Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock
Abstract
Background
Mortality from sepsis and septic shock remains high. Results of trials on intravenous immunoglobulins (IVIG) as adjunctive therapy for sepsis have been conflicting. This is an update of a Cochrane review (2002).
Objectives
To estimate the effects of IVIG on mortality and duration of hospitalization in patients with sepsis or septic shock.
Search methods
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE (1966 to October 2008), and EMBASE (1988 to October 2008). We contacted investigators in the field for unpublished data.
Selection criteria
We included randomized controlled trials comparing IVIG (monoclonal or polyclonal) with placebo or no intervention in patients with bacterial sepsis or septic shock.
Data collection and analysis
Two reviewers independently assessed the studies for inclusion, methodologic quality and data abstraction. We conducted pre‐specified subgroup analyses by type of immunoglobulin preparation.
Main results
Forty‐two of 84 potentially eligible studies met our inclusion criteria. Pooled analysis of polyclonal and monoclonal IVIG was not done due to clinical heterogeneity. Subgroup analysis of 10 polyclonal IVIG trials in adults (n = 1430) and seven trials on IgM‐enriched polyclonal IVIG (n = 528) showed significant reductions in mortality compared to placebo or no intervention (RR 0.81; 95% CI 0.70 to 0.93 and RR 0.66; 95% CI 0.51 to 0.85, respectively). Subgroup analysis of polyclonal IVIG in neonates showed no significant reduction in mortality for standard (RR 0.90; 95% CI 0.46 to 1.76; 4 trials, n = 174) and IgM‐enriched polyclonal IVIG (RR 0.57; 95% CI 0.31 to 1.04; 3 trials, n = 164). Sensitivity analysis of trials with low risk of bias showed no reduction in mortality with polyclonal IVIG in adults (RR 0.97; 95% CI 0.81 to 1.15; 5 trials, n = 945) and neonates (RR 0.41; 95% CI 0.16 to 1.08; 3 trials, n = 128). Mortality was not reduced among patients (8 trials, n = 4671) who received anti‐endotoxin antibodies (RR 0.99; 95% CI 0.91 to1.06) while anti‐cytokines (9 trials, n = 7893) demonstrated a marginal reduction in mortality (RR 0.92; 95% CI 0.86 to 0.97).
Authors' conclusions
Polyclonal IVIG reduced mortality among adults with sepsis but this benefit was not seen in trials with low risk of bias. Among neonates, no reduction in mortality was seen with polyclonal IVIG. Most of the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.
PICOs
Plain language summary
Intravenous immunoglobulin for treating patients with severe sepsis and septic shock
Sepsis is the inflammatory response of the body to severe infection, which can be caused by a variety of bacteria. Deaths due to sepsis and septic shock remain high despite giving antibiotics, especially if the performance of people's vital organs such as the lungs, heart and kidney are affected. Several studies have looked into other agents to help the body fight the effects of sepsis. Intravenous immunoglobulin preparations contain antibodies that help the body to neutralize bacterial toxins. There are two types of preparations, polyclonal immunoglobulins contain several antibodies and monoclonal immunoglobulins target a specific antigen. This updated review found 24 trials of polyclonal immunoglobulins, with 17 in adults (1958 participants) and seven in newborn infants (338 participants); 18 trials (a total of 13,413 participants) were of monoclonal antibodies. Both standard and IgM‐enriched polyclonal immunoglobulins decreased the number of deaths in adults but not in infants. No reductions in deaths of adults or infants were seen with polyclonal IVIG using high quality trials only. In the monoclonal immunoglobulin trials, anti‐endotoxin antibodies showed no benefit while the anti‐cytokines showed a very small reduction in deaths among adults with sepsis. The polyclonal immunoglobulin trials were small compared to the trials of monoclonal preparations. The reduction in deaths observed with polyclonal preparations needs to be confirmed in large studies that use high quality methods.
