Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Infectious Disease Reports
Published in: Current Infectious Disease Reports 12/2014

01-12-2014 | Cardiovascular Infections (D Levine, Section Editor)

Use of Intravenous Immunoglobulin in Critically Ill Patients

Authors: Summer Donovan, Gonzalo M. L. Bearman

Published in: Current Infectious Disease Reports | Issue 12/2014

Login to get access

Abstract

Intravenous immunoglobulin (IVIG) has been suggested for the treatment of many ailments due to its ability to modulate the immune system and to provide passive immunity to commonly circulating pathogens. Its use as primary and adjunctive therapy for the treatment of conditions affecting critically ill patients is an attractive option, especially when alternative therapy does not exist. The body of literature on the use of IVIG for the treatment of several serious conditions, including sepsis, toxic shock syndrome, acute myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and H1N1 influenza, were reviewed. Despite advances in treatment of these conditions since they were first described, there remains a paucity of well-designed studies on the use of IVIG for their treatment. Therefore, the use of IVIG for treatment of these conditions remains controversial.
Literature
1.
American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. Pickering LK, ed. 29th ed. Elk Grove Village, IL; 2012:56-62.
2.
Kawada K, Terasaki PI. Evidence for immunosuppression by high dose gammaglobulin. Exp Hematol. 1987;15:133–6.PubMed
3.
Tsubakio T, Kurata Y, Katagiri S, et al. Alteration of T cell subsets and immunoglobulin synthesis in vitro during high dose gamma-globulin therapy in patients with idiopathic thrombocytopenic purpura. Clin Exp Immunol. 1983;53:697.PubMedCentralPubMed
4.
Delfraissy JF, Tchernia G, Laurian Y, et al. Suppressor cell function after intravenous gammaglobulin treatment in adult chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1985;60:315.PubMedCrossRef
5.
Koffman BM, Dalakas MC. Effect of high-dose intravenous immunoglobulin on serum chemistry, hematology, and lymphocyte subpopulations: assessments based on controlled treatment trials in patients with neurological diseases. Muscle Nerve. 1997;20:1102.PubMedCrossRef
6.
Anderson J, Skansen-Saphir U, Sparrelid E, et al. Intravenous immune globulin affects cytokine production in T lymphocytes and monocytes/macrophages. Clin Exp Immunol. 1996;104 Suppl 1:10–20.
7.
Menezes MCS, Benard G, Sato MN, et al. In vitro inhibitory activity of tumor necrosis factor alpha and interleukin-2 of human immunoglobulin preparations. Int Arch Allergy Immunol. 1997;114:323–8.PubMedCrossRef
8.
Shimozato T, Iwata M, Tamura N. Suppression of tumor necrosis factor alpha production by a human immunoglobulin preparation for intravenous use. Infect Immun. 1990;58:1384.PubMedCentralPubMed
9.
Samuelsson A, Towers TL, Ravetch JV. Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science. 2001;291:484.PubMedCrossRef
10.
Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature. 2011;475:110.PubMedCentralPubMedCrossRef
11.
Gupta M, Noel GJ, Schaefer M, et al. Cytokine modulation with immune γ-globulin in peripheral blood of normal children and its implications in Kawasaki disease treatment. J Clin Immunol. 2001;21:193–9.PubMedCrossRef
12.
Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest. 1993;91:602–7.PubMedCentralPubMedCrossRef
13.
Aukrust P, Froland SS, Liabakk NB, et al. Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobulin administration in vivo. Blood. 1994;84:2136–43.PubMed
14.
Kam JC, Szefler SJ, Surs W, et al. Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. J Immunol. 1993;151:3460–6.PubMed
15.
Spahn JD, Leung DYM, Chan MTS, et al. Mechanisms of glucocorticoid reduction in asthmatics treated with intravenous immunoglobulin. J Allergy Clin Immunol. 1999;103:421–6.PubMedCrossRef
16.
Modiano JF, Amran D, Lack G, et al. Posttranscriptional regulation of T cell IL-2 production by human pooled immunoglobulin. Clin Immunol Immunopathol. 1997;83:77–85.PubMedCrossRef
17.
Vassilev T, Gelin C, Kaveri SV. Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIG). Clin Exp Immunol. 1993;92:369–72.PubMedCentralPubMedCrossRef
18.•
Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012;367:2015–25. This paper provides a thorough review of currently proposed mechanisms of action of IVIG.PubMedCrossRef
19.
Sylvestre D, Clynes R, Ma M. Immunoglobulin G-mediated inflammatory responses develop normally in complement-deficient mice. J Exp Med. 1996;184:2385–92.PubMedCentralPubMedCrossRef
20.
Tackenberg B, Jelcic I, Baerenwaldt A, et al. Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci U S A. 2009;106:4788–92.PubMedCentralPubMedCrossRef
21.
Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546–54.PubMedCrossRef
22.
Werdan K, Pilz G, Bujdoso O, et al. Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit Care Med. 2007;35:2693.PubMedCrossRef
23.
Alejandria MM, Lansang MA, Dans LF, Mantaring 3rd JB. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013;9, CD001090.PubMed
24.
Pildal J, Gøtzsche PC. Polyclonal immunoglobulin for treatment of bacterial sepsis: a systematic review. Clin Infect Dis. 2004;39:38.PubMedCrossRef
25.
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.PubMedCrossRef
26.
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.PubMedCrossRef
27.
El-Nawawy A, El-Kinany H, Hamdy El-Sayed M, Boshra N. Intravenous polyclonal immunoglobulin administration to sepsis syndrome patients: a prospective study in a pediatric intensive care unit. J Trop Pediatr. 2005;51:271.PubMedCrossRef
28.
Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst. Rev. 2010. CD001239
29.•
INIS Collaborative Group, Brocklehurst P, Farrell B, et al. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med. 2011;365:1201. This large randomized, controlled trial provided definitive evidence for lack of benefit of IVIG for the treatment of neonatal sepsis.PubMedCrossRef
30.
Que YA, Moreillon P. Staphylococcus aureus (including staphylococcal toxic shock). In: Mandell: Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, 7th ed. Philadelphia: Churchill Livingstone, An Imprint of Elsevier; 2009: 2543-74
31.
Vergeront JM, Stolz SJ, Crass BA, et al. Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implications for toxic-shock syndrome. J Infect Dis. 1983;148(4):692–8.PubMedCrossRef
32.
Stolz SJ, Davis JP, Vergeront JM, et al. Development of serum antibody to toxic shock toxin among individuals with toxic shock syndrome in Wisconsin. J Infect Dis. 1985;151(5):883–9.PubMedCrossRef
33.
Yanagisawa C, Hanaki H, Natae T, et al. Neutralization of staphylococcal exotoxins in vitro by human-origin intravenous immunoglobulin. J Infect Chemother. 2007;13:368–72.PubMedCrossRef
34.
Norrby-Teglund A, Kaul R, Low DE, et al. Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production. J Immunol. 1996;156:3057.PubMed
35.
Norrby-Teglund A, Kaul R, Low DE, et al. Evidence for the presence of streptococcal-superantigen-neutralizing antibodies in normal polyspecific immunoglobulin G. Infect Immun. 1996;64:5395.PubMedCentralPubMed
36.
Darenberg J, Söderquist B, Normark BH, Norrby-Teglund A. Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome. Clin Infect Dis. 2004;38:836.PubMedCrossRef
37.
Barry W, Hudgins L, Donta ST, Pesanti EL. Intravenous immunoglobulin therapy for toxic shock syndrome. JAMA. 1992;267:3315.PubMedCrossRef
38.
Lamothe F, D’Amico P, Ghosn P, et al. Clinical usefulness of intravenous human immunoglobulins in invasive group A streptococcal infections: case report and review. Clin Infect Dis. 1995;21(6):1469–70.PubMedCrossRef
39.
Kaul R, McGeer A, Norrby-Teglund A, et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome—a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis. 1999;28:800–7.PubMedCrossRef
40.
Darenberg J, Ihendyane N, Sjölin J, et al. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37:333.PubMedCrossRef
41.
42.
Schrage B, Duan G, Yang LP, et al. Different preparations of intravenous immunoglobulin vary in their efficacy to neutralize streptococcal superantigens: implications for treatment of streptococcal toxic shock syndrome. Clin Infect Dis. 2006;43:743.PubMedCrossRef
43.
Takada H, Kishimoto C, Hiraoka Y. Therapy with immunoglobulin suppresses myocarditis in a murine coxsackievirus B3 model. Antiviral and anti-inflammatory effects. Circulation. 1995;92(6):1604–11.PubMedCrossRef
44.
Kishimoto C, Takada H, Kawamata H, et al. Immunoglobulin treatment prevents congestive heart failure in murine encephalomyocarditis viral myocarditis associated with reduction of inflammatory cytokines. J Pharmacol Exp Ther. 2001;299(2):645–51.PubMed
45.
McNamara DM, Rosenblum WD, Janosko KM, et al. Intravenous immune globulin in the therapy of myocarditis and acute cardiomyopathy. Circulation. 1997;95(11):2476–8.PubMedCrossRef
46.
Nigro G, Bastianon V, Colloridi V, et al. Human parvovirus B19 infection in infancy associated with acute and chronic lymphocyte myocarditis and high cytokine levels: report of 3 cases and review. Clin Infect Dis. 2001;31:65–9.CrossRef
47.
Takeda Y, Yasuda S, Miyazaki S, et al. High-dose immunoglobulin G therapy for fulminant myocarditis. Jpn Circ J. 1998;62:871–2.PubMedCrossRef
48.
Tedeschi A, Giannini S, Ciceri L, Massari FM. High-dose intravenous immunoglobulin in the treatment of acute myocarditis. A case report and review of the literature. J Intern Med. 2002;251:169–73.PubMedCrossRef
49.
McNamara DM, Holubkov R, Starling RC, et al. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation. 2001;103:2254–9.PubMedCrossRef
50.
Drucker NA, Colan SD, Lewis AB, et al. Gamma-globulin treatment of acute myocarditis in the pediatric population. Circulation. 1994;89:252.PubMedCrossRef
51.
Duvic M. Urticaria, drug hypersensitivity rashes, nodules and tumors, and atrophic diseases. In: Goldman: Goldman’s Cecil medicine, 24th ed. Saunders, An Imprint of Elsevier; 2011: 2532-43
52.
Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science. 1998;282:490–3.PubMedCrossRef
53.
Phan TG, Wong RC, Crotty K, Aldestein S. Toxic epidermal necrolysis in acquired immunodeficiency syndrome treated with intravenous gammaglobulin. Aust J Dermatol. 1999;40(3):153–7.CrossRef
54.
Magina S, Lisboa C, Goncalves E, et al. A case of toxic epidermal necrolysis treated with intravenous immunoglobulin. Br J Dermatol. 2000;142(1):191–2.PubMedCrossRef
55.
Tristani-Firouzi P, Peterson MJ, Saffle JR. Treatment of toxic epidermal necrolysis with intravenous immunoglobulin in children. J Am Acad Dermatol. 2002;47(4):548–52.PubMedCrossRef
56.
Wolff K, Tappeiner G. Treatment of toxic epidermal necrolysis: the uncertainty persist but the fog is dispersing. Arch Dermatol. 2003;139(1):85–6.PubMedCrossRef
57.
Comparin C, Hans Filho G, Takita LC, et al. Treatment of toxic epidermal necrolysis with intravenous immunoglobulin: a series of three cases. An Bras Dermatol. 2012;87(3):477–81.PubMedCrossRef
58.
Chen J, Wang B, Zeng Y, Xu H. High-dose intravenous immunoglobulins in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese patients: a retrospective study of 82 cases. Eur J Dermatol. 2010;20(6):743–7. doi:10.​1684/​ejd.​2010.​1077.PubMed
59.
Schneck J, Fagot JP, Sekula P, et al. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008;58:33–40.PubMedCrossRef
60.
Stella M, Clemente A, Bollero D, et al. Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS): experience with high-dose intravenous immunoglobulins and topical conservative approach. A retrospective analysis. Burns. 2007;33:452–9.PubMedCrossRef
61.
62.
To KK, Wong SS, Li IW, et al. Concurrent comparison of epidemiology, clinical presentation and outcome between adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and the seasonal influenza A virus infection. Postgrad Med J. 2010;86:515–21.PubMedCrossRef
63.
Katz J, Hancock K, Veguilla V, et al. Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. Morb Mortal Wkly Rep. 2009;58:521–4.
64.
Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006;145(8):599–609.PubMedCrossRef
65.
Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007;357:1451.CrossRef
66.
Chong JL, Sapari S, Kuan YC. A case of acute respiratory distress syndrome associated with novel H1N1 treated with intravenous immunoglobulin G. J Microbiol Immunol Infect. 2011;44:319–22.PubMedCrossRef
67.
Hong DK, Tremoulet AH, Burns JC, et al. Cross-reactive neutralizing antibody against pandemic 2009 H1N1 influenza A virus in intravenous immunoglobulin preparations. Pediatr Infect Dis J. 2011;30:67–9.PubMedCentralPubMedCrossRef
68.
Yunoki M, Kubota-Koketsu R, Urayama T, et al. Significant neutralizing activity of human immunoglobulin preparations against pandemic 2009 H1N1. Br J Haematol. 2010;148:953–55.PubMedCentralPubMedCrossRef
69.
Hagiwara K, Kawami S, Kato-Mori Y, et al. Protective role of human intravenous immunoglobulin from influenza A virus infection in mice. Open Hemotol J. 2012;6:8–11.CrossRef
70.
Hung I, To K, Lee CK, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A (H1N1) infection. Chest. 2013;144:464–73.PubMedCrossRef
71.
Gordon CL, Johnson PD, Permezel M, et al. Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency. Clin Infect Dis. 2010;50:672–8.PubMed
72.
Gordon CL, Holmes NE, Grayson ML, et al. Comparison of immunoglobulin G subclass concentrations in severe community-acquired pneumonia and severe pandemic 2009 influenza A (H1N1) infection. Clin Vaccine Immunol. 2012;19:446–8.PubMedCentralPubMedCrossRef
73.
Gordon CL, Langan K, Charles P, et al. Pooled human immunoglobulin therapy in critically ill patients with pandemic 2009 influenza A (H1N1) pneumonitis and immunoglobulin G2 subclass (IgG2) deficiency. Clin Infect Dis. 2011;52:422–6.PubMedCrossRef
74.
Wong HK, Lee CK, Hung I, et al. Practical limitations of convalescent plasma collection: a case scenario in pandemic preparation for influenza A (H1N1) infection. Transfusion. 2010;50:1967–71.PubMedCrossRef
75.
76.
Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the primary immunodeficiency committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006;117:S525–553.PubMedCrossRef
77.
Kalbfleisch JD, Lawless JF. Estimating the incubation time distribution and expected number of cases of transfusion-associated acquired immune deficiency syndrome. Transfusion. 1989;29(8):672.PubMedCrossRef
78.
79.
Yang H, Gregori L, Asher DM, et al. Risk assessment for transmission of variant Creutzfeldt-Jakob disease by transfusion of red blood cells in the United States. Transfusion. 2014 Apr 1
80.
Teljeur C, Flattery M, Harrington P, et al. Cost-effectiveness of prion filtration of red blood cells to reduce the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease in the Republic of Ireland. Transfusion. 2012;52(11):2285–93.PubMedCrossRef
81.
Correll PK, Law MG, Seed CR, et al. Variant Creutzfeldt-Jakob disease in Australian blood donors: estimation of risk and the impact of deferral strategies. Vox Sang. 2001;81(1):6–11.PubMedCrossRef
Metadata
Title
Use of Intravenous Immunoglobulin in Critically Ill Patients
Authors
Summer Donovan
Gonzalo M. L. Bearman
Publication date
01-12-2014
Publisher
Springer US
Published in
Current Infectious Disease Reports / Issue 12/2014
Print ISSN: 1523-3847
Electronic ISSN: 1534-3146
DOI
https://doi.org/10.1007/s11908-014-0447-4

Other articles of this Issue 12/2014

Current Infectious Disease Reports 12/2014 Go to the issue

Pediatric Infectious Diseases (I Brook, Section Editor)

A Concise Critical Analysis of Serologic Testing for the Diagnosis of Lyme Disease

Central Nervous System Infections (J Lyons, Section Editor)

Imaging in Neurologic Infections I: Bacterial and Parasitic Diseases

Intra-abdominal Infections, Hepatitis, and Gastroenteritis (D Bobak, Section Editor)

Update on the Pathogenesis and Management of Pouchitis

Respiratory Infections (F Arnold, Section Editor)

Biomarkers for Community-Acquired Pneumonia in the Emergency Department

Cardiovascular Infections (D Levine, Section Editor)

The Characteristics and Outcome of Infective Endocarditis Involving Implantable Cardiac Devices

Central Nervous System Infections (J Lyons, Section Editor)

Antibiotic-Induced Neurotoxicity
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits