scholarly journals Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Esther J. Nossent ◽  
Alex R. Schuurman ◽  
Tom D.Y. Reijnders ◽  
Anno Saris ◽  
Ilse Jongerius ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Growth Factors ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Complement System ◽  
Host Response ◽  
Distress Syndrome ◽  
Response Biomarkers

RationaleSystemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.ObjectivesTo evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.MethodsPaired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.Measurements and Main ResultsIn all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.ConclusionsCritically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory “storm” in severe COVID-19.

scholarly journals Effectiveness and Outcome of Methylprednisolone versus Hydrocortisone in Treatment of Acute Respiratory Distress Syndrome(ARDS)

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S A S Elbrassi ◽  
K M Maghawry ◽  
R M M Ali ◽  
R H Abdelhafiez
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Low Dose ◽  
Distress Syndrome ◽  
Patient Discharge ◽  
P Value ◽  
D Dimer

Abstract Introduction Acute respiratory distress syndrome (ARDS) is the clinical manifestation of severe acute lung injury. It is characterized by dyspnea, profound hypoxemia, diffuse bilateral infiltrates secondary to non-cardiogenic pulmonary edema on chest radiography, and decreased lung compliance and systemic inflammations are the pathophysiologic hallmarks of this syndrome and the use of low-dose corticosteroids was associated with improved mortality and morbidity outcomes without increased adverse reactions. Aim The aim of this study is to compare the outcome and effectiveness of hydrocortisone to methylprednisolone in treatment of acute respiratory distress syndrome in critically ill adult patients. Patients The current study was performed as a randomized prospective observational study on critically ill patients at age between 18-85 years. Methods Critically ill patients diagnosis with ARDS were managed with standard treatment in addition to methylprednisolone 1mg/kg as loading dose followed by an infusion of 1 mg/kg/d for one week and then gradual tapering over two weeks as following (0.5 mg/kg/d in the second week and 0.25 mg/kg/d in the third week) or hydrocortisone 50mg given every six hours for one week. Results Mean age of included patients was 65.20 years with mean BMI 28.14 kg/m2, in our result the PaO2/FIO2 ratio revealed significant statistically increase in methylprednisolone-treated patients compared to hydrocortisone -treated patients (160.49±54.75, 138.55±60.99, P value 0.029), Regarding the inflammatory marker the results of the plasma level of C-reactive protein and d-dimer showed significant difference between both group, the result of SOFA score showed no significant different from day 1 to day 3 (8.25±3.11, 8.29±2.29 P value 0.980). But with the beginning of the fifth day was observed significant change in the results, methylprednisolone-treated patients compared to hydrocortisone -treated patients (8.28±3.84, 9.8±4.23, P value 0.036), Regarding to ICU length of stay and decrease duration of mechanical ventilation, the results of our study didn’t show significant different among both groups. The two groups showed a decrease in the time spended on the mechanical ventilation and the stay in the ICU before day7. According to the number of patient discharge from ICU at day 7 and the number of extubated patient at day 7, the results of our study didn’t show significant different among both groups. Conclusion Despite the both applied drug doses show improvement regarding the finial total outcome. However, Methylprednisolone showed superior benefit compare to Hydrocortisone in improvement of PaO2/FiO2 ratio, suppress systemic inflammation (CRP and D- dimer), increase extubated patient before day 7, increase number of patient discharge from ICU before day 7, reduction of SOFA score and hospital morality rate. Recommendations The study recommends to use of low dose methylprednisolone superior to hydrocortisone in treatment of ARDS. But, still more researches are need.

scholarly journals Therapeutic Iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo-Trial): a prospective, randomized, multicenter phase II study

2019 ◽  
Author(s):  
Helene Anna Haeberle ◽  
Stefanie Prohaska ◽  
Peter Martus ◽  
Andreas Straub ◽  
Alexander Zarbock ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Phase Ii ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Serum Levels ◽  
Inflammatory Processes

Abstract Background Acute respiratory distress syndrome (ARDS) is caused by rapid onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of ARDS patients, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS.Methods The Therapeutic Iloprost during ARDS ( ThIIo-Trial) is a multicenter, randomized, clinical phase II trial assessing the efficacy of inhaled Iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index, a health care-related questionnaire and frailty (Vulnerable Elderly Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90-day all-cause mortality, SOFA scores during the study period up to day 90, the duration of mechanical ventilation, the length of ICU stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness and discharge localization. The study will be conducted in three university ARDS centers in Germany.Discussion The results of the ThIlo-Trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in ARDS patients.

scholarly journals Therapeutic Iloprost for the treatment of acute respiratory distress syndrome (ARDS) (the ThIlo-Trial): a prospective, randomized, multicenter phase II study

2020 ◽  
Author(s):  
Helene Anna Haeberle ◽  
Stefanie Prohaska ◽  
Peter Martus ◽  
Andreas Straub ◽  
Alexander Zarbock ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Phase Ii ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Serum Levels ◽  
Inflammatory Processes

Abstract Background Acute respiratory distress syndrome (ARDS) is caused by rapid onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of ARDS patients, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods The Therapeutic Iloprost during ARDS ( ThIIo-Trial) is a multicenter, randomized, clinical phase II trial assessing the efficacy of inhaled Iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index, a health care-related questionnaire and frailty (Vulnerable Elderly Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO 2 /FiO 2 . Secondary endpoints include 90-day all-cause mortality, SOFA scores during the study period up to day 90, the duration of mechanical ventilation, the length of ICU stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion The results of the ThIlo-Trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in ARDS patients.

First reported case of Weissella confusa abundance in the lung microbiota of a critically ill trauma patient with acute respiratory distress syndrome - caution warranted in the use of the Weissella genus as a probiotic

2020 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Distress Syndrome ◽  
Joint Infection ◽  
Starter Cultures ◽  
Trauma Patients ◽  
Virulence Determinants ◽  
Prosthetic Joint

Weissella strains are currently being used for biotechnological and probiotic purposes [1]. While, Weissella hellenica found in flounder intestine had probiotic effects [2], certain species from this genus are opportunistic pathogens in humans. Apart from being implicated in disease in farmed rainbow trout [3], Weissella has been found to cause the following disease in humans.1. endocarditis [4,5]2. bacteraemia [6]3. prosthetic joint infection [7]Whole genome sequences ‘find several virulence determinants such as collagen adhesins, aggregation sub- stances, mucus-binding proteins, and hemolysins in some species’, as well as antibiotic resistance-encoding genes [8]. Caution is warranted in selecting of Weissella strains as starter cultures or probiotics, if at all, since the other option, Lactobacillus, are rarely involved in human disease.Here, the analysis of the lung microbiota in critically ill trauma patients suffering from acute respiratory distress syndrome [9] shows (Accid:ERR1992912) shows complete colonization of Weissella (Fig 1). While, the study mentions ‘significant enrichment of potential pathogens including Streptococcus, Fusobacterium, Prevotella, Haemophilus and Treponema’, there is no reference to the Weissella genus. The percentages of Weissella strains are :confusa=81, soli=7 ,hellenica=5 ,diestrammenae=2. I believe this is the first reported case of Weissella causing ARDS in humans.

A Ventilator-associated Pneumonia Prediction Model in Patients With Acute Respiratory Distress Syndrome

2020 ◽  
Vol 71 (Supplement_4) ◽  
pp. S400-S408
Author(s):  
Zongsheng Wu ◽  
Yao Liu ◽  
Jingyuan Xu ◽  
Jianfeng Xie ◽  
Shi Zhang ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Neuromuscular Blocking ◽  
Calibration Plot ◽  
Binary Logistic Regression Analysis ◽  
Ventilator Associated Pneumonia ◽  
Mechanical Ventilation Duration

Abstract Background Mechanical ventilation is crucial for acute respiratory distress syndrome (ARDS) patients and diagnosis of ventilator-associated pneumonia (VAP) in ARDS patients is challenging. Hence, an effective model to predict VAP in ARDS is urgently needed. Methods We performed a secondary analysis of patient-level data from the Early versus Delayed Enteral Nutrition (EDEN) of ARDSNet randomized controlled trials. Multivariate binary logistic regression analysis established a predictive model, incorporating characteristics selected by systematic review and univariate analyses. The model’s discrimination, calibration, and clinical usefulness were assessed using the C-index, calibration plot, and decision curve analysis (DCA). Results Of the 1000 unique patients enrolled in the EDEN trials, 70 (7%) had ARDS complicated with VAP. Mechanical ventilation duration and intensive care unit (ICU) stay were significantly longer in the VAP group than non-VAP group (P < .001 for both) but the 60-day mortality was comparable. Use of neuromuscular blocking agents, severe ARDS, admission for unscheduled surgery, and trauma as primary ARDS causes were independent risk factors for VAP. The area under the curve of the model was .744, and model fit was acceptable (Hosmer-Lemeshow P = .185). The calibration curve indicated that the model had proper discrimination and good calibration. DCA showed that the VAP prediction nomogram was clinically useful when an intervention was decided at a VAP probability threshold between 1% and 61%. Conclusions The prediction nomogram for VAP development in ARDS patients can be applied after ICU admission, using available variables. Potential clinical benefits of using this model deserve further assessment.

scholarly journals Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia

2021 ◽  
Vol 10 (13) ◽  
pp. 2935
Author(s):  
Jose Bordon ◽  
Ozan Akca ◽  
Stephen Furmanek ◽  
Rodrigo Silva Cavallazzi ◽  
Sally Suliman ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Critical Illness ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Distress Syndrome ◽  
Invasive Mechanical Ventilation ◽  
Overall Mortality

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic’s death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.

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