Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors.
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Comparative Study Clinical Trial
Improvements in compliance with resuscitation bundles and achievement of end points after an educational program on the management of severe sepsis and septic shock.
The objectives of this study were to determine whether an educational program could improve compliance with resuscitation bundles and the outcomes of patients with severe sepsis or septic shock and to evaluate which resuscitation bundle end points were associated with in-hospital mortality. This was a retrospective observational study of 366 patients (163 of historical controls and 203 of treatment patients) with severe sepsis or septic shock who presented to the emergency department between May 2007 and July 2009. Compliance with resuscitation bundles and achievement of the corresponding end points were compared before and after the 3-month educational program. ⋯ The achievement of target ScvO₂ within the first 6 h was significantly improved (62% vs. 88%, P < 0.001). In-hospital mortality was independently associated with adequate fluid challenge (odds ratio [OR], 0.161; 95% confidence interval [CI], 0.046-0.559) and the achievement of target mean arterial pressure (OR, 0.056; 95% CI, 0.008-0.384) and ScvO₂ (OR, 0.251; 95% CI, 0.072-0.875) among the five sepsis resuscitation bundles. In conclusion, an educational program can improve compliance with resuscitation bundles and achievement of their corresponding end points.
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Severe inflammation leads to cardiac diastolic dysfunction, an independent prognostic marker for the mortality of critically ill patients. We investigated the possible molecular mechanism from inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) causing left ventricular (LV) diastolic dysfunction in critically burned patients. We consecutively enrolled 56 critically burned patients who were admitted to the intensive care unit and performed transthoracic echocardiography to evaluate LV diastolic function. ⋯ There was a significant correlation between LV diastolic dysfunction and in-hospital mortality in critically burned patients (hazard ratio, 3.92; P = 0.034) after risk factors were adjusted. Inflammatory cytokines may be associated with cardiac diastolic, which could be an independent prognostic factor in burn patients. Novel therapeutic strategies may be applied in critically burned patients with LV diastolic dysfunction by modulating inflammatory reactions.
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The release of hematopoietic progenitor cells (HPCs) from bone marrow (BM) is under tight homeostatic control. Under stress conditions, HPCs migrate from BM and egress into circulation to participate in immune response, wound repair, or tissue regeneration. Hemorrhagic shock with resuscitation (HS/R), resulting from severe trauma and major surgery, promotes HPC mobilization from BM, which, in turn, affects post-HS immune responses. ⋯ Secreted granulocyte colony-stimulating factor, in turn, induces HPC egress from BM. We also show that activation of β-adrenergic receptors on Mϕ by catecholamine mediates the HS/R-induced release of high-mobility group box 1. These data indicate that HS/R, a global ischemia-reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuroendocrine and innate immune systems, in which Mϕ play a central role.
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The development of sepsis is multifactorial. Tissue damage and organ dysfunction may be caused not only by the microorganisms but also by the inflammatory mediators released in response to the infection. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) levels in serum are well known to be upregulated in humans with sepsis and can be used to predict outcome. ⋯ In summary, our data suggest that LPS rapidly upregulates GEF-H1 expression. Activated Rho-associated kinase by GEF-H1 subsequently activates p38 and ERK1/2, thereby increasing IL-6/TNF-α expression in endothelial cells. P38 and ERK1/2 regulate LPS-induced IL-6/TNF-α expression through an NF-κB-dependent manner and an NF-κB-independent manner, respectively.