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Background: Bacterial pneumonia is one of the most common causes of acute respiratory distress syndrome. In fulminant cases, when mechanical ventilation fails, veno-venous extracorporeal membrane oxygenation is required. However, this method is still associated with significant mortality and a wide range of potential complications. However, there are now many case reports of good outcomes even in patients with prolonged extracorporeal oxygenation, as in our rather complicated case report. Case presentation: Our case report describes a complicated but successful treatment of a severe, devastating bacterial pneumonia in a 39-year-old European polymorbid woman with a rare form of diabetes mellitus, which had been poorly compensated for a long time with limited compliance, in the context of a combined immunodeficiency that strongly influenced the course of the disease. The patient's hospitalization required a total of 30 days of veno-venous extracorporeal membrane oxygenation therapy and more than 50 days of mechanical ventilation. Numerous complications, particularly bleeding, required seven chest drains, two extracorporeal membrane oxygenation circuit changes, and one surgical revision. The patient's mental state required repeated psychiatric intervention. Conclusion: It is possible that even the initially severely damaged lung parenchyma can develop its regenerative potential if suitable conditions are provided for this process, including a sufficiently long period of extracorporeal membrane oxygenation. We believe that this case report may also contribute to the consideration of the indications and contraindications of extracorporeal support. The authors also discuss the limitations and risks of prolonged veno-venous extracorporeal membrane oxygenation support and periprocedural anticoagulation strategies. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods: Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results: Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes. Conclusions: Coagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports. Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201). Clinical Perspective: Coagulation disorders such as thrombotic or hemorrhagic events are frequent in COVID-19 ARDS patients receiving ECMO. While older age, pre-existing cardiac disease, and diabetes were independently associated with bleeding, prone positioning and a longer time from admission to ECMO were associated with a higher percentage of thrombotic events. A longer duration of ECMO was linked to an increased rate of combined hemorrhagic and thrombotic events. [ABSTRACT FROM AUTHOR]

Background: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and after lower respiratory tract PCR testing, Legionella was determined to be the cause. She was successfully treated and decannulated from VV-ECMO after eight days. Case presentation: A 53-year-old female presented with one week of dyspnea and a positive COVID-19 test. She was hypoxemic, hypotensive and had bilateral infiltrates on imaging. She received supplemental oxygen, intravenous fluids, vasopressors, broad spectrum antibiotics, and was transferred to a tertiary care center. She developed progressive hypoxemia and suffered a cardiac arrest, requiring ten minutes of CPR and endotracheal intubation to achieve return of spontaneous circulation. Despite mechanical ventilation and paralysis, she developed refractory hypoxemia and was cannulated for VV-ECMO. Dexamethasone and remdesivir were given for presumed COVID-19. Bronchoscopy with bronchoalveolar lavage (BAL) performed with PCR testing was positive for Legionella pneumophila and negative for COVID-19. Steroids and remdesivir were discontinued and she was treated with azithromycin. Her lung compliance improved, and she was decannulated after eight days on VV-ECMO. She was discharged home on hospital day 16 breathing room air and neurologically intact. Conclusions: This case illustrates the utility of rapid PCR testing to diagnose Legionella in patients with respiratory failure and the early use of VV-ECMO in patients with refractory hypoxemia secondary to Legionella infection. Moreover, many patients encountered in the ICU may have prior COVID-19 immunity, and though a positive COVID-19 test may be present, further investigation with lower respiratory tract PCR testing may provide alternative diagnoses. Patients with ARDS should undergo Legionella-specific testing, and if Legionella is determined to be the causative organism, early VV-ECMO should be considered in patients with refractory hypoxemia given reported high survival rates. [ABSTRACT FROM AUTHOR]

Background: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. Methods: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. Results: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19–2.63], p = 0.005 and 1.97 [1.02–3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14–0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. Conclusions: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is still a major contributor to the global health burden. Pulmonary TB can lead to life-threatening respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) therapy. However, data on ECMO experience in the management of TB patients are scarce. Methods: We conducted a systematic review of the literature using the search terms ECMO, extracorporeal membrane oxygenation, TB and tuberculosis in three databases (Medline, Web of Science and EMBASE). Clinical data were extracted by two independent investigators. Clinical parameters, such as mode of ECMO therapy, duration of treatment and clinical outcomes, were assessed. Results: Overall, 43 patients from 15 countries were included in the analysis. The age ranged from 0 to 65 years, 39.5% were male, and 60.5% were female. The majority of patients suffered from ARDS (83.4%), with a mean Horovitz quotient of 68.1 (range 30.0–131.0). 83.7% received VV-ECMO, and 24.3% received VA-ECMO. Coinfections and complications were frequently observed (45.5% and 48.6% respectively). At the end of the respective observation period, the overall outcome was excellent, with 81.4% survival. Discussion: ECMO therapy in TB patients appears to be a feasible therapeutic option, providing a bridge until antimycobacterial therapy takes effect. As the underlying cause is reversible, we advocate for the evaluation of ECMO usage in these patients with acute cardiac or respiratory failure. [ABSTRACT FROM AUTHOR]

Background: Venovenous extracorporeal membrane oxygenation (VV ECMO) has been widely used for severe acute respiratory distress syndrome (ARDS) in recent years. However, the role of hemoadsorption in ARDS patients requiring VV ECMO is unclear. Methods: Therefore, we conducted a systematic review to describe the effect of hemoadsorption on outcomes of ARDS patients requiring VV ECMO and elucidate the risk factors for adverse outcomes. We conducted and reported a systematic literature review based on the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The systematic review searched Embase, CINHAL, and Pubmed databases for studies on ARDS patients receiving hemoadsorption and VV ECMO. The demographic data, clinical data and biological data of the patients were collected. Results: We ultimately included a total of 8 articles including 189 patients. We characterized the population both clinically and biologically. Our review showed most studies described reductions in inflammatory markers and fluid resuscitation drug dosage in ARDS patients with Coronavirus disease 2019 (COVID-19) or sepsis after hemoadsorption. Conclusion: Because most of the studies have the characteristics of high heterogeneity, we could only draw very cautious conclusions that hemoadsorption therapy may enhance hemodynamic stability in ARDS patients with COVID-19 or sepsis receiving VV ECMO support. However, our results do not allow us to draw conclusions that hemoadsorption could reduce inflammation and mortality. Prospective randomized controlled studies with a larger sample size are needed in the future to verify the role of hemoadsorption in ARDS patients requiring VV ECMO. [ABSTRACT FROM AUTHOR]

Background: VenoVenous ExtraCorporeal Membrane Oxygenation (VV-ECMO) has been widely used as supportive therapy for severe respiratory failure related to Acute Respiratory Distress Syndrome (ARDS) due to coronavirus 2019 (COVID-19). Only a few data describe the maximum time under VV-ECMO during which pulmonary recovery remains possible. The main objective of this study is to describe the outcomes of prolonged VV-ECMO in patients with COVID-19-related ARDS. Methods: This retrospective study was conducted at a tertiary ECMO center in Brussels, Belgium, between March 2020 and April 2022. All adult patients with ARDS due to COVID-19 who were managed with ECMO therapy for more than 50 days as a bridge to recovery were included. Results: Fourteen patients met the inclusion criteria. The mean duration of VV-ECMO was 87 ± 29 days. Ten (71%) patients were discharged alive from the hospital. The 90-day survival was 86%, and the one-year survival was 71%. The evolution of the patients was characterized by very impaired pulmonary compliance that started to improve slowly and progressively on day 53 (± 25) after the start of ECMO. Of note, four patients improved substantially after a second course of steroids. Conclusions: There is potential for recovery in patients with very severe ARDS due to COVID-19 supported by VV-ECMO for up to 151 days. [ABSTRACT FROM AUTHOR]

Background: Patients with influenza-related acute respiratory distress syndrome (ARDS) are critically ill and require mechanical ventilation (MV) support. Prolonged mechanical ventilation (PMV) is often seen in these cases and the optimal management strategy is not established. This study aimed to investigate risk factors for PMV and factors related to weaning failure in these patients. Methods: This retrospective cohort study was conducted by eight medical centers in Taiwan. All patients in the intensive care unit with virology-proven influenza-related ARDS requiring invasive MV from January 1 to March 31, 2016, were included. Demographic data, critical illness data and clinical outcomes were collected and analyzed. PMV is defined as mechanical ventilation use for more than 21 days. Results: There were 263 patients with influenza-related ARDS requiring invasive MV enrolled during the study period. Seventy-eight patients had PMV. The final weaning rate was 68.8% during 60 days of observation. The mortality rate in PMV group was 39.7%. Risk factors for PMV were body mass index (BMI) > 25 (kg/m2) [odds ratio (OR) 2.087; 95% confidence interval (CI) 1.006–4.329], extracorporeal membrane oxygenation (ECMO) use (OR 6.181; 95% CI 2.338–16.336), combined bacterial pneumonia (OR 4.115; 95% CI 2.002–8.456) and neuromuscular blockade use over 48 h (OR 2.8; 95% CI 1.334–5.879). In addition, risk factors for weaning failure in PMV patients were ECMO (OR 5.05; 95% CI 1.75–14.58) use and bacteremia (OR 3.91; 95% CI 1.20–12.69). Conclusions: Patients with influenza-related ARDS and PMV have a high mortality rate. Risk factors for PMV include BMI > 25, ECMO use, combined bacterial pneumonia and neuromuscular blockade use over 48 h. In addition, ECMO use and bacteremia predict unsuccessful weaning in PMV patients. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous–venous extracorporeal membrane oxygenation has been reported in a small number of cases. Case presentation: We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous–venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous–venous extracorporeal membrane oxygenation, which was discontinued after 12 days. Conclusion: Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5–7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication. [ABSTRACT FROM AUTHOR]

