BACKGROUND: Albumin may persist intravascularly for a shorter time in patients after major surgery than in healthy volunteers due to a surgery-induced breakdown (shedding) of the endothelial glycocalyx layer. METHODS: In this nonrandomized clinical trial, an IV infusion of 3 mL/kg of 20% albumin was given at a constant rate during 30 minutes to 15 patients on the first day after major open abdominal surgery (mean operating time 5.9 h) and to 15 conscious volunteers. Blood samples and urine were collected during 5 h and mass balance calculations used to estimate the half-lives of the administered albumin molecules and the induced plasma volume expansion, based on measurements of hemodilution and the plasma albumin concentration. RESULTS: At the end of the infusions, albumin had diluted the plasma volume by 13.3% ± 4.9% (mean ± SD) in the postoperative patients and by 14.2% ± 4.8% in the volunteers (mean difference −0.9, 95% CI, −4.7 to 2.9; 1-way ANOVA P = .61), which amounted to twice the infused volume. The intravascular half-life of the infused albumin molecules was 9.1 (5.7–11.2) h in the surgical patients and 6.0 (5.1–9.0) h in the volunteers (Mann-Whitney U test, P = .26; geometric mean difference 1.2, 95% CI, 0.8–2.0). The half-life of the plasma volume expansion was 10.3 (5.3–17.6; median and interquartile range) h in the surgical patients and 7.6 (3.5–9.0) h in the volunteers (P = .10; geometric mean difference 1.5, 95% CI, 0.8–2.8). All of these parameters correlated positively with the body mass index (correlation coefficients being 0.42–0.47) while age and sex did not affect the results. CONCLUSIONS: Twenty percent albumin caused a long-lasting plasma volume expansion of similar magnitude in postoperative patients and volunteers.

The infusion of 20% albumin significantly increases the plasma volume by recruiting interstitial fluid. After completing the infusion, there is a delay of 20 minutes until maximum plasma dilution is reached, and the duration of the plasma volume expansion lasts far beyond 5 hours.

Background: Burn injury is associated with a long-standing inflammatory reaction. The use of albumin solutions for plasma volume support is controversial because of concerns of increased capillary leakage, which could aggravate the commonly seen interstitial oedema. Methods: In the present open controlled clinical trial, an intravenous infusion of 20% albumin at 3 mL/kg was given over 30 min to 15 burn patients and 15 healthy volunteers. Blood samples and urine were collected for 5 h. Plasma dilution, plasma albumin and colloid osmotic pressure were compared. Mass balance calculations were used to estimate plasma volume expansion and capillary leakage of fluid and albumin. Results: The patients were studied between 4 and 14 (median, 7) days after the burn injury, which spread over 7-48% (median, 15%) of the total body surface area. The albumin solution expanded the plasma volume by almost 15%, equivalent to twice the infused volume, in both groups. The urinary excretion exceeded the infused volume by a factor of 2.5. Capillary leakage of albumin occurred at a rate of 3.4 ± 1.5 g/h in burn patients and 3.7 ± 1.6 g/h in the volunteers (P = 0.61), which corresponded to 2.4 ± 1.0% and 2.5 ± 1.2% per hour of the intravascular pool (P = 0.85). The median half-life of the plasma volume expansion was 5.9 (25th-75th percentiles 2.7-11.7) h in the burn patients and 6.9 (3.4-8.5) h in the volunteers (P = 0.56). Conclusions: Albumin 20% was an effective volume expander in patients at 1 week post-burn. No relevant differences were found between burn patients and healthy volunteers.

Aims: A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery.Methods: An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1 st day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individualspecific covariates were added in sequence. Results:The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k 21 ), but it also increased losses of fluid from the kinetic system (k b ). The balance between k 21 and k b maintained the rise in plasma albumin and plasma volume at a virtual steadystate for almost 2 hours. The rate constant for urinary excretion (k 10 ) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates.Conclusions: There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers.

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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.

Background Elevated plasma concentrations of syndecan‐1 and heparan sulfate in studies of trauma, sepsis, and major surgery are commonly assumed to indicate acute glycocalyx degradation. We explored a possible role of the kidneys for these elevations. Methods Plasma and urine concentrations of syndecan‐1, heparan sulfate, and biomarkers of inflammation were measured over 5 hours in 15 hospital patients treated for post‐burn injury. The renal clearances of syndecan‐1 and heparan sulfate (CLR) were calculated and their influence on the plasma concentration predicted by simulation. Results The urine/plasma concentration ratio was 0.9 (0.3‐3.0) for syndecan‐1 and 2.8 (2.0‐4.3) for heparan sulfate. The CLR varied 250‐fold for syndecan‐1 and 10‐fold for heparan sulfate. Multiple linear regression analysis showed that CLR for syndecan‐1 was positively associated with the creatinine clearance (P < .0032) and the urine flow (P < .015). CLR for heparan sulfate increased with interleukin‐6 (P < .003) and the urine flow (P < .01). Simulations suggested that a change in CLR from the mean of the highest 3 to the lowest three values would double plasma syndecan‐1 within 4 hours and cause a 7‐fold rise after 24 hours. A similar change in CLR for heparan sulfate would triple the plasma level within 24 hours, even if no increased shedding of the glycocalyx takes place. Conclusions The renal elimination of syndecan‐1 and heparan sulfate varied greatly. A change in kidney function, which is common after trauma and major surgery, might alone induce several‐fold changes in their plasma concentrations.

Background: Albumin for intravenous infusion is marketed in two concentrations, 20% and 5%, but how they compare with regard to plasma volume expansion over time is unclear.Methods: In a prospective crossover study, 12 volunteers received 3 ml kg À1 of 20% albumin and, on another occasion, 12 ml kg À1 of 5% albumin over 30 min. Hence, equivalent amounts of albumin were given. Blood was collected on 15 occasions over 6 h. Mass balance and volume kinetics were used to estimate the plasma volume