Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock

Dhainaut, Jean-François; Antonelli, Massimo; Wright, Patrick E.; Desachy, Arnaud; Reignier, Jean; Lavoué, Sylvain; Charpentier, Julien; Belger, Mark; Cobas-Meyer, M.; Maier, Cornelia; Mignini, Mariano Alejandro; Janes, Jonathan

doi:10.1007/s00134-009-1502-8

Cited by 7 publications

(11 citation statements)

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“…These four studies targeted the following interventions: selenium, talactoferrin, esmolol and ulinastatin [22][23][24][25]. A subgroup analysis of intervention efficacy, grouped by type of intervention, revealed a significantly higher relative mortality risk for the intervention in trials studying modulation of coagulation and inflammation [26][27][28][29][30][31] (RR = 1.113; 95% CI 1.019 to 1.216; p = 0.02; Table 2). This subgroup analysis included Higgin's I 2 test to evaluate the potential heterogeneity in the selected subgroups.…”

Section: Efficacy Of Study Interventionsmentioning

confidence: 99%

Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002–2016

et al. 2019

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Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control armAbstract Background: Epidemiologic data have shown an increasing incidence and declining mortality rate in sepsis. However, confounding effects due to differences in disease classification might have contributed to these trends. To assess if a declining mortality over time could be supported by data derived from high-quality prospective studies, we performed a meta-analysis using data from randomised controlled trials (RCTs) on sepsis. The primary aim was to assess whether the mortality in sepsis trials has changed over time. The secondary aim was to investigate how many of the included trials could show efficacy of the studied intervention regarding 28-day mortality.Methods: We searched PubMed for RCTs enrolling patients with severe sepsis and septic shock, published between 2002 and 2016. The included trials were assessed for quality and sorted by date of first inclusion. A meta-analysis was performed to synthesise data from the individual sepsis trials.Results: Of 418 eligible articles, 44 RCTs on sepsis were included in the analysis, enrolling 13,315 patients in the usual care arm between 1991 and 2013. In this time period, mortality decreased by 0.42% annually (p = 0.04) to give a total decline of 9.24%. In subgroup analyses with adjustments for APACHE II, SAPS II and SOFA scores, the observed time trend was not significant (p = 0.45, 0.23 and 0.98 respectively). Only four of the included trials showed any efficacy with regard to mortality.Conclusions: Data from RCTs show a declining trend in 28-day mortality in severe sepsis and septic shock patients during the years from 1991 to 2013. However, when controlling for severity at study inclusion, there was no significant change in mortality over time. The number of trials presenting new treatment options was low.

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Section: Efficacy Of Study Interventionsmentioning

confidence: 99%

Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002–2016

et al. 2019

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“…Further, antiinflammatory properties of APC are the result of it blocking the formation of tumor necrosis factor, interleukin-6, and interleukin-8 and by inhibiting neutrophil chemotaxis (Table 3). 32,58,[62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] Several studies have reported that levels of circulating protein C are low in severe sepsis and that these levels predict outcome. 79,80 A logical hypothesis to test was whether the replacement of APC would modify the coagulation and inflammation changes associated with its depletion in severe sepsis.…”

Section: Activated Protein C In the Treatment Of Sepsismentioning

confidence: 99%

“…86 A meta-analysis of novel anticoagulant therapies (APC, tissue factor pathway inhibitor, and antithrombin III) in patients with sepsis also failed to show mortality differences but did show significant risk of bleeding complications. 87 Current reviews of the treatment of severe sepsis (Table 3) 32,58,[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] have echoed caution and careful patient selection in the use of APC. 88,89 The Surviving Sepsis Campaign Guidelines of 2008 gave APC use in severe sepsis with high risk for death a 2B (weak recommendation with moderate quality of evidence) for most patients and a 2C (weak recommendation with low quality of evidence) for postoperative patients.…”

Section: Activated Protein C In the Treatment Of Sepsismentioning

confidence: 99%

Controversies in the Treatment of Sepsis

Sandrock

Albertson

2010

Semin Respir Crit Care Med

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Sepsis is a common illness of intensive care unit patients that carries a high morbidity, mortality, and increases hospital cost. Although mortality from sepsis remains high when compared with other critical illnesses, it has declined over the last few decades due to several adjunctive therapies and focused care programs or guidelines. Many interventions, such as early appropriate antibiotic therapy and lung protective, low tidal volume ventilation are commonplace and carry little controversy in their benefit. However, other therapies still have an unclear benefit and remain controversial. This article discusses the controversial roles of intensive insulin therapy, corticosteroids, and activated protein C in the treatment of sepsis.

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“…For example, we could have used APC concentrate (Xigris 1 ; Eli Lilly and Co, Indianapolis, IN), which has been used extensively to treat patients with severe sepsis [5,17] and patients with congenital protein C deficiency [18]. Our patient did not have sepsis; therefore, the endothelial activation of zymogen protein C was expected to be normal, making the infusion and subsequent activation of zymogen protein C a more physiologic and safe process with respect to bleeding risks.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Perioperative Use of Protein C Concentrate for Protein C Deficiency in THA

Thakkar¹,

Streiff²,

Bruley³

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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Background Perioperative management of patients with heterozygous protein C deficiency is challenging because of the competing risks of bleeding and recurrent thrombosis. Case Description We report the case of a 74-year-old man with protein C deficiency and heterozygous prothrombin G20210A gene mutation who had a successful left THA with perioperative administration of human zymogen protein C concentrate in addition to anticoagulation with enoxaparin. Literature Review Several studies have reported the use of protein C concentrate in severe sepsis-associated purpura fulminans in patients with severe congenital protein C deficiency who have had thrombotic events. We reviewed studies and case reports pertinent to the treatment of patients with protein C deficiency, especially in the perioperative setting. We report the case of a patient undergoing THA in whom we used human zymogen protein C concentrate. Purposes and Clinical Relevance THA, a particularly high-risk procedure, is associated with a 40% to 70% incidence of venographic deep venous thrombosis and a 2% to 3% incidence of symptomatic deep venous thrombosis. These risks are greater in people with thrombophilic defects such as protein C deficiency. The use of human zymogen protein C in our patient with heterozygous protein C deficiency during the perioperative period of a THA was associated with no evidence of excessive bleeding, hematoma, deep venous thrombosis, or pulmonary embolism.

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Extended drotrecogin alfa (activated) treatment in patients with prolonged septic shock

Abstract: Unfortunately this article contained neither the list of primary investigators and participating centres nor a link to the electronic supplementary material. These errors are rectified here.

Cited by 7 publications

References 0 publications

Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002–2016

Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002–2016

Controversies in the Treatment of Sepsis

Case Report: Perioperative Use of Protein C Concentrate for Protein C Deficiency in THA

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