Der Anaesthesist

, Volume 55, Supplement 1, pp 30–35 | Cite as

Identifikation chirurgischer Patienten für die Therapie mit aktiviertem Drotrecogin alfa

Leitthema
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Zusammenfassung

Es besteht Unsicherheit, ob die Therapie der schweren Sepsis mit aktiviertem Protein C auch für chirurgische Patienten von Vorteil ist. In die Studien „Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis“ (PROWESS) und „Extended Evaluation of Recombinant Activated Protein C“ (ENHANCE) wurden insgesamt 4068 Patienten aufgenommen; davon wurden 3228 mit aktiviertem Protein-C-Verum behandelt. Etwa 28% der PROWESS-Teilnehmer und etwa 41% der ENHANCE-Teilnehmer waren chirurgische Patienten. Diese Subgruppe profitiert in gleicher Weise von der Therapie mit aktiviertem Protein C wie das Gesamtkollektiv. Das relative Risiko betrug 0,9 [95%-Konfidenzintervall (95%-CI) 0,7–1,25; absolute Risikoreduktion 3,2%). Insbesondere Patienten mit intraabdominalen Infektionen haben einen Gewinn. Hier betrug das relative Risiko 0,7 (95%-CI 0,5–1,05; absolute Risikoreduktion 9,1%). Blutungen treten unter Therapie gering vermehrt auf: 2,4–3,6% vs. 1,0% unter Placebo. Bei chirurgischen Patienten sind Blutungen nicht häufiger als bei nichtchirurgischen (3,1% vs. 2,1%; Unterschied nicht signifikant). Chirurgische Patienten mit schwerer Sepsis, insbesondere mit Peritonitis, sollten bei ausreichender Schwere der Erkrankung mit aktiviertem Protein C therapiert werden.

Schlüsselwörter

Aktiviertes Protein C Sepsis Chirurgie Postoperativ Peritonitis 

Identification of surgical patients for therapy with activated Drotrecogin alfa

Abstract

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.

Keywords

Activated protein C Sepsis Surgery Postoperative Peritonitis 
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Notes

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Literatur

  1. 1.
    Abraham E, Laterre PF, Garg R et al. (2005) Drotrecogin alfa (activated) for adult patients with severe sepsis and a low risk of death. N Engl J Med 353: 1332–1341PubMedCrossRefGoogle Scholar
  2. 2.
    Annane D, Sébille V, Charpentier C et al. (2000) Effect of a treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288: 862–871CrossRefGoogle Scholar
  3. 3.
    Barie PS, Williams MD, McCollam JS et al. and PROWESS Surgical Evaluation Committee (2004) Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis. Am J Surg 188: 212–220PubMedCrossRefGoogle Scholar
  4. 4.
    Beale R, Vincent JL, Doig C et al. (2004) The incidence of serious bleeding events in a global, single-arm, open-label trial of drotrecogin alfa (activated) in adult patients with severe sepsis comparison with PROWESS. Crit Care 8 [Suppl 1]: 116Google Scholar
  5. 5.
    Berghe G van den, Wouters P, Weekers F (2001) Intensive insuline therapy in critically ill patients. N Engl J Med 345: 1359–1367CrossRefGoogle Scholar
  6. 6.
    Bernard GR, Vincent JL, Laterre PF et al., Recombinant Protein C Worldwide Evaluation in Severe Sepsis (PROWESS Study Group) (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344: 699–709PubMedCrossRefGoogle Scholar
  7. 7.
    Bernard GR, Macias WL, Vincent JL (2002) Drotrecogin alfa (activated) cumulative safety update. Chest 122 [Suppl]: S141Google Scholar
  8. 8.
    Bernard GR, Margolis BD, Shanies HM (2004) Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): a single-arm, phase 3b multicenter study of drotrecogin alfa (activated) in patients with severe sepsis. Chest 125(6): 2206–2216PubMedCrossRefGoogle Scholar
  9. 9.
    Dellinger RP, Carlet JM, Masur H et al. (2004) Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32: 858–873PubMedCrossRefGoogle Scholar
  10. 10.
    Dhainaut JF, Laterre PF, Janes JM et al. (2003) Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial. Intensive Care Med 29: 894–903PubMedGoogle Scholar
  11. 11.
    Dhainaut JF, Laterre PF, Rosa SP la et al. (2003) The clinical evaluation committee in a large multicenter phase 3 trial of drotrecogin alfa (activated) in patients with severe sepsis (PROWESS): role, methodology and results. Crit Care Med 31: 2291–2301PubMedCrossRefGoogle Scholar
  12. 12.
    Joseph E (1907) Ein Beitrag zum Wesen der Entzündung. Dtsch Z Chirurgie 28: 425–442Google Scholar
  13. 13.
    Laterre PF, Bernard GR, Trzaskoma BL, Sashegyi A (2003) INDEPTH – An integrated database of severe sepsis patients. Crit Care Med 31 [Suppl]: 116Google Scholar
  14. 14.
    Olsen KM, Martin SJ (2002) Pharmacokinetics and clinical use of drotrecogin alfa (activated) in patients with severe sepsis. Pharmocotherapy 22(12 Pt 2): 196S–205SCrossRefGoogle Scholar
  15. 15.
    Payen D, Williams MD, Sarwat S, Janes J (2004) Safety and efficacy of drotrecogin alfa (activated) ) in adult surgical patients with severe sepsis. Intensive Care Med 30 [Suppl 1]: 134Google Scholar
  16. 16.
    Rivers E, Nguyen B, Havstad S et al. (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345: 1368–1377PubMedCrossRefGoogle Scholar
  17. 17.
    Siegel JP (2002) Assessing the use of activated protein C in the treatment of severe sepsis. N Engl J Med 347: 1030–1034PubMedCrossRefGoogle Scholar
  18. 18.
    Vincent JL, Levy MM, Macias WL, Trzaskoma B (2003) Early intervention with drotrecogin alfa (activated) improves survival benefit. Crit Care Med 31 [Suppl]: 123Google Scholar
  19. 19.
    Vincent JL, Macias WL, Levy MM et al. (2003) Early response to therapy predicts eventual survival in severe sepsis. Intensive Care Med 29 [Suppl 1]: 74Google Scholar

Copyright information

© Springer Medizin Verlag 2006

Authors and Affiliations

  1. 1.Abt. Allgemein- und ViszeralchirurgieChirurgische UniversitätsklinikFreiburg i.Br.

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