Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation

Critical Care

Christopher J. Lindsell¹  Derek C. Angus²  John A. Kellum²  Ryo Uchimido³  Patrick D. Tyler³  Ryan C. Burke³  Nathan I. Shapiro³  Donald M. Yealy⁴  Sarah A. McMurtry⁵  James F. Colbert⁵  Eric P. Schmidt⁵  Joseph A. Hippensteel⁵  Xiaorui Han⁶  Robert J. Linhardt⁶  Fuming Zhang⁶ 

[1] Department of Biostatistics, Vanderbilt University Medical Center;Department of Critical Care Medicine, University of Pittsburgh;Department of Emergency Medicine, Beth Israel Deaconess Medical Center;Department of Emergency Medicine, University of Pittsburgh;Department of Medicine, University of Colorado Denver;Departments of Chemistry and Chemical Biology, Chemical and Biological Engineering, and Biomedical Engineering, Rensselaer Polytechnic Institute;

关键词: Sepsis;    Multiple organ failure;    Endothelial glycocalyx;    Fluid resuscitation;   

DOI  :  10.1186/s13054-019-2534-2

来源: DOAJ

【 摘 要 】

Abstract Background Intravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation. Methods We used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma heparan sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma heparan sulfate. Results Consistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113–341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45–79] ng/ml), as well as in a second cohort of sepsis patients (283 [155–584] ng/ml) at emergency department presentation) compared to controls (177 [144–262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate (p = 0.006) at 24 h after enrollment. Conclusions Glycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.

【 授权许可】

Unknown