• MIMIC-IV database
• Mechanical ventilation
• Non-invasive ventilation
• Sepsis

• Humans
• Hospital Mortality
• Male
• Sepsis/mortality
• Sepsis/therapy
• Female
• Aged
• Middle Aged
• Respiration, Artificial
• Databases, Factual
• Noninvasive Ventilation
• Propensity Score
• Organ Dysfunction Scores
• Intensive Care Units
• Aged, 80 and over
• Retrospective Studies
• Proportional Hazards Models

• LR2022003 Elderly health research project of Jiangsu Province

• diaphragm atrophy
• diaphragm contraction
• non-invasive ventilation
• phrenic nerve stimulation
• rapid magnetic stimulation
• reliability
• tidal volume
• transdiaphragmatic pressure

• acute respiratory distress syndrome (ARDS)
• hypoxemic respiratory failure
• mechanical ventilation
• optimal PEEP
• positive end-expiratory pressure (PEEP)

• Humans
• Positive-Pressure Respiration/methods
• Respiration, Artificial/methods
• Randomized Controlled Trials as Topic
• Intensive Care Units
• Respiratory Distress Syndrome/therapy
• Adult

• Acute respiratory failure
• Gas exchange
• Lung protective ventilation
• V-V ECMO

• Acute respiratory failure
• helmet support
• mechanical ventilation
• noninvasive ventilation
• positive end-expiratory pressure

Mechanical stretch is one type of common physiological activities such as during heart beating, lung breathing, blood flow through the vessels, and physical exercise. The mechanical stimulations regulate cellular functions and maintain body homeostasis. It still remains to further characterize the mechanical-biomechanical coupling mechanism. Here we applied fluorescence resonance energy transfer (FRET) technology to visualize ERK activity in airway smooth muscle (ASM) cells under cyclic stretch stimulation in airway smooth muscle (ASM) cells, and studied the mechanosensing pathway. FRET measurements showed apparent ERK activation by mechanical stretch, which was abolished by ERK inhibitor PD98059 pretreatment. Inhibition of extracellular Ca²⁺ influx reduced ERK activation, and selective inhibition of inositol 1,4,5-trisphosphate receptor (IP₃R) Ca²⁺ channel or SERCA Ca²⁺ pump on endoplasmic reticulum (ER) blocked the activation. Chemical inhibition of the L-type or store-operated Ca²⁺ channels on plasma membrane, or inhibition of integrin β1 with siRNA had little effect on ERK activation. Disruption of actin cytoskeleton but not microtubule one inhibited the stretch-induced ERK activation. Furthermore, the ER IP₃R-dependent ERK activation was not dependent on phospholipase C-IP₃ signal, indicating possibly more mechanical mechanism for IP₃R activation. It is concluded from our study that the mechanical stretch activated intracellular ERK signal in ASM cells through membrane Ca²⁺ channels mechanosensation but not integrin β1, which was mediated by actin cytoskeleton.

• National Natural Science Foundation of China
• Natural Science Foundation of Jiangsu Province
• Jiangsu Provincial Department of Education

The purpose of this study was to investigate the key nursing factors associated with ventilator-associated pneumonia (VAP) in critical care patients.

Through the quality control platform of Hebei Province, questionnaires were sent to intensive care nurses in 32 tertiary hospitals in Hebei Province, China to collect data concerning the incidence of VAP and the status of the nursing staff. All the data were analyzed using an independent t-test and a one-way analysis of variance (ANOVA). The Pearson correlation coefficient was used to analyse the correlation between the nursing factors and the incidence of VAP. Multivariate logistic regression analysis was used to determine the risk factors affecting VAP.

In terms of nursing, the incidence of VAP was affected by the differential nursing strategies. Multivariate logistic regression analysis showed that the incidence of VAP was significantly associated with the following six variables: the ratio of nurses to beds (p = 0.000), the ratio of nurses with a bachelor's degree or higher (p = 0.000), the ratio of specialist nurses (p = 0.000), the proportion of nurses with work experience of 5–10 years (p = 0.04), the number of patients nurses were responsible for at night (p = 0.01) and the frequency of oral care (p = 0.000).

The incidence of VAP is closely related to nursing factors. In terms of nursing human resources, even junior nurses (less experienced nurses) can play an essential role in reducing VAP. In addition, to reduce VAP, the number of patients that nurses are responsible for at night should be reduced as much as possible, and improving nursing qualifications.

• ICU
• VAP
• nurse human resources
• nursing practice
• risk factors

• ARDS
• ICU
• MPI
• PEEP
• mechanical ventilation
• myocardial function

Acute respiratory failure (ARF) is a major adverse event commonly encountered in severe coronavirus disease 2019 (COVID-19). Although noninvasive mechanical ventilation (NIV) has long been used in the management of ARF, it has several adverse events which may cause patient discomfort and lead to treatment complication. Recently, high-flow nasal cannula (HFNC) has the potential to be an alternative for NIV in adults with ARF, including COVID-19 patients. The objective was to investigate the efficacy of HFNC compared to NIV in COVID-19 patients.

This meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Literature search was carried out in electronic databases for relevant articles published prior to June 2021. The protocol used in this study has been registered in International Prospective Register of Systematic Reviews (CRD42020225186).

Although the success rate of NIV is higher compared to HFNC (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.16–0.97; P=0.04), this study showed that the mortality in the NIV group is also significantly higher compared to HFNC group (OR, 0.49; 95% CI, 0.39–0.63; P<0.001). Moreover, this study also demonstrated that there was no significant difference in intubation rates between the two groups (OR, 1.35; 95% CI, 0.86–2.11; P=0.19).

Patients treated with HFNC showed better outcomes compared to NIV for ARF due to COVID-19. Therefore, HFNC should be considered prior to NIV in COVID-19-associated ARF. However, further studies with larger sample sizes are still needed to better elucidate the benefit of HFNC in COVID-19 patients.

Mechanical ventilation can induce lung injury and exacerbate brain injury due to lung-brain interaction. The current study sought to investigate the mechanism of lung-brain interaction induced by mechanical ventilation and offer theoretical insight into the management of ventilator-induced brain injury. The experimental mice were assigned into the spontaneously breathing group and the mechanical ventilation group and injected with dopamine (DA) receptor antagonist haloperidol or P2Y1 receptor antagonist MRS2279 before ventilation. In vitro assay was conducted using lung epithelial cells MLE-12 hippocampal neuron cells and HT-22. Mouse recognition function and lung injury were examined. The condition and concentration of neurons in the hippocampus were observed. The levels of several inflammatory factors, DA, adenosine triphosphate (ATP), P2Y1R, and dysbindin-1 were detected. Mechanical ventilation induced lung and brain injury in mice, manifested in increased inflammatory factors in the bronchoalveolar lavage fluid and hippocampus, prolonged escape latency, and swimming distance and time in the target quadrant with a weakened concentration of neurons in the hippocampus. Our results presented elevated ATP and P2Y1R expressions in the mechanically ventilated mice and stretched MLE-12 cells. The mechanically ventilated mice and P2Y1 receptor activator MRS2365-treated HT-22 cells presented with elevated levels of DA and dysbindin-1. Inactivation of P2Y1 receptor in the hippocampus or blockage of DA receptor alleviated brain injury induced by mechanical ventilation in mice. To conclude, the current study elicited that lung injury induced by mechanical ventilation exacerbated brain injury in mice by increasing ATP production, activating the P2Y1 receptor, and thus promoting DA release.

• ATP
• Mechanical ventilation
• P2Y1R
• bronchoalveolar lavage fluid
• cognitive dysfunction
• dopamine
• hippocampus
• lung-brain interaction

• Analgesia/methods
• Analgesics, Opioid
• Humans
• Interleukin-6
• Nerve Block/methods
• Pain Measurement
• Pain, Postoperative/prevention & control
• Prospective Studies
• Sufentanil
• Thoracic Surgery, Video-Assisted
• Ultrasonography, Interventional/methods

• calcium
• endoplasmic reticulum stress
• inositol 1,4,5-trisphosphate receptor
• mitochondrial dysfunction
• ventilator-induced lung injury

The benefits of high-flow nasal cannula (HFNC) as primary intervention in patients with acute hypoxemic respiratory failure (AHRF) are still a matter in debate. Our objective was to compare HFNC therapy versus conventional oxygen therapy (COT) in the prevention of endotracheal intubation in this group of patients.

An open-label, controlled and single-centre clinical trial was conducted in patients with severe AHRF, defined by a PaO₂/FIO₂ ratio ⩽200, to compare HFNC with a control group (CG) treated by COT delivered through a face mask, with the need to perform intubation as the primary outcome. The secondary outcomes included tolerance of the HFNC device and to look for the predictive factors for intubation in these patients.

A total of 46 patients were included (22 in the COT group and 24 in the HFNC group) 48% of whom needed intubation: 63% in the COT group and 33% in the HFNC group, with significant differences both in intention to treat [χ² = 4.2; p = 0.04, relative risk (RR) = 0.5; confidence interval (CI) 95%: 0.3–1.0] and also in treatment analysis (χ² = 4.7; p = 0.03; RR = 0.5; IC 95%: 0.3–0.9) We obtained a number needed to treat (NNT) = 3 patients treated to avoid an intubation. Intubation occurred significantly later in the HFNC group. Estimated PaO₂/FIO₂, respiratory rate and dyspnea were significantly better in the HFNC group. Patients treated with HFNC who required intubation presented significant worsening after the first 8 h, as compared with non-intubated HFNC group patients. Mortality was 22% with no differences. The HFNC group patients were hospitalized for almost half of the time in the intensive care unit (ICU) and in the ward, with significantly less hospital length of stay. A total of 14 patients in the HFNC group (58%) complained of excessive heat and 17% of noise; 3 patients did not tolerate HFNC.

