Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001; 29(7): 1303-1310.
Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 March 8; 344(10): 699-709.
Dalton HJ. Recombinant activated protein C in pediatric sepsis. Pediatr Infect Dis J. 2003 August; 22(8): 743-45.
Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004; 32(3):858-873.
Dhainaut JF, Yan SB, Joyce DE, Pettila V, Basson B, Brandt JT, Sundin DP, Levi M. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. 2004; 2:1924-33.
Eichacker PQ, Danner RL, Suffredini AF, Cui X, Natanson C, Magnuson WG. Reassessing recombinant human activated protein C for sepsis: Time for a new randomized controlled trial. Crit Care Med. 2005; 33(10): 2426-2428.
Eli Lilly and Company, Sepsis Overview. Available at:
http://www.sepsis.com/overview/pathophys.jsp?reqNavId=1.3 , Accessed on 2005 October 3.
Ely EW, Angus DC, Williams MD, Bates B, Qualy R, Bernard GR. Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin Infect Dis. 2003 July 15; 37:187-195.
Esmon CT. Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation. Crit Care Med. 2001 Jul 01; 29 Suppl 7: S48-51.
Fein AM, Abraham EM, Balk RA, Bernard GR, Bone RC, Dantzker DR, Fink MP, editors. Sepsis and Multiorgan Failure. Baltimore: Williams & Wilkins; 1997.
Girard TD, Opal SM, Ely EW. Insights into severe sepsis in older patients: from epidemiology to evidence-based management. Clin Infect Dis. 2004 Mar 01; 40: 719-727.
Giroir BP. Recombinant human activated protein C for the treatment of severe sepsis: is there a role in pediatrics? Curr Opin Pediatr. 2003; 15:92-96.
Grinnell BW, Joyce D. Recombinant human activated protein C: A system modulator of vascular function for treatment of severe sepsis. Crit Care Med. 2001; 29 Suppl 7: S53-61.
Kerr M. Drotrecogin plus heparin efficacious for adults with severe sepsis. Available at:
http://www. medscape .com/ viewarticle /521768 , Accessed on 2006 February 2.
Kumar V, Abbas AK, Fausto N, editors. Robbins and Cotran Pathological Basis of Disease. 7 th ed. Philadelphia: Elsevier Inc.; 2005.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 April; 31(4): 1250-56.
Liaw PCY, Esmon CT, Kahnamoui K, Schmidt S, Kahnamoui S, Ferrell G, et al. Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood. 2004 December 15; 104(13): 3958-3964.
McLeay AM. Drotrecogin alfa: A role in emergency department treatment of severe sepsis? Emerg Med Australas. 2004; 16:324-335.
Shapiro NI, Howell M, Talmor D. A blueprint for a sepsis protocol. Acad Emerg Med. 2005; 12(4): 352-359.
Society of Critical Care Medicine, Press Room: Sepsis Guide. Available at:
http://www. sccm .org/press_room/sepsis_guide.asp , Accessed on 2005 October 3.
Taylor A FB Jr., Chang A, Esmon CT, et al. Protein C prevent the coagulopathic and lethal effect of E. coli infusion in the baboon. J Clin Invest. 1987; 79:918-925
Taylor B FB Jr., Stearns-Kurosawa DJ, Kurosawa S, et al. The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood. 2000; 95:1680-1686.
U.S. Food and Drug Administration A , A catalog of FDA approved drug products. Label and Approval history for Xigris. Label approved on 6/23/05. Available at:
http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist , Accessed on 2005 October 3.
U.S. Food and Drug Administration B , The FDA Safety Information and Adverse Event Reporting Program. 2005 Safety Alert: Xigris [drotrecogin alfa (activated)]. Available at: http://www.fda.gov/medwatch/SAFETY/2005/xigris_DHCP.htm , Accessed on 2006 February 3.
Vincent JL A , Carlet J, Opal SM, editors. The Sepsis Text. Boston: Kluwer Academic Publishers; 2002.
Vincent JL B , Bernard GR, Beal R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J. Drotrecogin alfa (activated treatment in sever sepsis from the global open-label trial ENHANCE: Further evidence for survival and safety and implications for early treatment. Crit Care Med. 2005; 33(10): 2266-2277.
Vincent JL C , Nadel S, Kutsogiannis DJ, Noel Gibney RT, Yan SB, Wyss VL, Bailey JE, Mitchell CL, Sarwat S, Shinall SM, Janes JM. Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies. Crit Care. 2005; 9(4): R331-R343.
Warren HS, Suffredini AF, Eichacker PQ, Munford RS. Risks and Benefits of Activated Protein C Treatment for Severe Sepsis. N Engl J Med. 2002 September 26; 347(13):1027-1030.
Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. American Journal of Respiratory and Critical Care Medicine. 2003; 167: 695-701.
White B, Livingstone W, Murphy C, Hodgson A, Rafferty M, Smith OP. An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood. 2000 December 1; 96(12): 3719-3724.
Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcome in severe sepsis. Chest. 2001 September; 120(3): 915-922.