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

败血症被2016年SCCM/ESICM工作组定义为“由于宿主对感染的反应失调而导致的危及生命的器官功能障碍”，仍然是急诊和重症监护医学的主要问题，也是住院患者最常见的死亡原因。最近对调节血管内皮细胞的控制通路的实验研究阐明了这一单细胞层如何在静止和激活之间切换，从而影响休克和多器官功能障碍综合征(MODS)的发展。长期以来，炎症导致的血管渗漏一直被归因于内皮细胞本身的故障。然而，最近的研究提供了令人信服的证据，证明内皮细胞受到管腔一侧一种高度水合的负电荷涂层的保护，这种涂层被称为内皮糖萼。在活体内对内皮细胞糖萼进行成像一直是一项具有挑战性的工作，主要是因为它的精细结构。直到最近，一种新的相机和分析软件(GlycoCheck)才开始商业化，该软件能够分析舌下微血管的血流边界区域(PBR)，PBR是舌下微血管内皮细胞糖萼尺寸的逆参数。我们的团队可以在一项验证研究中成功地表明，这种成像技术可以很容易地提供可重现的结果。我们坚信，这种方法可能是一种重要的非侵入性工具，可以在我们急诊室入院时识别有风险的脓毒症患者，支持医生决定哪些患者需要加强观察和干预。与我们的临床研究部合作，我们已经计划并已经启动了一项观察性研究，以识别有风险的脓毒症患者(急诊室患者中的糖盏损伤早期检测(EDGE))，在使用GlycoCheck进行筛查后，将对疑似感染的患者进行风险分层。EDGE观察性研究将用于根据脓毒症的严重程度确定PBR值，并确定PBR临界值以预测临床相关结果。EDGE的研究结果将成为计划和实施MPG(医疗器械法案)干预研究的基础，以改善经PBR筛查确定的高危患者的预后：“急诊室患者中预防败血症器官功能障碍并改善预后的早期糖萼导向治疗”(EGOShOOTER)试验。我们的最终目标是将高危患者纳入这项干预性临床研究，并将他们随机分为标准治疗组或“糖萼友好型”治疗组，其中包括一系列强化观察和特定干预措施。

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.