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

Severe sepsis in lung transplant recipients is a challenging problem and carries a high mortality. Recombinant human activated protein C (drotrecogin alfa [activated]) has been approved for use in patients with severe sepsis. Its use has been shown to be safe and impart a survival advantage. However, the safety of drotrecogin alfa activated has not been evaluated in lung transplant recipients. We report for the first time on the use of drotrecogin alfa activated in six lung transplant recipients. Clinical trials are warranted to further evaluate the use of drotrecogin alfa activated in transplant recipients.
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PMID:A case series of drotrecogin alfa (activated) in lung transplant recipients. 1679 42

Severe sepsis, a lethal syndrome after infection or injury, is the third leading cause of mortality in the United States. The pathogenesis of severe sepsis is characterized by organ damage and accumulation of apoptotic lymphocytes in the spleen, thymus, and other organs. To examine the potential causal relationships of apoptosis to organ damage, we administered Z-VAD-FMK, a broad-spectrum caspase inhibitor, to mice with sepsis. We found that Z-VAD-FMK-treated septic mice had decreased levels of high mobility group box 1 (HMGB1), a critical cytokine mediator of organ damage in severe sepsis, and suppressed apoptosis in the spleen and thymus. In vitro, apoptotic cells activate macrophages to release HMGB1. Monoclonal antibodies against HMGB1 conferred protection against organ damage but did not prevent the accumulation of apoptotic cells in the spleen. Thus, our data indicate that HMGB1 production is downstream of apoptosis on the final common pathway to organ damage in severe sepsis.
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PMID:Role of HMGB1 in apoptosis-mediated sepsis lethality. 1681 69

Sepsis is a common and life-threatening condition with a high mortality rate. Severe sepsis includes multiorgan dysfunction syndrome. The organ most often affected is the lung, with development of acute lung injury (ALI), which, in its most severe form, is referred to as acute respiratory distress syndrome (ARDS). Our understanding of inflammation in the pathogenesis of sepsis and ALI is continually growing. However, therapies aimed at the inflammatory cascade in sepsis have been unsuccessful. These failures have led investigators to consider other pathways that may be important in the development of sepsis and ALI, including the coagulation and fibrinolytic cascades. In fact, the first therapy to reduce mortality in sepsis modulates the coagulation cascade. With this clinical success, administration of drotecogin alfa (recombinant activated protein C), the importance of coagulation in the pathogenesis of human sepsis is becoming clearer. This review summarizes the current understanding of the role of coagulation and fibrinolytic abnormalities in sepsis and the development of ALI and ARDS. Both in vitro and in vivo studies of the role of the coagulation cascade in sepsis and lung injury will be discussed, including initiation of coagulation through modulation of tissue factor and tissue factor pathway inhibitor, propagation of coagulation via protein C and thrombomodulin, inhibition of thrombin generation and resolution through thrombolysis by plasminogen activator, and plasminogen activator inhibitor-1.
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PMID:The role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome. 1690 70

Severe sepsis is a common and commonly fatal disease and is essentially an exaggerated inflammatory response. The epidemiology of severe sepsis and septic shock has been difficult to determine because of an inconsistent approach to definitions and diagnosis. Patients with sepsis account for approximately a third of hospital and intensive care unit bed days in the UK and mortality ranges from 25% to 80%. A number of interventions have recently been shown to improve outcomes. The Surviving Sepsis Campaign recommends a package of evidence based interventions known as the sepsis resuscitation bundles and the sepsis treatment bundles. The aim is to ensure that eligible patients receive all appropriate treatments in a timely fashion, utilising protocol driven prescriptions.
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PMID:Critical care in the emergency department: severe sepsis and septic shock. 1692 Oct 89

Severe sepsis, involving a systemic inflammatory response caused by infection and acute organ dysfunction, is one of the most common non-cardiac causes of death in intensive care unit patients worldwide. The mainstay of treatment for severe sepsis is aggressive antibiotic therapy combined with supportive care for associated organ dysfunction. In 2001, recombinant human activated protein C was shown to improve survival in patients with severe sepsis, but two further studies of the immunomodulatory effects of endogenous anticoagulant agents did not show any survival benefit. Importantly, all three studies showed potential confounding by patients receiving low-dose heparin during the study period, raising the possibility that heparin may also have important immunomodulatory actions. This has increased the focus on the non-anticoagulatory actions of heparin, and its potential therapeutic immunodulatory effects during severe sepsis. This review summarises the known clinical effects of heparin and explores the significant implications of its widespread therapeutic use.
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PMID:Heparin: the cheap alternative for immunomodulation in sepsis? 1693 Jan 12

Severe sepsis is at present serious medical and social problem. In contrast to many other diseases its incidence shows an upward tendency and so does mortality due to sepsis. From the point of view of pathogenesis the cause of this complaint is a disturbed response to infection. The basis of this disruption is either a huge local inflammation that goes hand in hand with the penetration of proinflammatory cytokines into systemic circulation or an excessive proinflammatory systemic response. In the first instance the consequence is a systemic proinflammatory response accompanied by a disruption of macrocirculation, later also of microcirculation and finally mitochondrial failure. These mechanisms are responsible for the gradual failure of distant organs. In the second instance the consequence is a deactivation of systemic and local immunocompetent cells accompanied by the risk of uncontrolled proliferation of microorganisms. Affected are organs with a disturbed antimicrobial barrier, especially the lungs du ring mechanical ventilation, the bloodstream or the urinary system during catheterization. A large group of selectively acting preparations has been clinically tested in the management of this disorder, but only very few of these preparations were efficacious. We may postulate that the great diversity of the investigated population of patients was responsible for this lack of success.
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PMID:[Pathogenesis of severe sepsis--from macrocirculation to mitochondria]. 1717 49

Severe sepsis is a common and frequently fatal condition. Evidence showing a link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alfa (activated) as an agent in the treatment of severe sepsis. Recent studies have shown that the mode of action is actually more complex than initially thought. This recombinant form of the natural anticoagulant, activated protein C, has been demonstrated to reduce mortality in a large randomized controlled, Phase III study involving 1690 patients, even though the results of this and subsequent studies and the licensing of drotrecogin alfa (activated) have generated considerable debate. Administration of drotrecogin alfa (activated) is associated with an increased risk of bleeding and its use is contraindicated in patients with a high risk of bleeding or recent hemorrhagic events.
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PMID:Drotrecogin alfa (activated) in the treatment of severe sepsis. 1700 34

Severe sepsis is a major cause of morbidity and mortality in the critically ill patient. Management involves identification and treatment of the underlying causative infection, with antimicrobial agents and surgery where necessary, haemodynamic resuscitation with fluids and vasoactive agents, steroids (for septic shock) and immunomodulation with drotrecogin-alpha (activated), where not contraindicated. Every effort must be made to identify sepsis early so as to optimise the patient's chances of a good outcome.
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PMID:Management of sepsis in the critically ill patient: key aspects. 1702 Apr 31

Severe sepsis and septic shock are common causes of morbidity and mortality. Interventions directed at specific endpoints, when initiated early in the "golden hours" of patient arrival at the hospital, seem to be promising. Early hemodynamic optimization, administration of appropriate antimicrobial therapy, and effective source control of infection are the cornerstones of successful management. In patients with vasopressor-dependent septic shock, provision of physiologic doses of replacement steroids may result in improved survival. Administration of drotrecogin alfa (activated), (activated protein C) has been shown to improve survival in patients with severe sepsis and septic shock who have a high risk of mortality. In this article we review the multi-modality approach to early diagnosis and intervention in the therapy of patients with severe sepsis and septic shock.
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PMID:Management of sepsis during the early "golden hours". 1704 83

Severe malaria is characterized by the presence of asexual forms of Plasmodium falciparum in the blood and the presence of one or more OMS 2000 criterion. Imported malaria is defined as malarial infection acquired in an endemic country (often in sub-Saharan Africa) and treated in France. The largest patient group includes African patients, long-term residents in France, coming back from a vacation in their native country. In non-immunized adults, severe malaria causes multiple organe failure such as severe Gram-negative sepsis, with variable degrees of altered mental status. Severe sepsis is treated in an intensive care unit (mechanically assisted ventilation, kidney dialysis, vasoconstrictors...). Intravenous quinine is the reference treatment, but artemisinin derivatives (arthemeter and artesunate) are the most rapidly acting antimalarial drugs.
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PMID:[Severe imported malaria in adults]. 1705 7


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