Mortality In Respiratory Distress Syndrome Research Articles

Effectiveness of prone position with its moderating factors in non-intubated acute respiratory distress syndrome patients: a meta-analysis

Introduction: While numerous meta-analyses have explored the efficacy of awake prone position (APP), most have concentrated solely on intubation rate among Covid-19 patients without comprehensively identifying the influencing factors. This study aims to evaluate the efficacy of APP along with its moderating factors on oxygenation, intubation rate, and mortality in non-intubated acute respiratory distress syndrome (ARDS) patients. Methods: We conducted a systematic search in PubMed, Web of Science, and CINAHL from inception to December 2022. JBI critical appraisal tools were used to assess the study quality. Random-effects model was employed to calculate pooled standardized mean difference for continuous outcomes and risk ratio for dichotomous outcomes. Results: Among the 39 studies included, most patients were suffering from Covid-19, using conventional oxygen therapy, and receiving APP outside the ICU. APP significantly improved the PaO2/FiO2 ratio (SMD=0.70, 95% CI=0.51-0.88) and SpO2/FiO2 ratio (SMD=0.76, 95% CI=0.51-1.01), while also reducing the risk of intubation (RR=0.66, 95% CI=0.51-0.85) and mortality (RR=0.62, 95% CI=0.49-0.78). Factors including severity, respiratory device, body mass index, detail of position, use of medication assistance, total duration, follow-up time, position at follow-up, and study design significantly influence the effectiveness of APP. APP did not lead to significant improvements in length of stay and adverse events Conclusions: APP is a safe and beneficial intervention, enhancing oxygenation and reducing intubation and mortality rates in non-intubated ARDS patients. Importantly, various patient and intervention characteristics should be taken into account when implementing APP. Further well-designed experimental studies are needed to strengthen the evidence base.

Relationship between strain energy and alveolar overdistension in patients with acute respiratory distress syndrome: The research protocol

Background: Energy produced during mechanical ventilation has been es¬tablished as a contributor to mortality in acute respiratory distress syndrome (ARDS) patients, elucidated through ventilator-induced lung injury (VILI). How¬ever, the potential association between strain energy, an engineering-based concept, and the risk of VILI remains unexplored. Objectives: This study aims to investigate the correlation between strain en¬ergy and alveolar overdistension and the relationship between strain energy and single-breath mechanical power (MP) calculated by a simplified formula in patients with ARDS. Methods: A prospective observational study will be conducted on moderate to severe ARDS patients under sedation and paralysis. We will gradually reduce positive end-expiratory pressure (PEEP) by two cmH2O every two minutes from 20 to 8 cmH2O in pressure-controlled ventilation mode. During decremental PEEP titration, patients would be monitored simultaneously for esophageal pressure and electrical impedance tomography (EIT). Data gathered from the mechanical ventilator and EIT during the decrementing PEEP titration were fo¬cused on seven PEEP levels: 20, 18, 16, 14, 12, 10, and 8 cmH2O, providing a dataset of 7 events per patient for analysis. Strain energy and single-breath MP were calculated from ventilator parameters, while EIT provided data on alveolar overdistension. Hypothesis: We hypothesized that strain energy and single-breath mechanical MP correlate with alveolar overdistension in ARDS patients. Conclusions: This study aims to assess the correlation between strain energy and alveolar overdistension, as well as the correlation between strain energy and single-breath MP in ARDS patients. Ethics and dissemination: The study protocol has been approved by the fac¬ulty of medicine ethics committee, Ramathibodi Hospital, Mahidol University (COA MURA2023/718). Trial registration: TCTR20240320001

SEH activity is associated with mortality in patients with ARDS: a retrospective cohort study.

Aim: We hypothesized plasma sEH activity correlates with mortality in acute respiratory distress syndrome (ARDS) patients.Methods: Adult patients diagnosed with ARDS enrolled between 2017 and 2019 were included in this study.Results: A total of 337 adult patients met our inclusion criteria. Among them, 107 patients died within 28days. The plasma sEH activity was higher in nonsurvivors relative to survivors. And a receiver operating characteristic curve with the area under the curve of 0.81 (95% confidence interval: 0.74-0.89) for the prediction of 28-day mortality was obtained. Its sensitivity and specificity were 72.5% and 74.6%, respectively.Conclusion: Elevated plasma sEH activity is associated with higher 28-day mortality in adult patients with ARDS.

Incidence of acute kidney injury and attributive mortality in acute respiratory distress syndrome randomized trials.

The development of acute kidney injury (AKI) after the acute respiratory distress syndrome (ARDS) reduces the chance of organ recovery and survival. The purpose of this study was to examine the AKI rate and attributable mortality in ARDS patients. We performed an individual patient-data analysis including 10 multicenter randomized controlled trials conducted over 20years. We employed a Super Learner ensemble technique, including a time-dependent analysis, to estimate the adjusted risk of AKI. We calculated the mortality attributable to AKI using an inverse probability of treatment weighting estimator integrated with the Super Learner. There were 5148 patients included in this study. The overall incidence of AKI was 43.7% (n = 2251). The adjusted risk of AKI ranged from 38.8% (95% confidence interval [CI], 35.7 to 41.9%) in ARMA, to 55.8% in ROSE (95% CI, 51.9 to 59.6%). 37.1% recovered rapidly from AKI, with a significantly lower recovery rate in recent trials (P < 0.001). The 90-day excess in mortality attributable to AKI was 15.4% (95% CI, 12.8 to 17.9%). It decreased from 25.4% in ARMA (95% CI, 18.7 to 32%), to 11.8% in FACTT (95% CI, 5.5 to 18%) and then remained rather stable over time. The 90-dayoverall excess in mortality attributable to acute kidney disease was 28.4% (95% CI, 25.3 to 31.5%). The incidence of AKI appears to be stable over time in patients with ARDS enrolled in randomized trials. The development of AKI remains a significant contributing factor to mortality. These estimates are essential for designing future clinical trials for AKI prevention or treatment.

Association of coagulation function with the risk of in-hospital mortality in patients with severe acute respiratory distress syndrome

BackgroundTo evaluate the association of coagulation disorder score with the risk of in-hospital mortality in acute respiratory distress syndrome (ARDS) patients. MethodsIn this cohort study, 7,001 adult patients with ARDS were identified from the Medical Information Mart for Intensive Care Database-IV (MIMIC-IV). Univariate and multivariate Logistic stepwise regression models were used to explore the associations of coagulation-associated biomarkers with the risk of in-hospital mortality in patients with ADRS. Restricted cubic spline (RCS) was plotted to explore the association between coagulation disorder score and in-hospital mortality of ARDS patients. ResultsThe follow-up time for in-hospital death was 7.15 (4.62, 13.88) days. There were 1,187 patients died and 5,814 people survived in hospital. After adjusting for confounding factors, increased risk of in-hospital mortality in ARDS patients was observed in those with median coagulation disorder score [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.01–1.47) and high coagulation disorder score (OR = 1.38, 95% CI: 1.06–1.80). The results of RCS indicated that when the coagulation disorder score >2, the trend of in-hospital mortality rose gradually, and OR was >1. ConclusionsPoor coagulation function was associated with increased risk of in-hospital mortality in ARDS patients. The findings implied that clinicians should regularly detect the levels of coagulation-associated biomarkers for the management of ARDS patients.

Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Antiinflammatory Therapies

BackgroundThe association of plasma biomarkers and clinical outcomes in acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 predate the evidence-based use of immunomodulators. Research QuestionWhich plasma biomarkers associate with clinical outcomes in ARDS patients with SARS-CoV-2 treated routinely with immunomodulators? Study Design and MethodsWe collected plasma from ARDS patients with SARS-CoV-2 within 24 hours of admission to the intensive care unit (ICU) between December 2020-March 2021 (n=69). We associated 16 total biomarkers of inflammation (e.g., IL-6), coagulation (e.g., D-dimer), epithelial injury (e.g., surfactant protein-D), and endothelial injury (e.g., angiopoietin-2) with the primary outcome of in-hospital mortality and secondary outcome of ventilatory ratio (at baseline and day 3). ResultsThirty patients (43.5%) died within 60 days. All patients received corticosteroids and 6% also received tocilizumab. Compared to survivors, non-survivors had a higher baseline modified SOFA score (8.5 [7-9] vs 7 [5-8]), p=0.004), lower PaO2/FiO2 (153 [118-182] vs 184 [142-247], p=0.04), and higher ventilatory ratio (2.0 [1.9-2.3] vs 1.5 [1.4-1.9], p<0.001). There was no difference in inflammatory, coagulation, or epithelial biomarkers between groups. Non-survivors had higher median NEDD9 (8.4 [7.0-11.2] vs 6.9 [5.5-8.0] ng/mL, p=0.0025), von Willebrand factor domain A2 (8.7 [7.9-9.7] vs 6.5 [5.7-8.7] ng/mL, p=0.007), angiopoietin-2 (9.0 [7.9-14.1] vs 7.0 [5.6-10.6] ng/mL, p=0.01), and syndecan-1 (15.9 [14.5-17.5] vs 12.6 [10.5-16.1] ng/mL, p=0.01). Only NEDD9 met the adjusted threshold for significance (p<0.003). Plasma NEDD9 associated with 60-day mortality (adjusted OR 9.7, 95% CI 1.6-60.4, p=0.015). Syndecan-1 correlated with both baseline (ρ=0.4, p=0.001) and day 3 ventilatory ratio (ρ=0.5, p<0.001). InterpretationBiomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes in a small cohort of ARDS patients uniformly treated with immunomodulators. However, endothelial biomarkers, including plasma NEDD9, associated with 60-day mortality.

Association between Age and Mortality in Pediatric and Adult Acute Respiratory Distress Syndrome.

Rationale: The epidemiology, management, and outcomes of acute respiratory distress syndrome (ARDS) differ between children and adults, with lower mortality rates in children despite comparable severity of hypoxemia. However, the relationship between age and mortality is unclear.Objective: We aimed to define the association between age and mortality in ARDS, hypothesizing that it would be nonlinear.Methods: We performed a retrospective cohort study using data from two pediatric ARDS observational cohorts (n = 1,236), multiple adult ARDS trials (n = 5,547), and an adult observational ARDS cohort (n = 1,079). We aligned all datasets to meet Berlin criteria. We performed unadjusted and adjusted logistic regression using fractional polynomials to assess the potentially nonlinear relationship between age and 90-day mortality, adjusting for sex, PaO2/FiO2, immunosuppressed status, year of study, and observational versus randomized controlled trial, treating each individual study as a fixed effect.Measurements and Main Results: There were 7,862 subjects with median ages of 4 years in the pediatric cohorts, 52 years in the adult trials, and 61 years in the adult observational cohort. Most subjects (43%) had moderate ARDS by Berlin criteria. Ninety-day mortality was 19% in the pediatric cohorts, 33% in the adult trials, and 67% in the adult observational cohort. We found a nonlinear relationship between age and mortality, with mortality risk increasing at an accelerating rate between 11 and 65 years of age, after which mortality risk increased more slowly.Conclusions: There was a nonlinear relationship between age and mortality in pediatric and adult ARDS.

Advanced Respiratory Support Days as a Novel Marker of Mortality in COVID-19 Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

Emerging evidence suggests prolonged use of noninvasive respiratory support may increase mortality of patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome who require extracorporeal membrane oxygenation (ECMO). Using a database of adults receiving ECMO for COVID-19, we calculated survival curves and multivariable Cox regression to determine the risk of death associated with pre-ECMO use of high-flow nasal oxygen (HFNO), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) days. We investigated the performance of a novel variable, advanced respiratory support days (composite of HFNO, NIV, and IMV days), on Respiratory ECMO Survival Prediction (RESP) score. Subjects (N = 146) with increasing advanced respiratory support days (<5, 5-9, and ≥10) had a stepwise increase in 90 day mortality (32.2%, 57.7%, and 75.4%, respectively; p = 0.002). Ninety-day mortality was significantly higher in subjects (N = 121) receiving NIV >4 days (81.8% vs. 52.4%, p < 0.001). Each additional pre-ECMO advanced respiratory support day increased the odds of right ventricular failure (odds ratio [OR]: 1.066, 95% confidence interval [CI]: 1.002-1.135) and in-hospital mortality (1.17, 95% CI: 1.08-1.27). Substituting advanced respiratory support days for IMV days improved RESP score mortality prediction (area under the curve (AUC) or: 0.64 vs. 0.71). Pre-ECMO advanced respiratory support days were associated with increased 90 day mortality compared with IMV days alone. Adjusting the RESP score for advanced respiratory support days improved mortality prediction.

Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS)

BackgroundInflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was...

Prognostic value of time-varying dead space estimates in mechanically ventilated patients with acute respiratory distress syndrome

BackgroundThe dead space fraction (VD/VT) has proven to be a powerful predictor of higher mortality in acute respiratory distress syndrome (ARDS). However, its measurement relies on expired carbon dioxide, limiting its widespread application in clinical practice. Several estimates employing routine variables have been found to be reliable substitutes for direct measurement of VD/VT. In this study, we evaluated the prognostic value of these dead space estimates obtained in the first 7 days following the initiation of ventilation. MethodsThis retrospective observational study was conducted using data from the Chinese database in intensive care (CDIC). Eligible participants were adult ARDS patients receiving invasive mechanical ventilation while in the intensive care unit between 1st January 2014 and 31st March 2021. We collected data during the first 7 days of ventilation to calculate various dead space estimates, including ventilatory ratio (VR), corrected minute ventilation (V˙Ecorr), VD/VT (Harris–Benedict), VD/VT (Siddiki estimate), and VD/VT (Penn State estimate) longitudinally. A time-dependent Cox model was used to handle these time-varying estimates. ResultsA total of 392 patients (median age 66 [interquartile range: 55–77] years, median SOFA score 9 [interquartile range: 7–12]) were finally included in our analysis, among whom 132 (33.7%) patients died within 28 days of admission. VR (hazard ratio [HR]=1.04 per 0.1 increase, 95% confidence interval [CI]: 1.01 to 1.06; P=0.013), V˙Ecorr (HR=1.08 per 1 increase, 95% CI: 1.04 to 1.12; P < 0.001), VD/VT (Harris–Benedict) (HR=1.25 per 0.1 increase, 95% CI: 1.06 to 1.47; P=0.006), and VD/VT (Penn State estimate) (HR=1.22 per 0.1 increase, 95% CI: 1.04 to 1.44; P=0.017) remained significant after adjustment, while VD/VT (Siddiki estimate) (HR=1.10 per 0.1 increase, 95% CI: 1.00 to 1.20; P=0.058) did not. Given a large number of negative values, VD/VT (Siddiki estimate) and VD/VT (Penn State estimate) were not recommended as reliable substitutes. Long-term exposure to VR >1.3, V˙Ecorr >7.53, and VD/VT (Harris–Benedict) >0.59 was independently associated with an increased risk of mortality in ARDS patients. These findings were validated in the fluid and catheter treatment trial (FACTT) database. ConclusionsIn cases where VD/VT cannot be measured directly, early time-varying estimates of VD/VT such as VR, V˙Ecorr, and VD/VT (Harris–Benedict) can be considered for predicting mortality in ARDS patients, offering a rapid bedside application.

Dead-Space Ventilation Indices and Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

Acute respiratory distress syndrome (ARDS) is associated with high ventilation-perfusion heterogeneity and dead-space ventilation. However, whether the degree of dead-space ventilation is associated with outcomes is uncertain. In this systematic review and meta-analysis, we evaluated the ability of dead-space ventilation measures to predict mortality in patients with ARDS. MEDLINE, CENTRAL, and Google Scholar from inception to November 2022. Studies including adults with ARDS reporting a dead-space ventilation index and mortality. Two reviewers independently identified eligible studies and extracted data. We calculated pooled effect estimates using a random effects model for both adjusted and unadjusted results. The quality and strength of evidence were assessed using the Quality in Prognostic Studies and Grading of Recommendations, Assessment, Development, and Evaluation, respectively. We included 28 studies in our review, 21 of which were included in our meta-analysis. All studies had a low risk of bias. A high pulmonary dead-space fraction was associated with increased mortality (odds ratio [OR], 3.52; 95% CI, 2.22-5.58; p < 0.001; I2 = 84%). After adjusting for other confounding variables, every 0.05 increase in pulmonary-dead space fraction was associated with an increased odds of death (OR, 1.23; 95% CI, 1.13-1.34; p < 0.001; I2 = 57%). A high ventilatory ratio was also associated with increased mortality (OR, 1.55; 95% CI, 1.33-1.80; p < 0.001; I2 = 48%). This association was independent of common confounding variables (OR, 1.33; 95% CI, 1.12-1.58; p = 0.001; I2 = 66%). Dead-space ventilation indices were independently associated with mortality in adults with ARDS. These indices could be incorporated into clinical trials and used to identify patients who could benefit from early institution of adjunctive therapies. The cut-offs identified in this study should be prospectively validated.

Relationship between D-dimers and dead-space on disease severity and mortality in COVID-19 acute respiratory distress syndrome: A retrospective observational cohort study

BackgroundDespite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices, markers of inflammation, immunothrombosis, severity and intensive care unit (ICU) mortality. ResultsRetrospective data including demographics, gas exchange, ventilatory parameters, and respiratory mechanics in the first 24 h of invasive ventilation. Plasma concentrations of D-dimers and ferritin were not significantly different across C-ARDS severity categories. Weak relationships were found between D-dimers and VR (r = 0.07, p = 0.13), PETCO2/PaCO2 (r = −0.1, p = 0.02), or estimated dead space fraction (r = 0.019, p = 0.68). Age, PaO2/FiO2, pH, PETCO2/PaCO2 and ferritin, were independently associated with ICU mortality. We found no association between D-dimers or ferritin and any dead-space indices adjusting for PaO2/FiO2, days of ventilation, tidal volume, and respiratory system compliance. ConclusionsWe report no association between dead space and inflammatory markers in mechanically ventilated patients with C-ARDS. Our results support theories suggesting that multiple mechanisms, in addition to immunothrombosis, play a role in the pathophysiology of respiratory failure and degree of dead space in C-ARDS.

Delayed mechanical ventilation with prolonged high-flow nasal cannula exposure time as a risk factor for mortality in acute respiratory distress syndrome due to SARS-CoV-2

In a high proportion of patients, infection by COVID-19 progresses to acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation (IMV) and admission to an intensive care unit (ICU). Other devices, such as a high-flow nasal cannula (HFNC), have been alternatives to IMV in settings with limited resources. This study evaluates whether HFNC exposure time prior to IMV is associated with mortality. This observational, analytical study was conducted on a historical cohort of adults with ARDS due to SARS-CoV-2 who were exposed to HFNC and subsequently underwent IMV. Univariate and multivariate logistic regression was used to analyze the impact of HFNC exposure time on mortality, controlling for multiple potential confounders. Of 325 patients with ARDS, 41 received treatment with HFNC for more than 48 h before IMV initiation. These patients had a higher mortality rate (43.9% vs. 27.1%, p: 0.027) than those using HFNC < 48 h. Univariate analysis evidenced an association between mortality and HFNC ≥ 48 h (OR 2.16. 95% CI 1.087–4.287. p: 0.028). Such an association persisted in the multivariable analysis (OR 2.21. 95% CI 1.013–4.808. p: 0.046) after controlling for age, sex, comorbidities, basal severity of infection, and complications. This study also identified a significant increase in mortality after 36 h in HFNC (46.3%, p: 0.003). In patients with ARDS due to COVID-19, HFNC exposure ≥ 48 h prior to IMV is a factor associated with mortality after controlling multiple confounders. Physiological mechanisms for such an association are need to be defined.

Aging-related predictive factors for oxygenation improvement and mortality in COVID-19 and acute respiratory distress syndrome (ARDS) patients exposed to prone position: A multicenter cohort study

