Severe Acute Respiratory Distress Syndrome Research Articles

Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis

Abstract Objective To investigate the relationship between the expression levels of serum forkhead box protein M1(FOXM1) and insulin-like growth factor 2 (IGF2) mRNA in patients with acute respiratory distress syndrome (ARDS) condition and prognosis. Methods Ninety patients with ARDS admitted to our hospital were regarded as the ARDS group, according to the prognosis, they were grouped into death group (n = 64) and survival group (n = 126); the control group consisted of 190 healthy individuals. Results Compared with the control group, the level of serum FOXM1 mRNA in ARDS group was obviously lower, and the level of IGF2 mRNA was higher. The serum IGF2 mRNA, serum creatinine, inhaled oxygen concentration (FiO2), and mechanical ventilation time in the death group were higher than those in the control group, and the arterial oxygen partial pressure (PaO2), FOXM1 mRNA, and oxygenation index (PaO2/FiO2) were lower than those in control group. Logistic regression analysis indicated that FOXM1, IGF2, and PaO2/FiO2 were significant factors influencing the prognosis and mortality in ARDS patients. Correlation analysis showed that there was a negative correlation between serum FOXM1 and IGF2 mRNA levels in patients with ARDS. Conclusion Serum FOXM1 and IGF2 mRNA in patients with ARDS are correlated with the severity and prognosis of ARDS.

Does prone positioning affect achievement of medical nutritional goals?

Objective: Prone position (PP) is used in the treatment of severe acute respiratory distress syndrome (ARDS). The aim of our study was to evaluate the effect of PP (>24 hours) on achieving medical nutritional goals. Materials and Methods: Between 2018 and 2022, a total of 385 patients in the Anesthesiology and Reanimation Intensive Care Unit (ICU) were included, 183 of whom were in the prone group and 202 in the Non-prone (NP) group, who underwent Invasive Mechanical Ventilator (IMV) support with ARDS. Demographic data, comorbidities and medical nutrition (MN) status of the patients were analysed retrospectively from the electronic database. The rate of achievement of MN targets on days 3.7.14 of the PP and NP groups was compared. Results: A statistically significant low level negative correlation was found in the correlation analysis between prone time and the rate of achievement of calorie and protein targets in the PP group patients (r=-0.370, p<0.001) (r=0.303, p<0.001). The rate of severe ARDS was statistically significantly higher in the PP group than in the NP group (P<0.001). The median duration of IMV in both patient groups was over 15 days and was statistically significantly higher in the PP patient group (p<0.001). Conclusion: PP delays the achievement of the target calorie and protein ratio, and some patients did not reach the target calorie and protein ratio.

Severe community-acquired pneumonia compared to severe community-acquired Acinetobacter baumannii pneumonia in Reunion Island: A retrospective study.

Acinetobacter baumannii (Ab) has emerged in the last decades as a cause of community-acquired pneumonia (CAP) in tropical and subtropical regions. We previously conducted the first investigation on this topic in France with a case series of severe CAP-Ab in Reunion Island over an eight-year period. In the present work, we aim to highlight the specific aspects of CAP-Ab by comparing our case series with an historical cohort (PAC_RUN), obtained by retrospective chart review (2016-2021) of severe community-acquired pneumonia cases on Reunion Island, in which CAP-Ab was ruled out. During the study period, eight CAP-Ab cases were identified, giving an incidence of 0.1 cases per 100,000 people/year, and an incidence of 16.5 cases per 100,000 people/year for non-Ab-related CAP (n = 761). By comparing with non-Ab-related CAP, patients had more excessive alcohol use (75% vs. 25.6%, p = 0.005) and lower body mass index (21 vs. 24 kg/m2, p = 0.004). Six cases (75%) of CAP-Ab occurred during the rainy season (p = 0.06). Mortality was higher (62.5% vs. 24.3%, p = 0.02) and time to death was shorter (median 2 days vs. 7, p = 0.009) in the CAP-Ab group. Bacteraemic pneumonia was strongly associated with CAP-Ab (62.5% vs. 15.7%, p = 0.004). Significant differences were found in the need for renal replacement therapy (75% vs. 17.2%, p < 0.001), catecholamine use (100% vs. 54.5%, p = 0.01) and use of invasive mechanical ventilation (100% vs. 62.7%, p = 0.03). Also, in the proportion of severe acute respiratory distress syndrome (62.5% vs. 23.2%, p = 0.02), septic shock (100% vs. 40.6%, p < 0.001), and cardiogenic shock (87.5% vs. 15.9%, p < 0.001). Compared to severe non-Ab-related CAP, severe CAP-Ab is characterised by higher mortality, associated with a high frequency of multiple organ failure. Excessive alcohol consumption and malnutrition seem to be risk factors. To improve outcomes, broader spectrum antibiotic therapy must be immediately proposed when CAP-Ab is suspected.

