Emergency Department Interleukin-6 Levels and Organ Dysfunction in Sepsis Across Multiple Centers

Assessing early systemic inflammation and organ dysfunction in sepsis remains challenging in the emergency department (ED). The Symphony system (Bluejay Diagnostics) measures Interleukin-6 (IL-6) from whole blood or plasma in ~20 minutes that can be leveraged in the ED. The objective of this study was to evaluate the association between IL-6 levels and organ dysfunction as assessed by Sequential Organ Failure Assessment (SOFA) scores during the first 3 days of hospitalization.

We conducted a multicenter observational pilot study across seven United States hospitals enrolling adults (≥ 22 years) with sepsis or septic shock defined by Sepsis-3 criteria between 1/17/24 – 5/6/24. IL-6 levels were measured from whole blood or plasma samples collected within 24 hours of ED arrival using the Symphony system with ~20-minute turnaround time. The primary outcome of 28-day all-cause mortality was reported previously. This prespecified secondary analysis evaluated the relationship between IL-6 levels and SOFA scores from hospital days 0-3. Associations were assessed by comparing median levels across SOFA score ranges, and by using Pearson correlation coefficients with 95% confidence intervals (CIs) and positive likelihood ratios for prediction of organ dysfunction.

A total of 138 patients were included, of whom 27% presented with septic shock. Median IL-6 levels increased across SOFA strata: SOFA 2-4: 747 pg/mL (95% CI 281–1212), SOFA 5-7: 1,334 pg/mL (806–1862), and 8-16: 2,434 pg/mL (1733–3135), p<0.001 by ANOVA. IL-6 measured on hospital days 0, 1, and 2 predicted severe organ dysfunction defined as (SOFA≥8), with positive likelihood ratios of 1.40 (1.10–1.78; p=0.003), 1.47 (1.14–1.91; p=0.002), and 1.26 (0.98–1.61; p=0.002), respectively. IL-6 levels were positively correlated with SOFA scores on day 0 (r=0.30, 95% CI 0.13–0.44; p=0.001), day 1 (r=0.22,0.04–0.38; p=0.018), day 2 (r=0.45, 0.27–0.59; p<0.0001), and day 3 (r=0.46, 0.29–0.60; p<0.001).

Early IL-6 levels measured in the ED were associated with greater subsequent organ dysfunction in patients with sepsis during the early part of hospitalization. These findings support the potential utility of rapid IL-6 measurement for early risk stratification and prognostication of organ dysfunction in sepsis. Larger prospective studies are needed to validate these findings and determine clinical impact.