Corticosteroids in Late Adult Respiratory Distress Syndrome – Towards a Better Use

Abstract

Accessible online at: http://BioMedNet.com/karger Adult respiratory distress syndrome (ARDS) is a very severe form of lung injury, which occurs associated with a variety of pulmonary and extrapulmonary pathologies [1]. The response of the lung to injury is stereotyped and mainly results from the disruption of the alveolar-capillary unit. However, in the diffuse alveolar damage which characterizes the disease, sequential phases that correlate with the clinical evolution of the disease can be identified [2]. The exudative phase, in which oedema and haemorrhage occur in alveoli, develops within approximately 1 week after the onset of respiratory failure. In this early phase, the distinctive features of ARDS are hyaline membranes which derive from the leakage of plasma proteins through the damaged endothelium-epithelial barrier into the alveolar space. The second or fibroproliferative phase derives from the organization of intra-alveolar and interstitial exudates and takes place between the first and the third weeks after injury. Now fibroblasts and myofibroblasts proliferate and migrate through the alveolar basement membrane into the alveolar exudate. Within the alveolar wall, fibroblats also cause alveolar septal fibrosis. Finally, in the last phases of ARDS, pulmonary vessels are extensively remodelled, and both chronic interstitial emphysema and pulmonary hypertension can develop. The term ‘late ARDS’ refers to its clinical stage in which the lungs attempt to repair the initial and persistent injury to the respiratory unit. The histologic correspondent is termed ‘fibroproliferative phase’ because it can lead to extensive fibrosis [3]. Mortality associated with ARDS can be as high as 50– 70%. The two major causes of death in patients with late ARDS (13 days), which are frequently unrecognized before death, are sepsis related to nosocomial pneumonia and pulmonary fibrosis. Sepsis has been claimed to be responsible for both endothelial-alveolar damage and multiple organ failure. However, uncontrolled activation of mediators of inflammation has also been described in the so-called sepsis syndrome, in which the clinical features of sepsis are present, but no focus of infection can be demonstrated [4]. In order to better understand the evolution of oedema and haemorrhage into interstitial fibrosis, several interleukins (IL-1, IL-6, IL-8) and TNF have been studied. In addition, locally produced cytokines are probably also responsible for chemotaxis and activation of lung fibroblasts and thus facilitate the development of fibrosis [5]. From the clinical point of view, it is always difficult to differentiate sepsis from the fibroproliferative evolution of the disease. Patients in the fibroproliferative phase of ARDS can have fever, leucocytosis, new or worsening localized infiltrates on a chest roentgenogram, purulent tracheal secretions and marked uptake of gallium in the lungs wihtout any identifiable infection. Bronchoscopy with collection and analysis of distal airway secretions excludes bacterial pneumonia, even in patients with clinical findings suggesting bronchial infection. In these cases, open lung biopsy or transbronchial biopsy indicate the presence of an inflammatory process [4, 6]. From the therapeutic point of view, a precise diagnosis is important because, while sepsis must be treated with adequate antibiotic therapy, the fibroproliferative phase may be responsive to steroid treatment and reversible [7, 8]. Prospective clinical studies have shown that short courses (!48 h) of high-dose corticosteroids are not beneficial when thay have been administered at the onset of