Markers of endothelial damage and coagulation impairment in patients with severe sepsis resuscitated with hydroxyethyl starch 130/0.42 vs Ringer acetate

TY - JOUR

T1 - Markers of endothelial damage and coagulation impairment in patients with severe sepsis resuscitated with hydroxyethyl starch 130/0.42 vs Ringer acetate

AU - Müller, Rasmus Beier

AU - Ostrowski, Sisse Rye

AU - Haase, Nicolai

AU - Wetterslev, Jørn

AU - Perner, Anders

AU - Johansson, Pär Ingemar

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - PURPOSE: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased mortality in patients resuscitated with hydroxyethyl starch 130/0.42 (HES) vs Ringer acetate. Different effects of the fluids on the endothelium may have contributed to the observed outcome. We aimed to investigate associations between HES vs Ringer and changes in plasma biomarkers reflecting endothelial damage and coagulation impairment.MATERIALS AND METHODS: Six biomarkers, including soluble thrombomodulin (sTM) and plasminogen activator inhibitor 1 (PAI-1), were assessed in a subgroup of 208 patients from the 6S trial. We analyzed differences in plasma concentration in the 2 intervention groups using linear or logistic regression models.RESULTS: The increase in plasma sTM was lower in the HES group (-1.8 ng/mL; 95% confidence interval, -2.9 to -0.7; P = .002). The change was not statistically significant associated with mortality whereas increase in plasminogen activator inhibitor 1 was (odds ratio for 1-unit increase, 1.04; 95% confidence interval, 1.01-1.08; P = .01).CONCLUSIONS: Resuscitation with HES vs Ringer decreased early endothelial damage. Although this finding should be interpreted with caution, it indicates that the increased mortality observed with HES in the 6S trial may not be explained by endothelial damage and it emphasizes the challenge of using surrogate markers as outcome.

AB - PURPOSE: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased mortality in patients resuscitated with hydroxyethyl starch 130/0.42 (HES) vs Ringer acetate. Different effects of the fluids on the endothelium may have contributed to the observed outcome. We aimed to investigate associations between HES vs Ringer and changes in plasma biomarkers reflecting endothelial damage and coagulation impairment.MATERIALS AND METHODS: Six biomarkers, including soluble thrombomodulin (sTM) and plasminogen activator inhibitor 1 (PAI-1), were assessed in a subgroup of 208 patients from the 6S trial. We analyzed differences in plasma concentration in the 2 intervention groups using linear or logistic regression models.RESULTS: The increase in plasma sTM was lower in the HES group (-1.8 ng/mL; 95% confidence interval, -2.9 to -0.7; P = .002). The change was not statistically significant associated with mortality whereas increase in plasminogen activator inhibitor 1 was (odds ratio for 1-unit increase, 1.04; 95% confidence interval, 1.01-1.08; P = .01).CONCLUSIONS: Resuscitation with HES vs Ringer decreased early endothelial damage. Although this finding should be interpreted with caution, it indicates that the increased mortality observed with HES in the 6S trial may not be explained by endothelial damage and it emphasizes the challenge of using surrogate markers as outcome.

KW - Journal Article

U2 - 10.1016/j.jcrc.2015.11.025

DO - 10.1016/j.jcrc.2015.11.025

M3 - Journal article

C2 - 26810483

SN - 0883-9441

VL - 32

SP - 16

EP - 20

JO - Journal of Critical Care

JF - Journal of Critical Care

ER -