Risk Stratification in Severe Sepsis: Organ Failure Scores, PIRO or Both?

  • R. P. Moreno
  • P. Metnitz
  • P. Bauer
Conference paper


The use of all-cause hospital mortality as the sole or major endpoint for the evaluation of clinical trials in intensive care was challenged in the mid 1980s, in the aftermath of a very long series of negative clinical trials in patients with sepsis, severe sepsis, and septic shock [1]. This outcome measure, until then viewed as the golden standard in clinical trials in intensive care, is, beyond any doubt, a very relevant endpoint both for researchers and for clinicians. Its use has been contested because hospital policy can and does change the location of deaths (e.g., discharging patients to the ward to die) and mortality rates can, therefore, be significantly underestimated in hospitals that discharge patients very early in the course of their disease to other facilities [2].


Septic Shock Severe Sepsis Organ Dysfunction Systemic Inflammatory Response Syndrome Drotrecogin Alfa 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sibbald WJ, Vincent JL (1995) Round table conference on clinical trials for the treatment of sepsis. Brussels, March 12–14, 1994. Intensive Care Med 21: 184–189CrossRefPubMedGoogle Scholar
  2. 2.
    Jencks SF, Williams DK, Kay TL (1988) Assessing hospital-associated deaths from discharge data. The role of length of stay and comorbidities. JAMA 260: 2240–2246CrossRefPubMedGoogle Scholar
  3. 3.
    Panacek EA, Marshall JC, Albertson TE, et al (2004) Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med 32: 2173–2182PubMedGoogle Scholar
  4. 4.
    Cohen J, Guyatt G, Bernard GR, et al (2001) New strategies for clinical trials in patients with sepsis and septic shock. Crit Care Med 29: 880–886CrossRefPubMedGoogle Scholar
  5. 5.
    Bernard GR, Vincent JL, Laterre PF, et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344: 699–709CrossRefPubMedGoogle Scholar
  6. 6.
    Ely EW, Laterre PF, Angus DC, et al (2003) Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis. Crit Care Med 31: 12–19CrossRefPubMedGoogle Scholar
  7. 7.
    Abraham E, Laterre PF, Garg R, et al (2005) Drotrecogin alfa (Activated) for adults with severe sepsis and a low risk of death. N Engl J Med 353: 1332–1341CrossRefPubMedGoogle Scholar
  8. 8.
    Bertolini G, Rossi C, Anghileri A, Livigni S, Addis A, Poole D (2007) Use of Drotrecogin alfa (activated) in Italian intensive care units: the results of a nationwide survey. Intensive Care Med 33: 426–434CrossRefPubMedGoogle Scholar
  9. 9.
    Kanji S, Perreault MM, Chant C, Williamson D, Burry L (2007) Evaluating the use of Drotrecogin alfa (activated) in adult severe sepsis: a Canadian multicenter observational study. Intensive Care Med 33: 517–523CrossRefPubMedGoogle Scholar
  10. 10.
    Eichacker PQ, Natanson C (2007) Increasing evidence that the risks of rhAPC may outweigh its benefits. Intensive Care Med 33: 396–399CrossRefPubMedGoogle Scholar
  11. 11.
    Finfer S, Ranieri VM, Thompson BT, et al (2008) Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock. Intensive Care Med 34: 1935–1947CrossRefPubMedGoogle Scholar
  12. 12.
    Sprung CL, Annane D, Keh D, et al (2008) Hydrocortisone Therapy for Patients with Septic Shock. N Engl J Med 358: 111–124CrossRefPubMedGoogle Scholar
  13. 13.
    Annane D, Sebille V, Charpentier C, et al (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288: 862–871CrossRefPubMedGoogle Scholar
  14. 14.
    Moreno R, Sprung C, Annane D, et al (2007) Organ dysfunction/failure in patients with septic shock: results of the CORTICUS study. Intensive Care Med 33: S186 (abst)Google Scholar
  15. 15.
    Petros AI, Marshall JC, van-Saene HK, (1995) Should morbidity replace mortality as an endpoint for clinical trials in intensive care? Lancet 345: 369–371CrossRefPubMedGoogle Scholar
  16. 16.
    Knaus WA, Wagner DP, Harrell FE, Draper EA (1994) What determines prognosis in sepsis? Evidence for a comprehensive individual patient risk assessment approach to the design and analysis of clinical trials. In: Reinhart K, Eyrich K, Sprung C (eds) Sepsis: Current Perspectives in Pathophysiology and Therapy. Springer-Verlag, Berlin Heidelberg, pp 23–37Google Scholar
  17. 17.
    Le Gall J-R, Lemeshow S, Leleu G, et al (1995) Customized probability models for early severe sepsis in adult intensive care patients. JAMA 273: 644–650CrossRefPubMedGoogle Scholar
  18. 18.
    Knaus WA, Harrell FE, Fisher CJ, et al (1993) The clinical evaluation of new drugs for sepsis. A prospective study design based on survival analysis. JAMA 270: 1233–1241CrossRefPubMedGoogle Scholar
  19. 19.
    Knaus WA (1994) Principles of severity stratification and outcome prediction in sepsis and shock. Intensive Care Med 20: S115 (abst)Google Scholar
  20. 20.
    Vincent J-L, Moreno R, Takala J, et al (1996) The SOFA (Sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med 22: 707–710CrossRefPubMedGoogle Scholar
  21. 21.
    Moreno R, Vincent J-L, Matos R, et al (1999) The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Intensive Care Med 25: 686–696CrossRefPubMedGoogle Scholar
  22. 22.
    Marshall JC, Cook DA, Christou NV, Bernard GR, Sprung CL, Sibbald WJ (1995) Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med 23: 1638–1652CrossRefPubMedGoogle Scholar
  23. 23.
    Le Gall JR, Klar J, Lemeshow S, et al (1996) The logistic organ dysfunction system. A new way to assess organ dysfunction in the intensive care unit. JAMA 276: 802–810CrossRefPubMedGoogle Scholar
  24. 24.
    Chang RW, Jacobs S, Lee B (1988) Predicting outcome among intensive care unit patients using computerised trend analysis of daily Apache II scores corrected for organ system failure. Intensive Care Med 14: 558–566CrossRefPubMedGoogle Scholar
  25. 25.
    Timsit JF, Fosse JP, Troche G, et al (2001) Accuracy of a composite score using daily SAPS II and LOD scores for predicting hospital mortality in ICU patients hospitalized for more than 72 h. Intensive Care Med 27: 1012–1021CrossRefPubMedGoogle Scholar
  26. 26.
    Vincent JL (1997) Dear SIRS, I'm sorry to say that I don't like you … Crit Care Med 25: 372–374CrossRefPubMedGoogle Scholar
  27. 27.
    Levy MM, Fink MP, Marshall JC, et al (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 29: 530–538PubMedGoogle Scholar
  28. 28.
    Marshall JC, Vincent J-L, Fink MP, et al (2003) Measures, markers, and mediators: Toward a staging system for clinical sepsis. A Report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25–26, 2000. Crit Care Med 31: 1560–1567CrossRefPubMedGoogle Scholar
  29. 29.
    Vincent JL, Wendon J, Groeneveld J, Marshall JC, Streat S, Carlet J (2003) The PIRO Concept: o is for organ dysfunction. Crit Care 7: 260–264CrossRefPubMedGoogle Scholar
  30. 30.
    Angus DC, Burgner D, Wunderink R, et al (2003) The PIRO Concept: P is for predisposition. Crit Care 7: 248–251CrossRefPubMedGoogle Scholar
  31. 31.
    Gerlach H, Dhainaut JF, Harbarth S, Reinhart K, Marshall JC, Levy M (2003) The PIRO Concept: R is for response. Crit Care 7: 256–259CrossRefPubMedGoogle Scholar
  32. 32.
    Vincent JL, Opal S, Torres A, Bonten M, Cohen J, Wunderink R (2003) The PIRO Concept: I is for infection. Crit Care 7: 252–255CrossRefPubMedGoogle Scholar
  33. 33.
    Finkielman JD, Dara SI, Mohammad Z, Sujay B, Afessa B (2004) Sepsis mortality prediction based on predisposition, infection, response and organ dysfunction (PIRO). Crit Care Med 32: A134 (abst)CrossRefGoogle Scholar
  34. 34.
    Metnitz PG, Moreno RP, Almeida E, et al (2005) SAPS 3. From evaluation of the patient to evaluation of the intensive care unit. Part 1: Objectives, methods and cohort description. Intensive Care Med 31: 1336–1344CrossRefPubMedGoogle Scholar
  35. 35.
