Interleukin-6 improves infection identification when added to physician judgment during evaluation of potentially septic patients

Background: Identifying infection is critical in early sepsis screening. This study assessed whether biomarkers of endothelial activation and/or inflammation could improve identification of infection among Emergency Department (ED) patients with organ dysfunction.

Methods: We performed a prospective, observational study at two urban, academic EDs, between June 2016 and December 2017. We included admitted adults with 1) two systemic inflammatory response syndrome criteria and organ dysfunction, 2) systolic blood pressure < 90 mmHg, or 3) lactate ≥4.0 mmol/L. We excluded patients with trauma, transferred for intracranial hemorrhage, or without available blood samples. Treating ED physicians reported presence of infection (yes/no) at inpatient admission. Assays for angiopoietin-1, angiopoietin-2, soluble tumor necrosis factor receptor-1, interleukin-6, and interleukin-8 were performed using ED blood samples. The primary outcome was infection, adjudicated by paired physician review. Using logistic regression, we compared the performance of physician judgment, biomarkers, and physician judgment-biomarkers combination to predict infection. Area under the curve (AUC) and AUC 95% confidence intervals were estimated by bootstrap procedure.

Results: Of 421 patients enrolled, 306 patients met final study criteria. Of these, 154(50.3%) patients had infectious etiologies. Physicians correctly discriminated infectious from non-infectious etiologies in 239 (78.1%). Physician judgment performed moderately when discriminating infection (AUC 0.78, 95% CI: 0.74-0.82) and outperformed the best biomarker model, interleukin-6 alone, (AUC 0.71, 0.66-0.76). Physician judgment improved when including interleukin-6 (AUC 0.84, 0.79-0.87), with modest AUC improvement: 0.06 (0.03-0.08).

Conclusions: In ED patients with organ dysfunction, plasma interleukin-6 may improve infection discrimination when added to physician judgment.