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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Semin Respir Crit Care Med · Aug 2006
ReviewThe role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury.
Mortality rates from acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) range from 30 to 65%. Although mechanical ventilation (MV) may delay mortality in critically ill patients with ALI/ARDS, it may also cause a lung injury that further promotes and perpetuates ALI/ARDS and multiorgan dysfunction syndrome (MODS). Recent studies have demonstrated that lung protective strategies of MV, as compared with the injurious strategy of conventional MV (CMV) can reduce absolute mortality rates during ALI/ARDS. ⋯ Both human and animal studies suggest that alveolar cell deformation from CMV leads to the release of cytokines/chemokines which orchestrate the extravasation, activation, and recruitment of leukocytes, causing ventilator-associated lung injury (VALI) and ventilator-induced lung injury (VILI). Moreover, VALI/VILI can perpetuate the chronic inflammatory response during ALI/ARDS and MODS. This article explores the role of cytokines/chemokines during the pathogenesis of VALI/VILI.
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Semin Respir Crit Care Med · Aug 2006
ReviewEpidemiology of acute lung injury and acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is a heterogeneous disorder that may be triggered by myriad etiologies (both pulmonary and extrapulmonary). Mortality rates for ARDS range from 30 to 75%, and most deaths are a consequence of multiorgan failure (MOF). ⋯ This review discusses limitations of various criteria utilized to diagnosis ARDS and ALI, and why some criteria may be problematic when designing clinical trials. Also discussed are the myriad causes of ARDS, incidence, epidemiology, mortality, and factors that influence outcome.
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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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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.