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  • Dongelmans, D. A.  (3)
  • Hollmann, M. W.  (3)
  • 1
    Online Resource
    Online Resource
    Endothelial Permeability and the Angiopoietin/Tie2 System Following Mild and Severe COVID-19
    Springer Science and Business Media LLC ; 2023
    In:  Artery Research Vol. 29, No. 3 ( 2023-07-12), p. 83-93
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    In: Artery Research, Springer Science and Business Media LLC, Vol. 29, No. 3 ( 2023-07-12), p. 83-93
    Abstract: Endotheliopathy plays a role in the development of acute kidney and lung injury in COVID-19, probably due to inflammation, endothelial permeability, vascular leakage and edema formation. This study examined alterations in the circulation of patients with mild and severe COVID-19 on in vitro endothelial permeability and its relation to the endothelial angiopoietin/Tie2 system, which is involved in the regulation of endothelial permeability. Plasma was obtained from COVID-19 patients admitted to the ward ( n  = 14) or ICU ( n  = 20) at admission and after 1 and 2 weeks and healthy controls ( n  = 5). Human kidney and lung endothelial cells were exposed to patient plasma and treated with recombinant angiopoietin-1. In vitro endothelial barrier function was assessed using electric cell-substrate impedance sensing. Circulating markers of the angiopoietin/Tie2 system, endothelial dysfunction and glycocalyx degradation were measured by ELISA. Plasma from COVID-19 patients reduced endothelial resistance compared to healthy controls, but COVID-19 plasma-induced drop in endothelial resistance did not differ between ward and ICU patients. Circulating angiopoietin-2, soluble Tie2 and soluble Tie1 levels increased over time in ICU patients, whereas levels remained stable in ward patients. The increase in angiopoietin-2 was able to predict 90-day mortality (AUC = 0.914, p   〈  0.001). Treatment with recombinant angiopoietin-1 did not restore COVID-19 plasma-induced hyperpermeability. In conclusion, these results suggest that indirect effects of the virus represented in the circulation of COVID-19 patients induced endothelial hyperpermeability irrespective of disease severity and changes in the endothelial angiopoietin/Tie2 system. Nonetheless, angiopoietin-2 might be of interest in the context of organ injury and patient outcome in COVID-19.
    Type of Medium: Online Resource
    ISSN: 1876-4401
    URL: Article
    DOI: 10.1007/s44200-023-00036-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2364789-9
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  • 2
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    Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study
    Springer Science and Business Media LLC ; 2021
    In:  Critical Care Vol. 25, No. 1 ( 2021-12)
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    In: Critical Care, Springer Science and Business Media LLC, Vol. 25, No. 1 ( 2021-12)
    Abstract: The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure. Methods We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality. Results In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88–1.18]; P  = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01–1.36]; P  = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01–1.30]; P  = 0.028). Conclusions In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342 ).
    Type of Medium: Online Resource
    ISSN: 1364-8535
    URL: Article
    DOI: 10.1186/s13054-021-03710-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2051256-9
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  • 3
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    Online Resource
    Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients — insights from the PRoVENT-COVID study: a national, multicenter, observational cohort analysis
    Springer Science and Business Media LLC ; 2022
    In:  Critical Care Vol. 26, No. 1 ( 2022-06-01)
    Details
    In: Critical Care, Springer Science and Business Media LLC, Vol. 26, No. 1 ( 2022-06-01)
    Abstract: Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). Methods We analyzed data from the multicenter observational ‘PRactice of VENTilation in COVID-19 patients’ study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. Results Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27–7.72 L), 0.78 L (0.26–1.27 L), and − 0.35 L (− 6.52–0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77–0.95, P  = 0.0047). Sensitivity analyses showed similar results. Conclusions In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 1364-8535
    URL: Article
    DOI: 10.1186/s13054-022-04023-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2051256-9
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