Critical care medicine
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Critical care medicine · Apr 2003
ReviewLung-protective ventilation strategies in acute lung injury.
To review the challenges of providing mechanical ventilatory support for respiratory failure while avoiding ventilator-associated lung injury in patients with acute lung injury. To review the results of several randomized clinical trials of lung-protective ventilation strategies using conventional mechanical ventilators. ⋯ Evidence supports the use of a volume- and pressure-limited approach to mechanical ventilation in patients with acute lung injury. It is not yet clear whether the open-lung approach will further reduce mortality in patients receiving volume- and pressure-limited ventilation support.
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To review the rationale for evaluating anticoagulant therapies in acute lung injury (ALI) and to review selected data regarding the effectiveness of anticoagulants in animals and human patients with ALI and acute respiratory distress syndrome. ⋯ In the lung, alveolar and interstitial fibrin deposition are the hallmarks of early phase ALI. Local procoagulant activity and reduced fibrinolysis constitute the rationale for anticoagulant use in the treatment of ALI. An activated complex of tissue factor and factor VIIa triggers procoagulant activity in the lung, with subsequent thrombin formation and fibrin deposition. Increased pulmonary vascular permeability and leukocyte accumulation have been successfully prevented in animals treated with tissue factor/activated factor VII pathway inhibitor. In humans, a phase II study evaluating tissue factor pathway inhibitor in the treatment of severe sepsis suggested that lung function in acute respiratory distress syndrome patients was improved. However, the phase III trial failed to demonstrate a survival benefit; data regarding respiratory dysfunction have not yet been published. Heparin, despite effectively inhibiting thrombin formation, has not shown consistent benefits in reducing lung injury, and its efficacy has not yet been evaluated in a controlled study. Antithrombin administration in animals has shown consistent benefits with ALI, but clinical studies have failed to demonstrate reductions in mortality and lung injury. Activated protein C administration has been shown to improve survival and lung function in both animal and clinical studies. Soluble thrombomodulin has been shown to improve ALI in animals, and it is currently being evaluated in humans with sepsis. Finally, plasminogen activators may improve gas exchange in ALI, but studies in humans are limited.
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Neutrophils are an important component of the inflammatory response that characterizes acute lung injury (ALI). This discussion aims to review the contribution of neutrophils to the development and progression of ALI and to highlight the major intracellular signaling pathways that are involved in neutrophil activation in the setting of ALI. ⋯ The accumulation of activated neutrophils in the lungs is an early step in the pulmonary inflammatory process that leads to ALI. Although experimental models indicate that the activation of p38, Akt, and nuclear factor-kappaB in neutrophils contributes to ALI, the relative importance of these pathways in critically ill patients remains to be determined. Nevertheless, modulation of the activation of p38, Akt, and nuclear factor-kappaB in neutrophils appears to be an appropriate therapeutic target in severely ill patients with ALI.
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Critical care medicine · Apr 2003
Impact of antibiotic-resistant Gram-negative bacilli infections on outcome in hospitalized patients.
The impact of resistant (vs. nonresistant) Gram-negative infections on mortality remains unclear. We sought to define risk factors for and excess mortality from these infections. ⋯ rGNRs are associated with prolonged hospital stay and increased mortality. Infection with rGNRs independently predicts mortality; however, this may be more closely related to selection of certain bacterial species with a high frequency of resistance rather than actual resistance to antibiotic therapy. Therefore, altering infection-control practices to limit the dissemination of certain bacterial species may be more effective than attempts to control only antibiotic-resistant isolates.
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Critical care medicine · Apr 2003
Six-month neuropsychological outcome of medical intensive care unit patients.
To examine neuropsychological function, depression, and quality of life 6 months after discharge in patients who received mechanical ventilation in the intensive care unit. ⋯ Prolonged neuropsychological impairment is common among survivors of the medical intensive care unit and occurs with greater than anticipated frequency when compared with relevant normative data. Future investigations are warranted to elucidate the nature of the association between critical illness, neuropsychological impairment, depression, and decreased quality of life.