Timing IgM Treatment in Sepsis: Is Procalcitonin the Answer?

  • Z. Molnár
  • J. Fogas
Part of the Annual Update in Intensive Care and Emergency Medicine book series (AUICEM, volume 2012)


Modern intensive care therapy could, with a small stretch of the imagination, be argued to equal severe sepsis and septic shock therapy. This does not mean that every patient on the intensive care unit (ICU) is septic, but every critically ill patient certainly has the potential risk of acquiring sepsis. Furthermore, almost everything that we know today about critical illness is somehow linked to what we have learned from experimental and clinical sepsis studies. However, after decades of intense research we are still struggling to improve mortality on our ICUs, although there is a tendency towards some improvement (from 37 to 30.7 %) [1, 2]. So, is it ‘much ado about nothing’? Absolutely not! The devil, as always, lies in the details. We keep forgetting that what we call ‘sepsis’ is not a definitive disease, or diagnosis, but a syndrome, for which the criteria were defined by consensus by a group of scientists led by the late Roger Bone in a Las Vegas hotel room back in the 1980s, and a few years later on at a consensus conference [3–5]. In the case of definitive conditions such as, for example, fractured neck of femur or myocardial infarction, we have specific tools for diagnosis, and treatment. Unfortunately, this is not the case for sepsis. There is no exact diagnostic measure to capture the moment when systemic inflammatory response syndrome (SIRS), infection, sepsis, severe sepsis or septic shock occurs, nor to precisely differentiate between them. This uncertainty will inevitably lead to inhomogeneous groups of patients with selection bias, sampling error in our studies, and eventually failure to produce significant results [6–8].


Septic Shock Severe Sepsis Systemic Inflammatory Response Syndrome Septic Patient Sequential Organ Failure Assessment Score 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    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: 108–121PubMedCrossRefGoogle Scholar
  2. 2.
    Levy MM, Dellinger RP, Townsend SR (2010) The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 36: 222–231PubMedCrossRefGoogle Scholar
  3. 3.
    Bone RC, Fisher CJ, Clemmer TP, et al (1987) A controlled clinical trial of high dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317: 654–658CrossRefGoogle Scholar
  4. 4.
    Marshall JC, Aarts MA (2001) From Celsus to Galen to Bone: The illnesses, syndromes, and diseases of acute inflammation. In: Vincent JL (ed), Yearbook of intensive care and emergency medicine, Springer-Verlag, Berlin, pp: 3–12Google Scholar
  5. 5.
    American College of Chest Physicians — Society of Critical Care Medicine (1992) Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864–875CrossRefGoogle Scholar
  6. 6.
    Natanson C, Esposito CJ, Banks St (1998) The sirens’ songs of confirmatory sepsis trials: Selection bias and sampling error. Crit Care Med 26: 1927–1931PubMedCrossRefGoogle Scholar
  7. 7.
    Cohen J (1999) The “failure” of clinical trials in sepsis. Curr Opinion Crit Care 330: 339–340CrossRefGoogle Scholar
  8. 8.
    Vincent JL (2010) We should abandon randomized controlled trials in the intensive care unit. Crit Care Med 38 (Suppl): S534–S538PubMedCrossRefGoogle Scholar
  9. 9.
    Werdan K (2007) Mirror, mirror on the wall, which is the fairest meta-analysis of all? Crit Care Med 35: 2852–2854PubMedCrossRefGoogle Scholar
  10. 10.
    Kreymann KG, Geraldine H, Nierhaus A, Kluge S (2007) Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med 35: 2677–2685PubMedCrossRefGoogle Scholar
  11. 11.
    Alejandria MM, Lansang MAD, Dans LF, Mantaring III JB (2001) Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev CD001090Google Scholar
  12. 12.
    Neugebauer EAM (2007) To use or not to use? Polyclonal intravenous immunoglobulins for the treatment of sepsis and septic shock. Crit Care Med 35:2855PubMedCrossRefGoogle Scholar
  13. 13.
    Schedel I, Dreikhausen U, Nentwig B, et al (1991) Treatment of gram-negative septic shock with an immunoglobulin preparation: A prospective, randomised clinical tial. Crit Care Med 19: 1104–1113PubMedCrossRefGoogle Scholar
  14. 14.
    Tugrul S, Ozcan P E, Akinci O, et al (2002) The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis. Crit Care 6: 357–362PubMedCrossRefGoogle Scholar
  15. 15.
    Karatzas S, Boutzouka E, Venetsanou K, et al (2002) The effect of IgM-enriches immunoglobilin preparations in patients with severe sepsis: another pont of view. Crit Care 6: 543–544PubMedCrossRefGoogle Scholar
  16. 16.
    Rodríguez A, Rello J, Neira J, et al (2005) Effects of high dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery. Shock 23: 298–304PubMedCrossRefGoogle Scholar
  17. 17.
    Hentrich M, Fehnle K, Ostermann H, et al (2006) IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: A randomized, controlled, multiple-center trial. Crit Care Med 34: 1319–1325PubMedCrossRefGoogle Scholar
  18. 18.
    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: 699–709PubMedCrossRefGoogle Scholar
  19. 19.
    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: 12–19PubMedCrossRefGoogle Scholar
  20. 20.
    Dellinger RP, Levy MM, Carlet JM, et al (2008) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34: 17–60PubMedCrossRefGoogle Scholar
  21. 21.
    Simon L, Gauvin F, Amre DK, et al (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 39: 206–217PubMedCrossRefGoogle Scholar
  22. 22.
    Berlot G, Vassallo MC, Busetto N, et al (2012) Relationship between the timing of administration of IgM and IgA enriched immunoglobulins in patients with severe sepsis and septic shock and the outcome: A retrospective analysis. J Crit Care (in press)Google Scholar
  23. 23.
    Castelli GP, Pognani C, Meisner M, et al (2004) Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction. Crit Care 8: R234–R240PubMedCrossRefGoogle Scholar
  24. 24.
    Jensen JU, Heslet L, Jensen TH, et al (2006) Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 34: 2596–2602PubMedCrossRefGoogle Scholar
  25. 25.
    Ventetuolo CE, Levy MM (2008) Biomarkers: Diagnosis and risk assessment in sepsis. Clin Chet Med 29: 591–603CrossRefGoogle Scholar
  26. 26.
    Molnar Z, Bogar L (2006) Let’s go dynamic with procalcitonin! Crit Care Med 34: 2687–2688PubMedCrossRefGoogle Scholar
  27. 27.
    Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster randomised, single blinded intervention trial. Lancet 363: 600–607Google Scholar
  28. 28.
    Müller F, Christ-Crain M, Bregenzer T, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest 138: 121–129Google Scholar
  29. 29.
    Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J (2008) Use of procalcitonin to shorten antibiotic treatment duration in septic patients. Am J Respir Crit Care Med 177: 498–505PubMedCrossRefGoogle Scholar
  30. 30.
    Bouadma L, Luyt CE, Tubach F, et al (2010) Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 375: 463–474PubMedCrossRefGoogle Scholar
  31. 31.
    Jensen JU, Hein L, Lundgren B, et al (2011) Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: A randomized trial. Crit Care Med 39: 2048–2058PubMedCrossRefGoogle Scholar
  32. 32.
    Szakmany T, Molnar Z (2003) Procalcitonin levels do not predict mortality following major abdominal surgery. Can J Anaesth 50: 1082–1083PubMedCrossRefGoogle Scholar
  33. 33.
    Lindberg M, Hole A, Johnsen H, et al (2002) Reference intervals for procalcitonin and Creactive protein after major abdominal surgery. Scand J Clin Lab Invest 62: 189–194PubMedCrossRefGoogle Scholar
  34. 34.
    Clec’h C, Fosse JP, Karoubi P, et al (2006) Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock. Crit Care Med 34: 102–107CrossRefGoogle Scholar
  35. 35.
    Reith HB, Rauchschwalbe SK, Mittelkötter U, et al (2004) IgM-enriched immunoglobulin (Pentaglobin) positively influences the course of post-surgical intra-abdominal infections. Eur J Med Res 9: 479–484PubMedGoogle Scholar
  36. 36.
    Szakmany T, Toth I, Molnar Z, Leiner T, Mikor A, Bogar L (2006). Effects of polyclonal IGM in septic shock accompanied by severe respiratory failure: a randomized trial. Intensive Care Med 32 (Suppl 1): S226 (abst)Google Scholar
  37. 37.
    Reinhart K, Brunkhorst FM, Bone Hg, et al (2010) Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine. Ger Med Sci 8: Doc 14Google Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Z. Molnár
  • J. Fogas

There are no affiliations available

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