The relationship between different power equations and the severity of acute respiratory distress syndrome (ARDS) remains unclear. This study aimed to evaluate various power equations: total mechanical power, total elastic power (comprising elastic static and elastic dynamic power), and resistive power, in a cohort of mechanically ventilated patients with and without ARDS. Bayesian analysis was employed to refine estimates and quantify uncertainty by incorporating a priori distributions.

A Bayesian post-hoc analysis was conducted on data from the Mechanical Power Day study.

113 intensive care units across 15 countries and 4 continents.

Adults who received invasive mechanical ventilation in volume-controlled mode, with (mild and moderate/severe ARDS) and without ARDS.

None.

ARDS, Elastic static power.

Elastic static power was 5.8 J/min (BF: 0.3) in patients with mild ARDS and 7.4 J/min (BF: 0.9) in moderate/severe ARDS patients. Bayesian regression and modeling analysis revealed that elastic static power was independently correlated with mild (a posteriori Mean: 1.3; 95% Credible Interval [Cred. Interval]: 0.2-2.2) and moderate/severe ARDS (a posteriori Mean: 2.8; 95% Cred. Interval: 1.7-3.8) more strongly than other power equations.

Elastic static power was found to have the strongest correlation with ARDS severity among the power equations studied. Prospective studies are needed to further validate these findings.

Mechanical power is a crucial concept in understanding ventilator-induced lung injury (VILI). We adopted the null hypothesis that under the same mechanical power, resulting from combinations of different static and dynamic variables-some with high stress per cycle and others without-would inflict similar degrees of damage on lung epithelial and endothelial cells as well as on the extracellular matrix in experimental acute respiratory distress syndrome (ARDS). To test this hypothesis, we varied tidal volume (Vt), which correlates with the stretching force per cycle, while adjusting respiratory rate (RR) to yield similar mechanical power values for identical durations across all experimental groups.

Animal study.

Laboratory investigation.

Thirty male Wistar rats (333 ± 26 g).

Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, animals were anesthetized and mechanically ventilated (positive end-expiratory pressure = 3 cm H2O) with combination of Vt and RR sufficient to induce similar mechanical power (n = 8/group): Vt = 6 mL/kg, RR = 140 breaths/minute (low Vt-high RR [LVT-HRR]); Vt = 12 mL/kg, RR = 70 breaths/minute (high Vt-low RR [HVT-LRR]); and Vt = 18 mL/kg, RR = 50 breaths/minute (very-high Vt-very-low RR [VHVT-VLRR]). All groups were ventilated for 80 minutes. A control group, not subjected to mechanical ventilation (MV), was used for molecular biology analyses.

After 80 minutes of MV, lung overdistension, alveolar/interstitial edema, fractional area of E-cadherin, and biomarkers of lung inflammation (interleukin-6), lung stretch (amphiregulin), damage to epithelial (surfactant protein B) and endothelial cells (vascular cell adhesion molecule 1 and angiopoietin-2), and extracellular matrix (versican and syndecan) were higher in group VHVT-VLRR than LVT-HRR. Plateau pressure and driving pressure increased progressively from LVT-HRR to HVT-LRR and VHVT-VLRR.

In the current experimental model of ARDS, mechanical power alone is insufficient to account for VILI. Instead, the manner in which its components are applied determines the extent of injury at a given mechanical power value.

Identifying the mechanisms of ventilator/ventilation-induced lung injury requires an understanding of the pulmonary physiology involved in the mechanical properties of the lung along with the involvement of the inflammatory cascade. Accurately measuring parameters that represent physiologic lung stress and lung strain at the bedside can be clinically challenging. Although surrogates for lung stress and strain have been proposed, such as plateau pressure and driving pressure, these values only represent a static variable in the ventilator breath. It has been proposed that a single variable could be used as a unifying parameter to identify a threshold for the safe application of mechanical ventilation. The concept of "mechanical power" applies an energy load transfer designation to the ventilator settings and output of tidal volume, airway pressures, and flow. However, there is a potential disconnect between the use of "absolute" mechanical power and the variability of body weight throughout a mixed medical population. Using ideal body weight as an influential factor to express mechanical power can potentially allow for a more accurate depiction of energy applied to the lungs and a potentially reliable injurious mechanical ventilation threshold indicator.

In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.

Mechanical power (MP) serves as a crucial predictive indicator for ventilator-induced lung injury and plays a pivotal role in tailoring the management of mechanical ventilation. However, its application across different diseases and stages remains nuanced.

Using AmsterdamUMCdb, we conducted a retrospective study to analyze the causal relationship between MP and outcomes of invasive mechanical ventilation, specifically SpO2/FiO2 ratio (P/F) and ventilator-free days at day 28 (VFD28). We employed causal inferential analysis with backdoor linear regression and double machine learning, guided by directed acyclic graphs, to estimate the average treatment effect (ATE) in the whole population and conditional average treatment effect (CATE) in the individual cohort. Additionally, to enhance interpretability and identify MP thresholds, we conducted a simulation analysis.

In the study, we included 11,110 unique admissions into analysis, of which 58.3% (6391) were surgical admissions. We revealed a negative and significant causal effect of median MP on VFD28, with estimated ATEs of -0.135 (95% confidence interval [CI]: -0.15 to -0.121). The similar effect was not observed in Maximal MP and minimal MP. The effect of MP was more pronounced in the medical subgroup, with a CATE of -0.173 (95% CI: -0.197 to -0.143) determined through backdoor linear regression. Patients with cardio, respiratory, and infection diagnoses, who required long-term intubation, sustained higher impact on CATEs across various admission diagnoses. Our simulations showed that there is no single MP threshold that can be applied to all patients, as the optimal threshold varies depending on the patient's condition.

