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      Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis

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          Abstract

          Background

          The endothelial glycocalyx (eGC) covers the luminal surface of the vascular endothelium and plays an important protective role in systemic inflammatory states and particularly in sepsis. Its breakdown leads to capillary leak and organ dysfunction. Moreover, sepsis-induced alterations of sublingual microcirculation are associated with a worse clinical outcome. The present study was performed to investigate the associations between eGC dimensions and established parameters of microcirculation dysfunction in sepsis.

          Methods

          This observational, prospective, cross-sectional study included 40 participants, of which 30 critically ill septic patients were recruited from intensive care units of a university hospital and 10 healthy volunteers served as controls. The established microcirculation parameters were obtained sublingually and analyzed according to the current recommendations. In addition, the perfused boundary region (PBR), an inverse parameter of the eGC dimensions, was measured sublingually, using novel data acquisition and analysis software (GlycoCheck™). Moreover, we exposed living endothelial cells to 5% serum from a subgroup of study participants, and the delta eGC breakdown, measured with atomic force microscopy (AFM), was correlated with the paired PBR values.

          Results

          In septic patients, sublingual microcirculation was impaired, as indicated by a reduced microvascular flow index (MFI) and a reduced proportion of perfused vessels (PPV) compared to those in healthy controls (MFI, 2.93 vs 2.74, p = 0.002; PPV, 98.53 vs 92.58, p = 0.0004). PBR values were significantly higher in septic patients compared to those in healthy controls, indicating damage of the eGC (2.04 vs 2.34, p < 0.0001). The in vitro AFM data correlated exceptionally well with paired PBR values obtained at the bedside (rs = − 0.94, p = 0.02). Both PBR values and microcirculation parameters correlated well with the markers of critical illness. Interestingly, no association was observed between the PBR values and established microcirculation parameters.

          Conclusion

          Our findings suggest that eGC damage can occur independently of microcirculatory impairment as measured by classical consensus parameters. Further studies in critically ill patients are needed to unravel the relationship of glycocalyx damage and microvascular impairment, as well as their prognostic and therapeutic importance in sepsis.

          Trial registration

          Retrospectively registered: Clinicaltrials.gov, NCT03960307

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2542-2) contains supplementary material, which is available to authorized users.

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          Most cited references32

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          The endothelial glycocalyx: composition, functions, and visualization

          This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging.
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            Mechanisms and treatment of organ failure in sepsis

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              Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine

              Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients. This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation. Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables.
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                Author and article information

                Contributors
                alexandros.rovas@ukmuenster.de
                laura.seidel@ukmuenster.de
                hvink@microvascular.com
                timo.pohlkoetter@web.de
                hermann.pavenstaedt@ukmuenster.de
                ertmer@anit.uni-muenster.de
                michael.hessler@uni-muenster.de
                philipp.kuempers@ukmuenster.de
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                24 July 2019
                24 July 2019
                2019
                : 23
                : 260
                Affiliations
                [1 ]ISNI 0000 0004 0551 4246, GRID grid.16149.3b, Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, , University Hospital Muenster, ; Albert-Schweitzer-Campus 1, 48149 Münster, Germany
                [2 ]ISNI 0000 0004 0551 4246, GRID grid.16149.3b, Department of Anesthesiology, Intensive Care, and Pain Therapy, , University Hospital Muenster, ; Münster, Germany
                [3 ]ISNI 0000 0001 0481 6099, GRID grid.5012.6, Department of Physiology, Cardiovascular Research Institute Maastricht, , Maastricht University, ; Maastricht, The Netherlands
                Author information
                http://orcid.org/0000-0001-9929-0703
                Article
                2542
                10.1186/s13054-019-2542-2
                6657098
                31340868
                5900df17-d4b4-43d1-9da4-45ad01a388c4
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 March 2019
                : 16 July 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004870, Medizinische Fakultät, Westfälische Wilhelms-Universität Münster;
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                endothelial glycocalyx,microcirculation,perfused boundary region,pbr,intravital microscopy,sepsis,intensive care unit,sidestream dark field microscopy,incident dark field illumination imaging,glycosaminoglycans

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