Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: a prospective study
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Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis : a prospective study. / Ostrowski, Sisse R; Berg, Ronan M G; Windeløv, Nis A; Meyer, Martin A S; Plovsing, Ronni R; Møller, Kirsten; Johansson, Pär I.
In: Journal of Critical Care, Vol. 28, No. 5, 10.2013, p. 586-96.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis
T2 - a prospective study
AU - Ostrowski, Sisse R
AU - Berg, Ronan M G
AU - Windeløv, Nis A
AU - Meyer, Martin A S
AU - Plovsing, Ronni R
AU - Møller, Kirsten
AU - Johansson, Pär I
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/10
Y1 - 2013/10
N2 - PURPOSE: The aim of this study was to investigate associations between circulating catecholamines, endothelial damage, and coagulopathy in experimental human endotoxemia and septic patients.MATERIALS AND METHODS: Nine healthy male volunteers undergoing endotoxemia (4-hour 0.5 ng/kg/hour infusion of E. coli lipopolysaccharide, blood sampling at 0, 4, and 6 hours) and 20 patients with severe sepsis. Analysis of plasma biomarkers (adrenaline, noradrenaline, thrombomodulin, syndecan-1, soluble vascular endothelial cadherin, histone-complexed DNA fragments, soluble CD40 ligand [sCD40L], protein C, tissue-type plasminogen activator, plasminogen activator inhibitor 1) and routine coagulation tests.RESULTS: Endotoxemia increased heart rate, temperature, white blood cell count, C-reactive protein and procalcitonin, decreased blood pressure and induced a hemostatic response with platelet consumption, reduced protein C and sCD40L levels and enhanced tissue-type plasminogen activator release (all P<.05). Septic patients had increased levels of noradrenaline, syndecan-1, thrombomodulin, histone-complexed DNA and sCD40L but reduced soluble vascular endothelial cadherin and plasminogen activator inhibitor 1 (all P<.05) and plasma catecholamines correlated positively with syndecan-1 (adrenaline and noradrenaline) and sTM (only noradrenaline) (all P<.05), biomarkers reflecting endothelial damage. Furthermore, noradrenaline, syndecan-1 and thrombomodulin levels correlated with INR and disease severity scores (noradrenaline and thrombomodulin) (all P<.05).CONCLUSIONS: Experimental endotoxemia induced a discrete hemostatic response without sympathoadrenal activation or endothelial damage. Septic patients had high levels of catecholamines and endothelial damage biomarkers that correlated with each other and with markers of hypocoagulability and disease severity.
AB - PURPOSE: The aim of this study was to investigate associations between circulating catecholamines, endothelial damage, and coagulopathy in experimental human endotoxemia and septic patients.MATERIALS AND METHODS: Nine healthy male volunteers undergoing endotoxemia (4-hour 0.5 ng/kg/hour infusion of E. coli lipopolysaccharide, blood sampling at 0, 4, and 6 hours) and 20 patients with severe sepsis. Analysis of plasma biomarkers (adrenaline, noradrenaline, thrombomodulin, syndecan-1, soluble vascular endothelial cadherin, histone-complexed DNA fragments, soluble CD40 ligand [sCD40L], protein C, tissue-type plasminogen activator, plasminogen activator inhibitor 1) and routine coagulation tests.RESULTS: Endotoxemia increased heart rate, temperature, white blood cell count, C-reactive protein and procalcitonin, decreased blood pressure and induced a hemostatic response with platelet consumption, reduced protein C and sCD40L levels and enhanced tissue-type plasminogen activator release (all P<.05). Septic patients had increased levels of noradrenaline, syndecan-1, thrombomodulin, histone-complexed DNA and sCD40L but reduced soluble vascular endothelial cadherin and plasminogen activator inhibitor 1 (all P<.05) and plasma catecholamines correlated positively with syndecan-1 (adrenaline and noradrenaline) and sTM (only noradrenaline) (all P<.05), biomarkers reflecting endothelial damage. Furthermore, noradrenaline, syndecan-1 and thrombomodulin levels correlated with INR and disease severity scores (noradrenaline and thrombomodulin) (all P<.05).CONCLUSIONS: Experimental endotoxemia induced a discrete hemostatic response without sympathoadrenal activation or endothelial damage. Septic patients had high levels of catecholamines and endothelial damage biomarkers that correlated with each other and with markers of hypocoagulability and disease severity.
KW - Adult
KW - Biomarkers/blood
KW - Blood Coagulation Disorders/blood
KW - Catecholamines/blood
KW - Endotoxemia/blood
KW - Healthy Volunteers
KW - Humans
KW - Male
KW - Prospective Studies
KW - Sepsis/blood
KW - Severity of Illness Index
U2 - 10.1016/j.jcrc.2013.04.010
DO - 10.1016/j.jcrc.2013.04.010
M3 - Journal article
C2 - 23731819
VL - 28
SP - 586
EP - 596
JO - Journal of Critical Care
JF - Journal of Critical Care
SN - 0883-9441
IS - 5
ER -
ID: 236993380