Remimazolam Alleviates Ventilator-Induced Lung Injury by Activating TSPO to Inhibit Macrophage Pyroptosis.

BACKGROUND: Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI. METHODS: A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments. RESULTS: Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1ß, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis. CONCLUSION: Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.

AARC Clinical Practice Guideline: Patient-Ventilator Assessment.

Given the important role of patient-ventilator assessments in ensuring the safety and efficacy of mechanical ventilation, a team of respiratory therapists and a librarian used Grading of Recommendations, Assessment, Development, and Evaluation methodology to make the following recommendations: (1) We recommend assessment of plateau pressure to ensure lung-protective ventilator settings (strong recommendation, high certainty); (2) We recommend an assessment of tidal volume (VT) to ensure lung-protective ventilation (4-8 mL/kg/predicted body weight) (strong recommendation, high certainty); (3) We recommend documenting VT as mL/kg predicted body weight (strong recommendation, high certainty); (4) We recommend an assessment of PEEP and auto-PEEP (strong recommendation, high certainty); (5) We suggest assessing driving pressure to prevent ventilator-induced injury (conditional recommendation, low certainty); (6) We suggest assessing FIO2 to ensure normoxemia (conditional recommendation, very low certainty); (7) We suggest telemonitoring to supplement direct bedside assessment in settings with limited resources (conditional recommendation, low certainty); (8) We suggest direct bedside assessment rather than telemonitoring when resources are adequate (conditional recommendation, low certainty); (9) We suggest assessing adequate humidification for patients receiving noninvasive ventilation (NIV) and invasive mechanical ventilation (conditional recommendation, very low certainty); (10) We suggest assessing the appropriateness of the humidification device during NIV and invasive mechanical ventilation (conditional recommendation, low certainty); (11) We recommend that the skin surrounding artificial airways and NIV interfaces be assessed (strong recommendation, high certainty); (12) We suggest assessing the dressing used for tracheostomy tubes and NIV interfaces (conditional recommendation, low certainty); (13) We recommend assessing the pressure inside the cuff of artificial airways using a manometer (strong recommendation, high certainty); (14) We recommend that continuous cuff pressure assessment should not be implemented to decrease the risk of ventilator-associated pneumonia (strong recommendation, high certainty); and (15) We suggest assessing the proper placement and securement of artificial airways (conditional recommendation, very low certainty).

Recruitment-to-inflation ratio for bedside PEEP selection in acute respiratory distress syndrome.

In acute respiratory distress syndrome, the role of positive end-expiratory pressure (PEEP) to prevent ventilator-induced lung injury is controversial. Randomized trials comparing higher versus lower PEEP strategies failed to demonstrate a clinical benefit. This may depend on the inter-individually variable potential for lung recruitment (i.e. recruitability), which would warrant PEEP individualization to balance alveolar recruitment and the unavoidable baby lung overinflation produced by high pressure. Many techniques have been used to assess recruitability, including lung imaging, multiple pressure-volume curves and lung volume measurement. The Recruitment-to-Inflation ratio (R/I) has been recently proposed to bedside assess recruitability without additional equipment. R/I assessment is a simplified technique based on the multiple pressure-volume curve concept: it is measured by monitoring respiratory mechanics and exhaled tidal volume during a 10-cmH2O one-breath derecruitment maneuver after a short high-PEEP test. R/I scales recruited volume to respiratory system compliance, and normalizes recruitment to a proxy of actual lung size. With modest R/I (<0.3-0.4), setting low PEEP (5-8 cmH2O) may be advisable; with R/I>0.6-0.7, high PEEP (≥15 cmH2O) can be considered, provided that airway and/or transpulmonary plateau pressure do not exceed safety limits. In case of intermediate R/I (≈0.5), a more granular assessment of recruitability may be needed. This could be accomplished with advanced monitoring tools, like sequential lung volume measurement with granular R/I assessment or electrical impedance tomography monitoring during a decremental PEEP trial. In this review, we discuss R/I rationale, applications and limits, providing insights on its clinical use for PEEP selection in moderate-to-severe acute respiratory distress syndrome.

Advancing ICU patient care with a Real-Time predictive model for mechanical Power to mitigate VILI.

BACKGROUND: Invasive Mechanical Ventilation (IMV) in Intensive Care Units (ICU) significantly increases the risk of Ventilator-Induced Lung Injury (VILI), necessitating careful management of mechanical power (MP). This study aims to develop a real-time predictive model of MP utilizing Artificial Intelligence to mitigate VILI. METHODOLOGY: A retrospective observational study was conducted, extracting patient data from Clinical Information Systems from 2018 to 2022. Patients over 18 years old with more than 6 h of IMV were selected. Continuous data on IMV variables, laboratory data, monitoring, procedures, demographic data, type of admission, reason for admission, and APACHE II at admission were extracted. The variables with the highest correlation to MP were used for prediction and IMV data was grouped in 15-minute intervals using the mean. A mixed neural network model was developed to forecast MP 15 min in advance, using IMV data from 6 h before the prediction and current patient status. The model's ability to predict future MP was analyzed and compared to a baseline model predicting the future value of MP as equal to the current value. RESULTS: The cohort consisted of 1967 patients after applying inclusion criteria, with a median age of 63 years and 66.9 % male. The deep learning model achieved a mean squared error of 2.79 in the test set, indicating a 20 % improvement over the baseline model. It demonstrated high accuracy (94 %) in predicting whether MP would exceed a critical threshold of 18 J/min, which correlates with increased mortality. The integration of this model into a web platform allows clinicians real-time access to MP predictions, facilitating timely adjustments to ventilation settings. CONCLUSIONS: The study successfully developed and integrated in clinical practice a predictive model for MP. This model will assist clinicians allowing for the adjustment of ventilatory parameters before lung damage occurs.

Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review.

BACKGROUND: Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. MAIN TEXT: Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. CONCLUSIONS: This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Rutin targets AKT to inhibit ferroptosis in ventilator-induced lung injury.

Our previous research confirmed that rutin reduced ventilator-induced lung injury (VILI) in mice. Ferroptosis has been reported to participate in the pathogenic process of VILI. We will explore whether rutin inhibits ferroptosis to alleviate VILI. A mouse model of VILI was constructed with or without rutin pretreatment to perform a multiomics analysis. Hematoxylin-eosin (HE) staining and transmission electron microscopy were used to evaluate lung injury in VILI mice. Dihydroethidium (DHE) staining and the malondialdehyde (MDA) and superoxide dismutase (SOD) levels were detected. Molecular docking was performed to determine the binding affinity between rutin and ferroptosis-related proteins. Western blot analysis, real-time PCR (RT-PCR) and immunohistochemical (IHC) staining were conducted to detect the expression levels of GPX4, XCT, ACSL4, FTH1, AKT and p-AKT in lung tissues. Microscale thermophoresis (MST) was used to evaluate the binding between rutin and AKT1. Transcriptomic and proteomic analyses showed that ferroptosis may play a key role in VILI mice. Metabolomic analysis demonstrated that rutin may affect ferroptosis via the AKT pathway. Molecular docking analysis indicated that rutin may regulate the expression of ferroptosis-related proteins. Moreover, rutin upregulated GPX4 expression and downregulated the expression of XCT, ACSL4 and FTH1 in the lung tissues. Rutin also increased the ratio of p-AKT/AKT and p-AKT expression. MST analysis showed that rutin binds to AKT1. Rutin binds to AKT to activate the AKT signaling pathway, contributing to inhibit ferroptosis, thus preventing VILI in mice. Our study elucidated a possible novel strategy of involving the use of rutin for preventing VILI.

Electrical impedance tomography-guided positive end-expiratory pressure titration in ARDS: a systematic review and meta-analysis.

PURPOSE: Assessing efficacy of electrical impedance tomography (EIT) in optimizing positive end-expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) patients to enhance respiratory system mechanics and prevent ventilator-induced lung injury (VILI), compared to traditional methods. METHODS: We carried out a systematic review and meta-analysis, spanning literature from January 2012 to May 2023, sourced from Scopus, PubMed, MEDLINE (Ovid), Cochrane, and LILACS, evaluated EIT-guided PEEP strategies in ARDS versus conventional methods. Thirteen studies (3 randomized, 10 non-randomized) involving 623 ARDS patients were analyzed using random-effects models for primary outcomes (respiratory mechanics and mechanical power) and secondary outcomes (PaO2/FiO2 ratio, mortality, stays in intensive care unit (ICU), ventilator-free days). RESULTS: EIT-guided PEEP significantly improved lung compliance (n = 941 cases, mean difference (MD) = 4.33, 95% confidence interval (CI) [2.94, 5.71]), reduced mechanical power (n = 148, MD = - 1.99, 95% CI [- 3.51, - 0.47]), and lowered driving pressure (n = 903, MD = - 1.20, 95% CI [- 2.33, - 0.07]) compared to traditional methods. Sensitivity analysis showed consistent positive effect of EIT-guided PEEP on lung compliance in randomized clinical trials vs. non-randomized studies pooled (MD) = 2.43 (95% CI - 0.39 to 5.26), indicating a trend towards improvement. A reduction in mortality rate (259 patients, relative risk (RR) = 0.64, 95% CI [0.45, 0.91]) was associated with modest improvements in compliance and driving pressure in three studies. CONCLUSIONS: EIT facilitates real-time, individualized PEEP adjustments, improving respiratory system mechanics. Integration of EIT as a guiding tool in mechanical ventilation holds potential benefits in preventing ventilator-induced lung injury. Larger-scale studies are essential to validate and optimize EIT's clinical utility in ARDS management.

Electrical impedance tomography: Usefulness for respiratory physiotherapy in critical illnesses.

Respiratory physiotherapy, including the management of invasive mechanical ventilation (MV) and noninvasive mechanical ventilation (NIV), is a key supportive intervention for critically ill patients. MV has potential for inducing ventilator-induced lung injury (VILI) as well as long-term complications related to prolonged bed rest, such as post-intensive care syndrome and intensive care unit acquired weakness. Physical and respiratory therapy, developed by the critical care team, in a timely manner, has been shown to prevent these complications. In this pathway, real-time bedside monitoring of changes in pulmonary aeration and alveolar gas distribution associated with postural positioning, respiratory physiotherapy techniques and changes in MV strategies can be crucial in guiding these procedures, providing safe therapy and prevention of potential harm to the patient. Along this path, electrical impedance tomography (EIT) has emerged as a new key non-invasive bedside strategy free of radiation, to allow visualization of lung recruitment. This review article presents the main and potential applications of EIT in relation to physiotherapy techniques in the ICU setting.

Guide to Lung-Protective Ventilation in Cardiac Patients.

The incidence of acute respiratory insufficiency has continued to increase among patients admitted to modern-day cardiovascular intensive care units. Positive pressure ventilation (PPV) remains the mainstay of treatment for these patients. Alterations in intrathoracic pressure during PPV has distinct effects on both the right and left ventricles, affecting cardiovascular performance. Lung-protective ventilation (LPV) minimizes the risk of further lung injury through ventilator-induced lung injury and, hence, an understanding of LPV and its cardiopulmonary interactions is beneficial for cardiologists.

Imp7 siRNA nanoparticles protect against mechanical ventilation-associated liver injury by inhibiting HMGB1 production and NETs formation.

Mechanical ventilation (MV) has the potential to induce extra-pulmonary organ damage by adversely affecting the lungs and promoting the secretion of inflammatory cytokines. High-mobility group box 1 protein (HMGB1) is a pro-inflammatory mediator in ventilator-induced lung injury (VILI), but its effect on MV-associated liver injury and the mechanisms are poorly understood. In the present study, mice were subjected to high-volume MV (20 ml/kg) to induce VILI. MV-induced HMGB1 prompted neutrophil extracellular traps (NETs) formation and PANoptosis within the liver. Inhibiting NETs formation by DNase I or PAD4 inhibitor, or by HMGB1 neutralizing ameliorated the liver injury. HMGB1 activated neutrophils to form NETs through TLR4/MyD88/TRAF6 pathway. Importantly, Importin7 siRNA nanoparticles inhibited HMGB1 release and protected against MV-associated liver injury. These data provide evidence of MV-induced HMGB1 prompted NETs formation and PANoptosis in the liver via the TLR4/MyD88/TRAF6 pathway. HMGB1 is a potential therapeutic target for MV-associated liver injury.

Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient's lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.

Setting positive end-expiratory pressure: using the pressure-volume curve.

PURPOSE OF REVIEW: To discuss the role of pressure-volume curve (PV curve) in exploring elastic properties of the respiratory system and setting mechanical ventilator to reduce ventilator-induced lung injury. RECENT FINDINGS: Nowadays, quasi-static PV curves and loops can be easily obtained and analyzed at the bedside without disconnection of the patient from the ventilator. It is shown that this tool can provide useful information to optimize ventilator setting. For example, PV curves can assess for patient's individual potential for lung recruitability and also evaluate the risk for lung injury of the ongoing mechanical ventilation setting. SUMMARY: In conclusion, PV curve is an easily available bedside tool: its correct interpretation can be extremely valuable to enlighten potential for lung recruitability and select a high or low positive end-expiratory pressure (PEEP) strategy. Furthermore, recent studies have shown that PV curve can play a significant role in PEEP and driving pressure fine tuning: clinical studies are needed to prove whether this technique will improve outcome.

Ventilation during extracorporeal gas exchange in acute respiratory distress syndrome.

PURPOSE OF REVIEW: Accumulating evidence ascribes the benefit of extracorporeal gas exchange, at least in most severe cases, to the provision of a lung healing environment through the mitigation of ventilator-induced lung injury (VILI) risk. In spite of pretty homogeneous criteria for extracorporeal gas exchange application (according to the degree of hypoxemia/hypercapnia), ventilatory management during extracorporeal membrane oxygenation (ECMO)/carbon dioxide removal (ECCO 2 R) varies across centers. Here we summarize the recent evidence regarding the management of mechanical ventilation during extracorporeal gas exchange for respiratory support. RECENT FINDINGS: At present, the most common approach to protect the native lung against VILI following ECMO initiation involves lowering tidal volume and driving pressure, making modest reductions in respiratory rate, while typically maintaining positive end-expiratory pressure levels unchanged.Regarding ECCO 2 R treatment, higher efficiency devices are required in order to reduce significantly respiratory rate and/or tidal volume. SUMMARY: The best compromise between reduction of native lung ventilatory load, extracorporeal gas exchange efficiency, and strategies to preserve lung aeration deserves further investigation.

Airway pressure release ventilation for lung protection in acute respiratory distress syndrome: an alternative way to recruit the lungs.

PURPOSE OF REVIEW: Airway pressure release ventilation (APRV) is a modality of ventilation in which high inspiratory continuous positive airway pressure (CPAP) alternates with brief releases. In this review, we will discuss the rationale for APRV as a lung protective strategy and then provide a practical introduction to initiating APRV using the time-controlled adaptive ventilation (TCAV) method. RECENT FINDINGS: APRV using the TCAV method uses an extended inspiratory time and brief expiratory release to first stabilize and then gradually recruit collapsed lung (over hours/days), by progressively 'ratcheting' open a small volume of collapsed tissue with each breath. The brief expiratory release acts as a 'brake' preventing newly recruited units from re-collapsing, reversing the main drivers of ventilator-induced lung injury (VILI). The precise timing of each release is based on analysis of expiratory flow and is set to achieve termination of expiratory flow at 75% of the peak expiratory flow. Optimization of the release time reflects the changes in elastance and, therefore, is personalized (i.e. conforms to individual patient pathophysiology), and adaptive (i.e. responds to changes in elastance over time). SUMMARY: APRV using the TCAV method is a paradigm shift in protective lung ventilation, which primarily aims to stabilize the lung and gradually reopen collapsed tissue to achieve lung homogeneity eliminating the main mechanistic drivers of VILI.

The place of positive end expiratory pressure in ventilator-induced lung injury generation.

PURPOSE OF REVIEW: Describe the rationale for concern and accumulating pathophysiologic evidence regarding the adverse effects of high-level positive end expiratory pressure (PEEP) on excessive mechanical stress and ventilator-induced lung injury (VILI). RECENT FINDINGS: Although the inclusion of PEEP in numerical estimates of mechanical power may be theoretically debated, its potential to increase stress, strain, and mean airway pressure are not. Recent laboratory data in a variety of animal models demonstrate that higher levels of PEEP coupled with additional fluids needed to offset its impediment of hemodynamic function are associated with increased VILI. Moreover, counteracting end-tidal hyperinflation by external chest wall pressure may paradoxically improve respiratory mechanics, indicating that lower PEEP helps protect the small 'baby lung' of advanced acute respiratory distress syndrome (ARDS). SUMMARY: The potentially adverse effects of PEEP on VILI can be considered in three broad categories. First, the contribution of PEEP to total mechanical energy expressed through mechanical power, raised mean airway pressure, and end-tidal hyperinflation; second, the hemodynamic consequences of altered cardiac loading, heightened pulmonary vascular stress and total lung water; and third, the ventilatory consequences of compromised carbon dioxide eliminating efficiency. Minimizing ventilation demands, optimized body positioning and care to avoid unnecessary PEEP are central to lung protection in all stages of ARDS.

Electroacupuncture Attenuates Ventilator-Induced Lung Injury by Modulating the Nrf2/HO-1 Pathway.

INTRODUCTION: Ventilator-induced lung injury (VILI) is the most common complication associated with mechanical ventilation. Electroacupuncture (EA) has shown potent anti-inflammatory effects. This study aimed to investigate the effects of EA on VILI and explore the underlying mechanisms. METHODS: Male C57BL/6 mice were subjected to high tidal volume ventilation to induce VILI. Prior to mechanical ventilation, mice received treatment with EA, nonacupoint EA, or EA combined with zinc protoporphyrin. RESULTS: EA treatment significantly improved oxygenation, as indicated by increased PaO2 levels in VILI mice. Moreover, EA reduced lung injury score, lung wet/dry weight ratio, and protein concentration in bronchoalveolar lavage fluid. EA also decreased the expression of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, IL-18, chemokine keratinocyte chemoattractant, macrophage inflammatory protein 2, and malondialdehyde. Furthermore, EA increased the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in VILI mice. At the molecular level, EA upregulated the expression of Nrf2 (nucleus) and heme oxygenase -1, while down-regulating the expression of p-NF-κB p65, NLR Family Pyrin Domain Containing 3, Cleaved Caspase-1, and ASC in VILI mice. Notably, the effects of EA were reversed by zinc protoporphyrin treatment, nonacupoint EA did not affect the aforementioned indicators of VILI. CONCLUSIONS: EA alleviates VILI by inhibiting the NLR Family Pyrin Domain Containing three inflammasome through activation of the Nrf2/HO-1 pathway.

Mechanical Power of Ventilation: From Computer to Clinical Implications.

Mechanical ventilation is a lifesaving intervention that may also induce further lung injury by exerting excessive mechanical forces on susceptible lung tissue, a phenomenon termed ventilator-induced lung injury (VILI). The concept of mechanical power (MP) aims to unify in one single variable the contribution of the different ventilatory parameters that could induce VILI by measuring the energy transfer to the lung over time. Despite an increasing amount of evidence demonstrating that high MP values can be associated with VILI development in experimental studies, the evidence regarding the association of MP and clinical outcomes remains controversial. In the present review, we describe the different determinants of VILI, the concept and computation of MP, and discuss the experimental and clinical studies related to MP. Currently, due to different limitations, the clinical application of MP is debatable. Further clinical studies are required to enhance our understanding of the relationship between MP and the development of VILI, as well as its potential impact on clinical outcomes.