Intravenous immunoglobulin in septic shock: review of the mechanisms of action and meta-analysis of the clinical effectiveness

Abstract

Introduction: Sepsis is characterized by a complex immune response. In this study we aimed to provide a review of the mechanisms of action of immunoglobulin (Ig) related to sepsis and an updated meta-analysis of the clinical effectiveness of the Ig use in septic patients.

Evidence acquisition: We performed two separate searches of Medline and other databases with the keywords Ig, sepsis, septic shock, septicemia, septicemia with no language restrictions in order to review the mechanisms of action of Igs in sepsis and to update the previous meta-analysis on the effects of the Ig therapy on the mortality of adult patients with septic shock.

Evidence synthesis: Pathogens and toxin clearance, anti-inflammatory effects and anti-apoptotic effects on immune cells seems to be the main mechanisms of action of Ig therapy in sepsis. The meta-analysis of 18 RCTs indicated that the use of intravenous Ig reduces the mortality risk of septic patients (odds ratio=0.50 [95% CI 0.34-0.71], I2=44.68%). Low study quality, heterogeneous dosing regimens and type of Ig preparations, and different control interventions (placebo or albumin) may have influenced our results.

Conclusions: Our study showed that the use of intravenous Ig therapy in adult septic patients may have a rationale and seems to be associated with a reduced mortality. Anyway, the treatment effect generally tended to be smaller or less consistent if considering only those studies that were deemed adequate on each indicator. So, the available evidence is not clearly sufficient to support the widespread use of Ig in the treatment of sepsis.