The Association Between Endothelial Biomarkers and Intravascular Albumin Loss After Major Abdominal Surgery—An Exploratory Pilot Study

Background: Elevated endothelial biomarkers may indicate damage to the endothelium and increased fluid loss after surgery. This study aimed to assess endothelial damage after pancreatic surgery with selected biomarkers and transvascular fluid loss assessed with radioactively labeled human serum albumin (HSA). Methods: This was a pilot study on patients undergoing major open pancreatic surgery at Rigshospitalet, Copenhagen, Denmark. Primary outcome apparent disappearance rate (k) during the first five postoperative days assessed by blood samples of ¹²⁵I labeled HSA. Secondary outcomes were transcapillary escape rate (TER) during the first postoperative hours assessed by vascular loss of ¹²⁵I labeled HSA, and changes in endothelial biomarkers (syndecan-1, thrombomodulin, E-selectin, platelet endothelial cell adhesion molecule [PECAM], and vascular endothelial growth factor receptors 1 [VEGFR-1]) for the first five postoperative days. Correlation between k and endothelial biomarkers was calculated using Spearman's rho test. A weighted risk model for k was constructed including information from all five endothelial biomarkers. Results: Ten patients were included. Mean k on postoperative day one through five was 0.9%/h (95% CI 0.8–1.1%/h) for all patients. Mean TER after surgery was 6.6%/h (95% CI 3.8–9.3%/h). The largest change in endothelial biomarkers from pre- to post-surgery was seen for Syndecan-1 (145% increase for all patients), with large variation in all endothelial biomarker changes. A positive correlation to k was observed for all endothelial biomarkers except VEGFR-1 (only significant for thrombomodulin). A weighted risk model for increased k using information from selected endothelial markers was constructed with an R² of 0.586 (p = 0.009). Conclusions: A positive correlation between increased albumin disappearance from the blood (k) and endothelial biomarkers was seen. A multi-biomarker model was constructed with significant correlation to k. The clinical relevance should be tested in prospective trials. Editorial Comment: This pilot study follows blood albumen kinetics in the early post-operative period in a major abdominal surgery cohort. Biomarkers related to glycocalyx and endothelial conditions are also reported, and these to describe capillary filtration including albumin egress from blood.