Ventilator-induced Lung Injury Research Articles

Evaluation of health care providers’ ability to identify patient-ventilator triggering asynchrony in intensive care unit: a translational observational study in China

BackgroundPatient-ventilator asynchrony (PVA) can result in ventilator-induced lung injury (VILI), prolong mechanical ventilation, and ventilator withdrawal failure. The ability of healthcare providers in China to recognize patient-ventilator asynchrony is unknown. The aim of our study was to evaluate the ability and potential influencing factors to correctly identify patient-ventilator triggering asynchrony in tertiary hospitals in China.MethodsThis was an observational study carried out in 53 tertiary hospitals in China. A total of 191 healthcare providers were asked to finish entry test and evaluation test sequentially. Entry test identified qualified professionals by matching concepts with its corresponding interpretations. Evaluation test assessed the ability in recognizing patient-ventilator asynchrony waveforms by matching asynchrony waveforms with corresponding concepts. A total of 109 qualified professionals were identified. Further analysis based on professional title, role in critical care team, years of experience in managing invasive mechanical ventilation, number of published articles in the field of clinical critical respiratory medicine and training in respiratory waveform/respiratory mechanics was carried out among qualified professionals. A self-innovate Remote-VentlateView platform was used to discriminate the patient-ventilator triggering asynchrony.ResultsAmong 109 qualified professionals, the average recognition accuracy was 3.45 out of 8 sets. Inconsistency of concept cognition and waveform recognition of patient-ventilator asynchrony was found among all types of asynchronies. The accuracy of the trained professionals was greater than that of the nontrained professionals for ineffective trigger [76.7% vs. 59.2% (p = 0.009)], auto-trigger [26.7% vs. 12.2% (p = 0.014)] and reverse triggers [30.8% vs. 12.2% (p = 0.002)]. Professionals who published more than 2 articles in the field of critical respiratory performed better on auto-triggers [41.7% vs. 15.9% (p = 0.001)] and reverse triggers [38.9% vs. 19.2% (p = 0.018)]. Neither experience in managing invasive mechanical ventilation nor professional title was associated with the ability of healthcare providers to identify asynchrony.ConclusionsReceiving training in mechanical ventilation and conducting critical respiratory clinical research may increase healthcare providers’ ability to identify patient-ventilator asynchrony by using waveform analysis. The Remote-VentlateView platform may assist in identifying patient-ventilator asynchronies.

Comparison of airway pressure release ventilation (APRV) versus biphasic positive airway pressure (BIPAP) ventilation in COVID-19 associated ARDS using transpulmonary pressure monitoring

BackgroundAPRV has been used for ARDS in the past. Little is known about the risk of ventilator- induced lung- injury (VILI) in APRV vs. BIPAP in the management of in COVID19-associated ARDS (CARDS). This study aimed to compare transpulmonary pressures (TPP) in APRV vs. BIPAP in CARDS in regard to lung protective ventilator settings.MethodsThis retrospective, monocentric cohort study (ethical approval: 21-1553) assessed all adult ICU- patients with CARDS who were ventilated with BIPAP vs. APRV and monitored with TPP from 03/2020 to 10/2021. Ventilator-settings / -pressures, TPP, hemodynamic and arterial blood gas parameters were compared in both modes.Results20 non- spontaneously breathing patients could be included in the study: Median TPPendexpiratory was lower / negative in APRV (-1.20mbar; IQR − 4.88 / +4.53) vs. positive in BIPAP (+ 3.4mbar; IQR + 1.95 / +8.57; p < .01). Median TPPendinspiratory did not differ. In APRV, mean tidal- volume per body- weight (7.05 ± 1.28 vs. 5.03 ± 0.77 ml; p < .01) and mean airway- pressure (27.08 ± 1.67 vs. 22.68 ± 2.62mbar; p < .01) were higher. There was no difference in PEEP, peak-, plateau- or driving- pressure, compliance, oxygenation and CO2- removal between both modes.ConclusionDespite higher tidal- volumes / airway-pressures in APRV vs. BIPAP, TPPendinspiratory was not increased. However, in APRV median TPPendexpiratory was negative indicating an elevated risk of occult atelectasis in APRV- mode in CARDS. Therefore, TPP- monitoring could be a useful tool for monitoring a safe application of APRV- mode in CARDS.

An optimal protective ventilation strategy in lung resection surgery: a prospective, single-center, three-arm randomized controlled trial.

Protective ventilation reduces ventilator-induced acute lung injury postoperatively; however, the optimal strategy for one-lung ventilation (OLV) remains unclear. This study compared three protective ventilation strategies with a postoperative partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio to reduce the incidence of immediate postoperative pulmonary complications (PPCs) in patients undergoing lung resection surgery. Eighty-seven patients with ASA physical status I-III requiring OLV for lung resection surgery were randomized into three groups according to the applied ventilation strategies: low tidal volume (VT) of 4mL/kg of predicted body weight (PBW) (LV group), medium VT of 6mL/kg of PBW (MV group), and high VT of 8mL/kg of PBW (HV group). All patients received 5 cmH2O of positive end-expiratory pressure (PEEP). The primary outcome was the mean difference of PaO2/FiO2 ratio after surgery. The radiologic findings of acute lung injuries were also evaluated. The incidence of immediate PPCs was determined by PaO2/FiO2 ratio of < 300mmHg and/or newly developed radiological findings within 72h after surgery. The MV group showed the highest PaO2/FiO2 ratio at 6h postoperatively (P = 0.010). There were no significant among-group differences in radiological findings in 3 postoperative days. The MV group showed the lowest incidence of immediate PPCs among the three groups (P = 0.007). During OLV in lung resection surgery, protective ventilation at a VT of 6mL/kg with PEEP of 5 cmH2O may achieve a higher postoperative PaO2/FiO2 ratio, reducing the incidence of immediate PPCs.

The impact of pneumoperitoneum on respirtory system: complications and managment strategies in laparoscopic surgery

Laparoscopic surgery, a cornerstone of contemporary surgical practice, revolutionizes traditional surgical techniques by employing minimally invasive procedures. However, this innovative approach poses intricate challenges, particularly in respiratory management, necessitating a comprehensive understanding of its physiological implications. Pneumoperitoneum involves insufflating the abdominal cavity with carbon dioxide (CO2) to create a suitable working space. The introduction of CO2 into the peritoneal cavity elevates intra-abdominal pressure, prompting physiological adaptations that compromise respiratory function. These alterations, including increased peak inspiratory pressure, decreased dynamic respiratory system compliance, and the promotion of intraoperative atelectasis, underscore the intricate interplay between pneumoperitoneum and respiratory physiology.Amidst these challenges, positive end-expiratory pressure emerges as a crucial intervention for mitigating the adverse effects of pneumoperitoneum on respiratory mechanics. By maintaining airway patency and preventing alveolar collapse during expiration, positive end-expiratory pressure helps counteract the reduction in functional residual capacity associated with elevated intra-abdominal pressure. Additionally, positive endexpiratory pressure serves to optimize lung recruitment, thereby improving ventilation-perfusion matching and enhancing oxygenation.Mechanical ventilation during laparoscopic procedures further complicates respiratory management, potentially exacerbating lung injury. The application of protective lung ventilation strategies, such as low tidal volume combined with judicious positive end-expiratory pressure titration, represents a cornerstone in mitigating ventilator-induced lung injury and reducing postoperative pulmonary complications. However, the optimal implementation of these strategies remains a subject of ongoing debate, highlighting the need for personalized approaches tailored to individual patient characteristics and surgical contexts.Understanding the pivotal role of positive end-expiratory pressure in mitigating the adverse respiratory effects of pneumoperitoneum underscores its importance as a cornerstone intervention in laparoscopic surgery. By optimizing positive end-expiratory pressure levels based on patient characteristics and procedural requirements, healthcare practitioners can effectively mitigate the risk of pulmonary complications and enhance surgical outcomes.

