Effects of low-dose intravenous immunoglobulin as the adjunctive therapy in septic shock patients with and without hypogammaglobulinemia: a retrospective cohort study

Abstract

Intravenous immunoglobulin (IVIG) therapy has a reported adjunctive effect in the treatment of sepsis, but in light of results from a large-scale randomized control trial (RCT), evidence for improved prognosis with IVIG therapy is currently deemed insufficient. In recent years, there have been many reports of low serum immunoglobulin G (IgG) as a poor prognostic factor in septic patients. Under Japan's national health insurance system, IVIG is administered for severe infections at a dose of 5 g/day for three days (total 15 g or 0.3 g/kg). At present, IVIG administration is not specifically formulated for septic patients with hypogammaglobulinemia. It is clinically significant to investigate whether serum IgG levels can serve as a biomarker to predict the efficacy of IVIG treatment for septic shock and help to identify those patients who might benefit from an adjunctive IVIG treatment. The purpose of this study was to compare the efficacy of this low-dose IVIG as an adjunctive therapy in septic shock patients with and without hypogammaglobulinemia. In this retrospective cohort study, patients who received low-dose IVIG (5 g/day for 3 days) as adjuvant therapy for septic shock were enrolled. These patients were divided into two groups based on a median serum IgG level of 829 mg/dL (<830 mg/dL defined as hypogammaglobulinemia) prior to IVIG administration. To assess the efficacy of low-dose IVIG administration (0.3 g/kg), 28-day survival probability as the primary outcome, and the lengths of artificial ventilation and intensive care unit (ICU) stays as the secondary outcomes were compared using the Kaplan-Meier method, the log-rank test, the Wilcoxon or Mann-Whitney U test. A total of 80 patients with septic shock that underwent IVIG treatment in the ICU were enrolled. These patients were divided into two groups based on a median serum IgG level. Survival probabilities at 28 days were 90.0% and 85.0% in the high- and low-level groups, respectively, and there was no significant difference between the two groups (P=0.457). There are not also significant differences in median lengths of artificial ventilation (6 vs. 9 days, P=0.215) and ICU stays (10 vs. 12 days, P=0.199) after IVIG administration. Logistic regression revealed that these clinical outcomes were not associated with serum IgG after adjusting for confounding factors as the antibiotics. Serum IgG levels was not associated with the clinical outcomes by low-dose IVIG treatment. Our results suggest that the prognosis of low-dose IVIG as adjunctive therapy in patients with septic shock might be no different with and without hypogammaglobulinemia.