Acute respiratory distress syndrome (ARDS) is a common condition in intensive care medicine. Various intra- and extrapulmonal causes may trigger an epithelial and endothelial permeability increase, which leads to impaired gas exchange due to fluid overload of the alveoli and transmigration of leukocytes. This results in hypoxemia and hypercapnia, as well as deleterious consequences for the macro- and microcirculation with the risk of multi-organ failure and high mortality. This review summarizes ARDS pathophysiology and clinical consequences.

Background: Acute respiratory distress syndrome (ARDS) occurs commonly in intensive care units. The reported mortality rates in studies evaluating ARDS are highly variable. Objective: To investigate mortality rates due to ARDS from before the 2009 H1N1 influenza pandemic began until the start of coronavirus disease 2019 (COVID-19) pandemic. Design: We performed a systematic search and then ran a proportional meta-analysis for mortality. We ran our analysis in three ways: for randomised controlled trials only, for observational studies only, and for randomised controlled trials and observational studies combined. Data sources: MEDLINE and Embase, using a highly sensitive criterion and limiting the search to studies published from January 2009 to December 2019. Review methods: Two of us independently screened titles and abstracts to first identify studies and then complete full text reviews of selected studies. We assessed risk of bias using the Cochrane RoB-2 (a risk-of-bias tool for randomised trials) and the Cochrane ROBINS-1 (a risk-of-bias tool for non-randomised studies of interventions). Results: We screened 5844 citations, of which 102 fully met our inclusion criteria. These included 34 randomised controlled trials and 68 observational studies, with a total of 24 158 patients. The weighted pooled mortality rate for all 102 studies published from 2009 to 2019 was 39.4% (95% CI, 37.0-41.8%). Mortality was higher in observational studies compared with randomised controlled trials (41.8% [95% CI, 38.9-44.8%] v 34.5% [95% CI, 30.6-38.5%]; P = 0.005). Conclusions: Over the past decade, mortality rates due to ARDS were high. There is a clear distinction between mortality in observational studies and in randomised controlled trials. Future studies need to report mortality for different ARDS phenotypes and closely adhere to evidence-based medicine. PROSPERO registration: CRD42020149712 (April 2020).

The novel coronavirus, which was declared a pandemic by the World Health Organization in early 2020 has brought with itself major morbidity and mortality. It has increased hospital occupancy, heralded economic turmoil, and the rapid transmission and community spread have added to the burden of the virus. Most of the patients are admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure often secondary to acute respiratory distress syndrome (ARDS). Based on the limited data available, there have been different opinions about the respiratory mechanics of the ARDS caused by coronavirus disease 2019 (COVID-19). Our article provides an insight into COVID-19 pathophysiology and how it differs from typical ARDS. Based on these differences, our article explains the different approach to ventilation in COVID-19 ARDS compared to typical ARDS. We critically analyze the role of positive end-expiratory pressure (PEEP) and proning in the ICU patients. Through the limited data and clinical experience are available, we believe that early proning in COVID-19 patients improves oxygenation and optimal PEEP should be titrated based on individual lung compliance.

Clinical and epidemiological differences between acute respiratory distress syndrome (ARDS) that presents at the initiation of mechanical ventilation [MV] (ARDS at MV onset) and that which develops during the course of MV (ARDS after MV onset) are not well understood. We conducted an observational study in five Peruvian ICUs to characterize differences between ARDS at MV onset and after MV onset and identify risk factors for the development of ARDS after MV onset.

We consecutively enrolled critically ill patients with acute respiratory failure requiring at least 24 h of mechanical ventilation and followed them prospectively during the first 28 days and compared baseline characteristics and clinical outcomes by ARDS status.

We enrolled 1657 participants on MV (mean age 60.0 years, 55% males) of whom 334 (20.2%) had ARDS at MV onset and 180 (10.9%) developed ARDS after MV onset. Average tidal volume at the initiation of MV was 8.7 mL/kg of predicted body weight (PBW) for participants with ARDS at MV onset, 8.6 mL/kg PBW for those who developed ARDS after MV onset, and 8.5 mL/kg PBW for those who never developed ARDS (p = 0.23). Overall, 90-day mortality was 56% and 55% for ARDS after MV onset and ARDS at MV onset, respectively, as compared to 46% among those who never developed ARDS (p < 0.01). Adults with ARDS had a higher body mass index (BMI) than those without ARDS (27.3 vs 26.5 kg/m2, p < 0.01). Higher peak pressure (adjusted interquartile OR = 1.51, 95% CI 1.21-1.88), higher mean airway pressure (adjusted interquartile OR = 1.41, 95% CI 1.13-1.76), and higher positive end-expiratory pressure (adjusted interquartile OR = 1.29, 95% CI 1.10-1.50) at MV onset were associated with a higher odds of developing ARDS after MV onset.

In this study of mechanically ventilated patients, 31% of study participants had ARDS at some point during their ICU stay. Optimal lung-protective ventilation was not used in a majority of patients. Patients with ARDS after MV onset had a similar 90-day mortality as those with ARDS at MV onset. Higher airway pressures at MV onset, higher PEEP, and higher BMI were associated with the development of ARDS after MV onset.

Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia.

In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis.

There was a significant decrease in partial pressure of oxygen in arterial blood (PaO₂) for both groups at T2 and T3 compared to T1 but in group B the PaO₂ at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO₂) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO₂ and PaCO₂ between the groups.

Decreased oxygenation by pneumoperitoneum was improved and PaCO₂ did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

This study aimed to apply the dead space fraction [ratio of dead space to tidal volume (VD/VT)] to titrate the optimal positive end-expiratory pressure (PEEP) in a swine model of acute respiratory distress syndrome (ARDS). Twelve swine models of ARDS were constructed. A lung recruitment maneuver was then conducted and the PEEP was set at 20 cm H₂O. The PEEP was reduced by 2 cm H₂O every 10 min until 0 cm H₂O was reached, and VD/VT was measured after each decrement step. VD/VT was measured using single-breath analysis of CO₂, and calculated from arterial CO₂ partial pressure (PaCO₂) and mixed expired CO₂ (PeCO₂) using the following formula: VD/VT = (PaCO₂ - PeCO₂)/PaCO₂. The optimal PEEP was identified by the lowest VD/VT method. Respiration and hemodynamic parameters were recorded during the periods of pre-injury and injury, and at 4 and 2 cm H₂O below and above the optimal PEEP (Po). The optimal PEEP in this study was found to be 13.25±1.36 cm H₂O. During the Po period, VD/VT decreased to a lower value (0.44±0.08) compared with that during the injury period (0.68±0.10) (P<0.05), while the intrapulmonary shunt fraction reached its lowest value. In addition, a significant change of dynamic tidal respiratory compliance and oxygenation index was induced by PEEP titration. These results indicate that minimal VD/VT can be used for PEEP titration in ARDS.

Noninvasive ventilation (NIV) is used as an initial ventilatory support in acute respiratory distress syndrome (ARDS), but its utility is unclear, and persistence in those who do not improve may delay intubation and lead to adverse outcomes. Hence, it becomes imperative to have a clear understanding of selecting patients who will benefit from this modality.

In this prospective observational study, we included all consecutive adults, over a 3-year period, who fulfilled criteria for ARDS by the Berlin definition. Basic demographics, ventilatory support, intensive care unit course, and outcome were recorded.

Of 170 patients, 96 (56.47%) were initially managed with NIV. Noninvasive ventilation failure was seen in 42 (43.75%) of 96, and low baseline PaO2/FIO2, shock, and ARDS severity were associated with NIV failure. Overall intensive care unit mortality was 63 (37.1%) of 170, and high Acute Physiology and Chronic Health Evaluation II score, low PaO2/FIO2, shock, and ARDS severity were associated with increased mortality. Noninvasive ventilation failure and mortality were significantly higher in moderate and severe ARDS.

Noninvasive ventilation maybe useful in selected patients with mild ARDS but should be used with great caution in moderate and severe ARDS, as failure risk is high. In addition, low PaO2/FIO2 and shock are associated with NIV failure. Acute Physiology and Chronic Health Evaluation II score, shock, low PaO2/FIO2, and ARDS severity are associated with increased mortality.

Acute Respiratory Distress Syndrome (ARDS) is due to many causes. The absence of a universal definition up until now has led to a series of practical problems for a definitive diagnosis. The incidences of ARDS and Acute Lung Injury (ALI) vary widely in the current literature. The American-European Consensus Conference definition has been applied since its publication in 1994 and has helped to improve knowledge about ARDS. However, 18 years later, in 2011, the European Intensive Medicine Society, requested a team of international experts to meet in Berlin to review the ARDS definition. The purpose of the Berlin definition is not to use it as a prognostic tool, but to improve coherence between research and clinical practice.

Lung tissue of patients with acute respiratory distress syndrome (ARDS) is heterogeneously damaged and prone to develop atelectasis. During inflation, atelectatic regions may exhibit alveolar recruitment accompanied by prolonged filling with air in contrast to regions with already open alveoli with a fast increase in regional aeration. During deflation, derecruitment of injured regions is possible with ongoing loss in regional aeration. The aim of our study was to assess the dynamics of regional lung aeration in mechanically ventilated patients with ARDS and its dependency on positive end-expiratory pressure (PEEP) using electrical impedance tomography (EIT).

Twelve lung healthy and twenty ARDS patients were examined by EIT during sustained step increases in airway pressure from 0, 8 and 15 cm H2O to 35 cm H2O and during subsequent step decrease to the corresponding PEEP. Regional EIT waveforms in the ventral and dorsal lung regions were fitted to bi-exponential equations. Regional fast and slow respiratory time constants and the sizes of the fast and slow compartments were subsequently calculated.

ARDS patients exhibited significantly lower fast and slow time constants than the lung healthy patients in ventral and dorsal regions. The time constants were significantly affected by PEEP and differed between the regions. The size of the fast compartment was significantly lower in ARDS patients than in patients with healthy lung under all studied conditions.

These results show that regional lung mechanics can be assessed by EIT. They reflect the lower respiratory system compliance of injured lungs and imply more pronounced regional recruitment and derecruitment in ARDS patients.

Our objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition.

The European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2 days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision.

The Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1 week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO(2)/FiO(2) thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy.

This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice.

The delicate structure of the lung epithelium makes it susceptible to surface tension induced injury. For example, the cyclic reopening of collapsed and/or fluid-filled airways during the ventilation of injured lungs generates hydrodynamic forces that further damage the epithelium and exacerbate lung injury. The interactions responsible for epithelial injury during airway reopening are fundamentally multiscale, since air-liquid interfacial dynamics affect global lung mechanics, while surface tension forces operate at the molecular and cellular scales. This article will review the current state-of-knowledge regarding the effect of surface tension forces on (a) the mechanics of airway reopening and (b) epithelial cell injury. Due to the complex nature of the liquid-epithelium system, a combination of computational and experimental techniques are being used to elucidate the mechanisms of surface-tension induced lung injury. Continued research is leading to an integrated understanding of the biomechanical and biological interactions responsible for cellular injury during airway reopening. This information may lead to novel therapies that minimize ventilation induced lung injury.

To perform a systematic review and meta-analysis of the literature to evaluate the effects of high PEEP versus conventional PEEP on mortality and on the risk of barotrauma in patients with the acute respiratory distress syndrome (ARDS).

Computer search of Medline, Embase, CINAHL, CANCERLIT, Pascal-Biomed, ACP Journal Club, Cochrane library (CDSR, DARE, CCTR), ISI Proceedings, Current Contents, and Web of Science, as well as manual search of selected references.

Controlled random clinical trials published after NAECC (1994) that evaluated the effect of two levels of PEEP and that reported the mortality and incidence of barotrauma in the series.

By two investigators working independently, with discrepancies resolved by group consensus. Contingency tables were elaborated and the RRs with corresponding confidence intervals were obtained for each study.

Four articles were selected for the meta-analysis of mortality and three for the meta-analysis of barotrauma. No effects of PEEP level on mortality were found (RR 0.73, 95% CI: 0.49 to 1.10) or on the incidence of barotrauma (RR 0.50, 95% CI: 0.14 to 1.73). However, an analysis of the studies in which PEEP was individualized in function of Pflex showed a significant decrease in mortality (RR 0.59, 95% CI: 0.43 to 0.82) (p=0.001)

The use of high or conventional PEEP in function of oxygenation does not affect mortality or the incidence of barotrauma in patients with ARDS. However, there might be a decrease in mortality associated to high PEEP individualized in function of the pulmonary mechanics of each patient.

This article describes the pathophysiologic basis and clinical role for lung recruitment maneuvers. It reviews the literature and presents the authors' clinical experience of over 15 years in the collaboration between Erasmus MC and the University of Rochester. The authors are hopeful that these lung-protective strategies are presented in a useful format that may be useful to the practicing intensivist, thus bringing laboratory and clinical research to bedside practice.

This review addresses the physiological background and the current status of evidence regarding ventilator-induced lung injury and lung protective strategies. Lung protective ventilatory strategies have been shown to reduce mortality from adult respiratory distress syndrome (ARDS). We review the latest knowledge on the progression of lung injury by mechanical ventilation and correlate the findings of experimental work with results from clinical studies. We describe the experimental and clinical evidence of the effect of lung protective ventilatory strategies and open lung strategies on the progression of lung injury and current controversies surrounding these subjects. We describe a rational strategy, the open lung strategy, to accomplish an open lung, which may further prevent injury caused by mechanical ventilation. Finally, the clinician is offered directions on lung protective ventilation in the early phase of ARDS which can be applied on the intensive care unit.

Kinetic therapy (KT) has been shown to reduce complications and to shorten hospital stay in trauma patients. Data in non-surgical patients are inconclusive, and kinetic therapy has not been tested in patients with cardiogenic shock.

The present analysis compares KT with standard care in patients with cardiogenic shock.

A retrospective analysis of 133 patients with cardiogenic shock admitted to 1 academic heart center was performed. Patients with standard care (SC, turning every 2 h by the staff) were compared with kinetic therapy (KT, using oscillating air-flotation beds).

68 patients with KT were compared with 65 patients with SC. Length of ventilator therapy was 11 days in KT and 18 days in SC (p=0.048). The mortality was comparable in both groups. Pneumonia occurred in 14 patients in KT and 39 patients in SC (p<0.001); pressure ulcers were reduced by 50% (p<0.001). Length of ICU stay (21 days in SC and 13 days in KT, p=0.009) and length of hospital stay were reduced in the patients treated with kinetic therapy.

The use of KT shortens hospital stay and reduces rates of pneumonia and pressure ulcers as compared to SC.

In the acute respiratory distress syndrome (ARDS), positive end-expiratory pressure (PEEP) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed. Since the effects of PEEP probably depend on the recruitability of lung tissue, we conducted a study to examine the relationship between the percentage of potentially recruitable lung, as indicated by computed tomography (CT), and the clinical and physiological effects of PEEP.

Sixty-eight patients with acute lung injury or ARDS underwent whole-lung CT during breath-holding sessions at airway pressures of 5, 15, and 45 cm of water. The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored at airway pressures between 5 and 45 cm of water.

The percentage of potentially recruitable lung varied widely in the population, accounting for a mean (+/-SD) of 13+/-11 percent of the lung weight, and was highly correlated with the percentage of lung tissue in which aeration was maintained after the application of PEEP (r2=0.72, P<0.001). On average, 24 percent of the lung could not be recruited. Patients with a higher percentage of potentially recruitable lung (greater than the median value of 9 percent) had greater total lung weights (P<0.001), poorer oxygenation (defined as a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen) (P<0.001) and respiratory-system compliance (P=0.002), higher levels of dead space (P=0.002), and higher rates of death (P=0.02) than patients with a lower percentage of potentially recruitable lung. The combined physiological variables predicted, with a sensitivity of 71 percent and a specificity of 59 percent, whether a patient's proportion of potentially recruitable lung was higher or lower than the median.

In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP.

Most critical care physicians believe that randomized, controlled trials provide the best available evidence. This review contends that the importance of randomized, controlled trials was overemphasized and that they do not add more to knowledge and practice than physiologic and observational studies. In addition, protection of both patients and proxies may be less adequately ensured during randomized, controlled trials than during observational studies.

An analysis of the recent literature on critical care shows that conclusions from randomized, controlled trials are either disputable or do not affect existing practice. In addition, several papers reveal potential conflicts between randomized, controlled trials and ethical principles.

We may see in the future the twilight of randomized, controlled trials in critically ill patients because scientific, ethical, and sociologic substrata will be progressively lacking as will be funding.

The purpose of this paper is to review the mechanisms of ventilator-induced lung injury as a basis for providing the less damaging mechanical ventilation in patients with acute respiratory failure.

In normal lungs, high tidal volume causes an immediate gene upregulation and downregulation. Although the importance of alveolar inflammatory reaction is well known, recent findings suggest the potential role of airway distension in causing ventilator-induced lung injury. The initial activation has been shown to occur in the airways, accounting for the damages induced by high peak flow. The healthier lung regions are more exposed to the injury, since they may be subjected to strain. Challenge with endotoxin enhances in a synergistic manner the pulmonary inflammation induced by mechanical ventilation. However, mechanical strain and endotoxin seem to trigger lung inflammation through two different pathways. Despite convincing experimental and clinical evidences of lung injury, the clinical implementation of low tidal volume ventilation is still limited and has not yet become part of standard clinical practice. Setting positive end-expiratory pressure remains an open problem because the ALVEOLI study did not provide any exhaustive answers, likely because of methodologic problems and, unphysiologic design.

Gentle lung ventilation must be standard practice. Because stress and strain are the triggers of ventilator-induced lung injury, their clinical equivalents should be measured (transpulmonary pressure and the ratio between tidal volume and end-expiratory lung volume). For a rational application of positive end-expiratory pressure, the potential for recruitment in any single patient should be estimated.

With biologically variable ventilation [BVV--using a computer-controller to add breath-to-breath variability to respiratory frequency (f) and tidal volume (VT)] gas exchange and respiratory mechanics were compared using the ARDSNet low VT algorithm (Control) versus an approach using mathematical modelling to individually optimise VT at the point of maximal compliance change on the convex portion of the inspiratory pressure-volume (P-V) curve (Experimental).

Pigs (n = 22) received pentothal/midazolam anaesthesia, oleic acid lung injury, then inspiratory P-V curve fitting to the four-parameter logistic Venegas equation F(P) = a + b[1 + e-(P-c)/d]-1 where: a = volume at lower asymptote, b = the vital capacity or the total change in volume between the lower and upper asymptotes, c = pressure at the inflection point and d = index related to linear compliance. Both groups received BVV with gas exchange and respiratory mechanics measured hourly for 5 hrs. Postmortem bronchoalveolar fluid was analysed for interleukin-8 (IL-8).

All P-V curves fit the Venegas equation (R2 > 0.995). Control VT averaged 7.4 +/- 0.4 mL/kg as compared to Experimental 9.5 +/- 1.6 mL/kg (range 6.6 - 10.8 mL/kg; p < 0.05). Variable VTs were within the convex portion of the P-V curve. In such circumstances, Jensen's inequality states "if F(P) is a convex function defined on an interval (r, s), and if P is a random variable taking values in (r, s), then the average or expected value (E) of F(P); E(F(P)) > F(E(P))." In both groups the inequality applied, since F(P) defines volume in the Venegas equation and (P) pressure and the range of VTs varied within the convex interval for individual P-V curves. Over 5 hrs, there were no significant differences between groups in minute ventilation, airway pressure, blood gases, haemodynamics, respiratory compliance or IL-8 concentrations.

No difference between groups is a consequence of BVV occurring on the convex interval for individualised Venegas P-V curves in all experiments irrespective of group. Jensen's inequality provides theoretical proof of why a variable ventilatory approach is advantageous under these circumstances. When using BVV, with VT centred by Venegas P-V curve analysis at the point of maximal compliance change, some leeway in low VT settings beyond ARDSNet protocols may be possible in acute lung injury. This study also shows that in this model, the standard ARDSNet algorithm assures ventilation occurs on the convex portion of the P-V curve.

This paper aims to provide a condensed review of the most essential and current research findings in the field of acute lung injury over the past year.

We review the most recent important findings in both laboratory-based and clinical research in the field of acute lung injury. Significant advances have been made in the past year with respect to our understanding of the pathogenesis of acute lung injury, and how key pathological events relate to prognosis, outcomes, and the promise of new potential therapeutic interventions. In particular, significant advances have been made in our understanding of the prognostic roles of neutrophil recruitment and clearance, fibrinogenesis, inflammatory cytokines, alveolar fluid clearance, and endothelial injury and activation. Paramount studies have provided greater skepticism over the efficacy of prone positioning and the currently available surfactant replacement therapies. In addition, new research has fostered an improved appreciation of the long-term sequelae of acute lung injury.

Recent advances in our understanding of the pathogenesis of acute lung injury have provided the promise of exciting potential interventions to modify intravascular and extravascular fibrinogenesis, neutrophil activation and clearance, and alveolar fluid clearance. Our new understanding of prolonged disability and post-traumatic stress in acute lung injury survivors will ultimately change the standard for how these patients are managed in the intensive care unit and followed beyond their hospital stay.

A recent study by the Acute Respiratory Distress Syndrome Network compared the traditional lower end-expiratory pressure strategy with a higher end-expiratory pressure strategy in patients with the acute respiratory distress syndrome ventilated with low tidal volumes. Clinical outcomes were similar whether lower or higher positive end-expiratory pressure (PEEP) levels were used. We applied both the lower (9 +/- 2 cm H2O) and higher (16 +/- 1 cm H2O) PEEP strategy in 19 patients. In nine recruiters, the higher end-expiratory pressure strategy resulted in significant alveolar recruitment (587 +/- 158 ml), improvement in arterial oxygen partial pressure/inspired oxygen fraction ratio (from 150 +/- 36 to 396 +/- 138), and reduction in static lung elastance (from 23 +/- 3 to 20 +/- 2 cm H2O/L). In 10 nonrecruiters, alveolar recruitment was minimal, oxygenation did not improve, and static lung elastance significantly increased (from 26 +/- 5 to 28 +/- 6 cm H2O/L). The increase in oxygenation, the reduction in static lung elastance, and the shape of the volume-pressure curve during the lower PEEP strategy were independently associated with alveolar recruitment. In conclusion, the protocol proposed by the Acute Respiratory Distress Syndrome Network, lacking solid physiologic basis, frequently fails to induce alveolar recruitment and may increase the risk of alveolar overinflation.