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Background: Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded., Results: All pigs presented airway closure (AOP > 0.5cmH 2 O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13-19] to 9%[IQR:4-12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16-30] to 23%[IQR:14-27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases., Conclusions: In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation., (© 2024. The Author(s).)

Rationale: It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objectives: To compare PEEP targeting minimal overdistention or minimal collapse or using a compromise between collapse and overdistention in a randomized trial and to assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. Methods: In a porcine model of ARDS, lung collapse and overdistention were estimated using electrical impedance tomography during a decremental PEEP titration. Pigs were randomized to three groups and ventilated for 12 hours: PEEP set at ⩽3% of overdistention (low overdistention), ⩽3% of collapse (low collapse), and the crossing point of collapse and overdistention. Measurements and Main Results: Thirty-six pigs (12 per group) were included. Median (interquartile range) values of PEEP were 7 (6-8), 11 (10-11), and 15 (12-16) cm H 2 O in the three groups ( P  < 0.001). With low overdistension, 6 (50%) pigs died, whereas survival was 100% in both other groups. Cause of death was hemodynamic in nature, with high transpulmonary vascular gradient and high epinephrine requirements. Compared with the other groups, pigs surviving with low overdistension had worse respiratory mechanics and gas exchange during the entire protocol. Minimal differences existed between crossing-point and low-collapse animals in physiological parameters, but postmortem alveolar density was more homogeneous in the crossing-point group. Inflammatory markers were not significantly different. Conclusions: PEEP to minimize overdistention resulted in high mortality in an animal model of ARDS. Minimizing collapse or choosing a compromise between collapse and overdistention may result in less lung injury, with potential benefits of the compromise approach.

Background: Reverse triggering (RT) was described in 2013 as a form of patient-ventilator asynchrony, where patient's respiratory effort follows mechanical insufflation. Diagnosis requires esophageal pressure (P es ) or diaphragmatic electrical activity (EA di ), but RT can also be diagnosed using standard ventilator waveforms., Hypothesis: We wondered (1) how frequently RT would be present but undetected in the figures from literature, especially before 2013; (2) whether it would be more prevalent in the era of small tidal volumes after 2000., Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from 1950 to 2017, with key words related to asynchrony to identify papers with figures including ventilator waveforms expected to display RT if present. Experts labelled waveforms. 'Definite' RT was identified when P es or EA di were in the tracing, and 'possible' RT when only flow and pressure waveforms were present. Expert assessment was compared to the author's descriptions of waveforms., Results: We found 65 appropriate papers published from 1977 to now, containing 181 ventilator waveforms. 21 cases of 'possible' RT and 25 cases of 'definite' RT were identified by the experts. 18.8% of waveforms prior to 2013 had evidence of RT. Most cases were published after 2000 (1 before vs. 45 after, p = 0.03). 54% of RT cases were attributed to different phenomena. A few cases of identified RT were already described prior to 2013 using different terminology (earliest in 1997). While RT cases attributed to different phenomena decreased after 2013, 60% of 'possible' RT remained missed., Conclusion: RT has been present in the literature as early as 1997, but most cases were found after the introduction of low tidal volume ventilation in 2000. Following 2013, the number of undetected cases decreased, but RT are still commonly missed. Reverse Triggering, A Missed Phenomenon in the Literature. Critical Care Canada Forum 2019 Abstracts. Can J Anesth/J Can Anesth 67 (Suppl 1), 1-162 (2020). https://doi-org.myaccess.library.utoronto.ca/ https://doi.org/10.1007/s12630-019-01552-z ., (© 2024. The Author(s).)

Background: Pre-clinical studies suggest that dyssynchronous diaphragm contractions during mechanical ventilation may cause acute diaphragm dysfunction. We aimed to describe the variability in diaphragm contractile loading conditions during mechanical ventilation and to establish whether dyssynchronous diaphragm contractions are associated with the development of impaired diaphragm dysfunction., Methods: In patients receiving invasive mechanical ventilation for pneumonia, septic shock, acute respiratory distress syndrome, or acute brain injury, airway flow and pressure and diaphragm electrical activity (Edi) were recorded hourly around the clock for up to 7 days. Dyssynchronous post-inspiratory diaphragm loading was defined based on the duration of neural inspiration after expiratory cycling of the ventilator. Diaphragm function was assessed on a daily basis by neuromuscular coupling (NMC, the ratio of transdiaphragmatic pressure to diaphragm electrical activity)., Results: A total of 4508 hourly recordings were collected in 45 patients. Edi was low or absent (≤ 5 µV) in 51% of study hours (median 71 h per patient, interquartile range 39-101 h). Dyssynchronous post-inspiratory loading was present in 13% of study hours (median 7 h per patient, interquartile range 2-22 h). The probability of dyssynchronous post-inspiratory loading was increased with reverse triggering (odds ratio 15, 95% CI 8-35) and premature cycling (odds ratio 8, 95% CI 6-10). The duration and magnitude of dyssynchronous post-inspiratory loading were associated with a progressive decline in diaphragm NMC (p < 0.01 for interaction with time)., Conclusions: Dyssynchronous diaphragm contractions may impair diaphragm function during mechanical ventilation., Trial Registration: MYOTRAUMA, ClinicalTrials.gov NCT03108118. Registered 04 April 2017 (retrospectively registered)., (© 2024. The Author(s).)

