Moderate Acute Respiratory Distress Syndrome Research Articles

Abstract 185: Regional Oxygen Saturation and Capnography Monitoring During Resuscitation After Cardiac Arrest in a Swine Pediatric ARDS Model

Introduction: Survival and outcomes after cardiac arrest (CA) depend largely on the effectiveness of cardiopulmonary resuscitation (CPR). Traditional invasive methods of monitoring CPR can be challenging out-of-hospital and are lacking in more than 50% of in-hospital pediatric CA. Regional oxygen saturation (rSO 2 ) monitoring with Near Infrared Spectroscopy (NIRS) and volumetric capnography offers a noninvasive approach that could potentially overcome these challenges. Aim: To determine the feasibility and effectiveness of NIRS and volumetric capnography monitoring in a swine model of pediatric hypoxia induced CA. Approach: Juvenile pigs were sedated and mechanically ventilated. Mild to moderate Acute Respiratory Distress Syndrome (ARDS) was induced by continuous oleic acid infusion. Respiratory and hemodynamic variables were monitored using invasive and noninvasive (NIRS and capnography) monitoring to assess efficacy of CPR. Animals were randomized into one of the two groups: High-quality CPR (hqCPR) to achieve coronary perfusion pressure of 25-30 mmHg and low-quality CPR (lqCPR) to achieve coronary perfusion pressure of 10-15 mmHg. Trajectories over time were analyzed using regression analyses. The discriminatory ability to distinguish between groups based on trajectories were analyzed using receiver operating characteristics curve (ROC) analysis. Results: 39 animals (23±3 kg) were included in our study. In the hqCPR group, there are generally higher values for cerebral and renal rSO 2 , ETCO 2 , volume of CO 2 elimination (VCO 2 ), and carotid blood flow, compared to the lqCPR group (p<0.0001). Cerebral and renal rSO 2 values increase over time, while ETCO 2 , VCO 2 , and carotid flow values decrease in the hqCPR group. Cerebral rSO2 had a ROC AUC of 0.76 (95% CI: 0.58-0.94), whereas renal rSO2 had a ROC AUC of 0.54 (95% CI: 0.22-0.87) representing nearly no discrimination ability. ETCO 2 had a ROC AUC of 0.66 (95% CI: 0.49-0.84), whereas VCO 2 had a ROC AUC of 0.62 (95% CI: 0.38-0.85). Conclusions: Higher mean cerebral rSO2 values during CPR might be used to assess quality of CPR effectiveness and provide real-time adjustments as needed. This could guide healthcare providers in optimizing CPR quality and improving outcomes for cardiac arrest patients.

Effect and mechanical mechanism of spontaneous breathing on oxygenation and lung injury in mild or moderate animal ARDS

ObjectiveThe present study aimed to determine the effect and mechanical mechanism of spontaneous breathing during mechanical ventilation on oxygenation and lung injury using Beagles dogs mild or moderate acute respiratory distress syndrome (ARDS) model.MethodsAfter inducing mild or moderate ARDS by infusion of oleic acid, Eighteen Beagles dogs were randomly split into Spontaneous breathing group (BIPAPSB, n = 6), and Complete muscle paralysis group (BIPAPPC, n = 6),Six Beagles without ventilator support comprised the control group. Both groups were ventilated for 8 h under BIPAP mode. High-pressure was titrated TV to 6 ml/kg. A multi-pair esophageal balloon electrode catheter was used to measure respiratory mechanics and electromyogram. End-expiratory lung volume (EELV), gas exchange and respiratory variables were recorded in the process of mechanical ventilation. The contents of Interleukin (IL)-6 and IL-8 in lung tissue were measure using qRT-PCR. Besides, lung injury score was calculated in the end of mechanical ventilation.ResultsBased on the comparable setting of ventilator, BIPAPSB group exhibited higher safety peak transpulmonary pressure, abdominal pressure, EELV and P/F(PaO2/FiO2) than BIPAPPC group, whereas mean transpulmonary pressure, the mRNA levels of the IL-6 and IL-8 in the lung tissues and lung injury score in BIPAPSB group were lower than those in BIPAPPC group.ConclusionIn mild to moderate ARDS animal models, during mechanical ventilation, SB may improve respiratory function and reduce ventilator-induced lung injury. The mechanism may be that spontaneous inspiration up-regulates peak transpulmonary pressure and EELV; Spontaneous expiration decreases mean transpulmonary pressure by up-regulating intra-abdominal pressure, thereby reducing stress and strain.

Prediction model for in-hospital mortality in patients at high altitudes with ARDS due to COVID-19.

The diagnosis of acute respiratory distress syndrome (ARDS) includes the ratio of pressure arterial oxygen and inspired oxygen fraction (P/F) ≤ 300, which is often adjusted in locations more than 1,000 meters above sea level (masl) due to hypobaric hypoxemia. The main objective of this study was to develop a prediction model for in-hospital mortality among patients with ARDS due to coronavirus disease 2019 (COVID-19) (C-ARDS) at 2,600 masl with easily available variables at patient admission and to compare its discrimination capacity with a second model using the P/F adjusted for this high altitude. This study was an analysis of data from patients with C-ARDS treated between March 2020 and July 2021 in a university hospital located in the city of Bogotá, Colombia, at 2,600 masl. Demographic and laboratory data were extracted from electronic records. For the prediction model, univariate analyses were performed to screen variables with p <0.25. Then, these variables were automatically selected with a backward stepwise approach with a significance level of 0.1. The interaction terms and fractional polynomials were also examined in the final model. Multiple imputation procedures and bootstraps were used to obtain the coefficients with the best external validation. In addition, total adjustment of the model and logistic regression diagnostics were performed. The same methodology was used to develop a second model with the P/F adjusted for altitude. Finally, the areas under the curve (AUCs) of the receiver operating characteristic (ROC) curves of the two models were compared. A total of 2,210 subjects were included in the final analysis. The final model included 11 variables without interaction terms or nonlinear functions. The coefficients are presented excluding influential observations. The final equation for the model fit was g(x) = age(0.04819)+weight(0.00653)+height(-0.01856)+haemoglobin(-0.0916)+platelet count(-0.003614)+ creatinine(0.0958)+lactate dehydrogenase(0.001589)+sodium(-0.02298)+potassium(0.1574)+systolic pressure(-0.00308)+if moderate ARDS(0.628)+if severe ARDS(1.379), and the probability of in-hospital death was p (x) = e g (x)/(1+ e g (x)). The AUC of the ROC curve was 0.7601 (95% confidence interval (CI) 0.74-0, 78). The second model with the adjusted P/F presented an AUC of 0.754 (95% CI 0.73-0.77). No statistically significant difference was found between the AUC curves (p value = 0.6795). This study presents a prediction model for patients with C-ARDS at 2,600 masl with easily available admission variables for early stratification of in-hospital mortality risk. Adjusting the P/F for 2,600 masl did not improve the predictive capacity of the model. We do not recommend adjusting the P/F for altitude.

The Use of High-Flow Nasal Cannula and Non-Invasive Mechanical Ventilation in the Management of COVID-19 Patients: A Prospective Study.

High-flow nasal cannula (HFNC) and ventilator-delivered non-invasive mechanical ventilation (NIV) were used to treat acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia, especially in low- and middle-income countries (LMICs), due to lack of ventilators and manpower resources despite the paucity of data regarding their efficacy. This prospective study aimed to analyse the efficacy of HFNC versus NIV in the management of COVID-19 ARDS. A total of 88 RT-PCR-confirmed COVID-19 patients with moderate ARDS were recruited. Linear regression and generalized estimating equations (GEEs) were used for trends in vital parameters over time. A total of 37 patients were on HFNC, and 51 were on NIV. Patients in the HFNC group stayed slightly but not significantly longer in the ICU as compared to their NIV counterparts (HFNC vs. NIV: 8.00 (4.0-12.0) days vs. 7.00 (2.0-12.0) days; p = 0.055). Intubation rates, complications, and mortality were similar in both groups. The switch to HFNC from NIV was 5.8%, while 37.8% required a switch to NIV from HFNC. The resolution of respiratory alkalosis was better with NIV. We conclude that in patients with COVID-19 pneumonia with moderate ARDS, the duration of treatment in the ICU, intubation rate, and mortality did not differ significantly with the use of HFNC or NIV for respiratory support.

Efficacy of Wharton Jelly Mesenchymal Stromal Cells infusions in moderate to severe SARS-Cov-2 related acute respiratory distress syndrome: a phase 2a double-blind randomized controlled trial.

The COVID-19 pandemic caused a wave of acute respiratory distress syndrome (ARDS) with a high in-hospital mortality, especially in patients requiring invasive mechanical ventilation. Wharton Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) may counteract the pulmonary damage induced by the SARS-CoV-2 infection through pro-angiogenic effects, lung epithelial cell protection, and immunomodulation. In this randomized, double-blind, placebo-controlled phase 2a trial, adult patients receiving invasive mechanical ventilation for SARS-CoV-2 induced moderate or severe ARDS were assigned to receive 1 intravenous infusion of 1 × 106 WJ-MSCs/kg or placebo within 48 h of invasive ventilation followed by 2 infusions of 0.5 × 106 WJ-MSCs/kg or placebo over 5 days. The primary endpoint was the percentage of patients with a PaO2/FiO2 > 200 on day 10. Thirty patients were included from November 2020 to May 2021, 15 in the WJ-MSC group and 15 in the placebo group. We did not find any significant difference in the PaO2/FiO2 ratio at day 10, with 18 and 15% of WJ-MSCs and placebo-treated patients reaching a ratio >200, respectively. Survival did not differ in the 2 groups with a 20% mortality rate at day 90. While we observed a higher number of ventilation-free days at 28 days in the WJ-MSC arm, this difference was not statistically significant (median of 11 (0-22) vs. 0 (0-18), p = 0.2). The infusions were well tolerated, with a low incidence of anti-HLA alloimmunization after 90 days. While treatment with WJ-MSCs appeared safe and feasible in patients with SARS-CoV2 moderate or severe ARDS in this phase 2a trial, the treatment was not associated with an increased percentage of patients with P/F > 200 at 10d, nor did 90 day mortality improve in the treated group. https://beta.clinicaltrials.gov/study/NCT04625738, identifier NCT04625738.

The Efficacy of High-Dose Pulse Therapy vs. Low-Dose Intravenous Methylprednisolone on Severe to Critical COVID-19 Clinical Outcomes: A Randomized Clinical Trial.

It remains unclear which formulation of the corticosteroid regimen has the optimum efficacies on COVID-19 pneumonia. The aim of this study was to compare the clinical outcomes of 2 different regimens in the treatment of acute respiratory distress syndrome (ARDS) caused by COVID-19: Methylprednisolone at a dose of 1 mg/kg every 12 hours (low-dose group) and 1000 mg/day pulse therapy for 3 days following 1 mg/kg methylprednisolone every 12 hours (high-dose group). In this randomized clinical trial, patients with mild to moderate ARDS due to COVID-19 were randomly assigned to receive either low-dose (n = 47) or high-dose (n = 48) intravenous methylprednisolone regimens. Two groups were matched for age, gender, body mass index (BMI), comorbidities, leukocytes, lymphocytes, neutrophil/lymphocyte, platelet, hemoglobin, and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and ferritin). Both regimens were initiated upon admission and continued for 10 days. The clinical outcome and secondary complications were evaluated. Evaluating in-hospital outcomes, no difference was revealed in the duration of intensive care unit (ICU) stays (5.4 ± 4.6 vs. 4.5 ± 4.9; P = 0.35), total hospital stays (8 ± 3.1 vs. 6.9 ± 3.4; P = 0.1), requirement rate for invasive ventilation (29.2% vs. 36.2%; P = 0.4) or non-invasive ventilation (16.6% vs 23.4%; P = 0.4), and hemoperfusion (16.6% vs 11.3%; P = 0.3) between the low- and high-dose groups. There was no significant difference in fatality due to ARDS (29.2% vs. 38.3%; P = 0.3) and septic shock (4.2% vs. 6.4%; P = 0.3) between the low- and high-dose groups. Patients in the high-dose group had significantly higher bacterial pneumonia co-infection events compared with those in the low-dose group (18.7% vs 10.6%; P = 0.01). The use of adjuvant pulse therapy with intravenous methylprednisolone did not result in improved in-hospital clinical outcomes among patients with mild to moderate ARDS due to COVID-19. A higher risk of bacterial pneumonia should be considered in such cases as receiving a higher dose of steroids.

Capnometry after an inspiratory breath hold, PLAT CO2 , as a surrogate for in mild to moderate pediatric acute respiratory distress syndrome: A feasibility study.

Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end-tidal measured immediately after a 3-s inspiratory-hold (PLAT CO2 ) by capnometry and measured by arterial blood gases (ABG) in PARDS. Prospective cohort study. Seven-bed Pediatric Intensive Care Unit, Hospital El Carmen de Maipú, Chile. Thirteen mechanically ventilated patients aged ≤15 years old undergoing neuromuscular blockade as part of management for PARDS. None. All patients were in volume-controlled ventilation mode. The regular end-tidal (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory-hold of 3 s was performed for lung mechanics measurements, recording in the breath following the inspiratory-hold. (PLAT CO2 ). End-tidal alveolar dead space fraction (AVDSf) was calculated as and its surrogate (S)AVDSf as . Measurements of were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland-Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2-11) months. Tidal volume was 5.8 (5.7-6.3) mL/kg, PEEP 8 (6-8), driving pressure 10 (8-11), and plateau pressure 17 (17-19) cm H2 O. Forty-one paired measurements were analyzed. was higher than (52 mmHg [48-54] vs. 42 mmHg [38-45], p < 0.01), and there were no significant differences with PLAT CO2 (50 mmHg [46-55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between and PLAT CO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67-0.90]; and rho = 0.80, p < 0.001.), and for were weak and strong (ρc = 0.27 [95% CI: 0.15-0.38]; and rho = 0.63, p < 0.01). The bias between PLAT CO2 and was -0.4 ± 3.5 mmHg (LoA -7.2 to 6.4), and between and was -8.5 ± 4.1 mmHg (LoA -16.6 to -0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was -0.5 ± 5.6% (LoA -11.5 to 10.5). This pilot study showed the feasibility of measuring end-tidal CO2 after a 3-s end-inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.

COVID-19-Induced Acute Respiratory Distress Syndrome Treated with Hyperbaric Oxygen: Interim Safety Report from a Randomized Clinical Trial (COVID-19-HBO).

A few prospective trials and case series have suggested that hyperbaric oxygen therapy (HBOT) may be efficacious for the treatment of severe COVID-19, but safety is a concern for critically ill patients. We present an interim analysis of the safety of HBOT via a randomized controlled trial (COVID-19-HBO). A randomized controlled, open-label, clinical trial was conducted in compliance with good clinical practice to explore the safety and efficacy of HBOT for severe COVID-19 in critically ill patients with moderate acute respiratory distress syndrome (ARDS). Between 3 June 2020, and 17 May 2021, 31 patients with severe COVID-19 and moderate-to-severe ARDS, a ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) < 26.7 kPa (200 mmHg), and at least two defined risk factors for intensive care unit (ICU) admission and/or mortality were enrolled in the trial and randomized 1:1 to best practice, or HBOT in addition to best practice. The subjects allocated to HBOT received a maximum of five treatments at 2.4 atmospheres absolute (ATA) for 80 min over seven days. The subjects were followed up for 30 days. The safety endpoints were analyzed. Adverse events (AEs) were common. Hypoxia was the most common adverse event reported. There was no statistically significant difference between the groups. Numerically, serious adverse events (SAEs) and barotrauma were more frequent in the control group, and the differences between groups were in favor of the HBOT in PaO2/FiO2 (PFI) and the national early warning score (NEWS); statistically, however, the differences were not significant at day 7, and no difference was observed for the total oxygen burden and cumulative pulmonary oxygen toxicity dose (CPTD). HBOT appears to be safe as an intervention for critically ill patients with moderate-to-severe ARDS induced by COVID-19. NCT04327505 (31 March 2020) and EudraCT 2020-001349-37 (24 April 2020).

HYPERTENSION AND RISK FACTOR TO MORTALITY IN CORONAVIRUS DISEASE (COVID-19)

Objective: the aim of this study is to assess whether hypertension was considered a risk factor for mortality in in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS). Design and method: Retrospective study with analysis of electronic medical records of adult patients admitted for mild and moderate COVID-19 and related acute respiratory distress syndrome in a single quaternary private hospital in Rio de Janeiro, Brazil. Consecutive patients aged 18 years and older with COVID-19 confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) testing. ll data were collected in spreadsheets in Microsoft Excel version 365 (Microsoft Corp., Redmon – WA – USA) and the statistical analysis was performed using SAS Guide 4.3 (SAS Institute Inc., Cary – NV – USA). Results: Two hundred and two patients were were consecutively admitted for mild or moderate COVID-19 related ARDS and were included in this study. The mean age of the studied population was 69.1 ± 14.8 years. Of these, 130 patients (64.4%) were male. The mean BMI was 29.9 ± 6 kg/m2. Hypertension was present in 134 patients, corresponding to 67% of the studied population. 35.8% of patients had diabetes and 10.45% dyslipidemia. Among hypertensive patients, 58 (74%) died, with a relative risk of 1.45 (CI 0.96-2.2) Conclusions: The studies presented systemic arterial hypertension as the most common chronic disease in subjects diagnosed with covid-19. Hypertension is one of the main risk factors for adverse outcomes in subjects with covid-19. The results found in this study suggest that hypertension is associated with an increased risk of developing the severe form of covid-19, and increased mortality. Future studies should include the analysis of individual variables that may influence the outcome of systemic arterial hypertension subjects infected by SARS-CoV-2, such as genetic factors, race/ethnicity, occupation, lifestyle habits, in addition to the evaluation of educational level and diagnosis of the socioeconomic and environmental situation.

Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome

Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 106 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.

Phrenic nerve stimulation mitigates hippocampal and brainstem inflammation in an ARDS model.

Rationale: In porcine healthy-lung and moderate acute respiratory distress syndrome (ARDS) models, groups that received phrenic nerve stimulation (PNS) with mechanical ventilation (MV) showed lower hippocampal apoptosis, and microglia and astrocyte percentages than MV alone. Objectives: Explore whether PNS in combination with MV for 12h leads to differences in hippocampal and brainstem tissue concentrations of inflammatory and synaptic markers compared to MV-only animals. Methods: Compare tissue concentrations of inflammatory markers (IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, TNFα and GM-CSF), pre-synaptic markers (synapsin and synaptophysin) and post-synaptic markers (disc-large-homolog 4, N-methyl-D-aspartate receptors 2A and 2B) in the hippocampus and brainstem in three groups of mechanically ventilated pigs with injured lungs: MV only (MV), MV plus PNS every other breath (MV + PNS50%), and MV plus PNS every breath (MV + PNS100%). MV settings in volume control were tidal volume 8ml/kg, and positive end-expiratory pressure 5cmH2O. Moderate ARDS was achieved by infusing oleic acid into the pulmonary artery. Measurements and Main Results: Hippocampal concentrations of GM-CSF, N-methyl-D-aspartate receptor 2B, and synaptophysin were greater in the MV + PNS100% group compared to the MV group, p = 0.0199, p = 0.0175, and p = 0.0479, respectively. The MV + PNS100% group had lower brainstem concentrations of IL-1β, and IL-8 than the MV group, p = 0.0194, and p = 0.0319, respectively; and greater brainstem concentrations of IFN-γ and N-methyl-D-aspartate receptor 2A than the MV group, p = 0.0329, and p = 0.0125, respectively. Conclusion: In a moderate-ARDS porcine model, MV is associated with hippocampal and brainstem inflammation, and phrenic nerve stimulation on every breath mitigates that inflammation.

Predictive value of postoperative serum procalcitonin concentration for moderate to severe acute respiratory distress syndrome in patients undergoing cardiopulmonary bypass surgery

To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS. Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS. 108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (μg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 μg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001]. Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 μg/L.

Mortality Predictors of Pre-variant SARS-CoV-2 Infected ARDS Patients Receiving Favipiravir and Tocilizumab

Objective: In this study, we investigated the risk factors affecting mortality of critically ill COVID-19-related acute respiratory distress syndrome (ARDS) patients who were followed up in the intensive care unit (ICU) and received tocilizumab and favipiravir treatments together before vaccination. Materials and Methods: The data of patients who were followed up and treated between 1, July 2020 and 5, October 2020 were retrospectively analyzed. Demographic data of the patients (age, gender), acute physiology and chronic health evaluation score II (APACHE II), sequential organ failure assessment (SOFA) score, RT-PCR of oro-nasopharyngeal swabs, the severity of ARDS on the day of tocilizumab admission, time from RT-PCR positivity to tocilizumab administration, respiratory support treatments, all other medical treatments, and ICU outcomes were recorded. Risk factors affecting mortality were evaluated with multiple regression analysis. Results: A total of 60 patients with a median age of 69.8 (24-87) years, 25 females and 35 males were included in the study. The mean APACHE II score was 18.9 ± 8.0, and the SOFA score was 4.5 ± 2.0. Fifty-two (86.7%) patients had positive oro-nasopharyngeal swabs for SARS-CoV-2 by RT-PCR; (13,3%) patients had positive IgM/Ig G rapid antibody tests for SARS-CoV-2. Tocilizumab was given on an average of 2.5th days (± 2.0 days). On the day of tocilizumab administration, 1 (1.7%) patient had mild ARDS, 30 (50.0%) had moderate ARDS, and 29 (48.3%) had severe ARDS. The PaO2/FIO2 ratio of the study group on the day of tocilizumab administration was 96.7 ± 36.6 mmHg. Thirty-four (56.7%) patients were intubated during follow-up. Forty (66.7%) patients died, while 20 (33.3%) patients were transferred to the ward. The mean length of stay in the ICU was 11.4 ± 5.5 days. Advanced age (Hazard ratio (HR) 1.8; 95% confidence interval (CI) 0.88-0.93; p &lt; 0.001), higher APACHE II score (HR 0.81, 95% CI 0.74-0.98; p = 0.001), higher SOFA score on the day of tocilizumab administration (HR 1.47, 95% CI 0.39-0.79; p = 0.001), and lower PaO2/FIO2 ratio (HR 2.54, 95% CI 2.33-3.79; p &lt; 0.001) were determined as independent risk factors for mortality. Conclusion: Patients administered tocilizumab and favipiravir in our ICU were mostly patients with moderate-severe ARDS and had higher inflammatory markers. The reason for the high mortality in this study was attributed to the fact that all of the patients had moderate-severe COVID-19-related ARDS, rather than severe COVID-19.

Levels of neutrophil extracellular traps in neonates with acute respiratory distress syndrome

To study the changes in cell free-DNA (cf-DNA), a marker of neutrophil extracellular traps (NETs), in neonates with acute respiratory distress syndrome (ARDS), and to evaluate its relationship with the severity and early diagnosis of ARDS. The neonates diagnosed with ARDS in the Affiliated Hospital of Jiangsu University from January 2021 to June 2022 were enrolled in the prospective study. The neonates were divided into mild, moderate, and severe ARDS groups based on the oxygen index (OI) (4≤OI<8, 8≤OI<16, and OI≥16, respectively). The control group was selected from jaundice neonates who were observed in the neonatal department of the hospital during the same period, and they had no pathological factors causing neonatal jaundice. Peripheral blood samples were collected on day 1, day 3, and day 7 after admission for the ARDS group, and on the day of admission for the control group. Serum cf-DNA levels were measured using a fluorescence enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured using enzyme-linked immunosorbent assay. A Pearson correlation analysis was used to evaluate the correlation of serum cf-DNA levels with serum IL-6 and TNF-α levels. A total of 50 neonates were enrolled in the ARDS group, including 15 neonates with mild ARDS, 25 with moderate ARDS, and 10 with severe ARDS. Twenty-five neonates were enrolled in the control group. Compared with the control group, the serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased (P<0.05). Compared with the mild ARDS group, the serum levels of cf-DNA, IL-6, and TNF-α in the moderate and severe ARDS groups were significantly increased (P<0.05), and the increase was more significant in the severe ARDS group (P<0.05). The serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased on day 3 after admission and significantly decreased on day 7 after admission compared with those on day 1 after admission (P<0.05). The Pearson correlation analysis showed that there was a positive correlation between serum cf-DNA levels and IL-6 levels as well as TNF-α levels in 50 neonates with ARDS (P<0.05). There is an excessive expression of NETs in neonates with ARDS, and dynamic monitoring of serum cf-DNA levels has certain clinical value in evaluating the severity and early diagnosis of ARDS in neonates.

Trans-tricuspid L and L′ waves

Originally described in left ventricular (LV) diastolic assessment, L wave represents an abnormal mid-diastolic component, occurring between the E and the A waves. It was detected in presence of either a significant delay in active relaxation and/or elevated atrial pressure leading to a flow during diastasis, when, in physiological conditions, an equalization of atrioventricular gradient occurs. The L wave and its corresponding L′ wave at tissue Doppler imaging (TDI) were observed, respectively, at trans-tricuspid pulse wave Doppler and tricuspid valve TDI (Figure 1A and B) in a patient undertaking mechanical ventilation due to moderate acute respiratory distress syndrome (positive end-expiratory pressure 13 cmH2O and driving pressure 13 cmH2O). Right ventricular (RV) systolic function was normal (tricuspid annular plane systolic excursion 16 mm; RV/LV ratio 0.56). Additionally, a pre-systolic pulmonary A wave, an anterograde pulmonary flow occurring during atrial contraction related to a restrictive diastolic pattern, was observed (Figure 1C). RV diastolic function is mostly neglected although it represents a key determinant of cardiac performance, patient’s clinical profile, and prognosis. Although L and L′ waves, along with pulmonary A wave, need a validation in the critically ill population, these signs may be considered as parameters of atrioventricular altered compliance related to RV overload.

Identification of a pediatric acute hypoxemic respiratory failure signature in peripheral blood leukocytes at 24 hours post-ICU admission with machine learning.

There is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200. We used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked gene lists were selected for pathway analysis. Pathway and network analysis was performed using the Pathway Network Analysis Visualizer (PANEV) and Reactome was used to perform an over-representation gene network analysis of the top-ranked genes common to both cohorts. Changes in metabolic pathways involved in energy balance, fundamental cellular processes such as protein translation, mitochondrial function, oxidative stress, immune signaling, and inflammation are differentially regulated early in pediatric ARDS and sepsis-induced AHRF compared to both healthy controls and to milder acute hypoxemia. Specifically, fundamental pathways related to the severity of hypoxemia emerged and included (1) ribosomal and eukaryotic initiation of factor 2 (eIF2) regulation of protein translation and (2) the nutrient, oxygen, and energy sensing pathway, mTOR, activated via PI3K/AKT signaling. Cellular energetics and metabolic pathways are important mechanisms to consider to further our understanding of the heterogeneity and underlying pathobiology of moderate and severe pediatric acute respiratory distress syndrome. Our findings are hypothesis generating and support the study of metabolic pathways and cellular energetics to understand heterogeneity and underlying pathobiology of moderate and severe acute hypoxemic respiratory failure in children.

To Establish an Early Prediction Model for Acute Respiratory Distress Syndrome in Severe Acute Pancreatitis Using Machine Learning Algorithm.

To develop binary and quaternary classification prediction models in patients with severe acute pancreatitis (SAP) using machine learning methods, so that doctors can evaluate the risk of patients with acute respiratory distress syndrome (ARDS) and severe ARDS at an early stage. A retrospective study was conducted on SAP patients hospitalized in our hospital from August 2017 to August 2022. Logical Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Decision Tree (DT), and eXtreme Gradient Boosting (XGB) were used to build the binary classification prediction model of ARDS. Shapley Additive explanations (SHAP) values were used to interpret the machine learning model, and the model was optimized according to the interpretability results of SHAP values. Combined with the optimized characteristic variables, four-class classification models, including RF, SVM, DT, XGB, and Artificial Neural Network (ANN), were constructed to predict mild, moderate, and severe ARDS, and the prediction effects of each model were compared. The XGB model showed the best effect (AUC = 0.84) in the prediction of binary classification (ARDS or non-ARDS). According to SHAP values, the prediction model of ARDS severity was constructed with four characteristic variables (PaO2/FiO2, APACHE II, SOFA, AMY). Among them, the overall prediction accuracy of ANN is 86%, which is the best. Machine learning has a good effect in predicting the occurrence and severity of ARDS in SAP patients. It can also provide a valuable tool for doctors to make clinical decisions.

Precision of CT-derived alveolar recruitment assessed by human observers and a machine learning algorithm in moderate and severe ARDS

BackgroundAssessing measurement error in alveolar recruitment on computed tomography (CT) is of paramount importance to select a reliable threshold identifying patients with high potential for alveolar recruitment and to rationalize positive end-expiratory pressure (PEEP) setting in acute respiratory distress syndrome (ARDS). The aim of this study was to assess both intra- and inter-observer smallest real difference (SRD) exceeding measurement error of recruitment using both human and machine learning-made lung segmentation (i.e., delineation) on CT. This single-center observational study was performed on adult ARDS patients. CT were acquired at end-expiration and end-inspiration at the PEEP level selected by clinicians, and at end-expiration at PEEP 5 and 15 cmH2O. Two human observers and a machine learning algorithm performed lung segmentation. Recruitment was computed as the weight change of the non-aerated compartment on CT between PEEP 5 and 15 cmH2O.ResultsThirteen patients were included, of whom 11 (85%) presented a severe ARDS. Intra- and inter-observer measurements of recruitment were virtually unbiased, with 95% confidence intervals (CI95%) encompassing zero. The intra-observer SRD of recruitment amounted to 3.5 [CI95% 2.4–5.2]% of lung weight. The human–human inter-observer SRD of recruitment was slightly higher amounting to 5.7 [CI95% 4.0–8.0]% of lung weight, as was the human–machine SRD (5.9 [CI95% 4.3–7.8]% of lung weight). Regarding other CT measurements, both intra-observer and inter-observer SRD were close to zero for the CT-measurements focusing on aerated lung (end-expiratory lung volume, hyperinflation), and higher for the CT-measurements relying on accurate segmentation of the non-aerated lung (lung weight, tidal recruitment…). The average symmetric surface distance between lung segmentation masks was significatively lower in intra-observer comparisons (0.8 mm [interquartile range (IQR) 0.6–0.9]) as compared to human–human (1.0 mm [IQR 0.8–1.3] and human–machine inter-observer comparisons (1.1 mm [IQR 0.9–1.3]).ConclusionsThe SRD exceeding intra-observer experimental error in the measurement of alveolar recruitment may be conservatively set to 5% (i.e., the upper value of the CI95%). Human–machine and human–human inter-observer measurement errors with CT are of similar magnitude, suggesting that machine learning segmentation algorithms are credible alternative to humans for quantifying alveolar recruitment on CT.

Comparison of the Montreux definition with the Berlin definition for neonatal acute respiratory distress syndrome.

To compare the similarities and differences between the Montreux definition and the Berlin definition in terms of the prevalence, mortality, and complications of neonatal acute respiratory distress syndrome (ARDS). We retrospectively analyzed the data of neonates with respiratory failure treated in a neonatal intensive care unit (NICU) between 1 November 2019 and 31 December 2021. In total, 554 infants had neonatal ARDS (524 infants, Montreux definition; 549 infants, Berlin definition). The prevalence (3.1% vs. 3.3%, p = 0.438) and mortality (18.9% vs.18.0%, p = 0.716) of neonatal ARDS did not differ between the definitions. Among the 519 infants meeting both definitions, key clinical outcomes did not differ between the definitions such as ventilation duration, NICU stay, complication rates, and antibiotic use, except for nitric oxide inhalation. The Montreux and Berlin definitions identified an additional 5 and 30 patients, respectively, not captured by the other definition. The rate of inhaled nitric oxide treatment (20.0% vs. 0%, p = 0.013), air leaks (20.0% vs. 0%, p = 0.013), and invasive ventilation duration (110.00 vs.0.00h, p = 0.002) significantly differed between the above two groups. Sixty-two patients had moderate and severe ARDS according to the Montreux and Berlin definitions, respectively. The rates of adverse outcomes (e.g., mortality, invasive ventilation time) among these patients were similar to the rates among patients with moderate ARDS according to both definitions than among patients with severe ARDS according to both definitions. Conclusion: The prevalence, mortality, and most complications of neonatal ARDS were similar between the Montreux and Berlin definitions, which mainly differed in terms of the severity of neonatal ARDS. What is Known: • The Montreux definition was first proposed for the diagnosis of neonatal acute respiratory distress syndrome and was established in 2017. To date, the Montreux definition has not been compared with other diagnostic definitions of ARDS. What is New: • The study suggests that perinatal lung disease need not be excluded in the diagnosis of neonatal ARDS, and that the Montreux definition is more applicable to neonates, taking into account their specific physiological characteristics.

Safety and efficacy of clinical-grade, cryopreserved menstrual blood mesenchymal stromal cells in experimental acute respiratory distress syndrome.

Background: Treatment for critical care conditions, such as acute respiratory distress syndrome (ARDS), requires ready-to-administer injectable mesenchymal stromal cells (MSCs). A validated cryopreserved therapy based on MSCs derived from menstrual blood (MenSCs) is an attractive option that offers advantages over freshly cultured cells and allows its use as an off-the-shelf therapy in acute clinical conditions. The main goal of this study is to provide evidence on the impact of cryopreservation on different biological functions of MenSCs and to determine the optimal therapeutic dose, safety, and efficacy profile of clinical-grade, cryopreserved (cryo)-MenSCs in experimental ARDS. Methods: Biological functions of fresh versus cryo-MenSCs were compared in vitro. The effects of cryo-MenSCs therapy were evaluated in vivo in ARDS-induced (Escherichia coli lipopolysaccharide) C57BL/6 mice. After 24 h, the animals were treated with five doses ranging from 0.25×105 to 1.25×106 cells/animal. At 2 and 7 days after induction of ARDS, safety and efficacy were evaluated. Results: Clinical-grade cryo-MenSCs injections improved lung mechanics and reduced alveolar collapse, tissue cellularity, and remodelling, decreasing elastic and collagen fiber content in alveolar septa. In addition, administration of these cells modulated inflammatory mediators and promoted pro-angiogenic and anti-apoptotic effects in lung-injured animals. More beneficial effects were observed with an optimal dose of 4×106 cells/Kg than with higher or lower doses. Conclusion: From a translational perspective, the results showed that clinical-grade cryopreserved MenSCs retain their biological properties and exert a therapeutic effect in mild to moderate experimental ARDS. The optimal therapeutic dose was well-tolerated, safe, and effective, favouring improved lung function. These findings support the potential value of an off-the-shelf MenSCs-based product as a promising therapeutic strategy for treating ARDS.