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

Statins have a variety of properties that are independent of their lipid lowering ability. These anti-inflammatory, antioxidant, immunomodulatory, and antiapoptotic features have been collectively referred to as pleiotropic effects. Severe sepsis is an intense infection-induced inflammatory syndrome that ultimately results in organ dysfunction. Because so many cascades are triggered during sepsis, merely blocking a single component may be insufficient to arrest the inflammatory process. A growing body of evidence suggests that statins may indeed have a protective effect against severe sepsis and reduce the rate of infection-related mortality. This novel primary prevention concept may have far-reaching implications for the future management of serious infections. Moreover, it was recently shown that statins potentially improve outcome after the onset of sepsis. The stage is now set for randomized clinical trials that will determine the precise role, if any, that statins may have in preventing and treating sepsis.
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PMID:Do statins have a role in preventing or treating sepsis? 1646 22

Severe sepsis is a common disease process in the critically ill and is associated with substantial morbidity and mortality. Continuing research has provided considerable insight into the pathophysiology of sepsis over recent years, enabling various aspects of the sepsis response to be targeted. Discoveries related to the link between coagulation and inflammation have been particularly exciting, leading to the development of recombinant activated protein C. This review will discuss current definitions of sepsis, describe new approaches to classification and diagnosis of patients with sepsis, present recommendations for management, and briefly highlight areas of ongoing and future research.
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PMID:Sepsis diagnosis and management: work in progress. 1649 85

Severe sepsis is sepsis associated with acute organ dysfunction. Septic shock in turn, implies severe sepsis that has led to circulatory shock refractory to fluid resuscitation alone. The immediate approach to severe sepsis follows the ABCs of resuscitation: Airway, Breathing, and Circulation. Special emphasis on the circulation involves early goal-directed therapy, adequate fluid resuscitation, and vasopressor/inotropic support. Once the patient's cardiorespiratory status is stabilized, efforts must be directed at uncovering the source and empirically yet accurately treating the infective underpinnings of severe sepsis. Following that, each of the patient's other organ systems at risk needs to be addressed: Renal/metabolic, gastrointestinal, hematological, and endocrine. Novel treatments will target both the proinflammatory and procoagulation cascades of sepsis.
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PMID:Severe sepsis and septic shock in adult patients: an approach to management and future trends. 1655 67

Drotrecogin alfa (activated) has been approved by the United States Food and Drug Administration for treatment of patients at high risk of death from severe sepsis. Severe sepsis is common, and its occurrence increases dramatically with age. Clinical use data, however, suggest that drotrecogin alfa (activated) may be underused in older patients, possibly due to concern over the drug's anticoagulant effects and perceived high cost. In addition, clinicians often treat older patients less aggressively than younger patients. We reviewed a subgroup analysis of patients aged 75 years and older from a large clinical trial evaluating efficacy and safety of drotrecogin alfa (activated), as well as cost-effectiveness data from real-world clinical use of the drug in older patients. We also explored ethical dilemmas of treating older patients with sepsis. Drotrecogin alfa (activated) is safe, effective, and cost-effective in older patients with severe sepsis and should be considered for elderly intensive care patients who are high risk of death and who have no contraindications to treatment.
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PMID:Use of drotrecogin alfa (activated) in older patients with severe sepsis. 1655 13

Patients with cirrhosis are susceptible to bacterial infection, which can result in circulatory dysfunction, renal failure, hepatic encephalopathy, and a decreased survival rate. Severe sepsis is frequently associated with adrenal insufficiency, which may lead to hemodynamic instability and a poor prognosis. We evaluated adrenal function using short corticotropin stimulation test (SST) in 101 critically ill patients with cirrhosis and severe sepsis. Adrenal insufficiency occurred in 51.48% of patients. The patients with adrenal insufficiency had a higher hospital mortality rate when compared with those with normal adrenal function (80.76% vs. 36.7%, P < .001). The cumulative rates of survival at 90 days were 15.3% and 63.2% for the adrenal insufficiency and normal adrenal function groups, respectively (P < .0001). The hospital survivors had a higher cortisol response to corticotropin (16.2 +/- 8.0 vs. 8.5 +/- 5.9 microg/dL, P < .001). The cortisol response to corticotropin was inversely correlated with various disease severity, Model for End-Stage Liver Disease, and Child-Pugh scores. Acute physiology, age, chronic health evaluation III score, and cortisol increment were independent factors to predict hospital mortality. Mean arterial pressure on the day of SST was lower in patients with adrenal insufficiency (60 +/- 14 vs. 74.5 +/- 13 mm Hg, P < .001), and a higher proportion of these patients required vasopressors (73% vs. 24.48%, P < .001). Mean arterial pressure, serum bilirubin, vasopressor dependency, and bacteremia were independent factors that predicted adrenal insufficiency. In conclusion, adrenal insufficiency is common in critically ill patients with cirrhosis and severe sepsis. It is related to functional liver reserve and disease severity and is associated with hemodynamic instability, renal dysfunction, and increased mortality.
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PMID:Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. 1655 38

Severe sepsis and septic shock are frequent pathologies accounting for approximately 11% of all admissions in intensive care units (ICU). In the United States, between 1979 and 2000 the incidence of sepsis increased by 8,7% annually and septic shock) remains the second most frequent cause of death in non-coronary ICU. Although our understanding of the host defense mechanisms against infections and of the pathogenesis of septic shock have progressed during the last decade, these progresses have not yet yielded the anticipated advantages. Recent new therapeutic approaches, especially early-goal directed therapy, activated protein C (drotrecogin alpha activated), moderate doses of corticosteroids and intensive insulin therapy have given encouraging results.
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PMID:[Severe sepsis and septic shock]. 1667 20

Severe sepsis leads to long-term alterations in the immune response of surviving individuals. We have modeled this alteration in host immunity by studying the survivors of severe experimental sepsis (murine cecal ligation and puncture), which were subsequently challenged with lung granuloma-inducing Schistosoma mansoni eggs. This granulomatous response is a well-studied cell-mediated immune reaction characterized by elevated levels of type-2 cytokines. Pulmonary granulomas induced by S. mansoni eggs in cecal ligation and puncture survivors were significantly larger and contained more eosinophils than granulomas in sham-operated mice. Significantly lower interleukin (IL)-12p40 mRNA and IL-12p70 protein levels were observed in the lungs of postseptic mice with developing granulomas, compared with controls. Postseptic mice had significantly fewer dendritic cells in the lungs during the granulomatous response. Isolated lung dendritic cells from postseptic mice at days 8 and 16 after S. mansoni egg challenge exhibited defective IL-12 synthesis but enhanced IL-10 synthesis after Toll-like receptor agonist challenge. Pulmonary transfection with an IL-12-expressing adenovirus in postseptic mice reversed the skewing of the pulmonary cytokine profile and normalized the lung granulomatous response. Our data indicate that severe sepsis shifts the pulmonary cytokine environment, presumably via effects on pulmonary dendritic cells, which in turn alters the lung cell-mediated immune response.
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PMID:Severe sepsis exacerbates cell-mediated immunity in the lung due to an altered dendritic cell cytokine profile. 1672 9

Two international multicentre randomised controlled trials of drotrecogin alfa (activated) (DrotAA), the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) and Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) trials, have produced inconsistent results. When 28-day mortality data from these trials for patients with severe sepsis and at high risk of death are pooled using a standard random-effects meta-analysis technique, there is no statistically significant survival benefit (for patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more), or a borderline significant benefit (for patients with multi-organ failure). We argue that two important methodological issues might explain the disparate results between the two trials. These issues centre on early trial stopping, which exaggerates treatment effects, and reliance on subgroup analyses, which for DrotAA yields inconsistent results across different definitions of high risk. These concerns call into question the effectiveness of DrotAA in any patients with severe sepsis. Consequently, further randomised trials of this agent in prospectively defined high-risk patients are required to clarify its role in the management of severe sepsis.
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PMID:Drotrecogin alfa (activated): does current evidence support treatment for any patients with severe sepsis? 1709 91

Severe sepsis and septic shock are as common and lethal as other acute life-threatening conditions that emergency physicians routinely confront such as acute myocardial infarction, stroke, and trauma. Recent studies have led to a better understanding of the pathogenic mechanisms and the development of new or newly applied therapies. These therapies place early and aggressive management of severe sepsis and septic shock as integral to improving outcome. This independent review of the literature examines the recent pathogenic, diagnostic, and therapeutic advances in severe sepsis and septic shock for adults, with particular relevance to emergency practice. Recommendations are provided for therapies that have been shown to improve outcomes, including early goal-directed therapy, early and appropriate antimicrobials, source control, recombinant human activated protein C, corticosteroids, and low tidal volume mechanical ventilation.
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PMID:Severe sepsis and septic shock: review of the literature and emergency department management guidelines. 1678 20

Severe sepsis is an ongoing challenge for clinicians and health-care administrators mainly because is associated with a high incidence, mortality rate and costs. In recent years, several epidemiological studies about the incidence of sepsis have come out in different and prestigious journals. However, it is not advisable to draw direct conclusions from those studies considering methodological flaws or even different approaches. Hence, we have to be familiar with those obstacles and know how to overcome them. This review paper highlights the methods which have been used in these studies and depicts the results of occurrence rate or incidence of sepsis in countries and in intensive care units.
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PMID:Epidemiology of severe sepsis around the world. 1678 96


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