Background: Aerosol barrier enclosure systems have been designed to prevent airborne contamination, but their safety has been questioned. A vacuum tent was designed with active continuous suctioning to minimize risks of aerosol dispersion. We tested its efficacy, risk of rebreathing, and usability on a bench, in healthy volunteers, and in an ergonomic clinical assessment study., Methods: First, a manikin with airway connected to a breathing simulator was placed inside the vacuum tent to generate active breathing, cough, and CO 2 production; high-flow nasal cannula (HFNC) was applied in the manikin's nares. Negative pressure was applied in the vacuum tent's apex port using wall suction. Fluorescent microparticles were aerosolized in the vacuum tent for qualitative assessment. To quantify particles inside and around vacuum tent (aerosol retention), an airtight aerosol chamber with aerosolized latex microparticles was used. The vacuum tent was tested on healthy volunteers breathing with and without HFNC. Last, its usability was assessed in 5 subjects by 5 different anesthesiologists for delivery of full anesthesia, including intubation and extubation., Results: The vacuum tent was adjusted until no leak was visualized using fluorescent particles. The efficacy in retaining microparticles was confirmed quantitatively. CO 2 accumulation inside the vacuum tent showed an inverse correlation with the suction flow in all conditions (normal breathing and HFNC 30 or 60 L/min) in bench and healthy volunteers. Particle removal efficacy and safe breathing conditions (CO 2 , temperature) were reached when suctioning was at least 60 L/min or 20 L/min > HFNC flow. Five subjects were successfully intubated and anesthetized without ergonomic difficulties and with minimal interference with workflow and an excellent overall assessment by the anesthesiologists., Conclusions: The vacuum tent effectively minimized aerosol dispersion. Its continuous suction system set at a high suction flow was crucial to avoid the spread of aerosol particles and CO 2 rebreathing., Competing Interests: Dr Rezende-Neto invented the vacuum tent and is the cofounder of InventoRR MD. Dr Brochard’s laboratory discloses relationships with STIMIT, Medtronic, Dräger, Sentec, Philips, and Fisher & Paykel. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Hypoxemic respiratory failure is one of the leading causes of mortality in intensive care. Frequent assessment of individual physiological characteristics and delivery of personalized mechanical ventilation (MV) settings is a constant challenge for clinicians caring for these patients. Electrical impedance tomography (EIT) is a radiation-free bedside monitoring device that is able to assess regional lung ventilation and changes in aeration. With real-time tomographic functional images of the lungs obtained through a thoracic belt, clinicians can visualize and estimate the distribution of ventilation at different ventilation settings or following procedures such as prone positioning. Several studies have evaluated the performance of EIT to monitor the effects of different MV settings in patients with acute respiratory distress syndrome, allowing more personalized MV. For instance, EIT could help clinicians find the positive end-expiratory pressure that represents a compromise between recruitment and overdistension and assess the effect of prone positioning on ventilation distribution. The clinical impact of the personalization of MV remains to be explored. Despite inherent limitations such as limited spatial resolution, EIT also offers a unique noninvasive bedside assessment of regional ventilation changes in the ICU. This technology offers the possibility of a continuous, operator-free diagnosis and real-time detection of common problems during MV. This review provides an overview of the functioning of EIT, its main indices, and its performance in monitoring patients with acute respiratory failure. Future perspectives for use in intensive care are also addressed.

Background: Lung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCO 2 R) to achieve LDP targets., Methods: An in silico clinical trial was conducted using a previously published mathematical model of patient-ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics. Ventilation and sedation were titrated according to a pre-defined algorithm in pressure support ventilation (PSV) and proportional assist ventilation (PAV+) modes, with or without adjunctive ECCO 2 R, and using ECCO 2 R alone (without ventilation or sedation). Random forest modelling was employed to identify patient-level factors associated with achieving targets., Results: After titration, the proportion of patients achieving targets was lower in PAV+ vs. PSV (37% vs. 43%, odds ratio 0.78, 95% CI 0.73-0.85). Adjunctive ECCO 2 R substantially increased the probability of achieving targets in both PSV and PAV+ (85% vs. 84%). ECCO 2 R alone without ventilation or sedation achieved LDP targets in 9%. The main determinants of success without ECCO 2 R were lung compliance, ventilatory ratio, and strong ion difference. In silico trial results corresponded closely with the results obtained in a clinical trial of the LDP titration algorithm (n = 30)., Conclusions: In this in silico trial, many patients required ECCO 2 R in combination with mechanical ventilation and sedation to achieve LDP targets. ECCO 2 R increased the probability of achieving LDP targets in patients with intermediate degrees of derangement in elastance and ventilatory ratio., (© 2024. The Author(s).)

Purpose of Review: Determining the optimal positive end-expiratory pressure (PEEP) setting remains a central yet debated issue in the management of acute respiratory distress syndrome (ARDS).The 'best compliance' strategy set the PEEP to coincide with the peak respiratory system compliance (or 2 cmH 2 O higher) during a decremental PEEP trial, but evidence is conflicting., Recent Findings: The physiological rationale that best compliance is always representative of functional residual capacity and recruitment has raised serious concerns about its efficacy and safety, due to its association with increased 28-day all-cause mortality in a randomized clinical trial in ARDS patients.Moreover, compliance measurement was shown to underestimate the effects of overdistension, and neglect intra-tidal recruitment, airway closure, and the interaction between lung and chest wall mechanics, especially in obese patients. In response to these concerns, alternative approaches such as recruitment-to-inflation ratio, the nitrogen wash-in/wash-out technique, and electrical impedance tomography (EIT) are gaining attention to assess recruitment and overdistention more reliably and precisely., Summary: The traditional 'best compliance' strategy for determining optimal PEEP settings in ARDS carries risks and overlooks some key physiological aspects. The advent of new technologies and methods presents more reliable strategies to assess recruitment and overdistention, facilitating personalized approaches to PEEP optimization., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1 ) identify patients with the currently accepted conceptual framework for ARDS, 2 ) facilitate rapid ARDS diagnosis for clinical care and research, 3 ) be applicable in resource-limited settings, 4 ) be useful for testing specific therapies, and 5 ) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1 ) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2 ) use Pa O 2 :Fi O 2  ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry Sp O 2 :Fi O 2  ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3 ) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4 ) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Background: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS)., Methods: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔP es 100 ms ]) and inspiratory effort (as the esophageal pressure-time product per minute [PTP min ]). We performed repeated measures analysis with post-hoc tests and mixed-effects models., Results: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔP es 100 ms of -2.8 [-3.8--1.9] cm H 2 O, -3.6 [-3.9--2.4] cm H 2 O and -2.1 [-2.5--1.1] cm H 2 O, respectively, p < 0.001 for both comparisons; PTP min of 155 [118-209] cm H 2 O s/min, 197 [145-269] cm H 2 O s/min, and 134 [93-169] cm H 2 O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (β = -2.771, p-value < 0.001) and inspiratory effort (β = 0.026, p  < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTP min (β = 2.606, p = 0.010 for NAVA, and β = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (β = 2.643, p = 0.009 for PAV +)., Conclusions: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV., (© 2023. The Author(s).)

Rationale: Limited information exists about the epidemiology, outcomes, and predictors of weaning from mechanical ventilation in patients with spinal cord injury. Objectives: Our aim was to investigate predictors of weaning outcomes for patients with traumatic spinal cord injury (tSCI) and develop and validate a prognostic model and score for weaning success. Methods: This was a registry-based, multicentric cohort study including all adult patients with tSCI requiring mechanical ventilation (MV) and admitted to one of the intensive care units (ICUs) of the Trauma Registry at St. Michael's Hospital (Toronto, ON, Canada) and the Canadian Rick Hansen Spinal Cord Injury Registry between 2005 and 2019. The primary outcome was weaning success from MV at ICU discharge. Secondary outcomes included weaning success at Days 14 and 28, time to liberation from MV accounting for competing risk of death, and ventilator-free days at 28 and 60 days. Associations between baseline characteristics and weaning success or time to liberation from MV were measured using multivariable logistic and competing risk regressions. A parsimonious model to predict weaning success and ICU discharge was developed and validated via bootstrap. A prediction score for weaning success at ICU discharge was derived, and its discriminative ability was assessed using receiver operating characteristic curve analysis and compared with the Injury Severity Score (ISS). Results: Of 459 patients analyzed, 246 (53.6%), 302 (65.8%), and 331 (72.1%) were alive and free of MV at Day 14, Day 28, and ICU discharge, respectively; 54 (11.8%) died in the ICU. Median time to liberation from MV was 12 days. Factors associated with weaning success were B lunt injury (odds ratio [OR], 2.96; P  = 0.010), I SS (OR, 0.98; P  = 0.025), C omplete syndrome (OR, 0.53; P  = 0.009), age in Y ears (OR, 0.98; P  = 0.003), and C ervical LE sion (OR, 0.60; P  = 0.045). The BICYCLE score showed a greater area under the curve than the ISS (0.689 [95% confidence interval (CI), 0.631-0.743] vs. 0.537 [95% CI, 0.479-0.595]; P  < 0.0001). Factors predicting weaning success also predicted time to liberation. Conclusions: In a large multicentric cohort, 72% of patients with tSCI were weaned and discharged alive from the ICU. Readily available admission characteristics can reasonably predict weaning success and help prognostication.

Critical care and mechanical ventilation have a relatively brief history in medicine. Premises existed through the seventeenth to nineteenth centuries but modern mechanical ventilation started in the twentieth century. Noninvasive ventilation techniques had started both in the intensive care unit and for home ventilation at the end of the 1980s and the 1990s. The need for mechanical ventilation is increasingly influenced worldwide by the spread of respiratory viruses, and the last coronavirus disease 2019 pandemic has seen a massive successful use of noninvasive ventilation., Competing Interests: Conflicts of interest L.J. Brochard’s laboratory received research grants from Medtronic, Draeger, Vitalaire and Stimit; equipment from Sentec, Fisher Paykel and Philips; lecture fees from Fisher Paykel., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Previous studies reported an association between higher driving pressure (∆P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on ∆P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic ∆P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation., Design: For this comparative effectiveness study, we emulated pragmatic clinical trials using data from the Toronto Intensive Care Observational Registry recorded between April 2014 and August 2021. The per-protocol effect of the interventions was estimated using the parametric g-formula, a method that controls for baseline and time-varying confounding, as well as for competing events in the analysis of longitudinal exposures., Setting: Nine ICUs from seven University of Toronto-affiliated hospitals., Patients: Adult patients (≥18 yr) requiring greater than or equal to 24 hours of mechanical ventilation., Interventions: Receipt of a ventilation strategy that limited either daily static or dynamic ∆P less than or equal to 15 cm H 2 O compared with usual care., Measurements and Main Results: Among the 12,865 eligible patients, 4,468 of (35%) were ventilated with dynamic ∆P greater than 15 cm H 2 O at baseline. Mortality under usual care was 20.1% (95% CI, 19.4-20.9%). Limiting daily dynamic ∆P less than or equal to 15 cm H 2 O in addition to traditional lung-protective ventilation reduced adherence-adjusted mortality to 18.1% (95% CI, 17.5-18.9%) (risk ratio, 0.90; 95% CI, 0.89-0.92). In further analyses, this effect was most pronounced for early and sustained interventions. Static ∆P at baseline were recorded in only 2,473 patients but similar effects were observed. Conversely, strict interventions on tidal volumes or peak inspiratory pressures, irrespective of ∆P, did not reduce mortality compared with usual care., Conclusions: Limiting either static or dynamic ∆P can further reduce the mortality of patients requiring mechanical ventilation., Competing Interests: Dr. Urner received funding from Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (CIHR). Dr. Brochard’s institution received funding from Medtronic, Draeger, Stimit, and Vitalair; he disclosed the equipment was from Fisher & Paykel and Sentec. Drs. Ferguson and Fan received funding from Baxter. Dr. Ferguson received funding from Getinge and Xenios. Dr. Fan received funding from the New Investigator Award from the CIHR, Abbott, ALung Technologies, Fresenius Medical Care, MC3 Cardiopulmonary, Aerogen, GE Healthcare, Inspira, and Vasomune. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H 2 O (ΔCollapse 24-6 ). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse 24-6 . Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H 2 O for low versus medium versus high recruitability ( P  < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H 2 O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Background: The Oxylator is an automatic resuscitator, powered only by an oxygen cylinder with no electricity required, that could be used in acute respiratory failure in situations in which standard mechanical ventilation is not available or feasible. We aimed to assess the feasibility and safety of mechanical ventilation by using this automatic resuscitator in an animal model of ARDS., Methods: A randomized experimental study in a porcine ARDS model with 12 pigs randomized to the Oxylator group or the control group (6 per group) and ventilated for 4 h. In the Oxylator group, peak pressure was set at 20 cm H 2 O and PEEP was set at the lowest observed breathing frequency during a decremental PEEP titration. The control pigs were ventilated with a conventional ventilator by using protective settings and PEEP at the crossing point of collapse and overdistention, as indicated by electrical impedance tomography. Our end points were feasibility and safety as well as respiratory mechanics, gas exchange, and hemodynamics., Results: After lung injury, the mean ± SD respiratory system compliance and P aO 2 /F IO 2 were 13 ± 2 mL/cm H 2 O and 61 ± 17 mm Hg, respectively. The mean ± SD total PEEP was 10 ± 2 cm H 2 O and 13 ± 2 cm H 2 O in the control and Oxylator groups, respectively ( P = .046). The mean plateau pressure was kept to < 30 cm H 2 O in both groups. In the Oxylator group, the tidal volume was transiently > 8 mL/kg but was 6 ± 0.4 mL/kg at 4 h, whereas the breathing frequency increased from 38 ± 4 to 48 ± 3 breaths/min ( P < .001). There was no difference in driving pressure, compliance, P aO 2 /F IO 2 , and pulmonary shunt between the groups. The mean ± SD P aCO 2 was higher in the Oxylator group after 4 h, 74 ± 9 mm Hg versus 58 ± 6 mm Hg ( P < .001). There were no differences in hemodynamics between the groups, including blood pressure and cardiac output., Conclusions: Short-term mechanical ventilation by using an automatic resuscitator and a fixed pressure setting in an ARDS animal model was feasible and safe., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Background: Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19., Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2., Findings: Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05]., Interpretation: The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO., Funding: None., Competing Interests: Declaration of interests RPB is Chair of the Extracorporeal Life Support Organization (ELSO) registry. GM serves on the Board of Directors for ELSO. KR reports honoraria from Baxter and Faesenius, outside of the submitted work. LJB reports research support from Medtronic and Draeger, and honoraria from Fisher Paykel, outside of the submitted work. NDF reports consulting fees from Baxter and Xenios, outside of the submitted work. ASS reports consulting fees from Baxter and Xenios, outside of the submitted work. He is the Chair of the Scientific Committee of the International ECMO Network (ECMONet). EF reports personal fees from ALung Technologies, Aerogen, Baxter, Boehringer-Ingelheim, GE Healthcare, Inspira, and Vasomune, outside of the submitted work. He is the Chair of the Data Committee of ECMONet. DB reports research support from Alung Technologies, outside of the submitted work. He has been on medical advisory boards for Abiomed, Xenios, Medtronic, LivaNova, Inspira, and Cellenkos, and is the President-Elect of ELSO and the Chair of the Executive Committee of ECMONet. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting Pa O 2 :Fi O 2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation ( n  = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P  = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P  = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P  = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P  = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).

Treatment of respiratory failure has improved dramatically since the polio epidemic in the 1950s with the use of invasive techniques for respiratory support: mechanical ventilation and extracorporeal respiratory support. However, respiratory support is only a supportive therapy, designed to "buy time" while the disease causing respiratory failure abates. It ensures viable gas exchange and prevents cardiorespiratory collapse in the context of excessive loads. Because the use of invasive modalities of respiratory support is also associated with substantial harm, it remains the responsibility of the clinician to minimize such hazards. Direct iatrogenic consequences of mechanical ventilation include the risk to the lung (ventilator-induced lung injury) and the diaphragm (ventilator-induced diaphragm dysfunction and other forms of myotrauma). Adverse consequences on hemodynamics can also be significant. Indirect consequences (e.g., immobilization, sleep disruption) can have devastating long-term effects. Increasing awareness and understanding of these mechanisms of injury has led to a change in the philosophy of care with a shift from aiming to normalize gases toward minimizing harm. Lung (and more recently also diaphragm) protective ventilation strategies include the use of extracorporeal respiratory support when the risk of ventilation becomes excessive. This review provides an overview of the historical background of respiratory support, pathophysiology of respiratory failure and rationale for respiratory support, iatrogenic consequences from mechanical ventilation, specifics of the implementation of mechanical ventilation, and role of extracorporeal respiratory support. It highlights the need for appropriate monitoring to estimate risks and to individualize ventilation and sedation to provide safe respiratory support to each patient., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H 2 O; dynamic transpulmonary driving pressure ≤ 15 cm H 2 O) during AHRF., Methods: In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort., Results: Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets., Conclusion: Respiratory effort is frequently absent  under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy., Trial Registration: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583)., (© 2022. The Author(s).)

Among mechanically ventilated patients, asymmetrical lung injury is probably extremely frequent in the intensive care unit but the lack of standardized measurements does not allow to describe any prevalence among mechanically ventilated patients. Many past studies have focused only on unilateral injury and have mostly described the effect of lateral positioning. The good lung put downward might receive more perfusion while the sick lung placed upward receive more ventilation than supine. This usually results in better oxygenation but can also promote atelectasis in the healthy lung and no consensus has emerged on the clinical indication of this posture. Recently, electrical impedance tomography (EIT) has allowed for the first time to precisely describe the distribution of ventilation in each lung and to better study asymmetrical lung injury. At low positive-end-expiratory pressure (PEEP), a very heterogeneous ventilation exists between the two lungs and the initial increase in PEEP first helps to recruit the sick lung and protect the healthier lung. However, further increasing PEEP distends the less injured lung and must be avoided. The right level can be found using EIT and transpulmonary pressure. In addition, EIT can show that in the two lungs, airway closure is present but with very different airway opening pressures (AOPs) which cannot be identified on a global assessment. This may suggest a very different PEEP level than on a global assessment. Lastly, epidemiological studies suggest that in hypoxemic patients, the number of quadrants involved has a strong prognostic value. The number of quadrants is more important than the location of the unilateral or bilateral nature of the involvement for the prognosis, and hypoxemic patients with unilateral lung injury should probably be considered as requiring lung protective ventilation as classical acute respiratory distress syndrome., Competing Interests: LB's laboratory received research grant from Medtronic and Drager, equipment from Sentec, Fisher Paykel, Philps, and fees for lectures from Fisher Paykel., (Thieme. All rights reserved.)

High-flow nasal cannula (HFNC) is extensively used for acute respiratory failure. However, questions remain regarding its physiological effects. We explored 1) whether HFNC produced similar effects to continuous positive airway pressure (CPAP); 2) possible explanations of respiratory rate changes; 3) the effects of mouth opening. Two studies were conducted: a bench study using a manikin's head with lungs connected to a breathing simulator while delivering HFNC flow rates from 0 to 60L/min; a physiological cross-over study in 10 healthy volunteers receiving HFNC (20 to 60L/min) with the mouth open or closed and CPAP 4cmH 2 O delivered through face-mask. Nasopharyngeal and esophageal pressures were measured; tidal volume and flow were estimated using calibrated electrical impedance tomography. In the bench study, nasopharyngeal pressure at end-expiration reached 4cmH 2 O with HFNC at 60L/min, while tidal volume decreased with increasing flow. In volunteers with HFNC at 60L/min, nasopharyngeal pressure reached 6.8cmH 2 O with mouth closed and 0.8cmH 2 O with mouth open; p<0.001. When increasing HFNC flow, respiratory rate decreased by lengthening expiratory time, tidal volume did not change, and effort decreased (pressure-time product of the respiratory muscles); at 40L/min, effort was equivalent between CPAP and HFNC40L/min and became lower at 60L/min (p=0.045). During HFNC with mouth closed, and not during CPAP, resistance to breathing was increased, mostly during expiration. In conclusion, mouth closure during HFNC induces a positive nasopharyngeal pressure proportional to flow rate and an increase in expiratory resistance that might explain the prolonged expiration and reduction in respiratory rate and effort, and contribute to physiological benefits.

Background: Our purpose was to summarise the prognostic associations between various clinical risk factors and development of acute respiratory distress syndrome (ARDS) following traumatic injury., Methods: We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with development of post-traumatic ARDS, as defined by either the American-European Consensus Conference or Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS (Quality in Prognosis Studies) tool and certainty of findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology., Results: We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with development of post-traumatic ARDS (adjusted OR 1.19, 95% CI 1.15-1.24 for each additional litre of crystalloid administered within the first 6 h after injury; high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic White race, blunt mechanism of injury, presence of head injury, pulmonary contusion or rib fracture and increasing chest injury severity., Conclusions: We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform development of risk stratification tools., Competing Interests: Conflict of interest: A. Tran has nothing to disclose. Conflict of interest: S.M. Fernando has nothing to disclose. Conflict of interest: L.J. Brochard has nothing to disclose. Conflict of interest: E. Fan reports receiving personal fees from ALung Technologies, Baxter, Fresenius Medical Care, Getinge and MC3 Cardiopulmonary, outside of the submitted work. Conflict of interest: K. Inaba has nothing to disclose. Conflict of interest: N.D. Ferguson has nothing to disclose. Conflict of interest. C. Calfee receives grant funding from the NIH (related) as well as Roche-Genentech and Quantum Leap Healthcare Collaborative, outside of the submitted work; she has served as a medical advisor to Roche-Genentech, Bayer, CSL Behring, Quark Pharmaceuticals, Vasomune and Gen1e Life Sciences, outside of the submitted work. Conflict of interest: C.S. Calfee has nothing to disclose. K.E.A. Burns is supported by a Physician Services Incorporated-50 Mid-Career Clinical Research Award. Conflict of interest: D. Brodie reports receiving research support from ALung Technologies, outside of the submitted work, and was previously on their medical advisory board; he has been on the medical advisory boards for Baxter, Abiomed, Xenios AG and Hemovent. Conflict of interest: V.A. McCredie has nothing to disclose. Conflict of interest: D.Y. Kim has nothing to disclose. Conflict of interest: K. Kyeremanteng has nothing to disclose. Conflict of interest: J. Lampron has nothing to disclose. Conflict of interest: A.S. Slutsky reports consulting for Baxter and Xenios AG. Conflict of interest: A. Combes reports receiving personal fees from Maquet, Xenios AG and Baxter International Inc., outside of the submitted work. Conflict of interest: B. Rochwerg is supported by a Hamilton Health Sciences New Investigator Grant., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: External chest-wall compression (ECC) is sometimes used in ARDS patients despite lack of evidence. It is currently unknown whether this practice has any clinical benefit in patients with COVID-19 ARDS (C-ARDS) characterized by a respiratory system compliance (C rs ) < 35 mL/cmH 2 O., Objectives: To test if an ECC with a 5 L-bag in low-compliance C-ARDS can lead to a reduction in driving pressure (DP) and improve gas exchange, and to understand the underlying mechanisms., Methods: Eleven patients with low-compliance C-ARDS were enrolled and underwent 4 steps: baseline, ECC for 60 min, ECC discontinuation and PEEP reduction. Respiratory mechanics, gas exchange, hemodynamics and electrical impedance tomography were recorded. Four pigs with acute ARDS were studied with ECC to understand the effect of ECC on pleural pressure gradient using pleural pressure transducers in both non-dependent and dependent lung regions., Results: Five minutes of ECC reduced DP from baseline 14.2 ± 1.3 to 12.3 ± 1.3 cmH 2 O (P < 0.001), explained by an improved lung compliance. Changes in DP by ECC were strongly correlated with changes in DP obtained with PEEP reduction (R 2  = 0.82, P < 0.001). The initial benefit of ECC decreased over time (DP = 13.3 ± 1.5 cmH 2 O at 60 min, P = 0.03 vs. baseline). Gas exchange and hemodynamics were unaffected by ECC. In four pigs with lung injury, ECC led to a decrease in the pleural pressure gradient at end-inspiration [2.2 (1.1-3) vs. 3.0 (2.2-4.1) cmH 2 O, P = 0.035]., Conclusions: In C-ARDS patients with C rs  < 35 mL/cmH 2 O, ECC acutely reduces DP. ECC does not improve oxygenation but it can be used as a simple tool to detect hyperinflation as it improves C rs and reduces P pl gradient. ECC benefits seem to partially fade over time. ECC produces similar changes compared to PEEP reduction., (© 2022. The Author(s).)

