Intravenous immunoglobulin for treating sepsis and septic shock

Abstract

Objectives: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality. This review summarises the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital.

Search strategy: We searched the Cochrane Controlled Trials Register, MEDLINE 1966 to 2000, EMBASE 1988 to February 1999; we contacted investigators active in the field for unpublished data.

Selection criteria: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock.

Data collection and analysis: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation.

Main results: Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95% CI 0.86 to 0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318 in 4 good quality studies; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69).

Reviewer's conclusions: In our opinion, polyclonal IVIG significantly reduces mortality and can be used as an adjuvant treatment for sepsis and septic shock. Adjunctive therapy with monoclonal IVIGs remains experimental.