IgM-enriched Immunoglobulins in Sepsis

  • F. Esen
  • S. Tugrul


The role of intravenous immunoglobulins (IVIGs) as an adjunctive treatment in sepsis has been a subject of debate for years. The main critique has been the lack of randomized trials of adequate size showing the effect of IVIGs on outcome. For that reason, many of the guidelines on sepsis have not addressed the use of IVIG treatment. Likewise, the Surviving Sepsis Guidelines [1] did not consider the use of immunoglobulins in adult patients with sepsis.


Severe Sepsis IVIG Treatment Critical Illness Polyneuropathy Immunoglobulin Preparation Severe Systemic Inflammatory Response Syndrome 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dellinger RP, Carlet JM, Masur H, et al (2004) Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 32: 858–873CrossRefPubMedGoogle Scholar
  2. 2.
    Ziegler EJ, McCutchan JA, Fierer J, et al (1982) Treatment of Gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 307: 1225–1230PubMedCrossRefGoogle Scholar
  3. 3.
    Alejandria MM, Lansang MA, Dans LF, Mantaring JB (2002) Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev CD0011090Google Scholar
  4. 4.
    Kreymann KG, de Heer G, Nierhaus A, Kluge S (2007) Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med 35: 2677–2685CrossRefPubMedGoogle Scholar
  5. 5.
    Norrby-Teglund A, Haque KN, Hammarström L (2006) Intravenous polyclonal IgM-enriched immunoglobulin therapy in sepsis: a review of clinical efficacy in relation to microbiological aetiology and severity of sepsis. J Intern Med 260: 509–516CrossRefPubMedGoogle Scholar
  6. 6.
    Laupland KB, Kirkpatrick AW, Delaney A (2007) Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: a systematic review and meta-analysis. Crit Care Med 35: 2686–2692CrossRefPubMedGoogle Scholar
  7. 7.
    Pildal J, Gøtzsche PC(2004) Polyclonal immunoglobulin for treatment of bacterial sepsis: a systematic review. Clin Infect Dis 39: 38–46CrossRefPubMedGoogle Scholar
  8. 8.
    Turgeon AF, Hutton B, Fergusson DA, et al (2007) Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis. Ann Intern Med 146: 193–203PubMedGoogle Scholar
  9. 9.
    Werdan K, Pilz G, Bujdoso O, et al (2007) Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit Care Med 35: 2693–2701CrossRefPubMedGoogle Scholar
  10. 10.
    Negi VS, Elluru S, Sibéril S, et al (2007) Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 27: 233–245CrossRefPubMedGoogle Scholar
  11. 11.
    Werdan K (2001) Intravenous immunoglobulin for prophylaxis and therapy of sepsis. Curr Opin Crit Care 7: 354–361CrossRefPubMedGoogle Scholar
  12. 12.
    Stephan W (1989) Investigations to demonstrate the antibacterial and antitoxic efficacy of an IgM-Enriched intravenous immunoglobulin preparation. In: Faist E, Ninnemann J, Green D (eds) Immune Consequences of Trauma; Shock and Sepsis. Springer-Verlag, Heidelberg, pp 501–507Google Scholar
  13. 13.
    Stephan W, Dichtelmüller H, Schedel I (1985) [Properties and efficacy of a human immunoglobulin M preparation for intravenous administration]. Arzneimittelforschung 35: 933–936PubMedGoogle Scholar
  14. 14.
    Garbett ND, Matharu GS, Cole PJ (1989) Defective opsonization of Haemophilus influenzae by sera of elderly patients. Clin Exp Immunol 76: 73–75PubMedGoogle Scholar
  15. 15.
    Rieben R, Roos A, Muizert Y, Tinguely C, Gerritsen AF, Daha MR (1999) Immunoglobulin Menriched human intravenous immunoglobulin prevents complement activation in vitro an in vivo in a rat model of acute inflammation. Blood 93: 942–951PubMedGoogle Scholar
  16. 16.
    Trautmann M, Held TK, Susa M, et al (1998) Bacterial lipopolysaccharide (LPS)-specific antibodies in commercial human immunoglobulin preparations: superior antibody content of an IgM-enriched product. Clin Exp Immunol 111: 81–90CrossRefPubMedGoogle Scholar
  17. 17.
    Berger D, Schleich S, Seidelmann M, Berger HG (1993) Antiendotoxic therapy with polyclonal and polyvalent immunoglobulins: in vitro an in vivo studies. In: Faist E Meakins JL, Schildberg FW (eds) Host Defense Dysfunction in Trauma, Shock and Sepsis. Springer-Verlag, Heidelberg, pp 1164–1174Google Scholar
  18. 18.
    Norrby-Teglund A, Ihendyane N, Kansal R, et al (2000) Relative neutralizing activity in polyspecific IgM, IgA, and IgG preparations against group A streptococcal superantigens. Clin Infect Dis 31: 1175–1182CrossRefPubMedGoogle Scholar
  19. 19.
    Oesser S, Schulze C, Seifert J (1999) Protective capacity of an IgM/IgA-enriched polyclonal immunoglobulin-G preparation in endotoxemia. Res Exp Med 198: 325–339CrossRefGoogle Scholar
  20. 20.
    Jacobs S, Sobki S, Morais C, Tariq M. (2000) Effect of pentaglobin and piperacillin on survival in a rat model of faecal peritonitis: importance of intervention timings. Acta Anaesthesiol Scand 44: 88–95CrossRefPubMedGoogle Scholar
  21. 21.
    Hoffman JN, Fertmann JM, Vollmar B, Laschke MW, Jauch KW, Menger MD (2008) Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte-endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia. Shock 29: 133–139CrossRefPubMedGoogle Scholar
  22. 22.
    Stehr SN, Knels L, Weissflog C, et al (2008) Effects of IGM-enriched solution on polymorphonuclear neutrophil function, bacterial clearance, and lung histology in endotoxemia. Shock 29: 167–172PubMedGoogle Scholar
  23. 23.
    Lachmann RA, van Kaam AH, Haitsma JJ, Verbrugge SJ, Delreu F, Lachmann B (2004) Immunoglobulin M-enriched intravenous polyclonal immunoglobulins reduce bacteremia following Klebsiella pneumoniae infection in an acute respiratory distress syndrome rat model. Exp Lung Res 30: 251–260CrossRefPubMedGoogle Scholar
  24. 24.
    Schedel I, Dreikhausen U, Nentwig B, et al (1991) Treatment of gram-negative septic shock with an immunoglobulin preparation: A prospective, randomized clinical trial. Crit Care Med 19: 1104–1113CrossRefPubMedGoogle Scholar
  25. 25.
    Tugrul S, Ozcan PE, Akinci O, et al (2002) The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis. Crit Care 6: 357–362CrossRefPubMedGoogle Scholar
  26. 26.
    Karatzas S, Boutzouka E, Venetsanou K, Myrianthefs P, Fildisis G, Baltopoulos G (2002) The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis: another point of view. Crit Care 6: 543–544CrossRefPubMedGoogle Scholar
  27. 27.
    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: 298–304CrossRefPubMedGoogle Scholar
  28. 28.
    Hentrich M, Fehnle K, Ostermann H, et al (2006) IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiplecenter trial. Crit Care Med 34: 1319–1325CrossRefPubMedGoogle Scholar
  29. 29.
    Werdan K, Pilz G, Müller-Werdan U, et al (2008) Immunoglobulin G treatment of postcardiac surgery patients with score-identified severe systemic inflammatory response syndrome—the ESSICS study. Crit Care Med 36: 716–723CrossRefPubMedGoogle Scholar
  30. 30.
    Pilz G, Kreuzer E, Kaab S, Appel R, Werdan K (1994) Early sepsis treatment with immunoglobulins after cardiac surgery in score-identified high-risk patients. Chest 105: 76–82CrossRefPubMedGoogle Scholar
  31. 31.
    Pilz G, Appel R, Kreuzer E, Werdan K (1997) Comparison of early IgM-enriched immunoglobulin vs polyvalent IgG administration in score-identified postcardiac surgical patients at high risk for sepsis. Chest 111: 419–426CrossRefPubMedGoogle Scholar
  32. 32.
    Buda S, Riefolo A, Biscione R, et al (2005) Clinical experience with polyclonal IgM-enriched Immunoglobulins in a group of patients affected by sepsis after cardiac surgery. J Cardiothorac Vasc Anesth 19: 440–445CrossRefPubMedGoogle Scholar
  33. 33.
    Kress HG, Scheidewing C, Schmidt H, Silber R (1999) Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A-and immunoglobulin M-enriched preparation in anergic patients undergoing cardiac surgery. Crit Care Med 27: 1281–1287CrossRefPubMedGoogle Scholar
  34. 34.
    Haque K, Remo C, Bahakim H (1995) Comparison of two types of intravenous immunoglobulins in the treatment of neonatal sepsis. Clin Exp Immunol 101: 328–333PubMedGoogle Scholar
  35. 35.
    Mohr M, Englisch L, Roth A, Burchardi H, Zielmann S (1997) Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gram-negative sepsis. Intensive Care Med 23: 1144–1149CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • F. Esen
    • 1
  • S. Tugrul
    • 1
  1. 1.Department of Anesthesiology and Intensive Care Medical Faculty of IstanbulUniversity of IstanbulIstanbulTurkey

Personalised recommendations