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Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: A systematic review and meta-analysis *

Laupland, Kevin B. MD, MSc; Kirkpatrick, Andrew W. MD; Delaney, Anthony MBBS, MSc

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Objectives: To systematically review the literature to assess whether adjunctive therapy with polyclonal intravenous immunoglobulin (ivIg) reduces mortality among critically ill adults with severe sepsis and septic shock.

Data Source: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases; the meta-register of controlled trials; and the Medical Editors Trial Amnesty register.

Study Selection: Prospective randomized clinical trials (RCTs) evaluating ivIg treatment in critically ill adults with severe sepsis or septic shock were included. Two reviewers conducted assessment of suitability for inclusion.

Data Extraction: Two authors independently determined the validity of included studies and extracted data.

Data Synthesis: The effect of ivIg on all-cause mortality was quantified using a fixed-effect meta-analysis.

Results: Fourteen RCTs published between 1988 and 2006 were included. Most were small, used relatively low doses of ivIg, and included predominantly surgical patients with Gram-negative infections. There was a significant reduction in mortality associated with use of ivIg treatment with a pooled odds ratio of 0.66 (95% confidence interval 0.53–0.83;p< .0005). In general, a greater treatment effect was seen among studies of lower methodological quality, studies using higher doses of ivIg, and studies that did not use albumin as a control. There was evidence of between-study heterogeneity (chi-squarep= .009), and this was at least moderate as measured by theI2 value (I2 = 53.8%). When only high-quality studies were pooled, the odds ratio for mortality was 0.96 (95% confidence interval 0.71–1.3;p= .78).

Conclusions: This meta-analysis demonstrates an overall reduction in mortality with the use of ivIg for the adjunctive treatment of severe sepsis and septic shock in adults, although significant heterogeneity exists among the included trials and this result was not confirmed when only high-quality studies were analyzed. These data warrant a well-designed, adequately powered, and transparently reported clinical trial.

From the Department of Critical Care Medicine (KBL, AWK), Department of Community Health Sciences (KBL), Department of Medicine (KBL), and Department of Surgery (AWK), University of Calgary, Calgary, AB, Canada; the Intensive Care Unit, Royal North Shore Hospital, Sydney, NSW, Australia (AD); and Northern Clinical School, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia (AD).

No external funding support was obtained for this study. The authors had complete autonomy in the conduct and reporting of this study. The authors have not disclosed any potential conflicts of interest.

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*See also pp. 2852 and 2855.

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