The need for mechanical ventilation due to severe hypoxemia and acute respiratory distress syndrome has increased dramatically in the global pandemic of severe respiratory infectious diseases. In clinical scenarios, it is sometimes necessary to briefly disconnect the ventilator pipeline from the artificial airway. Still, this operation can lead to a sharp drop in airway pressure, which is contrary to the protective lung ventilation strategy and increases the risk of environmental exposure to bioaerosol, posing a serious threat to patients and medical workers. At present, there is yet to be a practical solution. A new artificial airway device was designed by the medical staff from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University, based on many years of research experience in respiratory support therapy, and recently obtained the National Utility Model Patent of China (ZL 2019 2 0379605.4). The device comprises two connecting pipes, the sealing device body, and the globe valve represented by the iridescent optical ring. It has a simple structure, convenient operation, and low production cost. The device is installed between the artificial airway and the ventilator pipeline and realizes the instantaneous sealing of the artificial airway by adjusting the shut-off valve. Using this device to treat mechanically ventilated patients can minimize the ventilator-induced lung injury caused by the repeated disconnection of pipelines, avoid iatrogenic transmission of bioaerosols, and realize dual protection for patients and medical workers. It has extensive clinical application prospects and high health and economic value.
Humans ; Respiration, Artificial/adverse effects* ; Ventilators, Mechanical/adverse effects* ; Respiratory Distress Syndrome/therapy* ; Ventilator-Induced Lung Injury/prevention & control* ; Hypoxia/complications*

For patients receiving mechanical ventilation, mechanical ventilation is also an injury factor at the same time of treatment, which can lead to or aggravate lung injury, that is, ventilator-induced lung injury (VILI). The typical feature of VILI is that the mechanical stress is transmitted to cells through the pathway, leading to uncontrollable inflammatory cascade reaction, which causes the activation of inflammatory cells in the lung and the release of a large number of cytokines and inflammatory mediators. Among them, innate immunity is also involved in the occurrence and development of VILI. A large number of studies have shown that damaged lung tissue in VILI can regulate inflammatory response by releasing a large number of damage associated molecular pattern (DAMP). Pattern recognition receptor (PRR) participates in the activation of immune response by combining with DAMP, and releases a large number of inflammatory mediators to promote the occurrence and development of VILI. Recent studies have shown that inhibition of DAMP/PRR signaling pathway can play a protective role in VILI. Therefore, this article will mainly discuss the potential role of blocking DAMP/PRR signal pathway in VILI, and provide new ideas for the treatment of VILI.
Humans ; Respiration, Artificial ; Respiration ; Immunity, Innate ; Ventilator-Induced Lung Injury ; Inflammation ; Inflammation Mediators ; Lung

This paper compares and describes the tidal volume (Vt) used in mechanically ventilated dogs under a range of clinical conditions. Twenty-eight dogs requiring mechanical ventilation (MV) were classified into 3 groups: healthy dogs mechanically ventilated during surgery (group I, n = 10), dogs requiring MV due to extra-pulmonary reasons (group II, n = 7), and dogs that required MV due to pulmonary pathologies (group III, n = 11). The median Vt used in each group was 16 mL/kg (interquartile range [IQR], 15.14–21) for group I, 12.59 mL/kg (IQR, 9–14.25) for group II, and 12.59 mL/kg (IQR, 10.15–14.96) for group III. The Vt used was significantly lower in group III than in group I (p = 0.016). The thoraco-pulmonary compliance was significantly higher in group I than in groups II and III (p = 0.011 and p = 0.006, respectively). The median driving pressure was similar among the groups with a median of 9, 11, and 10 cmH2O in groups I, II, and III, respectively (p = 0.260). Critically-ill dogs requiring MV due to the primary pulmonary pathology received a significantly lower Vt than healthy dogs but with a range of values that were markedly higher than those recommended by human guidelines.
Animals ; Compliance ; Dogs ; Humans ; Pathology ; Respiration, Artificial ; Tidal Volume ; Ventilator-Induced Lung Injury

Lung-protective ventilation (such as low tidal volume and application of positive end-expiratory pressure) is beneficial for patients with acute lung injury or acute respiratory distress syndrome (ARDS) and has become the standard treatment in intensive care unit (ICU). However, some experts now question whether the protective ventilation strategy for ARDS patients in the ICU is equally beneficial for patients after surgery, especially for most patients without any pre-existing lung lesions. This review will discuss preoperative, intraoperative, and postoperative lung protection strategies to reduce the risk of complications associated with anesthesia.
Humans ; Positive-Pressure Respiration ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; Tidal Volume ; Ventilator-Induced Lung Injury

