Impact of extended lung protection during mechanical ventilation on lung recovery in patients with COVID-19 ARDS: a phase II randomized controlled trial.

BACKGROUND: Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. METHODS: We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates. RESULTS: The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups. CONCLUSIONS: The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

Effects of Bariatric Surgery on Sarcopenic Obesity Outcomes: A One-Year Prospective Study in Middle-Aged Women.

INTRODUCTION: Sarcopenic obesity (SO) is characterised by the confluence of muscle deterioration and high adiposity. When non-surgical interventions prove insufficient, bariatric surgery (BS) becomes the primary approach. This study aimed to address BS effects on SO outcomes 1 year post-surgery among middle-aged women, also considering physical exercise's impact. METHODS: Prospective single-centre study of 140 patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between November 2019 and December 2022. Participants were categorised into tertiles according to SO's diagnosis and severity (group 1-patients with the most severe SO; group 2-intermediate; group 3-the least severe or without SO), calculated considering the consensus issued by ESPEN and EASO in 2022. Evaluations of clinical and biochemical parameters were conducted before and 12 months after BS, and the variation was used for comparative purposes. Body composition was assessed using bone density scans. Linear regression analysis accounted for both surgery type and baseline body mass index (BMI). RESULTS: Before BS, SO prevalence in the overall sample was 89.3%, decreasing to 2.9% after BS. Group 1 had more body fat mass (56.9 vs 54.8 vs 50.7 kg, p < 0.001), total, trunk and leg fat at baseline and a significantly lower total skeletal muscle mass (47.2 vs 49.4 vs 51.8 kg, p < 0.001). One year post-BS, group 1 presented more weight loss (- 39.8 ± 11.4 kg, p = 0.031), BMI reduction (- 15.9 ± 4.6 kg/m2, p = 0.005) and lost more fat mass (- 32.6 vs - 30.5 vs - 27.9 kg, p = 0.005), but not total skeletal muscle mass (- 5.8 vs - 5.9 vs - 6.8 kg, p = 0.130). Remission rates for comorbidities were substantial among all groups, but more marked among patients within group 1 (type 2 diabetes mellitus 75%, hypertension 47.1% and dyslipidemia 52.8%). Engagement in physical exercise of any kind has increased post-BS (33.1% vs 79.1%). CONCLUSION: Despite concerns about malabsorptive mechanisms potentially worsening muscle loss, patients with the most severe SO undergoing BS lost more fat mass while experiencing the smallest reduction in total skeletal muscle mass. Remission rates for comorbidities following BS were notable among all groups.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

High Mechanical Power and Driving Pressures are Associated With Postoperative Respiratory Failure Independent From Patients' Respiratory System Mechanics.

OBJECTIVES: High mechanical power and driving pressure (ΔP) have been associated with postoperative respiratory failure (PRF) and may be important parameters guiding mechanical ventilation. However, it remains unclear whether high mechanical power and ΔP merely reflect patients with poor respiratory system mechanics at risk of PRF. We investigated the effect of mechanical power and ΔP on PRF in cohorts after exact matching by patients' baseline respiratory system compliance. DESIGN: Hospital registry study. SETTING: Academic hospital in New England. PATIENTS: Adult patients undergoing general anesthesia between 2008 and 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was high (≥ 6.7 J/min, cohort median) versus low mechanical power and the key-secondary exposure was high (≥ 15.0 cm H 2 O) versus low ΔP. The primary endpoint was PRF (reintubation or unplanned noninvasive ventilation within seven days). Among 97,555 included patients, 4,030 (4.1%) developed PRF. In adjusted analyses, high intraoperative mechanical power and ΔP were associated with higher odds of PRF (adjusted odds ratio [aOR] 1.37 [95% CI, 1.25-1.50]; p < 0.001 and aOR 1.45 [95% CI, 1.31-1.60]; p < 0.001, respectively). There was large variability in applied ventilatory parameters, dependent on the anesthesia provider. This facilitated matching of 63,612 (mechanical power cohort) and 53,260 (ΔP cohort) patients, yielding identical baseline standardized respiratory system compliance (standardized difference [SDiff] = 0.00) with distinctly different mechanical power (9.4 [2.4] vs 4.9 [1.3] J/min; SDiff = -2.33) and ΔP (19.3 [4.1] vs 11.9 [2.1] cm H 2 O; SDiff = -2.27). After matching, high mechanical power and ΔP remained associated with higher risk of PRF (aOR 1.30 [95% CI, 1.17-1.45]; p < 0.001 and aOR 1.28 [95% CI, 1.12-1.46]; p < 0.001, respectively). CONCLUSIONS: High mechanical power and ΔP are associated with PRF independent of patient's baseline respiratory system compliance. Our findings support utilization of these parameters for titrating mechanical ventilation in the operating room and ICU.

Pronation Reveals a Heterogeneous Response of Global and Regional Respiratory Mechanics in Patients With Acute Hypoxemic Respiratory Failure.

OBJECTIVES: Experimental models suggest that prone position and positive end-expiratory pressure (PEEP) homogenize ventral-dorsal ventilation distribution and regional respiratory compliance. However, this response still needs confirmation on humans. Therefore, this study aimed to assess the changes in global and regional respiratory mechanics in supine and prone positions over a range of PEEP levels in acute respiratory distress syndrome (ARDS) patients. DESIGN: A prospective cohort study. PATIENTS: Twenty-two intubated patients with ARDS caused by COVID-19 pneumonia. INTERVENTIONS: Electrical impedance tomography and esophageal manometry were applied during PEEP titrations from 20 cm H2O to 6 cm H2O in supine and prone positions. MEASUREMENTS: Global respiratory system compliance (Crs), chest wall compliance, regional lung compliance, ventilation distribution in supine and prone positions. MAIN RESULTS: Compared with supine position, the maximum level of Crs changed after prone position in 59% of ARDS patients (n = 13), of which the Crs decreased in 32% (n = 7) and increased in 27% (n = 6). To reach maximum Crs after pronation, PEEP was changed in 45% of the patients by at least 4 cm H2O. After pronation, the ventilation and compliance of the dorsal region did not consistently change in the entire sample of patients, increasing specifically in a subgroup of patients who showed a positive change in Crs when transitioning from supine to prone position. These combined changes in ventilation and compliance suggest dorsal recruitment postpronation. In addition, the subgroup with increased Crs postpronation demonstrated the most pronounced difference between dorsal and ventral ventilation distribution from supine to prone position (p = 0.01), indicating heterogeneous ventilation distribution in prone position. CONCLUSIONS: Prone position modifies global respiratory compliance in most patients with ARDS. Only a subgroup of patients with a positive change in Crs postpronation presented a consistent improvement in dorsal ventilation and compliance. These data suggest that the response to pronation on global and regional mechanics can vary among ARDS patients, with some patients presenting more dorsal lung recruitment than others.

Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels. Sheep were protectively ventilated (16-24 h) and imaged for lung density, pulmonary capillary perfusion (13Nitrogen-saline), and inflammation (18F-fluorodeoxyglucose) using positron emission and computed tomography. We studied four conditions: permissive atelectasis (PEEP = 0 cmH2O); and ARDSNet low-stretch PEEP-setting strategy with supine moderate or mild endotoxemia, and prone mild endotoxemia. Perfusion/density heterogeneity increased pre-ARDS in all groups. Perfusion redistribution to density depended on ventilation strategy and endotoxemia level, producing more atelectasis in mild than moderate endotoxemia (P = 0.010) with the oxygenation-based PEEP-setting strategy. The spatial distribution of 18F-fluorodeoxyglucose uptake was related to local Q/D (P < 0.001 for Q/D group interaction). Moderate endotoxemia yielded markedly low/zero perfusion in normal-low density lung, with 13Nitrogen-saline perfusion indicating nondependent capillary obliteration. Prone animals' perfusion was remarkably homogeneously distributed with density. Lung perfusion redistributes heterogeneously to density during pre-ARDS protective ventilation in animals. This is associated with increased inflammation, nondependent capillary obliteration, and lung derecruitment susceptibility depending on endotoxemia level and ventilation strategy.NEW & NOTEWORTHY Perfusion redistribution does not follow lung density redistribution in the first 16-24 h of systemic endotoxemia and protective tidal volume mechanical ventilation. The same oxygenation-based positive end-expiratory pressure (PEEP)-setting strategy can lead at different endotoxemia levels to different perfusion redistributions, PEEP values, and lung aerations, worsening lung biomechanical conditions. During early acute lung injury, regional perfusion-to-tissue density ratio is associated with increased neutrophilic inflammation, and susceptibility to nondependent capillary occlusion and lung derecruitment, potentially marking and/or driving lung injury.

Effect of general anesthesia and controlled mechanical ventilation on pulmonary ventilation distribution assessed by electrical impedance tomography in healthy children.

INTRODUCTION: General anesthesia is associated with the development of atelectasis, which may affect lung ventilation. Electrical impedance tomography (EIT) is a noninvasive imaging tool that allows monitoring in real time the topographical changes in aeration and ventilation. OBJECTIVE: To evaluate the pattern of distribution of pulmonary ventilation through EIT before and after anesthesia induction in pediatric patients without lung disease undergoing nonthoracic surgery. METHODS: This was a prospective observational study including healthy children younger than 5 years who underwent nonthoracic surgery. Monitoring was performed continuously before and throughout the surgical period. Data analysis was divided into 5 periods: induction (spontaneous breathing, SB), ventilation-5min, ventilation-30min, ventilation-late and recovery-SB. In addition to demographic data, mechanical ventilation parameters were also collected. Ventilation impedance (Delta Z) and pulmonary ventilation distribution were analyzed cycle by cycle at the 5 periods. RESULTS: Twenty patients were included, and redistribution of ventilation from the posterior to the anterior region was observed with the beginning of mechanical ventilation: on average, the percentage ventilation distribution in the dorsal region decreased from 54%(IC95%:49-60%) to 49%(IC95%:44-54%). With the restoration of spontaneous breathing, ventilation in the posterior region was restored. CONCLUSION: There were significant pulmonary changes observed during anesthesia and controlled mechanical ventilation in children younger than 5 years, mirroring the findings previously described adults. Monitoring these changes may contribute to guiding the individualized settings of the mechanical ventilator with the goal to prevent postoperative complications.

Effect of flow rate on the end-expiratory lung volume in infants with bronchiolitis using high-flow nasal cannula evaluated through electrical impedance tomography.

OBJECTIVES: To evaluate the effects of four flow rates on the functional residual capacity (FRC) and pulmonary ventilation distribution while using a high-flow nasal cannula (HFNC). WORKING HYPOTHESIS: Our hypothesis is that flow rates below 1.5 L·kg-1 ·min-1 lead to FRC loss and respiratory distress. STUDY DESIGN: A single-center, prospective clinical study. PATIENT SELECTION: Infants diagnosed with acute viral bronchiolitis were given HFNC. METHODOLOGY: Through a prospective clinical study, the effects of four different flow rates, 2.0, 1.5, 1.0, and 0.5 L·kg-1 ·min-1 , on FRC and the pulmonary ventilation pattern were evaluated using electrical impedance tomography. The impedance variation (delta Z), end-expiratory lung volume (EELZ), respiratory rate, heart rate, respiratory distress score, and saturation/fraction of inspired oxygen ratio (SpO2 /FI O2 ), were also evaluated at each flow rate. RESULTS: Among the 11 infants included, There was a decrease in respiratory distress score at a flow rate of 1.5 L·kg-1 ·min-1 (*p = 0.021), and at a flow rate of 2.0 L·kg-1 ·min-1 (**p = 0.003) compared to 0.5 L·kg-1 ·min-1 . There was also a small but significant increase in SpO2 /FiO2 at flow rates of 1.5 (*p = 0.023), and 2.0 L·kg-1 ·min-1 (**p = 0.008) compared to 0.5 L·kg-1 ·min-1 . There were no other significant changes in the clinical parameters. In the global EELZ measurements, there was a significant increase under a flow rate of 2.0 L·kg-1 ·min-1 as compared to 0.5 L·kg-1 ·min-1 (p = 0.03). In delta Z values, there were no significant variations between the different flow rates. CONCLUSION: The ∆EELZ increases at the highest flow rates were accompanied by decreased distress scores and improved oxygenation.

Mechanical Power during General Anesthesia and Postoperative Respiratory Failure: A Multicenter Retrospective Cohort Study.

BACKGROUND: Mechanical power during ventilation estimates the energy delivered to the respiratory system through integrating inspiratory pressures, tidal volume, and respiratory rate into a single value. It has been linked to lung injury and mortality in the acute respiratory distress syndrome, but little evidence exists regarding whether the concept relates to lung injury in patients with healthy lungs. This study hypothesized that higher mechanical power is associated with greater postoperative respiratory failure requiring reintubation in patients undergoing general anesthesia. METHODS: In this multicenter, retrospective study, 230,767 elective, noncardiac adult surgical out- and inpatients undergoing general anesthesia between 2008 and 2018 at two academic hospital networks in Boston, Massachusetts, were included. The risk-adjusted association between the median intraoperative mechanical power, calculated from median values of tidal volume (Vt), respiratory rate (RR), positive end-expiratory pressure (PEEP), plateau pressure (Pplat), and peak inspiratory pressure (Ppeak), using the following formula: mechanical power (J/min) = 0.098 × RR × Vt × (PEEP + ½[Pplat - PEEP] + [Ppeak - Pplat]), and postoperative respiratory failure requiring reintubation within 7 days, was assessed. RESULTS: The median intraoperative mechanical power was 6.63 (interquartile range, 4.62 to 9.11) J/min. Postoperative respiratory failure occurred in 2,024 (0.9%) patients. The median (interquartile range) intraoperative mechanical power was higher in patients with postoperative respiratory failure than in patients without (7.67 [5.64 to 10.11] vs. 6.62 [4.62 to 9.10] J/min; P < 0.001). In adjusted analyses, a higher mechanical power was associated with greater odds of postoperative respiratory failure (adjusted odds ratio, 1.31 per 5 J/min increase; 95% CI, 1.21 to 1.42; P < 0.001). The association between mechanical power and postoperative respiratory failure was robust to additional adjustment for known drivers of ventilator-induced lung injury, including tidal volume, driving pressure, and respiratory rate, and driven by the dynamic elastic component (adjusted odds ratio, 1.35 per 5 J/min; 95% CI, 1.05 to 1.73; P = 0.02). CONCLUSIONS: Higher mechanical power during ventilation is statistically associated with a greater risk of postoperative respiratory failure requiring reintubation.

