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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Sepsis and septic shock are frequently encountered in the intensive care unit. Despite the evolution of intensive care medicine during the last decades, septic shock is still associated with high mortality and complications of sepsis such as cholestasis, liver dysfunction, and massive intravascular volume deficit. Little is known about the whole pattern of changes at the transcriptional level during the development of acute sepsis. ⋯ Although after 21 h these animals are expected to die within the next 3 to 4 h from massive complications, functional induction of apoptosis could not be confirmed. Computer analysis identified three key regulator genes (IL8, CCL2, and CXCL2) among the first genes to be upregulated specifically in the sepsis group, and these can directly or indirectly control the bulk of the sepsis response. Induction of inflammatory mediators by sepsis was supported by the detection of corresponding cytokines (interleukin 6 and interleukin 8) in the blood.
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Hemodynamic instability plays a major role in the pathogenesis of systemic inflammation, tissue hypoxia, and multiple organ dysfunction in sepsis. Aggressive fluid replacement is one of the key interventions for the hemodynamic support in severe sepsis. In this scenario, the ability to restore the imbalance between tissue oxygen demand and supply, the heterogeneity in microcirculation, and endothelial dysfunction in the early stages of sepsis are associated with reduced mortality. ⋯ However, external validation of this trial remains to be carried out. To date, there is no unequivocal evidence that such strategy is both universally feasible and effective. In the present article, we review the current evidence and comment on the future perspectives on early fluid resuscitation in severe sepsis.
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Sepsis accounts for a huge number of deaths in intensive care units worldwide. Encouraging data from recent studies show that some interventions are able to reverse such a picture. Surviving Sepsis Campaign (SSC) bundles were built based on these interventions. ⋯ In the same way, the impact of interventions might be different according to each institution's epidemiological profile. Interventions not impacting in low-mortality-rate institutions can be important for places where mortality is high. In Brazil, mortality rates are very high, and the results of Brazilian SSC network are presented and discussed.
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Microcirculatory dysfunction plays a pivotal role in the pathogenesis of severe sepsis and septic shock; hence, microcirculation blood flow monitoring has gained increasing attention. However, microcirculatory imaging is still investigational in human sepsis and has not yet been incorporated into routine clinical practice for several reasons, including the difficult interpretation of microcirculation imaging data, difficulty to draw a parallel between sublingual microcirculation imaging and organ microcirculation dysfunction, as well as the absence of microvessel dysfunction parameters defining sequential microcirculatory changes from the early to late stages of the disease, which could aid in the context of therapeutic approaches and of prognostic parameters. The purpose of this review was to bridge the experimental abdominal organ microvascular derangement kinetics and clinical aspects of microcirculatory findings in the early phase of severe sepsis/septic shock.
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Sepsis is the systemic inflammatory response syndrome secondary to a local infection, and severe sepsis and septic shock are the more devastating scenarios of this disease. In the last decade, considerable achievements were obtained in sepsis knowledge, and an international campaign was developed to improve the treatment of this condition. However, sepsis is still one of the most important causes of death in intensive care units. ⋯ This dysfunction, which may occur in patients presenting normal vital signs, can be accompanied by a significant increase in both morbidity and mortality. The early identification of high-risk sepsis patients through tissue perfusion markers such as lactate and venous oxygen saturation is crucial for prompt initiation of therapeutic support, which includes early goal-directed therapy as necessary. The purpose of this article was to review the most commonly used hemodynamic and perfusion parameters for hemodynamic optimization in sepsis, emphasizing the physiological background for their use and the studies that demonstrated their effectiveness as goals of volemic resuscitation.