There is ongoing debate about the efficacy of polyvalent immunoglobulins as adjunctive therapy for sepsis or septic shock. Two meta-analyses by the Cochrane collaboration calculated a significant reduction in mortality. However, data of the largest study were missing in one, and a subset of four high-quality studies failed to show an effect in the other. To broaden the database, we performed a meta-analysis of all randomized controlled studies published so far.Data Source:
MEDLINE, EMBASE, Cochrane Library of randomized trials, and personal files.Study Selection:
Meta-analysis of all published randomized controlled studies published on polyvalent immunoglobulins (Ig) for treatment of sepsis or septic shock in adults, children, or neonates.Data Extraction:
Twenty-seven trials with a total of 2,202 patients fulfilled the inclusion criteria.Data Synthesis:
As the immunologic state of neonates is different than that of adults or older children, data were evaluated separately for each group. Fifteen trials on 1,492 adults could be included. The pooled effect on mortality was a relative risk of death (RR) of 0.79 (95% confidence interval [CI] 0.69–0.90,p<= .0003). There was a strong trend in favor of an immunoglobulin preparation enriched with IgA and IgM (IgGAM) (RR = 0.66, 95% CI 0.51–0.84,p<= .0009) compared with preparations containing only IgG (RR = 0.85, 95% CI 0.73–0.99,p<= .04). In 12 trials on 710 neonates, the pooled effect on mortality was 0.56 (95% CI 0.42–0.74,p<= .0001). There was also a positive although less pronounced trend favoring the effect of IgGAM (RR = 0.50, 95% CI 0.34–0.73,p<= .0003) compared with IgG (RR = 0.63, 95% CI 0.42–0.96,p<= .03). A sensitivity analysis selecting eight trials in adults and ten in neonates of highest methodological quality confirmed these results.Conclusions:
Polyvalent immunoglobulins exert a significant effect on mortality in sepsis and septic shock, with a trend in favor of IgGAM.