OBJECTIVE: To investigate the relationship between different tidal volume (VT) mechanical ventilation (MV) and autophagy and mitochondrial damage in rats. METHODS: A total of 120 clean-grade male Sprague-Dawley (SD) rats were divided into five groups (n = 24) by random number table method, and then given 0 (spontaneous breathing), 10, 20, 30, 40 mL/kg VT for MV. The rats in each group were subdivided into four subgroups of 1, 2, 3, and 4 hours according to ventilation time, with 6 rats in each subgroup. The lung tissue and bronchoalveolar lavage fluid (BALF) were harvested, and alveolar macrophages (AMs) and type II alveolar epithelial cells (AEC II) were cultured in vitro. The mRNA and protein expressions of autophagy-associated protein microtubule-associated protein 1 light chain 3B-II (LC3B-II) and autophagy-related genes Beclin1 and p62 were determined by reverse transcription-polymerase chain reaction (RT-PCR) or Western Blot. Lung autophagosome formation was observed under transmission electron microscope. The levels of adenosine triphosphate (ATP), reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in lung tissue were determined for assessing mitochondrial damage. RESULTS: There were no significant differences in the mRNA and protein expressions of LC3B-II, p62 and Beclin1 at 1 hour after ventilation among the groups. With the prolonged ventilation time, the mRNA and protein expressions of LC3B-II, p62 and Beclin1 in MV groups were increased gradually, peaked at 2-3 hours, and they were increased significantly in 30 mL/kg VT group as compared with those in spontaneous respiration group with statistical significances [ventilation for 2 hours: LC3B-II mRNA (2^-ΔΔCt) was 2.44±0.24 vs. 1.12±0.04, LC3B-II/LC3B-I was 1.42±0.16 vs. 0.57±0.03, p62 mRNA (2^-ΔΔCt) was 2.96±0.14 vs. 1.14±0.02, Beclin1 mRNA (2^-ΔΔCt) was 2.80±0.13 vs. 1.14±0.02; ventilation for 3 hours: p62/β-actin was 1.14±0.15 vs. 0.55±0.04, Beclin1/β-actin was 1.27±0.06 vs. 0.87±0.04, all P < 0.05]. Autophagosomes and autolysosomes were found in AEC II after ventilation for 2 hours at 30 mL/kg VT by transmission electron microscopy, but not in AEC I. Compared with spontaneous breathing group, ATP synthesis in AMs was significantly decreased at 2 hours of ventilation in 30 mL/kg VT group (A value: 0.82±0.05 vs. 1.00±0.00, P < 0.05), ROS accumulate in AMs and AEC II were significantly increased [ROS in AMs: (33.83±4.00)% vs. (6.90±0.62)%, ROS in AEC II: (80.68±0.90)% vs. (2.16±0.19)%, both P < 0.05]. With the increase in VT and the prolongation of ventilation time, ATP and ROS levels in AMs and AEC II were gradually decreased, the ATP (A value) in AMs at 4 hours of ventilation in 40 mL/kg VT group was 0.41±0.05, the ROS in AMs was (12.95±0.88)%, and the ROS in AEC II was (40.43±2.29)%. With the increase in VT and the prolongation of ventilation time, MMP levels were gradually increased, the MMP (green/red fluorescence intensity ratio) in AMs at 2 hours of ventilation in 30 mL/kg VT group was 1.11±0.17, the MMP in AEC II was 0.96±0.04, and the MMP (green/red fluorescence intensity ratio) at 4 hours of ventilation in 40 mL/kg VT group was 0.51±0.07 and 0.49±0.06, respectively. CONCLUSIONS The MV with high VT could induce autophagy activation and mitochondrial damage in lung tissue of rats, and the longer the ventilation time, the more obvious autophagy in the lung.
Animals ; Autophagy/physiology* ; Male ; Mitochondria/pathology* ; Rats ; Rats, Sprague-Dawley ; Respiration, Artificial/adverse effects* ; Tidal Volume ; Time Factors ; Ventilator-Induced Lung Injury

OBJECTIVE: To investigate the role and mechanism of Ly6C^high monocyte in mice with ventilator-induced lung injury (VILI). METHODS: Forty-eight healthy male SPF C57BL/6 mice were divided into spontaneous breathing group (n = 8), normal tidal volume (VT) group (VT was 8 mL/kg, n = 8), and high VT group (VT was 20 mL/kg, n = 32). The mice in the high VT group were subdivided into 1, 2, 3 and 4 hours subgroups, with 8 mice in each subgroup. All mice underwent direct tracheal intubation, those in the spontaneous breathing group maintained spontaneous breathing, and those in the normal VT group and high VT group were mechanically ventilated with different VT. After ventilation for 4 hours, bronchoalveolar lavage fluid (BALF) was collected to determine total protein, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immune sorbent assay (ELISA). The lung tissues were harvested to determine the wet/dry (W/D) ratio, and lung tissue injury was assessed in terms of lung histopathologic examination after hematoxylin-eosin (HE) staining under the light microscope. The protein expressions of monocyte chemotactic protein-1 (MCP-1) and CC-chemokine receptor 2 (CCR2) in lung tissues were determined by Western Blot. Flow cytometry was used to detect the proportion of Ly6C^high monocyte in lung tissue. RESULTS: The histopathology of lung tissue structures was normal in the spontaneous breathing group and the normal VT group. Inflammatory reaction began to appear at 2 hours of high VT ventilation, and inflammatory reaction was gradually aggravated with the time extension. Compared with the spontaneous breathing group, the total protein, TNF-α, and IL-1β levels in BALF, the lung W/D ratio and MCP-1 expression were increased from 2 hours of high VT ventilation [total protein in BALF (g/L): 1.05±0.13 vs. 0.58±0.11, TNF-α in BALF (ng/L): 116.86±16.14 vs. 38.27±8.00, IL-1β in BALF (ng/L): 178.98±10.41 vs. 117.56±23.40, lung W/D ratio: 5.76±0.27 vs. 4.98±0.39, MCP-1/GAPDH: 0.87±0.19 vs. 0.29±0.12, all P < 0.05], and CCR2 expression and the proportion of Ly6C^high monocyte was significantly increased from 3 hours of high VT ventilation [CCR2/GAPDH: 0.84±0.19 vs. 0.24±0.11, Ly6C^high monocyte proportion: (9.01±2.47)% vs. (1.06±0.35)%, both P < 0.05], and they all showed an increased tendency with the time extension. There was no significant difference in the parameters mentioned above among the spontaneous breathing group, normal VT group and high VT ventilation 1-hour group. CONCLUSIONS Ly6C^high monocytes are involved in VILI, which aggravate VILI by activating the MCP-1/CCR2 axis.
Animals ; Antigens, Ly/metabolism* ; Lung ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes ; Rats ; Rats, Sprague-Dawley ; Tidal Volume ; Tumor Necrosis Factor-alpha ; Ventilator-Induced Lung Injury

The ventilator-induced lung injury (VILI) was centered on the "static" characteristics of the mechanical ventilation in early phases (tidal volume, plateau pressure, positive end-expiratory pressure and driving pressure). But the "dynamic" characteristics of ventilation must not be ignored (respiratory rate and flow). Mechanical energy and mechanical power (the pace of performing energy load) regarding all factor have won wide spread attention. The energy generated by mechanical ventilation is mainly used to expand respiratory system and overcome resistance, a fraction of energy acts on lung tissues probably inducing "heat" and inflammation that is related to lung injury. The review described recent conceptual advances regarding the mechanical energy and power, and the relationship with VILI, hoping to help further understanding the risk factors for VILI.
Humans ; Lung ; Positive-Pressure Respiration ; Respiration, Artificial ; Respiratory Distress Syndrome ; Tidal Volume ; Ventilator-Induced Lung Injury

BackgroundVentilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.

MethodsFor the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.

ResultsIn vivo, compared with Group C, total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = -28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-α (t = -19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P < 0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = -14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = -21.111, P < 0.01) and TNF-α (t = -15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = -3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.

ConclusionsHigh tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.

Animals ; Cadherins ; metabolism ; Catenins ; metabolism ; Glutamine ; metabolism ; Inflammation ; metabolism ; Interleukin-6 ; metabolism ; Lung ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Ventilator-Induced Lung Injury ; immunology ; metabolism

ObjectiveMechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.

Data SourcesThis review was based on articles in the PubMed database up to December 2017 using the following keywords: "ventilator-induced lung injury", "pathogenesis", "mechanism", and "biotrauma".

Study SelectionOriginal articles and reviews pertaining to mechanisms of VILI were included and reviewed.

ResultsThe pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction.

ConclusionsBarotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.

Animals ; Barotrauma ; metabolism ; Humans ; Reactive Oxygen Species ; metabolism ; Ventilator-Induced Lung Injury ; metabolism ; Wounds and Injuries ; metabolism

Management of mechanical ventilation is essential for patients with neuro-critical illnesses who may also have impairment of airways, lungs, respiratory muscles, and respiratory drive. However, balancing the approach to mechanical ventilation in the intensive care unit (ICU) with the need to prevent additional lung and brain injury, is challenging to intensivists. Lung protective ventilation strategies should be modified and applied to neuro-critically ill patients to maintain normocapnia and proper positive end expiratory pressure in the setting of neurological closed monitoring. Understanding the various parameters and graphic waveforms of the mechanical ventilator can provide information about the respiratory target, including appropriate tidal volume, airway pressure, and synchrony between patient and ventilator, especially in patients with neurological dysfunction due to irregularity of spontaneous respiration. Several types of asynchrony occur during mechanical ventilation, including trigger, flow, and termination asynchrony. This review aims to present the basic interpretation of mechanical ventilator waveforms and utilization of waveforms in various clinical situations in the neuro-ICU.
Brain Injuries ; Humans ; Intensive Care Units ; Lung ; Positive-Pressure Respiration ; Respiration ; Respiration, Artificial ; Respiratory Muscles ; Tidal Volume ; Ventilation ; Ventilator-Induced Lung Injury ; Ventilators, Mechanical