Glycocalyx degradation is associated with increased circulating unmeasured ions after cardiopulmonary bypass

Unmeasured anions are commonly detected in critically ill patients, yet their nature remains unclear. We examined whether endothelial glycocalyx degradation may be related to this unexplained anionic burden through release of polyanionic heparan sulfate fragments. In a prospective subanalysis embedded in a randomized trial of cardiopulmonary bypass priming, 34 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were studied. A total of 150 serial measurements of strong ion gap, heparan sulfate, and syndecan-1 were obtained at five timepoints from post-induction to the first 24 h of intensive care unit admission. In mixed-effects models accounting for repeated measurements and timepoint effects, strong ion gap was associated with heparan sulfate (β = 0.20, 95%CI 0.06-0.33; p = 0.005), but not syndecan-1. These findings suggest that glycocalyx-derived heparan sulfate may be related to persistent unmeasured anions extending from cardiopulmonary bypass into the subsequent intensive care unit admission, a period characterized by acute inflammation and volume loading. The absence of an association with syndecan-1 suggests a specific association to circulating polyanionic glycosaminoglycans rather than all glycocalyx degradation products. These findings are hypothesis-generating and suggest a possible relationship between circulating glycocalyx degradation and a persistent strong ion gap in critically ill patients, although comprehensive gap fractionation is required to quantify the contribution of heparan sulfate and determine whether it can be modified by resuscitation strategy.