Journal of Anesthesia

, Volume 27, Issue 4, pp 618–622 | Cite as

Effects of IgM-Enriched Immunoglobulin Therapy in Septic-Shock–Induced Multiple Organ Failure: Pilot Study

  • Ildiko Toth
  • Andras Mikor
  • Tamas Leiner
  • Zsolt Molnar
  • Lajos Bogar
  • Tamas SzakmanyEmail author
Short Communication


Mortality due to septic-shock–induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.


Septic shock Immunoglobulin Procalcitonin Respiratory failure Mortality Organ failure C-reactive protein 


  1. 1.
    Flaatten H, Gjerde S, Guttormsen AB, Haugen O, Høivik T, Onarheim H, Aardal S. Outcome after acute respiratory failure is more dependent on dysfunction in other vital organs than on the severity of the respiratory failure. Crit Care. 2003;7:R72–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36:222–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877–87.PubMedCrossRefGoogle Scholar
  4. 4.
    Alejandria MM, Lansang MA, Dans LF, Mantaring JB. Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev. 2002;4:CD001090.Google Scholar
  5. 5.
    Berlot G, Vassallo MC, Busetto N, Bianchi M, Zornada F, Rosato I, Tartamella F, Prisco L, Bigotto F, Bigolin T, Ferluga M, Batticci I, Michelone E, Borelli M, Viviani M, Tomasini A. 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. 2012;27:167–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Yavuz L, Aynali G, Aynali A, Alaca A, Kutuk S, Ceylan BG. The effects of adjuvant immunoglobulin M-enriched immunoglobulin therapy on mortality rate and renal function in sepsis-induced multiple organ dysfunction syndrome: retrospective analysis of intensive care unit patients. J Int Med Res. 2012;40:1166–74.PubMedCrossRefGoogle Scholar
  7. 7.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. 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;101:1644–55.PubMedCrossRefGoogle Scholar
  8. 8.
    Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23:1638–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Laupland KB, Kirkpatrick AW, Delaney A. 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. 2007;35:2686–92.PubMedCrossRefGoogle Scholar
  10. 10.
    Werdan K, Pilz G, Bujdoso O, Fraunberger P, Neeser G, Schmieder RE, Viell B, Marget W, Seewald M, Walger P, Stuttmann R, Speichermann N, Peckelsen C, Kurowski V, Osterhues HH, Verner L, Neumann R, Müller-Werdan U. Score-based immunoglobulin therapy of sepsis (SBITS) study group. Crit Care Med. 2007;35:2693–701.Google Scholar
  11. 11.
    Kreymann KG, de Heer G, Nierhaus A, Kluge S. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med. 2007;35:2677–85.PubMedCrossRefGoogle Scholar
  12. 12.
    Rodríguez A, Rello J, Neira J, Maskin B, Ceraso D, Vasta L, Palizas F. Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery. Shock. 2005;23:298–304.PubMedCrossRefGoogle Scholar
  13. 13.
    Pilz G, Kreuzer E, Kääb S, Appel R, Werdan K. Early sepsis treatment with immunoglobulins after cardiac surgery in score-identified post-cardiac patients at high risk for sepsis. Chest. 1994;105:76–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Kress HG, Scheidewig C, Schmitt H, Silber R. Reduced incidence of postoperative infections following intravenous application of an IgA and IgM-enriched immunoglobulin preparation in anergic patients undergoing cardiac surgery. Crit Care Med. 1999;27:1281–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Opal SM. Immunologic alterations and the pathogenesis of organ failure in the ICU. Semin Respir Crit Care Med. 2011;32:569–80.PubMedCrossRefGoogle Scholar
  16. 16.
    Norrby-Teglund A, Haque KN, Hammarström L. 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. 2006;260:509–16.PubMedCrossRefGoogle Scholar
  17. 17.
    Tugrul S, Ozcan PE, Akinci O, Seyhun Y, Cagatay A, Cakar N, Esen F. The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830]. Crit Care. 2002;6:357–62.PubMedCrossRefGoogle Scholar
  18. 18.
    Vincent JL, Nelson DR, Williams MD. Is worsening multiple organ failure the cause of death in patients with severe sepsis? Crit Care Med. 2011;39:1050–5.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Society of Anesthesiologists 2013

Authors and Affiliations

  • Ildiko Toth
    • 1
  • Andras Mikor
    • 1
    • 2
  • Tamas Leiner
    • 1
  • Zsolt Molnar
    • 1
    • 2
  • Lajos Bogar
    • 1
  • Tamas Szakmany
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of Anaesthesiology and Intensive TherapyUniversity of PecsPecsHungary
  2. 2.Department of Anaesthesiology and Intensive TherapyAlbert Szent-Gyorgyi University of SzegedSzegedHungary
  3. 3.Department of Anaesthetics, Theatres and Critical CareCwm Taf LHBLlantrisantWales, UK
  4. 4.Department of Anaesthesia, Intensive Care and Pain Medicine, Medical SchoolCardiff UniversityCardiffWales, UK

Personalised recommendations