Early Detection of Glycocalyx Damage in Emergency Room Patients – The EDGE Study

• Applicant: Dr. Alexander-Henrik Lukasz
• Subject Area: Clinical Infectiology and Tropical Medicine
• Term: from 2018 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 400731961

Sepsis has been defined as a "life-threatening organ dysfunction due to dysregulated host response to infection" by 2016 SCCM/ESICM Task Force and still remains a major problem of emergency and intensive care medicine, as well as the most frequent cause of death in the hospitalized patients. Recent experimental studies of control pathways regulating the vascular endothelium have illuminated how this single cell layer toggles between quiescence and activation to affect the development of shock and multiorgan dysfunction syndrome (MODS). Inflammation-induced vascular leakage has long been ascribed to a malfunction of the endothelial cell itself. However, recent studies provided compelling evidence that the endothelium is protected against pathogenic insults by a highly hydrated negatively charged coating on the luminal side called the endothelial glycocalyx. Imaging of the endothelial glycocalyx in vivo has been challenging, mostly because of its delicate structure. Only recently, a novel camera and analysis software (GlycoCheck) able to analyze the perfused boundary region (PBR), an inverse parameter of endothelial glycocalyx dimensions in sublingual microvessels, has become commercially available. Our group could successfully show in a validation study, that this imaging technique can easily deliver reproducible results. We strongly believe that this method may be an important non-invasive tool to identify septic patients at risk, already on admission to our emergency room, supporting the physician to decide, which patients need intensified observation and intervention. In collaboration with our department of clinical studies, we have planned and already started an observational study to identify septic patients at risk (Early Detection of Glycocalyx Damage in Emergency Room Patients (EDGE)), where patients with suspected infect will be risk-stratified after being screened with the use of GlycoCheck. The EDGE observational study will serve to define PBR values according to sepsis severity and to identify PBR cut-off values for the prediction of clinically relevant outcomes. Results from EDGE will be the basis to plan and conduct a MPG (medical devices act) interventional study to improve outcome in high-risk patients identified by PBR screening: "Early glycocalyx-directed therapy to prevent septic organ dysfunction and improve outcome in Emergency Room patients" (EGOShOOTER) Trial. Our final goal is to enroll high-risk patients in this interventional clinical study and randomize them to either standard or "glycocalyx friendly" treatment consisting of a bundle of intensified observation and specific interventions.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Philipp Kümpers