OBJECTIVE: To assess whether the use of Tanreqing (TRQ) Injection could show improvements in time to extubation, intensive care unit (ICU) mortality, ventilator-associated events (VAEs) and infection-related ventilator associated complication (IVAC) among patients receiving mechanical ventilation (MV). METHODS: A time-dependent cox-regression analysis was conducted using data from a well-established registry of healthcare-associated infections at ICUs in China. Patients receiving continuous MV for 3 days or more were included. A time-varying exposure definition was used for TRQ Injection, which were recorded on daily basis. The outcomes included time to extubation, ICU mortality, VAEs and IVAC. Time-dependent Cox models were used to compare the clinical outcomes between TRQ Injection and non-use, after controlling for the influence of comorbidities/conditions and other medications with both fixed and time-varying covariates. For the analyses of time to extubation and ICU mortality, Fine-Gray competing risk models were also used to measure competing risks and outcomes of interest. RESULTS: Overall, 7,685 patients were included for the analyses of MV duration, and 7,273 patients for the analysis of ICU mortality. Compared to non-use, patients with TRQ Injection had a lower risk of ICU mortality (Hazards ratios (HR) 0.761, 95% CI, 0.581-0.997), and was associated with a higher hazard for time to extubation (HR 1.105, 95% CI, 1.005-1.216), suggesting a beneficial effect on shortened time to extubation. No significant differences were observed between TRQ Injection and non-use regarding VAEs (HR 1.057, 95% CI, 0.912-1.225) and IVAC (HR 1.177, 95% CI, 0.929-1.491). The effect estimates were robust when using alternative statistic models, applying alternative inclusion and exclusion criteria, and handling missing data by alternative approaches. CONCLUSION Our findings suggested that the use of TRQ Injection might lower mortality and improve time to extubation among patients receiving MV, even after controlling for the factor that the use of TRQ changed over time.
Humans ; Respiration, Artificial/adverse effects* ; Intensive Care Units ; Proportional Hazards Models ; Registries ; Length of Stay

OBJECTIVE: To systematically review safety and tolerance of enteral nutrition (EN) in a prone position, as well as the risks of increased gastric residual volume (GRV), vomiting, aspiration, and ventilator-associated pneumonia, and determine the ways to improve EN tolerance in patients with acute respiratory distress syndrome (ARDS). METHODS: Databases including PubMed, Embase and Wanfang Medical data of the English and Chinese literatures were retrieved up from January 1979 to January 2022 to collet the randomized controlled trial (RCT), non-RCT, and observational studies, concerning safety and tolerance of EN in a prone position with ARDS. All trials must have a minimum of two patient groups, one of which must be prone to ARDS and receive EN. Data searching extracting and quality evaluation were assessed by two reviewers independently. RevMan 5.4 software was used for analysis. RESULTS: A total of 9 studies were included, including 2 RCTs, 2 non-RCTs, 4 prospective observational studies, and 1 retrospective observational study. The starting and increasing rate of EN were typically well tolerated in the prone position compared to the supine position in patients with ARDS, there was no significant increase in GRV (mL: 95 vs. 110), and the incidence of vomiting was not noticeably higher (0%-35% vs. 33%-57%). The incidence of ventilator-associated pneumonia with EN was not significantly higher in the prone position than in the supine position in patients with ARDS (6%-35% vs. 15%-24%). Aspiration occurred at a similar rate in patients in the nasogastric tube and post-pyloric feeding groups with EN in patients with ARDS in the prone position (22% vs. 20%). EN tolerability with nasogastric and nasojejunal tubes was similar in prone positions, with no significant difference in EN intolerance incidences (15% vs. 22%). Head elevation (30 degree angle-45 degree angle) improved EN tolerance in the prone position in patients with ARDS, thereby increasing the early EN dose [odds ratio (OR) = 0.48, 95% confidence interval (95%CI) was 0.22-1.08, P = 0.08]. Additionally, prophylactic application of gastrointestinal motility drugs, such as erythromycin, at the start of EN in a prone position significantly improved patients' EN tolerance (OR = 1.14, 95%CI was 0.63-2.05, P = 0.67). CONCLUSIONS The use of gastric tube for EN in prone position and similar feeding speed to the supine position in patients with ARDS is safe and well tolerated. The initiation and dosing of EN should not be delayed in the prone position. EN tolerance may be increased by elevating the head of the bed during enteral feeding in a prone position, and gastrointestinal motility medications should be promptly administered with EN initiation in patients with ARDS.
Humans ; Pneumonia, Ventilator-Associated/etiology* ; Enteral Nutrition ; Prone Position ; Respiration, Artificial/adverse effects* ; Respiratory Distress Syndrome/etiology* ; Randomized Controlled Trials as Topic ; Observational Studies as Topic

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*

OBJECTIVE: To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process. METHODS: The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis. RESULTS: Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/β-actin: 1.40±0.02 vs. 1, BIP/β-actin: 2.79±0.07 vs. 1, PDI/β-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/β-actin: 0.53±0.03 vs. 1.40±0.02, BIP/β-actin: 1.73±0.15 vs. 2.79±0.07, PDI/β-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group. CONCLUSIONS MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.
Mice ; Animals ; Pulmonary Fibrosis/chemically induced* ; Lung Injury ; Respiration, Artificial/adverse effects* ; Actins/metabolism* ; Tubulin ; Mice, Inbred C57BL ; Endoplasmic Reticulum Stress ; RNA, Small Interfering

OBJECTIVES: To study the application value of transport ventilator in the inter-hospital transport of critically ill children. METHODS: The critically ill children in Hunan Children's Hospital who were transported with or without a transport ventilator were included as the observation group (from January 2019 to January 2020; n=122) and the control group (from January 2018 to January 2019; n=120), respectively. The two groups were compared in terms of general data, the changes in heart rate, respiratory rate, and blood oxygen saturation during transport, the incidence rates of adverse events, and outcomes. RESULTS: There were no significant differences between the two groups in sex, age, oxygenation index, pediatric critical illness score, course of disease, primary disease, heart rate, respiratory rate, and transcutaneous oxygen saturation before transport (P>0.05). During transport, there were no significant differences between the two groups in the changes in heart rate, respiratory rate, and transcutaneous oxygen saturation (P>0.05). The incidence rates of tracheal catheter detachment, indwelling needle detachment, and sudden cardiac arrest in the observation group were lower than those in the control group during transport, but the difference was not statistically significant (P>0.05). Compared with the control group, the observation group had significantly shorter duration of mechanical ventilation and length of stay in the pediatric intensive care unit and significantly higher transport success rate and cure/improvement rate (P<0.05). CONCLUSIONS The application of transport ventilator in the inter-hospital transport can improve the success rate of inter-hospital transport and the prognosis in critically ill children, and therefore, it holds promise for clinical application in the inter-hospital transport of critically ill children.
Child ; Humans ; Critical Illness ; Respiration, Artificial/adverse effects* ; Intensive Care Units, Pediatric ; Ventilators, Mechanical ; Prognosis

OBJECTIVES: To investigate the effect of sequential sedative and analgesic drugs in preventing delirium and withdrawal symptoms in children after ventilator weaning. METHODS: A retrospective analysis was performed on 61 children who were admitted and received mechanical ventilation support for ≥5 days in the Pediatric Intensive Care Unit of Dongguan Children's Hospital Affiliated to Guangdong Medical University from December 2019 to September 2021. The children were divided into a control group (30 children with no maintenance of analgesic and sedative drugs after ventilator weaning) and an observation group (31 children with sequential sedative and analgesic drugs maintained for 48 hours after ventilator weaning). The two groups were compared in terms of the Sophia Observation Withdrawal Symptoms Scale (SOS) score, the Pediatric Delirium Scale (PD) score, the Richmond Agitation-Sedation Scale (RASS) score, and the incidence rates of delirium or withdrawal symptoms at 24 and 72 hours after ventilator weaning. RESULTS: There was no significant difference in the incidence rate of delirium at 24 hours and 72 hours after ventilator weaning between the two groups (P>0.05). Compared with the control group, the observation group had significantly lower incidence rate of withdrawal symptoms and scores of SOS, PD, and RASS scales at 24 hours and 72 hours after ventilator weaning (P<0.01). CONCLUSIONS Sequential sedation and analgesia after ventilator weaning can reduce the incidence of withdrawal symptoms within 72 hours after ventilator weaning, but it cannot reduce the incidence rate of delirium.
Analgesia ; Analgesics/therapeutic use* ; Child ; Delirium/prevention & control* ; Humans ; Hypnotics and Sedatives/therapeutic use* ; Intensive Care Units, Pediatric ; Pain ; Prospective Studies ; Respiration, Artificial/adverse effects* ; Retrospective Studies ; Substance Withdrawal Syndrome/prevention & control* ; Ventilator Weaning

Neurocritical care (NCC) is not only generally guided by principles of general intensive care, but also directed by specific goals and methods. This review summarizes the common pulmonary diseases and pathophysiology affecting NCC patients and the progress made in strategies of respiratory support in NCC. This review highlights the possible interactions and pathways that have been revealed between neurological injuries and respiratory diseases, including the catecholamine pathway, systemic inflammatory reactions, adrenergic hypersensitivity, and dopaminergic signaling. Pulmonary complications of neurocritical patients include pneumonia, neurological pulmonary edema, and respiratory distress. Specific aspects of respiratory management include prioritizing the protection of the brain, and the goal of respiratory management is to avoid inappropriate blood gas composition levels and intracranial hypertension. Compared with the traditional mode of protective mechanical ventilation with low tidal volume (Vt), high positive end-expiratory pressure (PEEP), and recruitment maneuvers, low PEEP might yield a potential benefit in closing and protecting the lung tissue. Multimodal neuromonitoring can ensure the safety of respiratory maneuvers in clinical and scientific practice. Future studies are required to develop guidelines for respiratory management in NCC.
Humans ; Lung ; Lung Diseases/etiology* ; Positive-Pressure Respiration/methods* ; Respiration, Artificial/adverse effects* ; Tidal Volume

Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established (P<0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant (P<0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) (P<0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline (P<0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group (P<0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.
Animals ; Extravascular Lung Water ; Lung/physiology* ; Paraquat/toxicity* ; Respiration, Artificial/adverse effects* ; Respiratory Distress Syndrome/chemically induced* ; Swine

OBJECTIVE: To elucidate the pathogenic role of leukotriene B4 (LTB4) in pulmonary hyper-permeability and inflammation induced by lung-protective mechanical ventilation (LPMV) in rabbits. METHODS: Thirty-two healthy Japanese white rabbits were randomized into 4 groups for treatment with vehicle or bestatin (a leukotriene A4 hydrolase inhibitor that inhibits LTB4 production) administered intragastrically at the daily dose of 8 mg/kg for 5 days, followed by sham operation (group S and group BS, respectively, in which the rabbits were anesthetized only) or LPMV (group PM and group BPM, respectively, in which the rabbits received ventilation with 50% oxygen at a tidal volume of 8 mL/kg for 5 h). The concentrations of LTB4 and cyclic adenosine monophosphate (cAMP) in the lung tissues were analyzed by ELISA. cAMP content, protein kinase A (PKA) protein expression and the Rap1-GTP protein to total Rap1 protein ratio were determined to assess the activities of cAMP/PKA and Rap1 signaling pathways. The lung injury was evaluated by assessing lung permeability index, lung wet/dry weight ratio, polymorphonuclear leukocyte (PMN) count in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity and lung histological scores. RESULTS: None of the examined parameters differed significantly between group S and group BS. All the parameters with the exception of lung histological score increased significantly in group PM and group BPM as compared to those in group S ( CONCLUSIONS LPMV can induce LTB4 overproduction to down-regulate cAMP/PKA and Rap1 signaling pathways in the lungs of rabbits, which results in lung hyper-permeability and inflammation. Bestatin can inhibit LTB4 production in the lungs to protect against LPMV-induced lung hyper-permeability and inflammation.
Animals ; Bronchoalveolar Lavage Fluid ; Leukotriene B4 ; Lung ; Lung Injury/prevention & control* ; Neutrophils ; Rabbits ; Respiration, Artificial/adverse effects*

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