Phrenic Nerve Block and Respiratory Effort in Pigs and Critically Ill Patients with Acute Lung Injury.

BACKGROUND: Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. METHODS: An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. RESULTS: Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. CONCLUSIONS: Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation.

Ventilatory Variables and Mechanical Power in Patients with Acute Respiratory Distress Syndrome.

Rationale: Mortality in acute respiratory distress syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower Vt, lower driving pressure (ΔP), lower respiratory rates (RR), and higher end-expiratory pressure have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from the ventilator to the patient, calculated from a combination of several ventilator variables.Objectives: To assess the impact of mechanical power on mortality in patients with ARDS as compared with that of primary ventilator variables such as the ΔP, Vt, and RR.Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of patients with ARDS who had participated in six randomized clinical trials of protective mechanical ventilation and one large observational cohort of patients with ARDS. The primary outcome was mortality at 28 days or 60 days.Measurements and Main Results: We included 4,549 patients (38% women; mean age, 55 ± 23 yr). The average mechanical power was 0.32 ± 0.14 J · min-1 · kg-1 of predicted body weight, the ΔP was 15.0 ± 5.8 cm H2O, and the RR was 25.7 ± 7.4 breaths/min. The driving pressure, RR, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of the ΔP on mortality was four times as large as that of the RR.Conclusions: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS, but a simpler model using only the ΔP and RR was equivalent.

Electrical impedance tomography in pulmonary arterial hypertension.

The characterization of pulmonary arterial hypertension (PAH) relies mainly on right heart catheterization (RHC). Electrical impedance tomography (EIT) provides a non-invasive estimation of lung perfusion that could complement the hemodynamic information from RHC. To assess the association between impedance variation of lung perfusion (ΔZQ) and hemodynamic profile, severity, and prognosis, suspected of PAH or worsening PAH patients were submitted simultaneously to RHC and EIT. Measurements of ΔZQ were obtained. Based on the results of the RHC, 35 patients composed the PAH group, and eight patients, the normopressoric (NP) group. PAH patients showed a significantly reduced ΔZQ compared to the NP group. There was a significant correlation between ΔZQ and hemodynamic parameters, particularly with stroke volume (SV) (r = 0.76; P < 0.001). At 60 months, 15 patients died (43%) and 1 received lung transplantation; at baseline they had worse hemodynamics, and reduced ΔZQ when compared to survivors. Patients with low ΔZQ (≤154.6%.Kg) presented significantly worse survival (P = 0.033). ΔZQ is associated with hemodynamic status of PAH patients, with disease severity and survival, demonstrating EIT as a promising tool for monitoring patients with pulmonary vascular disease.

Effect of Lowering Vt on Mortality in Acute Respiratory Distress Syndrome Varies with Respiratory System Elastance.

Rationale: If the risk of ventilator-induced lung injury in acute respiratory distress syndrome (ARDS) is causally determined by driving pressure rather than by Vt, then the effect of ventilation with lower Vt on mortality would be predicted to vary according to respiratory system elastance (Ers). Objectives: To determine whether the mortality benefit of ventilation with lower Vt varies according to Ers. Methods: In a secondary analysis of patients from five randomized trials of lower- versus higher-Vt ventilation strategies in ARDS and acute hypoxemic respiratory failure, the posterior probability of an interaction between the randomized Vt strategy and Ers on 60-day mortality was computed using Bayesian multivariable logistic regression. Measurements and Main Results: Of 1,096 patients available for analysis, 416 (38%) died by Day 60. The posterior probability that the mortality benefit from lower-Vt ventilation strategies varied with Ers was 93% (posterior median interaction odds ratio, 0.80 per cm H2O/[ml/kg]; 90% credible interval, 0.63-1.02). Ers was classified as low (<2 cm H2O/[ml/kg], n = 321, 32%), intermediate (2-3 cm H2O/[ml/kg], n = 475, 46%), and high (>3 cm H2O/[ml/kg], n = 224, 22%). In these groups, the posterior probabilities of an absolute risk reduction in mortality ≥ 1% were 55%, 82%, and 92%, respectively. The posterior probabilities of an absolute risk reduction ≥ 5% were 29%, 58%, and 82%, respectively. Conclusions: The mortality benefit of ventilation with lower Vt in ARDS varies according to elastance, suggesting that lung-protective ventilation strategies should primarily target driving pressure rather than Vt.