BackgroundElderly patients are more susceptible to Coronavirus Disease-2019 (COVID-19) and are more likely to develop it in severe forms, (e.g., Acute Respiratory Distress Syndrome [ARDS]). Prone positioning is a treatment strategy for severe ARDS; however, its response in the elderly population remains poorly understood. The main objective was to evaluate the predictive response and mortality of elderly patients exposed to prone positioning due to ARDS-COVID-19. MethodsThis retrospective multicenter cohort study involved 223 patients aged ≥ 65 years, who received prone position sessions for severe ARDS due to COVID-19, using invasive mechanical ventilation. The PaO2/FiO2 ratio was used to assess the oxygenation response. The 20-point improvement in PaO2/FiO2 after the first prone session was considered for good response. Data were collected from electronic medical records, including demographic data, laboratory/image exams, complications, comorbidities, SAPS III and SOFA scores, use of anticoagulants and vasopressors, ventilator settings, and respiratory system mechanics. Mortality was defined as deaths that occurred until hospital discharge. ResultsMost patients were male, with arterial hypertension and diabetes mellitus as the most prevalent comorbidities. The non-responders group had higher SAPS III and SOFA scores, and a higher incidence of complications. There was no difference in mortality rate. A lower SAPS III score was a predictor of oxygenation response, and the male sex was a risk predictor of mortality. ConclusionThe present study suggests the oxygenation response to prone positioning in elderly patients with severe COVID-19-ARDS correlates with the SAPS III score. Furthermore, the male sex is a risk predictor of mortality.

Development and Internal Validation of a Novel Prognostic Score to Predict Mortality in Acute Respiratory Distress Syndrome - Driving Pressure, Oxygenation and Nutritional Evaluation - "DRONE Score".

There are few scores for mortality prediction in acute respiratory distress syndrome (ARDS) incorporating comprehensive ventilatory, acute physiological, organ dysfunction, oxygenation, and nutritional parameters. This study aims to determine the risk factors of ARDS mortality from the above-mentioned parameters at 48 h of invasive mechanical ventilation (IMV), which are feasible across most intensive care unit settings. Prospective, observational, single-center study with 150 patients with ARDS defined by Berlin definition, receiving IMV with lung protective strategy. Our study had a mortality of 41.3% (62/150). We developed a 9-point novel prediction score, the driving pressure oxygenation and nutritional evaluation (DRONE) score comprising of driving pressure (DP), oxygenation accessed by the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) ratio and nutritional evaluation using the modified nutrition risk in the critically ill (mNUTRIC) score. Each component of the DRONE score with the cutoff value to predict mortality was assigned a particular score (the lowest DP within 48 h in a patient being always ≥15 cmH2O a score of 2, the highest achievable PaO2/FiO2 <208 was assigned a score of 4 and the mNUTRIC score ≥4 was assigned a score of (3). We obtained the DRONE score ≥4, area under the curve 0.860 to predict mortality. Cox regression for the DRONE score >4 was highly associated with mortality (P < 0.001, hazard ratio 5.43, 95% confidence interval [2.94-10.047]). Internal validation was done by bootstrap analysis. The clinical utility of the DRONE score ≥4 was assessed by Kaplan-Meier curve which showed significance. The DRONE score ≥4 could be a reliable predictor of mortality at 48 h in ARDS patients receiving IMV.

Validation of Prognostic Club Cell Secretory Protein (CC16) Cut-point in an Independent ALTA Cohort.

Club cell secretory protein (CC16) has demonstrated utility as a lung-specific biomarker in predicting mortality in acute respiratory distress syndrome (ARDS). These findings have been observed in pre-clinical trials and a re-analysis of a large, randomized controlled trial of ARDS (Fluid and Catheter Treatment Trial (FACTT)). The purpose of this study was to validate previous findings by evaluating CC16 level as a mortality predictor in patients from the albuterol to treat acute lung injury (ALTA) trial. In this secondary biomarker analysis, plasma CC16 level was measured from 100 ALTA subjects using enzyme-linked immunosorbent assay (ELISA). The rate of mortality was assessed in patients with high (⩾45 ng/mL) versus low CC16 (<45 ng/mL) levels. This cut-off level was applied based on our previous analysis from FACTT trial. Significance was assessed using Kaplan-Meier curves and a log-rank test. Subjects were an average of 50 years old and 46% of them were females. Patients with high CC16 levels had higher 90-day mortality compared to those with low CC16 levels, (37.73% vs 8.95%, P < .001). Other clinical outcomes including ICU-free days, ventilator-free days, and organ failure free days were significantly different between the groups (All P < .05). In this validation study, we demonstrated that ARDS patients with high plasma CC16 concentration had a higher mortality rate than those with low CC16 levels, confirming previous findings that CC16 levels are associated with ARDS mortality.

Incidence, Outcome and Predictors of Mortality in Respiratory distress syndrome (RDS): A Prospective Cohort Study at Tertiary Care Hospital in Nepal

Introduction: With advances in therapies during antenatal and perinatal period, there has been apparent decrease in incidence and mortality due to respiratory distress syndrome (RDS). However, there is paucity of data on exact incidence and outcome of RDS in resource limited setting. This study was conducted with the primary aim to describe the outcome of RDS and analyze the predictors for mortality. Methods: A prospective observational study was conducted in the Neonatal Intensive Care Unit (NICU) and Neonatal Unit of Tribhuvan University Teaching Hospital (TUTH), Kathmandu, Nepal from October 2019 to April 2021. Results: A total of 94 preterm newborns developed RDS giving prevalence of 20.5 per 1000 live birth cohort at TUTH. Incidence of RDS among preterm babies was 14.6%. The median duration of continuous positive airway pressure (CPAP) was 48 hours (Range 8 - 192 hours). Inhospital mortality rate was 15 (15.96%). Lower gestational age and premature rupture of membrane (PROM) were significantly associated with higher mortality whereas Normal Vaginal delivery (NVD) was associated with lower mortality. Logistic regression analysis for risk of dying for the cohort predicted that lower birth weight (AOR = 0.99; 95% CI = 0.99 - 0.99; P = 0:01), sepsis (AOR = 145.14; 95% CI = 5.04 - 4175.15; P = 0:004) are independently associated with increased risk of dying whereas increase duration of NICU stay decreased the risk (AOR = 0.71; 95% CI = 0.54 - 0.91; P = 0:01). Conclusions: The mortality rate decreases with increasing gestational age and birth weight. A number of neonatal factors, either in isolation or in combination, were significantly associated with in-hospital mortality

Initial oxygenation as early predictor of mortality in acute respiratory distress syndrome: a retrospective study

Introduction: Acute respiratory distress syndrome (ARDS) is a major contributor to mortality and morbidity of adult patients admitted to intensive care units (ICU). Numerous scoring systems have been developed for critically ill patients with the goal of more accurately predicting clinical outcomes. However, the variability in these scores among individual patients, and consequently, their individual predictive ability is quite limited. Aim: To evaluate the role of initial oxygenation as an early predictor of mortality in ARDS patients. Methodology: One hundred and six mechanically ventilated adult patients with ARDS were enrolled retrospectively. Baseline parameters from the day of ICU admission were recorded. The details of ventilation, inspired oxygen fraction required, positive end-expiratory pressure and number of days on ventilation along with duration of hospital stay were recorded. Similarly, the status of oxygenation was assessed using PaO2/FiO2 (P/F) ratio. Survival of the patients was correlated with the baseline status of oxygenation. Results: Of the 106 patients, 65 were males and 41 female. The mean (± SD) age was 44 years (16.08). The difference in the P/F ratio between survivors and nonsurvivors was statistically significant. The ROC curve showed a cutoff value for P/F ratio of 108. Among survivors, the ICU stay was shorter in patients in pulmonary group compared to extrapulmonary group. Conclusion: Mortality is high if the baseline P/F ratio at admission is below 108. There is no difference in mortality due to lung injury caused by pulmonary or extrapulmonary aetiologies. ICU stay is longer among survivors if cause of ARDS is extrapulmonary.

Mechanical power in AVM-2 versus conventional ventilation modes in various ARDS lung models. Bench study

Introduction Mechanical power has been linked to ventilator induced lung injury and mortality in acute respiratory distress syndrome (ARDS). Adaptive Ventilator Mode-2 is a closed-loop pressure-controlled mode with an optimal targeting scheme based on the inspiratory power equation that adjusts the respiratory rate and tidal volume to achieve a target minute ventilation. Conceptually, this mode should reduce the mechanical power delivered to the patients and thus reduce the incidence of ventilator induced lung injury. Methods A bench study using a lung simulator was conducted. We constructed three passive single compartment ARDS models (Mild, Moderate, Severe) with compliance of 40, 30, 20 ml/cmH2O respectively, and resistance of 10 cmH2O/L/s, with IBW 70 kg. We compared three different ventilator modes: AVM-2, Pressure Regulated Volume Control (PRVC), and Volume Controlled Ventilation (VCV) in six different scenarios: 3 levels of minute ventilation 7, 10.5, and 14 Lit/min (Experiment 1, 2, and 3 respectively), each with 3 different PEEP levels 10, 15, and 20 cmH2O (Experiment A, B, and C respectively) termed 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B, 3C respectively for a total of 81 experiments. The AVM-2 mode automatically selects the optimal tidal volume and respiratory rate per the dialed percent minute ventilation with an I:E ratio of 1:1. In the PRVC and VCV (constant flow) we selected target tidal volume 6ml/kg/IBW (420 ml) and respiratory rate adjusted to match the minute ventilation for the AVM-2 mode. I:E ratio was kept 1:2. The mechanical power delivered by the ventilator for each mode was computed and compared between the three modes in each experiment. Statistical analysis was done using Kruskal-Wallis test to analyze the difference between the three modes, post HOC Tukey test was used to analyze the difference between each mode where P &lt; 0.05 was considered statistically significant. The Power Compliance Index was calculated and compared in each experiment. Multiple regression analysis was performed in each mode to test the correlation of the variables of mechanical power to the total calculated power. Results There were statistically significant differences (P &lt; 0.001) between all the three modes regarding the ventilator delivered mechanical power. AVM-2 mode delivered significantly less mechanical power than VCV which in turn was less than PRVC. The Power Compliance index was also significantly lower (P &lt; 0.01) in the AVM-2 mode compared to the other conventional modes. Multiple regression analysis indicated that in AVM-2 mode, the driving pressure (P = 0.004), tidal volume (P &lt; 0.001), respiratory rate (P = 0.011) and PEEP (P &lt; 0.001) were significant predictors in the model. In the VCV mode, the respiratory rate (P 0&lt; 0.001) and PEEP (P &lt; 0.001) were significant predictors, but the driving pressure was a non-significant predictor (P = 0.08). In PRVC mode, the respiratory rate (P &lt; 0.001), PEEP (P &lt; 0.001) and driving pressure (P &lt; 0.001) were significant predictors. Conclusion AVM2 mode delivered less mechanical power compared to two conventional modes using low tidal volume in an ARDS lung model with different severities. This might translate to the reduction of the incidence of ventilator induced lung injury. Results need to be validated in clinical studies.

Identification of early biomarkers of transcriptomics in alveolar macrophage for the prognosis of intubated ARDS patients

BackgroundCurrently, the rate of morbidity and mortality in acute respiratory distress syndrome (ARDS) remains high. One of the potential reasons for the poor and ineffective therapies is the lack of early and credible indicator of risk prediction that would help specific treatment of severely affected ARDS patients. Nevertheless, assessment of the clinical outcomes with transcriptomics of ARDS by alveolar macrophage has not been performed.MethodsThe expression data GSE116560 was obtained from the Gene Expression Omnibus databases (GEO) in NCBI. This dataset consists of 68 BAL samples from 35 subjects that were collected within 48 h of ARDS. Differentially expressed genes (DEGs) of different outcomes were analyzed using R software. The top 10 DEGs that were up- or down-regulated were analyzed using receiver operating characteristic (ROC) analysis. Kaplan–Meier survival analysis within two categories according to cut-off and the value of prediction of the clinical outcomes via DEGs was verified. GO enrichment, KEGG pathway analysis, and protein–protein interaction were also used for functional annotation of key genes.Results24,526 genes were obtained, including 235 up-regulated and 292 down-regulated DEGs. The gene ADORA3 was chosen as the most obvious value to predict the outcome according to the ROC and survival analysis. For functional annotation, ADORA3 was significantly augmented in sphingolipid signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction. Four genes (ADORA3, GNB1, NTS, and RHO), with 4 nodes and 6 edges, had the highest score in these clusters in the protein–protein interaction network.ConclusionsOur results show that the prognostic prediction of early biomarkers of transcriptomics as identified in alveolar macrophage in ARDS can be extended for mechanically ventilated critically ill patients. In the long term, generalizing the concept of biomarkers of transcriptomics in alveolar macrophage could add to improving precision-based strategies in the ICU patients and may also lead to identifying improved strategy for critically ill patients.