Meta-analysis: Intravenous immunoglobulin in critically ill adult patients with sepsis

Background: Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended. Purpose: To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis. Data Sources: MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition). Study Selection: All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. Data extraction: Data were independently extracted by 2 investigators using a standardized form. Data Synthesis: The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 [95% CI, 0.62 to 0.89]) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 [CI, 0.58 to 0.89]) (17 trials [n = 1865]) and blinded trials (risk ratio, 0.61 [CI, 0.40 to 0.93) (7 trials [n = 896]). Severe sepsis or septic shock (risk ratio, 0.64 [CI, 0.52 to 0.79]) (11 trials [n = 689]), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 [CI, 0.40 to 0.94]) (7 trials [n = 560]), and receiving therapy for longer than 2 days (risk ratio, 0.66 [CI, 0.53 to 0.82]) (17 trials [n = 1847]) were strongly associated with this survival benefit. Limitations: Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced. Conclusions: A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy.