Nejvíce citovaný článek - PubMed ID 28006947
Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome
The inflammation present in acute respiratory distress syndrome (ARDS) and thereby associated injury to the alveolar-capillary membrane and pulmonary surfactant can potentiate respiratory failure. Even considering the high mortality rate of severe ARDS, glucocorticoids appear to be a reasonable treatment option along with an appropriate route of delivery to the distal lung. This study aimed to investigate the effect of budesonide therapy delivered intratracheally by high-frequency oscillatory ventilation (HFOV) on lung function and inflammation in severe ARDS. Adult New Zealand rabbits with respiratory failure (P/F<13.3 kPa) induced by intratracheal instillation of hydrochloric acid (HCl, 3 ml/kg, pH 1.5) followed by high tidal ventilation (VT 20 ml/kg) to mimic ventilator-induced lung injury (VILI) were treated with intratracheal bolus of budesonide (0.25 mg/kg, Pulmicort) delivered by HFOV (frequency 8 Hz, MAP 1 kPa, deltaP 0.9 kPa). Saline instead of HCl without VILI with HFOV delivered air bolus instead of therapy served as healthy control. All animals were subjected to lung-protective ventilation for 4 h, and respiratory parameters were monitored regularly. Postmortem, lung injury, wet-to-dry weight ratio, leukocyte shifts, and levels of cytokines in plasma and lung were evaluated. Budesonide therapy improved the lung function (P/F ratio, oxygenation index, and compliance), decreased the cytokine levels, reduced lung edema and neutrophils influx into the lung, and improved lung architecture in interstitial congestion, hyaline membrane, and atelectasis formation compared to untreated animals. This study indicates that HFOV delivered budesonide effectively ameliorated respiratory function, and attenuated acid-induced lung injury in a rabbit model of severe ARDS.
Acute lung injury is characterized by acute respiratory insufficiency with tachypnea, cyanosis refractory to oxygen, decreased lung compliance, and diffuse alveolar infiltrates on chest X-ray. The 1994 American-European Consensus Conference defined "acute respiratory distress syndrome, ARDS" by acute onset after a known trigger, severe hypoxemia defined by PaO2/FiO2=200 mm Hg, bilateral infiltrates on chest X-ray, and absence of cardiogenic edema. Milder form of the syndrome with PaO2/FiO2 between 200-300 mm Hg was named "acute lung injury, ALI". Berlin Classification in 2012 defined three categories of ARDS according to hypoxemia (mild, moderate, and severe), and the term "acute lung injury" was assigned for general description or for animal models. ALI/ARDS can originate from direct lung triggers such as pneumonia or aspiration, or from extrapulmonary reasons such as sepsis or trauma. Despite growing understanding the ARDS pathophysiology, efficacy of standard treatments, such as lung protective ventilation, prone positioning, and neuromuscular blockers, is often limited. However, there is an increasing evidence that direct and indirect forms of ARDS may differ not only in the manifestations of alterations, but also in the response to treatment. Thus, individualized treatment according to ARDS subtypes may enhance the efficacy of given treatment and improve the survival of patients.
- MeSH
- akutní poškození plic patofyziologie terapie MeSH
- lidé MeSH
- syndrom dechové tísně patofyziologie terapie MeSH
- umělé dýchání metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH