Mortality In Acute Respiratory Distress Syndrome Research Articles

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

BackgroundHypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype.MethodsWe studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support.ResultsThe PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004).ConclusionsThe PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Evaluation of the effect of aminophylline on inflammatory parameters in COVID-19 patients with acute respiratory distress syndrome

Background: In Acute respiratory distress syndrome (ARDS), invasion and activation of pro- and anti-inflammatory mediators and cytokines result in oxidative damage to the lung tissue. Aminophylline is a combination of theophylline and ethyl diamine, has anti-inflammatory, bronchodilator, ROS inhibitor effects, and stimulates surfactant release. Mortality of ARDS in COVID-19 patients is high; aminophylline is expected to reduce the incidence of mortality. Information regarding the use of aminophylline in COVID-19 patients with ARDS is still limited. Objective: To evaluate the efficacy of aminophylline in inflammatory parameters in COVID-19 patients with ARDS. Methods: It was a retrospective cohort observational study at the Universitas Airlangga Hospital. Samples were hospitalised COVID-19 patients with ARDS who received a loading dose of 240-480 mg and a maintenance dose of 720-960 mg aminophylline. The primary outcomes were improved C-reactive protein (CRP), IL-6, lymphocytes, neutrophils, and Neutrophil-lymphocyte ratio (NLR), which were measured before and after administration of aminophylline with a duration of therapy of 1-5 days. Result: A total of 50 patients with ARDS were enrolled in the study. Lymphocyte and CRP decreased (p = 0.002; p = 0.128). IL-6, neutrophil, and NLR increased (p = 0.255; p = 0.064; p = 0.005). Conclusion: It can be concluded that the administration of aminophylline has not improved inflammatory parameters.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFβ signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Mortality Due to Acute Respiratory Distress Syndrome in Latin America.

Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America. We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023. We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality. Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pao2/Fio2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation). Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pao2/Fio2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression. ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]).

Influence of simultaneous comorbidities on COVID-associated acute respiratory distress syndrome mortality in people with diabetes

ObjectivesThis study analyzed the influence of 23 comorbidities on COVID-associated acute distress respiratory syndrome (CARDS) mortality in people with a history of diabetes mellitus. MethodsAn observational, analytical, cross sectional study was utilized to investigate data from 6723 health services in Brazil, comprising 5433 people with diabetes. Adjusted logistic regression models for demographic factors such as age, sex, and race were used to analyze the association between CARDS mortality and comorbidities. ResultsPersons with two (p < 0.001), three (p < 0.001), four (p < 0.001), and five (p < 0.001) simultaneous comorbidities had a higher chance of dying. We identified that diabetes patients who had concomitant metabolic diseases (p = 0.019), neurological disorders (p < 0.001), or were smokers (p < 0.001) had a higher predicted mortality risk based on CADRS. ConclusionThe number of comorbidities plays a determining role in CARDS mortality in people with diabetes, especially those who suffer from smoking and neurological diseases simultaneously.

Blood group O is associated with ARDS development but exhibits lower mortality in the intensive care unit – A retrospective multicentre study

ABSTRACT Background Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in the intensive care unit (ICU). Previous studies have suggested that blood group A increases the risk of developing ARDS following sepsis and major trauma. This study investigated the association between ABO and Rh blood groups and ARDS development and mortality in ARDS. Methods Patients admitted to the ICUs at Skåne University Hospital in Lund and Malmö, Sweden, in 2016 were retrospectively screened for ARDS according to the Berlin definition. Clinical data, patient characteristics, lab results, and survival data were collected from medical records and registry data. In addition, chest radiographs were reviewed by radiologists. ARDS development and 30-day mortality were analysed using multivariable logistic regression. Results A total of 1439 ICU patients were included. Of these, 10% had ARDS. Blood group O was associated with an increased risk of having or developing ARDS compared to blood group A (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.13–2.84, p = 0.014). Among ARDS patients, blood group O had decreased 30-day mortality compared to blood group A (OR 0.25, 95% CI 0.09–0.67, p = 0.007). The Rh blood group was not associated with ARDS development or mortality. Conclusion In this study of ICU patients, blood group O was associated with an increased risk of having or developing ARDS but a decreased mortality in ARDS compared to blood group A. Further studies are needed to clarify the relationship and underlying mechanisms of the ABO blood group and ARDS.

Post-operative sepsis-induced acute respiratory distress syndrome: risk factors for a life-threatening complication.

Prevalence and mortality of the acute respiratory distress syndrome (ARDS) in intensive care units (ICU) are unacceptably high. There is scarce literature on post-operative sepsis-induced ARDS despite that sepsis and major surgery are conditions associated with ARDS. We aimed to examine the impact of post-operative sepsis-induced ARDS on 60-day mortality. We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups depending on whether they met criteria for ARDS. Primary outcome was 60-day mortality of post-operative sepsis-induced ARDS. Secondary outcome measures were potential risk factors for post-operative sepsis-induced ARDS, and for 60-day mortality. Higher SOFA score (OR 1.1, 95% CI 1.0-1.3, p = 0.020) and higher lactate (OR 1.9, 95% CI 1.2-2.7, p = 0.004) at study inclusion were independently associated with ARDS. ARDS patients (n = 45) had higher ICU stay [14 (18) vs. 5 (11) days, p < 0.001] and longer need for mechanical ventilation [6 (14) vs. 1 (5) days, p < 0.001] than non-ARDS patients (n = 409). Sixty-day mortality was higher in ARDS patients (OR 2.7, 95% CI 1.1-6.3, p = 0.024). Chronic renal failure (OR 4.0, 95% CI 1.2-13.7, p = 0.026), elevated lactate dehydrogenase (OR 1.7, 95% CI 1.1-2.7, p = 0.015) and higher APACHE II score (OR 2.7, 95% CI 1.3-5.4, p = 0.006) were independently associated with 60-day mortality. Post-operative sepsis-induced ARDS is associated with higher 60-day mortality compared to non-ARDS post-operative septic patients. Post-operative septic patients with higher severity of illness have a greater risk of ARDS and worse outcomes. Further investigation is needed in post-operative sepsis-induced ARDS to prevent ARDS.

Attributable mortality of ARDS among critically ill patients with sepsis: a multicenter, retrospective cohort study

BackgroundBoth sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis.MethodsThe data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis.Results2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS’s overall 30-day attributable mortality was 11.9% (95% CI 7.5–16.3%, p < 0.001). Subgroup analysis showed that the 30-day attributable mortality of mild, moderate, and severe ARDS was 10.5% (95% CI 4.0-16.8%, p < 0.001), 11.6% (95% CI 4.7–18.4%, p < 0.001) and 18.1% (95% CI 4.5–30.9%, p = 0.006), respectively. ARDS was an independent risk factor for 30-day mortality, with adjusted hazard ratios of 1.30 (95% CI 1.03–1.64, p = 0.027), 1.49 (95% CI 1.20–1.85, p < 0.001), and 1.95 (95% CI 1.51–2.52, p < 0.001) for mild, moderate, and severe ARDS, respectively.ConclusionsThe overall 30-day attributable mortality of ARDS among critically ill patients with sepsis was 11.9%. Compared with mild and moderate ARDS, severe ARDS contributed more to death. ARDS was significantly associated with an increase in the 30-day mortality.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.

Historically considered a metabolically inert cellular layer separating the blood from the underlying tissue, the endothelium is now recognized as a highly dynamic, metabolically active tissue that is critical to organ homeostasis. Under homeostatic conditions, lung endothelial cells (ECs) in healthy subjects are quiescent, promoting vasodilation, platelet disaggregation, and anti-inflammatory mechanisms. In contrast, lung ECs are essential contributors to the pathobiology of acute respiratory distress syndrome (ARDS), as the quiescent endothelium is rapidly and radically altered upon exposure to environmental stressors, infectious pathogens, or endogenous danger signals into an effective and formidable regulator of innate and adaptive immunity. These dramatic perturbations, produced in a tsunami of inflammatory cascade activation, result in paracellular gap formation between lung ECs, sustained lung edema, and multi-organ dysfunction that drives ARDS mortality. The astonishing plasticity of the lung endothelium in negotiating this inflammatory environment and efforts to therapeutically target the aberrant ARDS endothelium are examined in further detail in this review.

Novel Oxygenation and Saturation Indices for Mortality Prediction in COVID-19 ARDS Patients: The Impact of Driving Pressure and Mechanical Power.

Background: The oxygenation index (OI) and oxygen saturation index (OSI) are proven mortality predictors in pediatric and adult patients, traditionally using mean airway pressure (Pmean). We introduce novel indices, replacing Pmean with DP (ΔPinsp), MPdyn, and MPtot, assessing their potential for predicting COVID-19 acute respiratory distress syndrome (ARDS) mortality, comparing them to traditional indices. Methods: We studied 361 adult COVID-19 ARDS patients for 7 days, collecting ΔPinsp, MPdyn, and MPtot, OI-ΔPinsp, OI-MPdyn, OI-MPtot, OSI-ΔPinsp, OSI-MPdyn, and OSI-MPtot. We compared these in surviving and non-surviving patients over the first 7 intensive care unit (ICU) days using Mann-Whitney U test. Logistic regression receiver operating characteristic (ROC) analysis assessed AUC and CI values for ICU mortality on day three. We determined cut-off values using Youden's method and conducted multivariate Cox regression on parameter limits. Results: All indices showed significant differences between surviving and non-surviving patients on the third day of ICU care. The AUC values of OI-ΔPinsp were significantly higher than those of P/F and OI-Pmean (P values .0002 and <.0001, respectively). Similarly, AUC and CI values of OSI-ΔPinsp and OSI-MPdyn were significantly higher than those of SpO2/FiO2 and OSI-Pmean values (OSI-ΔPinsp: P < .0001, OSI-MPdyn: P values .047 and .028, respectively). OI-ΔPinsp, OSI-ΔPinsp, OI-MPdyn, OSI-MPdyn, OI-MPtot, and OSI-MPtot had AUC values of 0.72, 0.71, 0.69, 0.68, 0.66, and 0.64, respectively, with cut-off values associated with hazard ratios and P values of 7.06 (HR = 1.84, P = .002), 8.04 (HR = 2.00, P ≤ .0001), 7.12 (HR = 1.68, P = .001), 5.76 (HR = 1.70, P ≤ .0001), 10.43 (HR = 1.52, P = .006), and 10.68 (HR = 1.66, P = .001), respectively. Conclusions: Critical values of all indices were associated to higher ICU mortality rates and extended mechanical ventilation durations. The OI-ΔPinsp, OSI-ΔPinsp, and OSI-MPdyn indices displayed the strongest predictive capabilities for ICU mortality. These novel indices offer valuable insights for intensivists in the clinical management and decision-making process for ARDS patients.

Association between pre-ICU statin use and ARDS mortality in the MIMIC-IV database: a cohort study.

Acute respiratory distress syndrome (ARDS) is a severe condition associated with high morbidity, mortality, and healthcare costs. Despite extensive research, treatment options for ARDS are suboptimal. This study encompassed patients diagnosed with ARDS from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Pre-intensive care unit (ICU) statin use was assessed as the exposure variable. Kaplan-Meier survival analysis was conducted to evaluate mortality at 30 and 90 days. Adjusted multivariable Cox models were utilized to estimate hazard ratios. Subgroup analyses and propensity score-matching (PSM) were undertaken for further validation. Our study comprised 10,042 participants diagnosed with ARDS, with an average age of 61.8 ± 15.3 years. Kaplan-Meier survival analysis demonstrated a significantly lower prevalence of mortality at 30 and 90 days in individuals who used statins before ICU admission. Adjusted multivariable Cox models consistently showed a significant decrease in mortality prevalence associated with pre-ICU statin use. After accounting for confounding factors, patients who used statins before ICU admission experienced a 39% reduction in 30-day mortality and 38% reduction in 90-day mortality. We found a significant decrease in ICU stay (0.84 days) for those who used statins before ICU admission. These results were supported by subgroup analyses and PSM. This large cohort study provides evidence supporting the association between pre-ICU statin use, reduced risk of death, and shorter ICU stay in patients with ARDS, thereby suggesting the potential benefits of statin use in critically ill patients.

Abstract 17260: Endothelium-Targeted Nanoparticle Delivery of FOXM1 Reactivates Aging-Impaired Endothelial Regeneration for Vascular Repair and Inflammatory Lung Injury Resolution: Precision Gene Therapy of Acute Respiratory Distress Syndrome

Introduction: Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). However, the underlying molecular mechanisms remain elusive and there is no effective therapy for ARDS. Hypothesis: Impaired endothelial regeneration and vascular repair in aged lungs causes persistent lung injury leading to high incidence of ARDS and high mortality in elderly patients following sepsis challenge. Methods: Genetic lineage tracing was employed to determine the cell origin of endothelial regeneration. Aged Foxm1Tg mice was used for assessing the role of FoxM1 in activating endothelial regeneration. Endothelium-targeted nanoparticles were employed to deliver FOXM1 gene selectively to endothelial cells (ECs) in aged mice. Methylation analysis was employed to determine how aging impairs FoxM1 expression. Results: Genetic lineage tracing study showed that endothelial regeneration was mediated by lung endothelial proliferation in adult mice whereas this intrinsic regenerative program was impaired in aged mice. Expression of FoxM1, an important mediator of endothelial regeneration in young adult mice, was not induced in lungs of aged mice due to aging-induced hypermethylation of the Foxm1 promoter. Transgenic FOXM1 expression or in vivo endothelium-targeted nanoparticle delivery of FOXM1 gene reactivated endothelial regeneration, normalized vascular repair and promoted survival of aged mice following sepsis. Furthermore, nanoparticle delivery of FoxM1 gene selectively in lung ECs also reactivated endothelial regeneration in aged mice, supporting the novel concept of precision gene therapy. In COVID-19 lung autopsy samples, FOXM1 expression was not induced in vascular ECs of elderly patients in contrast to mid-age patients, validating the clinical relevance of our findings. Conclusions: We have demonstrate that persistent lung injury and high mortality in aged mice following sepsis challenge is ascribed to impaired endothelial regeneration and vascular repair. Therapeutic reactivation of FoxM1-dependent endothelial regeneration and vascular repair represents a potential effective therapy for elderly ARDS patients by endothelium-targeted nanoparticle delivery of FOXM1 gene.

Outcomes and time trends of acute respiratory distress syndrome patients with and without liver cirrhosis: an observational cohort

BackgroundIn studies prior to lung-protective ventilation, liver cirrhosis in acute respiratory distress syndrome (ARDS) was associated with high mortality rates. Since patients with cirrhosis have been excluded from many trials on ARDS, their outcome when treated with lung-protective ventilation is unclear. The objectives were to assess whether cirrhosis is associated with mortality in ARDS and trends over time in mortality and severity.MethodsWe conducted a retrospective analysis of a prospective observational cohort conducted in a 20-bed tertiary ICU from October 2003 to December 2021. All consecutive adult critically ill patients with ARDS were included. ARDS was defined by the Berlin criteria. The primary outcome was 90 day mortality, assessed with Kaplan–Meier curves and multivariate Cox analysis. Time trends were assessed on 90 day mortality, Sequential Organ-Function Assessment score (SOFA) and non-hepatic SOFA. Ventilation settings were compared between patients with and without cirrhosis.ResultsOf the 7155 patients screened, 863 had a diagnosis of ARDS. Among these ARDS patients, 157(18%) had cirrhosis. The overall 90 day mortality was of 43% (378/863), 57% (90/157) in patients with cirrhosis and 41% (288/706) in patients without cirrhosis (p < 0.001). On survival curves, cirrhosis was associated with 90 day mortality (p < 0.001). Cirrhosis was independently associated with 90 day mortality in multivariate analysis (hazard ratio = 1.56, 95% confidence interval 1.20–2.02). There was no change in mortality over time in ARDS patients with and without cirrhosis. SOFA (p = 0.04) and non-hepatic SOFA (p = 0.02) increased over time in ARDS patients without cirrhosis, and remained stable in ARDS patients with cirrhosis. Tidal volume, positive end-expiratory pressure, plateau pressure and driving pressure were not different between ARDS patients with and without cirrhosis.ConclusionsAlthough ARDS management improved over the last decades, the 90 day mortality remained high and stable over time for both ARDS patients with (57%) and without cirrhosis (41%). Nevertheless, the severity of patients without cirrhosis has increased over time, while the severity of patients with cirrhosis has remained stable.Graphical

Early vvECMO implantation may be associated with lower mortality in ARDS

BackgroundVenovenous extracorporeal membrane oxygenation (vvECMO) is used to treat hypoxia in patients with severe acute respiratory distress syndrome (ARDS). Nevertheless, uncertainty exists regarding the optimal timing of initiation of vvECMO therapy. We aimed to investigate the association between number of days of invasive mechanical ventilation (IMV) prior to vvECMO implantation and mortality.MethodsIn this retrospective observational study, we included patients treated at an academic intensive care unit with vvECMO for severe ARDS. The primary outcome was all-cause 28-day mortality. We conducted a multivariate logistic regression analysis to estimate the association between number of days of IMV prior to vvECMO implantation and mortality after adjustment for confounders.ResultsOut of 274 patients who underwent ECMO for severe ARDS, 158 patients (median age: 58 years) with relevant data were included in the analysis. The mean duration of IMV prior to vvECMO was significantly shorter in survivors than in nonsurvivors [survivors median: 1; interquartile range: 1–3; non-survivors median 4; interquartile range: 1–5.75; p = 0.0001). Logistic regression showed an association between the duration of ventilation prior to vvECMO and patient mortality. The odds ratio for the all-cause 28-day mortality and in-hospital mortality was significantly reduced in patients who received vvECMO within the first 5 days of IMV.ConclusionsEarly vvECMO implantation may be associated with lower mortality in ARDS.

Drivers of mortality in COVID ARDS depend on patient sub-type

The most common cause of death in people with COVID-19 is Acute Respiratory Distress Syndrome (ARDS). Prior studies have demonstrated that ARDS is a heterogeneous syndrome and have identified ARDS sub-types (phenoclusters). However, non-COVID-19 ARDS phenoclusters do not clearly apply to COVID-19 ARDS patients. In this retrospective cohort study, we implemented an iterative approach, combining supervised and unsupervised machine learning methodologies, to identify clinically relevant COVID-19 ARDS phenoclusters, as well as characteristics that are predictive of the outcome for each phenocluster. To this end, we applied a supervised model to identify risk factors for hospital mortality for each phenocluster and compared these between phenoclusters and the entire cohort. We trained the models using a comprehensive, preprocessed dataset of 2,864 hospitalized COVID-19 ARDS patients. Our research demonstrates that the risk factors predicting mortality in the overall cohort of COVID-19 ARDS may not necessarily apply to specific phenoclusters. Additionally, some risk factors increase the risk of hospital mortality in some phenoclusters but decrease mortality in others. These phenocluster-specific risk factors would not have been observed with a single predictive model. Heterogeneity in phenoclusters of COVID-19 ARDS as well as the drivers of mortality may partially explain challenges in finding effective treatments for all patients with ARDS.

Long short-term memory model identifies ARDS and in-hospital mortality in both non-COVID-19 and COVID-19 cohort

ObjectiveTo identify the risk of acute respiratory distress syndrome (ARDS) and in-hospital mortality using long short-term memory (LSTM) framework in a mechanically ventilated (MV) non-COVID-19 cohort and a COVID-19 cohort.MethodsWe...

Circulatory HMGB1 is an early predictive and prognostic biomarker of ARDS and mortality in a swine model of polytrauma.

Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in polytrauma patients. Pharmacological treatments of ARDS are lacking, and ARDS patients rely on supportive care. Accurate diagnosis of ARDS is vital for early intervention and improved outcomes but is presently delayed up to days. The use of biomarkers for early identification of ARDS development is a potential solution. Inflammatory mediators high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1), and C3a have been previously proposed as potential biomarkers. For this study, we analyzed these biomarkers in animals undergoing smoke inhalation and 40% total body surface area burns, followed by intensive care for 72h post-injury (PI) to determine their association with ARDS and mortality. We found that the levels of inflammatory mediators in serum were affected, as well as the degree of HMGB1 and Toll-like receptor 4 (TLR4) signal activation in the lung. The results showed significantly increased HMGB1 expression levels in animals that developed ARDS compared with those that did not. Receiver operating characteristic (ROC) analysis showed that HMGB1 levels at 6h PI were significantly associated with ARDS development (AUROC=0.77) and mortality (AUROC=0.82). Logistic regression analysis revealed that levels of HMGB1 ≥24.10 ng/ml are associated with a 13-fold higher incidence of ARDS [OR:13.57 (2.76-104.3)], whereas the levels of HMGB1 ≥31.39 ng/ml are associated with a 12-fold increase in mortality [OR: 12.00 (2.36-93.47)]. In addition, we found that mesenchymal stem cell (MSC) therapeutic treatment led to a significant decrease in systemic HMGB1 elevation but failed to block SDC-1 and C3a increases. Immunohistochemistry analyses showed that smoke inhalation and burn injury induced the expression of HMGB1 and TLR4 and stimulated co-localization of HMGB1 and TLR4 in the lung. Interestingly, MSC treatment reduced the presence of HMGB1, TLR4, and the HMGB1-TLR4 co-localization. These results show that serum HMGB1 is a prognostic biomarker for predicting the incidence of ARDS and mortality in swine with smoke inhalation and burn injury. Therapeutically blocking HMGB1 signal activation might be an effective approach for attenuating ARDS development in combat casualties or civilian patients.

Mechanical ventilation in patients with acute brain injury: a systematic review with meta-analysis

ObjectiveTo describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation.DesignSystematic review with an individual data meta-analysis.SettingObservational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt < 8 ml/Kg of IBW versus Vt > = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) < or > = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes.PopulationPatients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h.Main outcome measuresThe primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio.ResultsThe meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p < 0.01).ConclusionsLow tidal volume, moderate to high PEEP, or protective ventilation were not associated with mortality and lower incidence of ARDS in patients with acute brain injury undergoing invasive mechanical ventilation. However, protective ventilation improved oxygenation and could be safely considered in this setting. The exact role of ventilatory management on the outcome of patients with a severe brain injury needs to be more accurately delineated.

Same but Different? Comparing the Epidemiology, Treatments and Outcomes of COVID-19 and Non-COVID-19 ARDS Cases in Germany Using a Sample of Claims Data from 2021 and 2019.

Acute respiratory distress syndrome (ARDS) is a severe lung condition that can be caused by a variety of underlying illnesses. Due to SARS-CoV-2, the number of cases with ARDS has increased worldwide, making it essential to compare this form of acute respiratory failure with classical causes of ARDS. While there have been several studies investigating the differences between COVID-19 and non-COVID-19 ARDS in early stages of the pandemic, little is known about the differences in later phases, especially in Germany. The aim of this study is to characterize and compare the comorbidities, treatments, adverse events, and outcomes of COVID-19-associated ARDS and non-COVID-19 ARDS using a representative sample of German health claims data from the years 2019 and 2021. We compare percentages and median values of the quantities of interest from the COVID-19 and non-COVID-19 ARDS group, with p-values calculated after conducting Pearson's chi-squared test or the Wilcoxon rank sum test. We also run logistic regressions to access the effect of comorbidities on mortality for COVID-19 ARDS and non-COVID-19 ARDS. Despite many similarities, we find that that there are some remarkable differences between COVID-19 and non-COVID-19 ARDS cases in Germany. Most importantly, COVID-19 ARDS cases display fewer comorbidities and adverse events, and are more often treated with non-invasive ventilation and nasal high-flow therapy. This study highlights the importance of comprehending the contrasting epidemiological features and clinical outcomes of COVID-19 and non-COVID-19 ARDS. This understanding can aid in clinical decision making and guide future research initiatives aimed at enhancing the management of patients afflicted with this severe condition.