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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Severe sepsis and septic shock have long been a challenge in intensive care because of their common occurrence, high associated costs of care, and significant mortality. The Surviving Sepsis Campaign (SSC) was developed in an attempt to address clinical inertia in the adoption of evidence-based strategies. The campaign relies on worldwide support from professional societies and has gained consensus on the management of patients with severe sepsis. ⋯ The idea of the campaign is based on a 25% reduction in the relative risk of death from severe sepsis and septic shock within 5 years in the SSC-participating Brazilian hospitals. Ideally, the mortality rate should come to a 41.2% level subject to the 2009 deadline. This article aims to describe the actual scenario of the SSC implementation in Brazilian institutions and to report on some initiatives that have been used to overcome barriers.
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Sepsis is the systemic inflammatory response syndrome secondary to a local infection. Septic shock, the severe complication of sepsis associated with refractory hypotension, is frequently a near-fatal condition requiring prompt diagnosis and management. ⋯ In this review, we will briefly discuss the ongoing standard treatment of septic shock and describe novel potential therapies, aiming to improve hemodynamic support and/or control inflammatory response in sepsis. These therapies were associated with benefits in experimental studies and have been tested or are currently under testing in randomized controlled studies with septic patients.
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The pathogenesis of sepsis involves complex interaction between the host and the infecting microorganism. Bacterial recognition and signaling are essential functions of the cells of innate immune systems and drive a coordinated immune response. One of the more intriguing aspects of sepsis is the fact that the protective and damaging host response are part of the same process, that is, the inflammatory response that is aimed to control the infectious process also underscores many of the pathophysiological events of sepsis. ⋯ The results obtained by our group show that TLR and other cellular surface receptors may be differently regulated on mononuclear cells and neutrophils, and that they are dynamically modulated across the stages of sepsis. Toll-like receptor signaling gene expression in mononuclear cells is decreased in more severe forms of the disease. In contrast, up-regulated genes are seen along the clinical spectrum of sepsis in neutrophils.
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In awake spontaneously breathing mice, inhaling gaseous hydrogen sulfide (H2S) produced a "suspended animation-like" metabolic status with hypothermia and reduced O2 demand, thus protecting from lethal hypoxia. Murine models may be questioned, however, because due to their large surface area/mass ratio, rodents can rapidly drop their core temperature. Therefore, we investigated whether intravenous H2S (Na2S, sodium sulfide) would induce a comparable metabolic response in anesthetized and mechanically ventilated pigs. ⋯ The parameters of inflammation and oxidative stress did not differ. Intravenous sulfide allowed reducing energy expenditure in an anesthetized large-animal model and improved the noradrenaline responsiveness during reperfusion after aortic occlusion. Investigations are warranted, hence, whether it may also protect other organs after I/R injury.
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Granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays a critical role in innate immunity by stimulating the differentiation of tissue macrophages via the transcription factor PU.1. Previous studies showed that GMCSF-deficient(GM-CSF-/-) mice had susceptibility to and impaired clearance of group B streptococcal bacteria by macrophages. For these studies, we hypothesized that GM-CSF-/- mice have increased susceptibility to peritonitis caused by immune dysfunction of peritoneal macrophages. ⋯ In vitro studies demonstrated reduced secretion of TNF-alpha and IL-6 by peritoneal macrophages isolated from sham GM-CSF-/- mice as compared with macrophages from sham control mice. Peritoneal instillation of GM-CSF-/-/PU.1+ macrophages, but not GM-CSF-/-/PU.1+ macrophages into GM-CSF-/- mice conferred susceptibility to death after CLP or peritoneal LPS exposure. These results demonstrate that GM-CSFY/PU.1-dependent peritoneal macrophage responses are a critical determinant of survival after experimentally induced peritonitis/sepsis or exposure to LPS and have implications for therapies to treat such infections.