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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Editorial Review
Impact of antimicrobial resistance on the treatment and outcome of patients with sepsis.
Antimicrobial therapy is one of the main stones of sepsis therapy. A recent study of septic shock patients showed that each hour of delay in antimicrobial administration during the ensuing 6 h after the onset of hypotension was associated with a decrease in survival rates. However, many questions regarding the impact of infection caused by antimicrobial-resistant pathogens on the mortality of patients with sepsis still need to be clarified. ⋯ Most studies have had inadequate sample size, inadequate adjustment for predictors of adverse outcomes, and inadequate definition of appropriate antibiotic therapy. Despite the fact that appropriate therapy is essential to treat sepsis, it seems that severity of underlying diseases and comorbidities are more important than resistance, although the studies were not well designed to examine the real impact of resistance on outcome. Finally, new technologies such as microarray that can identify different microorganisms, genes of resistance, and virulence in a few hours might have a great impact on the treatment of sepsis due to antimicrobial-resistant pathogens in the future.
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During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. ⋯ Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or maintained blood flow, an important proportion of muscle lactate release is regulated by a beta2 receptor stimulation and not secondary to a reduced oxygen availability.
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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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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 2002, the declaration of Barcelona launched a worldwide campaign that proposed to decrease in sepsis-related mortality by the introduction of evidence-based medicine into the management of sepsis. This paved the way for the publication of a wide selection of recommendations entitled the Surviving Sepsis Campaign (SSC) Guidelines. Whereas most of the medical community received the guidelines with enthusiasm, dissonant voices were made public just after its publication, and in recent years, the SSC guidelines were a source of intense debate, resulting in a recent revision of the guidelines. ⋯ In our opinion, whereas many relevant aspects of the SSC guidelines have been discussed, there are three major limitations that deserve a closer look, and they are sepsis as a public health issue, the weight of the evidence behind the recommendations, and the absence of recommendations related to the prevention of sepsis. In conclusion, although we recognize that the SSC is a valuable initiative, many of its present aspects must be revised to provide a clear message for clinicians taking care of sepsis patients at bedside. New guidelines should be based on solid evidence, have no interference from the pharmaceutical or medical equipment industry, and should have a stronger preventive and public health approach.