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Erschienen in: Medizinische Klinik - Intensivmedizin und Notfallmedizin 5/2017

27.09.2016 | Originalien

Serum IgG levels and mortality in patients with severe sepsis and septic shock

The SBITS data

verfasst von: S. Dietz, C. Lautenschläger, U. Müller-Werdan, G. Pilz, P. Fraunberger, M. Päsler, H. Ebelt, A. K. Walli, K. Werdan, Dr. S. Nuding

Erschienen in: Medizinische Klinik - Intensivmedizin und Notfallmedizin | Ausgabe 5/2017

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Abstract

Background

The role of intravenous immune globulin (Ig) therapy in patients with severe sepsis and septic shock is discussed controversially. Low initial IgG levels could help to identify those patients who might benefit from an adjunctive Ig treatment.

Objectives

To investigate the effect of initial serum IgG levels on 28-day mortality in patients with severe sepsis and septic shock.

Materials and methods

In this retrospective analysis of the SBITS trial data, 543 patients were allocated to four groups (quartiles) depending on their initial serum IgG levels (1: IgG ≤ 6.1 g/l; 2: IgG 6.2–8.4 g/l; 3: IgG 8.5–11.9 g/l; 4: IgG > 11.9 g/l). The third quartile was taken as the reference quartile. For the applied logistic regression model clinically relevant confounders were defined and integrated into further risk-adjusted calculations.

Results

Patients with the lowest IgG levels had a mortality rate similar to those patients with initial IgG levels in the second and third quartile, representing the physiological IgG range in healthy people. Surprisingly, patients with the highest IgG levels even showed a significantly higher mortality in a risk-adjusted calculation compared to the reference quartile (OR 1.69, CI 1.01–2.81, p = 0.05). Subgroup analyses revealed that initial IgG levels were of no prognostic value in patients presenting with vasopressor-dependent septic shock on admission as well as in patients with either gram-positive or gram-negative sepsis.

Conclusions

Initially low IgG levels do not discriminate between survival and nonsurvival in patients with severe sepsis and septic shock. Therefore, low IgG cannot help to identify those patients who might benefit from an adjunctive IgG sepsis therapy. Whether a high initial IgG serum level is an independent mortality risk factor needs to be investigated prospectively.
Fußnoten
1
The results of this study have been presented in part at the annual meeting of the German and Austrian Society of Critical Care and Emergency Medicine in Hamburg, June 10–13, 2009 and at the International Symposium on Intensive Care and Emergency Medicine in Brussels, March 9–12, 2010.
 
Literatur
1.
Zurück zum Zitat Werdan K, Pilz G, Bujdoso O et al (2007) Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit Care Med 35:2693–2701CrossRefPubMed Werdan K, Pilz G, Bujdoso O et al (2007) Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit Care Med 35:2693–2701CrossRefPubMed
2.
Zurück zum Zitat The ARDS Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342:1301–1308CrossRef The ARDS Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 342:1301–1308CrossRef
4.
Zurück zum Zitat Kaukonen KM, Bailey M, Suzuki S et al (2014) Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–1316CrossRefPubMed Kaukonen KM, Bailey M, Suzuki S et al (2014) Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–1316CrossRefPubMed
5.
Zurück zum Zitat Hall MJ, Williams SN, DeFrances CJ et al (2011) Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief 62:1–8 Hall MJ, Williams SN, DeFrances CJ et al (2011) Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief 62:1–8
6.
Zurück zum Zitat Shankar-Hari M, Spencer J, Sewell WA et al (2012) Bench-to-bedside review: immunoglobulin therapy for sepsis – biological plausibility from a critical care perspective. Crit Care 16:206CrossRefPubMedPubMedCentral Shankar-Hari M, Spencer J, Sewell WA et al (2012) Bench-to-bedside review: immunoglobulin therapy for sepsis – biological plausibility from a critical care perspective. Crit Care 16:206CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat 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 35:2686–2692CrossRefPubMed 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 35:2686–2692CrossRefPubMed
8.
Zurück zum Zitat Kreymann KG, de Heer G, Nierhaus A et al (2007) Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med 35:2677–2685CrossRefPubMed Kreymann KG, de Heer G, Nierhaus A et al (2007) Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med 35:2677–2685CrossRefPubMed
9.
Zurück zum Zitat Alejandria MM, Lansang MA, Dans LF et al (2013) Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 9:CD001090 Alejandria MM, Lansang MA, Dans LF et al (2013) Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 9:CD001090
10.
Zurück zum Zitat Soares MO, Welton NJ, Harrison DA et al (2012) An evaluation of the feasibility, cost and value of information of a multicentre randomised controlled trial of intravenous immunoglobulin for sepsis (severe sepsis and septic shock): incorporating a systematic review, meta-analysis and value of information analysis. Health Technol Assess 16:1–186CrossRefPubMedCentral Soares MO, Welton NJ, Harrison DA et al (2012) An evaluation of the feasibility, cost and value of information of a multicentre randomised controlled trial of intravenous immunoglobulin for sepsis (severe sepsis and septic shock): incorporating a systematic review, meta-analysis and value of information analysis. Health Technol Assess 16:1–186CrossRefPubMedCentral
11.
Zurück zum Zitat Cafiero F, Gipponi M, Bonalumi U et al (1992) Prophylaxis of infection with intravenous immunoglobulins plus antibiotic for patients at risk for sepsis undergoing surgery for colorectal cancer: results of a randomized, multicenter clinical trial. Surgery 112:24–31PubMed Cafiero F, Gipponi M, Bonalumi U et al (1992) Prophylaxis of infection with intravenous immunoglobulins plus antibiotic for patients at risk for sepsis undergoing surgery for colorectal cancer: results of a randomized, multicenter clinical trial. Surgery 112:24–31PubMed
13.
Zurück zum Zitat Kaul R, McGeer A, Norrby-Teglund A et al (1999) Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome – a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis 28:800–807CrossRefPubMed Kaul R, McGeer A, Norrby-Teglund A et al (1999) Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome – a comparative observational study. The Canadian Streptococcal Study Group. Clin Infect Dis 28:800–807CrossRefPubMed
14.
Zurück zum Zitat Menezes MC, Benard G, Sato MN et al (1997) In vitro inhibitory activity of tumor necrosis factor alpha and interleukin-2 of human immunoglobulin preparations. Int Arch Allergy Immunol 114:323–328CrossRefPubMed Menezes MC, Benard G, Sato MN et al (1997) In vitro inhibitory activity of tumor necrosis factor alpha and interleukin-2 of human immunoglobulin preparations. Int Arch Allergy Immunol 114:323–328CrossRefPubMed
15.
Zurück zum Zitat Andersson J, Skansen-Saphir U, Sparrelid E et al (1996) Intravenous immune globulin affects cytokine production in T lymphocytes and monocytes/macrophages. Clin Exp Immunol 104(Suppl 1):10–20PubMed Andersson J, Skansen-Saphir U, Sparrelid E et al (1996) Intravenous immune globulin affects cytokine production in T lymphocytes and monocytes/macrophages. Clin Exp Immunol 104(Suppl 1):10–20PubMed
16.
Zurück zum Zitat Andersson JP, Andersson UG (1990) Human intravenous immunoglobulin modulates monokine production in vitro. Immunology 71:372–376PubMedPubMedCentral Andersson JP, Andersson UG (1990) Human intravenous immunoglobulin modulates monokine production in vitro. Immunology 71:372–376PubMedPubMedCentral
17.
Zurück zum Zitat 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 31:1175–1182CrossRefPubMed 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 31:1175–1182CrossRefPubMed
18.
Zurück zum Zitat Werdan K (2001) Intravenous immunoglobulin for prophylaxis and therapy of sepsis. Curr Opin Crit Care 7:354–361CrossRefPubMed Werdan K (2001) Intravenous immunoglobulin for prophylaxis and therapy of sepsis. Curr Opin Crit Care 7:354–361CrossRefPubMed
20.
Zurück zum Zitat Markiewski MM, Lambris JD (2007) The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am J Pathol 171:715–727CrossRefPubMedPubMedCentral Markiewski MM, Lambris JD (2007) The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am J Pathol 171:715–727CrossRefPubMedPubMedCentral
21.
22.
Zurück zum Zitat Rieben R, Roos A, Muizert Y et al (1999) Immunoglobulin M‑enriched human intravenous immunoglobulin prevents complement activation in vitro and in vivo in a rat model of acute inflammation. Blood 93:942–951PubMed Rieben R, Roos A, Muizert Y et al (1999) Immunoglobulin M‑enriched human intravenous immunoglobulin prevents complement activation in vitro and in vivo in a rat model of acute inflammation. Blood 93:942–951PubMed
23.
Zurück zum Zitat Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 41:580–637CrossRefPubMed Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 41:580–637CrossRefPubMed
24.
Zurück zum Zitat Brocklehurst P, Farrell B, King A et al (2011) Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 365:1201–1211CrossRefPubMed Brocklehurst P, Farrell B, King A et al (2011) Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 365:1201–1211CrossRefPubMed
25.
Zurück zum Zitat Brunkhorst FM, Gastmeier P, Kern W et al (2010) Prevention and follow-up care of sepsis. 1st revision of S2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e. V., DSG) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinare Vereinigung fur Intensiv- und Notfallmedizin, DIVI). Internist (Berl) 51:925–932CrossRef Brunkhorst FM, Gastmeier P, Kern W et al (2010) Prevention and follow-up care of sepsis. 1st revision of S2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e. V., DSG) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinare Vereinigung fur Intensiv- und Notfallmedizin, DIVI). Internist (Berl) 51:925–932CrossRef
26.
Zurück zum Zitat Taccone FS, Stordeur P, De Backer D et al (2009) Gamma-globulin levels in patients with community-acquired septic shock. Shock 32:379–385CrossRefPubMed Taccone FS, Stordeur P, De Backer D et al (2009) Gamma-globulin levels in patients with community-acquired septic shock. Shock 32:379–385CrossRefPubMed
27.
Zurück zum Zitat Werdan K (2001) Pathophysiology of septic shock and multiple organ dysfunction syndrome and various therapeutic approaches with special emphasis on immunoglobulins. Ther Apher 5:115–122CrossRefPubMed Werdan K (2001) Pathophysiology of septic shock and multiple organ dysfunction syndrome and various therapeutic approaches with special emphasis on immunoglobulins. Ther Apher 5:115–122CrossRefPubMed
28.
Zurück zum Zitat Shankar-Hari M, Culshaw N, Post B et al (2015) Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis: systematic review and meta-analysis. Intensive Care Med 41:1393–1401CrossRefPubMed Shankar-Hari M, Culshaw N, Post B et al (2015) Endogenous IgG hypogammaglobulinaemia in critically ill adults with sepsis: systematic review and meta-analysis. Intensive Care Med 41:1393–1401CrossRefPubMed
29.
Zurück zum Zitat Werdan K, Pilz G, Muller-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 36:716–723CrossRefPubMed Werdan K, Pilz G, Muller-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 36:716–723CrossRefPubMed
30.
Zurück zum Zitat Päsler M, Dietz S, Werdan K (2012) Hypogammaglobulinemia in sepsis. In: Vincent J‑L (ed) Annual update in intensive care and emergency medicine 2012. Springer, Berlin, pp 98–109CrossRef Päsler M, Dietz S, Werdan K (2012) Hypogammaglobulinemia in sepsis. In: Vincent J‑L (ed) Annual update in intensive care and emergency medicine 2012. Springer, Berlin, pp 98–109CrossRef
31.
Zurück zum Zitat Welte T, Dellinger RP, Ebelt H et al (2015) Concept for a study design in patients with severe community-acquired pneumonia: a randomised controlled trial with a novel IGM-enriched immunoglobulin preparation – the CIGMA study. Respir Med 109:758–767CrossRefPubMed Welte T, Dellinger RP, Ebelt H et al (2015) Concept for a study design in patients with severe community-acquired pneumonia: a randomised controlled trial with a novel IGM-enriched immunoglobulin preparation – the CIGMA study. Respir Med 109:758–767CrossRefPubMed
Metadaten
Titel
Serum IgG levels and mortality in patients with severe sepsis and septic shock
The SBITS data
verfasst von
S. Dietz
C. Lautenschläger
U. Müller-Werdan
G. Pilz
P. Fraunberger
M. Päsler
H. Ebelt
A. K. Walli
K. Werdan
Dr. S. Nuding
Publikationsdatum
27.09.2016
Verlag
Springer Medizin
Erschienen in
Medizinische Klinik - Intensivmedizin und Notfallmedizin / Ausgabe 5/2017
Print ISSN: 2193-6218
Elektronische ISSN: 2193-6226
DOI
https://doi.org/10.1007/s00063-016-0220-6

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