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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Vascular hyperpermeability is a clinical complication associated with hemorrhagic shock (HS) and occurs mainly because of the disruption of the adherens junctional complex. The objective of this study was to understand the role of 17beta-estradiol in HS-induced hyperpermeability particularly focusing on estrogen receptors. In male Sprague-Dawley rats, HS was induced by withdrawing blood to reduce the mean arterial pressure to 40 mmHg for 1 hour followed by 1 hour of resuscitation to 90 mmHg. ⋯ Tamoxifen 5 mg/kg attenuated HS-induced hyperpermeability, whereas 10 mg/kg induced permeability (P < 0.05). Both alpha and beta estrogen receptor agonists inhibited HS-induced hyperpermeability (P < 0.05). 17beta-Estradiol decreased HS-induced reactive oxygen species formation and restored mitochondrial transmembrane potential. 17beta-Estradiol decreased both cytosolic cytochrome c level and activation of caspase-3 (P < 0.05). These findings suggest that 17beta-estradiol protects the microvasculature after HS, and that this protection may be mediated through the alpha and beta estrogen receptors.
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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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Sepsis remains a challenge for intensive care physicians, as it keeps up with high mortality rate in spite of the high costs associated with its treatment. Several studies indicate that the infusion of Drotrecogin-alpha activated (DrotAA) reduce mortality in patients at high risk of death when administered early and secured the appropriate initial treatment of sepsis as recommended by Surviving Sepsis Campaign. Europe and United States of America differ regarding the criteria of high risk of death in sepsis, two or more organ dysfunctions and Acute Physiology and Chronic Health Evaluation 25 or more, respectively. In addition to varied definitions of high risk of death for inclusion of patients in sepsis studies, the possibility of bleeding related to drug use and intrinsic limitations related to study design led the Company to develop a new randomized, multinational, placebo-controlled, double-blind study to assess the effectiveness of drug in patients with septic shock in adults.
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The use of echocardiography in the intensive care unit for patients in shock allows the accurate measurement of several hemodynamic variables in a noninvasive way. By using echocardiography as a hemodynamic monitoring tool, the clinician can evaluate several aspects of shock states, such as cardiac output and fluid responsiveness, myocardial contractility, intracavitary pressures, and biventricular interactions. However, to date, there have been few guidelines suggesting an objective hemodynamic-based examination in the intensive care unit, and most intensivists are usually not familiar with this tool. In this review, we describe some of the most important hemodynamic parameters that can be obtained at the bedside with transthoracic echocardiography.