Variation of The Dose of Norepinephrine in Septic Shock Patients Treated with an IgM and IgA-Enriched Immunoglobulin Preparation: Secondary Analysis of a Prospective Multicenter Observational Study

Background/Objectives: The use of IgM- and IgA-enriched intravenous immunoglobulins (eIg) in septic shock remains controversial due to the lack of high-quality evidence, despite indications from observational studies and meta-analyses suggesting potential benefit. Identifying patients who may respond favorably and determining whether extended treatment could be useful are ongoing challenges. This study evaluates baseline predictors and early treatment-related trends associated with outcomes in septic shock patients receiving eIg, with particular focus on immunoglobulin levels and norepinephrine (NE) requirements. Methods: This observational analysis used data from the multicenter SORRISO registry, including 248 septic shock patients treated with eIg from 2015 to 2022. Baseline clinical and biochemical variables were recorded at the start of eIg infusion (D0). Trends in IgA, IgG, IgM, lactate, and NE dose were assessed between D0 and D4. Restricted cubic spline (RCS) models examined non-linear associations with mortality, and Kaplan–Meier analyses evaluated 28‑day survival according to parameter trends. Statistical significance was defined as p < 0.05. Results: RCS curves showed no prognostic value at D0 for INR, CRP, PCT, IgA, or IgG. Lactate (p = 0.005) and platelet count (p = 0.001) demonstrated significant associations with mortality, while IgM (p = 0.076) and NE (p = 0.059) approached significance. Of 209 evaluable patients, NE requirements decreased in 191 (NE‑DOWN) and increased in 18 (NE‑UP). Survival was 67% in the NE‑DOWN group vs. 23% in NE‑UP (p < 0.0001). No D0 variable reliably predicted NE trajectory. In conclusion, among septic shock patients treated with eIg, increasing NE requirements during the first four days were strongly associated with higher mortality. Baseline biomarkers did not predict vasopressor trends.