Patients with severe acute hypoxemic respiratory failure who tolerate HFNC present a significantly lower need for endotracheal intubation compared with conventional oxygen therapy.

EUDRA CT number: 2012-001671-36

The reviews of this paper are available via the supplemental material section.

• acute respiratory failure
• endotracheal intubation
• high-flow oxygen therapy
• nasal cannula

• APACHE
• Aged
• Critical Illness
• Female
• Humans
• Intensive Care Units
• Kaplan-Meier Estimate
• Length of Stay
• Male
• Middle Aged
• Oxygen/blood
• Pneumonia, Ventilator-Associated
• Pneumothorax/etiology
• Positive-Pressure Respiration/adverse effects
• Positive-Pressure Respiration/methods
• Respiratory Insufficiency/therapy
• Ventilator Weaning

• ARDS
• Mechanical ventilation
• Positron emission tomography
• Regional ventilation
• Variable ventilation

Acute respiratory distress syndrome (ARDS) is often associated with severe hypoxemia and a high mortality rate. Prone positioning is a well-established intervention for ARDS. It has been shown to improve oxygenation and prevent ventilator-induced lung injury due to the more uniform distribution of lung stress and strain. This narrative review aims to compare the various factors that may influence how prone positioning affects mortality rates. We will examine the duration of time a patient is in the prone position, severity of ARDS, use of lung-protective ventilation, and the time elapsed between ARDS diagnosis and placing a patient in the prone position. A literature review on prone positioning in ARDS was performed and searched data from PubMed and Google Scholar for articles published from 2010 to 2020. Although no single variable used during prone positioning reduces mortality rates in ARDS patients, combining several optimal conditions may yield increased survival benefits. Early initiation of extended prone positioning sessions combined with low tidal volumes shows encouraging results in severe ARDS patients. Future research on this subject should focus on further examining these variables in a study enrolling a larger number of subjects in a setting with adequately trained staff familiar with proper prone positioning techniques.

• acute respiratory distress syndrome
• ards
• prone positioning

The coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands.

PRoVENT-COVID (‘study of PRactice of VENTilation in COVID-19’) is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH₂O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality.

PRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee.

PRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342).

• SARS-CoV-2
• critical care medicine
• mechanical ventilation
• the coronavirus disease 2019 (COVID-19)
• ventilator-free days

• Acute respiratory distress syndrome
• Compliance
• Intensive care mortality
• Lung size
• Mechanical power
• Ventilator-induced lung injury

• Unbound bilirubin
• infant
• phototherapy

Extracorporeal life support (ECLS) encompasses a wide range of extracorporeal modalities that offer short- and intermediate-term mechanical support to the failing heart or lung. Apart from the daily use of cardiopulmonary bypass (CPB) in the operating room, there has been a resurgence of interest and utilization of veno-arterial and veno-venous extracorporeal membrane oxygenation (VA- and VV-ECMO, respectively) and extracorporeal carbon dioxide removal (ECCO₂R) in recent years. This might be attributed to the advancement in technology, nonetheless the morbidity and mortality associated with the clinical application of this technology is still significant. The initiation of ECLS triggers a systemic inflammatory response, which involves the activation of the coagulation cascade, complement systems, endothelial cells, leukocytes, and platelets, thus potentially contributing to morbidity and mortality. This is due to the release of cytokines and other biomarkers of inflammation, which have been associated with multiorgan dysfunction. On the other hand, ECLS can be utilized as a therapy to halt the inflammatory response associated with critical illness and ICU therapeutic intervention, such as facilitating ultra-protective mechanical ventilation. In addition to addressing the impact on outcome of the relationship between inflammation and ECLS, two different but complementary pathophysiological perspectives will be developed in this review: ECLS as the cause of inflammation and ECLS as the treatment of inflammation. This framework may be useful in guiding the development of novel therapeutic strategies to improve the outcome of critical illness.

• Biomarkers
• Cardiopulmonary bypass
• Cytokines
• Extracorporeal carbon dioxide removal
• Extracorporeal life support
• Extracorporeal membrane oxygenation
• Inflammation

• ARDS
• VILI
• cyclic stretch
• focal adhesion
• integrin β4
• mechanical stress

• crystalloid
• fluid resuscitation
• hypovolemia
• lung profile
• ventilator

Mechanical ventilation may cause ventilator-induced lung injury (VILI). Canonical Wnt signaling has been reported to serve an important role in the pathogenesis of VILI. Bioinformatics analysis revealed that canonical and non-canonical Wnt signaling pathways were activated in VILI. However, the role of non-canonical Wnt signaling in the pathogenesis of VILI remains unclear. The present study aimed to analyze the potential role of non-canonical Wnt signaling in VILI pathogenesis. Lung injury was assessed via Evans blue albumin permeability and histological scoring, as well as by inflammatory cytokine expression and total protein concentration in bronchoalveolar lavage fluid. The relative protein expression of canonical and non-canonical Wnt signaling pathway components were examined via western blotting and immunohistochemistry. The results demonstrated that 6 h of mechanical ventilation at low tidal volume (LTV; 6 ml/kg) or moderate tidal volume (MTV; 12 ml/kg) induced lung injury in sensitive A/J mice. Ventilation with MTV increased the protein levels of Wnt-induced secreted protein 1 (WISP1), Rho-associated protein kinase 1 (ROCK1), phosphorylated (p)-Ras homolog gene family, member A and p-C-Jun N-terminal kinase (JNK). Inhibition of ROCK1 by Y27632 and JNK by SP600125 attenuated MTV-induced lung injury and decreased the expression of proteins involved in non-canonical Wnt signaling, including WISP1. In conclusion, non-canonical Wnt signaling participates in VILI by modulating WISP1 expression, which has been previously noted as critical for VILI development. Therefore, the non-canonical Wnt signaling pathway may provide a preventive and therapeutic target in VILI.

• Diaphragm
• Mechanical ventilation
• Phrenic stimulation
• Ventilator-induced diaphragmatic dysfunction
• Weaning

• acute lung injury
• acute respiratory distress syndrome
• rescue therapies
• extracorporeal membrane oxygenation
• neuromuscular blockade
• mechanical ventilation

• Evidence-Based Medicine
• Extracorporeal Membrane Oxygenation/methods
• High-Frequency Ventilation
• Humans
• Positive-Pressure Respiration
• Respiration, Artificial/methods
• Respiratory Distress Syndrome/physiopathology
• Respiratory Distress Syndrome/therapy
• Respiratory Insufficiency/physiopathology
• Respiratory Insufficiency/therapy
• Severity of Illness Index

• R01 HL051856 NHLBI NIH HHS
• R35 HL140026 NHLBI NIH HHS

• Urine biomarkers
• Ventilator-induced kidney injury

• Artificial ventilation
• Critical care
• Duration of ventilation
• Intensive care unit
• Invasive ventilation
• Mechanical ventilation
• Mortality
• Non-injured lungs
• PEEP
• Positive end-expiratory pressure

• Data Interpretation, Statistical
• Humans
• Intensive Care Units
• Multicenter Studies as Topic
• Positive-Pressure Respiration/adverse effects
• Positive-Pressure Respiration/methods
• Randomized Controlled Trials as Topic
• Respiratory Distress Syndrome/therapy
• Sample Size

• 80-84300-98-72053 ZonMw

• Ards
• Invasive Ventilation
• Mechanical Ventilation
• Middle-income Countries
• Outcomes
• Resource-limited Settings

• Adolescent
• Adult
• Asia
• Developing Countries
• Humans
• Intensive Care Units
• Multicenter Studies as Topic
• Observational Studies as Topic
• Prospective Studies
• Respiratory Distress Syndrome
• Treatment Outcome

• Unbound bilirubin
• hearing
• premature infant

High flow nasal cannula (HFNC) is known to increase global ventilation volume in healthy subjects. We sought to investigate the effect of HFNC on global and regional ventilation patterns in patients with hypoxia.

Patients were randomized to receive one of two oxygen therapies in sequence: nasal cannula (NC) followed by HFNC or HFNC followed by NC. Global and regional ventilation was assessed using electric impedance tomography.

Twenty-four patients participated. Global tidal variation (TV) in the lung was higher during HFNC (NC, 2,241 ± 1,381 arbitrary units (AU); HFNC, 2,543 ± 1,534 AU; P < 0.001). Regional TVs for four iso-gravitational quadrants of the lung were also all higher during HFNC than NC. The coefficient of variation for the four quadrants of the lung was 0.90 ± 0.61 during NC and 0.77 ± 0.48 during HFNC (P = 0.035). Within the four gravitational layers of the lung, regional TVs were higher in the two middle layers during HFNC when compared to NC. Regional TV values in the most ventral and dorsal layers of the lung were not higher during HFNC compared with NC. The coefficient of variation for the four gravitational layers of the lung were 1.00 ± 0.57 during NC and 0.97 ± 0.42 during HFNC (P = 0.574).

In patients with hypoxia, ventilation of iso-gravitational regions of the lung during HFNC was higher and more homogenized compared with NC. However, ventilation of gravitational layers increased only in the middle layers. (Clinical trials registration number: NCT02943863).

• electric impedance
• oxygen inhalation therapy
• pulmonary ventilation