TY - JOUR

T1 - The effect of prostacyclin infusion on markers of endothelial activation and damage in mechanically ventilated patients with SARS-CoV-2 infection

AU - Vigstedt, Martin

AU - Søe-Jensen, Peter

AU - Bestle, Morten H.

AU - Clausen, Niels E.

AU - Kristiansen, Klaus T.

AU - Lange, Theis

AU - Stensballe, Jakob

AU - Perner, Anders

AU - Johansson, Pär I.

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022

Y1 - 2022

N2 - Background: In a pilot study, we found a significant reduction in mean daily sequential organ failure assessment score in mechanically ventilated patients with COVID-19 who received prostacyclin, compared to placebo. We here investigate the effect on biomarkers of endothelial activation and damage. Methods: Post-hoc study of a randomized controlled trial in adult patients with confirmed SARS-CoV-2 infection, mechanically ventilated, with soluble thrombomodulin (sTM) plasma levels >4 ng/mL. Patients received prostacyclin infusion (1 ng/kg/min) or placebo. Blood samples were collected at baseline and 24 h. Results: Eighty patients were randomized (41 prostacyclin, 39 placebo). The median changes in syndecan-1 plasma levels at 24 h were −3.95 (IQR: −21.1 to 2.71) ng/mL in the prostacyclin group vs. 3.06 (IQR: −8.73 to 20.5) ng/mL in the placebo group (difference of the medians: -7.01 [95% CI: −22.3 to −0.231] ng/mL, corresponding to −3% [95% CI: −11% to 0%], p = 0.04). Changes in plasma levels of sTM, PECAM-1, p-selectin, and CD40L did not differ significantly between groups. Conclusions: Prostacyclin infusion, compared to placebo, resulted in a measurable decrease in endothelial glycocalyx shedding (syndecan-1) at 24 h, suggesting a protective effect on the endothelium, which may be related to the observed reduction in organ failure.

AB - Background: In a pilot study, we found a significant reduction in mean daily sequential organ failure assessment score in mechanically ventilated patients with COVID-19 who received prostacyclin, compared to placebo. We here investigate the effect on biomarkers of endothelial activation and damage. Methods: Post-hoc study of a randomized controlled trial in adult patients with confirmed SARS-CoV-2 infection, mechanically ventilated, with soluble thrombomodulin (sTM) plasma levels >4 ng/mL. Patients received prostacyclin infusion (1 ng/kg/min) or placebo. Blood samples were collected at baseline and 24 h. Results: Eighty patients were randomized (41 prostacyclin, 39 placebo). The median changes in syndecan-1 plasma levels at 24 h were −3.95 (IQR: −21.1 to 2.71) ng/mL in the prostacyclin group vs. 3.06 (IQR: −8.73 to 20.5) ng/mL in the placebo group (difference of the medians: -7.01 [95% CI: −22.3 to −0.231] ng/mL, corresponding to −3% [95% CI: −11% to 0%], p = 0.04). Changes in plasma levels of sTM, PECAM-1, p-selectin, and CD40L did not differ significantly between groups. Conclusions: Prostacyclin infusion, compared to placebo, resulted in a measurable decrease in endothelial glycocalyx shedding (syndecan-1) at 24 h, suggesting a protective effect on the endothelium, which may be related to the observed reduction in organ failure.

KW - COVID-19

KW - Endothelium

KW - Glycocalyx

KW - SARS-CoV-2

KW - Syndecan-1

KW - Thrombomodulin

U2 - 10.1016/j.jcrc.2022.154010

DO - 10.1016/j.jcrc.2022.154010

M3 - Journal article

C2 - 35183892

AN - SCOPUS:85124628233

VL - 69

JO - Journal of Critical Care

JF - Journal of Critical Care

SN - 0883-9441

M1 - 154010

ER -