Survival difference in patients treated with extracorporeal membrane oxygenation in COVID-19 vs. non-COVID ARDS: a systematic review and meta-analysis.

The COVID-19 pandemic has emphasized the need for effective management of severe acute respiratory distress syndrome (ARDS) using veno-venous extracorporeal membrane oxygenation (VV-ECMO). This meta-analysis aims to compare the effectiveness and outcomes of ECMO in patients with COVID-19 ARDS versus those with non-COVID ARDS, assessing its role in different respiratory virus infections. A systematic search was conducted in PubMed, Web of Science, and other relevant databases up to June 30, 2023, to identify studies comparing ECMO use in COVID-19 and non-COVID ARDS cases. This analysis adheres to PRISMA guidelines, with studies rigorously selected based on predefined inclusion and exclusion criteria and assessed for bias using validated tools. The meta-analysis included 24 studies with 2,121 patients, revealing that non-COVID ARDS patients treated with ECMO had a lower mortality risk compared to those with COVID-19 ARDS. Specifically, the overall pooled risk difference in survival was -0.11 (95% CI: -0.17 to -0.05, P<0.001), indicating a statistically significant advantage for non-COVID patients. The standardized mean difference for ECMO duration was significantly longer in COVID-19 patients (SMD=0.70, 95% CI: 0.32 to 1.08, P<0.001), reflecting more prolonged treatment needs. ECMO serves as a vital intervention in severe ARDS, with differential effectiveness observed between COVID-19 and non-COVID patients. The study's findings underline the need for precise patient selection and tailored ECMO application across different viral etiologies. These insights are crucial for enhancing clinical strategies and resource allocation during ongoing and future pandemics.

Determination of positive end-expiratory pressure in COVID-19-related acute respiratory distress syndrome

BACKGROUND The impact of high positive end-expiratory pressure (PEEP) ventilation and the optimization of PEEP titration in COVID-19-induced acute respiratory distress syndrome (ARDS) continues to be a subject of debate. In this systematic review, we investigated the effects of varying PEEP settings on patients with severe ARDS primarily resulting from COVID-19 (C-ARDS). OBJECTIVES Does higher or lower PEEP improve the outcomes in COVID-19 ARDS? Does individually titrated PEEP lead to better outcomes compared with PEEP set by standardised (low and high ARDS network PEEP tables) approaches? Does the individually set PEEP (best PEEP) differ from PEEP set according to the standardised approaches (low and high ARDS network PEEP tables)? DESIGN Systematic review of observational studies without metaanalysis. DATA SOURCES We performed an extensive systematic literature search in Cochrane COVID-19 Study Register (CCSR), PubMed, Embase.com, Web of Science Core Collection, World Health Organization COVID-19 Global literature on coronavirus disease, World Health Organization International Clinical Trials Registry Platform (ICTRP), medRxiv, Cochrane Central Register of Controlled Trials until 24/01/2024. ELIGIBILITY CRITERIA Ventilated adult patients (≧18 years) with C-ARDS. RESULTS We screened 16 026 records, evaluated 119 full texts, and included 12 studies (n = 1431 patients) in our final data synthesis, none of them being a randomised controlled trial. The heterogeneity of study procedures and populations did not allow conduction of a meta-analysis. The results of those studies that compared lower and higher PEEP strategies in C-ARDS were ambiguous pointing out either positive effects on oxygenation with high levels of PEEP, or negative changes in lung mechanics. CONCLUSION The available evidence does not provide sufficient guidance for recommendations on optimal PEEP settings in C-ARDS. In general, well designed platform studies are needed to answer the questions raised in this review and, in particular, to investigate the use of individualised PEEP titration techniques and the inclusion of patients with different ARDS entities, severities and disease stages. TITLE REGISTRATION Our systematic review protocol was registered with the international prospective register of systematic reviews (PROSPERO 2021: CRD42021260303).

Identification and validation of respiratory subphenotypes in patients with COVID-19 acute respiratory distress syndrome undergoing prone position

BackgroundThe heterogeneity of acute respiratory distress syndrome (ARDS) patients is a challenge for the development of effective treatments. This study aimed to identify and characterize novel respiratory subphenotypes of COVID-19 ARDS, with potential implications for targeted patient management.MethodsConsecutive ventilated patients with PCR-confirmed COVID-19 infection, in which prone positioning was clinically indicated for moderate or severe ARDS, were included in a prospective cohort. The patients were assigned to development or validation cohorts based on a temporal split. The PaO2/FiO2 ratio, respiratory compliance, and ventilatory ratio were assessed longitudinally throughout the first prone session. The subphenotypes were derived and validated using machine learning techniques. A K-means clustering implementation designed for joint trajectory analysis was utilized for the unsupervised classification of the development cohort. A random forest model was trained on the labeled development cohort and used to validate the subphenotypes in the validation cohort.Results718 patients were included in a prospective cohort analysis. Of those, 504 were assigned to the development cohort and 214 to the validation cohort. Two distinct subphenotypes, labeled A and B, were identified. Subphenotype B had a lower PaO2/FiO2 response during the prone session, higher ventilatory ratio, and lower compliance than subphenotype A. Subphenotype B had a higher proportion of females (p < 0.001) and lung disease (p = 0.005), higher baseline SAPS III (p = 0.002) and SOFA (p < 0.001) scores, and lower body mass index (p = 0.05). Subphenotype B had also higher levels of the pro-inflammatory biomarker IL-6 (p = 0.017). Subphenotype B was independently associated with an increased risk of 60-day mortality (OR 1.89, 95% CI 1.51–2.36). Additionally, Subphenotype B was associated with a lower number of ventilator-free days on day 28 (p < 0.001) and a lower hospital length of stay (p < 0.001). The subphenotypes were reproducible in the validation cohort.ConclusionOur study successfully identified and validated two distinct subphenotypes of COVID-19 ARDS based on key respiratory parameters. The findings suggest potential implications for better patient stratification, risk assessment, and treatment personalization. Future research is warranted to explore the utility of these novel subphenotypes for guiding targeted therapeutic strategies in COVID-19 ARDS.

A Pilot Study of a Modified Swallowing Screening Tool for Critically Ill Patients in the Intensive Care Unit.

The lack of early assessment tools for swallowing function in patients in the intensive care unit (ICU) may lead to delays in oral intake. This study assessed the effectiveness of a new bedside swallowing screening tool in detecting dysphagia in patients in the ICU or isolation settings, where isolation settings refer to conditions such as COVID-19, where patient mobility is limited. We assessed swallowing function in 13 patients with severe acute respiratory distress syndrome. To ensure patient safety, a bedside preliminary investigation was performed to assess the patient's alertness level, and ultrasound findings of the vocal cords were obtained. Patients were nasogastric(NG) tube feeding or fasted if they did not meet a certain readiness level. Additionally, patients who passed the preliminary investigation underwent methylene blue dye or citric acid swallowing tests if they had or had not undergone tracheostomy, respectively. The Gugging Swallowing Screen (GUSS) test was used to determine whether an oral diet was appropriate. Of the 13 patients, 1 failed to meet the criteria during the preliminary examination, and 12 underwent the examination and initiated oral intake. Significant differences were found in the GUSS scores between the tracheostomy and non-tracheostomy groups but not in the examination validity. NG tube was implemented if the examination criteria were not met at each stage. Patients who passed the newly developed dysphagia screening tool exhibited no aspiration symptoms post-oral feeding initiation, enabling their discharge. In conclusion, the proposed screening test can be performed safely and easily, allowing for early dysphagia detection, reduced aspiration risk, and safe oral feeding in patients in the ICU or isolation settings.

Epigenetic mechanisms mediate cytochrome P450 1A1 expression and lung endothelial injury caused by MRSA invitro and invivo.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of severe pneumonia and acute respiratory distress syndrome (ARDS). To advance our mechanistic understanding of this important pathogen, we characterized the effects of MRSA-induced epigenetic modification of histone 3 lysine 9 acetylation (H3K9ac), an activator of gene transcription, on lung endothelial cells (EC), a critical site of ARDS pathophysiology. Chromatin immunoprecipitation and sequencing (ChIP-seq) analysis revealed that MRSA induces H3K9ac in the promoter regions of multiple genes, with the highest ranked peak annotated to the CYP1A1 gene. Subsequent experiments confirm that MRSA increases CYP1A1 protein and mRNA expression, and its enzymatic activity in EC. Epigenetic inhibitors (C646, RVX-208) reduce MRSA-induced CYP1A1 expression and inflammatory responses, including cytokine release and adhesion molecule expression. Inhibition of the Aryl hydrocarbon receptor (Ahr), a known mediator of CYP1A1 expression, blocks MRSA-induced upregulation of CYP1A1 mRNA and protein expression, enzyme activity, and cytokine release. Reduction of CYP1A1 protein expression by siRNA or inhibition of its activity by rhapontigenin attenuated MRSA-induced EC permeability and inflammatory responses. In a mouse model of MRSA-induced acute lung injury (ALI), inhibition of CYP1A1 activity by rhapontigenin improved multiple indices of ALI, including bronchoalveolar lavage (BAL) protein concentration, cytokine levels, and markers of endothelial damage. Analysis of publicly available data suggests upregulation of CYP1A1 expression in ARDS patients compared to ICU controls. In summary, these studies provide new insights into MRSA-induced lung injury and identify a novel functional role for epigenetic upregulation of CYP1A1 in lung EC during ARDS pathogenesis.

Does the Intensity of Therapy Correspond to the Severity of Acute Respiratory Distress Syndrome (ARDS)?

Objectives: The intensity of respiratory treatment in acute respiratory distress syndrome (ARDS) is traditionally adjusted based on oxygenation severity, as defined by the mild, moderate, and severe Berlin classifications. However, ventilator-induced lung injury (VILI) is primarily determined by ventilator settings, namely tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP). All these variables, along with respiratory elastance, are included in the concept of mechanical power. The aim of this study is to investigate whether applied mechanical power is proportional to oxygenation severity. Methods: We analyzed 291 ARDS patients (71 mild, 155 moderate, and 65 severe). We defined low, middle, and high mechanical power by dividing the entire population into tertiles with a similar number of patients. In each oxygenation class, we measured computed tomography (CT) anatomy, gas exchange, respiratory mechanics, mechanical power, and mortality rate. Results: ARDS severity was proportional to lung anatomy impairment, as defined by quantitative CT scans (i.e., lung volume and well-aerated tissue decreased across the ARDS classes, while respiratory elastance increased, as did mortality). Mechanical power, however, was similarly distributed across the severity classes, as the decrease in tidal volume in severe ARDS was offset by an increase in respiratory rate. Within each ARDS class, mortality increased from low to high mechanical power (roughly 1% for each J/min increase). Conclusions: Both lung severity and mechanical power independently impact mortality rates. It is tempting to speculate that ARDS severity primarily reflects the natural course of the disease, while mechanical power primarily reflects the risk of VILI.

Severe Acute Respiratory Distress Syndrome in an Adult Patient With Human Metapneumovirus Infection Successfully Managed With Veno-Venous Extracorporeal Membrane Oxygenation.

Human metapneumovirus (hMPV), a ubiquitous RNA virus of the Pneumoviridae family, has been associated with respiratory tract infections for decades in various age groups and populations. Though most of the infections, especially in children, are mild and self-limited, severe infections ranging from bronchiolitis or asthma exacerbation to severe pneumonia and acute respiratory distress syndrome (ARDS) have occasionally been reported. Among patients who require hospitalization for severe infections, treatment is supportive as no current antivirals or vaccines are effective or recommended. The following is a 45-year-old Caucasian man who developed severe ARDS complicating hMPV infection, and despite maximal medical support, he developed refractory life-threatening hypoxemia that required rescue therapy with veno-venous extracorporeal membrane oxygenation (V-V ECMO). After several days of ECMO support, the patient eventually recovered and was discharged home. This case highlights the importance of recognizing hMPV as an occasional culprit for severe respiratory infections, discusses the new global definition of ARDS, and delineates the updated recommended management, including the early application of V-V ECMO as a rescue therapy in severe cases with refractory, life-threatening respiratory failure.

Systemic Coagulation Derangement as an Early Sign of Oxygenator Failure in Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) Without Anticoagulation

Background and Clinical Significance: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a widely accepted supportive treatment for severe acute respiratory distress syndrome (ARDS) in intensive care units (ICUs). Although it has gained popularity, some of its aspects, including optimal anticoagulation management and the best means of monitoring hemostasis, remain unresolved. Thrombosis and bleeding are still important complications of ECMO. Case Presentation: A 44-year-old male patient, with no underlying conditions, was diagnosed with severe acute respiratory distress syndrome (ARDS) due to AH1N1 influenza. He presented severe hypoxemia despite the use of mechanical ventilation, neuromuscular blocking agent infusion and prone position. VV ECMO was used, and coagulation was stopped on ECLS day 6 due to severe pulmonary hemorrhage. The systemic hemostatic disorders found in this patient were difficult to differentiate from disseminated intravascular coagulation (DIC) or sepsis-induced coagulopathy (SIC), improved transiently after circuit exchange, and resolved only after discontinuation of ECMO. The patient was discharged fully conscious and cooperative, with no apparent neurological deficit. Conclusions: Systemic hemostatic abnormalities may precede oxygenator failure and mimic DIC or SIC. Timely oxygenator exchange may therefore be considered. However, it is a high-risk procedure, especially in fully ECLS-dependent patients.

The use of a heated helium-oxygen mixture in patients with severe COVID-19 and ARDS against the background of standard therapy and noninvasive ventilation

Introduction. One of the insufficiently studied methods of Acute Respiratory Distress Syndrome (ARDS) therapy is therapy with a heated helium-oxygen mixture. Due to physico-chemical properties, helium demonstrates high efficiency in the treatment of various diseases of the pulmonological profile.Aim. To study the effect of a heated helium-oxygen mixture on the course of a severe form of COVID-19 occurring with the development of ARDS.Materials and methods. The study involved 58 patients with severe and extremely severe coronavirus infection and ARDS, divided into the NVL + t-He/O2 group (n = 30) and the NVL+O2 control group (n = 28). In addition to standard treatment, patients of the NVL + t-He/O2 group received noninvasive ventilation (NVL) and therapy with a heated helium-oxygen mixture, according to clinical recommendations. In the main group, inhalations took place daily for 60 minutes per day for 5 days.Results. Against the background of therapy with a heated helium-oxygen mixture, a more intense increase in the level of lymphocytes was observed: 1.39 (1.09–1.66) × 109/l in the NVL + t-He/O2 group versus 1.02 (0.78–1.40) × 109/l (p = 0.02). Also, as a result of treatment, there was a significant decrease in RR, D-dimer and CRP in the study group: the level of RR (21 (20–22)/minute versus 22.5 (21–24)/minute, p = 0.003), D-dimer (0.44 (0.29–0.60) FEU ng/ml versus 0.79 (0.42–1.34) FEU ng/ml, p = 0.02) and CRP (1.1 (0.7–3.1)mg/l versus 16.6 (8.5–29.5) mg/l, p = 0.03), respectively. Similarly to the NVL + t-He/O2 group, an increase in the level of PaO2 and the oxygenation index was noted. In addition, there were significantly fewer patients with grade III and IV lung damage in the NVL + t-He/O2 group compared with the control (p = 0.05).Conclusion. The use of a heated helium-oxygen mixture in patients with severe COVID-19, occurring with the development of ARDS, against the background of standard therapy and NIV has shown its safety and effectiveness: there was a decrease in the intensity of inflammation, improved oxygenation and a reduction in the need for respiratory support.

Evolution of the oxyhemoglobin dissociation curve in COVID-19 related ARDS patients.

Severe hypoxemia is the leading cause of admission in intensive care (ICU) in patients with COVID-19 related acute respiratory distress syndrome (ARDS). In these patients, several studies reported a left shift of the oxyhemoglobin dissociation curve associated with a lower mortality. However, these results are conflicting, as these studies include few patients and often no control groups. Moreover, the calculation of P50, representing the PaO2 value at which 50% of hemoglobin is saturated, is not corrected for factors known to influence it (pH, PaCO2 or temperature). For all of these reasons, we compared the corrected P50 between ICU patients with severe COVID-19 related ARDS on mechanical ventilation or not, and ARDS from other causes. We investigated the evolution of the corrected P50 during the first 3 days of ICU and its relationship with ICU mortality. We retrospectively calculated the corrected P50 in three groups of patients: intubated and mechanically ventilated COVID-19 related ARDS, non-intubated COVID-19 related ARDS and intubated patients with ARDS due to other infectious causes. The corrected P50 was calculated, on the worst blood gas analysis on days 1 and 3 of ICU admission, by the formula of Hill but modified by Dash et al., controlled for pH, PaCO2 and temperature. We collected ICU mortality. 463 blood gas analysis at days 1 and 3 from 214 ICU COVID-19 related ARDS patients (114 with intubation and 100 without) and 35 ICU patients with ARDS from other causes were analyzed. All patients were severely hypoxemic: PaO2/FiO2 of 76 [58-108] mmHg for intubated COVID-19, 79 [60-108] mmHg for non-intubated COVID-19 and 142 [78-197] mmHg for the third group (p < 0.001). The mortality rate was higher in intubated COVID-19 related ARDS patients (44.7 versus 14 versus 37% in ARDS from other causes; p < 0.001). The corrected P50 was significantly lower in COVID-19 patients, especially in non- intubated patients (21.2 [18.8-25.2] mmHg vs. 25.5 [19.2-30.3] mmHg in intubated patients; compared to ARDS from other causes: 27.2 [23.3-35.4] mmHg; p < 0.001. The corrected P50 does not change over the first 3 days, except for the non intubated COVID-19 related ARDS and is not correlated with ICU mortality (odds ratio = 0.98 [0.95-1.03]; p = 0.51), in contrast of PaO2/FiO2 and ICU gravity scores. The oxyhemoglobin dissociation curve at ICU admission was left shifting in severe COVID-19 related ARDS patients regardless of the type of ventilation. This deviation increases the third day only in non-intubated COVID-19 related ARDS and was not related to the outcome.

Study on the clinical characteristics, treatment, and outcome influencing factors of severe pneumonia complicated with ARDS.

To investigate the clinical characteristics, treatment methods, and factors influencing the prognosis of patients with severe pneumonia complicated by Acute Respiratory Distress Syndrome (ARDS), aiming to provide references for clinical decision-making and improve patient outcomes. A retrospective analysis was conducted on 118 patients with severe pneumonia complicated by ARDS treated at our hospital from June 2018 to December 2022. Based on treatment outcomes, patients were divided into a death group (n = 75) and a survival group (n = 43). General data and clinical laboratory indicators, including blood urea nitrogen, serum creatinine, C-reactive protein, procalcitonin, arterial partial pressure of oxygen, and arterial partial pressure of carbon dioxide, were collected and compared between the 2 groups to identify independent factors affecting prognosis. Among the 118 patients, the mortality rate was 63.56%. Patients in the death group had a significantly higher average age (57.15 ± 13.38 years) and a higher proportion of severe ARDS (66.67%) compared to the survival group (40.02 ± 11.41 years, 30.23%, P < .001). The death group had significantly lower white blood cell counts (8.10 ± 1.64 × 109/L), oxygenation index (19.82 ± 2.29), and duration of mechanical ventilation (7.79 ± 2.11 days) compared to the Survival group (8.92 ± 1.22 × 109/L, 13.42 ± 1.82, 12.23 ± 3.05 days, P < .05). Conversely, the death group had significantly higher levels of blood urea nitrogen (6.87 ± 1.80 mmol/L), C-reactive protein (130.55 ± 50.28 mg/L), procalcitonin (5.50 ± 2.11 ng/mL), arterial partial pressure of carbon dioxide (41.12 ± 5.56 mm Hg), and a higher proportion of viral infections (48.00%) compared to the survival group (5.90 ± 1.72 mmol/L, 101.77 ± 55.56 mg/L, 3.98 ± 1.15 ng/mL, 35.59 ± 6.22 mm Hg, 27.91%, P < .05). Logistic regression analysis revealed that age (odds ratios [OR] = 1.990, 95% confidence interval [CI]: 1.306-3.033, P < .001), oxygenation index (OR = 1.426, 95% CI: 1.123-1.649, P < .001), and duration of mechanical ventilation (OR = 0.694, 95% CI: 0.557-0.864, P < .001) were independent factors influencing patient prognosis. This indicates that an increase in age and a decrease in oxygenation index are associated with a significantly higher risk of mortality, while shorter mechanical ventilation duration is related to poorer prognosis. Advanced age, lower oxygenation index, and shorter duration of mechanical ventilation are unfavorable prognostic factors in patients with severe pneumonia complicated by ARDS. These findings aid clinicians in identifying high-risk patients, optimizing treatment plans, and improving patient prognosis.

