Elevated Plasma Concentrations of Syndecan-1 Do Not Correlate With Increased Capillary Leakage of 20% Albumin

Abstract

BACKGROUND: Preclinical experiments show that an inflammatory reaction causes degradation of the endothelial glycocalyx layer and accelerated capillary leakage of albumin and fluid. The hypothesis in the present study was that elevated plasma concentrations of glycocalyx degradation products are associated with greater capillary leakage in humans. METHODS: This open clinical trial involved administration of an intravenous infusion of 20% albumin at 3 mL/kg over 30 minutes to 15 postburn patients who showed an activated inflammatory response. Blood samples and urine were collected for 300 minutes. The plasma concentrations of 2 biomarkers of glycocalyx degradation—syndecan-1 and heparan sulfate—were measured at 0, 60, and 300 minutes and compared to the capillary leakage of albumin and fluid obtained by mass balance calculations and population kinetic analysis. RESULTS: Patients were studied at 7 days (median) after a burn injury that covered 15% (maximum 48%) of the body surface area. The median plasma syndecan-1 concentration was 71 (25th–75th percentiles, 41–185) ng/mL. The 2 patients with highest values showed 2279 and 2395 ng/mL (normal 15 ng/mL). Heparan sulfate concentrations averaged 915 (673–1539) ng/mL. The infused amount of albumin was 57 (48–62) g, and 6.3 (5.1–7.7)% of that leaked from the plasma per hour. Linear correlation analysis of the relationship between the 10logarithm of the mean syndecan-1 and the albumin leakage showed a slope coefficient of −1.3 (95% confidence interval [CI], −3.6 to 1.0) and a correlation coefficient of −0.33 (P = .24). The kinetic analysis revealed that syndecan-1 served as a statistically significant covariate to the albumin leakage, but the relationship was inverse (power exponent −0.78, 95% CI, −1.50 to −0.05; P < .02). Heparan sulfate levels did not correlate with the capillary leakage of albumin or fluid in any of the analyses. CONCLUSIONS: A raised plasma concentration of syndecan-1 alone cannot be extrapolated to indicate increased capillary leakage of albumin and fluid.

Kinetics of 5% and 20% albumin: A controlled crossover trial in volunteers

“…There were no differences between healthy volunteers and to postoperative and post‐burn patients with a marked inflammatory response 8,9 . The oncotic‐driven recruitment of fluid ( k 21 ) even attained an almost identical value in the present study as in edematous post‐burn patients 27 . However, the intravascular persistence of 20% albumin in patients undergoing lengthy but minor surgery was even longer than in the other studies 28 …”

“…8,9 The oncotic-driven recruitment of fluid (k 21 ) even attained an almost identical value in the present study as in edematous post-burn patients. 27 However, the intravascular persistence of 20% albumin in patients undergoing lengthy but minor surgery was even longer than in the other studies. 28 The kinetic profile of 5% albumin may not be as stable as for 20% albumin between different clinical situations, although this is not well studied.…”

“…Differences in kinetic profile are quite small between the present experiments and clinical studies using the same protoclol. 8,9,27,28 The similar pharmacologic profiles for 5% and 20% albumin suggest that both fluids can be used in clinical scenarios of moderate severity without concerns about altered kinetics. The long intravascular persistence is a concern, as four half-lives are required before 95% of the volume expansion has subsided.…”

The glycocalyx as a permeability barrier: basic science and clinical evidence

“…However, postoperative patients and post-burn patients with moderately severe inflammation (plasma C-reactive protein of 60–80 mg/L) and patients undergoing surgery with minor hemorrhage had the same intravascular half-life of exogenous albumin when compared with healthy volunteers [ 55 ]. The post-burn patients given 20% albumin even showed a normal capillary leakage of albumin and fluid despite major elevations, even up to 100-fold, of plasma syndecan-1 [ 56 ].…”

“…2 A) and in patients with inflammation due to cholecystitis and appendicitis [ 72 ]. The third study administered 20% albumin to post-burn patients who had dramatically increased plasma concentrations of both syndecan-1 and heparan sulfate [ 56 ] (Fig. 2 B).…”