Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

“…Comparable results were found in other meta-analyses [330]. However, after excluding low-quality trials, the recent Cochrane analysis [329] revealed no survival benefit.…”

“…One larger multicenter RCT (n = 624) [328] in adult patients found no benefit for IV immunoglobulin (IVIg). The most recent Cochrane meta-analysis [329] differentiates between standard polyclonal IV immunoglobulins (IVIgG) and immunoglobulin M-enriched polyclonal Ig (IVIgGM). In ten studies with IVIgG (1430 patients), mortality between 28 and 180 days was 29.6% in the IVIgG group and 36.5% in the placebogroup (RR 0.81; 95% CI 0.70-0.93), and for the seven studies with IVIgGM (528 patients), mortality between 28 and 60 days was 24.7% in the IVIgGM group and 37.5% in the placebo-group (RR 0.66; 95% CI 0.51-0.85).…”

A revival for immunoglobulin therapy in septic shock?

“…However, the interpretation of meta-analysis relies on several factors including an extensive assessment of the risk of bias, the respective weight related to the number of patients, as well as the marked influence of single-center studies on outcomes [11,12]. Restriction to high-quality studies with a low risk of confounding factors did not show any benefit from IVIG administration with both standard and IgMenriched preparations [10]. Most importantly, the heterogeneous quality of IVIG preparations may represent a major but non-measurable bias across studies [13].…”

“…A number of prospective studies that addressed the efficacy of polyclonal IVIG in the treatment of septic shock have been included in several meta-analysis, including the recently updated one from the Cochrane Collaboration [10]. A primary analysis indicated a benefit of IVIG in survival that seemed even more pronounced when using IgM-enriched preparations.…”

“…In a single-center retrospective study, Cavazzuti and colleagues [15] analyzed a cohort of septic shock patients who did (92 patients) or did not (76 patients) receive early treatment with polyclonal IgMenriched IVIG in addition to common 6-h and 24-h bundles. Routine administration of IgM-enriched IVIG preparations in septic patients was based on a published meta-analysis suggesting a survival benefit [10]. Administration of IgM was associated with a dramatic and impressive 21.1 % absolute improvement in 30-day survival (75 vs. 53.9 %) that persisted after appropriate adjustment through multivariate analysis as well as a propensity score-matching.…”