Serum hyaluronic acid in critically ill dogs and influence of intravenous fluid therapy

Abstract

Background The endothelial glycocalyx (EG) appears to play a critical role in physiological vasculo-endothelial function. Sepsis, trauma, and hemorrhagic shock are associated with EG shedding and intravenous fluids have the potential to worsen EG degradation. There is little available research evaluating the relationship between intravenous fluids, inflammation, and EG degradation in critically ill dogs. Objective To study EG degradation in critically ill dogs over their first 48 hours of hospitalization and characterize the influence of intravenous fluids and inflammation. Methods Hyaluronic acid (HA), a biomarker of EG degradation, was measured in dogs with non-pulmonary sepsis, pulmonary sepsis, or spontaneous hemoperitoneum at five pre-defined time points over 48 hours. The concentration of HA was trended over time, compared between groups, and studied for associations with the cumulative volume of intravenous fluids administered, a pro-inflammatory cytokine (interleukin-6, IL-6), and a biomarker of hypervolemia (atrial natriuretic peptide, ANP). Results Concentration of HA was not significantly different between the groups at each time point. It increased over the first 24 hours of the study before reaching a plateau in patients with sepsis and spontaneous hemoperitoneum. Concentration of IL-6 had a significant positive association with HA concentration on presentation in all groups (p = 0.026). Cumulative fluid volume had a significant association with HA concentration during hospitalization in all groups (p = 0.0002). There was no significant effect of ANP on HA concentration. Concentration of HA was associated with disease severity but not with outcome. Conclusions In the dogs studied, markers of inflammation and administration of larger volumes of intravenous fluids were associated with increasing HA concentration, and thus presumptive EG degradation. Further research is needed to explore the clinical impact of intravenous fluid therapy on the EG. These findings should be considered carefully by clinicians prescribing fluid resuscitation for critically ill dogs.