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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe sepsis and septic shock are among the most complex and challenging conditions treated by critical care practitioners. Although the pathophysiology of severe sepsis and septic shock is not fully understood, bacteria and immune responses are known to trigger the release of cytokines. These cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and sleepiness, as well as a host of physiologic events such as activation of the coagulation cascade, vasodilation, hypotension, and increased vessel permeability. As research advances the understanding of severe sepsis and septic shock, practitioners must become aware of the cellular basis of events so that treatments can be implemented knowledgeably and evaluated.
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PMID:The cellular basis of septic shock. 1259 36

Severe sepsis is a major public health concern and a burden on the healthcare system. Despite improvements in efforts to control the source of infection and increased recognition by healthcare providers of patients with the disease, the mortality rate remains unacceptably high, from 30% to 50%. The systemic inflammatory response syndrome criteria are used as diagnostic indicators of sepsis when they occur in patients with known or suspected infection. The outcome of a patient with severe sepsis is often related to the occurrence of sepsis-induced multiple organ dysfunction syndrome. Multiple organ dysfunction syndrome appears to result from a cascade of organism-related factors, inflammatory mediators, endothelial injury, disturbed hemostasis, and microcirculatory abnormalities. In patients with severe sepsis, derangements of inflammation and coagulation are tightly linked. Although numerous clinical trials focused on interventions in one or the other of the inflammatory and coagulation systems failed to show reduced mortality due to sepsis, a member of a new class of drugs called "cogins" was effective. In its active form, protein C has anti-inflammatory, antithrombotic, and profibrinolytic properties that can reduce organ injury associated with severe sepsis. A recombinant form of activated protein C, drotrecogin alfa (activated), significantly reduces 28-day mortality due to all causes in patients with severe sepsis and has an acceptable safety profile. This review provides an overview of severe sepsis, highlighting recent advances in treatment of the disease and the role of critical care nurses.
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PMID:Advances in the understanding of clinical manifestations and therapy of severe sepsis: an update for critical care nurses. 1262 70

Severe sepsis in immunosuppressed recipients of solid-organ transplants is associated with a high mortality. Conventional management of sepsis in this patient population has not specifically attempted to treat the underlying inflammatory or procoagulant responses that contribute to the development of multisystem organ failure. Drotrecogin alfa (activated, human activated protein C) has been shown to be a safe and effective adjuvant in the treatment of severe sepsis; however, experience in recipients of solid-organ transplants has not been addressed. The treatments and outcomes of three solid-organ transplant recipients (liver, kidney, and kidney-pancreas) who experienced episodes of severe sepsis are presented and demonstrate initial success with the use of drotrecogin alfa (activated).
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PMID:Solid-organ transplant recipients treated with drotrecogin alfa (activated) for severe sepsis. 1266 May 22

(1) Severe sepsis is fatal in 30-50% of cases, despite antibiotic therapy and intensive care. (2) The first specific treatment to be marketed in France was HA-IA monoclonal antibodies, in 1991. However, marketing approval was granted precipitously, on the basis of a single, controversial comparative trial, and the product was withdrawn after a second trial gave negative results. (3) Marketing authorization for drotrecogin alfa (recombinant activated protein C) was granted in 2002 for this indication. (4) The product was approved after a single comparative double-blind placebo-controlled trial in 1 690 patients. The protocol was modified during the trial, to exclude patients at high risk of death from causes unrelated to sepsis. The manufacturing process was also changed, making it difficult to interpret the results of this trial. (5) The trial found that drotrecogin alfa reduced mortality (by 6% in absolute values: 25% versus 31%), but also increased the risk of severe haemorrhage, the main adverse effect (3.5% versus 2%). (6) Retrospective subgroup analyses identified patients most likely to benefit from drotrecogin alfa, and also patients who would be needlessly exposed to an additional risk. (7) Drotrecogin alfa is a very expensive drug. (8) In practice, this clinical trial should be considered preliminary. Other, strictly designed and conducted trials are therefore required.
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PMID:Drotrecogin alfa: new preparation. For some cases of severe sepsis? 1267 16

Severe sepsis is the leading cause of death among patients in intensive care units. Recombinant activated protein C is the only substance known to directly improve morbidity and mortality. Adrenal insufficiency occurs frequently in patients with sepsis and is associated with poor outcome. Although high-dose glucocorticoids have not positively affected clinical outcome, small trials in which low-dose glucocorticoids were administered to patients with septic shock and relative adrenal insufficiency have shown decreased mortality. The main effect of glucocorticoids in low-doses apparently is exerted through correction of suppression of the hypothalamic-pituitary-adrenal axis. However, the therapeutic benefits of glucocorticoids may be related to their antiinflammatory properties and endogenous catecholamine-enhancing effects.
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PMID:The hypothalamic-pituitary-adrenal axis and low-dose glucocorticoids in the treatment of septic shock. 1268 Apr 81

In 1914, Schottmueller wrote "Septicemia is a state of microbial invasion from a portal of entry into the blood stream which causes signs of illness." In the last few decades, the evidence that sepsis results from an exaggerated systemic inflammatory host response induced by infecting organisms is compelling; inflammatory mediators are the key players in the pathogenesis of septic shock and multiorgan failure. Sepsis and its sequelae represent a continuum of clinical syndrome encompassing systemic inflammation, coagulopathy, and hemodynamic abnormalities. Severe sepsis and septic shock continue to be the major causes of morbidity and mortality in the United States; sepsis deaths currently match mortality from myocardial infarction. Despite significant advances in our understanding of the pathophysiology and technological innovations in the supportive management, mortality from septic shock remains excessive. After many disappointments with strategies to manipulate the inflammatory response, modulation of coagulation cascade to decrease sepsis mortality has become a clinical reality. This review will highlight and discuss recent advances in the pathophysiology and management of sepsis.
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PMID:Septic shock, multiple organ failure, and acute respiratory distress syndrome. 1268 65

Severe sepsis and septic shock are still the leading causes of death in the surgical ICU. The only curative therapies of sepsis are still surgery as well as antibiotic therapy to cure the focus. In addition a supportive therapy (analgesia and sedation, mechanical ventilation, titrated volume substitution and positive inotropes/vasopressor support, parenteral and enteral neutron, renal replacement therapies) should be started as early as possible. A new promising approach in sepsis therapy is the application of rhAPC. The PROWESS study revealed a significantly lower 28 day mortality in patients with severe sepsis who received drotrecogin alfa (activated) compared to patients not treated with drotrecogin alfa (activated). Guidelines for the use in severe sepsis and septic shock in surgical patients (risk of bleeding, costs) are strongly recommended.
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PMID:[Focal surgery, antibiotic therapy--and then? The role of rhAPC in sepsis]. 1270 33

The incidence of severe sepsis increases dramatically with advanced age, with a mortality rate that approaches 50%. The main purpose of this investigation was to determine both short- and long-term survival outcomes among 386 patients aged >or=75 years who were enrolled in the Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) trial. Subjects who were treated with drotrecogin alfa (activated; DAA) had absolute risk reductions in 28-day and in-hospital mortality of 15.5% and 15.6%, respectively (P=.002 for both), compared with placebo recipients. The relative risk (RR) for 28-day mortality was 0.68 (95% confidence interval [CI], 0.54-0.87), and the in-hospital RR was 0.70 (95% CI, 0.56-0.88). Resource use and patient disposition for DAA-treated patients compared favorably with those for placebo recipients. In addition, long-term follow-up data were available for 375 subjects (97.2%), and survival rates for DAA recipients were significantly higher over a 2-year period (P=.02). The incidences of serious adverse bleeding during the 28-day study period in the DAA and placebo groups were 3.9% and 2.2%, respectively (P=.34). There was no interaction between age and bleeding rates (P=.97). In conclusion, older patients with severe sepsis have higher short- and long-term survival rates when treated with DAA than when treated with placebo but an increased risk of serious bleeding that is not aged related.
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PMID:Drotrecogin alfa (activated) treatment of older patients with severe sepsis. 1285 11

Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30-50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.
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PMID:The coagulopathy of sepsis: pathophysiology and management. 1290 Dec 50

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.
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PMID:Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. 1294 Sep 1


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