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


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


METHODS
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.


METHODS
Two authors independently determined the validity of included studies and extracted data.


RESULTS
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-square p = .009), and this was at least moderate as measured by the I2 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.
Laupland
Kevin B
KB
Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.
Kirkpatrick
Andrew W
AW
Delaney
Anthony
A
D000328:Adult; D017052:Hospital Mortality; D006801:Humans; D007070:Immunoglobulin A / Q000008:administration & dosage*; D007075:Immunoglobulin M / Q000008:administration & dosage*; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D018805:Sepsis / Q000401:mortality / Q000628:therapy*; D012772:Shock, Septic / Q000401:mortality / Q000628:therapy; D015996:Survival Rate
D007070:Immunoglobulin A; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors