Critical care medicine
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Critical care medicine · Oct 2012
Ventilation with "clinically relevant" high tidal volumes does not promote stretch-induced injury in the lungs of healthy mice.
Ventilator-induced lung injury is a crucial determinant of the outcome of mechanically ventilated patients. Increasing numbers of mouse studies have identified numerous pathways and mediators that are modulated by ventilation, but it is conceptually difficult to reconcile these into a single paradigm. There is substantial variability in tidal volumes used in these studies and no certainty about the pathophysiology that such varied models actually represent. This study was designed to investigate whether ventilation strategies ranging from "very high" to more "clinically relevant" tidal volumes induce similar pathophysiologies in healthy mice or represent distinct entities. ⋯ Tidal volumes up to 20 mL/kg are unlikely to induce substantial lung overstretch in models using healthy, young mice. Signs of injury/inflammation using such models are likely to result from other factors, particularly alveolar derecruitment and atelectasis. The results of such studies may need to be reevaluated before clinical relevance can be accurately determined.
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Critical care medicine · Oct 2012
Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium.
To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation. ⋯ Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night, a practice associated with failed spontaneous breathing trials, coma, and delirium. Over the first 5 days in our study, patients spent 75% of their time in coma or delirium, outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit.
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Critical care medicine · Oct 2012
Previous prescription of β-blockers is associated with reduced mortality among patients hospitalized in intensive care units for sepsis.
Results from basic science and narrative reviews suggest a potential role of β-blockers in patients with sepsis. Although the hypothesis is physiologically appealing, it could be seen as clinically counterintuitive. We sought to assess whether patients previously prescribed chronic β-blocker therapy had a different mortality rate than those who did not receive treatment. ⋯ As far as we are aware, this pharmacoepidemiologic assessment is the largest to examine the potential association of previous β-blocker prescription and mortality in patients with sepsis. Chronic prescription of β-blockers may confer a survival advantage to patients who subsequently develop sepsis with organ dysfunction and who are admitted to an intensive care unit. Prospective randomized clinical trials should formally test this hypothesis.
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Critical care medicine · Oct 2012
Corticosteroid resistance in sepsis is influenced by microRNA-124--induced downregulation of glucocorticoid receptor-α.
Acquired glucocorticoid resistance frequently complicates the therapy of sepsis. It leads to an exaggerated proinflammatory response and has been related to altered expression profiles of glucocorticoid receptor isoforms glucocorticoid receptor-α (mediating anti-inflammatory effects) and glucocorticoid receptor-β (acting as a dominant negative inhibitor). We investigated the impact of glucocorticoid receptor isoforms on glucocorticoid effects in human T-cells. We hypothesized that 1) changes of the ratio of glucocorticoid receptor isoforms impact glucocorticoid resistance and 2) glucocorticoid receptor-α expression is controlled by microRNA-mediated gene silencing. ⋯ Glucocorticoid treatment induces expression of miR-124, which downregulates glucocorticoid receptor-α thereby limiting anti-inflammatory effects of glucocorticoids. Steroid treatment might aggravate glucocorticoid resistance in patients with high glucocorticoid receptor-β levels.