Content area
Full Text
The acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure that is often associated with multiple organ failure. Several clinical disorders can precipitate ARDS, including pneumonia, sepsis, aspiration of gastric contents, and major trauma. Physiologically, ARDS is characterized by increased permeability pulmonary edema, severe arterial hypoxemia, and impaired carbon dioxide excretion. Based on both experimental and clinical studies, progress has been made in understanding the mechanisms responsible for the pathogenesis and the resolution of lung injury, including the contribution of environmental and genetic factors. Improved survival has been achieved with the use of lung-protective ventilation. Future progress will depend on developing novel therapeutics that can facilitate and enhance lung repair.
Introduction
Since the original description of the acute respiratory distress syndrome (ARDS) in 1967, considerable progress has been made in understanding the pathogenesis and pathophysiology of acute lung injury (ALI) (1-4). The likelihood of survival is determined by the severity of lung injury, the extent of nonpulmonary organ dysfunction, preexisting medical conditions, and the quality of supportive care. Because ARDS is a complex syndrome with a broad clinical phenotype, it has been challenging to translate the results of cell and animal studies to pharmacologic therapies that reduce mortality in humans. Nevertheless, laboratory-based investigations have produced valuable insights into the mechanisms responsible for the pathogenesis and resolution of lung injury, and preclinical studies paved the way for important improvements in supportive care. Two of these therapies, lung-protective ventilation and fluid-conservative management, have reduced mortality and morbidity, respectively. This review of ARDS will focus on some of these issues, including new insights into the molecular mechanisms of lung injury and repair.
Definitions, epidemiology, incidence, and mortality
Criteria for the diagnosis of ARDS have evolved. The original description emphasized rapidly progressive respiratory failure from noncardiogenic pulmonary edema, requiring mechanical ventilation because of severe arterial hypoxemia and difficulty breathing (5). In 1988, a 4-point scoring system provided a quantitative assessment of lung injury severity based on the degree of hypoxemia, the level of positive end-expiratory pressure (PEEP), static respiratory compliance, and the extent of radiographic infiltrates (6), and this scoring system has been useful for research and clinical trials. In 1994, a consensus conference recommended simplified criteria: arterial hypoxemia with Pa02/FiC»2 ratio less than...