Bedside analysis of the sublingual microvascular glycocalyx in the emergency room and intensive care unit - the GlycoNurse study

Alexandros Rovas, Alexander-Henrik Lukasz, Hans Vink, Marc Urban, Jan Sackarnd, Hermann Pavenstädt, Philipp Kümpers, Alexandros Rovas, Alexander-Henrik Lukasz, Hans Vink, Marc Urban, Jan Sackarnd, Hermann Pavenstädt, Philipp Kümpers

Abstract

Background: Deterioration of the endothelial glycocalyx (eGC), a protective carbohydrate-rich layer lining the luminal surface of the endothelium, plays a key role in vascular barrier dysfunction and eventually organ-failure in systemic inflammatory response syndrome and sepsis. Early detection of glycocalyx damage could thus become an important goal in critical care. This study was designed to determine the feasibility and reproducibility of quantitative, real-time glycocalyx measurements performed at bedside in the emergency room (ER) and intensive care unit (ICU).

Methods: The observational study included 70 patients admitted to the ER or ICU of a university hospital. A physician and the nurse in charge of the patient performed sublingual microcirculatory measurements using sidestream dark field (SDF) imaging. A novel data acquisition and analysis software (GlycoCheck™) was used to analyze the perfused boundary region (PBR), an inverse parameter of endothelial glycocalyx dimensions in vessels with diameters of between 5 and 25 μm.

Results: The method showed a good intra-observer reproducibility. Specifically, intraclass correlation coefficient analysis showed an excellent reproducibility between the physician's measurements (0.77 [CI 95%: 0.52-0.89]). The bias between the two PBRs was - 0.077 ± 0.24 μm. Moreover, there were no significant differences in the PBR values obtained by the nurses when compared to those reported by the physician (regarded as the "gold standard" measurement). Intraclass correlation coefficient analysis showed excellent reproducibility between the nurses' and physician's PBRs (0.75 [95% CI: 0.52-0.87]). The mean difference between the two PBRs (i.e., the bias) was 0.007 ± 0.25 μm. The nurses' PBR assessment had a 90% sensitivity (95% CI: 60-99%) and 90% specificity (95% CI: 80-93%) to identify a severely impaired glycocalyx.

Conclusion: Glycocalyx dimensions can be measured at patients' bedside precisely by non-invasive assessment of the PBR. This assessment could become part of standard monitoring and contribute to clinical decision-making and resuscitation protocols in clinical trials and daily practice.

Keywords: Emergency room; Endothelial glycocalyx; Intensive care unit; Intravital microscopy; Perfused boundary region; Sidestream darkfield microscopy.

Conflict of interest statement

Consent for publication

Consent for publication has been obtained. Written informed consent has been obtained from all identifiable individuals.

Competing interests

AR, AL, MU, JS, HP, PK declare that they have no competing interests. HV is Chief Science Officer of GlycoCheck BV, The Netherlands.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Image acquisition with the use of GlycoCheck™ System. Measurements were performed by using the GlycoCheck™ System, which consists of a sidestream-darkfield (SDF) camera coupled to a high-performance laptop computer. a A.R. (left) and P.K. (right) conducting a sublingual GlycoCheck™ measurement in a healthy volunteer. b Schematic illustration of cross section of a microvessel. GlycoCheck™ detects the dynamic lateral movement into the glycocalyx, which is expressed as the perfused boundary region (PBR, in μm). An impaired glycocalyx allows more RBCs to penetrate deeper towards the endothelial surface, which is reflected by an increase in PBR. c Representative image of the sublingual mucosa acquired with the SDF camera. d Quality check being automatically performed by the GlycoCheck™ software. Invalid vascular segments are marked yellow and are automatically discarded, while all valid vascular segments (green lines) are further analyzed. PBR: perfused boundary region, RBC: red blood cell, RBCW: red blood cell width
Fig. 2
Fig. 2
Inter-observer reproducibility of Perfused Boundary Region (PBR) measured by the nurses and physician. Eight trained nurses and a physician obtained paired sets of measurements (random order) in a total of 40 patients (n = 25 in the ER and n = 15 in the ICU) to determine the inter-observer reproducibility. a Boxplots showing PBR values (in μm) obtained by the nurses and the physician. The Wilcoxon signed-rank test was used to compare the paired PBR values. b Bland-Altman plot showing the limits of agreement (bias ±1.96 SD) between paired values for the nurses’ and physician’s perfused boundary region (PBR) measurements. (ER: Emergency Department, ICU: Intensive Care Unit, PBR: perfused boundary region, RBC: red blood cell

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