scholarly journals Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Zachary M. Holliday ◽  
Alexander P. Earhart ◽  
Mohammed M. Alnijoumi ◽  
Armin Krvavac ◽  
Lee-Ann H. Allen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Extracellular Dna ◽  
Arterial Oxygen ◽  
P Value ◽  
Positive Effects ◽  
Dornase Alfa

BackgroundThe most severe cases of Coronavirus-Disease-2019 (COVID-19) develop into Acute Respiratory Distress Syndrome (ARDS). It has been proposed that oxygenation may be inhibited by extracellular deoxyribonucleic acid (DNA) in the form of neutrophil extracellular traps (NETs). Dornase alfa (Pulmozyme, Genentech) is recombinant human deoxyribonuclease I that acts as a mucolytic by cleaving and degrading extracellular DNA. We performed a pilot study to evaluate the effects of dornase alfa in patients with ARDS secondary to COVID-19.MethodsWe performed a pilot, non-randomized, case-controlled clinical trial of inhaled dornase for patients who developed ARDS secondary to COVID-19 pneumonia.ResultsImprovement in arterial oxygen saturation to inhaled fraction of oxygen ratio (PaO2/FiO2) was noted in the treatment group compared to control at day 2 (95% CI, 2.96 to 95.66, P-value = 0.038), as well as in static lung compliance at days 3 through 5 (95% CI, 4.8 to 19.1 mL/cmH2O, 2.7 to 16.5 mL/cmH2O, and 5.3 to 19.2 mL/cmH2O, respectively). These effects were not sustained at 14 days. A reduction in bronchoalveolar lavage fluid (BALF) myeloperoxidase-DNA (DNA : MPO) complexes (95% CI, -14.7 to -1.32, P-value = 0.01) was observed after therapy with dornase alfa.ConclusionTreatment with dornase alfa was associated with improved oxygenation and decreased DNA : MPO complexes in BALF. The positive effects, however, were limited to the time of drug delivery. These data suggest that degradation of extracellular DNA associated with NETs or other structures by inhaled dornase alfa can be beneficial. We propose a more extensive clinical trial is warranted.Clinical Trial RegistrationClinicalTrials.gov, Identifier: NCT04402970.

scholarly journals Comorbidities as Risk Factors for Mortality in COVID-19 Acute Respiratory Distress Syndrome Adult Patients: A Single-Center Retrospective Study

2021 ◽  
Vol 2 (6) ◽  
Author(s):  
Putra Kurnia Nugraha ◽  
Edward Kusuma ◽  
Soni Sunarso Sulistiawan ◽  
Teuku Aswin Husain
Keyword(s):  
Risk Factors ◽  
Acute Respiratory Distress Syndrome ◽  
Chronic Disease ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Hospital Death ◽  
P Value ◽  
Chronic Hypertension ◽  
Single Center

Background: Geriatric, obesity, and chronic disease are classified as risk factors for adverse outcomes of coronavirus disease 2019 (COVID-19). Studies regarding the importance of these comorbidities in COVID-19 with severe complications such as acute respiratory distress syndrome (ARDS) are scarce. This study aims to analyze age, obesity, and chronic disease comorbidities as risk factors for 28-days mortality in COVID-19 patients with ARDS. Methods: A retrospective, single-center study was conducted in Dr. Soetomo General Hospital, Surabaya, Indonesia between July-October 2020. We included all adult inpatients (≥18 years old) of confirmed COVID-19 with ARDS. Demographic, comorbidities, initial PaO2/FiO2 ratio, time of discharge or death were obtained from medical records and compared the ARDS severity between survivors and non-survivors. The univariate and multivariate logistic regression methods were used to identify risk factors associated with in-hospital death. Result: Among 102 patients of COVID-19 with ARDS, the median age is 52 years. Most of them are within 50 – 59 age categories. The median hospital length of stay (LOS) for survivor is 22 (15.7 – 26) days and 9 (4.25 – 14.4) days for non-survivor. The 28-days mortality rate is 48 (47.1%) patients. Age > 65 years old (HR= 2.7, 95% CI 1.39 – 5.44, p value= 0.004), obesity (HR= 2.2, 95% CI 1.16 – 4.51, p value= 0.016), and chronic hypertension (HR= 1.98, 95% CI 1.11 – 3.52, p value= 0.02) are the independent risk factors for 28-days mortality in COVID-19 with ARDS. Conclusion: Geriatric, obesity, and chronic hypertension comorbidities are the risk factors for mortality of COVID-19 with ARDS complications.

scholarly journals Efficacity of Ventilator strategy in A.R.D.S (Acute Respiratory Distress Syndrome).

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Alma Cani ◽  
Fadil Gradica ◽  
Fahri Kokiçi ◽  
Loreta Agolli
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Gradual Increase ◽  
Peep Level ◽  
Arterial Oxygen Tension ◽  
Experimental Models ◽  
Arterial Oxygen ◽  
Significance Level

Background: ARDS is defined as pulmonary inflammatory process characterized by increased capillary permeability associated with acute severe hypoxemia and bilateral  infiltrates on the chest radiograph. Chlinical manifestations of ARDS is associated with a reduction of  functional residual capacity and  static compliance of the respiratory system.Recently,after experimental models and physiological studies have just established the principles to understand  the potential beneficial effects  of PEEP and reduction in mortality to 22%. The benefit of PEEP has been demonstrated in terms of preventing cyclic opening and collapsing alveoli in acute respiratory distress syndrome patients (ARDS). Aim of study: To determine  the appropriate PEEP level in-patients with ARDS. Objective: By using optimal PEEP:to realize the maximal alveolar recruitment.To avoid the decrease of oxygen delivery (DO2) as result of an unfavourable reduction in cardiac output. Material and methods:Retrospectiv study of 120 patients which only 63 of them are included in study with age 18-70 years old.(2012-2014 )  The entry criteria were clinically (severe dyspnoea, tachypnea, cyanosis); PaO2/FiO2 <200mmHG, the presence of bilateral chest infiltrates. The exclusion criteria were: aged < 18 yrs, COPD in history of diseases, heart attack; PEEP was set the level that provided the greatest improvement in oxygenation. The optimal PEEP came as a result of gradual increase of PEEP from 2-5 cmH2O every 6 hours, depended on gas analyses. The right PEEP level is the PEEP allowing the highest PaO2 value without causing hemodynamic compromise. Results: During this study we conclude that the gradual increase of PEEP improves significantly arterial oxygen tension (PaO2). Per value of PEEP 9.6-15.8, CI 95% is 145.9-191.8. The  Pearson test  with a significant correlation coefficient of level 0.995 and significance level 0.000 shows also a very important result. It was considered significant statistically the value of P≤ 0.05.  Also  the value of Chi ² of PaO2 and of PEEP, has resulted significant in 0.950 with P < 0.001. Conclusion: Mechanical ventilation using optimal PEEP increases the value of PaO2. As a matter of fact 88% of cases with PaO2 > 220 mmHg survive. The role of PEEP in clinical practice is still debated but, in selected categories of patients with a careful monitoring, it may play an important role in improving outcome.

scholarly journals Effects of PDE3 Inhibitor Olprinone on the Respiratory Parameters, Inflammation, and Apoptosis in an Experimental Model of Acute Respiratory Distress Syndrome

2020 ◽  
Vol 21 (9) ◽  
pp. 3382
Author(s):  
Petra Kosutova ◽  
Pavol Mikolka ◽  
Sona Balentova ◽  
Marian Adamkov ◽  
Andrea Calkovska ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Arterial Oxygen Saturation ◽  
Oxygenation Index ◽  
Arterial Oxygen ◽  
Arterial Blood ◽  
Respiratory Parameters ◽  
Pde3 Inhibitor

This study aimed to investigate whether a selective phosphodiesterase-3 (PDE3) inhibitor olprinone can positively influence the inflammation, apoptosis, and respiratory parameters in animals with acute respiratory distress syndrome (ARDS) model induced by repetitive saline lung lavage. Adult rabbits were divided into 3 groups: ARDS without therapy (ARDS), ARDS treated with olprinone i.v. (1 mg/kg; ARDS/PDE3), and healthy ventilated controls (Control), and were oxygen-ventilated for the following 4 h. Dynamic lung–thorax compliance (Cdyn), mean airway pressure (MAP), arterial oxygen saturation (SaO2), alveolar-arterial gradient (AAG), ratio between partial pressure of oxygen in arterial blood to a fraction of inspired oxygen (PaO2/FiO2), oxygenation index (OI), and ventilation efficiency index (VEI) were evaluated every hour. Post mortem, inflammatory and oxidative markers (interleukin (IL)-6, IL-1β, a receptor for advanced glycation end products (RAGE), IL-10, total antioxidant capacity (TAC), 3-nitrotyrosine (3NT), and malondialdehyde (MDA) and apoptosis (apoptotic index and caspase-3) were assessed in the lung tissue. Treatment with olprinone reduced the release of inflammatory mediators and markers of oxidative damage decreased apoptosis of epithelial cells and improved respiratory parameters. The results indicate a future potential of PDE3 inhibitors also in the therapy of ARDS.

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