Effect of intravenous immunoglobulin in critically ill adult patients with sepsis: a meta-analysis

Context

Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet the benefit of the therapy remains unclear. Furthermore, its use is not currently recommended.

Objective

To evaluate the effect of polyclonal intravenous immunoglobulin therapy on mortality in critically ill adult patients with sepsis.

Data sources

Medline (1966-September 2005) and the Cochrane Register of Controlled Trials (September 2005).

Study selection

All randomized controlled trials of polyclonal intravenous immunoglobulin therapy with a placebo comparison or no intervention during the course of sepsis, severe sepsis or septic shock in critically ill adult patients. No restriction was made for language or type of publication.

Data extraction

Data were independently extracted by two investigators using a standardized form.

Data synthesis

The literature search identified 4462 articles, of which 32 were deemed potentially eligible. Nineteen trials (n = 2415) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio [RR] = 0.72, 95% confidence interval [CI], 0.59–0.88) compared with placebo or no intervention. The number needed to treat was 10 [95% CI: 4–16]. In sensitivity analyses, we documented improved survival when the analysis was limited to published and peer-reviewed trials (RR = 0.69, 95% CI, 0.55–0.87) (16 trials, n = 1659) and blinded trials (RR = 0.61, 95% CI, 0.40–0.93) (seven trials, n = 896). A dosage regimen higher than 1 g/kg and a duration of therapy longer than 2 days were strongly associated with this survival benefit.

Conclusion

We observed a survival benefit with the use of polyclonal intravenous immunoglobulin therapy in sepsis compared with placebo or no intervention. The magnitude of the benefit is advantageously comparable with activated protein C. Because of methodological limitations of the current literature, a large randomized controlled trial of this therapy is recommended.