Early Immune Phenotype-Guided Immunomodulatory Strategies and Intensive Care Outcomes in Septic Shock: A...

Septic shock is characterized by profound immune dysregulation, with marked heterogeneity in host inflammatory and immunosuppressive responses. This biological variability may contribute to the inconsistent effects observed in prior immunomodulatory interventions. Whether early immune phenotype-guided immunomodulation is associated with differential patterns of shock resolution and organ recovery remains incompletely understood.

We conducted a single-center retrospective observational cohort study of adult patients with septic shock. Immune phenotyping using routinely available biomarkers was performed as part of standard clinical care within the first hour after shock onset. Using a prespecified 24-hour landmark design, patients were retrospectively classified according to early treatment with hemoadsorption, IgM-enriched intravenous immunoglobulin (IVIG), or standard care. The primary outcome was vasopressor-free days through day 28. Secondary outcomes included 28-day mortality, lactate kinetics, ventilator-free days, and changes in Sequential Organ Failure Assessment score. Propensity score-weighted analyses were applied to adjust for baseline differences in patient characteristics associated with routine clinical practice.

Among 1,216 patients included in the landmark cohort, vasopressor-free days through day 28 were highest in patients treated with hemoadsorption, followed by those receiving IgM-enriched IVIG, and lowest in the standard care group. Hemoadsorption was associated with faster lactate clearance, whereas IgM-enriched IVIG was associated with greater improvement in Sequential Organ Failure Assessment score by day 5. Twenty-eight-day mortality differed across groups, with the lowest mortality observed in the hemoadsorption group.

Among patients with septic shock who survived beyond the first 24 hours, early immune phenotype-guided immunomodulatory strategies applied during routine care were associated with distinct patterns of hemodynamic stabilization and organ recovery. These findings should be interpreted as associative and hypothesis-generating and support further investigation in prospective phenotype-stratified studies.