Characterizing SV40-hTERT Immortalized Human Lung Microvascular Endothelial Cells as Model System for Mechanical Stretch-Induced Lung Injury.

Drug development for human disease relies on preclinical model systems such as human cell cultures and animal experiments before therapeutic treatments can ultimately be tested on humans in clinical studies. We here describe the generation of a novel human cell line (HLMVEC/SVTERT289) that we generated by transfection of microvascular endothelial cells from healthy donor lung tissue with the catalytic domain of telomerase and the SV40 large T/small t-antigen. These cells exhibited satisfactory growth characteristics and largely maintained their native characteristics, including morphology, cell surface marker expression, angiogenic potential and the protein composition of secreted extracellular vesicles. In order to test their suitability as a disease model, we simulated mechanical stress induced by cyclic stretch as encountered in ventilator-induced lung injury using the FlexCell® system and compared their performance to primary lung endothelial cells. In this setting, HLMVEC/SVTERT289 cells exhibited significantly higher neprilysin activity on the cell surface and extracellular vesicles secreted from the cell line exhibited higher Tissue Factor and ACE2 expression but lower ACE expression and ACE activity than vesicles released from the primary cells. This study provides an unprecedented and detailed characterization of the HLMVEC/SVTERT289 cell line, which should help to appraise its suitability in different molecular studies.

CAVIN2 attenuates ventilator-induced lung injury in rats by MAPK/ERK1/2 signaling pathway.

Mechanical ventilation is an important treatment in medical treatment, but it may cause or aggravate lung injury, which is called ventilator-induced lung injury (VILI). Studies have shown that CAVIN2 plays an important role in regulating inflammatory responses and cell death. However, its functional mechanism in VILI remains unclear. This study explores the potential role and mechanisms of CAVIN2 in the pathogenesis of VILI. We constructed rat and cell models of VILI. Real-time quantitative polymerase chain reactions (qRT-PCR), Western blot (WB), immunohistochemistry (IHC) and immunofluorescence (IF) were used to detect CAVIN2, ERK1/2, p-ERK1/2, autophagy-associated marker proteins LC3II/I, Beclin1 and P62, and the expression level of pro-inflammatory factors IL-1β and IL-6. Hematoxylin and eosin (H&E) staining were used to evaluate the degree of pathological injury of lung tissue, and the lung permeability was evaluated by measuring the wet-dry ratio of lung tissue and the total protein content in bronchoalveolar lavage fluid (BALF). Molecular docking, co-immunoprecipitation and immunofluorescence were used to verify the binding of CAVIN2 and ERK1/2, and the regulatory mechanisms of both were investigated by rescue experiments. CAVIN2 expression was downregulated in VILI rat lung tissues and ATII cells, whereas p-ERK1/2 expression was up-regulated. Overexpressing CAVIN2 alleviated pathological damage in VILI rat lung tissues and reduced the expression of pro-inflammatory factors and autophagy-related marker proteins in both lung tissues and ATII cells. Conversely, knockdown of CAVIN2 led to increased expression of pro-inflammatory factors and autophagy-related marker proteins in ATII cells. Further mechanism studies showed that CAVIN2 binds to ERK1/2 and inhibits ERK1/2 phosphorylation. Conversely when treated with the p-ERK1/2 agonist Ro67-7476, the protective, anti-inflammatory, and anti-autophagic effects of overexpressing CAVIN2 in VILI rats and ATII cells were reversed. CAVIN2 can bind to ERK1/2 and inhibit the activation of MAPK/ERK1/2 signaling pathway to reduce inflammatory response and autophagy in VILI, thereby reducing lung injury. Therefore, CAVIN2 may be a potential intervention target to provide a new strategy for the treatment of VILI.

