Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department

Abstract

Objectives: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool.

Design: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission.

Setting: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin).

Patients: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1.

Interventions: None.

Measurements and main results: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively.

Conclusions: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Figure 1.

Patient flow chart.

Figure 2.

Performance of biomarkers to predict the primary endpoint and time of sepsis onset after admission. A, Receiver operating characteristic (ROC) analysis—area under the curve (AUC) of biomarkers for the primary endpoint sepsis within 96 hr. B, ROC analysis—AUC of biomarkers combined with procalcitonin (PCT) for the primary endpoint sepsis within 96 hr. C, Time to onset of sepsis within the observation period of 96 hr. bioADM = bioavailable adrenomedullin, CRP = C-reactive protein, DPP3 = dipeptidyl peptidase 3, PCTsen = procalcitonin as measured using the sensitive Kryptor method, penKid = proenkephalin, proADM = proadrenomedullin.

Figure 3.

Receiver operating characteristic analysis— area under the curve of biomarkers for the secondary endpoint septic shock within 96 hr. bioADM = bioavailable adrenomedullin, CRP = C-reactive protein, DPP3 = dipeptidyl peptidase 3, PCTsen = procalcitonin as measured using the sensitive Kryptor method, penKid = proenkephalin, proADM = proadrenomedullin.