Background: Inter-facility transport of patients with acute respiratory distress syndrome (ARDS) in the prone position (PP) is a high-risk situation, compared to other strategies. We aimed to quantify the prevalence of complications during transport in PP, compared to transports with veno-venous extracorporeal membrane oxygenation (VV-ECMO) or in the supine position (SP). Methods: We performed a retrospective, single center cohort study in Lyon university hospital, France. We included patients ≥ 16 years with ARDS (Berlin definition) transported to an ARDS referral center between 01/12/2016 and 31/12/2021. We compared patients transported in PP, to those transported in SP without VV-ECMO, and those transported with VV-ECMO (in SP), by a multidisciplinary and specialized medical transport team, including an emergency physician and an intensivist. The primary outcome was the rate of transport-related complications (hypoxemia, hypotension, cardiac arrest, cannula or tube dislodgement) in each study groups, compared using a Fisher test. Results: One hundred thirty-four patients were enrolled (median PaO2/FiO2 70 [58–82] mmHg), of which 11 (8%) were transported in PP, 44 (33%) with VV-ECMO, and 79 (59%) in SP. The most frequent risk factor for ARDS in the PP group was bacterial pneumonitis, and viral pneumonitis in the other 2 groups. Transport-related complications occurred in 36% (n = 4) of transports in PP, compared to 39% (n = 30) in SP and 14% (n = 6) with VV-ECMO, respectively (p = 0.33). VV-ECMO implantation after transport was not different between SP and PP patients (n = 7, 64% vs. n = 31, 39%, p = 0.19). Conclusions: In the context of a specialized multi-disciplinary ARDS transport team, transport-related complication rates were similar between patients transported in PP and SP, while there was a trend of lower rates in patients transported with VV-ECMO. [ABSTRACT FROM AUTHOR]

Background: Current COVID-19 guidelines recommend the early use of systemic corticoids for COVID-19 acute respiratory distress syndrome (ARDS). It remains unknown if high-dose methylprednisolone pulse therapy (MPT) ameliorates refractory COVID-19 ARDS after many days of mechanical ventilation or rapid deterioration with or without extracorporeal membrane oxygenation (ECMO). Methods: This is a retrospective observational study. Consecutive patients with COVID-19 ARDS treated with a parenteral high-dose methylprednisolone pulse therapy at the intensive care units (ICU) of two University Hospitals between January 1st 2021 and November 30st 2022 were included. Clinical data collection was at ICU admission, start of MPT, 3-, 10- and 14-days post MPT. Results: Thirty-seven patients (mean age 55 ± 12 years) were included in the study. MPT started at a mean of 17 ± 12 days after mechanical ventilation. Nineteen patients (54%) received ECMO support when commencing MPT. Mean paO2/FiO2 significantly improved 3- (p = 0.034) and 10 days (p = 0.0313) post MPT. The same applied to the necessary FiO2 10 days after MPT (p = 0.0240). There were no serious infectious complications. Twenty-four patients (65%) survived to ICU discharge, including 13 out of 20 (65%) needing ECMO support. Conclusions: Late administration of high-dose MPT in a critical subset of refractory COVID-19 ARDS patients improved respiratory function and was associated with a higher-than-expected survival of 65%. These data suggest that high-dose MPT may be a viable salvage therapy in refractory COVID-19 ARDS. [ABSTRACT FROM AUTHOR]

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

The respiratory ECMO survival prediction (RESP) score is used to predict survival for patients managed with extracorporeal membrane oxygenation (ECMO), but its performance in patients with Coronavirus Disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is unclear. We evaluated the ability of the RESP score to predict survival for patients with both non-COVID 19 ARDS and COVID-19 ARDS managed with ECMO at our institution. Receiver operating characteristic area under the curve (AUC) analysis found the RESP score reasonably predicted survival in patients with non-COVID-19 ARDS (AUC 0.76, 95% CI 0.68–0.83), but not patients with COVID-19 ARDS (AUC 0.54, 95% CI 0.41–0.66). [ABSTRACT FROM AUTHOR]

Background: The study evaluates the impact of the time between commencing non-invasive ventilation (NIV) support and initiation of venovenous extracorporeal membrane oxygenation (VV-ECMO) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS). Methods: Prospective observational study design in an intensive Care Unit (ICU) of a tertiary hospital in Barcelona (Spain). All patients requiring VV-ECMO support due to COVID-19 associated ARDS between March 2020 and January 2022 were analysed. Survival outcome was determined at 90 days after VV-ECMO initiation. Demographic data, comorbidities at ICU admission, RESP (respiratory ECMO survival prediction) score, antiviral and immunomodulatory treatments received, inflammatory biomarkers, the need for vasopressors, the thromboprophylaxis regimen received, and respiratory parameters including the length of intubation previous to ECMO and the length of each NIV support (high-flow nasal cannula, continuous positive airway pressure and bi-level positive airway pressure), were also collated in order to assess risk factors for day-90 mortality. The effect of the time lapse between NIV support and VV-ECMO on survival was evaluated using logistic regression and adjusting the association with all factors that were significant in the univariate analysis. Results: Seventy-two patients finally received VV-ECMO support. At 90 days after commencing VV-ECMO 35 patients (48%) had died and 37 patients (52%) were alive. Multivariable analysis showed that at VV-ECMO initiation, age (p = 0.02), lactate (p = 0.001), and days from initiation of NIV support to starting VV-ECMO (p = 0.04) were all associated with day-90 mortality. Conclusions: In our small cohort of VV-ECMO patients with COVID-19 associated ARDS, the time spent between initiation of NIV support and VV-ECMO (together with age and lactate) appeared to be a better predictor of mortality than the time between intubation and VV-ECMO. [ABSTRACT FROM AUTHOR]

Background: The outcome of Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) in acute respiratory failure may be influenced by patient-related factors, center expertise and modalities of mechanical ventilation (MV) during ECMO. We determined, in a medium-size ECMO center in Switzerland, possible factors associated with mortality during VV-ECMO for acute respiratory failure of various etiologies. Methods: We retrospectively analyzed all patients treated with VV-ECMO in our University Hospital from 2012 to 2019 (pre-COVID era). Demographic variables, severity scores, MV duration before ECMO, pre and on-ECMO arterial blood gases and respiratory variables were collected. The primary outcome was ICU mortality. Data were compared between survivors and non-survivors, and factors associated with mortality were assessed in univariate and multivariate analyses. Results: Fifty-one patients (33 ARDS, 18 non-ARDS) were included. ICU survival was 49% (ARDS, 39%; non-ARDS 67%). In univariate analyses, a higher driving pressure (DP) at 24h and 48h on ECMO (whole population), longer MV duration before ECMO and higher DP at 24h on ECMO (ARDS patients), were associated with mortality. In multivariate analyses, ECMO indication, higher DP at 24h on ECMO and, in ARDS, longer MV duration before ECMO, were independently associated with mortality. Conclusions: DP on ECMO and longer MV duration before ECMO (in ARDS) are major, and potentially modifiable, factors influencing outcome during VV-ECMO. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma (PCC) crisis is a rare life-threatening endocrine emergency. The diagnosis and treatment of PCC crisis, with acute respiratory distress syndrome (ARDS) as the first manifestation, is highly challenging, and traditional PCC management strategies are no longer suitable for these patients. Case presentation: A 46-year-old female patient was admitted to the Intensive Care Unit (ICU) following sudden-onset acute respiratory distress and subsequent initiation of mechanical ventilation via endotracheal intubation. She was initially suspected of having a PCC crisis through the bedside critical care ultrasonic examination protocol. The computed tomography examination revealed a left adrenal neoplasm of 6.5cm × 5.9cm. The plasma-free metanephrine level was 100 times higher than the reference value. These findings were compatible with her PCC diagnosis. Alpha-blockers and fluid intake were started immediately. The endotracheal intubation was removed on the 11th day after admission to the ICU. The patient progressed to severe ARDS again, and invasive ventilation and continuous renal replacement therapy were needed. Despite aggressive therapy, her condition deteriorated. Therefore, she underwent veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-assisted emergency adrenalectomy after multidisciplinary discussion. Postoperatively, the patient was supported by VA-ECMO for 7days. She was discharged from the hospital on day 30 after tumor resection. Conclusions: This case highlighted the challenges in diagnosing and managing ARDS associated with PCC crisis. The traditional preoperative preparation protocol and optimal operation timing for patients with PCC are not suitable for patients with PCC crisis. Patients with life-threatening PCC crisis may benefit from early tumor removal, and VA-ECMO could maintain hemodynamic stability during and after surgery. [ABSTRACT FROM AUTHOR]

Background: It is clinically important to predict difficulty in short-term liberation from veno-venous extracorporeal membrane oxygenation (V-V ECMO) in patients with severe acute respiratory distress syndrome (ARDS) at the time of initiation of the support. The aim of this study was to identify the characteristics of pulmonary opacities on chest CT that is associated with difficulty in short-term liberation from V-V ECMO (< 14 days). Methods: This multicenter retrospective study was conducted in adult patients initiated on V-V ECMO for severe ARDS between January 2014 and June 2022. The pulmonary opacities on CT at the time of initiation of the ECMO support were evaluated in a blinded manner, focusing on the following three characteristics of the opacities: (1) their distribution (focal/diffuse on the dorso-ventral axis or unilateral/bilateral on the left-right axis); (2) their intensity (pure ground glass/pure consolidation/mixed pattern); and (3) the degree of fibroproliferation (signs of traction bronchiectasis or reticular opacities). Results: Among the 153 patients, 72 (47%) were successfully liberated from ECMO in the short term, while short-term liberation failed in the remaining 81 (53%) patients. Multivariate logistic regression analysis showed that the presence of mixed-pattern pulmonary opacities and signs of traction bronchiectasis, but not the distribution of the opacities, were independently associated with difficulty in short-term liberation (OR [95% CI]; 4.8 [1.4–16.5] and 3.9 [1.4–11.2], respectively). Conclusions: The presence of a mixed pattern of the pulmonary opacities and signs of traction bronchiectasis on the chest CT were independently associated with difficulty in short-term liberation from V-V ECMO in severe ARDS patients. [ABSTRACT FROM AUTHOR]

Background: Hemolysis is associated with increased mortality in patients with sepsis, ARDS, or therapy with extracorporeal membrane oxygenation (ECMO). To quantify a critical threshold of hemolysis in patients with ARDS and treatment with veno-venous ECMO, we aimed to identify cutoff values for cell-free hemoglobin (CFH) and haptoglobin (Hp) plasma concentrations associated with a significant increase in ICU mortality. Methods: Patients with ARDS admitted to a tertiary ARDS referral center between 01/2007 and 12/2018 and treatment with veno-venous ECMO were included. Cutoff values for mean CFH (mCFH) and mean Hp (mHp) plasma concentrations dividing the cohort into groups with significantly different ICU mortalities were calculated and patient characteristics were compared. A multiple logistic regression model with stepwise backward variable selection was included. In addition, cutoff values for vulnerable relative timespans for the respective CFH and Hp concentrations were calculated. Results: A quantitative cutoff value of 11 mg/dl for mCFH separated the cohort (n = 442) regarding ICU mortality (mCFH ≤ 11 mg/dl: 38%, [95%-CI: 32.22–43.93] (n = 277) vs. mCFH > 11 mg/dl: 70%, [61.99–76.47] (n = 165), p < 0.001). Analogously, a mHp cutoff value ≤ 0.39 g/l was associated with a significant increase in ICU mortality (mHp ≤ 0.39 g/l: 68.7%, [60.91–75.61] (n = 163) vs. mHp > 0.39 g/l: 38.7%, [33.01–44.72] (n = 279), p < 0.001). The independent association of ICU mortality with CFH and Hp cutoff values was confirmed by logistic regression adjusting for confounders (CFH Grouping: OR 3.77, [2.51–5.72], p < 0.001; Hp Grouping: OR 0.29, [0.19–0.43], p < 0.001). A significant increase in ICU mortality was observed when CFH plasma concentration exceeded the limit of 11 mg/dl on 13.3% of therapy days (≤ 13.3% of days with CFH > 11 mg/dl: 33%; [26.81–40.54] (n = 192) vs. > 13.3% of days with CFH > 11 mg/dl: 62%; [56.05–68.36] (n = 250), p < 0.001). Analogously, a mortality increase was detected when Hp plasma concentration remained ≤ 0.39 g/l for > 18.2% of therapy days (≤ 18.2% days with Hp ≤ 0.39 g/l: 27%; [19.80–35.14] (n = 138) vs. > 18.2% days with Hp ≤ 0.39 g/l: 60%; [54.43–65.70] (n = 304), p < 0.001). Conclusions: Moderate hemolysis with mCFH-levels as low as 11 mg/dl impacts mortality in patients with ARDS and therapy with veno-venous ECMO. Furthermore, a cumulative dose effect should be considered indicated by the relative therapy days with CFH-concentrations > 11 mg/dl. In addition, also Hp plasma concentrations need consideration when the injurious effect of elevated CFH is evaluated. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown an association between baseline arterial carbon dioxide pressure (PaCO2) and outcomes in patients with acute respiratory distress syndrome (ARDS). However, PaCO2 probably varies throughout the disease, and few studies have assessed the effect of longitudinal PaCO2 on prognosis. We thus aimed to investigate the association between time-varying PaCO2 and 28-day mortality in mechanically ventilated ARDS patients. Methods: In this retrospective study, we included all adult (≥ 18 years) patients diagnosed with ARDS who received mechanical ventilation for at least 24 h at a tertiary teaching hospital between January 2014 and March 2021. Patients were excluded if they received extracorporeal membrane oxygenation (ECMO). Demographic data, respiratory variables, and daily PaCO2 were extracted. The primary outcome was 28-day mortality. Time-varying Cox models were used to estimate the association between longitudinal PaCO2 measurements and 28-day mortality. Results: A total of 709 patients were eligible for inclusion in the final cohort, with an average age of 65 years, of whom 70.7% were male, and the overall 28-day mortality was 35.5%. After adjustment for baseline confounders, including age and severity of disease, a significant increase in the hazard of death was found to be associated with both time-varying PaCO2 (HR 1.07, 95% CI 1.03–1.11, p<0.001) and the time-varying coefficient of variation for PaCO2 (HR 1.24 per 10% increase, 95% CI 1.10–1.40, p<0.001) during the first five days of invasive mechanical ventilation. The cumulative proportion of exposure to normal PaCO2 (HR 0.72 per 10% increase, 95% CI 0.58–0.89, p = 0.002) was associated with 28-day mortality. Conclusion: PaCO2 should be closely monitored in mechanically ventilated ARDS patients. The association between PaCO2 and 28-day mortality persisted over time. Increased cumulative exposure to normal PaCO2 was associated with a decreased risk of death. [ABSTRACT FROM AUTHOR]

COVID–19 infection can lead to severe acute respiratory distress syndrome (ARDS), right ventricular (RV) failure and pulmonary hypertension. Venovenous extracorporeal membrane oxygenation (V-V ECMO) has been used for patients with refractory hypoxemia. More recently dual-lumen right atrium to pulmonary artery oxygenated right ventricular assist devices (Oxy-RVAD) have been utilized in the severe medical refractory COVID ARDS setting. Historically, animal data has demonstrated that high continuous non-pulsatile RVAD flows, leading to unregulated and unprotected circulation through the pulmonary vessels is associated with an increased risk of pulmonary hemorrhage and increased amount of extravascular lung water. These risks are heightened in the setting of ARDS with fragile capillaries, left ventricular (LV) diastolic failure, COVID cardiomyopathy, and anticoagulation. Concurrently, due to infection, tachycardia, and refractory hypoxemia, high V-V ECMO flows to match high cardiac output are often necessary to maintain systemic oxygenation. Increase in cardiac output without a concurrent increase in VV ECMO flow will result in a higher fraction of deoxygenated blood returning to the right heart and therefore resulting in hypoxemia. Several groups have suggested using a RVAD only strategy in COVID ARDS; however, this exposes the patients to the risk of pulmonary hemorrhage. We present one of the first known cases using an RV mechanical support, partial flow pulmonary circulation, oxygenated Veno-venopulmonary (V-VP) strategy resulting in RV recovery, total renal recovery, awake rehabilitation, and recovery. [ABSTRACT FROM AUTHOR]

A growing body of evidence supports the use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) refractory to maximal medical therapy. ARDS may develop in a proportion of patients hospitalized for coronavirus disease 2019 (COVID-19) and ECMO may be used to manage patients refractory to maximal medical therapy to mitigate the risk of ventilator-induced lung injury and provide lung rest while awaiting recovery. The mortality of COVID-19-related ARDS was variously reassessed during the pandemic. Veno-venous (VV) ECMO was the default choice to manage refractory respiratory failure; however, with concomitant severe right ventricular dysfunction, venoarterial (VA) ECMO or mechanical right ventricular assist devices with extracorporeal gas exchange (Oxy-RVAD) were also considered. ECMO has also been used to manage special populations such as pregnant women, pediatric patients affected by severe forms of COVID-19, and, in cases with persistent and seemingly irreversible respiratory failure, as a bridge to successful lung transplantation. In this narrative review, we outline and summarize the most recent evidence that has emerged on ECMO use in different patient populations with COVID-19-related ARDS. [ABSTRACT FROM AUTHOR]

Background: Severe adenovirus (Adv.) pneumonia can cause significant mortality in young children. There has been no worldwide consensus on the impact of extracorporeal membrane oxygenation (ECMO) in immunocompetent children with severe Adv. pneumonia. This study aimed to assess the impact of ECMO in immunocompetent children with severe Adv. pneumonia. Methods: This study evaluated the medical records of 168 hospitalized children with severe Adv. pneumonia at the Guangzhou Women and Children's Medical Center between 2019 and 2020.Nineteen patients in the ECMO group and 149 patients in the non-ECMO group were enrolled. Results: Between these two groups, there were no differences in host factors such as sex, age (all P > 0.05). Significant differences were observed in shortness of breath/increased work of breathing; cyanosis; seizures; tachycardia; the partial pressure of oxygen in arterial blood (PO2); the ratio of PaO2 to the fraction concentration of oxygen in inspired air (FiO2; P/F); white blood cell, lymphocyte, monocytes, lactate dehydrogenase (LDH), serum albumin, and procalcitonin levels; and, pulmonary consolidation (all P < 0.05). There were significant differences in the parameters of mechanical ventilation (MV) therapy and complications such as respiratory failure, acute respiratory distress syndrome, septic shock, length of hospitalization, and death (all P < 0.05). The maximum axillary temperatures, respiratory rates, heart rates and LDH levels after receiving ECMO were significantly lower than those before ECMO (all P < 0.05). Additionally, SPO2, PO2, and P/F were significantly higher than those before ECMO (all P < 0.05). In MV therapy, FiO2, PIP, and PEEP were significantly lower than those before ECMO (all P < 0.05). Conclusions: In our study, the clinical conditions of the patients in the ECMO group were much more severe than those in the non-ECMO group. Our study showed that ECMO might be beneficial for the patients with severe Adv. pneumonia. [ABSTRACT FROM AUTHOR]

Background: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is an effective, but highly resource intensive salvage treatment option in COVID patients with acute respiratory distress syndrome (ARDS). Right ventricular (RV) dysfunction is a known sequelae of COVID-19 induced ARDS, yet there is a paucity of data on the incidence and determinants of RV dysfunction on VV ECMO. We retrospectively examined the determining factors leading to RV failure and means of early identification of this phenomenon in patients on VV ECMO.Methods: The data was extracted from March 2020 to March 2021 from the regional University of Washington Extracorporeal Life Support database. The inclusion criteria included patients > 18 years of age with diagnosis of COVID-19. All had already been intubated and mechanically ventilated prior to VV ECMO deployment. Univariate analysis was performed to identify risk factors and surrogate markers for RV dysfunction. In addition, we compared outcomes between those with and without RV dysfunction.Results: Of the 33 patients that met inclusion criteria, 14 (42%) had echocardiographic evidence of RV dysfunction, 3 of whom were placed on right ventricular assist device support. Chronic lung disease was an independent risk factor for RV dysfunction (p = 0.0002). RV dysfunction was associated with a six-fold increase in troponin I (0.07 ng/ml vs. 0.44 ng/ml, p = 0.039) and four-fold increase in brain natriuretic peptide (BNP) (158 pg/ml vs. 662 pg/ml, p = 0.037). Deep vein thrombosis (DVT, 21% vs. 43%, p = 0.005) and pulmonary embolism (PE, 11% vs. 21%, p = 0.045) were found to be nearly twice as common in the RV dysfunction group. Total survival rate to hospital discharge was 39%. Data trended towards shorter duration of hospital stay (47 vs. 65.6 days, p = 0.15), shorter duration of ECMO support (21 days vs. 36 days, p = 0.06) and improved survival rate to hospital discharge (42.1% vs. 35.7%, p = 0.47) for those with intact RV function compared to the RV dysfunction group.Conclusions: RV dysfunction in critically ill patients with COVID-19 pneumonia in common. Trends of troponin I and BNP may be important surrogates for monitoring RV function in patients on VV ECMO. We recommend echocardiographic assessment of the RV on such patients. [ABSTRACT FROM AUTHOR]

Background: Crescent cannula adhesion in the setting of COVID-19 respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support is a novel complication. The objective of this case presentation is to highlight this rare complication and to explore potential predisposing factors and our management strategies.Case Presentation: We present the case of a 25 y.o. patient with COVID-19 respiratory failure requiring ECMO support for 16-days in which a 32 Fr crescent cannula became adherent to the SVC and proximal jugular vein. Attempts to remove the cannula at the bedside failed due to immobility of the cannula. Ultrasound of the right neck was unremarkable, so he was taken to the hybrid OR where both TEE and fluoroscopy were unrevealing. An upper sternotomy was performed, and the superior vena cava and proximal jugular vein were dissected revealing a 2 cm segment of the distal SVC and proximal jugular vein that was densely sclerosed and adherent to the cannula. The vessel was opened across the adherent area at the level of the innominate vein and the cannula was then able to be withdrawn. The patient suffered no ill effects and had an unremarkable recovery to discharge.Conclusions: To date, there have been no reports of crescent cannula adhesion related complications. In patients with COVID-19 respiratory failure requiring ECMO, clinicians should be aware of widespread hypercoagulability and the potential of unprovoked, localized venous sclerosis and cannula adhesion. We report our technique of decannulation in the setting of cannula adhesion and hope that presentation will shed further light on this complication allowing clinicians to optimize patient care. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS), a prevalent cause of admittance to intensive care units, is associated with high mortality. Prone positioning has been proven to improve the outcomes of moderate to severe ARDS patients owing to its physiological effects. Venovenous extracorporeal membrane oxygenation (VV ECMO) will be considered in patients with severe hypoxemia. However, for patients with severe hypoxemia supported with VV ECMO, the potential effects and optimal strategies of prone positioning remain unclear. This review aimed to present these controversial questions and highlight directions for future research. Main body: The clinically significant benefit of prone positioning and early VV ECMO alone was confirmed in patients with severe ARDS. However, a number of questions regarding the combination of VV ECMO and prone positioning remain unanswered. We discussed the potential effects of prone positioning on gas exchange, respiratory mechanics, hemodynamics, and outcomes. Strategies to achieve optimal outcomes, including indications, timing, duration, and frequency of prone positioning, as well as the management of respiratory drive during prone positioning sessions in ARDS patients receiving VV ECMO, are challenging and controversial. Additionally, whether and how to implement prone positioning according to ARDS phenotypes should be evaluated. Lung morphology monitored by computed tomography, lung ultrasound, or electrical impedance tomography might be a potential indication to make an individualized plan for prone positioning therapy in patients supported with VV ECMO. Conclusion: For patients with ARDS supported with VV ECMO, the potential effects of prone positioning have yet to be clarified. Ensuring an optimal strategy, especially an individualized plan for prone positioning therapy during VV ECMO, is particularly challenging and requires further research. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 infections are suspected to trigger the coagulation system through various pathways leading to a high incidence of thromboembolic complications, hypercoagulation and impaired fibrinolytic capacity were previously identified as potentially mechanisms. A reliable diagnostic tool for detecting both is still under discussion. This retrospective study is aimed to examine the prognostic relevance of early viscoelastic testing compared to conventional laboratory tests in COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods: All mechanically ventilated patients with COVID-19 related ARDS treated in our intensive care unit (ICU) between January and March 2021 were included in this study. Viscoelastic testing (VET) was performed using the ClotPro® system after admission to our ICU. Prevalence of thromboembolic events was observed by standardized screening for venous and pulmonary thromboembolism using complete compression ultrasound and thoracic computed tomography pulmonary angiography at ICU admission, respectively. We examined associations between the severity of ARDS at admission to our ICU, in-hospital mortality and the incidence of thromboembolic events comparing conventional laboratory analysis and VET. ECMO related coagulopathy was investigated in a subgroup analysis. The data were analyzed using the Mann–Whitney U test. Results: Of 55 patients enrolled in this study, 22 patients required treatment with ECMO. Thromboembolic complications occurred in 51% of all patients. Overall hospital mortality was 55%. In patients with thromboembolic complications, signs of reduced fibrinolytic capacity could be detected in the TPA assay with prolonged lysis time, median 460 s (IQR 350–560) vs 359 s (IQR 287–521, p = 0.073). Patients with moderate to severe ARDS at admission to our ICU showed increased maximum clot firmness as a sign of hypercoagulation in the EX-test (70 vs 67 mm, p < 0.05), FIB-test (35 vs 24 mm, p < 0.05) and TPA-test (52 vs 36 mm, p < 0.05) as well as higher values of inflammatory markers (CRP, PCT and IL6). ECMO patients suffered more frequently from bleeding complications (32% vs 15%). Conclusion: Although, the predictive value for thromboembolic complications or mortality seems limited, point-of-care viscoelastic coagulation testing might be useful in detecting hypercoagulable states and impaired fibrinolysis in critically ill COVID-19 ARDS patients and could be helpful in identifying patients with a potentially very severe course of the disease. [ABSTRACT FROM AUTHOR]

Background: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. Methods: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. Results: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4–8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). Conclusions: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries. [ABSTRACT FROM AUTHOR]

Background: Even an ultraprotective ventilation strategy in severe acute respiratory distress syndrome (ARDS) patients treated with extracorporeal membrane oxygenation (ECMO) might induce ventilator-induced lung injury and apneic ventilation with the sole application of positive end-expiratory pressure may, therefore, be an alternative ventilation strategy. We, therefore, compared the effects of ultraprotective ventilation with apneic ventilation on oxygenation, oxygen delivery, respiratory system mechanics, hemodynamics, strain, air distribution and recruitment of the lung parenchyma in ARDS patients with ECMO. Methods: In a prospective, monocentric physiological study, 24 patients with severe ARDS managed with ECMO were ventilated using ultraprotective ventilation (tidal volume 3 ml/kg of predicted body weight) with a fraction of inspired oxygen (FiO2) of 21%, 50% and 90%. Patients were then treated with apneic ventilation with analogous FiO2. The primary endpoint was the effect of the ventilation strategy on oxygenation and oxygen delivery. The secondary endpoints were mechanical power, stress, regional air distribution, lung recruitment and the resulting strain, evaluated by chest computed tomography, associated with the application of PEEP (apneic ventilation) and/or low VT (ultraprotective ventilation). Results: Protective ventilation, compared to apneic ventilation, improved oxygenation (arterial partial pressure of oxygen, p < 0.001 with FiO2 of 50% and 90%) and reduced cardiac output. Both ventilation strategies preserved oxygen delivery independent of the FiO2. Protective ventilation increased driving pressure, stress, strain, mechanical power, as well as induced additional recruitment in the non-dependent lung compared to apneic ventilation. Conclusions: In patients with severe ARDS managed with ECMO, ultraprotective ventilation compared to apneic ventilation improved oxygenation, but increased stress, strain, and mechanical power. Apneic ventilation might be considered as one of the options in the initial phase of ECMO treatment in severe ARDS patients to facilitate lung rest and prevent ventilator-induced lung injury. Trial registration: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013967. [ABSTRACT FROM AUTHOR]

Background: Amniotic fluid embolism (AFE) is a rare but potentially dangerous severe obstetrics complication, which is accompanied by an incidence between 1.9 and 6.1 per 100,000 births. Case presentation: Here, we report an AFE case after cesarean delivery diagnosed on a cardiac arrest complicated by acute respiratory distress syndrome and coagulopathy. Diagnosis, risk factors and pathophysiology for AFE have been fully discussed, besides, extracorporeal membrane oxygenation in the early management of cardiac arrest was used, describing the indication, efficacy and successful performed of open-chest cardiopulmonary resuscitation for the patient. Conclusion: In AFE with cute cardiovascular collapse, extracorporeal membrane oxygenation support can be considered as the alternative therapies. Highlights: The rare but dangerous amniotic fluid embolish after cesarean delivery was diagnosed. A cardiac arrest accompanied by acute respiratory distress syndrome and coagulopathy was recorded. Diagnosis, risk factors and pathophysiology for amniotic fluid embolish in this case were detailly discussed. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) has been used as a rescue strategy in patients with severe with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection, but there has been little evidence of its efficacy. Objectives: To describe the effect of ECMO rescue therapy on patient-important outcomes in patients with severe SARS-CoV-2. Methods: A case series study was conducted for the laboratory-confirmed SARS-CoV-2 patients who were admitted to the ICUs of 22 Saudi hospitals, between March 1, 2020, and October 30, 2020, by reviewing patient's medical records prospectively. Results: ECMO use was associated with higher in-hospital mortality (40.2% vs. 48.9%; p = 0.000); lower COVID-19 virological cure (41.3% vs 14.1%, p = 0.000); and longer hospitalization (20.2 days vs 29.1 days; p = 0.000), ICU stay (12.6 vs 26 days; p = 0.000) and mechanical ventilation use (14.2 days vs 22.4 days; p = 0.000) compared to non-ECMO group. Also, there was a high number of patients with septic shock (19.6%) and multiple organ failure (10.9%); and more complications occurred at any time during hospitalization [pneumothorax (5% vs 29.3%, p = 0.000), bleeding requiring blood transfusion (7.1% vs 38%, p = 0.000), pulmonary embolism (6.4% vs 15.2%, p = 0.016), and gastrointestinal bleeding (3.3% vs 8.7%, p = 0.017)] in the ECMO group. However, PaO2 was significantly higher in the 72-h post-ECMO initiation group and PCO2 was significantly lower in the 72-h post-ECMO start group than those in the 12-h pre-ECMO group (62.9 vs. 70 mmHg, p = 0.002 and 61.8 vs. 51 mmHg, p = 0.042, respectively). Conclusion: Following the use of ECMO, the mortality rate of patients and length of ICU and hospital stay were not improved. However, these findings need to be carefully interpreted, as most of our cohort patients were relatively old and had multiple severe comorbidities. Future randomized trials, although challenging to conduct, are highly needed to confirm or dispute reported observations. [ABSTRACT FROM AUTHOR]

Background: Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important.Case Presentation: This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department.Conclusions: To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered. [ABSTRACT FROM AUTHOR]

Background: We present an unusual bleeding complication in a patient with severe acute respiratory distress syndrome in coronavirus disease 2019.Case Presentation: The patient, a 63-year-old Caucasian man, received venovenous extracorporeal membrane oxygenation support after rapid deterioration of lung function on day 6 after admission to hospital. After initial stabilization on lung protective ventilation and prone positioning, he started to develop mild bleeding complications until he went into occult profound hemorrhagic shock. Causative was a massive hemothorax of the right hemithorax with mediastinal shifting due to spontaneous bleeding from a pulmonal artery in a heavily remodeled right inferior lobe. Histopathological examination of the resected tissue showed signs of an organizing fibrinous pneumonia with focal parenchyma necrosis. After surviving a massive bleeding event caused by necrotizing pneumonia, the patient made a swift recovery and was discharged to rehabilitation 31 days after initial hospital admission.Conclusions: The combination of severely elevated inflammatory markers and pulmonary hemorrhage should arouse suspicion of necrotizing pneumonia. In necrotizing pneumonia, the possibility of severe intrathoracic bleeding complications should be kept in mind if it comes to sudden deterioration of the patient. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to present the case of a boy with acute distress syndrome (ARDS) treated with low-dose umbilical cord blood (UCB) therapy and explore the underlying possible mechanism. Methods: A 7-year-old boy with severe Pneumocystis carinii pneumonia and severe ARDS was treated with allogeneic UCB as salvage therapy. Results: The patient did not improve after being treated with lung protective ventilation, pulmonary surfactant replacement, and extracorporeal membrane oxygenation (ECMO) for 30 days. However, his disease reversed 5 days after allogeneic UCB infusion, and he weaned from ECMO after 7 days of infusion. Bioinformatics confirmed that his Toll-like receptor (TLR) was abnormal before UCB infusion. However, after the infusion, his immune system was activated and repaired, and the TLR4/MyD88/NF-κB signaling pathway was recovered. Conclusion: Allogenic UCB could treat ARDS by repairing the TLR4/MyD88/NF-κB signaling pathway, thereby achieving stability of the immune system. [ABSTRACT FROM AUTHOR]

Background: Whether acute respiratory failure in patients with interstitial lung disease is reversible remains uncertain. Consequently, indications for extracorporeal membrane oxygenation in these patients are still controversial, except as a bridge to lung transplantation. The objective of this study was to clarify in-hospital mortality and prognostic factors in interstitial lung disease patients undergoing extracorporeal membrane oxygenation.Methods: In this case-control study using the Japanese Diagnosis Procedure Combination database, hospitalized interstitial lung disease patients receiving invasive mechanical ventilation and extracorporeal membrane oxygenation from 2010 to 2017 were reviewed. Patients' characteristics and treatment regimens were compared between survivors and non-survivors to identify prognostic factors. To avoid selection biases, patients treated with extracorporeal membrane oxygenation as a bridge to lung transplantation were excluded.Results: A total of 164 interstitial lung disease patients receiving extracorporeal membrane oxygenation were included. Their in-hospital mortality was 74.4% (122/164). Compared with survivors, non-survivors were older and received high-dose cyclophosphamide, protease inhibitors, and antifungal drugs more frequently, but macrolides and anti-influenza drugs less frequently. On multivariate analysis, the following factors were associated with in-hospital mortality: advanced age (odds ratio [OR] 1.043; 95% confidence interval [CI] 1.009-1.078), non-use of macrolides (OR 0.305; 95% CI 0.134-0.698), and use of antifungal drugs (OR 2.416; 95% CI 1.025-5.696).Conclusions: Approximately three-quarters of interstitial lung disease patients undergoing extracorporeal membrane oxygenation died in hospital. Moreover, advanced age, non-use of macrolides, and use of antifungal drugs were found to correlate with a poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal life support (ECLS) is an established tool to stabilize severely ill patients with therapy-refractory hemodynamic or respiratory failure. Recently, we established a mobile ECLS retrieval service at our institution. However, data on the outcome of patients receiving ECLS at outside hospitals for transportation into tertiary hospitals is still sparse.Methods: We have analyzed all patients receiving ECLS in outside hospitals (Transport group, TG) prior to transportation to our institution and compared the outcome to our in-house ECLS experience (Home Group, HG).Results: Between 2012 and 2018, we performed 978 ECLS implantations, 243 of which were performed on-site in tertiary hospitals for ECLS supported transportation. Significantly more veno-venous systems were implanted in TG (n = 129 (53%) vs. n = 327 (45%), p = 0.012). Indication for ECLS support differed between the groups, with more pneumonia; acute respiratory distress syndromes in the TG group and of course, more postcardiotomy patients in HG. Mean age was 47 (± 20) (HG) vs. 48 (± 18) (TG) years, p = 0.477 with no change over time. No differences were seen in ECLS support time (8.03 days ±8.19 days HG vs 7.81 days ±6.71 days TG, p = 0.675). 30-day mortality (n = 379 (52%) (HG) vs. n = 119 (49%) (TG) p = 0.265) and death on ECLS support (n = 322 (44%) (HG) vs. n = 97 (40%) TG, p = 0.162) were comparable between the two groups, despite a more severe SAVE score in the v-a TG (HG: - 1.56 (± 4.73) vs. TG -3.93 (± 4.22) p < 0.001). Mortality rates did not change significantly over the years. Multivariate risk analysis revealed Influenza, Peak Insp. Pressure at implantation, pO2/FiO2 ratio and ECLS Score (SAVE/RESP) as well as ECLS support time to be independent risk factors for mortality.Conclusion: Mobile ECLS support is a tremendous challenge. However, it is justified to offer 24 h/7d ECLS standby for secondary and primary hospitals as a tertiary hospital. Increasing indications and total numbers for ECLS support raise the need for further studies to evaluate outcome in these patients. [ABSTRACT FROM AUTHOR]

Background: Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach. Case presentation: A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg. Conclusions: An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient's oxygenation has to be ensured at the expense of lung protective ventilation concepts. [ABSTRACT FROM AUTHOR]

Extracorporeal life support treatments such as extracorporeal membrane oxygenation (ECMO) have been recommended for the treatment of severe acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). To date, many countries, including China, have adopted ECMO as a treatment for severe COVID-19. However, marked differences in patient survival rates have been reported, and the underlying reasons are unclear. This study aimed to summarize the experience of using ECMO to treat severe COVID-19 and provide suggestions for improving ECMO management. The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the pathophysiology of COVID-19 and the effects of ECMO on the clinical outcomes in patients with severe cases of COVID-19 were reviewed. Recent data from frontline workers involved in the use of ECMO in Wuhan, China, and those experienced in the implementation of artificial heart and lung support strategies were analysed. There is evidence that ECMO may complicate the pathophysiological state in COVID-19 patients. However, many studies have shown that the appropriate application of ECMO improves the prognosis of such patients. To expand our understanding of the benefits of ECMO for critically ill patients with COVID-19, further prospective, multicentre clinical trials are needed. [ABSTRACT FROM AUTHOR]

Background: The complexity of extracorporeal membrane oxygenation (ECMO) techniques continues to evolve. Different cannulation methods and configurations have been proposed as a response to a challenging cardiovascular and pulmonary physiology of the patients. The use of parallel ECMO circuits represents a unique and novel approach for patients with refractory respiratory failure and cardiovascular collapse with very large body surface areas. Case presentation: We present the case of a 25-year-old morbidly obese male patient admitted for severe acute respiratory distress syndrome (ARDS) and refractory hypoxemia, requiring institution of double cannulation for veno-venous ECMO. Since his hypoxemia persisted, likely due to insufficient flows given his large body surface area, an additional drainage venous cannula was implemented to provide higher flows, temporarily addressing his oxygenation status. Unfortunately, the patient developed concomitant cardiogenic shock refractory to inotropic support and extracorporeal fluid removal, further worsening his oxygenation status, thus the decision was to institute four-cannulation/parallel-circuits veno-venous and veno-arterial ECMO, successfully controlling both refractory hypoxemia and cardiogenic shock. Conclusions: Our case illustrates a novel and complex approach for combined severe ARDS and cardiovascular collapse through the use of parallel veno-venous and veno-arterial ECMO circuits, and exemplifies the expansion of ECMO techniques and its life-saving capabilities when conservative approaches are futile. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a fatal condition with insufficiently clarified etiology. Supportive care for severe hypoxemia remains the mainstay of essential interventions for ARDS. In recent years, adequate ventilation to prevent ventilator-induced lung injury (VILI) and patient self-inflicted lung injury (P-SILI) as well as lung-protective mechanical ventilation has an increasing attention in ARDS. Ventilation-perfusion mismatch may augment severe hypoxemia and inspiratory drive and consequently induce P-SILI. Respiratory drive and effort must also be carefully monitored to prevent P-SILI. Airway occlusion pressure (P0.1) and airway pressure deflection during an end-expiratory airway occlusion (Pocc) could be easy indicators to evaluate the respiratory drive and effort. Patient-ventilator dyssynchrony is a time mismatching between patient's effort and ventilator drive. Although it is frequently unrecognized, dyssynchrony can be associated with poor clinical outcomes. Dyssynchrony includes trigger asynchrony, cycling asynchrony, and flow delivery mismatch. Ventilator-induced diaphragm dysfunction (VIDD) is a form of iatrogenic injury from inadequate use of mechanical ventilation. Excessive spontaneous breathing can lead to P-SILI, while excessive rest can lead to VIDD. Optimal balance between these two manifestations is probably associated with the etiology and severity of the underlying pulmonary disease. High-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NPPV) are non-invasive techniques for supporting hypoxemia. While they are beneficial as respiratory supports in mild ARDS, there can be a risk of delaying needed intubation. Mechanical ventilation and ECMO are applied for more severe ARDS. However, as with HFNC/NPPV, inappropriate assessment of breathing workload potentially has a risk of delaying the timing of shifting from ventilator to ECMO. Various methods of oxygen administration in ARDS are important. However, it is also important to evaluate whether they adequately reduce the breathing workload and help to improve ARDS. [ABSTRACT FROM AUTHOR]

Background: Treating severe forms of the acute respiratory distress syndrome and cardiac failure, extracorporeal membrane oxygenation (ECMO) has become an established therapeutic option. Neonatal or pediatric patients receiving ECMO, and patients undergoing extracorporeal CO2 removal (ECCO2R) represent low-flow applications of the technology, requiring lower blood flow than conventional ECMO. Centrifugal blood pumps as a core element of modern ECMO therapy present favorable operating characteristics in the high blood flow range (4 L/min-8 L/min). However, during low-flow applications in the range of 0.5 L/min-2 L/min, adverse events such as increased hemolysis, platelet activation and bleeding complications are reported frequently.Methods: In this study, the hemolysis of the centrifugal pump DP3 is evaluated both in vitro and in silico, comparing the low-flow operation at 1 L/min to the high-flow operation at 4 L/min.Results: Increased hemolysis occurs at low-flow, both in vitro and in silico. The in-vitro experiments present a sixfold higher relative increased hemolysis at low-flow. Compared to high-flow operation, a more than 3.5-fold increase in blood recirculation within the pump head can be observed in the low-flow range in silico.Conclusions: This study highlights the underappreciated hemolysis in centrifugal pumps within the low-flow range, i.e. during pediatric ECMO or ECCO2R treatment. The in-vitro results of hemolysis and the in-silico computational fluid dynamic simulations of flow paths within the pumps raise awareness about blood damage that occurs when using centrifugal pumps at low-flow operating points. These findings underline the urgent need for a specific pump optimized for low-flow treatment. Due to the inherent problems of available centrifugal pumps in the low-flow range, clinicians should use the current centrifugal pumps with caution, alternatively other pumping principles such as positive displacement pumps may be discussed in the future. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hemorrhage is an important complication of leptospirosis. Once acute respiratory distress syndrome (ARDS) occurs as a secondary condition, treatment is extremely difficult and the mortality rate is very high.Case Presentation: The patient was a 49-year-old. He was admitted to the hospital because he had experienced a fever and cough for 4 days. Hemorrhage, respiratory failure, ARDS and other symptoms appeared soon after admission. Due to severe pulmonary hemorrhage secondary to ARDS, mechanical ventilation was performed through tracheal intubation. During intubation, the patient suffered cardiac arrest, and the patient's condition worsened. He was confirmed to have leptospirosis through second-generation sequencing of the alveolar lavage fluid. Finally, we successfully treated the patient with penicillin as an anti-infective medication and venous-venous extracorporeal membrane oxygenation (v-vECMO). To the best of our knowledge, this report is the first to describe the successful application of ECMO in mainland China.Conclusions: Leptospirosis can induce serious but transient ARDS with a better prognosis than other causes of ARDS. Our patient was successfully treated with V-vECMO. [ABSTRACT FROM AUTHOR]

The management of Acute Respiratory Distress Syndrome (ARDS) secondary to the novel Coronavirus Disease 2019 (COVID-19) proves to be challenging and controversial. Multiple studies have suggested the likelihood of an atypical pathophysiology to explain the spectrum of pulmonary and systemic manifestations caused by the virus. The principal paradox of COVID-19 pneumonia is the presence of severe hypoxemia with preserved pulmonary mechanics. Data derived from the experience of multiple centers around the world have demonstrated that initial clinical efforts should be focused into avoid intubation and mechanical ventilation in hypoxemic COVID-19 patients. On the other hand, COVID-19 patients progressing or presenting into frank ARDS with typical decreased pulmonary compliance, represents another clinical enigma to many clinicians, since routine therapeutic interventions for ARDS are still a subject of debate. [ABSTRACT FROM AUTHOR]

Background: RESP score and PRESERVE score have been validated for veno-venous Extracorporeal Membrane Oxygenation in severe ARDS to assume individual mortality risk. ARDS patients with low-flow Extracorporeal Carbon Dioxide Removal, especially pumpless Extracorporeal Lung Assist, have also a high mortality rate, but there are no validated specific or general outcome scores. This retrospective study tested whether these established specific risk scores can be validated for pumpless Extracorporeal Lung Assist in ARDS patients in comparison to a general organ dysfunction score, the SOFA score. Methods: In a retrospective single center cohort study we calculated and evaluated RESP, PRESERVE, and SOFA score for 73 ARDS patients with pumpless Extracorporeal Lung Assist treated between 2002 and 2016 using the XENIOS iLA Membrane Ventilator. Six patients had a mild, 40 a moderate and 27 a severe ARDS according to the Berlin criteria. Demographic data and hospital mortality as well as ventilator settings, hemodynamic parameters, and blood gas measurement before and during extracorporeal therapy were recorded. Results: Pumpless Extracorporeal Lung Assist of mechanical ventilated ARDS patients resulted in an optimized lung protective ventilation, significant reduction of PaCO2, and compensation of acidosis. Scoring showed a mean score of alive versus deceased patients of 3 ± 1 versus − 1 ± 1 for RESP (p < 0.01), 3 ± 0 versus 6 ± 0 for PRESERVE (p < 0.05) and 8 ± 1 versus 10 ± 1 for SOFA (p < 0.05). Using receiver operating characteristic curves, area under the curve (AUC) was 0.78 (95% confidence interval (CI) 0.67–0.89, p < 0.01) for RESP score, 0.80 (95% CI 0.70–0.90, p < 0.0001) for PRESERVE score and 0.66 (95% CI 0.53–0.79, p < 0.05) for SOFA score. Conclusions: RESP and PRESERVE scores were superior to SOFA, as non-specific critical care score. Although scores were developed for veno-venous ECMO, we could validate RESP and PRESERVE score for pumpless Extracorporeal Lung Assist. In conclusion, RESP and PRESERVE score are suitable to estimate mortality risk of ARDS patients with an arterio-venous pumpless Extracorporeal Carbon Dioxide Removal. [ABSTRACT FROM AUTHOR]

Background: Positive end-expiratory pressure (PEEP) at minimum respiratory elastance during mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) may improve patient care and outcome. The Clinical utilisation of respiratory elastance (CURE) trial is a two-arm, randomised controlled trial (RCT) investigating the performance of PEEP selected at an objective, model-based minimal respiratory system elastance in patients with ARDS.Methods and Design: The CURE RCT compares two groups of patients requiring invasive MV with a partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio ≤ 200; one criterion of the Berlin consensus definition of moderate (≤ 200) or severe (≤ 100) ARDS. All patients are ventilated using pressure controlled (bi-level) ventilation with tidal volume = 6-8 ml/kg. Patients randomised to the control group will have PEEP selected per standard practice (SPV). Patients randomised to the intervention will have PEEP selected based on a minimal elastance using a model-based computerised method. The CURE RCT is a single-centre trial in the intensive care unit (ICU) of Christchurch hospital, New Zealand, with a target sample size of 320 patients over a maximum of 3 years. The primary outcome is the area under the curve (AUC) ratio of arterial blood oxygenation to the fraction of inspired oxygen over time. Secondary outcomes include length of time of MV, ventilator-free days (VFD) up to 28 days, ICU and hospital length of stay, AUC of oxygen saturation (SpO2)/FiO2 during MV, number of desaturation events (SpO2 < 88%), changes in respiratory mechanics and chest x-ray index scores, rescue therapies (prone positioning, nitric oxide use, extracorporeal membrane oxygenation) and hospital and 90-day mortality.Discussion: The CURE RCT is the first trial comparing significant clinical outcomes in patients with ARDS in whom PEEP is selected at minimum elastance using an objective model-based method able to quantify and consider both inter-patient and intra-patient variability. CURE aims to demonstrate the hypothesized benefit of patient-specific PEEP and attest to the significance of real-time monitoring and decision-support for MV in the critical care environment.Trial Registration: Australian New Zealand Clinical Trial Registry, ACTRN12614001069640. Registered on 22 September 2014. (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366838&isReview=true) The CURE RCT clinical protocol and data usage has been granted by the New Zealand South Regional Ethics Committee (Reference number: 14/STH/132). [ABSTRACT FROM AUTHOR]

Objectives: The primary objective is to demonstrate that, in patients with PCR-confirmed SARS-CoV-2 resulting in Acute Respiratory Distress Syndrome (ARDS), administration of 120mg/kg of body weight of intravenous Prolastin®(plasma-purified alpha-1 antitrypsin) reduces circulating plasma levels of interleukin-6 (IL-6). Secondary objectives are to determine the effects of intravenous Prolastin® on important clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs).Trial Design: Phase 2, randomised, double-blind, placebo-controlled, pilot trial.Participants: The study will be conducted in Intensive Care Units in hospitals across Ireland. Patients with a laboratory-confirmed diagnosis of SARS-CoV-2-infection, moderate to severe ARDS (meeting Berlin criteria for a diagnosis of ARDS with a PaO2/FiO2 ratio <200 mmHg), >18 years of age and requiring invasive or non-invasive mechanical ventilation. All individuals meeting any of the following exclusion criteria at baseline or during screening will be excluded from study participation: more than 96 hours has elapsed from onset of ARDS; age < 18 years; known to be pregnant or breastfeeding; participation in a clinical trial of an investigational medicinal product (other than antibiotics or antivirals) within 30 days; major trauma in the prior 5 days; presence of any active malignancy (other than nonmelanoma skin cancer) which required treatment within the last year; WHO Class III or IV pulmonary hypertension; pulmonary embolism prior to hospital admission within past 3 months; currently receiving extracorporeal life support (ECLS); chronic kidney disease receiving dialysis; severe chronic liver disease with Child-Pugh score > 12; DNAR (Do Not Attempt Resuscitation) order in place; treatment withdrawal imminent within 24 hours; Prisoners; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; IgA deficiency.Intervention and Comparator: Intervention: Either a once weekly intravenous infusion of Prolastin® at 120mg/kg of body weight for 4 weeks or a single dose of Prolastin® at 120mg/kg of body weight intravenously followed by once weekly intravenous infusion of an equal volume of 0.9% sodium chloride for a further 3 weeks. Comparator (placebo): An equal volume of 0.9% sodium chloride intravenously once per week for four weeks.Main Outcomes: The primary effectiveness outcome measure is the change in plasma concentration of IL-6 at 7 days as measured by ELISA. Secondary outcomes include: safety and tolerability of Prolastin® in the respective groups (as defined by the number of SAEs and AEs); PaO2/FiO2 ratio; respiratory compliance; sequential organ failure assessment (SOFA) score; mortality; time on ventilator in days; plasma concentration of alpha-1 antitrypsin (AAT) as measured by nephelometry; plasma concentrations of interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA; development of shock; acute kidney injury; need for renal replacement therapy; clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO2/FiO2 or development of shock or mortality following a period of sustained clinical improvement; secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture.Randomisation: Following informed consent/assent patients will be randomised. The randomisation lists will be prepared by the study statistician and given to the unblinded trial personnel. However, the statistician will not be exposed to how the planned treatment will be allocated to the treatment codes. Randomisation will be conducted in a 1:1:1 ratio, stratified by site and age.Blinding (masking): The investigator, treating physician, other members of the site research team and patients will be blinded to treatment allocation. The clinical trial pharmacy personnel and research nurses will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set to maintain blinding.Numbers To Be Randomised (sample Size): A total of 36 patients will be recruited and randomised in a 1:1:1 ratio to each of the trial arms.Trial Status: In March 2020, version 1.0 of the trial protocol was submitted to the local research ethics committee (REC), Health Research Consent Declaration Committee (HRCDC) and the Health Products regulatory Authority (HPRA). REC approval was granted on April 1st 2020, HPRA approval was granted on April 24th 2020 and the HRCDC provided a conditional declaration on April 17th 2020. In July 2020 a substantial amendment (version 2.0) was submitted to the REC, HRCDC and HPRA. Protocol changes in this amendment included: the addition of trial sites; extending the duration of the trial to 12 months from 3 months; removal of inclusion criteria requiring the need for vasopressors; amendment of randomisation schedule to stratify by age only and not BMI and sex; correction of grammatical error in relation to infusion duration; to allow for inclusion of subjects who may have been enrolled in a clinical trial involving either antibiotics or anti-virals in the past 30 days; to allow for inclusion of subjects who may be currently enrolled in a clinical trial involving either antibiotics or anti-virals; to remove the need for exclusion based on alpha-1 antitrypsin phenotype; removal of mandatory isoelectric focusing of plasma to confirm Pi*MM status at screening; removal of need for mandatory echocardiogram at screening; amendment on procedures around plasma analysis to reflect that this will be conducted at the central site laboratory (as trial is multi-site and no longer single site); wording amended to reflect that interim analysis of cytokine levels taken at 7 days may be conducted. HRCDC approved version 2.0 on September 14th 2020, and HPRA approved on October 22nd 2020. REC approved the substantial amendment on November 23rd. In November 2020, version 3.0 of the trial protocol was submitted to the REC and HPRA. The rationale for this amendment was to allow for patients with moderate to severe ARDS from SARS-CoV-2 with non-invasive ventilation. HPRA approved this amendment on December 1st 2020 and the REC approved the amendment on December 8th 2020. Patient recruitment commenced in April 2020 and the last patient will be recruited to the trial in April 2021. The last visit of the last patient is anticipated to occur in April 2021. At time of writing, patient recruitment is now complete, however follow-up patient visits and data collection are ongoing.Trial Registration: EudraCT 2020-001391-15 (Registered 31 Mar 2020).Full Protocol: The full protocol (version 3.0 23.11.2020) is attached as an additional file accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). [ABSTRACT FROM AUTHOR]

Background: Double lumen intubation and one-lung ventilation should be applied without delay in cases of traumatic main bronchial rupture. In most cases, when the patients' vital signs have been stabilized, the repair can be performed. However, when one-lung ventilation is complicated by traumatic wet lung, the mortality rate is likely to be much higher.Case Presentation: In this case, the patient experienced a left main bronchial rupture, bilateral traumatic wet lung, and acute respiratory distress syndrome (ARDS) because of severe thoracic trauma. Though the patient was treated with intubation and mechanical ventilation (MV), his oxygenation was still not stable. Thus, veno-venous extracorporeal membrane oxygenation (V-V ECMO) was initiated; upon improvement of oxygenation, the patient received an exploratory thoracotomy. Unfortunately, the rupture proved to be irreparable, resulting in a total left pneumonectomy. As there was severe ARDS caused by trauma, ECMO and ultra-low tidal volume (VT) MV strategy (3 ml/kg) were utilized for lung protection post-op. ECMO was sustained up to the 10th day, and MV until the 20th day, post-operation. With the support of MV, ECMO and other comprehensive measures, the patient made a recovery.Conclusion: V-V ECMO and ultra-low VT MV helped this thoracic trauma patient survive the lung edema period and prevented ventilator associated pneumonia (VAP). In extreme situations, with the support of ECMO, the tidal volume may be lowered to 3 ml/kg. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening condition and the identification of the underlying direct (pulmonary) or indirect (non-pulmonary) cause is mandatory for a successful treatment. Intragastric balloon (IGB) therapy is a minimal invasive and supposedly harmless option to reduce body weight for the growing number of obese people. We present a case of a young patient who developed a direct ARDS due to initially undiagnosed abdominal pathologies caused by an IGB therapy. Case presentation: A 23-year old woman was admitted because of a direct ARDS for extracorporeal membrane oxygenation (ECMO) therapy. Weeks before, an IGB has been removed because of abdominal pain and free intraabdominal air. Diagnostic work-up of free intraabdominal air, previous pain of the left shoulder and newly developed abscess pneumonia revealed a perforation of the posterior wall of the gastral antrum. This resulted in a left subphrenic abscess with destruction of the diaphragm, development of pneumonia per continuitatem and subsequent direct lung injury. The gastric perforation was endoscopically clipped and the ARDS was successfully treated under ECMO therapy. Conclusion: This case illustrates that a patient presenting with direct ARDS may have upper abdominal pathologies caused by a rare complication of a supposedly harmless treatment. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below.Trial Design: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial.Participants: The study will be conducted in Intensive Care Units in hospitals across the United Kingdom. Patients with moderate to severe ARDS as defined by the Berlin definition, receiving invasive mechanical ventilation and with a diagnosis of COVID-19 based on clinical diagnosis or PCR test will be eligible. Patients will be excluded for the following reasons: more than 72 hours from the onset of ARDS; age < 16 years; patient known to be pregnant; major trauma in previous 5 days; presence of any active malignancy (other than non-melanoma skin cancer); WHO Class III or IV pulmonary hypertension; venous thromboembolism currently receiving anti-coagulation or within the past 3 months; patient receiving extracorporeal life support; severe chronic liver disease (Child-Pugh > 12); Do Not Attempt Resuscitation order in place; treatment withdrawal imminent within 24 hours; prisoners; declined consent; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; previously enrolled in the REALIST trial.Intervention and Comparator: Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x106 cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration. Comparator (placebo): Plasma-Lyte 148 Solution for Infusion (200mls). The cellular product (REALIST ORBCEL-C) was developed and patented by Orbsen Therapeutics.Main Outcomes: The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is Oxygenation Index (OI) at day 7. Secondary outcomes include: OI at days 4 and 14; respiratory compliance, driving pressure and PaO2/FiO2 ratio (PF ratio) at days 4, 7 and 14; Sequential Organ Failure Assessment (SOFA) score at days 4, 7 and 14; extubation and reintubation; ventilation free days at day 28; duration of mechanical ventilation; length of ICU and hospital stay; 28-day and 90-day mortality.Randomisation: After obtaining informed consent, patients will be randomised via a centralised automated 24-hour telephone or web-based randomisation system (CHaRT, Centre for Healthcare Randomised Trials, University of Aberdeen). Randomisation will be stratified by recruitment centre and by vasopressor use and patients will be allocated to REALIST ORBCEL-C or placebo control in a 1:1 ratio.Blinding (masking): The investigator, treating physician, other members of the site research team and participants will be blinded. The cell therapy facility and clinical trials pharmacist will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set.Numbers To Be Randomised (sample Size): A sample size of 60 patients with 30 patients randomised to the intervention and 30 to the control group. If possible, recruitment will continue beyond 60 patients to provide more accurate and definitive trial results. The total number of patients recruited will depend on the pandemic and be guided by the data monitoring and ethics committee (DMEC).Trial Status: REALIST Phase 1 completed in January 2020 prior to the COVID-19 pandemic. This was an open label dose escalation study of REALIST ORBCEL-C in patients with ARDS. The COVID-19 pandemic emerged as REALIST Phase 2 was planned to commence and the investigator team decided to repurpose the Phase 2 trial as a COVID-19 specific trial. This decision was discussed and approved by the Trial Steering Committee (TSC) and DMEC. Submissions were made to the Research Ethics Committee (REC) and MHRA to amend the protocol to a COVID-19 specific patient population and the protocol amendment was accepted by the REC on 27th March 2020 and MHRA on 30th March 2020 respectively. Other protocol changes in this amendment included an increase in the time of onset of ARDS from 48 to 72 hours, inclusion of clinical outcomes as secondary outcomes, the provision of an option for telephone consent, an indicative sample size and provision to continue recruitment beyond this indicative sample size. The current protocol in use is version 4.0 23.03.2020 (Additional file 1). Urgent Public Health status was awarded by the NIHR on 2 April 2020 and the trial opened to recruitment and recruited the first participant the same day. At the time of publication the trial was open to recruitment at 5 sites across the UK (Belfast Health and Social Care Trust, King's College London, Guys and St Thomas' Hospital London, Birmingham Heartlands Hospital and the Queen Elizabeth Hospital Birmingham) and 12 patients have been recruited across these sites. Additional sites are planned to open and appropriate approvals for these are being obtained. It is estimated recruitment will continue for 6 months.Trial Registration: ClinicalTrials.gov NCT03042143 (Registered 3 Feb 2017). EudraCT 2017-000585-33 (Registered 28 Nov 2017).Full Protocol: The full protocol (version 4.0 23.03.2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). [ABSTRACT FROM AUTHOR]

Background: Evidence concerning the efficacy and safety of extracorporeal membrane oxygenation (ECMO) in patients with influenza A (H7N9) has been was limited to case reports. Our study is aimed to investigate the current application, efficacy and safety of ECMO in for severe H7N9 pneumonia-associated acute respiratory distress syndrome (ARDS) in the Chinese population. Methods: A multicentre retrospective cohort study was conducted at 20 hospitals that admitted patients with avian influenza A (H7N9) viral pneumonia patients' admission from 9 provinces in China between October 1, 2016, and March 1, 2017. Data from the National Health and Family Planning Commission of China, including general conditions, outcomes and ECMO management, were analysed. Then, successfully weaned and unsuccessfully weaned groups were compared. Results: A total of 35 patients, aged 57 ± 1 years, were analysed; 65.7% of patients were male with 63% mortality. All patients underwent invasive positive pressure ventilation (IPPV), and rescue ventilation strategies were implemented for 23 cases (65.7%) with an average IPPV duration of 5 ± 1 d, PaO2/FiO2 of 78 ± 23 mmHg, tidal volume (VT) of 439 ± 61 ml and plateau pressure (Pplat) of 29±8 cmH2O pre-ECMO. After 48 h on ECMO, PaO2 improved from 56 ± 21 mmHg to 90 ± 24 mmHg and PaCO2 declined from 52 ± 24 mmHg to 38 ± 24 mmHg. Haemorrhage, ventilator-associated pneumonia (VAP) and barotrauma occurred in 45.7%, 60% and 8.6% of patients, respectively. Compared with successfully weaned patients (n = 14), the 21 unsuccessfully weaned patients had a longer duration of IPPV pre-ECMO (6 ± 4 d vs. 2 ± 1 d, P < 0.01) as well as a higher Pplat (25 ± 5 cmH2O vs. 21 ± 3 cmH2O, P < 0.05) and VT (343 ± 96 ml vs. 246 ± 93 ml, P < 0.05) after 48 h on ECMO support. Furthermore, the unsuccessfully weaned group had a higher mortality (100% vs. 7.1%, P < 0.01) with more haemorrhage (77.3% vs. 28.6%, P < 0.01). Conclusions: ECMO is effective at improving oxygenation and ventilation of patients with avian influenza A (H7N9) induced severe ARDS. Early initiation of ECMO with appropriate IPPV settings and anticoagulation strategies are necessary to reduce complications. [ABSTRACT FROM AUTHOR]