Inhibition of lncEPS by TLR4/NF-κB pathway induces ventilator-induced lung injury by decreasing its binding to and upregulating Hspa5

Whether LincRNA erythroid prosurvival (LncEPS) reduces VILI remains unclear. A GSE200932 microarray was used to screen differentially expressed genes (DEGs). A VILI mouse model was constructed by mechanical ventilation (MV), with or without TAK242 or SN50 pretreatment. Airway transfection with adeno-associated virus (AAV) was used to overexpress lncEPS in alveolar macrophages (AMs). Lung tissues were collected to assess pathological injury and macrophage polarization. NLRP3 inflammasome, TLR4/ NF-κB pathway activation and heat shock protein family A member 5 (Hspa5) in lung tissue and AMs wre evaluated. LncEPS localization and regulatory changes were assessed using in situ hybridization and RT–PCR. Lung tissues after lncEPS overexpression were subjected to transcriptomics. Chromatin isolation and mass spectrometry (MS) were performed to identify proteins interacting with lncEPS. GSE200932 microarray showed that the DEGs were related to NF-κB pathway, Toll-like receptor pathway and NOD-like receptor pathway. TAK242 or SN50 treatment increased polarization of M2 macrophages and decreased NLRP3 inflammasome activation by inhibiting TLR4/NF-κB pathway in VILI. Inhibition of TLR4/NF-κB pathway upregulated lncEPS expression in AMs. Overexpression of lncEPS increased polarization of M2 macrophages and decreased NLRP3 inflammasome activation, eventually alleviating VILI in mice. Mechanistically, lncEPS bound to Hspa5 and downregulated its expression to inhibit inflammatory response.

Effect of Early Vs Late Intubation on Outcomes in Critically ill Patients with COVID-19 A Protocolised Approach

Introduction: COVID-19 related ARDS (CARDS) is associated with high mortality. Optimal timing of intubation in these patients is still under research. Early intubation could avoid alternate means of oxygenation like High Frequency Nasal Canula (HFNC) or Non Invasive Ventilation(NIV), which prevents Self Inflicting Lung Injury (SILI) in patients breathing spontaneously. At the same time intubation itself may generate aerosols and delaying of intubation may mean patient could be managed with other means of oxygenation thus preventing Ventilator Induced Lung Injury (VILI). Moreover, the concept of SILI is not supported by scientific data. This study investigated the effect of timing of intubation on 28-day mortality in CARDS patients. Methodology: A retrospective observational study was performed in patients admitted in COVID ICU, between January 1st and August 31st 2021, requiring ventilation. Following data collection patients were categorised into two groups. ‘Delayed ’intubation group consisted of patients receiving Non Re-Breathing Mask (NRBM) /HFNC /NIV initially and got intubated after 24 hrs of ICU admission. The remaining patients who were intubated within 24 hrs comprised the ‘early’ intubation group. The decision for early intubation was made by following the institution protocol for ventilatory management. Results: Among 114 ventilated patients 56 were intubated within 24 hours and 58 were intubated after 24 hours. The 28-day mortality in early and delayed intubation group were 39.7% and 60.3% respectively (p = 0.01). In early intubation group duration of mechanical ventilation (5±1.4), length of ICU stay (7.3±2.1) and hospital stay (9.4±4) were significantly less compared to delayed intubation group (p value &lt;0.05). Conclusion: Decision for intubation is complex and multifactorial which is usually individualized depending on the clinical condition. Early intubation is associated with improved survival rates and reduced duration of mechanical ventilation, length of ICU stay &amp; length of hospital stay in severe CARDS patients.

PEEP titration guided by electrical impedance tomography in critically ill mechanically ventilated patients with acute hypoxemic respiratory failure.

Positive end-expiratory pressure (PEEP) titration is crucial for improving oxygenation and preventing ventilator-induced lung injury in acute hypoxemic respiratory failure. Electrical impedance tomography (EIT) offers real-time, bedside monitoring of lung ventilation distribution, potentially guiding individualized PEEP settings.

Current concepts of ventilator-induced lung injury

Current concepts of ventilator-induced lung injury

Gas transport mechanisms during high-frequency ventilation

By virtue of applying small tidal volumes, high-frequency ventilation is advocated as a method of minimizing ventilator-induced lung injury. Lung protective benefits are established in infants, but not in other patient cohorts. Efforts to improve and extend the lung protection potential should consider how fundamental modes of gas transport can be exploited to minimize harmful tidal volumes while maintaining or improving ventilation.This research investigates different models of gas transport during high-frequency ventilation and discusses the extent to which the gas transport mechanisms are considered in each. The research focuses on the rationale for current ventilation protocols, how they were informed by these models, and investigates alternative protocols that may improve gas transport and lung protection. A review of high-frequency ventilation physiology and fluid mechanics literature was performed, and dimensional analyses were conducted showing the relationship between clinical data and the model outputs. We show that contemporary protocols have been informed by resistor-inductor-capacitor, or network, models of the airway-lung system that are formulated around a ventilation pressure cost framework. This framework leads to clinical protocol selection that ventilates patients at frequencies that excite a resonance in the lung. We extend on these models by considering frequencies that are much higher than resonance which further optimize gas transport in the airway via alternative gas transport mechanisms to bulk advection that operate for very low tidal volumes. Our findings suggest it is unlikely that gas transport is optimally exploited during current approaches to high-frequency ventilation and protocols that differ significantly from those currently in use could achieve ventilation while using very low tidal volumes.

Ferritinophagy mediated by the AMPK/ULK1 pathway is involved in ferroptosis subsequent to ventilator-induced lung injury

Ferritinophagy mediated by the AMPK/ULK1 pathway is involved in ferroptosis subsequent to ventilator-induced lung injury

Rethinking ARDS classification: oxygenation impairment fails to predict VILI risk

PurposeThe selection and intensity of respiratory support for ARDS are guided by PaO2/FiO2. However, ventilator-induced lung injury (VILI) is linked to respiratory mechanics and ventilator settings. We explored whether the VILI risk is related to ARDS severity based on oxygenation.MethodsWe analysed data on 228 ARDS subjects with PaO2/FiO2 < 200 mmHg, categorized into three severity groups: one based on PaO2/FiO2 ratio, and the others based on tertiles of predictors of VILI: mechanical power ratio (MPR) and driving pressure (DP). In each group of oxygenation-based ARDS severity and MPR and DP tertiles, we measured CT anatomy, gas exchange, respiratory mechanics, VILI prerequisites (lung elastance and lung gas volume), and VILI determinants (tidal volume, PEEP, airway pressures).ResultsPredictors of VILI, such as MPR and DP, were similar across ARDS severity groups based on PaO2/FiO2 ratio, while oxygenation remained comparable across different levels of VILI risk defined by MPR and DP. Oxygenation impairment was associated with increased lung weight, recruitability, and reduced well-inflated tissue. In contrast, MPR and DP tertiles affected variables associated with the baby lung size, such as lung gas volume and well-inflated tissue. Mechanical ventilation intensity increased progressively across MPR and DP tertiles, but remained similar across PaO2/FiO2 severity groups.ConclusionsARDS severity based on oxygenation impairment does not reflect the prerequisites and determinants of VILI. This should prompt a reconsideration of recommending respiratory support based on oxygenation impairment, rather than VILI determinants.

Immediate postinjury extracorporeal carbon dioxide removal reduces ventilator requirements and mitigates acute respiratory distress syndrome in swine.

Awareness of ventilator-induced lung injury contributed to increased use of extracorporeal interventions, but not immediately after injury, before acute respiratory distress syndrome (ARDS) ensues. Our objective was to evaluate the role of venovenous extracorporeal carbon dioxide removal (ECCO2R) in management of mechanically ventilated swine with smoke inhalation injury and 40% body surface area burns. Yorkshire swine (n = 29, 43.2 ± 0.5 kg) underwent anesthesia, instrumentation, severe smoke inhalation, and 40% body surface area burns, followed by 72 hours of round-the-clock intensive care unit care with mechanical ventilation, fluids, pressors, bronchoscopic cast removal, computer tomography scans, and arterial blood assays. Within 1 hour after injury, animals received ECCO2R with either MiniLung (Xenios AG, Heilbronn, Germany; n = 10) or Hemolung (ALung Technologies, Pittsburgh, PA; n = 10), or no ECCO2R in injured controls (INJC, n = 12). Immediate postinjury ECCO2R reduced minute ventilation (p < 0.001) and prevented ARDS in 37.5% of MiniLung and 11.1% of Hemolung animals. Time to ARDS (partial pressure of arterial oxygen to fraction of inspired oxygen ratio below 300) was shortest (14 ± 2.2 hours) in INJC, intermediate (21.6 ± 3.5 hours) in Hemolung (HEMO), and most delayed in MiniLung (31.1 ± 7.2 hours, p = 0.0121, log-rank test vs. INJC). Driving pressure was lower in MiniLung versus INJC (p < 0.0001) and HEMO versus INJC (p = 0.0005) at 48 hours. Extracorporeal CO2 removal reduced systemic levels of tumor necrosis factor α versus INJC. In swine with severe smoke inhalation and burns, immediate postinjury ECCO2R reduced ventilator settings, delayed or prevented ARDS, and reduced its severity. Proactive early percutaneous ECCO2R initiation via simplified, purpose-built devices should be considered as a low-maintenance lung injury management approach with significant disease modifying clinical benefit potential.

Acute respiratory distress syndrome: A review of ARDS across the life course.

Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung disease with significant morbidity and mortality that predominantly requires supportive care in its management. Although initially described in adult patients, the diagnostic definitions for ARDS have evolved over time to accurately describe this disease process in pediatric and, more recently, neonatal patients. The management of ARDS in each age demographic has converged in the application of lung-protective ventilatory strategies to mitigate the primary disease process and prevent its exacerbation by limiting ventilator-induced lung injury. However, differences arise in the preferred ventilatory strategies or adjunctive pulmonary therapies used to mitigate each type of ARDS. In this review, we compare and contrast the epidemiology, common etiologies, pathophysiology, diagnostic criteria, and outcomes of ARDS across the lifespan. Additionally, we discuss in detail the different management strategies used for each subtype of ARDS and spotlight how these strategies were applied to mitigate poor outcomes during the COVID-19 pandemic. This review is geared toward both clinicians and clinician-scientists as it not only summarizes the latest information on disease pathogenesis and patient management in ARDS across the lifespan but also highlights knowledge gaps for further investigative efforts. We conclude by projecting how future studies can fill these gaps in research and what improvements may be envisioned in the management of NARDS and PARDS based on the current breadth of literature on adult ARDS treatment strategies.

Association between driving pressure, systemic inflammation and non-pulmonary organ dysfunction in patients with acute respiratory distress syndrome, a prospective pathophysiological study.

Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction. Additionally, we analyzed this relationship for tidal volume/predicted body weight. Observational study that included adult patients with acute respiratory distress syndrome undergoing invasive mechanical ventilation admitted to the Hospital Clinic of Barcelona, Spain, between June 2019 and February 2021. We conducted mixed-effects models to assess the effects of driving pressure and tidal volume/predicted body weight on the evolution of 22 log-transformed biomarker variables during the first, third, and fifth days after study enrollment. These 22 systemic biomarkers characterized epithelial and endothelial pulmonary dysfunction, inflammation, and coagulation disorders in the included patients. In the same fashion, the association between driving pressure and non-pulmonary multiorgan dysfunction was evaluated by the non-pulmonary sequential organ failure assessment score (non-pulmonary SOFA) and its associated variables. Finally, we performed mediation analyses to assess whether the relationship between biomarkers and driving pressure was mediated by other ventilator-induced lung injury parameters. Thirty-eight patients were included. Driving pressure was independently associated with soluble Receptor for advanced glycation end-products, Interleukin (IL)-8, IL-6, IL-10, IL-17, Interferon-ɣ, Chemokine (C-C motif)-2, Vascular endothelial growth factor, Tissue factor, Protein C, Protein S, and higher dose of norepinephrine. However, this relationship attenuated over time. In contrast, tidal volume/predicted body weight was not associated with any of the 22 biomarkers tested . A concomitant increase in positive end-inspiratory plateau pressure or tidal volume did not mediate the effect of driving pressure on biomarkers. Conversely, the association between compliance of the respiratory system and pulmonary epithelial dysfunction was primarily mediated by driving pressure. Driving pressure, but not tidal volume/predicted body weight, was correlated with epithelial and endothelial pulmonary dysfunction, inflammation, coagulation disorders, and hemodynamic dysfunction. However, this relationship diminished over time.

The role of pleural pressure in inducing pneumothorax and other adverse effects of positive pressure ventilation.

Mechanical ventilation, essential for critically ill patients, contrasts with natural respiration, primarily due to differences in pleural pressure (Ppleural ). Natural inspiration decreases Ppleural , pulling the lungs away from the thoracic wall, whereas positive pressure inspiration increases Ppleural , pushing the lungs against the thoracic wall. This shift has several consequences. First, elevated Ppleural during positive pressure ventilation can lead to cyclic airway closure, particularly in the dependent lung regions. This increases the risk of atelectasis, that impairs oxygenation and may lead to further complications such as pneumonia. Second, the increase in Ppleural disrupts the balance maintained by negative Ppleural and capillary forces. This disruption reduces the lubricating pleural fluid between the pleurae, increasing friction and shear stress on the lung tissues, which may lead to damage and conditions such as ventilator-induced lung injury and pneumothorax. Furthermore, airway closure can worsen lung compliance, making mechanical ventilation more challenging and increasing the risk of lung overstretching. This necessitates careful management of ventilation settings, particularly the use of positive end-expiratory pressure (PEEP) and recruitment maneuvers to minimize these adverse effects. Protective strategies, such as synchronizing mechanical ventilation with the patient's breathing efforts, prone positioning, and careful application of PEEP, are crucial in reducing Ppleural and its associated risks. Since negative pressure ventilation (NPV) inherently lowers Ppleural , it may help avoid many of the adverse side effects previously discussed. Therefore, reconsidering and reintroducing NPV in a modern context should be seriously explored.

Dynamic driving pressure predicts ventilator-induced lung injury in mice with and without endotoxin-induced acute lung injury.

Mechanical ventilation is a necessary lifesaving intervention for patients with Acute Respiratory Distress Syndrome (ARDS) but it can cause ventilator induced lung injury (VILI), which contributes to the high ARDS mortality rate (≈40%). Bedside determination of optimally lung-protective ventilation settings is challenging because the evolution of VILI is not immediately reflected in clinically available, patient-level, data. The goal of this work was therefore to test ventilation waveform-derived parameters that represent the degree of ongoing VILI and can serve as targets for ventilator adjustments. VILI was generated at three different positive end expiratory pressures in a murine inflammation-mediated (lipopolysaccharide, LPS) acute lung injury model and in initially healthy controls. LPS injury increased expression of proinflammatory cytokines and caused widespread atelectasis, predisposing the lungs to VILI as measured in structure, mechanical function, and inflammation. Changes in lung function were used as response variables in an elastic net regression model that predicted VILI severity from tidal volume, dynamic driving pressure (PDDyn), mechanical power calculated by integration during inspiration or the entire respiratory cycle, and power calculated according to Gattinoni' s equation. Of these, PDDyn best predicted functional outcomes of injury using either data from the entire dataset or from 5-minute time windows. The windowed data shows higher predictive accuracy after a ≈1-hour 'run in' period and worse accuracy immediately following recruitment maneuvers. This analysis shows that low driving pressure is a computational biomarker associated with better experimental VILI outcomes and supports the use of driving pressure to guide ventilator adjustments to prevent VILI.

Emerging roles of mechanosensitive ion channels in ventilator induced lung injury: a systematic review.

The pathogenetic mechanisms of ventilator-induced lung injury (VILI) still need to be elucidated. The mechanical forces during mechanical ventilation are continually sensed and transmitted by mechanosensitive ion channels (MSICs) in pulmonary endothelial, epithelial, and immune cells. In recent years, MSICs have been shown to be involved in VILI. A systematic search across PubMed, the Cochrane Library, Web of Science, and ScienceDirect was performed from inception to March 2024, and the review was conducted in accordance with PRISMA guidelines. The potential eligible studies were evaluated by two authors independently. Study characteristics, quality assessment, and potential mechanisms were analyzed. We included 23 eligible studies, most of which were performed with murine animals in vivo. At the in vitro level, 52% and 48% of the experiments were conducted with human or animal cells, respectively. No clinical studies were found. The most reported MSICs include Piezo channels, transient receptor potential channels, potassium channels, and stretch-activated sodium channels. Piezo1 has been the most concerned channel in the recent five years. This study found that signal pathways, such as RhoA/ROCK1, could be enhanced by cyclic stretch-activated MSICs, which contribute to VILI through dysregulated inflammation and immune responses mediated by ion transport. The review indicates the emerging role of MSICs in the pathogenesis of VILI, especially as a signal-transmitting link between mechanical stretch and pathogenesis such as inflammation, disruption of cell junctions, and edema formation. Mechanical stretch stimulates MSICs to increase transcellular ion exchange and subsequently generates VILI through inflammation and other pathogeneses mediated by MSICs signal-transmitting pathways. These findings make it possible to identify potential therapeutic targets for the prevention of lung injury through further exploration and more studies. https://inplasy.com/inplasy-2024-10-0115/, identifier INPLASY2024100115.

Does the Intensity of Therapy Correspond to the Severity of Acute Respiratory Distress Syndrome (ARDS)?

Objectives: The intensity of respiratory treatment in acute respiratory distress syndrome (ARDS) is traditionally adjusted based on oxygenation severity, as defined by the mild, moderate, and severe Berlin classifications. However, ventilator-induced lung injury (VILI) is primarily determined by ventilator settings, namely tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP). All these variables, along with respiratory elastance, are included in the concept of mechanical power. The aim of this study is to investigate whether applied mechanical power is proportional to oxygenation severity. Methods: We analyzed 291 ARDS patients (71 mild, 155 moderate, and 65 severe). We defined low, middle, and high mechanical power by dividing the entire population into tertiles with a similar number of patients. In each oxygenation class, we measured computed tomography (CT) anatomy, gas exchange, respiratory mechanics, mechanical power, and mortality rate. Results: ARDS severity was proportional to lung anatomy impairment, as defined by quantitative CT scans (i.e., lung volume and well-aerated tissue decreased across the ARDS classes, while respiratory elastance increased, as did mortality). Mechanical power, however, was similarly distributed across the severity classes, as the decrease in tidal volume in severe ARDS was offset by an increase in respiratory rate. Within each ARDS class, mortality increased from low to high mechanical power (roughly 1% for each J/min increase). Conclusions: Both lung severity and mechanical power independently impact mortality rates. It is tempting to speculate that ARDS severity primarily reflects the natural course of the disease, while mechanical power primarily reflects the risk of VILI.