Understanding Restrictive Versus Liberal Fluid Therapy for Major Abdominal Surgery Trial Results: Did Liberal Fluids Associate With Increased Endothelial Injury Markers?

Abstract

The restrictive versus liberal fluid therapy for major abdominal surgery trial was an international, randomized, assessor-blinded trial comparing restrictive with liberal IV fluid regimens that represented traditional care in patients undergoing major abdominal surgery. Cohort of restrictive versus liberal fluid therapy for major abdominal surgery bloods was collected at a single major site (161 patients) prior to, day 1 and day 3 after surgery. Bloods were blindly and randomly batch analyzed for plasma markers of endothelial/glycocalyx injury-angiopoietin-1, angiopoietin-2, soluble tyrosine-protein kinase-2 receptor, soluble intracellular adhesion molecule-1, syndecan, and tumor necrosis factor-α. Data were examined as restrictive versus liberal enrollment groups and high versus low (± 5,000 mL) fluid groups. Differences were examined by linear mixed modeling. There were no significant differences in any biomarkers between the restrictive (n = 75) and liberal (n = 86) groups. When examined as low (n = 81) and high (n = 79) fluid groups, plasma angiopoietin-2 (p = 0.009) and soluble intracellular adhesion molecule-1 (p = 0.01) were elevated in the high fluid group. There were no differences in other biomarkers. Although these results are consistent with previous findings of vascular injury following liberal fluid therapy, they suggest alternative mechanisms underlie the clinical outcomes from restrictive versus liberal fluid therapy for major abdominal surgery study. NCT01424150.