ABSTRACT
BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with one-way endobronchial valves (EBV) has better outcomes when the target lobe has poor collateral ventilation, resulting in complete lobe atelectasis. High-inspired oxygen fraction (FIO2) promotes atelectasis through faster gas absorption after airway occlusion, but its application during BLVR with EBV has been poorly understood. We aimed to investigate the real-time effects of FIO2 on regional lung volumes and regional ventilation/perfusion by electrical impedance tomography (EIT) during BLVR with EBV. METHODS: Six piglets were submitted to left lower lobe occlusion by a balloon-catheter and EBV valves with FIO2 0.5 and 1.0. Regional end-expiratory lung impedances (EELI) and regional ventilation/perfusion were monitored. Local pocket pressure measurements were obtained (balloon occlusion method). One animal underwent simultaneous acquisitions of computed tomography (CT) and EIT. Regions-of-interest (ROIs) were right and left hemithoraces. RESULTS: Following balloon occlusion, a steep decrease in left ROI-EELI with FIO2 1.0 occurred, 3-fold greater than with 0.5 (p < 0.001). Higher FIO2 also enhanced the final volume reduction (ROI-EELI) achieved by each valve (p < 0.01). CT analysis confirmed the denser atelectasis and greater volume reduction achieved by higher FIO2 (1.0) during balloon occlusion or during valve placement. CT and pocket pressure data agreed well with EIT findings, indicating greater strain redistribution with higher FIO2. CONCLUSIONS: EIT demonstrated in real-time a faster and more complete volume reduction in the occluded lung regions under high FIO2 (1.0), as compared to 0.5. Immediate changes in the ventilation and perfusion of ipsilateral non-target lung regions were also detected, providing better estimates of the full impact of each valve in place. TRIAL REGISTRATION: Not applicable.
Subject(s)
Bronchoscopy , Electric Impedance , Animals , Swine , Bronchoscopy/methods , Pneumonectomy/methods , Lung/diagnostic imaging , Lung/physiopathology , Lung/surgery , Lung/physiology , Tomography/methods , Pulmonary Atelectasis/diagnostic imaging , Pulmonary Atelectasis/physiopathology , Lung Volume Measurements/methods , Time FactorsABSTRACT
BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.
Subject(s)
Respiratory Distress Syndrome , Tomography, X-Ray Computed , Male , Female , Swine , Animals , Electric Impedance , Respiratory Distress Syndrome/therapy , Lung , Perfusion , Tomography/methodsABSTRACT
BACKGROUND: A protective intra-operative lung ventilation strategy has been widely recommended for laparoscopic surgery. However, there is no consensus regarding the optimal level of positive end-expiratory pressure (PEEP) and its effects during pneumoperitoneum. Electrical impedance tomography (EIT) has recently been introduced as a bedside tool to monitor lung ventilation in real-time. OBJECTIVE: We hypothesised that individually titrated EIT-PEEP adjusted to the surgical intervention would improve respiratory mechanics during and after surgery. DESIGN: Randomised controlled trial. SETTING: First Medical Centre of Chinese PLA General Hospital, Beijing. PATIENTS: Seventy-five patients undergoing robotic-assisted laparoscopic hepatobiliary and pancreatic surgery under general anaesthesia. INTERVENTIONS: Patients were randomly assigned 2â:â1 to individualised EIT-titrated PEEP (PEEPEIT; nâ=â50) or traditional PEEP 5âcmH2O (PEEP5âcmH2O; nâ=â25). The PEEPEIT group received individually titrated EIT-PEEP during pneumoperitoneum. The PEEP5âcmH2O group received PEEP of 5âcmH2O during pneumoperitoneum. MAIN OUTCOME MEASURES: The primary outcome was respiratory system compliance during laparoscopic surgery. Secondary outcomes were individualised PEEP levels, oxygenation, respiratory and haemodynamic status, and occurrence of postoperative pulmonary complications (PPCs) within 7âdays. RESULTS: Compared with PEEP5âcmH2O, patients who received PEEPEIT had higher respiratory system compliance (mean values during surgery of 44.3â±â11.3 vs. 31.9â±â6.6,âmlâcmH2O-1; Pâ<â0.001), lower driving pressure (11.5â±â2.1 vs. 14.0â±â2.4âcmH2O; Pâ<â0.001), better oxygenation (mean PaO2/FiO2 427.5â±â28.6 vs. 366.8â±â36.4; Pâ=â0.003), and less postoperative atelectasis (19.4â±â1.6 vs. 46.3â±â14.8âg of lung tissue mass; Pâ=â0.003). Haemodynamic values did not differ significantly between the groups. No adverse effects were observed during surgery. CONCLUSION: Individualised PEEP by EIT may improve intra-operative pulmonary mechanics and oxygenation without impairing haemodynamic stability, and decrease postoperative atelectasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (www.chictr.org.cn) identifier: ChiCTR2100045166.
Subject(s)
Pneumoperitoneum , Pulmonary Atelectasis , Humans , Electric Impedance , Pneumoperitoneum/etiology , Lung/diagnostic imaging , Positive-Pressure Respiration/methods , Pulmonary Atelectasis/etiology , Pulmonary Atelectasis/prevention & control , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Tomography/methodsABSTRACT
Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).
Subject(s)
Pulmonary Atelectasis , Respiratory Distress Syndrome , Shock , Animals , Hemodynamics/physiology , Humans , Obesity/complications , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy , SwineABSTRACT
BACKGROUND: Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. METHODS: In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012-2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015-2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. RESULTS: The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13-0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74). CONCLUSION: Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.
Subject(s)
Obesity/mortality , Respiratory Distress Syndrome/mortality , APACHE , Adult , Aged , Body Mass Index , Cohort Studies , Female , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Lung/physiopathology , Male , Middle Aged , Obesity/epidemiology , Respiration, Artificial/methods , Respiratory Distress Syndrome/epidemiology , Retrospective StudiesABSTRACT
BACKGROUND: Obese patients are characterized by normal chest-wall elastance and high pleural pressure and have been excluded from trials assessing best strategies to set positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). The authors hypothesized that severely obese patients with ARDS present with a high degree of lung collapse, reversible by titrated PEEP preceded by a lung recruitment maneuver. METHODS: Severely obese ARDS patients were enrolled in a physiologic crossover study evaluating the effects of three PEEP titration strategies applied in the following order: (1) PEEPARDSNET: the low PEEP/FIO2 ARDSnet table; (2) PEEPINCREMENTAL: PEEP levels set to determine a positive end-expiratory transpulmonary pressure; and (3) PEEPDECREMENTAL: PEEP levels set to determine the lowest respiratory system elastance during a decremental PEEP trial following a recruitment maneuver on respiratory mechanics, regional lung collapse, and overdistension according to electrical impedance tomography and gas exchange. RESULTS: Fourteen patients underwent the study procedures. At PEEPARDSNET (13 ± 1 cm H2O) end-expiratory transpulmonary pressure was negative (-5 ± 5 cm H2O), lung elastance was 27 ± 12 cm H2O/L, and PaO2/FIO2 was 194 ± 111 mmHg. Compared to PEEPARDSNET, at PEEPINCREMENTAL level (22 ± 3 cm H2O) lung volume increased (977 ± 708 ml), lung elastance decreased (23 ± 7 cm H2O/l), lung collapse decreased (18 ± 10%), and ventilation homogeneity increased thus rising oxygenation (251 ± 105 mmHg), despite higher overdistension levels (16 ± 12%), all values P < 0.05 versus PEEPARDSnet. Setting PEEP according to a PEEPDECREMENTAL trial after a recruitment maneuver (21 ± 4 cm H2O, P = 0.99 vs. PEEPINCREMENTAL) further lowered lung elastance (19 ± 6 cm H2O/l) and increased oxygenation (329 ± 82 mmHg) while reducing lung collapse (9 ± 2%) and overdistension (11 ± 2%), all values P < 0.05 versus PEEPARDSnet and PEEPINCREMENTAL. All patients were maintained on titrated PEEP levels up to 24 h without hemodynamic or ventilation related complications. CONCLUSIONS: Among the PEEP titration strategies tested, setting PEEP according to a PEEPDECREMENTAL trial preceded by a recruitment maneuver obtained the best lung function by decreasing lung overdistension and collapse, restoring lung elastance, and oxygenation suggesting lung tissue recruitment.
Subject(s)
Obesity/physiopathology , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy , Adult , Aged , Cross-Over Studies , Female , Humans , Male , Middle Aged , Respiratory Mechanics/physiologyABSTRACT
OBJECTIVE: The aims of this study were to investigate the ability of contrast-enhanced dual-energy computed tomography (DECT) for assessing regional perfusion in a model of acute lung injury, using dynamic first-pass perfusion CT (DynCT) as the criterion standard and to evaluate if changes in lung perfusion caused by prone ventilation are similarly demonstrated by DECT and DynCT. METHODS: This was an institutional review board-approved study, compliant with guidelines for humane care of laboratory animals. A ventilator-induced lung injury protocol was applied to 6 landrace pigs. Perfused blood volume (PBV) and pulmonary blood flow (PBF) were respectively quantified by DECT and DynCT, in supine and prone positions. The lungs were segmented in equally sized regions of interest, namely, dorsal, middle, and ventral. Perfused blood volume and PBF values were normalized by lung density. Regional air fraction (AF) was assessed by triple-material decomposition DECT. Per-animal correlation between PBV and PBF was assessed with Pearson R. Regional differences in PBV, PBF, and AF were evaluated with 1-way analysis of variance and post hoc linear trend analysis (α = 5%). RESULTS: Mean correlation coefficient between PBV and PBF was 0.70 (range, 0.55-0.98). Higher PBV and PBF values were observed in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -10.24 mL/100 g per zone for PBV (P < 0.001) and -223.0 mL/100 g per minute per zone for PBF (P < 0.001). Prone ventilation also revealed higher PBV and PBF in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -16.16 mL/100 g per zone for PBV (P < 0.001) and -108.2 mL/100 g per minute per zone for PBF (P < 0.001). By contrast, AF was lower in dorsal versus ventral regions in supine position, with dorsal-to-ventral linear trend slope of +5.77%/zone (P < 0.05). Prone ventilation was associated with homogenization of AF distribution among different regions (P = 0.74). CONCLUSIONS: Dual-energy computed tomography PBV is correlated with DynCT-PBF in a model of acute lung injury, and able to demonstrate regional differences in pulmonary perfusion. Perfusion was higher in the dorsal regions, irrespectively to decubitus, with more homogeneous lung aeration in prone position.
Subject(s)
Acute Lung Injury/diagnostic imaging , Radiography, Dual-Energy Scanned Projection/methods , Tomography, X-Ray Computed/methods , Animals , Contrast Media , Disease Models, Animal , Predictive Value of Tests , Pulmonary Circulation , SwineABSTRACT
OBJECTIVES: Atelectasis develops in critically ill obese patients when undergoing mechanical ventilation due to increased pleural pressure. The current study aimed to determine the relationship between transpulmonary pressure, lung mechanics, and lung morphology and to quantify the benefits of a decremental positive end-expiratory pressure trial preceded by a recruitment maneuver. DESIGN: Prospective, crossover, nonrandomized interventional study. SETTING: Medical and Surgical Intensive Care Units at Massachusetts General Hospital (Boston, MA) and University Animal Research Laboratory (São Paulo, Brazil). PATIENTS/SUBJECTS: Critically ill obese patients with acute respiratory failure and anesthetized swine. INTERVENTIONS: Clinical data from 16 mechanically ventilated critically ill obese patients were analyzed. An animal model of obesity with reversible atelectasis was developed by placing fluid filled bags on the abdomen to describe changes of lung mechanics, lung morphology, and pulmonary hemodynamics in 10 swine. MEASUREMENTS AND MAIN RESULTS: In obese patients (body mass index, 48 ± 11 kg/m), 21.7 ± 3.7 cm H2O of positive end-expiratory pressure resulted in the lowest elastance of the respiratory system (18.6 ± 6.1 cm H2O/L) after a recruitment maneuver and decremental positive end-expiratory pressure and corresponded to a positive (2.1 ± 2.2 cm H2O) end-expiratory transpulmonary pressure. Ventilation at lowest elastance positive end-expiratory pressure preceded by a recruitment maneuver restored end-expiratory lung volume (30.4 ± 9.1 mL/kg ideal body weight) and oxygenation (273.4 ± 72.1 mm Hg). In the swine model, lung collapse and intratidal recruitment/derecruitment occurred when the positive end-expiratory transpulmonary pressure decreased below 2-4 cm H2O. After the development of atelectasis, a decremental positive end-expiratory pressure trial preceded by lung recruitment identified the positive end-expiratory pressure level (17.4 ± 2.1 cm H2O) needed to restore poorly and nonaerated lung tissue, reestablishing lung elastance and oxygenation while avoiding increased pulmonary vascular resistance. CONCLUSIONS: In obesity, low-to-negative values of transpulmonary pressure predict lung collapse and intratidal recruitment/derecruitment. A decremental positive end-expiratory pressure trial preceded by a recruitment maneuver reverses atelectasis, improves lung mechanics, distribution of ventilation and oxygenation, and does not increase pulmonary vascular resistance.
Subject(s)
Critical Illness , Lung/pathology , Obesity/physiopathology , Pulmonary Atelectasis/physiopathology , Respiration, Artificial/adverse effects , Animals , Disease Models, Animal , Electric Impedance , Humans , Intensive Care Units , Lung/diagnostic imaging , Obesity/therapy , Positive-Pressure Respiration, Intrinsic , Prospective Studies , Respiratory Mechanics , Swine , Tomography, X-Ray ComputedABSTRACT
Importance: Perioperative lung-protective ventilation has been recommended to reduce pulmonary complications after cardiac surgery. The protective role of a small tidal volume (VT) has been established, whereas the added protection afforded by alveolar recruiting strategies remains controversial. Objective: To determine whether an intensive alveolar recruitment strategy could reduce postoperative pulmonary complications, when added to a protective ventilation with small VT. Design, Setting, and Participants: Randomized clinical trial of patients with hypoxemia after cardiac surgery at a single ICU in Brazil (December 2011-2014). Interventions: Intensive recruitment strategy (n=157) or moderate recruitment strategy (n=163) plus protective ventilation with small VT. Main Outcomes and Measures: Severity of postoperative pulmonary complications computed until hospital discharge, analyzed with a common odds ratio (OR) to detect ordinal shift in distribution of pulmonary complication severity score (0-to-5 scale, 0, no complications; 5, death). Prespecified secondary outcomes were length of stay in the ICU and hospital, incidence of barotrauma, and hospital mortality. Results: All 320 patients (median age, 62 years; IQR, 56-69 years; 125 women [39%]) completed the trial. The intensive recruitment strategy group had a mean 1.8 (95% CI, 1.7 to 2.0) and a median 1.7 (IQR, 1.0-2.0) pulmonary complications score vs 2.1 (95% CI, 2.0-2.3) and 2.0 (IQR, 1.5-3.0) for the moderate strategy group. Overall, the distribution of primary outcome scores shifted consistently in favor of the intensive strategy, with a common OR for lower scores of 1.86 (95% CI, 1.22 to 2.83; P = .003). The mean hospital stay for the moderate group was 12.4 days vs 10.9 days in the intensive group (absolute difference, -1.5 days; 95% CI, -3.1 to -0.3; P = .04). The mean ICU stay for the moderate group was 4.8 days vs 3.8 days for the intensive group (absolute difference, -1.0 days; 95% CI, -1.6 to -0.2; P = .01). Hospital mortality (2.5% in the intensive group vs 4.9% in the moderate group; absolute difference, -2.4%, 95% CI, -7.1% to 2.2%) and barotrauma incidence (0% in the intensive group vs 0.6% in the moderate group; absolute difference, -0.6%; 95% CI, -1.8% to 0.6%; P = .51) did not differ significantly between groups. Conclusions and Relevance: Among patients with hypoxemia after cardiac surgery, the use of an intensive vs a moderate alveolar recruitment strategy resulted in less severe pulmonary complications while in the hospital. Trial Registration: clinicaltrials.gov Identifier: NCT01502332.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Hypoxia/therapy , Oxygen Inhalation Therapy/methods , Postoperative Complications/therapy , Pulmonary Alveoli/physiology , Respiration, Artificial/methods , Severity of Illness Index , Aged , Barotrauma/epidemiology , Blood Pressure/physiology , Critical Care/statistics & numerical data , Female , Heart Rate/physiology , Hospital Mortality , Humans , Hypoxia/etiology , Incidence , Length of Stay , Lung Diseases/prevention & control , Male , Middle Aged , Odds Ratio , Oxygen Inhalation Therapy/statistics & numerical data , Partial Pressure , Positive-Pressure Respiration/methods , Postoperative Complications/prevention & control , Tidal VolumeSubject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Electric Impedance , Pneumonia, Viral/physiopathology , Point-of-Care Systems , Pulmonary Ventilation/physiology , Tomography/methods , Aged , COVID-19 , Humans , Lung/diagnostic imaging , Lung/physiopathology , Male , Pandemics , SARS-CoV-2Subject(s)
Airway Extubation/methods , Obesity/complications , Positive-Pressure Respiration/methods , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. RESEARCH QUESTION: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? STUDY DESIGN AND METHODS: Sixteen patients with Pao2/Fio2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. RESULTS: ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H2O; interquartile range (IQR), 15-24 cm H2O vs median, 15 cm H2O; IQR, 13-23 cm H2O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance. INTERPRETATION: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04241874; URL: www. CLINICALTRIALS: gov.