IgM- and IgA-Enriched Polyclonal Intravenous Immunoglobulin Therapy in Sepsis: A Single-Center Retrospective Cohort...

Background/Objectives: Evidence for adjunctive intravenous immunoglobulin therapy in sepsis remains conflicting. This study evaluated the association of IgM- and IgA-enriched polyclonal intravenous immunoglobulin (IgGAM) therapy with clinical outcomes, including post hoc analyses according to initial empiric antibiotic therapy (IEAT) appropriateness. Methods: This single-center retrospective cohort study included 50 adults with sepsis or septic shock according to Sepsis-3 criteria, treated between November 2006 and March 2010. Twenty-five patients received adjunctive IgGAM plus standard sepsis management, and 25 received standard management alone. Primary outcomes were 28-day intensive care unit (ICU) mortality, overall ICU mortality, and in-hospital mortality. Results: Overall, 28-day ICU mortality was 28.0% with IgGAM and 32.0% with control (relative risk, 0.88; 95% confidence interval [CI], 0.37-2.05; p = 0.758); other mortality outcomes did not differ significantly. Kaplan-Meier survival distributions also did not differ significantly (log-rank p = 0.208). During the ICU stay, vasopressor therapy was required in 68% of the IgGAM group and 92% of the control group (p = 0.034); corresponding study day 1 requirements were 60% and 76% (p = 0.225). In the complete-case longitudinal analysis (IgGAM group, n = 20; control group, n = 25), SOFA scores decreased significantly over time within the IgGAM group (p = 0.017), whereas no significant within-group change was observed in the control group (p = 0.616). In the post hoc appropriate-IEAT subgroup, 28-day ICU mortality was 0.0% versus 36.8% (p = 0.026), in-hospital mortality was 25.0% versus 63.2% (p = 0.038), and Kaplan-Meier survival distributions differed significantly (log-rank p = 0.004). The 60-day restricted mean survival time was 58.1 versus 38.4 days, with a difference of 19.8 days (95% CI, 11.1-28.4). Conclusions: Adjunctive IgGAM therapy was not associated with significant differences in mortality overall. Findings in the post hoc appropriate-IEAT subgroup were hypothesis-generating and should be interpreted cautiously given potential selection bias, residual confounding, and multiple comparisons. Prospective evaluation within optimized sepsis care is warranted.