Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Aug 2006
ReviewAcute lung injury and acute respiratory distress syndrome: extracorporeal life support and liquid ventilation for severe acute respiratory distress syndrome in adults.
Acute respiratory distress syndrome (ARDS) has many underlying causes and carries an overall mortality of 40 to 60%. For those patients with severe ARDS who have a predicted mortality of 80 to 100%, extracorporeal life support (ECLS) can provide an extraordinary means of support. We recently demonstrated a survival to hospital discharge of 52% in this subset of patients. ⋯ Systemic heparinization is a mainstay of ECLS therapy because of platelet activation in the circuit. Mechanical complications and significant bleeding can occur in up to one quarter of patients, requiring close attention and prompt intervention should they occur. Although not currently in clinical practice, liquid ventilation using perfluorocarbons to provide gas exchange in the lungs is a potentially useful adjunct in the management of severe respiratory failure.
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The importance of pulmonary surfactant in maintaining normal lung function, and the observations that alterations in endogenous surfactant contribute to the lung dysfunction associated with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), provide a rationale for administering exogenous surfactant in this setting. The results of clinical trials have been variable, however, in part due to the various surfactant preparations used, the different delivery and dosing methods employed, and the types of patients targeted for this therapy. ⋯ Based on extensive in vitro data as well as in vivo animal studies demonstrating the anti-inflammatory and antibacterial functions of various surfactant components, administration of surfactant earlier in the course of the disease, when lung inflammation is present but before severe lung dysfunction occurs, may prove to be optimal. This review discusses both the biophysical and host defense functions of surfactant in the context of novel therapeutic approaches for patients with ALI/ARDS.
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Acute lung injury (ALI) is a complex syndrome involving the interplay of both environmental (such as the addition of mechanical ventilation) and genetic factors. Clinical models have identified risk factors for development and poor outcome but these strategies remain imprecise. ⋯ Although valuable information has been reported to date, intense analyses are needed in this developing discipline to assure significant clinical utility. The detailing of specific associated polymorphisms will continue to provide new insights in the understanding of disease pathogenesis, and promise to reveal novel molecular targets and personalized treatments to prevent the disease.
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Semin Respir Crit Care Med · Aug 2006
ReviewRadiological imaging in acute lung injury and acute respiratory distress syndrome.
Computed tomography (CT) has been utilized to study acute respiratory distress syndrome (ARDS) since the middle 1980s, when it revealed the inhomogeneous pattern of the lung lesion. Its advantages rely on the strict correlation between CT density and the lung physical density, allowing a quantification of lung compartments with different degrees of aeration. By CT scans, ARDS lung appeared to be "small" rather than "stiff," leading to the "baby lung" concept. ⋯ The amount of recruitable lung varies among ARDS patients. This knowledge is necessary for a rational positive end-expiratory pressure (PEEP) setting because the amount of tissue maintained aerated by PEEP is closely associated with the amount of recruitable lung. CT scans may also help to diagnose ARDS because CT provides a good estimate of the high-permeability lung edema, the characteristic lesion of this syndrome.
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Semin Respir Crit Care Med · Aug 2006
ReviewPathophysiology of acute lung injury and the acute respiratory distress syndrome.
Since the adult respiratory distress syndrome was first described substantial progress has been made in understanding the pathogenesis of this complex syndrome. This review summarizes our current understanding of the pathophysiology of what is now termed the acute respiratory distress syndrome (ARDS) and its less severe form acute lung injury (ALI), with an emphasis on cellular and molecular mechanisms of injury that may represent potential therapeutic targets. Although it is difficult to synthesize all of these abnormalities into a single, unified, pathogenetic pathway, a theme that emerges repeatedly is that of imbalance, be it between pro- and anti-inflammatory cytokines, oxidants and antioxidants, procoagulants and anticoagulants, neutrophil recruitment and activation and mechanisms of neutrophil clearance, or proteases and protease inhibitors. Future therapies aimed at restoring the overall balance of cytokines, oxidants, coagulants, and proteases may ultimately be successful where therapies that target individual cytokines or other mediators have not.