Background: The glycocalyx is an endovascular layer that contributes to vascular homeostasis. It is comprised of glycosaminoglycans, including heparan sulfate (HS). Sepsis is thought to disrupt the glycocalyx; intravenous fluid administration may exacerbate this process.
Objective: To test the hypothesis that (1) glycocalyx dysfunction is associated with sepsis severity, organ dysfunction (measured by Sequential Organ Failure Assessment (SOFA) score) and mortality; and (2) larger administered fluid volumes are associated with increased glycocalyx degradation.
Methods: This prospective cohort study enrolled ED patients >18 years presenting to a tertiary care (55,000 annual visits) or a community hospital (65,000 annual visits) with suspected sepsis and non-infected controls. Glycocalyx degradation was measured as circulating HS using mass spectroscopy. HS levels were compared among controls, and among patients with sepsis, severe sepsis, or septic shock using a Kruskal-Wallis test, and between survivors and non-survivors using a Wilcoxon test. A Spearman correlation evaluated the association between HS and SOFA score at baseline. Multivariable linear regression was used to model plasma HS at 24 hours based on fluid administered to 24 hours.
Results: We enrolled 99 patients with sepsis and 30 controls. Mortality was 11% among sepsis patients. HS levels increased with worsening sepsis syndrome severity, with a significant difference between groups (all p < 0.01). Median HS levels were: control 177 [IQR, 143-267]; sepsis (n=33), 164 [113-277]; severe sepsis (n=34), 278 [183-587]; septic shock (n=32), 547 [290-1163]. Median HS levels were higher in non-survivors vs survivors (569 [248-3254] vs 277 [153-563], p<0.05). HS level correlated with SOFA score (r = 0.45, p < 0.01). After adjusting for age, baseline SOFA score, and sepsis severity, each 1 liter of fluids administered was associated with a 200 ng/ml increase in circulating HS (model R2 = 0.149, p<0.01).
Conclusion: Increasing glycocalyx degradation was associated with worsening sepsis severity and organ dysfunction. Higher volumes of fluid administered in the first 24 hours of sepsis admission was associated with increased glycocalyx degradation. The glycocalyx is a promising diagnostic and therapeutic target in sepsis; fluids may injure the glycocalyx.