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

The SBITS data

Serum-IgG-Spiegel und Mortalität bei Patienten mit schwerer Sepsis und septischem Schock

Die SBITS-Daten

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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.

Zusammenfassung

Hintergrund

Die Rolle einer intravenösen Immunglobulin(Ig)-Therapie bei Patienten mit schwerer Sepsis und septischem Schock wird kontrovers diskutiert. Niedrige initiale IgG-Spiegel könnten dabei helfen, Patienten zu identifizieren, die von einer adjuvanten Ig-Therapie profitieren.

Fragestellung

Es wird der Einfluss der initialen IgG-Spiegel auf die 28-Tage-Mortalität bei Patienten mit schwerer Sepsis und septischem Schock untersucht.

Studiendesign und Untersuchungsmethoden

In dieser retrospektiven Analyse der SBITS-Daten wurden 543 Patienten in Abhängigkeit ihrer initialen Serum-IgG-Spiegel 4 Gruppen (Quartile) zugeordnet (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). Das 3. Quartil wurde als Referenzquartil angesehen. Für das verwendete logistische Regressionsmodell wurden klinisch relevante Einflussfaktoren definiert und in die weiteren risikoadjustierten Kalkulationen integriert.

Ergebnisse

Patienten mit den niedrigsten IgG-Spiegeln hatten eine den Patienten des 2. und 3. Quartils, die den physiologischen IgG-Spiegel-Bereich Gesunder repräsentiert, vergleichbare Mortalitätsrate. Überraschenderweise zeigten Patienten mit den höchsten IgG-Spiegeln in der risikoadjustierten Kalkulation sogar eine im Vergleich zum Referenzquartile statistisch signifikant höhere Mortalität (OR 1,69; CI 1,01–2,81; p = 0,05). Subgruppenanalysen zeigten, dass die initialen IgG-Spiegel ohne prognostische Aussagekraft sind, sowohl bei Patienten mit einem bei Aufnahme vasopressorenpflichtigen septischen Schock als auch bei Patienten mit grampositiver oder gramnegativer Sepsis.

Schlussfolgerung

Initial niedrige IgG-Spiegel diskrimieren nicht zwischen Überleben und Nichtüberleben bei Patienten mit schwerer Sepsis und septischem Schock. Daher können niedrige IgG-Spiegel nicht dabei helfen, Patienten zu identifizieren, die von einer adjuvanten IgG-Sepsis-Therapie profitieren. Ob ein hoher initialer IgG-Spiegel ein unabhängiger Mortalitätsrisikofaktor ist, muss prospektiv untersucht werden.

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Notes

  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.

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Acknowledgements

We gratefully thank Prof. Dr. med. Dr. h.c. Dietrich Seidel, MD (former director of the Department of Clinical Chemistry, University of Munich, Munich, Germany) and Mr. Oskar Bujdoso, MS (formerly Bayer HealthCare Pharmaceuticals, Wuppertal, Germany) for their support in conducting the trial.

We also greatfully thank all SBITS Investigators (cited in [1]) for having established the SBITS study.

Author information

Authors and Affiliations

  1. Klinik für Kardiologie, Angiologie und Internistische Intensivmedizin, St. Marien-Krankenhaus Siegen gem. GmbH, Kampenstraße 51, 57072, Siegen, Germany

    S. Dietz

  2. Institut für Medizinische Epidemiologie, Biometrie und Informatik, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Straße 8, 06112, Halle (Saale), Germany

    C. Lautenschläger

  3. Evangelisches Geriatriezentrum Berlin gGmbH, Reinickendorfer Str. 61, 13347, Berlin, Germany

    U. Müller-Werdan

  4. Klinik für Kardiologie, Krankenhaus Agatharied, Norbert-Kerkel-Platz, 83734, Hausham, Germany

    G. Pilz

  5. Medizinisches Zentrallabor, Carinagasse 41, 6800, Feldkirch/Vorarlberg, Austria

    P. Fraunberger

  6. Medizinische Klinik 8, Klinikum Nürnberg Süd, Breslauer Straße 201, 90471, Nürnberg, Germany

    M. Päsler

  7. Klinik für Innere Medizin II, Katholisches Krankenhaus St. Johann Nepomuk, Haarbergstraße 72, 99097, Erfurt, Germany

    H. Ebelt

  8. Institut für Klinische Chemie, Klinikum der Universität München, Marchionistraße 15, 81377, München, Germany

    A. K. Walli

  9. Klinik für Innere Medizin III, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle (Saale), Ernst-Grube-Straße 40, 06120, Halle (Saale), Germany

    K. Werdan &  S. Nuding

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  1. S. Dietz
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  2. C. Lautenschläger
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  4. G. Pilz
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  10. S. Nuding
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Corresponding author

Correspondence to S. Nuding.

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Conflict of interest

S. Dietz, C. Lautenschläger, G. Pilz, P. Fraunberger, M. Päsler, A.K. Walli and S. Nuding state they have no competing interest. H. Ebelt received lecture honoraria, reimbursement for congress fees and honoraria for advisory board activities of clinical studies from Biotest. U. Müller-Werdan received lecture honoraria, reimbursement of travel expenses and financial support for performing experimental and clinical studies from Biotest and Bayer. In addition, she received honoraria from Hartkopf & Schirdewahn GBR, assistenz3, Klinikum Merseburg, Helmholtz München, Tiasis business consulting and Medizinische Hochschule Hannover for scientific presentations. K. Werdan received honoraria and financial support for scientific activities, consultations and lectures from Bayer and Biotest.

This article does not contain any studies with human participants or animals performed by any of the authors.

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Dietz, S., Lautenschläger, C., Müller-Werdan, U. et al. Serum IgG levels and mortality in patients with severe sepsis and septic shock. Med Klin Intensivmed Notfmed 112, 462–470 (2017). https://doi.org/10.1007/s00063-016-0220-6

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  • DOI: https://doi.org/10.1007/s00063-016-0220-6

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