Early detection of glycocalyx and microvascular damage in suspected sepsis in the emergency department: the EDGE study

Background: The prompt identification of clinical deterioration in emergency department (ED) patients presenting with infection is crucial yet challenging. Microvascular dysfunction has been linked to poor clinical outcome in critically ill patients, but it remains unclear whether its detection can predict clinical deterioration in early sepsis. This study aims to evaluate the utility of quantitative microvascular videomicroscopy for predicting clinical deterioration in patients with suspected sepsis. Methods: In this prospective observational study, 299 ED patients with suspected infection or sepsis were enrolled, with the addition of 50 healthy volunteers, 14 non-infected ED patients and 34 intensive care unit (ICU) patients with sepsis as controls. All participants underwent sublingual sidestream darkfield videomicroscopy. The GlycoCheck™ software quantified vascular density, perfused boundary region (PBR; inverse marker of endothelial glycocalyx (eGC) thickness), and the Microvascular Health Score (MVHS™), which integrated capillary density and eGC dimensions. The primary outcome was disease progression within the first week, defined as progression from infection to sepsis or increase in SOFA score in septic patients. Secondary outcomes included in-hospital and 90-day mortality, ICU admission, or a composite outcome of progression or in-hospital death. Results: Sublingual videomicroscopy revealed significant differences in all microvascular variables between ED patients, healthy volunteers and control groups, correlating with disease severity. ED patients with disease progression showed lower capillary density, higher PBR, and lower MVHS at baseline than non-progressors. In patients presenting with infection without sepsis, MVHS demonstrated strong predictive discrimination for progression (AUC 0.79, p < 0.0001), outperforming procalcitonin and interleukin-6. An intact microvascular phenotype (high capillary density and low PBR) markedly reduced the risk of disease progression or in-hospital mortality (OR 0.17, p < 0.001), whereas combined glycocalyx damage and reduced capillary density significantly increased risk (OR 2.39, p = 0.01). Conclusion: Quantitative sublingual videomicroscopy predicts early disease progression within the first week and stratifies patients with suspected sepsis into high and low-risk groups at ED presentation. Trial registration: Clinicaltrials.gov Identifier NCT03126032, Registration Date 20.02.2017.