Effects of Prone Positioning on Respiratory Mechanics and Oxygenation in Critically Ill Patients With COVID-19 Requiring Venovenous Extracorporeal Membrane Oxygenation

Background:The effect of prone positioning (PP) on respiratory mechanics remains uncertain in patients with severe acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (VV-ECMO).Methods:We prospectively analyzed the effects of PP on respiratory mechanics from continuous data with over a thousand time points during 16-h PP sessions in patients with COVID-19 and ARDS under VV-ECMO conditions. The evolution of respiratory mechanical and oxygenation parameters during the PP sessions was evaluated by dividing each PP session into four time quartiles: first quartile: 0–4 h, second quartile: 4–8 h, third quartile: 8–12 h, and fourth quartile: 12–16 h.Results:Overall, 38 PP sessions were performed in 10 patients, with 3 [2–5] PP sessions per patient. Seven (70%) patients were responders to at least one PP session. PP significantly increased the PaO2/FiO2 ratio by 14 ± 21% and compliance by 8 ± 15%, and significantly decreased the oxygenation index by 13 ± 18% and driving pressure by 8 ± 12%. The effects of PP on respiratory mechanics but not on oxygenation persisted after supine repositioning. PP-induced changes in different respiratory mechanical parameters and oxygenation started as early as the first-time quartile, without any difference in PP-induced changes among the different time quartiles. PP-induced changes in driving pressure (−14 ± 14 vs. −6 ± 10%, p = 0.04) and mechanical power (−11 ± 13 vs. −0.1 ± 12%, p = 0.02) were significantly higher in responders (increase in PaO2/FiO2 ratio > 20%) than in non-responder patients.Conclusions:In patients with COVID-19 and severe ARDS, PP under VV-ECMO conditions improved the respiratory mechanical and oxygenation parameters, and the effects of PP on respiratory mechanics persisted after supine repositioning.

Risk factor analysis and nomogram for predicting in-hospital mortality in ICU patients with sepsis and lung infection

Background Lung infection is a common cause of sepsis, and patients with sepsis and lung infection are more ill and have a higher mortality rate than sepsis patients without lung infection. We constructed a nomogram prediction model to accurately evaluate the prognosis of and provide treatment advice for patients with sepsis and lung infection. Methods Data were retrospectively extracted from the Medical Information Mart for Intensive Care (MIMIC-III) open-source clinical database. The definition of Sepsis 3.0 [10] was used, which includes patients with life-threatening organ dysfunction caused by an uncontrolled host response to infection, and SOFA score ≥ 2. The nomogram prediction model was constructed from the training set using logistic regression analysis, and was then internally validated and underwent sensitivity analysis. Results The risk factors of age, lactate, temperature, oxygenation index, BUN, lactate, Glasgow Coma Score (GCS), liver disease, cancer, organ transplantation, Troponin T(TnT), neutrophil-to-lymphocyte ratio (NLR), and CRRT, MV, and vasopressor use were included in the nomogram. We compared our nomogram with the Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score II (SAPSII), the nomogram had better discrimination ability, with areas under the receiver operating characteristic curve (AUROC) of 0.743 (95% C.I.: 0.713–0.773) and 0.746 (95% C.I.: 0.699–0.790) in the training and validation sets, respectively. The calibration plot indicated that the nomogram was adequate for predicting the in-hospital mortality risk in both sets. The decision-curve analysis (DCA) of the nomogram revealed that it provided net benefits for clinical use over using the SOFA score and SAPSII in both sets. Conclusion Our new nomogram is a convenient tool for accurate predictions of in-hospital mortality among ICU patients with sepsis and lung infection. Treatment strategies that improve the factors considered relevant in the model could increase in-hospital survival for these ICU patients.

Identification of RAGE and OSM as New Prognosis Biomarkers of Severe Pneumonia

Objective. To investigate efficiency of RAGE and OSM as new prognosis biomarkers of severe pneumonia. Methods. Eligible patients were classified into hypoxemia and nonhypoxemia groups. Meanwhile, the same cohort was divided into survival and nonsurvival groups after a post-hospital stay of 30 days. We analyzed risk factors for the hypoxia and death among these patients. Results. Compared with nonsurvival group, significant increase was noticed in PH, lymphocyte, albumin and platelet level in survival group, while significant decline was noticed in neutrophils, RBC, hemoglobin, hematocrit, creatinine, total bilirubin, CRP, PCT, OSM, RAGE and neutrophils/lymphocyte level. Oxygenation index level was related to APACHE II, LIS, SOFA, NUTRIC score, WBC, neutrophils, lymphocyte, RAGE, and albumin level ( p < 0.05 ). LIS, SOFA, NUTRIC score, lac, lymphocyte, platelet, BUN, total bilirubin, PCT, and OSM levels were associated with mortality rate ( p < 0.05 ). Conclusions. RAGE and OSM may serve as a new biomarker for poor prognosis in pneumonia patients.

Survey of Opioid-Induced Respiratory Depression in Critically Ill Patients Without Mechanical Ventilation and Construction of a Risk Nomogram

Objectives To investigate the current status of opioid-induced respiratory depression (OIRD) and potential risk factors in critically ill patients without mechanical ventilation in the intensive care unit (ICU) and to construct a risk nomogram to predict OIRD. Methods A total of 103 patients without (or who were weaned from) mechanical ventilation who had stayed for more than 24 h in the ICU between June 1, 2021 and September 31, 2021, were included. Patient data, including respiratory depression events, were recorded. The least absolute shrinkage and selection operator regression model were used to select features that were then used to construct a prediction model by multivariate logistic regression analysis. A nomogram was established for the risk of respiratory depression events in patients without mechanical ventilation. The discriminatory performance and calibration of the nomogram were assessed with Harrell’s concordance index and a calibration plot, respectively, and a bootstrap procedure was used for internal validation. Results Respiratory depression was diagnosed in 49/103 (47.6%) patients. Factors included in the nomogram were cardiopulmonary disease (odds ratio [OR]=5.569, 95% confidence interval [CI]=0.751–118.083), respiratory disease (OR=32.833, 95% CI=4.189–725.164), sepsis (OR=6.898, 95% CI=1.756–33.000), duration of mechanical ventilation (OR=3.019, 95% CI=0.862–11.322), lack of mechanical ventilation (OR=20.757, 95% CI=2.409–502.222), and oxygenation index (OR=7.350, 95% CI=2.483–24.286). The nomogram showed good performance for predicting respiratory depression events in critically ill patients without mechanical ventilation. Conclusion The nomogram can be used to identify ICU patients without mechanical ventilation who are at risk of opioid-induced respiratory depression and may therefore benefit from early intervention.

The role of annexin A1 peptide in regulating PI3K/Akt signaling pathway to reduce lung injury after cardiopulmonary bypass in rats

Introduction Cardiopulmonary bypass (CPB) –induced lung ischemia-reperfusion (I/R) injury remains a large challenge in cardiac surgery; up to date, no effective treatment has been found. Annexin A1 (AnxA1) has an anti-inflammatory effect, and it has been proven to have a protective effect on CPB-induced lung injury. However, the specific mechanism of AnxA1 in CPB-induced lung injury is not well studied. Therefore, we established a CPB-induced lung injury model to explore the relevant mechanism of AnxA1 and try to find an effective treatment for lung protection. Methods Male rats were randomized into five groups ( n = 6, each): sham (S group), I/R exposure (I/R group), I/R + dimethyl sulfoxide (D group), I/R + Ac2-26 (AnxA1 peptide) (A group), and I/R + LY294002 (a PI3K specific inhibitor) (AL group). Arterial blood gas analysis and calculation of the oxygenation index, and respiratory index were performed. The morphological changes in lung tissues were observed under light and electron microscopes. TNF-α and IL-6 and total protein in lung bronchoalveolar lavage fluid were detected via enzyme-linked immunosorbent assay. The expressions of PI3K, Akt, and NF-κB (p65) as well as p-PI3K, p-Akt, p-NF-κB (p65), and AnxA1 were detected via western blotting. Results Compared with the I/R group, the A group showed the following: lower lung pathological damage score; decreased expression of IL-6 and total protein in the bronchoalveolar lavage fluid, and TNF-α in the lung; increased lung oxygenation index; and improved lung function. These imply the protective role of Ac2-26, and show that LY294002 inhibited the ameliorative preconditioning effect of Ac2-26. Conclusion This finding suggested that the AnxA1 peptide Ac2-26 decreased the inflammation reaction and CPB-induced lung injury in rats, the lung protective effects of AnxA1may be correlated with the activation of PI3K/Akt signaling pathway.

Sequential Organ Failure Assessment Outperforms Quantitative Chest CT Imaging Parameters for Mortality Prediction in COVID-19 ARDS

(1) Background: Respiratory insufficiency with acute respiratory distress syndrome (ARDS) and multi-organ dysfunction leads to high mortality in COVID-19 patients. In times of limited intensive care unit (ICU) resources, chest CTs became an important tool for the assessment of lung involvement and for patient triage despite uncertainties about the predictive diagnostic value. This study evaluated chest CT-based imaging parameters for their potential to predict in-hospital mortality compared to clinical scores. (2) Methods: 89 COVID-19 ICU ARDS patients requiring mechanical ventilation or continuous positive airway pressure mask ventilation were included in this single center retrospective study. AI-based lung injury assessment and measurements indicating pulmonary hypertension (PA-to-AA ratio) on admission CT, oxygenation indices, lung compliance and sequential organ failure assessment (SOFA) scores on ICU admission were assessed for their diagnostic performance to predict in-hospital mortality. (3) Results: CT severity scores and PA-to-AA ratios were not significantly associated with in-hospital mortality, whereas the SOFA score showed a significant association (p < 0.001). In ROC analysis, the SOFA score resulted in an area under the curve (AUC) for in-hospital mortality of 0.74 (95%-CI 0.63–0.85), whereas CT severity scores (0.53, 95%-CI 0.40–0.67) and PA-to-AA ratios (0.46, 95%-CI 0.34–0.58) did not yield sufficient AUCs. These results were consistent for the subgroup of more critically ill patients with moderate and severe ARDS on admission (oxygenation index <200, n = 53) with an AUC for SOFA score of 0.77 (95%-CI 0.64–0.89), compared to 0.55 (95%-CI 0.39–0.72) for CT severity scores and 0.51 (95%-CI 0.35–0.67) for PA-to-AA ratios. (4) Conclusions: Severe COVID-19 disease is not limited to lung (vessel) injury but leads to a multi-organ involvement. The findings of this study suggest that risk stratification should not solely be based on chest CT parameters but needs to include multi-organ failure assessment for COVID-19 ICU ARDS patients for optimized future patient management and resource allocation.

Shen-su-yin, a Traditional Herbal Medicine, Attenuates Lipopolysaccharide-induced Acute Lung Injury in Rats Through Its Anti-inflammatory and Anti-oxidative Effects

Most components of Shen-su-yin (SSY), an herbal formula, have anti-inflammatory and antioxidant activities. The present study was designed to investigate potential effects and mechanisms of SSY on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. 48 rats were randomly divided into 4 groups: control (Ctrl) group, LPS-induced ALI group, low- (SSY-LD) and high- (SSY-HD) dose SSY-treated ALI group. SSY was administered to SSY-treated rats immediately after LPS induction. After 24 hours, blood gas analysis and lactate determination were performed; and bronchoalveolar lavage fluid was collected for detecting protein concentration and levels of cytokines. Lung tissues were obtained for Western blot analysis, histopathological analysis, wet-to-dry weight ratio calculation and measurement of oxidative stress levels. SSY improved oxygenation index and mean arterial pressure, decreased levels of lactate and heart rate, alleviated lung histopathology indexes including lung injury score, wet-to-dry weight ratio and exudation of protein as well as inflammatory cells in ALI rats. Furthermore, SSY reduced levels of pro-inflammatory and oxidative mediums, while increasing levels of anti-inflammatory cytokine and anti-oxidative activity in lung tissues. SSY also suppressed NF-κB signalling pathway and further activated Keap1-Nrf2-ARE signalling pathway activated by LPS. Moreover, all the effects caused by SSY in the SSY-HD group were more encouraging than those in the SSY-LD group. The results indicate that the preventive use of SSY can alleviate ALI through the anti-inflammatory and antioxidant effects mediated by inhibition of NF-κB signalling pathway and activation of Keap1-Nrf2-ARE signalling pathway, and the effect of high dose is better.

Feasibility and effectiveness of prone position ventilation technique for postoperative acute lung injury in infants with congenital heart disease: study protocol for a prospective randomized study

Background Prone position ventilation is a widely used lung protection ventilation strategy. The strategy is more convenient to implement in children compared to adults. Due to the precise mechanism of improving oxygenation function, development of pediatric prone ventilation technology has been largely focused on children with acute respiratory distress syndrome. There is a paucity of high-quality studies investigating the effects of prone position ventilation after pediatric cardiac surgery. The purpose of this study is to evaluate the feasibility and effectiveness of prone position ventilation in infants who develop postoperative acute lung injury after surgery for congenital heart disease. Methods A single-center, randomized controlled trial of pediatric patients with acute lung injury after surgery for congenital heart disease who will receive prone position ventilation or usual care (control group). A total of 68 children will be enrolled according to the inclusion criteria. The main outcome measures will be lung compliance and oxygenation index. The secondary outcomes will be duration of mechanical ventilation, length of stay in cardiac intensive care unit, reintubation rate, and complication rate. Discussion This study will investigate the feasibility and effectiveness of prone position ventilation techniques in children who develop postoperative acute lung injury after surgery for congenital heart disease. The results may help inform strategies to improve airway management after surgery for congenital heart disease. Trial registration ClinicalTrials.gov NCT04607993. Initially registered on 29 October 2020.

Study on the Efficacy and Safety of Ambroxol Combined with Methylprednisolone in Patients with Acute Lung Injury

Background. There is no better treatment method towards paraquat-induced acute lung injury (ALI) at present. Ambroxol combined with methylprednisolone exhibits a significant improvement effect on ALI treatment, whereas their mechanism in ALI is still unclear. Methods. 64 patients with ALI caused by paraquat poisoning brought to our hospital from January 2015 to January 2018 were selected. They were separated into a combined treatment group (CTG) and a routine treatment group (RTG) on the basis of different treatment methods. The survival of patients was observed after 7 days of treatment. Arterial blood gas, oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), patient’s spontaneous respiratory rate (RR), tidal volume (VT), and positive end-expiratory pressure (PEEP) were observed before and after treatment for 7 days. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed. The differences of indexes between the dead patients and the survivors were observed, and the potential predictive value of death was analyzed. Results. After treatment, the indexes of patients were significantly improved in both groups compared with those before therapy. Further comparison showed that the improvement of PaO2, PaCO2, and PaO2/FiO2 in CTG was obviously higher than that in RTG ( p < 0.05 ). The improvement of RR, PEEP, and VT in CTG was obviously higher than that in RTG ( p < 0.05 ). The decreased degree of IL-6 and TNF-α in CTG was higher than that in RTG ( p < 0.05 ). The 7-day mortality rate of 64 patients was 39.06%, and there was no obvious difference in the 7-day survival rate in both groups ( p = 0.649 ). IL-6 and TNF-α were expected to be potential prediction indexes of paraquat-induced ALI. Conclusion. Ambroxol combined with methylprednisolone significantly improved the oxygen partial pressure and oxygenation index of patients with paraquat-induced ALI and inhibited the inflammatory response of patients.

Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury

Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model.Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na+-K+-ATPase activity was assessed using enzyme-linked immunosorbent assay.Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na+-K+-ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1β; increased the expression of AQP-1, AQP-5, αENaC, and βENaC; and increased Na+-K+-ATPase activity. Moreover, the regulation of AQPs, βENaC, and Na+-K+-ATPase and the inhibition of TNF-α and IL-1β by TFENF were found to be dose dependent.Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na+-K+-ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.