Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Extracorporeal membrane oxygenation support in adult patients: Comparing COVID-19- and non-COVID-19-associated respiratory failure.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a vital intervention for acute respiratory distress syndrome (ARDS), yet its efficacy with coronavirus disease 2019 (COVID-19) remains unknown. This study compared the long-term mortality rates of patients receiving ECMO for COVID-19 with those experiencing other respiratory disease-associated ARDS. METHODS: This retrospective cohort study included adults with ARDS receiving ECMO for respiratory disease (COVID-19 and non-COVID-19) based on information collected from the National Health Insurance Service of South Korea from February 1, 2020, to December 31, 2021. The primary outcome was all-cause mortality at 6 months and 1 year post-ECMO initiation. RESULTS: Data from 3094 patients with COVID-19 (N = 1095) and non-COVID-19 respiratory disease-associated ARDS (N = 1999) who received ECMO support were analyzed. Despite a higher Charlson Comorbidity index in the non-COVID group, patients with COVID-19 had higher cumulative mortality rates at 6 months and 1 year post-ECMO initiation compared to those with non-COVID-19 respiratory diseases, after adjusting for confounders. Patients with COVID-19 also experienced longer intensive care unit stays, higher hospitalization costs, longer ECMO and mechanical ventilation durations, and lower intensity coverage. CONCLUSIONS: Patients with COVID-19 requiring ECMO showed higher mortality rates, possibly due to its distinct long-lasting and potentially fatal consequences compared to other respiratory illnesses.

Laryngeal Mask for Minimally-Invasive Surfactant Administration: A Narrative Review.

The cornerstone of treatment for respiratory distress syndrome in preterm infants is surfactant administration, traditionally performed through an invasive procedure involving tracheal intubation and mechanical ventilation. Consequently, there has been a growing interest in exploring less invasive methods of surfactant delivery to mitigate the associated risks. Currently, several techniques are under evaluation, including intratracheal instillation using a thin catheter, aerosolized or nebulized administration, and guided administration by supraglottic airway devices. One such method is surfactant administration through laryngeal or supraglottic airway, which involves placing a laryngeal mask without the need for laryngoscopy and administering surfactant through the device. The simplicity of laryngeal mask insertion could potentially streamline the surfactant delivery process, eliminating the necessity for advanced skills. This narrative review aimed to assess the current evidence in the literature regarding the benefits and risks associated with surfactant administration through a laryngeal supraglottic airway.

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part II: In vivo Efficacy Testing in a Rabbit Surfactant Washout Model.

PURPOSE: Surfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product. In this study, we compare the in vivo performance of the new aerosol product with standard-of-care liquid instillation. METHODS: Juvenile rabbits were sedated, anesthetized, intubated, and ventilated. Endogenous surfactant was depleted via whole lung lavage. Animals received either a standard dose of liquid Curosurf (200 mg PL/kg) instilled via a tracheal catheter, SLS-EEG powder aerosol (60 mg device loaded dose; equivalent to 24 mg PL/kg), or sham control. Gas exchange, lung compliance, and indices of disease severity were recorded every 30 min for 3.5 h and macro- and microscopy images were acquired at necropsy. RESULTS: While aerosol was administered at an approximately tenfold lower PL dose, both liquid-instilled and aerosol groups had similar, nearly complete recoveries of arterial oxygenation (PaO2; 96-100% recovery) and oxygenation index, and the aerosol group had superior recovery of compliance (P < 0.05). The SLS-EEG aerosol group showed less lung tissue injury, greater uniformity in lung aeration, and more homogenous surfactant distribution at the alveolar surfaces compared with liquid Curosurf. CONCLUSIONS: The new dry powder aerosol SLS product (which includes the delivery strategy, formulation, and delivery system) has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation.

Impact of time intervals on drug efficacy and phenotypic outcomes in acute respiratory distress syndrome in mice.

Acute respiratory distress syndrome is a severe lung condition resulting from various causes, with life-threatening consequences that necessitate intensive care. The phenomenon can be modeled in preclinical models, notably through the use of lipopolysaccharide (LPS) instillation in mice. The phenotype induced closely recapitulates the human syndrome, including pulmonary edema, leukocyte infiltration, acute inflammation, impaired pulmonary function, and histological damage. However, the experimental designs using LPS instillations are extremely diverse in the literature. This highly complicates the interpretation of the induced phenotype chronology for future study design and hinders the proper identification of the optimal time frame to assess different readouts. Therefore, the definition of the treatment window in relation to the beginning of the disease onset also presents a significant challenge to address questions or test compound efficacy. In this context, the temporality of the different readouts usually measured in the model was evaluated in both normal and neutrophil-depleted male C57bl/6 mice using LPS-induction to assess the best window for proper readout evaluation with an optimal dynamic response range. Ventilation parameters were evaluated by whole-body plethysmography and neutrophil recruitment were evaluated in bronchoalveolar lavage fluids and in lung tissues directly. Imaging evaluation of myeloperoxidase along with activity in lung lysates and fluids were compared, along with inflammatory cytokines and lung extravasation by enzyme-linked immunoassays. Moreover, dexamethasone, the gold standard positive control in this model, was also administered at different times before and after phenotype induction to assess how kinetics affected each parameter. Overall, our data demonstrate that each readout evaluated in this study has a singular kinetic and highlights the key importance of the timing between ARDS phenotype and treatment administration and/or analysis. These findings also strongly suggest that analyzes, both in-life and post-mortem should be conducted at multiple time points to properly capture the dynamic phenotype of the LPS-ARDS model and response to treatment.

The influence of antenatal betamethasone timing on neonatal outcome in late preterm infants: a single-center cohort study.

PURPOSE: Many pregnancies continue after antenatal corticosteroid exposure. Since long-term effects on late preterm neonatal outcome remain controversial, it remains unknown whether pregnant women who are at risk for preterm birth during the late preterm period and had prior antenatal corticosteroid exposure would benefit from an additional course of antenatal corticosteroids. We evaluated the need for future trials on this topic by comparing short term effects from antenatal betamethasone to long-term effects. We also examined the value of a risk-adapted approach. METHODS: We observed neonatal outcomes in late preterm infants (34/0-36/0 weeks of gestation) who were exposed to antenatal betamethasone either up to 10 days prior birth (n = 8) or earlier in pregnancy (n = 89). We examined a real world population from the University Hospital Magdeburg (Germany) between 01 January 2012 and 31 December 2018, and a simulated high-risk population that was derived from the original data. RESULTS: The indicators for relevant adverse outcomes did not differ in the unselected population. In the simulated high-risk population, recent antenatal corticosteroid administration significantly reduced the incidence of relevant cardiorespiratory morbidities (OR = 0.00, p = 0.008), and reduced the number needed to treat from 3.7 to 1.5. CONCLUSION: The superiority of recent antenatal corticosteroid administration in the late preterm period over earlier exposure strongly depended on the prevalence of respiratory disease. Before considering clinical trials on additional antenatal corticosteroid courses in the late preterm period, antenatal assessment tools to predict respiratory morbidity need to be developed.

Impact of cardiovascular risk factors and cardiac diseases on mortality in patients with moderate to severe ARDS: A retrospective cohort study.

Background: History of coronary artery disease (CAD) and/or atrial fibrillation (AF) and/or valvular replacement (VR) are prevalent among patients admitted to intensive care units (ICUs). The impact of these conditions on outcomes in patients with acute respiratory distress syndrome (ARDS) remains insufficiently explored. Methods: We performed a retrospective study on prospectively collected data from patients with ARDS and a PaO2/FiO2 ratio ≤150 mmHg. Patients were admitted between January 2006 and March 2022. We used multivariable logistic regression analysis. The primary outcome was 1-year mortality from admission to the ICU; secondary outcomes included mortality at 28 days and 90 days. Results: Among 1.033 patients, 181 (17.5 %) had a history of CAD and/or AF and/or VR. History of CAD and/or AF and/or VR was independently associated with 1-year mortality (Odds-Ratio (OR) = 2.59, 95 % confidence interval (CI) 1.76-3.82, p < 0.001), with mortality at 90 days (OR = 1.87, 95 % CI 1.27-2.76, p = 0.001), but not with mortality at 28 days (OR = 1.40, 95 % CI 0.93-2.11, p = 0.10). In sensitivity analyses, history of CAD and/or AF and/or VR remained independently associated with 1-year mortality in ICU survivors (OR = 3.58, 95 % CI = 2.41-7.82, p < 0.001). Conclusions: History of CAD and/or AF and/or VR was associated with mortality in ARDS. Prompt referral to cardiologists for comprehensive management post-ICU discharge may be warranted to optimize outcomes in this vulnerable population.

Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation.

BACKGROUND: The optimal timing of weaning from venovenous extracorporeal membrane oxygenation (VV ECMO) and its modalities have been rarely studied. METHODS: Retrospective, multicenter cohort study over 7 years in two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients with ARDS on ECMO and successfully weaned from VV ECMO were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning. RESULTS: 292 adult patients with severe ARDS were weaned from controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95% CI], 1.23 [0.84-1.82]). ECMO-related complications were not statistically different between patients receiving these two mechanical ventilation strategies. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy, but not mechanical ventilation modalities during SGOT, were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning. CONCLUSIONS: Time to successful weaning from mechanical ventilation within 90 days post-ECMO was not associated with the mechanical ventilation strategy used during SGOT. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes.

Predicting Mortality in Sepsis-Associated Acute Respiratory Distress Syndrome: A Machine Learning Approach Using the MIMIC-III Database.

BACKGROUND: To develop and validate a mortality prediction model for patients with sepsis-associated Acute Respiratory Distress Syndrome (ARDS). METHODS: This retrospective cohort study included 2466 patients diagnosed with sepsis and ARDS within 24 h of ICU admission. Demographic, clinical, and laboratory parameters were extracted from Medical Information Mart for Intensive Care III (MIMIC-III) database. Feature selection was performed using the Boruta algorithm, followed by the construction of seven ML models: logistic regression, Naive Bayes, k-nearest neighbor, support vector machine, decision tree, Random Forest, and extreme gradient boosting. Model performance was evaluated using the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The study identified 24 variables significantly associated with mortality. The optimal ML model, a Random Forest model, demonstrated an AUC of 0.8015 in the test set, with high accuracy and specificity. The model highlighted the importance of blood urea nitrogen, age, urine output, Simplified Acute Physiology Score II, and albumin levels in predicting mortality. CONCLUSIONS: The model's superior predictive performance underscores the potential for integrating advanced analytics into clinical decision-making processes, potentially improving patient outcomes and resource allocation in critical care settings.

Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor.

BACKGROUND: Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases. AIM: To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models. METHODS: MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators. RESULTS: The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-ß and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05). CONCLUSION: MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals.

BACKGROUND: At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. METHODS: A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. RESULTS: Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at < 34 weeks of gestation (90·0% inborn vs. 50·0% outborn, p < 0·001). The median fraction of inspired oxygen (FiO2) for initial resuscitation was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001). Surfactant was used in 51·6% of the DRs. Less invasive surfactant administration (LISA) was used in 49·7% of the hospitals (tertiary hospitals: 55·3% vs. secondary hospitals: 31·5%, p < 0·001). Primary non-invasive ventilation was initiated in approximately 80·0% of the patients. High-frequency oscillation ventilation was primarily reserved for rescue after conventional mechanical ventilation (MV) failure. Caffeine was routinely used during MV in 59·1% of the hospitals. Bedside lung ultrasonography was performed in 54·3% of the health facilities (tertiary hospitals: 61·6% vs. secondary hospitals: 30·4%, p < 0·001). Qualified breast milk banks and Family Integrated Care (FICare) were present in 30·2% and 63·7% of the hospitals, respectively. CONCLUSIONS: Significant disparities in resource availability and guidelines adherence were evident across hospitals. Future strategies should address DR facilities and medication access, technical training, staff allocation, and ancillary facility development for a better management of RDS patients in China.

Understanding ventilator-induced lung injury: The role of mechanical power.

Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches. The concept of mechanical power has emerged as a comprehensive metric encompassing key ventilator parameters associated with the genesis of ventilator-induced lung injury, including volume, pressure, flow, resistance, and respiratory rate. While numerous animal and human studies have linked mechanical power and ventilator-induced lung injury, its practical implementation at the bedside is hindered by calculation challenges, lack of equation consensus, and the absence of an optimal threshold. To overcome the constraints of measuring static respiratory parameters, dynamic mechanical power is proposed for all patients, regardless of their ventilation mode. However, establishing a causal relationship is crucial for its potential implementation, and requires further research. The objective of this review is to explore the role of mechanical power in ventilator-induced lung injury, its association with patient outcomes, and the challenges and potential benefits of implementing a ventilation strategy based on mechanical power.

Pressure Control Surrogate Formula for Estimating Mechanical Power in ARDS is Associated with Mortality.

BACKGROUND: Mechanical power applied to the respiratory system (MPRS) is associated with ventilator-induced lung injury (VILI) and ARDS mortality. Absent automated ventilator MPRS measurements, the alternative is clinically unwieldy equations. However, simplified surrogate formulas are now available and accurately reflect values produced by airway pressure-volume curves. This retrospective, observational study examined whether the surrogate pressure-control equation alone could accurately assess mortality risk in ARDS subjects managed almost exclusively with volume-control ventilation.METHODS: 948 subjects were studied in whom invasive mechanical ventilation and implementation of ARDSNet ventilator protocols commenced ≤ 24hr after ARDS onset, and who survived > 24hr. MPRS was calculated as 0.098 x respiratory frequency x VT x (PEEP + driving pressure [PDR]). MPRS was assessed as a risk factor for hospital mortality, and compared between non-survivors and survivors across Berlin Definition classifications. In addition, mortality was compared across 4 MPRS thresholds associated with VILI or mortality (ie. 15, 20, 25 and 30 J/m).RESULTS: MPRS was associated with increased mortality risk: Odds Ratio (95% CI) of 1.06 (1.04-1.07) per J/m, P<0.001). Median MPRS differentiated non-survivors from survivors in Mild (24.7 vs. 18.5 J/m, respectively, P==0.034); Moderate (25.7 vs. 21.3 J/m, P<0.001); and Severe ARDS (28.7 vs. 23.5 J/m, P<0.001). Across 4 MPRS thresholds mortality increased from 23-29% when MPRS was < threshold vs. 38-51% when MPRS was > threshold (P<0.001). In the > cohort the Odds Ratio (95%CI) increased from 2.03 (1.34-3.12) to 2.51 (1.87-3.33).CONCLUSION: The pressure control surrogate formula is sufficiently accurate to assess mortality in ARDS, even when using volume control ventilation. In our subjects when MPRS exceeds established cut-off values for VILI or mortality risk, we found mortality risk consistently increased by a factor of > 2.0.

Corticosteroid Treatment for Leptospirosis: A Systematic Review and Meta-Analysis.

Background: Leptospirosis, a zoonotic disease prevalent in tropical regions, often leads to severe complications such as Weil's disease and acute respiratory distress syndrome (ARDS). This pioneering meta-analysis investigated the role of corticosteroids in treating severe leptospirosis, addressing a critical gap in the current clinical knowledge. Methods: We systematically reviewed studies from PubMed and Scopus, focusing on randomized controlled trials and observational cohort studies involving adult patients diagnosed with leptospirosis. Five studies comprising 279 participants met the inclusion criteria. Results: Although some studies suggest potential benefits, particularly for pulmonary complications, the evidence remains inconclusive due to the limited number of studies and their methodological limitations. Notably, while four of the five reviewed studies indicated a possible positive role of corticosteroids, the single randomized controlled trial showed no significant benefit, highlighting the need for more robust research. Conclusions: While the current evidence provides a basis for potential benefits, it is not sufficient to make definitive clinical recommendations. Further research is essential to clarify the role of corticosteroids in the treatment of severe leptospirosis, with the aim of improving patient outcomes and guiding clinical practices effectively.

Pirfenidone Alleviates Inflammation and Fibrosis of Acute Respiratory Distress Syndrome by Modulating the Transforming Growth Factor-ß/Smad Signaling Pathway.

Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-ß1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-ß1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.

Predictors and outcomes associated with right ventricular function in patients with adult respiratory distress syndrome treated with Veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Right ventricular dysfunction is associated with mortality in patients with acute respiratory distress syndrome (ARDS) but information in veno-venous extracorporeal membrane oxygenation (ECMO) settings is limited. Study objectives were to examine factors associated with right ventricular (RV) systolic dysfunction (RVSD) and RV dilation in ECMO patients with ARDS, to compare outcomes in those with and without RVSD and RV dilation defined by qualitative and quantitative parameters, and to describe RVSD evolution during ECMO. METHODS: Retrospective observational study of adult ARDS patients supported with ECMO at a tertiary care hospital. RESULTS: Of a total of 62 patients, 56% had RVSD and 61% had RV dilation by qualitative assessment. Male gender, COVID-19, hypercarbia, and pneumothorax were associated with RVSD and RV dilation. In-hospital mortality was significantly higher in patients with RV dilation vs. no dilation (42% vs. 17%, p = .05) but comparisons for patients with and without RVSD (37% vs. 26%, respectively) did not reach statistical significance. Findings were similar when RV size and function were quantified by right to left ventricle end-diastolic area ratio and fractional area change (39% vs. 21% and 36% vs. 20% respectively; p = NS). Of 39 patients with multiple echocardiograms, 9 of 18 with initially normal RV function developed RVSD while RV function normalized in 10 of 21 patients who began ECMO with RVSD. CONCLUSIONS: Study results suggest an association of RV dilation and RVSD with worse outcomes and a dynamic nature of RV function necessitating close monitoring during the ECMO course.

Efficacy of high-flow nasal oxygen therapy started in the emergency room versus conventional oxygen therapy in patients with acute hypoxaemic respiratory distress: protocol for a French multicentric, prospective, open and randomised superiority study protocol (HIFLOWED).

INTRODUCTION: Acute respiratory failure is a life-threatening condition frequently found in the emergency department. High-flow nasal oxygen (HFNO) is increasingly used in emergency departments for patients with hypoxaemic acute respiratory failure. However, despite the increasing number of studies, its potential advantages regarding the need for therapeutic escalation and mortality have not been precisely evaluated. Our objective is to compare conventional oxygen therapy to HFNO when they are initiated during the first hour following the patient's arrival at the emergency department, with the hypothesis that HFNO would reduce the need for ventilatory therapy escalation. METHODS AND ANALYSIS: This is a multicentric, prospective, open and randomised superiority study. 500 inpatients will be randomised (1:1) to receive conventional oxygen therapy or HNFO. The primary outcome is a failure in the oxygen therapy defined as the need for a therapeutic escalation within 4 hours after therapy initiation. ETHICS AND DISSEMINATION: The study has been submitted and approved by the Comité de Protection des Personnes Nord Ouest IV (20 October 2020). As required, a notification was sent to the Agence nationale de sécurité du médicament et des produits de santé (22 October 2020). The research results will be published in peer-reviewed publications and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT04607967.

Early reapplication of prone position during venovenous ECMO for acute respiratory distress syndrome: a prospective observational study and propensity-matched analysis.

BACKGROUND: A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. METHODS: In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. RESULTS: A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). CONCLUSIONS: Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019.