Our study underscores the importance of tailoring MP adjustments on an individualized basis in ventilator management. This approach opens up new avenues for personalized treatment strategies and provides fresh insights into the real-time impact of MP in diverse clinical scenarios. It highlights the significance of median MP while acknowledging the absence of universally applicable thresholds.

Acute respiratory distress syndrome (ARDS) is a heterogeneous group of disease entities that are associated with acute hypoxic respiratory failure and significant morbidity and mortality. With a better understanding and phenotyping of lung injury, novel pathophysiologic mechanisms demonstrate the impact of a patient's excessive spontaneous breathing effort on perpetuating lung injury. Patient self-inflicted lung injury (P-SILI) is a recently identified phenomenon that delves into the impact of spontaneous breathing on respiratory mechanics in patients with lung injury. While the studies are hypothesis-generating and have been demonstrated in animal and human studies, further clinical trials are needed to identify its impact on ARDS management. The purpose of this review article is to highlight the physiologic mechanisms of P-SILI, novel tools and methods to detect P-SILI, and to review the current literature on non-invasive and invasive respiratory management in patients with ARDS.

Primary graft dysfunction (PGD) affects survival after lung transplant (LT). The current hypothesis was that prone positioning (PP), proposed as a rescue maneuver to treat refractory hypoxemia due to PGD, may improve LT outcomes, especially when applied early.

Bilateral LT recipients developing moderate-to-severe PGD within 24 hours from intensive care unit admission were enrolled. From January 2020 to November 2021, patients developing PGD after LT were turned prone between 24 and 48 hours after diagnosis, only in case of radiological or oxygenation worsening ("late PP" group). After November 2021, patients were routinely turned prone within 24 hours from PGD diagnosis ("early PP"). A propensity score-weighted analysis, adjusted for clinically relevant covariates, was applied.

Intensive care unit.

Bilateral LT recipients.

Early PP, late PP, or supine position.

130 LT patients were screened and 67 were enrolled. A total of 25 (37%) recipients were treated in the supine position, 24 (36%) in early PP, and 18 (27%) in late PP. After propensity score weighting, both supine treatment (estimated effect for 1 ventilator-free day = 8.23, standard error: 2.97, p = 0.007) and early PP treatment (estimated effect = 9.42, standard error: 2.59, p < 0.001) were associated with greater 28-day ventilator-free days than late PP treatment (reference). Compared with late PP, early PP was also associated with better oxygenation, driving pressure, and static respiratory system compliance. Compared with supine recipients, the early PP group showed better oxygenation at 72 hours after PGD diagnosis.

Early PP in LT recipients with moderate-to-severe PGD seems to be associated with better 28-day ventilator-free days, oxygenation, and driving pressure than late PP.

Evidence suggests that mechanical power (MP) normalized to dynamic compliance, which equals power density, may help identify prolonged ventilated patients at risk for spontaneous breathing trial (SBT) failure. This study compared MP density with traditional spontaneous breathing indexes to predict a patient's capacity to sustain a short trial of unassisted breathing.

A prospective observational study on 186 prolonged ventilated, tracheotomized patients. We analyzed the first 30-min SBT upon weaning center admission, comparing MP density with spontaneous breathing indexes (e.g., predicted body weight normalized tidal volume (VT/PBW), rapid shallow breathing index (RSBI), and the integrative weaning index (IWI)) regarding SBT failure prediction, with diagnostic accuracy expressed as the area under the receiver operating characteristic curve (AUROC).

SBT failure occurred in 51 out of 186 patients (27 %), who demonstrated significantly lower dynamic compliance (median 29 mL/cmH2O [IQR 26-37] vs. 39 mL/cmH2O [33-45]) and higher MP density (5837 cmH2O2/min [4512-7758] vs. 2922 cmH2O2/min [2001-4094]) before SBT, as well as lower spontaneous VT/PBW (5.7 mL∗kg-1 [5.0-6.7] vs. 6.6 mL∗kg-1 [5.9-7.8]), higher RSBI (73 min-1∗L-1 [57-100] vs. 59 min-1∗L-1 [45-76]), and lower IWI (40 L2/cmH2O∗%∗min∗10-3 [27-50] vs. 63 L2/cmH2O∗%∗min∗10-3 [46-91]) after 5 min of unassisted breathing. MP density was more accurate at predicting SBT failures (AUROC 0.86 [95%CI 0.80-0.91]) than VT/PBW (0.58 [0.50-0.65]), RSBI (0.54 [0.47-0.61]), or IWI (0.66 [0.58-0.73])).

MP density as a readiness criterion was more accurate at predicting weaning trial failures in prolonged ventilated, tracheotomized patients than traditional indexes assessed during unassisted breathing.

This study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality.

Based on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients.

A preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery.

The experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators.

The preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches. The concept of mechanical power has emerged as a comprehensive metric encompassing key ventilator parameters associated with the genesis of ventilator-induced lung injury, including volume, pressure, flow, resistance, and respiratory rate. While numerous animal and human studies have linked mechanical power and ventilator-induced lung injury, its practical implementation at the bedside is hindered by calculation challenges, lack of equation consensus, and the absence of an optimal threshold. To overcome the constraints of measuring static respiratory parameters, dynamic mechanical power is proposed for all patients, regardless of their ventilation mode. However, establishing a causal relationship is crucial for its potential implementation, and requires further research. The objective of this review is to explore the role of mechanical power in ventilator-induced lung injury, its association with patient outcomes, and the challenges and potential benefits of implementing a ventilation strategy based on mechanical power.

The impact of distinct primary colorectal cancer (CRC) sites on lung injury and complications remains largely unexplored, despite the palpable differences in surgical positions, procedures, and the resulting mechanically induced respiratory pressures at each site.

This study employed a forwards-looking approach utilising the propensity score matching (PSM) method; 300 patients with pathological CRC after laparoscopic surgery from April 2019 to May 2023 were enrolled. Two categories were bifurcated based on their surgical locations: the rectosigmoid colon (RSC) group and the descending/ascending colon (DAC) group, with a 2:1 ratio. The occurrence of postoperative pulmonary complications (PPCs) within a 30-day postoperative period was meticulously evaluated. Additionally, assessments have been performed for plasma biomarkers of immune response dynamics and lung injury (plasma soluble advanced glycation end-product receptor [sRAGE], angiopoietin-2 [ANG-2], interleukin-1β/6 [IL-1β/IL-6]) and other parameters.

Although the increase in postoperative lung epithelial damage, as indicated by the plasma sRAGE levels, was significant in the RSC group (DAC vs. RSC; 1029.6 [576.8-1365.2] vs. 1271.6 [896.3-1587.6]; odds ratio=0.999; 95% CI: 0.998 to 1.000; P=0.007), a significantly increased percentage of PPCs was observed in the DAC group (DAC vs. RSC; hazard ratio=1.669; 95% CI, 1.141 to 2.439; P=0.008). A univariate Cox proportional hazards model revealed that sRAGE, ANG-2, IL-1β, and IL-6 levels were not correlated with the incidence of time-to-PPCs across the two cohorts (P>0.05). Propensity score-weighted Cox regression and causal mediation analysis further demonstrated that the DAC site directly affected the incidence of PPCs, regardless of the other baseline confounders and clinical covariates related to the tumour site and PPCs.

The primary site of CRC is an independent predictor of the development of PPCs. Despite the steep Trendelenburg position of the RSC group inciting more pulmonary stress, inflammation and lung epithelial injury, as indicated by higher sRAGE, it demonstrated a lower PPCs occurrence relative to its DAC counterpart, with a slightly inclined or reversed Trendelenburg position. None of the plasma biomarkers of inflammation or lung injury indicated sufficient prognostic value for PPCs.

This study compared the ventilatory variables and computed tomography (CT) features of patients with coronavirus disease 2019 (COVID-19) versus those of patients with pulmonary non-COVID-19-related acute respiratory distress syndrome (ARDS) during the early phase of ARDS.

This prospective, observational cohort study of ARDS patients in Taiwan was performed between February 2017 and June 2018 as well as between October 2020 and January 2024. Analysis was performed on clinical characteristics, including consecutive ventilatory variables during the first week after ARDS diagnosis. Analysis was also performed on CT scans obtained within one week after ARDS onset.

A total of 222 ARDS patients were divided into a COVID-19 ARDS group (n = 44; 19.8%) and a non-COVID-19 group (all pulmonary origin) (n = 178; 80.2%). No significant difference was observed between the two groups in terms of all-cause hospital mortality (38.6% versus 47.8%, p = 0.277). Pulmonary non-COVID-19 patients presented higher values for mechanical power (MP), MP normalized to predicted body weight (MP/PBW), MP normalized to compliance (MP/compliance), ventilatory ratio (VR), peak inspiratory pressure (Ppeak), and dynamic driving pressure (∆P) as well as lower dynamic compliance from day 1 to day 7 after ARDS onset. In both groups, non-survivors exceeded survivors and presented higher values for MP, MP/PBW, MP/compliance, VR, Ppeak, and dynamic ∆P with lower dynamic compliance from day 1 to day 7 after ARDS onset. The CT severity score for each of the five lung lobes and total CT scores were all significantly higher in the non-COVID-19 group (all p < 0.05). Multivariable logistic regression models revealed that Sequential Organ Failure Assessment (SOFA) score was independently associated with mortality in the COVID-19 group. In the non-COVID-19 group, body mass index, immunocompromised status, SOFA score, MP/PBW and total CT severity scores were independently associated with mortality.

In the early course of ARDS, physicians should be aware of the distinctions between COVID-19-related ARDS and non-COVID-19-related ARDS in terms of ventilatory variables and CT imaging presentations. It is also important to tailor the mechanical ventilation settings according to these distinct subsets of ARDS.

In patients with acute respiratory distress syndrome, mechanical ventilation often leads to ventilation-induced lung injury (VILI), which is attributed to unphysiological lung strain (UPLS) in respiratory dynamics. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a transmembrane receptor, senses mechanical signals. The Src/STAT3 pathway plays a crucial role in the mechanotransduction network, concurrently triggering pyroptosis related inflammatory responses. We hypothesized that the mechanical stretch caused by UPLS can be sensed by PECAM-1 in the lungs, leading to VILI via the Src/STAT3 and pyroptosis pathway.

A VILI model was established in rats through UPLS. The link between lung strain and VILI as well as the change in the activation of PECAM-1, Src/STAT3, and pyroptosis was firstly being explored. Then, the inhibitors of PECAM-1, Src, STAT3 were adopted respectively, the effect on VILI, inflammation, the Src/STAT3 pathway, and pyroptosis was evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were used to validate the findings in vivo.

UPLS activated PECAM-1, Src/STAT3 signaling pathway, inflammation, and pyroptosis in the VILI model with rats, whereas inhibition of PECAM-1 or the Src/STAT3 signaling pathway decreased lung injury, inflammatory responses, and pyroptosis. Inhibition of PECAM-1 also reduced activation of the Src/STAT3 signaling pathway. The mechanism was validated with HUVECs exposed to overload mechanical cyclic stretch.

This study suggests that UPLS contributes to VILI by activating the PECAM-1/Src/STAT3 pathway and inducing inflammatory responses as well aspyroptosis.

Assessing the respiratory system of a patient receiving mechanical ventilation is complex. We provide an overview of an approach at the bedside underpinned by physiology. We discuss the importance of distinguishing between extensive and intensive ventilatory variables. We outline methods to evaluate both passive patients and those making spontaneous respiratory efforts during assisted ventilation. We believe a comprehensive assessment can influence setting mechanical ventilatory support to achieve lung and diaphragm protective ventilation.

This study aimed to identify the cyclical "on-off" flow of pulmonary microcirculation during inspiration and expiration by sidestream dark field imaging (SDF) technology in vivo and investigate the effects of volume status and driving pressure on cyclical "on-off" flow of microcirculation.

24 ARDS-modeled rabbits were randomly divided into high-driving pressure group (HDP group) and low-driving pressure group (LDP group). Lung microcirculation measurements were performed using the SDF microscope at two timepoints (T1 CVP 2-4 mmHg, T2 CVP 8-10 mmHg). From T1 to T2, 10 ml/kg saline was infused to increase CVP. The cyclical "on-off" pulmonary microcirculation was quantitatively assessed by the change of microcirculation between expiration and inspiration.

Proportion of perfused vessels (PPV), microvascular flow index (MFI), perfused vessel density (PVD), and total vessel density (TVD) at expiration were significantly higher than inspiration in the HDP group. The HDP group has a higher ΔPPV and ΔPVD. After fluid loading, ΔPPV and ΔMFI decreased. TNF-α, IL-6, Ang-2, and vWF levels in the HDP group were higher. The HDP group also has a higher lung wet-weight/body weight ratio, lung wet-to-dry weight ratio, and more severe damage of pulmonary capillaries than the LDP group.

The difference in alveolar perfused microcirculation between inspiration and expiration defined as cyclical "on-off flow" can be detected. High driving pressure can enhance the cyclical "on-off" flow, and fluid loading can relieve it. High driving pressure can potentially cause injury to pulmonary capillaries due to the phenomenon of "on-off" flow, thereby exacerbating ARDS.

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.

During laparoscopic surgery, the role of PEEP to improve outcome is controversial. Mechanistically, PEEP benefits depend on the extent of alveolar recruitment, which prevents ventilator-induced lung injury by reducing lung dynamic strain. The hypotheses of this study were that pneumoperitoneum-induced aeration loss and PEEP-induced recruitment are inter-individually variable, and that the recruitment-to-inflation ratio (R/I) can identify patients who benefit from PEEP in terms of strain reduction.

Sequential study.

Operating room.

Seventeen ASA I-III patients receiving robot-assisted prostatectomy during Trendelenburg pneumoperitoneum.

Patients underwent end-expiratory lung volume (EELV) and respiratory/lung/chest wall mechanics (esophageal manometry and inspiratory/expiratory occlusions) assessment at PEEP = 0 cmH2O before and after pneumoperitoneum, at PEEP = 4 and 12 cmH2O during pneumoperitoneum. Pneumoperitoneum-induced derecruitment and PEEP-induced recruitment were assessed through a simplified method based on multiple pressure-volume curve. Dynamic and static strain changes were evaluated. R/I between 12 and 4 cmH2O was assessed from EELV. Inter-individual variability was rated with the ratio of standard deviation to mean (CoV).

Pneumoperitoneum reduced EELV by (median [IqR]) 410 mL [80-770] (p < 0.001) and increased dynamic strain by 0.04 [0.01-0.07] (p < 0.001), with high inter-individual variability (CoV = 70% and 88%, respectively). Compared to PEEP = 4 cmH2O, PEEP = 12 cmH2O yielded variable amount of recruitment (139 mL [96-366] CoV = 101%), causing different extent of dynamic strain reduction (median decrease 0.02 [0.01-0.04], p = 0.002; CoV = 86%) and static strain increases (median increase 0.05 [0.04-0.07], p = 0.01, CoV = 33%). R/I (1.73 [0.58-3.35]) estimated the decrease in dynamic strain (p ≤0.001, r = -0.90) and the increase in static strain (p = 0.009, r = -0.73) induced by PEEP, while PEEP-induced changes in respiratory and lung mechanics did not.

Trendelenburg pneumoperitoneum yields variable derecruitment: PEEP capability to revert these phenomena varies significantly among individuals. High R/I identifies patients in whom higher PEEP mostly reduces dynamic strain with limited static strain increases, potentially allowing individualized settings.

Large variations in respiratory system compliance and resistance may cause the accuracy of tidal volume (VT) delivery beyond the declared range. This study aimed at evaluating the accuracy of VT delivery using a test lung model to simulate pulmonary mechanics under normal or disease conditions.

In vitro assessment of the VT delivery accuracy was carried out on two commercial ventilators. Measurements of the inspired and expired VT from the ventilator and FlowAnalyser were compared to evaluate the separated and combined influences of compliance and resistance on the delivered VT accuracy. To do this, the errors of five delivered volumes (30 ml, 50 ml, 100 ml, 300 ml, and 500 ml) were checked under 29 test conditions involving a total of 27 combinations of resistance and compliance.

For the tested ventilator S1 with a flow sensor near the expiratory valve, the average of expired VT errors (ΔVTexp) in three measurements (4 test conditions for each measurement) correlated to test lung compliance (r=-0.96, p = 0.044), and the average of inspired VT errors (ΔVTins) correlated to compliance (r = 0.89, p = 0.106); for the tested ventilator S2 with a flow sensor located at the Y piece, no clear relationship between compliance and ΔVTexp or ΔVTins was found. Furthermore, on two ventilators tested, the current measurements revealed a poor correlation between test lung resistance and ΔVTins or ΔVTexp, and the maximum values of ΔVTexp and ΔVTins correspond to the maximum resistance of 200 cmH2O/(L/s), at which the phenomenon of the flap fluttering in the variable orifice flow senor was observed, and the recorded peak inspiratory pressure (Ppeak) was much higher than the Ppeak estimated by the classical equation of motion. In contrast, at the lower resistance values of 5, 20, 50 and 100 cmH2O/(L/s), the recorded Ppeak was very close to the estimated Ppeak. Overall, the delivered VT errors were in the range of ± 14% on two ventilators studied.

Depending on the placement site of the flow sensor in the ventilator circuit, the compliance and resistance of the test lung have different influences on the accuracy of VT delivery, which is further attributed to different fluid dynamics effects of the compliance and resistance. The main influence of compliance is to raise the peak inspiratory pressure Ppeak, thereby increasing the compression volume within the ventilator circuit; whereas a high resistance not only contributes to elevating Ppeak, but more importantly, it governs the gas flow conditions. Ppeak is a critical predictive indicator for the accuracy of the VT delivered by a ventilator.

This study introduces a method to non-invasively and automatically quantify respiratory muscle effort (Pmus) during mechanical ventilation (MV). The methodology hinges on numerically solving the respiratory system's equation of motion, utilizing measurements of airway pressure (Paw) and airflow (Faw). To evaluate the technique's effectiveness, Pmus was correlated with expected physiological responses. In volume-control (VC) mode, where tidal volume (VT) is pre-determined, Pmus is expected to be linked to Paw fluctuations. In contrast, during pressure-control (PC) mode, where Paw is held constant, Pmus should correlate with VT variations.

The study utilized data from 250 patients on invasive MV. The data included detailed recordings of Paw and Faw, sampled at 31.25 Hz and saved in 131.1-second epochs, each covering 34 to 41 breaths. The algorithm identified 51,268 epochs containing breaths on either VC or PC mode exclusively. In these epochs, Pmus and its pressure-time product (PmusPTP) were computed and correlated with Paw's pressure-time product (PawPTP) and VT, respectively.

There was a strong correlation of PmusPTP with PawPTP in VC mode (R² = 0.91 [0.76, 0.96]; n = 17,648 epochs) and with VT in PC mode (R² = 0.88 [0.74, 0.94]; n = 33,620 epochs), confirming the hypothesis. As expected, negligible correlations were observed between PmusPTP and VT in VC mode (R² = 0.03) and between PmusPTP and PawPTP in PC mode (R² = 0.06).

The study supports the feasibility of assessing respiratory effort during MV non-invasively through airway signal analysis. Further research is warranted to validate this method and investigate its clinical applications.

Ventilator-induced lung injury (VILI) is a consequence of inflammation and increased alveolar-capillary membrane permeability due to alveolar hyperdistention or elevated intrapulmonary pressure, but the precise mechanisms remain unclear. The aim of the study was to analyze the mechanism by which angiotensin converting enzyme 2 (ACE2) alleviates endoplasmic reticulum stress (ERS) and protects alveolar cells from pyroptosis in VILI by regulating angiotensin (Ang)1-7/Mas.

VILI was induced in mice by mechanical ventilation by regulating the tidal volume. The alveolar cell line, A549, mimics VILI in vitro by cyclic stretch (CS). Ang (1-7) (100 nmol/L) was added to the medium. ERS was induced in cells by stimulating with tunicamycin (TM, 2 μg/mL). ERS was inhibited by tracheal instillation of 4-phenylbutyric acid (4-PBA) (1 mg/kg). ACE2's enzymatic function was activated or inhibited by subcutaneous injection of resorcinolnaphthalein (RES, 20 μg/kg) or MLN-4760 (20 μg/kg). pGLV-EF1a-GFP-ACE2 was instilled into the trachea to increase the protein expression of ACE2. The Ang (1-7) receptor, Mas, was antagonized by injecting A779 subcutaneously (80 μg/kg).

ACE2 protein levels decreased after modeling. Ang (1-7) level was decreased and Ang II was accumulated. ERS was significantly induced in VILI mice, and pyroptosis was observed in cells. When ERS was inhibited, pyroptosis under the VILI condition was significantly inhibited. Ang (1-7) alleviated ERS and pyroptosis under CS. When ERS was continuously activated, the function of Ang (1-7) in inhibiting pyroptosis was blocked. Resorcinolnaphthalein (RES) effectively promoted Ang II conversion, alleviated the Ang (1-7) level in VILI, ameliorated lung injury, and inhibited ERS and cell pyroptosis. Inhibiting ACE2's function in VILI hindered the production of Ang (1-7), promoted the accumulation of Ang II, and exacerbated ERS and pyroptosis, along with lung injury. The Mas antagonist significantly blocked the inhibitory effects of ACE2 on ERS and pyroptosis in VILI.

Reduced ACE2 expression in VILI is involved in ERS and pyroptosis-related injury. ACE2 can alleviate ERS in alveolar cells by catalyzing the production of Ang (1-7), thus inhibiting pyroptosis in VILI.

A prospective observational study comparing mechanical power density (MP normalized to dynamic compliance) with traditional spontaneous breathing indexes (e.g., predicted body weight normalized tidal volume [VT/PBW], rapid shallow breathing index [RSBI], or the integrative weaning index [IWI]) for predicting prolonged weaning failure in 140 tracheotomized patients. We assessed the diagnostic accuracy of these indexes at the start and end of the weaning procedure using ROC curve analysis, expressed as the area under the receiver operating characteristic curve (AUROC). Weaning failure occurred in 41 out of 140 patients (29%), demonstrating significantly higher MP density (6156 cmH2O2/min [4402-7910] vs. 3004 cmH2O2/min [2153-3917], P < 0.01), lower spontaneous VT/PBW (5.8 mL*kg-1 [4.8-6.8] vs. 6.6 mL*kg-1 [5.7-7.9], P < 0.01) higher RSBI (68 min-1*L-1 [44-91] vs. 55 min-1*L-1 [41-76], P < 0.01) and lower IWI (41 L2/cmH2O*%*min*10-3 [25-72] vs. 71 L2/cmH2O*%*min*10-3 [50-106], P < 0.01) and at the end of weaning. MP density was more accurate at predicting weaning failures (AUROC 0.91 [95%CI 0.84-0.95]) than VT/PBW (0.67 [0.58-0.74]), RSBI (0.62 [0.53-0.70]), or IWI (0.73 [0.65-0.80]), and may help clinicians in identifying patients at high risk for long-term ventilator dependency.

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.

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.

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.

To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19.

This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality.

We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure.

In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Mechanical ventilation (MV) is an essential therapy for acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. However, it can also induce mechanical ventilation-induced pulmonary fibrosis (MVPF) and the underlying mechanism remains unknown. Based on a mouse model of MVPF, the present study aimed to explore the role of the angiotensin-converting enzyme/angiotensin II/angiotensin type 1 receptor (ACE/Ang-2/AT1R) axis in the process of MVPF. In addition, recombinant angiotensin-converting enzyme 2(rACE2), AT1R inhibitor valsartan, AGTR1-directed shRNA and ACE inhibitor perindopril were applied to verify the effect of inhibiting ACE/Ang-2/AT1R axis in the treatment of MVPF. Our study found MV induced an inflammatory reaction and collagen deposition in mouse lung tissue accompanied by the activation of ACE in lung tissue, increased concentration of Ang-2 in bronchoalveolar lavage fluid (BALF), and upregulation of AT1R in alveolar epithelial cells. The process of pulmonary fibrosis could be alleviated by the application of the ACE inhibitor perindopril, ATIR inhibitor valsartan and AGTR1-directed shRNA. Meanwhile, rACE2 could also alleviate MVPF through the degradation of Ang-2. Our finding indicated the ACE/Ang-2/AT1R axis played an essential role in the pathogenesis of MVPF. Pharmacological inhibition of the ACE/Ang-2/AT1R axis might be a promising strategy for the treatment of MVPF.

Few data are available on the lung microbiota composition of patients with coronavirus disease 2019-related acute respiratory distress syndrome (C-ARDS) receiving invasive mechanical ventilation (IMV). Moreover, it has never been investigated whether there is a potential correlation between lung microbiota communities and respiratory mechanics. We performed a prospective observational study in two intensive care units of a university hospital in Italy. Lung microbiota was investigated by bacterial 16S rRNA gene sequencing, performed on bronchoalveolar lavage fluid samples withdrawn after intubation. The lung bacterial communities were analyzed after stratification by respiratory system compliance/predicted body weight (Crs) and ventilatory ratio (VR). Weaning from IMV and hospital survival were assessed as secondary outcomes. In 70 C-ARDS patients requiring IMV from 1 April through 31 December 2020, the lung microbiota composition (phylum taxonomic level, permutational multivariate analysis of variance test) significantly differed between who had low Crs vs those with high Crs (P = 0.010), as well as in patients with low VR vs high VR (P = 0.012). As difference-driving taxa, Proteobacteria (P = 0.017) were more dominant and Firmicutes (P = 0.040) were less dominant in low- vs high-Crs patients. Similarly, Proteobacteria were more dominant in low- vs high-VR patients (P = 0.013). After multivariable regression analysis, we further observed lung microbiota diversity as a negative predictor of weaning from IMV and hospital survival (hazard ratio = 3.31; 95% confidence interval, 1.52-7.20, P = 0.048). C-ARDS patients with low Crs/low VR had a Proteobacteria-dominated lung microbiota. Whether patients with a more diverse lung bacterial community may have more chances to be weaned from IMV and discharged alive from the hospital warrants further large-scale investigations.

Lung microbiota characteristics were demonstrated to predict ventilator-free days and weaning from mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). In this study, we observed that in severe coronavirus disease 2019 patients with ARDS who require invasive mechanical ventilation, lung microbiota characteristics were associated with respiratory mechanics. Specifically, the lung microbiota of patients with low respiratory system compliance and low ventilatory ratio was characterized by Proteobacteria dominance. Moreover, after multivariable regression analysis, we also found an association between patients' microbiota diversity and a higher possibility of being weaned from mechanical ventilation and discharged alive from the hospital. For these reasons, lung microbiota characterization may help to stratify patient characteristics and orient the delivery of target interventions. (This study has been registered at ClinicalTrials.gov on 17 February 2020 under identifier NCT04271345.).

Registered at ClinicalTrials.gov, 17 February 2020 (NCT0427135).

Extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) is systematically associated with decreased respiratory system compliance (CRS). It remains unclear whether transportation to the referral ECMO center, changes in ventilatory mode or settings to achieve ultra-protective ventilation, or the natural evolution of ARDS drives this change in respiratory mechanics. Herein, we assessed the precise moment when CRS decreases after ECMO cannulation and identified factors associated with decreased CRS.

To rule out the effect of transportation and the different modes of ventilation on CRS, we conducted a retrospective, single-center, observational cohort study from January 2013 to May 2020, on 22 patients with severe ARDS requiring on-site ECMO and ventilated in pressure-controlled mode to achieve ultra-protective ventilation. CRS was assessed at different time points ranging from 12 h before ECMO cannulation to 72 h after ECMO cannulation. The primary outcome was the relative change in CRS between 3 h before and 3 h after ECMO cannulation. The secondary outcomes included variables associated with the relative changes in CRS within the first 3 h after ECMO cannulation and the relative changes in CRS at each time point.

CRS decreased within the first 3 h after ECMO cannulation (-28.3%, 95% confidence interval [CI]: -38.8 to -17.9, P<0.001), while the decrease was mild before and after these first 3 h after ECMO cannulation. To achieve ultra-protective ventilation, respiratory rate decreased in the mean by -13 breaths/min (95% CI: -15 to -11) and driving pressure by -8.3 cmH2O (95% CI: -11.2 to -5.3), resulting in decreased tidal volume by -3.3 mL/kg of predicted body weight (95% CI: -3.9 to -2.6) as compared to before ECMO cannulation (P <0.001 for all). Plateau pressure reduction, driving pressure reduction, and tidal volume reduction were significantly associated with decreased CRS after ECMO cannulation, whereas neither respiratory rate, positive end-expiratory pressure, inspired fraction of oxygen, fluid balance, nor mean airway pressure was associated with decreased CRS.

Decreased driving pressure resulting in lower tidal volume to achieve ultra-protective ventilation after ECMO cannulation was associated with a marked decrease in CRS in ARDS patients with on-site ECMO cannulation.

Acute respiratory distress syndrome (ARDS) is a well-defined clinical entity characterized by the acute onset of diffuse pulmonary injury and hypoxemia not explained by fluid overload. The COVID-19 pandemic brought about an unprecedented volume of patients with ARDS and challenged our understanding and clinical approach to treatment of this clinical syndrome. Unique to COVID-19 ARDS is the disruption and dysregulation of the pulmonary vascular compartment caused by the SARS-CoV-2 virus, which is a significant cause of hypoxemia in these patients. As a result, gas exchange does not necessarily correlate with respiratory system compliance and mechanics in COVID-19 ARDS as it does with other etiologies. The purpose of this review is to relate the mechanics of COVID-19 ARDS to its underlying pathophysiologic mechanisms and outline the lessons we have learned in the management of this clinic syndrome.

Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV).

This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters.

Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9-10.6] versus 11.0 [6.6-14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1-5.0] versus 5.3 [3.3-7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP.

In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery.

German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

Mediastinal tumors pose a challenging respiratory and circulatory management during anesthesia procedures, there is a risk of circulatory collapse or complete airway obstruction, which in severe cases can lead to cardiac arrest. We reported a case of anesthetic management using a bronchial blocker placed outside the tracheal tube. In this case report, the patient's trachea was so severely compressed that the airway was extremely narrow, only 4 mm at its narrowest point. By reporting the anesthetic management of this patient, we intend to provide an unusual approach for airway management.

A 52-year-old male patient was admitted to the hospital due to cough and expectoration for one year. Additionally, the patient experienced chest tightness and asthma after physical activity. The enhanced computed tomography revealed there existed an irregular soft tissue mass in the right upper mediastinum, which significantly compressed the trachea and esophagus. The results of the mediastinal puncture pathology showed the presence of mesenchymal tumors. According to the results above, the patient was diagnosed with a mediastinal tumor and scheduled to undergo tumor resection under general anesthesia. We used a bronchial occluder outside the tracheal tube for general anesthesia. After surgery, the patient received thorough treatment and was subsequently discharged from the hospital.

In patients with severe airway compression from a mediastinal tumor airway compression, positioning a bronchial occluder externally to the tracheal tube is an effective method of airway management. However, we still need more clinical practice to help the process become more standardized.

Driving pressure (∆P) is a core therapeutic component of mechanical ventilation (MV). Varying levels of ∆P have been employed during MV depending on the type of underlying pathology and severity of injury. However, ∆P levels have also been shown to closely impact hard endpoints such as mortality. Considering this, conducting an in-depth review of ∆P as a unique, outcome-impacting therapeutic modality is extremely important. There is a need to understand the subtleties involved in making sure ∆P levels are optimized to enhance outcomes and minimize harm. We performed this narrative review to further explore the various uses of ∆P, the different parameters that can affect its use, and how outcomes vary in different patient populations at different pressure levels. To better utilize ∆P in MV-requiring patients, additional large-scale clinical studies are needed.

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.

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.

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)-1β, 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.

EA alleviates VILI by inhibiting the NLR Family Pyrin Domain Containing three inflammasome through activation of the Nrf2/HO-1 pathway.

Inadequate intraoperative mechanical ventilation (MV) can lead to ventilator-induced lung injury and increased risk for postoperative pulmonary complications (PPCs). Mechanical power (MP) was shown to be a valuable indicator for MV outcomes in critical care patients. The aim of this study is to assess the association between intraoperative MP in low-risk surgical patients undergoing general anesthesia and PPCs.

Two-hundred eighteen low-risk surgical patients undergoing general anesthesia for elective surgery were included in the study. Intraoperative mechanical ventilatory support parameters were collected for all patients. Postoperatively, patients were followed throughout their hospital stay and up to seven days post discharge for the occurrence of any PPCs.

Out of 218 patients, 35% exhibited PPCs. The average body mass index, tidal volume per ideal body weight, peak inspiratory pressure, and MP were significantly higher in the patients with PPCs than in the patients without PPCs (30.3 ± 8.1 kg/m2 vs. 26.8 ± 4.9 kg.m2, p < 0.001; 9.1 ± 1.9 ml/kg vs. 8.6 ± 1.4 ml/kg, p = 0.02; 20 ± 4.9 cmH2O vs. 18 ± 3.7 cmH2O, p = 0.001; 12.9 ± 4.5 J/min vs. 11.1 ± 3.7 J/min, p = 0.002). A multivariable regression analysis revealed MP as the sole significant predictor for the risk of postoperative pulmonary complications [OR 1.1 (95% CI 1.0-1.2, p = 0.036].

High intraoperative mechanical power is a risk factor for developing postoperative pulmonary complications. Furthermore, intraoperative mechanical power is superior to other traditional mechanical ventilation variables in identifying surgical patients who are at risk for developing postoperative pulmonary complications.

NCT03551899; 24/02/2017.

The effects of adoptive transferring myeloid-derived suppressor cells (MDSCs) to mice with ventilator-induced lung injury (VILI) are unclear. Our objective was to investigate the effects of adoptively transferring MDSCs in VILI. The mouse model was created by introducing mechanical ventilation through a high tidal volume of 20 ml/kg for 4 h. Inflammation-induced MDSCs (iMDSCs) were collected from the bone marrow of mice with cecal ligation and puncture. iMDSCs were administrated through retrobulbar angular vein 1 h before the mechanical ventilation. The control group was anesthetized and maintained spontaneous respiration. After the termination of mechanical ventilation, bronchoalveolar lavage fluid (BALF) and lung samples 6 h were collected. The concentrations of BALF protein, levels of inflammatory mediators, and white blood cells were all significantly decreased in mice treated with iMDSCs. Histological examinations indicated reduced lung damage after iMDSCs treatment. Moreover, adoptive transfer of iMDSCs could reduce CD4+ T-cell counts and inhibit its inflammatory cytokine secretion. iMDSCs treatment was found to had no immunostimulatory effects or cause secondary infections in mice. In conclusion, MDSCs might be a potential targeted therapy for alleviating the inflammatory response of VILI mice in a T-cell dependent manner.

Mechanical ventilation (MV) has played a crucial role in the medical field, particularly in anesthesia and in critical care medicine (CCM) settings. MV has evolved significantly since its inception over 70 years ago and the future promises even more advanced technology. In the past, ventilation was provided manually, intermittently, and it was primarily used for resuscitation or as a last resort for patients with severe respiratory or cardiovascular failure. The earliest MV machines for prolonged ventilatory support and oxygenation were large and cumbersome. They required a significant amount of skills and expertise to operate. These early devices had limited capabilities, battery, power, safety features, alarms, and therefore these often caused harm to patients. Moreover, the physiology of MV was modified when mechanical ventilators moved from negative pressure to positive pressure mechanisms. Monitoring systems were also very limited and therefore the risks related to MV support were difficult to quantify, predict and timely detect for individual patients who were necessarily young with few comorbidities. Technology and devices designed to use tracheostomies versus endotracheal intubation evolved in the last century too and these are currently much more reliable. In the present, positive pressure MV is more sophisticated and widely used for extensive period of time. Modern ventilators use mostly positive pressure systems and are much smaller, more portable than their predecessors, and they are much easier to operate. They can also be programmed to provide different levels of support based on evolving physiological concepts allowing lung-protective ventilation. Monitoring systems are more sophisticated and knowledge related to the physiology of MV is improved. Patients are also more complex and elderly compared to the past. MV experts are informed about risks related to prolonged or aggressive ventilation modalities and settings. One of the most significant advances in MV has been protective lung ventilation, diaphragm protective ventilation including noninvasive ventilation (NIV). Health care professionals are familiar with the use of MV and in many countries, respiratory therapists have been trained for the exclusive purpose of providing safe and professional respiratory support to critically ill patients. Analgo-sedation drugs and techniques are improved, and more sedative drugs are available and this has an impact on recovery, weaning, and overall patients' outcome. Looking toward the future, MV is likely to continue to evolve and improve alongside monitoring techniques and sedatives. There is increasing precision in monitoring global "patient-ventilator" interactions: structure and analysis (asynchrony, desynchrony, etc). One area of development is the use of artificial intelligence (AI) in ventilator technology. AI can be used to monitor patients in real-time, and it can predict when a patient is likely to experience respiratory distress. This allows medical professionals to intervene before a crisis occurs, improving patient outcomes and reducing the need for emergency intervention. This specific area of development is intended as "personalized ventilation." It involves tailoring the ventilator settings to the individual patient, based on their physiology and the specific condition they are being treated for. This approach has the potential to improve patient outcomes by optimizing ventilation and reducing the risk of harm. In conclusion, MV has come a long way since its inception, and it continues to play a critical role in anesthesia and in CCM settings. Advances in technology have made MV safer, more effective, affordable, and more widely available. As technology continues to improve, more advanced and personalized MV will become available, leading to better patients' outcomes and quality of life for those in need.