Association between intravenous fluid administration and endothelial glycocalyx shedding in humans: a systematic review

Introduction: Several studies have demonstrated associations between greater rate/volume of intravenous (IV) fluid administration and poorer clinical outcomes. One postulated mechanism for harm from exogenous fluids is shedding of the endothelial glycocalyx (EG). Methods: A systematic review using relevant search terms was performed using Medline, EMBASE and Cochrane databases from inception to October 2023. Included studies involved humans where the exposure was rate or volume of IV fluid administration and the outcome was EG shedding. The protocol was prospectively registered on PROSPERO: CRD42021275133. Results: The search yielded 450 articles, with 20 articles encompassing 1960 participants included in the review. Eight studies were randomized controlled clinical trials. Half of studies examined patients with sepsis and critical illness; the remainder examined perioperative patients or healthy subjects. Almost all reported blood measurements of soluble EG components; one study used in vivo video-microscopy to estimate EG thickness. Four of 10 sepsis studies, and 9 of 11 non-sepsis studies, found a positive relationship between IV fluid rate/volume and measures of EG shedding. Conclusions: A trend toward an association between IV fluid rate/volume and EG shedding was found in studies of stable patients, but was not consistently observed among studies of septic and critically ill patients.