Rationale: Reverse triggering dyssynchrony (RT) is a patient-ventilator interaction where a respiratory muscle contraction is triggered by a passive mechanical insufflation. Its impact on diaphragm structure and function is unknown. Objectives: To establish an animal model of RT with lung injury receiving lung-protective ventilation and to assess its impact on the structure and function of the diaphragm. Methods: Lung injury was induced by surfactant depletion and high-stress ventilation in 32 ventilated pigs. Animals were allocated to receive passive mechanical ventilation (Vt: 10 ml/kg; respiratory rate [RR]: 30-35 breaths/min; n  = 8) or a more lung-protective strategy (Vt: 6-8 ml/kg; n  = 24) with adjustments in RR to facilitate the occurrence of RT for 3 hours. Diaphragm function (transdiaphragmatic pressure [Pdi] during phrenic nerve stimulation [force/frequency curve]) and structure (biopsies) were assessed. The impact of RT on diaphragm function was analyzed according to the breathing effort assessed by the pressure-time product. Measurements and Main Results: Compared with passive ventilation, the protective ventilation group with RT received significantly lower Vt (7 vs. 10 ml/kg) and higher RR (45 vs. 31 breaths/min). An entrainment pattern of 1:1 was the most frequently occurring in 83% of the animals. Breathing effort induced by RT was highly variable across animals. RT with the lowest tercile of breathing effort was associated with 23% higher twitch Pdi compared with passive ventilation, whereas RT with high breathing effort was associated with a 10% lower twitch Pdi and a higher proportion of abnormal muscle fibers. Conclusions: In a reproducible animal model of RT with variable levels of breathing effort and entrainment patterns, RT with high effort is associated with impaired diaphragm function, whereas RT with low effort is associated with preserved diaphragm force.

Background: An abrupt lung deflation in rodents results in lung injury through vascular mechanisms. Ventilator disconnections during endo-tracheal suctioning in humans often cause cardio-respiratory instability. Whether repeated disconnections or lung deflations cause lung injury or oedema is not known and was tested here in a porcine large animal model., Methods: Yorkshire pigs (~ 12 weeks) were studied in three series. First, we compared PEEP abruptly deflated from 26 cmH 2 O or from PEEP 5 cmH 2 O to zero. Second, pigs were randomly crossed over to receive rapid versus gradual PEEP removal from 20 cmH 2 O. Third, pigs with relative volume overload, were ventilated with PEEP 15 cmH 2 O and randomized to repeated ETT disconnections (15 s every 15 min) or no disconnection for 3 h. Hemodynamics, pulmonary variables were monitored, and lung histology and bronchoalveolar lavage studied., Results: As compared to PEEP 5 cmH 2 O, abrupt deflation from PEEP 26 cmH 2 O increased PVR, lowered oxygenation, and increased lung wet-to-dry ratio. From PEEP 20 cmH 2 O, gradual versus abrupt deflation mitigated the changes in oxygenation and vascular resistance. From PEEP 15, repeated disconnections in presence of fluid loading led to reduced compliance, lower oxygenation, higher pulmonary artery pressure, higher lung wet-to-dry ratio, higher lung injury score and increased oedema on morphometry, compared to no disconnects., Conclusion: Single abrupt deflation from high PEEP, and repeated short deflations from moderate PEEP cause pulmonary oedema, impaired oxygenation, and increased PVR, in this large animal model, thus replicating our previous finding from rodents. Rapid deflation may thus be a clinically relevant cause of impaired lung function, which may be attenuated by gradual pressure release., (© 2022. The Author(s).)

Background: Prolonged need for mechanical ventilation greatly impacts life expectancy of patients after spinal cord injury (SCI). Weaning outcomes have never been systematically assessed. In this systematic review and meta-analysis, we aimed to investigate the probability of weaning success, duration of mechanical ventilation, mortality, and their predictors in mechanically ventilated patients with SCI., Methods: We searched six databases from inception until August 2021 for randomized-controlled trials and observational studies enrolling adult patients (≥ 16 years) with SCI from any cause requiring mechanical ventilation. Titles and abstracts were screened independently by two reviewers. Full texts of the identified articles were then assessed for eligibility. Data were extracted independently and in duplicate by pairs of authors, using a standardized data collection form. Synthetic results are reported as meta-analytic means and proportions, based on random effects models., Results: Thirty-nine studies (14,637 patients, mean age 43) were selected. Cervical lesions were predominant (12,717 patients had cervical lesions only, 1843 in association with other levels' lesions). Twenty-five studies were conducted in intensive care units (ICUs), 14 in rehabilitative settings. In ICU, the mean time from injury to hospitalization was 8 h [95% CI 7-9], mean duration of mechanical ventilation 27 days [20-34], probability of weaning success 63% [45-78] and mortality 8% [5-11]. Patients hospitalized in rehabilitation centres had a greater number of high-level lesions (C3 or above), were at 40 days [29-51] from injury and were ventilated for a mean of 97 days [65-128]; 82% [70-90] of them were successfully weaned, while mortality was 1% [0-19]., Conclusions: Although our study highlights the lack of uniform definition of weaning success, of clear factors associated with weaning outcomes, and of high-level evidence to guide optimal weaning in patients with SCI, it shows that around two-thirds of mechanically ventilated patients can be weaned in ICU after SCI. A substantial gain in weaning success can be obtained during rehabilitation, with additional duration of stay but minimal increase in mortality. The study is registered with PROSPERO (CRD42020156788)., (© 2021. The Author(s).)

Background: Ultrasound may be useful to assess the structure, activity, and function of the abdominal muscles in patients who are mechanically ventilated., Research Question: Does measurement of abdominal muscle thickening on ultrasound in patients who are mechanically ventilated provide clinically relevant information about abdominal muscle function and weaning outcomes?, Study Design and Methods: This study consisted of two parts, a physiological study conducted in healthy subjects and a prospective observational study in patients who were mechanically ventilated. Abdominal muscle thickness and thickening fraction were measured during cough and expiratory efforts in 20 healthy subjects, and prior to and during a spontaneous breathing trial in 57 patients being ventilated., Results: In healthy subjects, internal oblique and rectus abdominis thickening fraction correlated with pressure generated during expiratory efforts (P < .001). In patients being ventilated, abdominal muscle thickness and thickening fraction were feasible to measure in all patients, and reproducibility was moderately acceptable. During a failed spontaneous breathing trial, thickening fraction of transversus abdominis and internal oblique increased substantially from baseline (13.2% [95% CI, 0.9-24.8] and 7.2% [95% CI, 2.2-13.2], respectively). The combined thickening fraction of transversus abdominis, internal oblique, and rectus abdominis measured during cough was associated with an increased risk of reintubation or reconnection to the ventilator following attempted liberation (OR, 2.1; 95% CI, 1.1-4.4 per 10% decrease in thickening fraction)., Interpretation: Abdominal muscle thickening on ultrasound was correlated to the airway pressure generated by expiratory efforts. In patients who were mechanically ventilated, abdominal muscle ultrasound measurements are feasible and moderately reproducible. Among patients who passed a spontaneous breathing trial, reduced abdominal muscle thickening during cough was associated with a high risk of liberation failure., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03567564; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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 H 2 O, 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.

Background: Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS)., Methods: An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH 2 O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared., Findings: 12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved., Interpretation: More than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached., Competing Interests: Conflict of interest: T. Pham has nothing to disclose. Conflict of interest: A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. Conflict of interest: G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. Conflict of interest: G. Rubenfeld has nothing to disclose. Conflict of interest: E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. Conflict of interest: G. Bugedo has nothing to disclose. Conflict of interest: J.A. Lorente has nothing to disclose. Conflict of interest: A.D.V. Fernandes has nothing to disclose. Conflict of interest: F. Van Haren has nothing to disclose. Conflict of interest: A. Bruhn has nothing to disclose. Conflict of interest: F. Rios has nothing to disclose. Conflict of interest: A. Esteban has nothing to disclose. Conflict of interest: L. Gattinoni has nothing to disclose. Conflict of interest: A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. Conflict of interest: D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work; in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC; is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen's University of Belfast (http://www.google.com/patents/US8962032); and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. Conflict of interest: M. Ranieri has nothing to disclose. Conflict of interest: B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. Conflict of interest: H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. Conflict of interest: L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. Conflict of interest: J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., (Copyright ©ERS 2021.)

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 H 2 O/[ml/kg]; 90% credible interval, 0.63-1.02). Ers was classified as low (<2 cm H 2 O/[ml/kg], n  = 321, 32%), intermediate (2-3 cm H 2 O/[ml/kg], n  = 475, 46%), and high (>3 cm H 2 O/[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.