDS 1670 ± 791 ml and Compliance-matched-ARDS 1301 ± 627 ml, p < 0.05). The venous admixture was significantly related to the non-aerated tissue in PaO 2 /FiO 2 -matched-ARDS and Compliance-matched-ARDS (p < 0.001) but unrelated in COVID-19-ARDS (p = 0.75), suggesting that hypoxemia was not only due to the extent of non-aerated tissue. Increasing PEEP from 5 to 15 cmH 2 O improved oxygenation in all groups. However, while lung mechanics and dead space improved in PaO 2 /FiO 2 -matched-ARDS, suggesting recruitment as primary mechanism, they remained unmodified or worsened in COVID-19-ARDS and Compliance-matched-ARDS, suggesting lower recruitment potential and/or blood flow redistribution., Conclusions: COVID-19-ARDS is a subset of ARDS characterized overall by higher compliance and lung gas volume for a given PaO 2 /FiO 2 , at least when considered within the timeframe of our study.

The World Health Organization defines overweight and obesity as the condition where excess or abnormal fat accumulation increases risks to health. The prevalence of obesity is increasing worldwide and is around 20% in ICU patients. Adipose tissue is highly metabolically active, and especially visceral adipose tissue has a deleterious adipocyte secretory profile resulting in insulin resistance and a chronic low-grade inflammatory and procoagulant state. Obesity is strongly linked with chronic diseases such as type 2 diabetes, hypertension, cardiovascular diseases, dyslipidemia, non-alcoholic fatty liver disease, chronic kidney disease, obstructive sleep apnea and hypoventilation syndrome, mood disorders and physical disabilities. In hospitalized and ICU patients and in patients with chronic illnesses, a J-shaped relationship between BMI and mortality has been demonstrated, with overweight and moderate obesity being protective compared with a normal BMI or more severe obesity (the still debated and incompletely understood "obesity paradox"). Despite this protective effect regarding mortality, in the setting of critical illness morbidity is adversely affected with increased risk of respiratory and cardiovascular complications, requiring adapted management. Obesity is associated with increased risk of AKI and infection, may require adapted drug dosing and nutrition and is associated with diagnostic and logistic challenges. In addition, negative attitudes toward obese patients (the social stigma of obesity) affect both health care workers and patients.

Purpose: We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO 2 R) to facilitate ultra-protective ventilation (V T 4 mL/kg and P PLAT  ≤ 25 cmH 2 O) in patients with moderate acute respiratory distress syndrome (ARDS)., Methods: Prospective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO 2 not increasing more than 20% from baseline, and arterial pH > 7.30. Severe adverse events (SAE) and ECCO 2 R-related adverse events (ECCO 2 R-AE) were reported to an independent data and safety monitoring board. We used lower CO 2 extraction and higher CO 2 extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30 m 2 ; flow 300-500 mL/min vs. 800-1000 mL/min, respectively)., Results: Ninety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68-89%) and 82% (78 out of 95 patients; 95% confidence interval 76-88%), respectively. ECCO 2 R was maintained for 5 [3-8] days. Six SAEs were reported; two of them were attributed to ECCO 2 R (brain hemorrhage and pneumothorax). ECCO 2 R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge., Conclusions: Use of ECCO 2 R to facilitate ultra-protective ventilation was feasible. A randomized clinical trial is required to assess the overall benefits and harms. CLINICALTRIALS.GOV: NCT02282657.

We report a case of a 20-year-old male patient suffering from motorcycle accident complicated by rapid development of severe refractory hypoxemia and hypercapnia due to serious bilateral lung contusions and lacerations. Positive pressure mechanical ventilation induced pressure-dependent massive air leak from disrupted pulmonary tissue. Simultaneous implementation of veno-venous extracorporeal membrane oxygenation together with surfactant application allowed prolonged disconnection of patient from mechanical ventilation ("total lung rest" mode). Despite considerable areas of nonaerated tissue on computed tomography prior to the disconnection from mechanical ventilation, almost total functional recovery of lungs was eventually achieved.

Purpose: Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV)., Methods: A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (P high ) set at the last plateau airway pressure (P plat ), not to exceed 30 cmH 2 O) and low airway pressure ( P low ) set at 5 cmH 2 O; the release phase (T low ) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; P plat not exceeding 30 cmH 2 O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO 2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, P plat , respiratory system compliance, and patient outcomes., Results: Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower P plat , and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance)., Conclusions: Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased P plat and reduced the duration of both mechanical ventilation and ICU stay.

Diaphragm weakness is highly prevalent in critically ill patients. It may exist prior to ICU admission and may precipitate the need for mechanical ventilation but it also frequently develops during the ICU stay. Several risk factors for diaphragm weakness have been identified; among them sepsis and mechanical ventilation play central roles. We employ the term critical illness-associated diaphragm weakness to refer to the collective effects of all mechanisms of diaphragm injury and weakness occurring in critically ill patients. Critical illness-associated diaphragm weakness is consistently associated with poor outcomes including increased ICU mortality, difficult weaning, and prolonged duration of mechanical ventilation. Bedside techniques for assessing the respiratory muscles promise to improve detection of diaphragm weakness and enable preventive or curative strategies. Inspiratory muscle training and pharmacological interventions may improve respiratory muscle function but data on clinical outcomes remain limited.

Purpose: Open lung strategy during ARDS aims to decrease the ventilator-induced lung injury by minimizing the atelectrauma and stress/strain maldistribution. We aim to assess how much of the lung is opened and kept open within the limits of mechanical ventilation considered safe (i.e., plateau pressure 30 cmH 2 O, PEEP 15 cmH 2 O)., Methods: Prospective study from two university hospitals. Thirty-three ARDS patients (5 mild, 10 moderate, 9 severe without extracorporeal support, ECMO, and 9 severe with it) underwent two low-dose end-expiratory CT scans at PEEP 5 and 15 cmH 2 O and four end-inspiratory CT scans (from 19 to 40 cmH 2 O). Recruitment was defined as the fraction of lung tissue which regained inflation. The atelectrauma was estimated as the difference between the intratidal tissue collapse at 5 and 15 cmH 2 O PEEP. Lung ventilation inhomogeneities were estimated as the ratio of inflation between neighboring lung units., Results: The lung tissue which is opened between 30 and 45 cmH 2 O (i.e., always closed at plateau 30 cmH 2 O) was 10 ± 29, 54 ± 86, 162 ± 92, and 185 ± 134 g in mild, moderate, and severe ARDS without and with ECMO, respectively (p < 0.05 mild versus severe without or with ECMO). The intratidal collapses were similar at PEEP 5 and 15 cmH 2 O (63 ± 26 vs 39 ± 32 g in mild ARDS, p = 0.23; 92 ± 53 vs 78 ± 142 g in moderate ARDS, p = 0.76; 110 ± 91 vs 89 ± 93, p = 0.57 in severe ARDS without ECMO; 135 ± 100 vs 104 ± 80, p = 0.32 in severe ARDS with ECMO). Increasing the applied airway pressure up to 45 cmH 2 O decreased the lung inhomogeneity slightly (but significantly) in mild and moderate ARDS, but not in severe ARDS., Conclusions: Data show that the prerequisites of the open lung strategy are not satisfied using PEEP up to 15 cmH 2 O and plateau pressure up to 30 cmH 2 O. For an effective open lung strategy, higher pressures are required. Therefore, risks of atelectrauma must be weighted versus risks of volutrauma., Trial Registration: Clinicaltrials.gov identifier: NCT01670747 ( www.clinicaltrials.gov ).