Critical care : the official journal of the Critical Care Forum
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Lung fibrosis, reduced lung compliance, and severe hypoxemia found in patients with acute lung injury often result in a need for the support of mechanical ventilation. High-tidal-volume mechanical ventilation can increase lung damage and fibrogeneic activity but the mechanisms regulating the interaction between high tidal volume and lung fibrosis are unclear. We hypothesized that high-tidal-volume ventilation increased pulmonary fibrosis in acute lung injury via the serine/threonine kinase-protein kinase B (Akt) and mitogen-activated protein kinase pathways. ⋯ We conclude that high-tidal-volume ventilation-induced microvascular permeability, lung fibrosis, and chemokine production were dependent, in part, on activation of the Akt and ERK1/2 pathways.
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Comparative Study
Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models.
Pneumonia is a very common nosocomial infection in intensive care units (ICUs). Many studies have investigated risk factors for the development of infection and its consequences. However, the evaluation in most of theses studies disregards the fact that there are additional competing events, such as discharge or death. ⋯ More studies using competing risk models, which provide more accurate data compared to naive survival curves or logistic models, should be carried out to verify the impact of risk factors and patient characteristics for the acquisition of nosocomial infections and infection-associated mortality.
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High mobility group box 1 protein (HMGB1) is a pleiotropic cytokine, recently implicated in the pathophysiology of the systemic inflammatory response syndrome (SIRS) and sepsis. Data from experimental sepsis models show that administration of anti-HMGB1 antibodies significantly decreased mortality, even when administration was delayed for 24 hours, providing a window of opportunity for therapeutic intervention if transferred into a clinical setting. Whether genetic variation in the human HMGB1 gene is associated with disease susceptibility is unknown. ⋯ The present article is the first report of clinical implications of variation in the human HMGB1 gene. Two polymorphisms were determined as significant risk factors associated with early and late mortality, which may provide insight into the molecular background of SIRS and sepsis, suggesting a possible role for HMGB1 genetics in future prognostic evaluation.
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During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock. ⋯ Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.
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Comparative Study
Health care costs, long-term survival, and quality of life following intensive care unit admission after cardiac arrest.
The purpose of this study was to investigate the costs and health status outcomes of intensive care unit (ICU) admission in patients who present after sudden cardiac arrest with in-hospital or out-of-hospital cardiopulmonary resuscitation. ⋯ Patients who leave the hospital following cardiac arrest without severe neurological disabilities may expect a reasonable quality of life compared with age- and gender-matched controls. Quality-adjusted costs for this patient group appear to be within ranges considered reasonable for other groups of patients.