Journal of Critical Care
Volume 23, Issue 4 , Pages 484-492 , December 2008

Patient-specific decision modeling to guide the use of drotrecogin α (activated) in patients with severe sepsis

  • Daniel P. Schauer, MD, MSc

      Affiliations

    • Division of General Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA
    • Institute for the Study of Health, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA
    • Corresponding Author InformationCorresponding author. University of Cincinnati Medical Center, PO Box 670535, Cincinnati, OH 45267-0535, USA. Tel.: +1 513 558 2048; fax: +1 513 558 2744.
    • ,
  • Anthony C. Leonard, PhD

      Affiliations

    • Division of General Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA
    • Institute for the Study of Health, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA
    • ,
  • Richard W. Hornung, DrPH

      Affiliations

    • Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45224-3039, USA
    • ,
  • Joseph A. Johnston, MD, MSc

      Affiliations

    • Division of General Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA
    • U.S. Outcomes Research, Eli Lilly, Indianapolis, IN 46285, USA
    • ,
  • Mark H. Eckman, MD, MS

      Affiliations

    • Division of General Internal Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA
    • Institute for the Study of Health, University of Cincinnati Medical Center, Cincinnati, OH 45267-0535, USA

References 

  1. Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–829
  2. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101:1644–1655
  3. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1310
  4. Goldhill DR, Sumner A. Outcome of intensive care patients in a group of British intensive care units. Crit Care Med. 1998;26:1337–1345
  5. Brun-Buisson C, Doyon F, Carlet J, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995;274:968–974
  6. 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:S53–S60discussion S60-51
  7. Joyce DE, Gelbert L, Ciaccia A, et al. Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. J Biol Chem. 2001;276:11199–11203
  8. Joyce DE, Grinnell BW. Recombinant human activated protein C attenuates the inflammatory response in endothelium and monocytes by modulating nuclear factor-kappaB. Crit Care Med. 2002;30:S288–S293
  9. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709
  10. Angus DC, Laterre PF, Helterbrand J, et al. The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis. Crit Care Med. 2004;32:2199–2206
  11. Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med. 2005;353:1332–1341
  12. Siegel JP. Assessing the use of activated protein C in the treatment of severe sepsis. N Engl J Med. 2002;347:1030–1034
  13. Forsyth L. FDA Clinical Review: drotrecogin alfa (activated). Report No.: BLA 125029/0:. Federal Drug Administration; 2001;This source was accessed at: http://www.fda.gov/cder/biologics/review/droteli112101r1p2.pdf
  14. Johnston JA. Determinants of mortality in patients with severe sepsis. Med Decis Making. 2005;25:374–386
  15. Angus DC, Linde-Zwirble WT, Clermont G, et al. Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis. Crit Care Med. 2003;31:1–11
  16. Manns BJ, Lee H, Doig CJ, et al. An economic evaluation of activated protein C treatment for severe sepsis. N Engl J Med. 2002;347:993–1000
  17. Betancourt M, McKinnon PS, Massanari RM, et al. An evaluation of the cost effectiveness of drotrecogin alfa (activated) relative to the number of organ system failures. Pharmacoeconomics. 2003;21:1331–1340
  18. Neilson AR, Burchardi H, Chinn C, et al. Cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in Germany. J Crit Care. 2003;18:217–227
  19. Liang J, Streat S, Torrance J, et al. Drotrecogin alfa (recombinant human activated protein C) in severe sepsis—a New Zealand viewpoint. N Z Med J. 2003;116:U586
  20. Fowler RA, Hill-Popper M, Stasinos J, et al. Cost-effectiveness of recombinant human activated protein C and the influence of severity of illness in the treatment of patients with severe sepsis. J Crit Care. 2003;18:181–191[discussion 191-184]
  21. Detsky AS, Naglie G, Krahn MD, et al. Primer on medical decision analysis: part 1—getting started. Med Decis Making. 1997;17:123–125
  22. Lau J, Kassirer JP, Pauker SG. Decision Maker 3.0. Improved decision analysis by personal computer. Med Decis Making. 1983;3:39–43
  23. Bernard GR, Macias WL, Joyce DE, et al. Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis. Crit Care. 2003;7:155–163
  24. Tengs TO, Wallace A. One thousand health-related quality-of-life estimates. Med Care. 2000;38:583–637
  25. Oppenheim-Eden A, Glantz L, Eidelman LA, et al. Spontaneous intracerebral hemorrhage in critically ill patients: incidence over six years and associated factors. Intensive Care Med. 1999;25:63–67
  26. Inagawa T. What are the actual incidence and mortality rates of intracerebral hemorrhage?. Neurosurg Rev. 2002;25:237–246
  27. Tengs TO, Yu M, Luistro E. Health-related quality of life after stroke a comprehensive review. Stroke. 2001;32:964–972
  28. Eckman MH, Rosand J, Knudsen KA, et al. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke. 2003;34:1710–1716
  29. Lai SM, Alter M, Friday G, et al. Prognosis for survival after an initial stroke. Stroke. 1995;26:2011–2015
  30. Wu AH, Parsons L, Every NR, et al. Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J Am Coll Cardiol. 2002;40:1389–1394
  31. Spencer FA, Meyer TE, Goldberg RJ, et al. Twenty year trends (1975-1995) in the incidence, in-hospital and long-term death rates associated with heart failure complicating acute myocardial infarction: a community-wide perspective. J Am Coll Cardiol. 1999;34:1378–1387
  32. Behrend T, Miller SB. Acute renal failure in the cardiac care unit: etiologies, outcomes, and prognostic factors. Kidney Int. 1999;56:238–243
  33. Cuchural GJ, Levey AS, Pauker SG. Kidney failure or cancer. Should immunosuppression be continued in a transplant patient with malignant melanoma?. Med Decis Making. 1984;4:82–107
  34. Weller JM, Port FK, Swartz RD, et al. Analysis of survival of end-stage renal disease patients. Kidney Int. 1982;21:78–83
  35. Arias E. United States Life Tables, 2001. Natl Vital Stat Rep. 2004;52:1–39
  36. Doubilet P, Begg CB, Weinstein MC, et al. Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach. Med Decis Making. 1985;5:157–177
  37. Kucher N, Koo S, Quiroz R, et al. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med. 2005;352:969–977

☆ Financial support for this study was provided entirely by an unrestricted educational grant from the Eli Lilly Company. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. The following author is employed by the sponsor: Joseph A. Johnston, MD, MSc.

PII: S0883-9441(08)00022-1

doi: 10.1016/j.jcrc.2007.12.016

Journal of Critical Care
Volume 23, Issue 4 , Pages 484-492 , December 2008

Article Tools

* Image Usage & Resolution