scholarly journals N-acetylcysteine in Mechanically Ventilated Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: The Effect of Intravenous Dose on Oxidative Damage and Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1885
Author(s):  
Maros Kolomaznik ◽  
Pavol Mikolka ◽  
Juliana Hanusrichterova ◽  
Petra Kosutova ◽  
Katarina Matasova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Respiratory Distress Syndrome ◽  
Oxidative Damage ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Suitable Model ◽  
Mechanically Ventilated ◽  
Lung Oedema ◽  
Lung Functions

Treatment of acute respiratory distress syndrome (ARDS) is challenging due to its multifactorial aetiology. The benefit of antioxidant therapy was not consistently demonstrated by previous studies. We evaluated the effect of two different doses of intravenous (i.v.) N-acetylcysteine (NAC) on oxidative stress, inflammation and lung functions in the animal model of severe LPS-induced lung injury requiring mechanical ventilation. Adult Wistar rats with LPS (500 μg/kg; 2.2 mL/kg) were treated with i.v. NAC 10 mg/kg (NAC10) or 20 mg/kg (NAC20). Controls received saline. Lung functions, lung oedema, total white blood cell (WBC) count and neutrophils count in blood and bronchoalveolar lavage fluid, and tissue damage in homogenized lung were evaluated. NAC significantly improved ventilatory parameters and oxygenation, reduced lung oedema, WBC migration and alleviated oxidative stress and inflammation. NAC20 in comparison to NAC10 was more effective in reduction of oxidative damage of lipids and proteins, and inflammation almost to the baseline. In conclusion, LPS-instilled and mechanically ventilated rats may be a suitable model of ARDS to test the treatment effects at organ, systemic, cellular and molecular levels. The results together with literary data support the potential of NAC in ARDS.

scholarly journals Methylprednisolone Treatment Versus Standard Supportive Care for Adult Covid19 Mechanically Ventilated, Acute Respiratory Distress Syndrome Patients

2021 ◽  
Author(s):  
Masood Ur Rahman ◽  
Satish Chandra Nair ◽  
Mehraj Ud Din ◽  
Mohd Dar ◽  
Murriam Masood ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Length Of Stay ◽  
Respiratory Distress Syndrome ◽  
Supportive Care ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Hospital Length Of Stay ◽  
Care Group ◽  
Mechanically Ventilated ◽  
Methylprednisolone Treatment

Abstract A myriad of symptoms presented by severely ill mechanically ventilated Covid19 patients has added pressure on the caregivers to explore therapeutic options. Systemic steroids have been reported to therapeutically benefit patients with elevated inflammatory markers, during the severe acute respiratory syndrome, and the Middle East respiratory syndrome outbreak. Covid19 disease is characterized by inflammation of the respiratory system and acute respiratory distress syndrome. Given the lack of specific treatment for Covid19, the aim of the current study was to evaluate the therapeutic benefit of methylprednisolone as an add-on treatment for mechanically ventilated hospitalized COVID19 patients with severe covid pneumonia. Data was collected retrospectively from the electronic patient medical records, and inter-rater reliability was determined to limit selection bias. Descriptive and inferential statistical methods were used to analyze the data. The variables were cross-tabulated with the clinical outcome and the Chi-Square test used to determine association between the outcomes and other independent variables. Patients. Sixty-one percent (43/70) of the Covid19 ARDS patients received standard supportive care, and the remainder were administered. methylprednisolone (40 mg daily to 40 mg q 6 hours). A 28-day all-cause mortality rate, in the methylprednisolone group was 18% (5/27, p < 0.01) significantly lower, compared to the group receiving standard supportive care (51%, 22/43). The median number of days, for the hospital length of stay (18 days), ICU-length of stay (9.5 days), and the number of days intubated (6 days) for the methylprednisolone treated group was significantly lower (p < 0.01), when compared with the standard supportive care group. Methylprednisolone treatment also reduced the C-reactive protein levels, compared to the standard care group on day 7. Our results strengthen the evidence for the role of steroids in reducing mortality, ICU LOS, and ventilator days in mechanically ventilated Covid 19 patients with respiratory distress syndrome.

Etiology-associated heterogeneity in acute respiratory distress syndrome

2020 ◽  
Author(s):  
Sheng-Yuan Ruan ◽  
Chun-Ta Huang ◽  
Ying-Chun Chien ◽  
Chun-Kai Huang ◽  
Jung-Yien Chien ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Bacterial Pneumonia ◽  
Distress Syndrome ◽  
Hemodynamic Instability ◽  
Mechanically Ventilated ◽  
Significant Difference ◽  
Failure Assessment ◽  
Chi Squared

Abstract Background: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.Methods: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. Results: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.Conclusion: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

scholarly journals Pharmacodynamics and Atracurium and Laudanosine Concentrations during a Fixed Continuous Infusion of Atracurium in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

2002 ◽  
Vol 30 (4) ◽  
pp. 422-427 ◽  
Author(s):  
J-Y. Lefrant ◽  
C. Farenc ◽  
J-E. De La Coussaye ◽  
L. Muller ◽  
J. Ripart ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Renal Impairment ◽  
Respiratory Distress Syndrome ◽  
Liver Failure ◽  
Respiratory Distress ◽  
Continuous Infusion ◽  
Distress Syndrome ◽  
Fixed Rate ◽  
Mechanically Ventilated ◽  
Train Of Four

The present study was designed to assess the pharmacodynamics and the plasma levels of atracurium and laudanosine found during a 72-hour fixed rate infusion of atracurium in acute respiratory distress syndrome patients without renal or liver failure. Nine sedated and mechanically ventilated acute respiratory distress syndrome patients without renal or liver failure were paralysed with a bolus of atracurium (1 mg.kg -1 ) followed by a 72-hour continuous infusion (1 mg.kg -1 .h -1 ). The count of train-of-four (TOF) and TOF ratio were monitored by an accelerograph until full neuromuscular recovery (T4/T1 0.7). Atracurium and laudanosine concentrations were measured from the onset to four days after cessation of the infusion. An electroencephalogram was recorded daily. Analysis showed that TOF count was always 3 until cessation of the infusion. Following cessation, neuromuscular recovery occurred between 31 and 96 minutes (median value=45 min). The highest atracurium and laudanosine concentrations ranged from 3.3 to 5.8 μg.ml –1 and from 3 to 20 μg.ml –1 respectively. In four patients with renal impairment, the highest laudanosine concentration was > 10 μg.ml –1. No seizure was recorded. A fixed infusion rate of atracurium in acute respiratory distress syndrome patients provided an effective muscle paralysis with a rapid neuromuscular recovery but can lead to accumulation of laudanosine in patients with renal impairment.

Letters to the Editor

1998 ◽  
Vol 85 (5) ◽  
pp. 1998-2000
Author(s):  
Hans-G. Sonander
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Goodness Of Fit ◽  
Distress Syndrome ◽  
Letters To The Editor ◽  
Mechanically Ventilated ◽  
Pulmonary Pressure ◽  
Volume Curve ◽  
Pressure Volume Curve

The following is the abstract of the article discussed in the subsequent letter: Venegas, José G., R. Scott Harris, and Brett A. Simon. A comprehensive equation for the pulmonary pressure-volume curve. J. Appl. Physiol. 84(1): 389–395, 1998.—Quantification of pulmonary pressure-volume (P-V) curves is often limited to calculation of specific compliance at a given pressure or the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure or volume used in the comparison and may lead to erroneous conclusions. We evaluated a sigmoidal equation of the form, V = a + b[1 +  e −(P− c)/ d ]−1, for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal and hypocapnic pneumoconstricted dog lungs ( n = 9), oleic acid-induced acute respiratory distress syndrome ( n = 2), and mechanically ventilated patients with acute respiratory distress syndrome ( n = 10). In this equation, a corresponds to the V of a lower asymptote, b to the V difference between upper and lower asymptotes, c to the P at the true inflection point of the curve, and d to a width parameter proportional to the P range within which most of the V change occurs. The equation fitted equally well inflation and deflation limbs of P-V curves with a mean goodness-of-fit coefficient ( R 2) of 0.997 ± 0.02 (SD). When the data from all analyzed P-V curves were normalized by the best-fit parameters and plotted as (V −  a)/ b vs. (P −  c)/ d, they collapsed into a single and tight relationship ( R 2 = 0.997). These results demonstrate that this sigmoidal equation can fit with excellent precision inflation and deflation P-V curves of normal lungs and of lungs with alveolar derecruitment and/or a region of gas trapping while yielding robust and physiologically useful parameters.

scholarly journals Alveolar CCN1 is associated with mechanical stretch and acute respiratory distress syndrome severity

2020 ◽  
Vol 319 (5) ◽  
pp. L825-L832
Author(s):  
Eric D. Morrell ◽  
Serge Grazioli ◽  
Chi Hung ◽  
Osamu Kajikawa ◽  
Susanna Kosamo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Mechanical Stretch ◽  
Mechanically Ventilated ◽  
Alveolar Epithelial ◽  
Protein Levels

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI ( n = 6) versus noninjured controls ( n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS ( n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS ( n = 45) ( P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.

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