Sublingual microcirculation in patients with SARS-CoV-2 undergoing veno-venous extracorporeal membrane oxygenation

Casarotta, Erika; Scorcella, Claudia; Domizi, Roberta; Montomoli, Jonathan; Gasparri, F; Gabbanelli, Vincenzo; Pantanetti, Simona; Carozza, Roberto; Adrario, Erica; Donati, Abele

doi:10.1016/j.mvr.2020.104064

Cited by 19 publications

(25 citation statements)

References 9 publications

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“…Capillary clogging by fibrinous microthrombi, which has been shown by autopsy studies in lungs from COVID-19 patients [5,21], is thus the putative histopathological correlate of capillary rarefication in sublingual capillaries as well. Consistent with this notion, d-dimers levels were closely associated with microcirculatory alterations in our and the abovementioned studies [19,20].…”

Section: Discussionsupporting

confidence: 91%

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Microvascular dysfunction in COVID-19: the MYSTIC study

et al. 2020

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Rationale Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. Objectives To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. Methods Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. Measurements and main results COVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4–6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. Conclusions Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19.

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Section: Discussionsupporting

confidence: 91%

“…An unspecified, small reduction in total and perfused vascular density in sublingual microvessels of ventilated COVID-19 patients has been recently reported [19,20]. However, neither outcome nor endothelial or glycocalyx markers have been assessed in these studies.…”

Section: Discussionmentioning

confidence: 99%

Microvascular dysfunction in COVID-19: the MYSTIC study

et al. 2020

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“…In a previous microcirculatory study on 9 COVID-19 patients under ECMO therapy, Carsetti et al found that TVD and PVD were inversely correlated with D-dimer [ 19 ]. The same team found similar results on 12 COVID-19 patients under mechanical ventilation [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Microvascular flow alterations in critically ill COVID-19 patients: A prospective study

et al. 2021

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Background Data on microcirculatory pattern of COVID-19 critically ill patients are scarce. The objective was to compare sublingual microcirculation parameters of critically ill patients according to the severity of the disease. Methods The study is a single-center prospective study with critically ill COVID-19 patients admitted in ICU. Sublingual microcirculation was assessed by IDF microscopy within 48 hours of ICU admission. Microcirculatory flow index (MFI), proportion of perfused vessel (PPV), total vessel density (TVD), De Backer score (DBS), perfused vessel density (PVD) and heterogeneity index (HI) were assessed. Patients were divided in 2 groups (severe and critical) according to the World health organization definition. Findings From 19th of March to 7th of April 2020, 43 patients were included. Fourteen patients (33%) were in the severe group and twenty-nine patients (67%) in the critical group. Patients in the critical group were all mechanically ventilated. The critical group had significantly higher values of MFI, DBS and PVD in comparison to severe group (respectively, PaCO2: 49 [44–45] vs 36 [33–37] mmHg; p<0,0001, MFI: 2.8 ± 0.2 vs 2.5 ± 0.3; p = 0.001, DBS: 12.7 ± 2.6 vs 10.8 ± 2.0 vessels mm-2; p = 0.033, PVD: 12.5 ± 3.0 vs 10.1 ± 2.4 mm.mm-2; p = 0.020). PPV, HI and TVD were similar between groups Correlation was found between microcirculatory parameters and PaCO2 levels. Conclusion Critical COVID-19 patients under mechanical ventilation seem to have higher red blood cell velocity than severe non-ventilated patients.

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“…In a recent report, we described the sublingual microcirculation of mechanically ventilated patients with severe SARS-COV-2 pneumonia and showed an inverse correlation between perfused vessel density (PVD) and D-dimers [ 4 ]. This relationship was confirmed in SARS-COV-2 patients on veno-venous extracorporeal membrane oxygenation [ 5 ]. Unfortunately, we could not evaluate the relationship with physiological dead space, because V D / V T data were not available for our cohort.…”

mentioning

confidence: 81%