Aerosolized Surfactant Improves Pulmonary Function in Endotoxin-induced Lung Injury
Charles J. LutzDavid E. CarneyChristine FinckAnthony PiconeLouis A. GattoAndrew M. PaskanikEdward G. LangenbackGary F. Nieman
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Abstract:
Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 μ g/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial Po 2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 ± 19 mm Hg; LPS = 74 ± 19 mm Hg, p < 0.05) while venous admixture (Q˙ s/Q˙ t) increased in these groups (LPS + PEEP = 43.3 ± 3.9%; LPS = 47.7 ± 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in Po 2 (142 ± 20 mm Hg) and rise in Q˙ s/Q˙ t (15.1 ± 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 ± 0.2 cells/6,400 μ m2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 ± 0.1 cells/6,400 μ m2). LPS + PEEP + Sf (2.3 ± 0.2 cells/6,400 μ m2) significantly decreased while LPS + PEEP significantly increased (4.0 ± 0.2 cells/6,400 μ m2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.Keywords:
Positive End-Expiratory Pressure
Aerosolization
2019-20 coronavirus outbreak
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Fifteen years have passed since lung protective strategy to the patients with acute respiratory distress syndrome (ARDS) established. Recently, the new Berlin Definition of ARDS has been developed and this classified ARDS into three stages (mild, moderate, and severe ARDS), depending on the PaO2/FiO2. After this new definition of ARDS, each treatment to the patients with ARDS should be considered, depending on the severity of lung injury, such as prone position to the patients with severe ARDS, muscle paralysis to the patients with severe ARDS. In this review article, we review the history of lung protective strategy and ARDS definition, discuss the novel physiological approaches to minimizing ventilator-induced lung injury, and highlight a numbers of experimental/clinical studies to support these concepts.
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Objective To explore the clinical value of serum Ang-1,Ang-2 and IL-8 in ARDS prediction.Methods Totally 283 critically ill patients admitted in EICU of the Hunan Provincial People's Hospital from January 2012 to July 2013 were enrolled in this study and divided into the non-ARDS group (n =251) and ARDS group (n =32) depending on the development of ARDS.According to the occurrence of death in the following 60 days,the non-ARDS group and the ARDS group were further subdivided into the non-ARDS survival group,the non-ARDS death group,thc ARDS survival group and the ARDS death group.The differences in serum Ang-1,Ang-2 and IL-8 concentrations between these four groups measured by ELISA on admission were analyzed by statistical methods and ROC curve.Results The EICU stays,duration of mechanical ventilation,APACHE Ⅱ score、serum Ang-2 and IL-8 levels in the ARDS group were significantly higher than those in the non-ARDS group,while the Ang-1 level in the ARDS group was significantly lower than that in the non-ARDS group.The serum Ang-2 and IL-8 concentrations in the ARDS death group were significantly higher than those in the non-ARDS survival group and the non-ARDS death group,and the serum Ang-2 concentrations in the ARDS death group were also significantly higher than those in the ARDS survival group.Further ROC curve analysis showed that the area under the curve of Ang-2 for ARDS diagnosis and ARDS death prediction were 0.907 and 0.899 respectively and their diagnostic sensitivity and specificity were 0.969 and 0.725,0.907 and 0.882 respectively,illustrating that Ang-2 possess the best diagnostic efficiency.Conclusions Ang-2 functions as a valuable biomarker for early diagnosis and prognosis of ARDS.
Key words:
Acute respiratory distress syndrome; Angiopoietin-1; Angiopoietin-2; Interleukin-8
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Acute respiratory distress syndrome (ARDS) is one the leading causes of mortality and morbidity in patients with COVID-19 and Influenza, with only small number of studies comparing these two viral illnesses in the setting of ARDS. Given the pathogenic differences in the two viruses, this study shows trends in national hospitalization and outcomes associated with COVID-19- and Influenza-related ARDS. To evaluate and compare the risk factors and rates of the adverse clinical outcomes in patients with COVID-19 associated ARDS (C-ARDS) relative to Influenza-related ARDS (I-ARDS), we utilized the National Inpatient Sample (NIS) database 2020. Our sample includes 106,720 patients hospitalized with either C-ARDS or I-ARDS between January and December 2020, of which 103,845 (97.3%) had C-ARDS and 2875 (2.7%) had I-ARDS. Propensity-matched analysis demonstrated a significantly higher in-hospital mortality (aOR 3.2, 95% CI 2.5–4.2, p < 0.001), longer mean length of stay (18.7 days vs. 14.5 days, p < 0.001), higher likelihood of requiring vasopressors (aOR 1.7, 95% CI 2.5–4.2) and invasive mechanical ventilation (IMV) (aOR 1.6, 95% CI 1.3–2.1) in C-ARDS patients. Our study shows that COVID-19-related ARDS patients had a higher rate of complications, including higher in-hospital mortality and a higher need for vasopressors and invasive mechanical ventilation relative to Influenza-related ARDS; however, it also showed an increased utilization of mechanical circulatory support and non-invasive ventilation in Influenza-related ARDS. It emphasizes the need for early detection and management of COVID-19.
2019-20 coronavirus outbreak
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Mechanical ventilation is one of the important measures for the treatment of acute respiratory distress syndrome(ARDS).As in recent years,further study of the pathology of ARDS,mechanical ventilation strategy gradually developed from past tidal volume lung protective ventilation strategy.This paper described the new development of mechanical ventilation strategy for ARDS patients,provide a reference for clinical ventilation in the treatment of patients with ARDS.
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Introduction: It is uncertain whether ventilation management in patients with COVID-19 ARDS differs from that in patients with ARDS from another origin. Aim: To compare ventilation management in published cohorts of COVID-19 patients vs patients with ARDS from another origin. Methods: Two literature searches in PubMed were performed to identify observational studies reporting on ventilation management–one for COVID-19 ARDS, and one for ARDS from another origin. Results: The two searches identified 14 studies in COVID–19 ARDS patients, and 8 studies in patients with ARDS from another origin. In patients with COVID-19 ARDS, ventilation with a lower VT (median from 5.8 to 7.0 ml/kg PBW) was applied more rigorously than in patients with ARDS from another origin (median from 6.7 to 8.4 ml/kg PBW), albeit that Pplat was comparable between patients with COVID-19 ARDS (median from 24 to 27 cm H2O) and patients with ARDS from another origin (median from 19 to 26 cm H2O). PEEP and FiO2 were higher in patients with COVID-19 ARDS (median from 10 to 15 cm H2O, and from 60 to 80%) than in patients with ARDS from another origin (median from 7.5 to 10 cm H2O, and from 45 to 50%). Prone positioning was used more often in patients with COVID-19 ARDS (17 to 76%) than in patients with ARDS from another origin (1%, 6% and 16% in mild, moderate and severe ARDS). Conclusions: Remarkable differences exist in ventilation management of patients with COVID-19 ARDS vs patients with ARDS from another origin. Differences may, at least in part originate from disparities in oxygenation problems, that are more severe in COVID-19 ARDS patients.
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Background & objectives: The decrease in surfactant protein-A (SP-A level) has recently been implicated in the pathophysiology of acute respiratory distress syndrome (ARDS). Mechanical ventilation is the main modality of treatment of ARDS. But information on the SP-A levels after mechanical ventilation is scanty. We therefore studied the effect of mechanical ventilation on SP-A levels in patients with ARDS. Methods: In a prospective, observational study conducted in the Respiratory Intensive Care Unit of a tertiary care hospital in north India, 13 patients with ARDS requiring mechanical ventilation were included. SP-A levels in the bronchial aspirates were serially estimated by ELISA at the start of mechanical ventilation and after 24 and after 48 h. Results: The SP-A level at the start of mechanical ventilation was 3.06±2.56 µg/ml. The levels gradually increased to 3.99±2.39 and 6.64±2.72 µg/ml, at 24 and 48 h respectively, and this increase was statistically significant (P<0.05). Patients having an infectious etiology had lower SP-A levels compared to those with non-infections causes. Neither the initial SP-A level nor the increase in SP-A level correlated with the improvement in lung function or duration of ventilation. Interpretation & conclusion : The present study showed a progressive increase in the SP-A levels in patients with ARDS on mechanical ventilation. Further studies are required to confirm that the increase in SP-A levels may be one of the contributors for recovery in ARDS.
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The ExPress Trial examined the role of a positive end-expiratory pressure (PEEP) strategy targeting increased alveolar recruitment versus minimal alveolar distension in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Although lung protective ventilation in ALI and ARDS showed significant mortality benefit, the optimal PEEP strategy was unclear. The primary outcome of the study was 28 day mortality. Secondary outcomes included ventilator-free days, organ failure–free days, and barotrauma-related adverse events. Even though there was no significant difference in mortality between the two arms of the study, a significant difference was identified in ventilator-free days and organ failure–free days, which supported an increased recruitment PEEP strategy in the ALI/ARDS population and encouraged further examination.
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