Heterogeneous Treatment Effects of High-Frequency Oscillatory Ventilation for Acute Respiratory Distress Syndrome: A Post Hoc Analysis of the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) Trial.

We sought to evaluate whether different subgroups of adults with acute respiratory distress syndrome (ARDS) respond differently to high-frequency oscillatory ventilation (HFOV). The Oscillation for ARDS Treated Early (OSCILLATE) trial was a randomized controlled trial of HFOV vs. conventional ventilation that found an increased risk of in-hospital mortality (primary outcome) with HFOV. In a post hoc analysis, we applied three different approaches to evaluate heterogeneity of treatment effect for in-hospital mortality: 1) subgroup analyses based on baseline Pao2:Fio2 ratio and oxygenation index (OI); 2) a risk-based approach using a multivariable outcome prediction model; and 3) a clustering approach via multivariable latent class analysis. We used multivariable logistic regression models to assess for interaction. Thirty-nine ICUs, five countries. Five hundred forty-eight adults with moderate to severe ARDS. HFOV vs. conventional mechanical ventilation with low tidal volume and higher positive end-expiratory pressure. The effect of HFOV on in-hospital mortality was consistent across categories of Pao2:Fio2 ratio (adjusted odds ratio [aOR], 2.04; 95% CI, 1.32-3.17 and aOR, 1.16; 95% CI, 0.49-2.75 for groups with Pao2:Fio2 above or equal to 80, vs. below 80, respectively; interaction p = 0.23) and OI (aOR, 1.78; 95% CI, 0.67-4.70; aOR, 3.19; 95% CI, 1.44-7.09; aOR, 1.73; 95% CI, 0.82-3.65; and aOR, 1.33; 95% CI, 0.61-2.90 for quartiles of baseline OI, respectively; interaction p = 0.44). Point estimates for the effect of HFOV were consistent across risk categories (aOR, 2.44; 95% CI, 0.40-14.83; aOR, 1.69; 95% CI, 0.75-3.85; and aOR, 2.10; 95% CI, 0.59-7.54 for the lowest, moderate, and highest risk categories, respectively; interaction p = 0.32). Using a clustering approach, point estimates for HFOV were also consistent (cluster 1: aOR, 1.85; 95% CI, 1.15-3.00 and cluster 2: aOR, 1.75; 95% CI, 0.91-3.38; interaction p = 0.75). We did not identify heterogeneity in the effect of HFOV across different subgroups of patients with ARDS.

Anticoagulation management during veno-venous ECMO support because of ARDS: Single-center experience

BackgroundPatients with severe acute respiratory distress syndrome (ARDS) show a high mortality rate of up to 60 %. In such cases, extracorporeal membrane oxygenation (ECMO) support is often required, which would necessitate anticoagulation therapy, predominantly with heparin. Some bleeding events occurred more frequently in patients during the COVID-19 pandemic who were on venovenous (V-V) ECMO, so it is necessary to investigate whether anticoagulation management should be adjusted. MethodsWe collected data on 90 patients with severe ARDS who underwent ECMO support at the University Hospital Magdeburg between 2014 and 2022. In order to estimate the role of anticoagulation therapy as a cause of bleeding, patients were divided into two groups based on their mean activated partial thromboplastin time (aPTT): one group with a mean aPTT of more than 58 s (45 patients) and another with a mean aPTT of less than 58 s (45 patients). Demographic data, data before, during ECMO support, and bleeding complications were retrospectively recorded. We compared laboratory parameters before ECMO, essential coagulation parameters on days 3, 7, 10 of ECMO support, before the bleeding event occurred, and analyzed hospital survival in both groups. ResultsThe incidence of major bleeding complications was significantly higher in the group of patients with higher aPTT (68.9 % vs 33.3 %, p < 0.001), the differences in the occurrence of hemothorax were especially significant (28.9 % vs 2.2 %, p < 0.001). We observed better hospital patients’ survival in the group with lower aPTT (40.0 % vs 68.9 %, p = 0.006). The results of the bivariate analysis indicate that the independent predictors of hospital mortality in adult patients receiving V-V ECMO support due to severe ARDS were COVID-19 (OR: 3.504; 95 % confidence interval [CI]: 1.415–8.681, p = 0.007) acute liver failure (OR: 8.0000; 95 % CI: 1.692–37.822; p = 0.009), high antithrombin level (%) (OR: 1.036; 95 % CI: 1.003–1.071, p = 0.035). A high mean aPTT level increased the risk of major bleeding (OR: 1.080; 95 % CI: 1.016–1.148, p = 0.014) without a significant increase in mortality. ConclusionProlonged aPTT during V-V ECMO support in patients with ARDS significantly impacts the risk of major bleeding, especially hemothorax, without significant increase in hospital mortality.

Vision Disturbance (not vision loss) following Epinephrine Injection

Patients with severe acute respiratory distress syndrome require supportive treatment with mechanical ventilation with or without extracorporeal membrane oxygenation to maintain optimal oxygenation. Persistent inefficient blood oxygenation can be related to severity of clinical presentation, technical issues, or concomitant diseases. In this case report, man previously suffering from chronic myeloid leukemia received extracorporeal membrane oxygenation for influenza A virus subtype H1N1. Despite invasive oxygenation therapy, it was not possible to achieve amelioration of arterial blood oxygenation. After a differential diagnosis, pathological hyperleukocytosis was identified as a potential reason of oxygenation impairment, which improved after introduction of concomitant chemotherapy that lowered leukocytes count.

The silent predictors: exploring galectin-3 and Irisin’s tale in severe COVID-19

ObjectiveThis study aimed to evaluate the roles of galectin-3 and irisin as biomarkers in predicting severe outcomes in COVID-19 patients.ResultsWe analyzed serum levels of galectin-3 and irisin in 59 patients with severe COVID-19 and 30 healthy controls. Elevated galectin-3 levels were associated with increased risks of mortality, need for intensive care, and severe acute respiratory distress syndrome. The optimal cut-off value for galectin-3 was 13.47 ng/ml, with a sensitivity of 72.7% and specificity of 76.6%. Irisin levels did not differ significantly between survivors and non-survivors at admission or on the 3rd day post-admission, but approached significance on the 7th day. These findings suggest that galectin-3 could be a valuable prognostic biomarker for severe COVID-19 outcomes, while irisin’s role remains to be clarified in further studies.

Identification of novel sub-phenotypes of severe ARDS requiring ECMO using latent class analysis

BackgroundSub-phenotyping of acute respiratory distress syndrome (ARDS) could be useful for evaluating the severity of ARDS or predicting its responsiveness to given therapeutic strategies, but no studies have yet investigated the heterogeneity of patients with severe ARDS requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO).MethodsWe conducted this retrospective multicenter observational study in adult patients with severe ARDS treated by V-V ECMO. We performed latent class analysis (LCA) for identifying sub-phenotypes of severe ARDS based on the radiological and clinical findings at the start of ECMO support. Multivariate Cox regression analysis was conducted to investigate the differences in mortality and association between the PEEP setting of ≥ 10 cmH2O and mortality by the sub-phenotypes.ResultsWe identified three sub-phenotypes from analysis of the data of a total of 544 patients with severe ARDS treated by V-V ECMO, as follows: Dry type (n = 185; 34%); Wet type (n = 169; 31%); and Fibrotic type (n = 190; 35%). The 90-days in-hospital mortality risk was higher in the patients with the Fibrotic type than in those with the Dry type (adjusted hazard ratio [95% confidence interval] 1.75 [1.10–2.79], p = 0.019) or the Wet type (1.50 [1.02–2.23], p = 0.042). The PEEP setting of ≥ 10 cmH2O during the first 3 days of ECMO decreased the 90-days in-hospital mortality risk only in patients with the Wet type, and not in those with the Dry or Fibrotic type. A significant interaction effect was observed between the Wet type and the PEEP setting of ≥ 10 cmH2O in relation to the 90-day in-hospital mortality (pinteraction = 0.036).ConclusionsThe three sub-phenotypes showed different mortality rates and different relationships between higher PEEP settings in the early phase of V-V ECMO and patient outcomes. Our data suggest that we may need to change our management approach to patients with severe ARDS during V-V ECMO according to their clinical sub-phenotype.

Pathophysiological Markers of Acute Respiratory Distress Syndrome Severity Are Correlated With Ventilation-Perfusion Mismatch Measured by Electrical Impedance Tomography.

Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch. Prospective observational study. General ICU of a university-affiliated hospital. Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation. Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers. Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure (r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph (r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue (r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan. In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance.