Outcome Of Acute Respiratory Distress Syndrome Research Articles

Outpatient insulin use in type 2 diabetes mellitus and acute respiratory distress syndrome outcomes: A retrospective cohort study.

The impact of type 2 diabetes mellitus (T2DM) on acute respiratory distress syndrome (ARDS) is debatable. T2DM was suspected to reduce the risk and complications of ARDS. However, during coronavirus disease 2019 (COVID-19), T2DM predisposed patients to ARDS, especially those who were on insulin at home. To evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes. We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database. Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus (DM) (IDDM) and non-insulin-dependent DM (NIDDM) groups. After applying exclusion criteria and matching over 20 variables, we compared cohorts for mortality, duration of mechanical ventilation, incidence of acute kidney injury (AKI), length of stay (LOS), hospitalization costs, and other clinical outcomes. Following 1:1 propensity score matching, the analysis included 274 patients in each group. Notably, no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates (32.8% vs 31.0%, P = 0.520), median hospital LOS (10 d, P = 0.537), requirement for mechanical ventilation, incidence rates of sepsis, pneumonia or AKI, median total hospitalization costs, or patient disposition upon discharge. Compared to alternative anti-diabetic medications, outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.

Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12–48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.

Association of ratios of visceral fat area/subcutaneous fat area and muscle area/standard body weight at T12 CT level with the prognosis of acute respiratory distress syndrome

BackgroundIt is well-known that body composition metrics can influence the prognosis of various diseases. This study investigated how body composition metrics predict acute respiratory distress syndrome (ARDS) prognosis, focusing on the ratio of visceral fat area (VFA) to subcutaneous fat area (SFA), SFA to standard body weight (SBW), VFA to SBW, and muscle area (MA) to SBW. These metrics were assessed at the level of the twelfth thoracic vertebra (T12 computed tomography [CT] level) to determine their correlation with the outcomes of ARDS. The goal was to utilize these findings to refine and personalize treatment strategies for ARDS. MethodsPatients with ARDS admitted to the intensive care units (ICUs) of three hospitals from January 2016 to July 2023 were enrolled in this study. Within 24 hours of ARDS onset, we obtained chest CT scans to measure subcutaneous fat, visceral fat, and muscle area at the T12 level. We then compared these ratios between survivors and non-survivors. Logistic regression was employed to identify prognostic risk factors. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cutoff for predictors of in-hospital mortality. Based on this cutoff, patients with ARDS were stratified. To reduce confounding factors, 1:1 propensity score matching (PSM) was applied. We conducted analyses of clinical feature and prognostic differences pre- and post-PSM between the stratified groups. Additionally, Kaplan–Meier survival curves were generated to compare the survival outcomes of these groups. ResultsOf 258 patients with ARDS, 150 survived and 108 did not. Non-survivors had a higher VFA/SFA ratio (P <0.001) and lower SFA/SBW and MA/SBW ratios (both P <0.001). Key risk factors were high VFA/SFA ratio (OR=2.081; P=0.008), age, acute physiology and chronic health evaluation (APACHE) II score, and lactate levels, while MA/SBW and albumin were protective. Patients with a VFA/SFA ratio ≥0.73 were associated with increased mortality, while those with an MA/SBW ratio >1.55 cm²/kg had lower mortality, both pre- and post-PSM (P=0.001 and P <0.001, respectively). Among 170 patients with pulmonary-origin ARDS, 87 survived and 83 did not. The non-survivor group showed a higher VFA/SFA ratio (P <0.001) and lower SFA/SBW and MA/SBW (P=0.003, P <0.001, respectively). Similar risk and protective factors were observed in this cohort. For VFA/SFA, a value above the cutoff of 1.01 predicted higher mortality, while an MA/SBW value below the cutoff of 1.48 cm²/kg was associated with increased mortality (both P <0.001 pre-/post-PSM). ConclusionsAmong all patients with ARDS, the VFA to SFA ratio, MA to SBW ratio at the T12 level, age, APACHE II score, and lactate levels emerged as independent risk factors for mortality.

449 Does incorporation of plasma biomarkers to the Lung Injury Prediction Score improve the predictive value for development of acute respiratory distress syndrome?

OBJECTIVES/GOALS: To determine if incorporating specific laboratory values and plasma biomarkers (club cell secretory protein (CC16), matrix metalloproteinase 3 (MMP3), interleukin 8 (IL-8), protein C) to the Lung Injury Prediction (LIP) Score improves the predictive value for development of acute respiratory distress syndrome (ARDS) in ICU patients. METHODS/STUDY POPULATION: Adult patients admitted to the ICU on supplemental oxygen over baseline requirement with a LIP Score ≥6 will be included. Patients admitted to the ICU &gt;24 hours, end-stage renal disease, decompensated heart failure, or &lt;100 µL plasma available will be excluded. Whole blood will be collected from the core lab, centrifuged, and plasma will be stored at -80°C. Protein biomarkers will be measured using enzyme-linked immunosorbent assay. Baseline characteristics, laboratory values, ventilator parameters, and clinical outcomes will be collected from the medical record. ARDS will be defined by the Berlin criteria. Machine learning methods will be used to identify the model with the highest predictive accuracy. Area under the receiver operating characteristic curve of each model will be compared to the LIP Score. RESULTS/ANTICIPATED RESULTS: Research is in progress. Plasma samples and clinical data have been collected for 148 of the 160 samples required to achieve power. Biomarker analysis will take place after sample collection is complete. We anticipate a machine learning model incorporating laboratory values and one or more plasma biomarkers into the LIP Score will outperform the baseline LIP Score for prediction of ARDS development. DISCUSSION/SIGNIFICANCE: Delayed diagnosis and intervention contribute to poor ARDS outcomes. Current predictive models for ARDS have low accuracy and enriching these models with plasma biomarkers may increase their predictive value. Development of accurate models may facilitate earlier ARDS diagnosis and intervention as well as enrichment strategies for ARDS trials.

Analysis of clinical treatment of acute respiratory distress syndrome assisted by artificial intelligence

To evaluate the clinical practice of intensive care unit (ICU) physicians at Hebei General Hospital in identifying patients meeting the diagnostic criteria for acute respiratory distress syndrome (ARDS) and the current status of invasive mechanical ventilation management and adjunctive therapy in these patients, and to analyze the incidence and clinical outcomes of ARDS. A retrospective cohort study was conducted. The patients who were hospitalized in the ICU of Hebei General Hospital from April 10, 2017 to June 30, 2022 and met the Berlin definition diagnostic criteria for ARDS were enrolled as study subjects. Artificial intelligence (AI) technology was applied to search the basic information (age, gender, height, body weight, etc.), auxiliary examination, electronic medical record, non-drug doctor's advice, drug doctor's advice, critical report, scoring system, monitoring master table and other data of the above medical records in the electronic medical record system of the hospital. The first set of laboratory indicators sequentially retrieved from the system daily from 05:00 to 10:00 and vital signs and mechanical ventilation-related parameters recorded in the "critical care report" at 06:00 daily were extracted, and outcome indicators of the patients were collected. After screening and analysis, a total of 255 patients who met the ARDS diagnostic criteria were finally enrolled. The overall incidence of ARDS in the ICU accounted for 3.4% (255/7 434) of the total number of ICU patients, of which mild, moderate and severe ARDS accounted for 22.4% (57/255), 49.0% (125/255), and 28.6% (73/255), respectively, while the recognition rates of clinical doctors were 71.9% (41/57), 58.4% (73/125) and 71.2% (52/73), respectively. During the ICU stay, 250 patients (98.0%) received only invasive mechanical ventilation, while 5 patients (2.0%) received both non-invasive and invasive mechanical ventilation. The tidal volume/ideal body weight of ARDS patients was 7.64 (6.49, 9.01) mL/kg, and the positive end-expiratory pressure (PEEP) was 8.0 (5.0, 10.0) cmH2O (1 cmH2O ≈ 0.098 kPa). In addition, during the diagnosis and detection of ARDS, only 7 patients were recorded the platform pressure and 6 patients were recorded the drive pressure. Regarding adjunctive therapies, 137 patients (53.7%) received deep sedation, 26 patients (10.2%) underwent lung recruitment, 55 patients (21.6%) received prone ventilation, 42 patients (16.5%) were treated with high-dose steroids, 19 patients (7.5%) were treated with neuromuscular blockade, and 8 patients (3.1%) were treated with extracorporeal membrane oxygenation (ECMO). Finally, 70 patients (27.5%) were discharged automatically, while 50 patients (19.6%) died in the ICU, of which the ICU mortality of mild, moderate, and severe ARDS patients were 15.8% (9/57), 22.4% (28/125), and 17.8% (13/73), respectively. After follow-up, it was found that all 70 patients discharged automatically died within 28 days after discharge, and the overall ICU mortality adjusted accordingly was 47.1% (120/255). The overall incidence of ARDS in ICU patients at Hebei General Hospital is relatively low, with a high recognition rate by clinical physicians. Despite the high level of compliance and implementation of lung protective ventilation strategies and auxiliary treatment measures, it is still necessary to further improve the level of standardization in the implementation of small tidal volume and respiratory mechanics monitoring. For the implementation of auxiliary measures such as prone ventilation, it is necessary to further improve the enthusiasm of medical staff. The mortality in ICU is relatively low in ARDS patients, while the rate of spontaneous discharge is relatively high.

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.

A pretrain-finetune approach for improving model generalizability in outcome prediction of acute respiratory distress syndrome patients

BackgroundEarly prediction of acute respiratory distress syndrome (ARDS) of critically ill patients in intensive care units (ICUs) has been intensively studied in the past years. Yet a prediction model trained on data from one hospital might not be well generalized to other hospitals. It is therefore essential to develop an accurate and generalizable ARDS prediction model adaptive to different hospital or medical centers. MethodsWe analyzed electronic medical records of 200,859 and 50,920 hospitalized patients within 24 h after being diagnosed with ARDS from the Philips eICU Institute (eICU-CRD) and the Medical Information Mart for Intensive Care (MIMIC-IV) dataset, respectively. Patients were sorted into three groups, including rapid death, long stay, and recovery, based on their condition or outcome between 24 and 72 h after ARDS diagnosis. To improve prediction performance and generalizability, a “pretrain-finetune” approach was applied, where we pretrained models on the eICU-CRD dataset and performed model finetuning using only a part (35%) of the MIMIC-IV dataset, and then tested the finetuned models on the remaining data from the MIMIC-IV dataset. Well-known machine-learning algorithms, including logistic regression, random forest, extreme gradient boosting, and multilayer perceptron neural networks, were employed to predict ARDS outcomes. Prediction performance was evaluated using the area under the receiver-operating characteristic curve (AUC). ResultsResults show that, in general, multilayer perceptron neural networks outperformed the other models. The use of pretrain-finetune yielded improved performance in predicting ARDS outcomes achieving a micro-AUC of 0.870 for the MIMIC-IV dataset, an improvement of 0.046 over the pretrain model.Conclusions.The proposed pretrain-finetune approach can effectively improve model generalizability from one to another dataset in ARDS prediction.

Inter- and Intra-donor Variability in Bone Marrow-Derived Mesenchymal Stromal Cells: Implications for Clinical Applications

Mesenchymal stromal cells (MSCs) are attractive as a therapeutic modality in multiple disease conditions characterized by inflammation and vascular compromise. Logistically they are advantageous since they can be isolated them from adult tissue sources, such as bone marrow (BM). The phase 2a START clinical trial determined BM-MSCs to be safe in patients with moderate to severe acute respiratory distress syndrome (ARDS). Herein, we examine a subset of the clinical doses of MSCs generated for the phase 2a START trial from three unique donors (1-3), where one of the donors’ donated BM on two separate occasions (Donor 3 and 3W). The main objective of this study was to correlate properties of the cells from the four lots with plasma biomarkers from treated patients and relevant to ARDS outcomes. To do this we evaluated MSC donor lots for (1) post-thaw viability, (2) growth kinetics, (3) metabolism, (4) surface marker expression, (5) protein expression, (6) immunomodulatory ability, and (7) their functional effects on regulating endothelial cell permeability. MSC-specific marker expression and protection of thrombin-challenged endothelial barrier permeability was similar among all four donor lots. Inter and intra-donor variability was observed in all the other in vitro assays. Furthermore, patient plasma ANG-2 and Protein C levels at 6 hours post-transfusion were correlated to cell viability in an inter- and intra-donor dependent manner. These findings highlight the potential of donor dependent (inter-) and collection dependent (intra-) effects in patient biomarker expression.

Prevalence, predictors, and outcomes of acute respiratory distress syndrome in severe stroke.

Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90days were explored. Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1week of admission. Procalcitonin (OR 1.310 95% CI 1.005-1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979-0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR0.994, 95% CI 0.989-0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90days. ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied.

Efficacy of the Cytokine Adsorption Therapy in Patients with Severe COVID-19-Associated Pneumonia: Lesson Learned from a Prospective Observational Study

Introduction: Severe COVID-19 pneumonia can activate a cytokine storm. Hemoperfusion can reduce pro-inflammatory cytokines in sepsis but is still debated in the COVID-19 setting. Thus, we sought to investigate the benefits of HA-330 cytokine adsorption through clinical and laboratory outcomes. Methods: We conducted a single-center prospective observational study in adults with severe COVID-19 pneumonia admitted to the intensive care unit at Chiang Mai University Hospital (Chiang Mai, Thailand). Those with cytokine storms indicated by organ injury, including acute respiratory distress syndrome (ARDS), and high inflammatory markers were included. Patients treated with the HA-330 device were classified as a hemoperfusion group, while those without cytokine adsorption were classified as a control group. We compared the outcomes on day 7 after treatment and evaluated the factors associated with 60-day mortality. Results: A total of 112 patients were enrolled. Thirty-eight patients received hemoperfusion, while 74 patients did not. Baseline cytokine storm parameters were comparable. In univariate analysis, there was an improvement in clinical and laboratory effects from hemoperfusion therapy. In multivariate analysis, APACHE II score, SOFA score, PaO₂/FiO₂, the number of hemoperfusion sessions, the amount of blood purified, high-sensitivity C-reactive protein, and IL-6 were associated with mortality. Using at least 3 sessions of hemoperfusion could mitigate, the 60-day mortality (adjusted odds ratio 0.25, 95% confidence interval: 0.03–0.33, p = 0.001). By categorizing the amount of blood treated into 3 groups of <1 L/kg, 1–2 L/kg, and ≥2 L/kg, there was a linear dose-response association with survival, which was better in the higher volume purified (mortality 60% vs. 33.3% vs. 0%, respectively, p = 0.015). Conclusions: The early initiation of HA-330 hemoperfusion could improve the severity score and laboratory outcomes of COVID-19 ARDS. The optimal dose of at least three sessions or the amount of blood purified greater than 1 L/kg was associated with a reduction in 60-day mortality.

Effect of pre-operative hypoxemia on the occurrence and outcomes of post-operative ARDS in Stanford type a aortic dissection patients

BackgroundPre-operative and post-operative hypoxemia are frequent complications of Stanford type A aortic dissection (AAD). This study explored the effect of pre-operative hypoxemia on the occurrence and outcome of post-operative acute respiratory distress syndrome (ARDS) in AAD.MethodA total of 238 patients who underwent surgical treatment for AAD between 2016 and 2021 were enrolled. Logistic regression analysis was conducted to investigate the effect of pre-operative hypoxemia on post-operative simple hypoxemia and ARDS. Post-operative ARDS patients were divided into pre-operative normal oxygenation group and pre-operative hypoxemia group that were compared for clinical outcomes. Post-operative ARDS patients with pre-operative normal oxygenation were classified as the real ARDS group. Post-operative ARDS patients with pre-operative hypoxemia, post-operative simple hypoxemia, and post-operative normal oxygenation were classified as the non-ARDS group. Outcomes of real ARDS and non-ARDS groups were compared.ResultLogistic regression analysis showed that pre-operative hypoxemia was positively associated with the risk of post-operative simple hypoxemia (odds ratios (OR) = 4.81, 95% confidence interval (CI): 1.67–13.81) and post-operative ARDS (OR = 8.514, 95% CI: 2.64–27.47) after adjusting for the confounders. The post-operative ARDS with pre-operative normal oxygenation group had significantly higher lactate, APACHEII score and longer mechanical ventilation time than the post-operative ARDS with pre-operative hypoxemia group (P < 0.05). Pre-operative the risk of death within 30 days after discharge was slightly higher in ARDS patients with pre-operative normal oxygenation than in ARDS patients with pre-operative hypoxemia, but there was no statistical difference(log-rank test, P = 0.051). The incidence of AKI and cerebral infarction, lactate, APACHEII score, mechanical ventilation time, intensive care unit and post-operative hospital stay, and mortality with 30 days after discharge were significantly higher in the real ARDS group than in the non-ARDS group (P < 0.05). After adjusting for confounding factors in the Cox survival analysis, the risk of death within 30 days after discharge was significantly higher in the real ARDS group than in the non-ARDS group (hazard ratio(HR): 4.633, 95% CI: 1.012–21.202, P < 0.05).ConclusionPreoperative hypoxemia is an independent risk factor for post-operative simple hypoxemia and ARDS. Post-operative ARDS with pre-operative normal oxygenation was the real ARDS, which was more severe and associated with a higher risk of death after surgery.

Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes. To test this hypothesis, we measured plasma Ang-2 in a cohort of 757 patients with sepsis, including 267 with ARDS, enrolled in the emergency department or early in their ICU course before the COVID-19 pandemic. Multivariable models were used to test the association of Ang-2 with the development of ARDS and 30-day morality. We found that early plasma Ang-2 in sepsis was associated with higher baseline severity of illness, the development of ARDS, and mortality risk. The association between Ang-2 and mortality was strongest among patients with ARDS and sepsis as compared to those with sepsis alone (OR 1.81 vs. 1.52 per log Ang-2 increase). These findings might inform models testing patient risk prediction and strengthen the evidence for Ang-2 as an appealing biomarker for patient selection for novel therapeutic agents to target vascular injury in sepsis and ARDS.

Lung Injury Risk in Traumatic Brain Injury Managed With Optimal Cerebral Perfusion Pressure Guided-Therapy.

Management of traumatic brain injury (TBI) has to counterbalance prevention of secondary brain injury without systemic complications, namely lung injury. The potential risk of developing acute respiratory distress syndrome (ARDS) leads to therapeutic decisions such as fluid balance restriction, high PEEP and other lung protective measures, that may conflict with neurologic outcome. In fact, low cerebral perfusion pressure (CPP) may induce secondary ischemic injury and mortality, but disproportionate high CPP may also increase morbidity and worse lung compliance and hypoxia with the risk of developing ARDS and fatal outcome. The evaluation of cerebral autoregulation at bedside and individualized (optimal CPP) CPPopt-guided therapy, may not only be a relevant measure to protect the brain, but also a safe measure to avoid systemic complications. We aimed to study the safety of CPPopt-guided-therapy and the risk of secondary lung injury association with bad outcome. Single-center retrospective analysis of 92 severe TBI patients admitted to the Neurocritical Care Unit managed with CPPopt-guided-therapy by PRx (pressure reactivity index). During the first 10 days, we collected data from blood gas, ventilation and brain variables. Evolution along time was analyzed using linear mixed-effects regression models. 86% were male with mean age 53±21 years. 49% presented multiple trauma and 21% thoracic trauma. At hospital admission, median GCS was 7 and after 3-months GOS was 3. Monitoring data was CPP 86±7mmHg, CPP-CPPopt -2.8±10.2mmHg and PRx 0.03±0.19. The average PFratio (PaO2/FiO2) was 305±88 and driving pressure 15.9±3.5cmH2O. PFratio exhibited a significant quadratic dependence across time and PRx and driving pressure presented significant negative association with PFRatio. CPP and CPPopt did not present significant effect on PFratio (p=0.533; p=0.556). A significant positive association between outcome and the difference CPP-CPPopt was found. Management of TBI using CPPopt-guided-therapy was associated with better outcome and seems to be safe regarding the development of secondary lung injury.

Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19

BackgroundThe use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN β) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocorticoids. Trial results showed deleterious effects of glucocorticoids when administered together with IFN β, and therefore, we aimed at finding the reason behind this.MethodsWe first sequenced the genes encoding the IFN α/β receptor of the patients, who participated in the INTEREST study (ClinicalTrials.gov Identifier: NCT02622724, November 24, 2015) in which the patients were randomized to receive an intravenous injection of IFN β-1a (144 patients) or placebo (152 patients). Genetic background was analyzed against clinical outcome, concomitant medication, and pro-inflammatory cytokine levels. Thereafter, we tested the influence of the genetic background on IFN α/β receptor expression in lung organ cultures and whether, it has any effect on transcription factors STAT1 and STAT2 involved in IFN signaling.ResultsWe found a novel disease association of a SNP rs9984273, which is situated in the interferon α/β receptor subunit 2 (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, more rapid decrease of IFN γ and interleukin-6 (IL-6) levels and better outcome in IFN β treated patients with ARDS, while the major allele associates with a poor outcome especially under concomitant IFN β and glucocorticoid treatment. Moreover, the minor allele of rs9984273 associates with a less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database.ConclusionsThe distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signaling and glucocorticoids.Graphical abstract

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

The future of paediatric acute respiratory distress syndrome

Heterogeneity is a familiar concept to paediatric intensive care physicians, because patients, pathologies, and treatments vary both within the paediatric intensive care unit (PICU) and within a given disease process. Paediatric acute respiratory distress syndrome (ARDS) typifies this problem. Children with ARDS vary in terms of age (and therefore lung development), underlying cause (pneumonia, sepsis, or trauma), pre-existing comorbid conditions, and baseline immunological state. There is not one pathway by which ARDS occurs or manifests, as indicated by the identification of hyperinflammatory and hypoinflammatory subtypes in adults and children. 1 Calfee CS Delucchi KL Sinha P et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018; 6: 691-698 Google Scholar , 2 Dahmer MK Yang G Zhang M et al. Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis. Lancet Respir Med. 2022; 10: 289-297 Google Scholar Furthermore, treatments probably differ in their effectiveness, with interventions that are beneficial in some patients but harmful in others, leading to a null population average treatment effect. 3 Prescott HC Calfee CS Thompson BT Angus DC Liu VX Toward smarter lumping and smarter splitting: rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med. 2016; 194: 147-155 Google Scholar Thus, important questions need to be addressed to improve the management and outcomes of paediatric ARDS. In a Series paper in The Lancet Respiratory Medicine, 4 Kneyber MCJ Khemani RG Bhalla A et al. Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome. Lancet Respir Med. 2022; (published online Dec 22.)https://doi.org/10.1016/S2213-2600(22)00483-0 Google Scholar Martin Kneyber and colleagues—a multinational group of paediatric ARDS experts—provide a welcome summary of where we are now as a field, and what tools are available to address challenges for the next generation of paediatric ARDS trials. Two key questions need to be considered to improve the management and outcomes of paediatric ARDS. First, can we improve outcomes by identifying mechanisms or pathways to target therapeutically within specific subgroups? And second, can this be done through a nuanced approach rather than through the use of blunt, pleiotropic instruments? Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndromePaediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Full-Text PDF

1210: THE METABOLIC SUBPHENOTYPE: A PROTECTIVE FACTOR IN ARDS SECONDARY TO SEPSIS OR PNEUMONIA

Introduction: Poor metabolic health increases the risk of COVID-19 acute respiratory distress syndrome (ARDS), however, its relationship with non-COVID-19 ARDS remains controversial. ARDS is often considered a heterogeneous disease caused by sepsis, pneumonia, trauma, transfusions, and aspiration. In this study, we hypothesized that metabolic inflammation may contribute to differential outcomes in ARDS primarily caused by infection. Methods: This was a secondary analysis of seven studies from the ARDS and Prevention and Early Treatment of Acute Lung Injury network trials within the Biologic Specimen and Data Repository Information Coordinating Center database. A metabolic subphenotype, defined by obesity, diabetes, and hypertension, was compared to a control population. The overall results showed lower adjusted mortality with this subphenotype. In this report, we performed stratified analyses to estimate effect modification by the metabolic subphenotype. We considered metabolic inflammation to reside along the causal pathway between infection and ARDS outcomes, and as such, stratified for primary ARDS etiology (e.g., sepsis or pneumonia as compared to other primary etiologies). The primary outcome was 28-day mortality. Secondary outcomes included 90-day mortality, ventilator free days, organ-failure free days, ICU free days, and length of hospital stay. Results: Among 4,288 ARDS trial participants, 3,205 (74.7%) had primary ARDS etiologies sepsis or pneumonia and 1,083 (25.3%) aspiration, trauma, transfusions, or other causes. Of those with sepsis or pneumonia, 364 (11.4%) met criteria for the subphenotype versus 2,841 (88.6%) control. In the non-infectious cohort, 90 (8.3%) met subphenotype criteria versus 993 (91.7%) control. In adjusted analyses, the subphenotype stratified by sepsis and pneumonia was associated with lower 28- and 90-day mortality (adjusted odds ratio [aOR] 0.64 [95%CI, 0.48-0.84] and aOR 0.69 [95%CI, 0.53-0.89], respectively). However, in ARDS due to other causes, analyses were not significant (mortality at 28 days, aOR 1.18 [95% CI, 0.70–1.99] and 90 days, aOR 1.26 [95% CI, 0.77–2.06]). Secondary outcomes were not significantly different. Conclusions: A metabolic subphenotype of ARDS is associated with lower risk of mortality in non-COVID ARDS primarily caused by sepsis or pneumonia.

PEEP titration by EIT strategies for patients with ARDS: A systematic review and meta-analysis

ObjectiveTo determine which method of Positive End-expiratory Pressure (PEEP) titration is more useful, and to establish an evidence base for the clinical impact of Electrical Impedance Tomography (EIT) based individual PEEP setting which appears to be a promising method to optimize PEEP in Acute Respiratory Distress Syndrome (ARDS) patients. DesignA systematic review and meta-analysis. Setting4 databases (PUBMED, EMBASE, Web Of Science, and the Cochrane Library) from 1980 to December 2020 were performed. ParticipantsRandomized clinical trials patients with ARDS. Main variablesPaO2/FiO2-ratio and respiratory system compliance. IntervensionThe quality of the studies was assessed with the Cochrane risk and bias tool. Results8 trials, including a total of 222 participants, were eligible for analysis. Meta-analysis demonstrates a significantly EIT-based individual PEEP setting for patients receiving higher PaO2/FiO2 ratio as compared to other PEEP titration strategies [5 trials, 202 patients, SMD 0.636, (95% CI 0.364−0.908)]. EIT-drived PEEP titration strategy did not significantly increase respiratory system compliance when compared to other peep titration strategies, [7 trials, 202 patients, SMD −0.085, (95% CI −0.342 to 0.172)]. ConclusionsThe benefits of PEEP titration with EIT on clinical outcomes of ARDS in placebo-controlled trials probably result from the visible regional ventilation of EIT. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of the EIT-based individual PEEP setting as a superior option for patients who undergo ARDS.

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. We present a first comprehensive molecular characterization of differences between two ARDS etiologies-COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.

Pneumonia and Related Conditions in Critically Ill Patients-Insights from Basic and Experimental Studies.

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia’s development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia. The theoretical study was carried out using the Columbia Open Health Data (COHD) resource, which provides access to clinical concept prevalence and co-occurrence from electronic health records. The experimental study included TREC/KREC assays in young adults (18–40 years) with community-acquired (CAP) (n = 164) or nosocomial (NP) (n = 99) pneumonia and healthy controls (n = 170). Co-occurring rates between pneumonia, sepsis, acute respiratory distress syndrome (ARDS) and some other related conditions common in intensive care units were the top among 4170, 3382 and 963 comorbidities in pneumonia, sepsis and ARDS, respectively. CAP patients had higher TREC levels, while NP patients had lower TREC/KREC levels compared to controls. Low TREC and KREC levels were predictive for the development of NP, ARDS, sepsis and lethal outcome (AUCTREC in the range 0.71–0.82, AUCKREC in the range 0.67–0.74). TREC/KREC analysis can be considered as a potential prognostic test in patients with pneumonia.