Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human activated protein C (rhAPC) also known as drotrecogin alfa (activated) has known antithrombotic, anti-inflammatory, and profibrinolytic properties in severe sepsis. Treatment with rhAPC (Xigris) has been shown to reduce mortality in patients with severe sepsis. The lack of any trials of rhAPC in trauma patients means that a definitive recommendation regarding its use in the polytraumatised patient, in whom severe head trauma or other contraindications for the use of rhAPC have been excluded remains controversial at present. This article describes the current evidence of its efficacy and safety in severe sepsis with relation to surgery and trauma.
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PMID:Coagulopathy and the role of recombinant human activated protein C in sepsis and following polytrauma. 1637 Sep 57

Sepsis, the systemic inflammatory response to infection, is common among severely ill patients and can be life-threatening. Over a quarter of patients in UK intensive care units (ICUs) have severe sepsis in the first 24 hours after admission. Of these, 35% die before leaving the ICU and 47% before leaving hospital despite standard therapy. Drotrecogin alfa (activated) (Xigris - Eli Lilly), a recombinant human activated protein C, is licensed for treating adults who have severe sepsis with multiple organ failure. Here we assess its efficacy and safety.
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PMID:Drotrecogin alfa (activated) for severe sepsis. 1642 99

Human activated protein C (APC) is a serineprotease and one of the most important physiological inhibitors of the coagulation system. Apart from anticoagulative effects, profibrinolytic and anti-inflammatory modes of action have been reported for APC. The administration of recombinant human activated protein C (rhAPC), drotrecogin alfa (activated), Xigris, to patients with severe sepsis and sepsis-induced multi-organ failure reduced mortality in large clinical trials. Anti-apoptotic and immunomodulatory effects of rhAPC have been examined in in vitro experiments and in experimental animal studies. Moreover, a reduction of endothelial cell permeability, enhanced endothelial cell survival as well as improvements of microcirculatory disorders have been proposed for rhAPC. The manifold mechanisms of action of APC may give reasons for its application in diseases other than sepsis, which are characterized by endothelial and microcirculatory dysfunction, e.g. acute pulmonary or renal failure, ischemic stroke, ischemia-reperfusion injury and acute pancreatitis. A better understanding of the anti-inflammatory, anti-apoptotic and immunomodulatory modes of action of APC could be relevant for dosing and mode of application and may lead to a broadening of the indication field for rhAPC.
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PMID:[Mechanisms of action of recombinant human activated Protein C]. 1652 Sep 28

Drotrecogin alpha (recombinant human activated protein C, rhAPC; Xigris) is an immune modulating treatment principle that has been shown to significantly reduce mortality in patients with severe sepsis. Currently, the identification of patients in intensive care that may benefit from such a treatment is insufficient. The importance of this evidence-based treatment modality is commonly ignored for reasons of increased cost. A medically justified and economically acceptable strategy with a medico-legal backing would be a procedure based on the design and the results of the PROWESS study. This may benefit patients with severe sepsis of not longer than 48 h duration, an APACHE II score of > or =25 or > or =2 failing organs and no exclusion criteria. Extending the indication beyond this group should be discussed as a last resort in patients with a fulminant clinical course, such as in meningitis, and based on data from retrospective subgroup analyses. Patients with severe sepsis following community-acquired pneumonia with progressive organ dysfunction may also benefit from activated protein C treatment in addition to an otherwise best standard of care.
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PMID:[Identification of patients suitable for therapy with activated Protein C]. 1655 81

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

There is uncertainty whether surgical patients with severe sepsis have a benefit from therapy with Drotrecogin alfa (activated). In the PROWESS and ENHANCE studies 4,068 patients were included and 3,228 were treated with Drotrecogin alfa (activated). Approximately 28% of the PROWESS patients and 41% of the ENHANCE patients were surgical patients. The subgroup of surgical patients showed the same benefit from therapy with Drotrecogin alfa (activated) as the overall cohort. The relative risk was 0.9 (95% CI 0.7-1.25, absolute risk reduction 3.2%). Patients with intraabdominal infections have a special benefit and here the relative risk was 0.7 (95% CI 0.5-1.0, absolute risk reduction 9.1%). Serious bleeding was more frequent in patients treated with Drotrecogin alfa (activated): 2.4-3.6% vs. 1.0% in the placebo group. In surgical patients bleeding was not more frequent than in non-surgical patients (3.1% vs. 2.1%, difference not significant). Surgical patients with severe sepsis, especially with peritonitis, should receive therapy with Drotrecogin alfa (activated), if severely ill.
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PMID:[Identification of surgical patients for therapy with activated Drotrecogin alfa]. 1660 16

Drotrecogin alfa (activated) (DrotAA) represents a therapeutic advance in the treatment of severe sepsis. In the pivotal PROWESS trial DrotAA had demonstrated a significant decrease in 28-day mortality, most evident in the subgroup of patients at higher risk of death. Thus, DrotAA was licensed throughout Europe for treatment of adult patients with severe sepsis with multiple organ failure when added to best standard care. The ADDRESS trial was mandated by the FDA to investigate prospectively the treatment effect of DrotAA in patients at low risk of death, e.g. single organ failure. The trial was prematurely stopped due to futility, because no reduction in mortality was observed in this non-indicated patient population. The ENHANCE open-label trial enrolled similar patients to the PROWESS trial and the observed 28-day mortality was consistent with the results seen in the PROWESS trial. Survival rates for patients receiving DrotAA early within 24 h from the first sepsis-induced organ dysfunction were significantly higher than in patients treated later. In this overview we will discuss the results of the ENHANCE and ADDRESS trials in the context of the PROWESS study and clinical implications for the treatment with DrotAA.
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PMID:[PROWESS, ENHANCE and ADDRESS: clinical implications for the treatment with drotrecogin alfa (activated)]. 1668 Apr 42

Descending necrotic mediastinitis is a serious illness which, among others, follows acute bacterial infections located in a cervical area. One of the most frequent causes of this illness, not connected with surgical interventions, is a peritonsillar and peridental abscess. The process originally placed in the peritonsillar area spreads along the cervical fascia engulfs mediastinum. Inflammatory process of the mediastinum considerably worsens the prognosis and obligates to decisive surgical (mediastinum drainage) and pharmacological (antibiotic therapy) treatments. The following works presents the course of the illness of a 55-year-old man who was diagnosed with severe sepsis in the course of the peritonsillar abscess. After surgical provision of the abscess (incision) the patient was qualified for the therapy with activated protein C (Xigris, Lilly). The patient condition initially improved, however, after 8 days a descending necrotic mediastinitis with ambilateral pleural abscess was diagnosed. The administration of the treatment within 48 days of hospitalization (antibiotic therapy, thoracotomy, flow drainage of the mediastinum, tracheotomy, respirotherapy) brought about the effect of complete recovery.
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PMID:[Severe sepsis as a complication of descending necrotizing mediastinitis due to a peritonsillar abscess. A case study]. 1690 40

We report on 2 cases of severe sepsis treated with drotrecogin-alpha (Xigris, Eli Lilly), where massive perioperative haemorrhage required administration of recombinant factor VIIa. The first patient developed severe sepsis after surgery (laparoscopic cholecystectomy, laparotomy due to peritonitis). After 18 h of treatment with Xigris, the patient developed massive, refractory gastrointestinal and abdominal bleeding. Effective haemostasis was achieved after 2 doses of NovoSeven (Novo Nordisk, Denmark). The patient died due to a cerebral bleed. The second patient developed septic shock in the course of pyelonephritis and right hydronephrosis. She was treated with Xigris and nephrectomy. Uncontrollable perioperative bleeding was effectively treated with 2 doses of NovoSeven. The patient survived.
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PMID:Recombinant factor VII (activated) for haemorrhagic complications of severe sepsis treated with recombinant protein C (activated). 1691 8

Drotrecogin alfa (activated) is a drug licensed for the treatment of severe sepsis. We describe the care of a 61-year-old man who developed multi-organ failure secondary to severe falciparum malaria infection with parasitaemia levels of 40%. Included in his care were an exchange blood transfusion and an infusion of Drotrecogin alfa (activated). Within hours of starting the infusion of Drotrecogin alfa (activated), the patient's clinical condition stopped deteriorating. Steady improvement followed with weaning from ventilatory assistance on day 14 post admission. The patient made a full recovery and was discharged home following rehabilitation. The indications for Drotrecogin alfa (activated) and the appropriateness of its use in severe malaria with multi-organ failure are discussed. Drotrecogin alfa (activated) may be a useful treatment in patients with multi-organ failure resulting from severe malaria.
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PMID:Drotrecogin alfa (activated) in severe falciparum malaria. 1692 59


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