    Moreno RP, Metnitz B, Adler L, et al (2008) Sepsis mortality prediction based on predisposition, infection and response. Intensive Care Med 34: 496–504CrossRefPubMedGoogle Scholar
  36. 36.
    Rubulotta F, Marshall JC, Ramsay G, Nelson D, Levy M, Williams M (2009) Predisposition, insult/infection, response, and organ dysfunction: A new model for staging severe sepsis. Crit Care Med 37: 1329–1335CrossRefPubMedGoogle Scholar
  37. 37.
    Lisboa T, Diaz E, Sa-Borges M, et al (2008) The ventilator-associated pneumonia PIRO Score: A tool for predicting ICU mortality and health-care resources use in ventilator-associated pneumonia. Chest 134: 1208–1216CrossRefPubMedGoogle Scholar
  38. 38.
    Rello J, Rodriguez A, Lisboa T, Gallego M, Lujan M, Wunderink R (2009) PIRO score for community-acquired pneumonia: A new prediction rule for assessment of severity in intensive care unit patients with community-acquired pneumonia. Crit Care Med 37: 456–462CrossRefPubMedGoogle Scholar
  39. 39.
    Flaatten H (2004) Epidemiology of sepsis in Norway in 1999. Crit Care 8: R180–R184CrossRefPubMedGoogle Scholar
  40. 40.
    Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348: 1546–1554CrossRefPubMedGoogle Scholar
  41. 41.
    Harrison DA (2006) The epidemiology of severe sepsis in England, Wales and Northern Ireland, 42.1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Crit Care 10: R42CrossRefPubMedGoogle Scholar
  42. 42.
    Martin CM, Priestap F, Fisher H, et al (2009) A prospective, observational registry of patients with severe sepsis: The Canadian Sepsis Treatment And Response Registry. Crit Care Med 37: 81–88CrossRefPubMedGoogle Scholar
  43. 43.
    Dellinger RP, Levy MM, Cadet JM, et al (2008) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34: 17–60CrossRefPubMedGoogle Scholar
  44. 44.
    Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273: 117–123CrossRefPubMedGoogle Scholar
  45. 45.
    Alberti C, Brun-Buisson C, Goodman SV, et al (2003) Influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients. Am J Respir Crit Care Med 168: 77–84CrossRefPubMedGoogle Scholar
  46. 46.
    Alberti C, Brun-Buisson C, Burchardi H, et al (2002) Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med 28: 108–121CrossRefPubMedGoogle Scholar
  47. 47.
    Rangel-Frausto MS (1999) The epidemiology of bacterial sepsis. Infect Clin North Am 13: 299–312CrossRefGoogle Scholar
  48. 48.
    Alberti C, Brun-Buisson C, Chevret S, et al (2005) Systemic inflammatory response and progression to severe sepsis in critically ill infected patients. Am J Respir Crit Care Med 171: 461–468CrossRefPubMedGoogle Scholar
  49. 49.
    Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL (2001) Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 286: 1754–1758CrossRefPubMedGoogle Scholar
  50. 50.
    Clermont G, Kaplan V, Moreno R, et al (2004) Dynamic microsimulation to model multiple outcomes in cohorts of critically ill patients. Intensive Care Med 30: 2237–2244CrossRefPubMedGoogle Scholar
  51. 51.
    Moreno RP, Metnitz PG, Almeida E, et al (2005) SAPS 3. From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 31: 1345–1355CrossRefPubMedGoogle Scholar
  52. 52.
    Moreno R, Jordan B, Metnitz P (2007) The changing prognostic determinants in the critically ill patient In: Vincent JL (ed) 2007 Yearbook of Intensive Care and Emergency Medicine. Springer-Verlag, pp 899–907.Google Scholar

Copyright information

© Springer Science + Business Media Inc. 2010

Authors and Affiliations

  • R. P. Moreno
    • 1
  • P. Metnitz
    • 2
  • P. Bauer
    • 3
  1. 1.Unit of Polyvalent Intensive Care Hospital de St. Antonio dos CapuchosCentro Hospitalar de Lisboa Central, E.P.E.LisbonPortugal
  2. 2.Department of Anesthesiology and General Intensive CareMedical University of ViennaViennaAustria
  3. 3.Department of Medical StatisticsMedical University of ViennaViennaAustria

Personalised recommendations