The glycocalyx: a novel diagnostic and therapeutic target in sepsis.

1. Crit Care. 2019 Jan 17;23(1):16. doi: 10.1186/s13054-018-2292-6. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Uchimido R(1), Schmidt EP(2), Shapiro NI(3). Author information: (1)Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA, 02215, USA. ruchimido@hsph.harvard.edu. (2)Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, 13001 E 17th Pl, Aurora, CO, 80045, USA. (3)Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA, 02215, USA. The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It is comprised of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and adherent plasma proteins. The glycocalyx maintains homeostasis of the vasculature, including controlling vascular permeability and microvascular tone, preventing microvascular thrombosis, and regulating leukocyte adhesion.During sepsis, the glycocalyx is degraded via inflammatory mechanisms such as metalloproteinases, heparanase, and hyaluronidase. These sheddases are activated by reactive oxygen species and pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta. Inflammation-mediated glycocalyx degradation leads to vascular hyper-permeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion. Clinical studies have demonstrated the correlation between blood levels of glycocalyx components with organ dysfunction, severity, and mortality in sepsis.Fluid resuscitation therapy is an essential part of sepsis treatment, but overaggressive fluid therapy practices (leading to hypervolemia) may augment glycocalyx degradation. Conversely, fresh frozen plasma and albumin administration may attenuate glycocalyx degradation. The beneficial and harmful effects of fluid and plasma infusion on glycocalyx integrity in sepsis are not well understood; future studies are warranted.In this review, we first analyze the underlying mechanisms of glycocalyx degradation in sepsis. Second, we demonstrate how the blood and urine levels of glycocalyx components are associated with patient outcomes. Third, we show beneficial and harmful effects of fluid therapy on the glycocalyx status during sepsis. Finally, we address the concept of glycocalyx degradation as a therapeutic target. DOI: 10.1186/s13054-018-2292-6 PMCID: PMC6337861 PMID: 30654825 [Indexed for MEDLINE] Conflict of interest statement: ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.