In various biomedical studies, analysis often focuses on data magnitudes, particularly when algebraic signs are irrelevant or lost. For repeated measures studies involving magnitude outcomes, incorporating random effects is essential as they account for individual heterogeneity, thereby enhancing parameter estimation precision. However, established regression methods specifically designed for magnitude outcomes that incorporate random effects are currently lacking. This article bridges this gap by introducing Bayesian regression modeling approaches for analyzing magnitude data, with a key focus on incorporating random effects. The proposed method is further extended to address multiple causes of informative dropout, a common challenge in repeated measures studies. To tackle this missing data challenge, a joint modeling strategy is developed, building upon the introduced regression techniques. Two numerical simulation studies assess the validity of our method. The chosen simulation scenarios are designed to resemble the conditions of our motivating study. Results demonstrate that the proposed method for magnitude data performs well in terms of estimation accuracy, and the joint models effectively mitigate bias due to missing data. Finally, we apply these models to analyze magnitude data from the motivating study, investigating whether sex impacts the magnitude change in diaphragm thickness over time for ICU patients.

BackgroundspaceExcessive respiratory effort may increase the risk of lung injury during noninvasive ventilation.Research QuestionspaceCan the pressures measured in the airway during a transient expiratory airway occlusion maneuver be used to detect elevated respiratory effort during noninvasive ventilation delivered by face mask?Study Design and MethodsspaceHealthy volunteers were recruited. Participants underwent noninvasive ventilation with varying applied inspiratory loads (dead space, inspiratory resistance, expiratory resistance, or combinations) at 2 levels of CPAP delivered using a mechanical ventilator (Getinge Servo-U). Under each condition, respiratory effort was assessed by esophageal manometry and brief airway occlusion maneuvers were performed on the ventilator to measure the airway occlusion pressure in the first 100 ms of inspiration (P0.1) and expiratory occlusion pressure (Pocc). Respiratory muscle pressure (Pmus) was computed from esophageal pressure swings using estimated chest wall elastance. The relationship between Pmusspaceand P0.1spaceor Poccspacewas assessed by linear regression and area under the receiver operating characteristic curve analysis.ResultsspaceTwenty participants were enrolled. Pmus, Pocc, and P0.1, but not respiratory rate (RR), increased progressively with applied ventilatory loads. P0.1spacemeasured on the ventilator was correlated with Pmusspace(marginalspaceR(2)space= 0.21; conditionalspaceR(2)space= 0.64;spacePspace< .001); the correlation between Poccspaceand Pmusspacewas weaker (marginalspaceR(2)space= 0.05; conditionalspaceR(2)space= 0.56;spacePspace= .01). RR was associated inversely with respiratory effort (marginalspaceR(2)space= 0.06; conditionalspaceR(2)space= 0.48;spacePspace= .02). P0.1spacewas sensitive and specific for the application of the highest load condition (inspiratory resistance plus dead space; area under the receiver operating characteristic curve, 0.90; 95% CI, 0.83-0.98).InterpretationspaceOur results show that P0.1spacemay be a useful parameter to assess for elevated respiratory effort and load during noninvasive ventilation. Further validation in critically ill patients is required.

Rationale: Excessive stress (distending pressure), strain (volume deformation), and drop in inspiratory alveolar pressure are proposed mechanisms for patient self-inflicted lung injury. Objectives: To dissect the influence of inspiratory effort, respiratory mechanics, and ventilation mode on lung stress, strain, and drop in inspiratory alveolar pressure; and explore their impact on oxygenation and lung compliance. Methods: International cohort study analyzing respiratory recordings (esophageal pressure) of patients with acute hypoxemic respiratory failure. Association between muscular pressure (Pmus), surrogates of stress (driving trans-alveolar pressure), strain (tidal volume), and inspiratory alveolar pressure relative to PEEP were explored with mixed-models, including interactions for ventilation mode, respiratory system elastance, and synchrony. Association between these and changes in oxygenation and lung compliance were explored. Measurements and main results: 60 patients from 15 centers represented 528 recordings (339,796 breaths). For each cmH(2)O Pmus increase there was an increase in driving trans-alveolar pressure (median[CI 95%] 0.28[0.27-0.29]cmH(2)O) and tidal volume (0.16[0.16-0.17]ml/kg of predicted body weight) and decrease in alveolar pressure (-0.25[0.24-0.6]cmH(2)O, p<0.001). Volume-control ventilation showed less increase in stress and strain surrogates than pressure-targeted modes, but more drop in alveolar pressure (p<0.001, Pmus:mode interaction). Breath-stacking was infrequent and associated with higher stress. Lower inspiratory alveolar pressure relative to PEEP was associated with subsequent worsening oxygenation (p=0.04) and higher stress with worsening lung compliance (p=0.023). Conclusion: Strong efforts are associated with high surrogates for lung stress, strain, and lower inspiratory alveolar pressure relative to PEEP, differently according to the mode of ventilation, being associated with subsequent worsening oxygenation and lung compliance.

Introduction There is increasing interest in patient and family-centered methods to improve research consent processes in the intensive care unit (ICU) environment. Because of the complexities of ICU care, measures of impact from multiple perspectives, including patients, substitute decision makers (SDMs) and research personnel, are required. Objective To determine what outcome measures have been used to assess the quality of informed consent for adult ICU-based research. Methods We conducted a scoping review of ICU-based clinical research, involving adult patients, SDMs, and/or research personnel, that reported any outcome measure assessing the quality of informed consent.Screening and data charting were completed in duplicate. Charted data included study, participant and outcome measure characteristics. We summarized characteristics using descriptive statistics and narrative summaries. Results We screened 18,164 unique citations, 102 full-texts, and included 9 studies. No studies used the same outcome measure. Most (n = 8, 89%) used a subjective questionnaire-based assessment of the consent process, while one (11%) measured quality by time to consent decision. We identified seven constructs assessed by outcomes: 1) consent discussion experience; 2) experience making consent decisions; 3) knowledge of parent study; 4) consent document experience; 5) perceived research risk; 6) experience of research, and 7) research processes. Conclusions We identified a limited, heterogeneous body of literature assessing the quality of informed consent for ICU-based research. This highlights an important gap and an unmet need for the development and validation of comprehensive outcome measures to evaluate the quality of informed consent from the perspectives of patients, SDMs and research personnel.

RATIONALE:Diaphragm dysfunction impedes weaning from mechanical ventilation. Transvenous diaphragm neurostimulation can increase diaphragm strength, but its impact on patient outcomes is uncertain. OBJECTIVES:To test the safety and effectiveness of transvenous diaphragm neurostimulation to increase successful weaning in patients with difficulty weaning from mechanical ventilation in comparison with standard of care. METHODS:This international, multicenter, open-label, randomized clinical trial (RESCUE-3) included adult patients requiring mechanical ventilation for ⩾96 hours who met readiness-to-wean criteria and failed two or more weaning attempts. Patients were randomized to twice-daily transvenous diaphragm neurostimulation (treatment) or standard of care (control). The primary outcome was successful weaning at Day 30. Secondary outcomes included duration of ventilation to Day 30 and mortality at Day 30. The prespecified primary analysis utilized a Bayesian approach with borrowing of prior information from a previous Phase-II randomized trial, downweighted to account for possible differences in trials. MEASUREMENTS AND MAIN RESULTS:Because of slow enrollment and financial considerations, the trial was halted at the first interim analysis after 200 patients were randomized. Overall, 216 patients were randomized in the modified intent-to-treat population (treatment group, n = 102; control group n = 114). At Day 30, 71 (70%) patients in the treatment group and 69 (61%) patients in the control group were successfully weaned (adjusted hazard ratio, 1.34; 95% credible interval = 1.01-1.78; posterior probability of superiority, 97.9%). Treatment reduced the duration of ventilation (adjusted difference, -2.5 d; 95% credible interval = -5.0 to 0.1; posterior probability of superiority, 97.1%). Serious adverse events were reported in 36% of patients in the treatment group and 24% of patients in the control group; 9.8% of patients in the treatment group and 10.5% of patients in the control group died (adjusted hazard ratio, 0.74; 95% credible interval = 0.37-1.46; posterior probability of superiority, 80.6%). CONCLUSIONS:Although the trial was stopped early because of slow enrollment, transvenous diaphragm neurostimulation showed a high probability of potential benefit for weaning success but with a possible increase in serious adverse events.

Background: Extubation failure occurs in approximately 10–15% of invasively ventilated adults and exceeds 20% in high-risk populations. Non-invasive respiratory support strategies—including conventional oxygen therapy (COT), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV)—are used after extubation to prevent respiratory failure and reintubation, yet their comparative effectiveness and safety remain uncertain. Objective: To compare the efficacy and safety of HFNC, NIV, and COT for post-extubation oxygenation in critically ill adults using a systematic review and network meta-analysis. Methods: We searched Embase, Cochrane CENTRAL, Web of Science, and Scopus from inception to November 7, 2025, for randomized clinical trials (RCTs) enrolling adults extubated in the intensive-care unit (ICU). Eligible trials compared any of HFNC, NIV, or COT used prophylactically immediately after extubation or as rescue therapy for post-extubation respiratory failure. Primary outcomes included reintubation and short-term mortality; secondary outcomes included tracheostomy, patient discomfort, and ICU length of stay. We performed a network meta-analysis and assessed certainty of evidence using GRADE for network meta-analysis. Results: Fifty-three RCTs enrolling 5,304 patients were included. Compared with COT, HFNC may reduce reintubation (RR 0.80, 95% CI 0.64–1.00; low certainty) and NIV probably reduces reintubation (RR 0.75, 95% CI 0.63–0.88; moderate certainty). The effect of NIV compared with HFNC on reintubation was uncertain (RR 0.93, 95% CI 0.76–1.15; low certainty). Neither HFNC nor NIV clearly reduced mortality relative to COT (both low certainty). HFNC may reduce tracheostomy compared with COT (RR 0.35, 95% CI 0.15–0.84; low certainty). Conclusions: Among critically ill adults undergoing extubation, prophylactic NIV or HFNC may reduce the risk of reintubation compared with COT. NIV probably provides the greatest reduction in reintubation, particularly in higher-risk populations, whereas HFNC is better tolerated and may reduce tracheostomy. Evidence for mortality and other clinical outcomes remains limited, underscoring the need for further high-quality trials evaluating post-extubation non-invasive respiratory support strategies.

Obtaining informed consent can be challenging in emergency and critical care research due to the acute and severe nature of the patient’s condition. However, such research is urgently needed to inform practice and optimise patient outcomes. While alternative consent approaches have been commonly used, opinions may vary, particularly among diverse and underserved patient groups and in the context of the recent COVID-19 pandemic. The objective of this review was to assess views of alternative consent methods in emergency and critical care research. We conducted a rapid systematic review to understand diverse opinions of alternative consent models used in emergency and critical care research with searches of MEDLINE, EMBASE, PsycINFO, Web of Science and CENTRAL carried out to July 31, 2024. We included quantitative and qualitative studies and summarised findings using narrative synthesis. We specifically investigated underserved groups and consent in the pandemic setting. From 9974 citations, we screened 289 full-text articles, and included 145 eligible studies from 26 countries. Consent methods included prospective informed consent, deferred consent, surrogate decision maker consent, healthcare professional consent and waived consent. Groups represented included previous trial participants, relatives of trial participants, patients, members of the general public, healthcare providers, researchers, site staff, and research ethics committees. It was recognised that prospective informed consent from the patient is not possible in all scenarios. In general, alternative consent models were acceptable, with emphasis on the inclusion of the patient and relatives in the decision-making process whenever possible. Acceptability of alternative consent models was influenced by previous research participation, experience of critical or emergency illness, perceived risk of participation, and invasiveness of the intervention. Study staff highlighted potential limitations of some alternative consent models, such as unavailability of relatives. Pandemic studies showed an increased need for alternative consent methods, and greater preparedness and engagement with ethics committees to facilitate implementation. Sub-analysis evaluating the views of underserved groups did not show consensus, and accommodations were largely not reported. Alternative consent models used for emergency, critical care and pandemic research including deferred consent, relative/surrogate decision maker consent, and physician consent were generally acceptable. PROSPERO CRD42023408305 (April 19, 2023).

The transcriptional repressor B cell lymphoma 6 (BCL6) is highly expressed in skeletal muscle. Although transcriptome-wide studies have shown BCL6 dysregulation in muscular dystrophies, investigations into its endogenous roles in muscle biology remain scarce. We therefore generated skeletal muscle-specific Bcl6 knockout (M-Bcl6 KO) mice and used adeno-associated virus to knockdown (KD) Bcl6 selectively in limb muscles of mice. In both models, Bcl6 deficiency led to reduced muscle mass and contractility. Single-nucleus RNA sequencing and biochemical analyses revealed upregulation of Socs2, and inhibition of the IGF1/AKT pathway. Mitochondrial respiration was significantly reduced in permeabilized myofibers upon Bcl6 KO and KD, and electron microscopy showed decreased mitochondrial density and altered morphology. Pathways regulating mitochondrial quality control were also downregulated. While Bcl6 KO did not significantly impair baseline treadmill running capacity, it blunted the adaptive response to endurance training. These findings demonstrate that Bcl6 is a critical regulator of skeletal muscle mass and mitochondrial bioenergetics, acting through transcriptional control of signaling and metabolic pathways essential for the maintenance of muscle mass and function.

OBJECTIVES:Acute hypoxemic respiratory failure (AHRF) is a leading cause of ICU admission and is associated with significant morbidity and mortality. Yet, epidemiological data on AHRF remain limited, and current management strategies largely derive from studies on acute respiratory distress syndrome (ARDS). We examined the prevalence of AHRF among ICU patients receiving supplemental oxygen or respiratory support for at least 4 hours, as well as initial respiratory support strategies and associated outcomes. DESIGN:Multicenter registry-based cohort study, 2014-2023. SETTING:Nine university of Toronto affiliated ICUs. PATIENTS:Adult ICU patients receiving supplemental oxygen or respiratory support who met AHRF criteria, defined as Pao2/Fio2 less than or equal to 300 mm Hg or, if Pao2 was not available, peripheral oxygen saturation (SpO2)/Fio2 less than or equal to 315, within the first 24 hours of ICU admission. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The primary outcome was AHRF prevalence. Secondary outcomes included ICU length of stay, invasive mechanical ventilation (IMV) duration, ventilator-free days, and ICU mortality, stratified by AHRF severity. Of 21,714 patients recorded in the registry, 10,832 (50%) met AHRF criteria, of whom 76% required IMV. Most received lung-protective ventilation. With increasing AHRF severity, ICU length of stay and IMV duration increased, while ventilator-free days and probability of ICU discharge at 30 days decreased. ICU mortality was 23% overall and 47% among patients on IMV with severe AHRF. CONCLUSIONS:AHRF is common early after ICU admission among patients requiring supplemental oxygen or respiratory support and is frequently managed using ARDS-based strategies. A pragmatic, standardized, and operationally feasible definition of AHRF may improve patient recognition, enable comparisons across studies, and guide future research.

Acute respiratory failure is a common reason for admission to cardiac intensive care units and the prevalence of respiratory failure in this cohort is increasing over time. Hypoxemia can occur due to a variety of mechanisms; the most common cause in the cardiac intensive care units remains cardiogenic pulmonary edema, but other etiologies, such as pneumonia and acute respiratory distress syndrome, are also common. This article provides an update on mechanisms of hypoxemia among patients with cardiac critical illness, heart lung interactions during spontaneous and positive pressure ventilation, optimization of sedation and ventilation for cardiac patients including novel ventilation strategies, and management of refractory hypoxemia among patients with cardiac critical illness.

Background Almost all large-scale trials of disease-modifying therapeutic agents in critical care have failed to show benefit for patients, which may be explained in part by the clinical and biological heterogeneity inherent in virtually all critical illness syndromes. Enrichment strategies have been developed to separate responders from non-responders and better target treatments. In patients with the acute respiratory distress syndrome, a critical illness syndrome involving severe lung inflammation, latent class analysis and other clustering approaches have led to the discovery of subgroups (phenotypes) that appear to respond differently to treatment based on retrospective analyses of published clinical trials and observational cohorts. The next step is to test these phenotypes in a prospective trial. Rapid, point-of-care analytical methods have now made such a trial possible. There is a need to advance treatment for patients with acute respiratory distress syndrome and other critical illness syndromes by incorporating a phenotype-based approach into prospective trial design. The hyperinflammatory and hypoinflammatory phenotypes, that have been identified in acute respiratory distress syndrome, will be the first to be included in such a trial, with scope for further phenotypes to be studied over time. Future work This Efficacy and Mechanism Evaluation report, through expert consensus, describes a new Phase II, multiarm, adaptive platform randomised controlled trial design that tests multiple pharmacological therapies in a population of patients with acute respiratory distress syndrome stratified by baseline inflammatory phenotype. This report also reviews issues to be considered in developing precision medicine trials in critical care, which are designed with newly developed clinical phenotypes in mind. This work has been used to develop the Precision medicine Adaptive Network platform Trial in Hypoxaemic acutE respiratory failuRe precision medicine trial in acute respiratory distress syndrome, which has been funded and will begin recruitment in June 2025. Limitations This report is the result of expert consensus review, rather than utilising strict review methodologies (e.g. Delphi consensus process). However, expert consensus has been found to generate similar results to consensus processes when a high degree of agreement is reached and > 70% agreement was reached for all included recommendations. Funding This article presents independent research funded by the (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR154493.

Rationale The impact of continuous positive airway pressure (CPAP) is currently unknown in patients with pulmonary arterial hypertension (PAH). The objective of the present study was to investigate the effect of CPAP on cardiopulmonary haemodynamics in patients with PAH compared to healthy volunteers. Methods All participants underwent an oesophageal catheter insertion followed by right heart catheterisation with and without the application of CPAP at 10 cmH2O. The primary outcome was the effect of CPAP on cardiopulmonary haemodynamics and intrapleural pressures within and between groups. Results In both PAH (n=18) and healthy (n=5) participants the acute application of CPAP increased the oesophageal pressure significantly from baseline (all p<0.007). There was a decline in cardiac output in both groups from baseline (p=0.047), which was due to a reduction in heart rate (p=0.027) rather than stroke volume (p=0.8). CPAP significantly reduced right ventricular end-diastolic pressure (p=0.02), without a significant impact on resistive right ventricular afterload. CPAP did not significantly change pulmonary artery or pulmonary vascular resistance in either group. The calculated dynamic pulmonary arterial compliance was increased in both groups. Conclusions In PAH and healthy participants, CPAP had a modest effect on intrapleural pressures. The transmural haemodynamic changes of CPAP were modest with a net increase in pulmonary vascular compliance in both groups, but no change in resistive right ventricular afterload in the PAH group. The current study did not demonstrate any deleterious effects of CPAP on pulmonary haemodynamics.

Ventilator-induced diaphragmatic dysfunction (VIDD) occurs in up to 60

Rationale: The optimal strategy to prevent reintubation in patients with obesity remains uncertain. Objectives: We aimed to determine whether noninvasive ventilation (NIV) with active humidification is superior to a high-flow nasal cannula (HFNC) in preventing reintubation in patients with obesity at intermediate risk. Methods: We conducted a randomized controlled trial in two ICUs in Spain (June 2020-June 2021). We included patients ready for planned extubation with a body mass index >30 and three or fewer risk factors for reintubation. Patients with hypercapnia at the end of the spontaneous breathing trial were excluded. Patients were randomized to undergo NIV with active humidification or HFNC for 48 hours after extubation. The primary outcome was the reintubation rate within 7 days after extubation. As a secondary analysis, we performed a post hoc Bayesian analysis using three different priors. Measurements and Main Results: Of 144 patients (median age, 61 [25th-75th percentile range, 61-67] yr; 65 [45%] men), 72 received NIV and 72 received an HFNC. Reintubation was required in 17 (23.6%) patients receiving NIV and in 24 (33.3%) patients receiving HFNC (difference between groups, 9.7; 95% confidence interval, -4.9, 24.4). All of the secondary analysis showed nonsignificant differences. In the exploratory Bayesian analysis, the probability of a reduction in reintubation with NIV was 99% (data-driven prior), 90% (minimally informative prior), or 89% (skeptical prior). Conclusions: Among adult critically ill patients with obesity at intermediate risk for extubation failure, the rate of reintubation was not significantly lower with NIV than with HFNC. Nevertheless, there is a risk for underpowered results. Clinical trial registered with www.clinicaltrials.gov (NCT04125342).

Background: In acute hypoxemic respiratory failure (AHRF), spontaneous breathing effort can generate excessive regional lung stress and strain manifesting as pendelluft. Higher PEEP may reduce pendelluft and reduce regional lung stress and strain during spontaneous breathing. This study aimed to establish whether higher or lower PEEP ameliorates pendelluft and to characterize factors determining the presence and magnitude of pendelluft during spontaneous breathing efforts. Methods: This study was a randomized crossover trial of higher versus lower PEEP applied after systematically initiating spontaneous breathing in subjects with moderate or severe AHRF. The presence and volume of pendelluft were assessed by electrical impedance tomography (EIT). Results: EIT recordings were available for 20 of 30 subjects enrolled in the trial. After initiating spontaneous breathing, 11/20 exhibited pendelluft (proportion 55% [95% CI 32-76]). Following PEEP titration, the prevalence of pendelluft was not different between higher versus lower PEEP levels (50% vs 50%, P = .55). When present, pendelluft volume was generally small (median 28 [interquartile range 8-93] mL) but ranged as high as 364 mL. Pendelluft was associated with higher respiratory effort (esophageal pressure [P-es] swing [Delta P-es] median -15 cm H2O vs Delta P-es median -8 cm H2O, P = .01), higher pulmonary flow resistance (median 8 cm H2O/L/s vs median 3 cm H2O/L/s, P < .001), and higher dynamic pulmonary elastance (median 5.0 cm H2O/mL/kg predicted body weight vs median 3.2 cm H2O/mL/kg predicted body weight, P = .03). Conclusions: Pendelluft reflecting increased regional lung stress and strain is likely common during spontaneous breathing effort in patients with AHRF but was not systematically affected by applying higher PEEP. The presence and magnitude of pendelluft depended on respiratory effort and lung mechanics.

We evaluated whether non-invasive estimated inspiratory muscle pressure (Pmus) predicts extubation outcomes in ICU patients. Estimated Pmus, reflecting the pressure generated by respiratory muscles, was measured before and after the spontaneous breathing trial (SBT). Lower pre-SBT estimated Pmus (<4.1 cmH₂O) and post-SBT (<4.4 cmH₂O) were associated with extubation failure (AUC ≈ 0.73). P0.1 and dynamic transpulmonary pressure (PL,dyn) showed no significant association. Estimated Pmus offers a simple bedside method to assess inspiratory muscle strength and may help identify patients at risk of extubation failure. Further multicenter studies are needed to validate these findings.

Introduction Ventilator-delivered pressures and patient efforts during assisted mechanical ventilation leave patients at risk of lung injury. Electrical diaphragm activity can provide continuous diaphragm monitoring because it provides an electromyographic measure of diaphragmatic effort. However, it is uncertain whether this can be used to assess respiratory effort of lung distending pressure during spontaneous breathing. Objectives Our primary objective was to establish the validity of using electrical diaphragm activity (Edi) to total lung-distending pressure (ΔPL,dyn). We then applied this method to a longitudinal cohort study to describe the distribution and magnitude of ΔPL,dyn during assisted mechanical ventilation. Methods We performed a secondary analysis based on two published studies. Pocc and Edi were measured in 16 mechanically ventilated patients. ΔPes was measured and observed ΔPL,dyn was computed. Similarly, ΔPes, ΔPL,dyn, Pocc, Edi,occ, and Edi,open were measured in an additional 12 mechanically ventilated patients.Estimated ΔPL,dyn for non-occluded breaths was computed as ΔPaw – Pocc/Edi,occ [asterisk] 2/3 [asterisk] Edi,open. The estimated ΔPL,dyn was validated against observed ΔPL,dyn via Pearson's correlation and Bland-Altman analysis. This method was then applied to 45 patients where ΔPaw, Edi,open, and Pocc were measured. Results The validation analysis was performed using 98 recordings obtained in 28 subjects. We found that the median ΔPL,dyn was 19cm H2O (15-23 cm H2O) and estimated ΔPL,dyn had a median of 20 cm H2O (IQR 16-25 cm H2O). The measured and predicted ΔPL,dyn, showed a moderate correlation (R2=0.70, p<0.0001) with a bias of 6% and limits of agreement approximating 28% – 40%. In the longitudinal cohort with 45 patients and 4508 study-hours, we computed the distribution of estimated ΔPL,dyn during assisted ventilation. Estimated ΔPL,dyn was elevated ( >25 cm H2O) in 21% of hours with spontaneous breathing and 35 patients had ≥1 hour of ΔPL,dyn >25 cm H2O. When estimated ΔPL,dyn exceeded 25 cm H2O, the contribution of respiratory effort to total lung-distending pressure was a median of 71% (IQR 58-82%). Conclusion Dynamic transpulmonary driving pressure, a measure of lung stress during spontaneous breathing, can be estimated by monitoring Edi and Pocc. Excessive respiratory effort may be an important and frequent contributor to excess lung stress and strain during mechanical ventilation.