Fluid volume kinetics of 20% albumin

Abstract

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 individual-specific 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 k₂₁ ), but it also increased losses of fluid from the kinetic system (k_b ). The balance between k₂₁ and k_b maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k₁₀ ) 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.

Keywords: albumin; fluid kinetics; heparan sulfate; hyperoncotic; syndecan-1.

Figure 1

A, Schematic drawing of the finally developed base model. B, the measured plasma dilution in all 30 subjects (green = volunteers, red = postoperative, open circles = females, stars = males) and the modelled curve according to the base model (thick line)

Figure 2

Distribution of key variables in the kinetic analysis. The plot of C‐reactive protein shows data for postoperative patients only, as the volunteers had very low concentrations

Figure 3

Predicted vs measured plasma dilution for the population (30 patients) without A, and with B, covariates. Predicted vs measured urinary excretion without C, and with D, covariates. Green = volunteers, red = postoperative, open circles = females, stars = males

Figure 4

A, Measured plasma dilution in all 30 subjects (points) and the predicted dilution when the individual‐specific covariate effects have been considered (green = volunteer, red = postoperative, dotted line = females, continuous line = male). B, the covariate effect of the preinfusion urinary creatinine concentration on k ₁₀ (green = volunteer, red = postoperative, open circle = female, star = male). C, Box‐plot showing the covariate effect of the preceding surgery on k ₁₀

Figure 5

Correlation between A, urine osmolality and the urinary creatinine concentration. B, Plasma albumin and the colloid osmotic pressure C, and the changes in these parameters during the study. Green = volunteers, red = postoperative, open circles = females, stars = males

Figure 6

The effect of 20% albumin on the volume expansion of V _c (the plasma) depending on A, whether the subjects were volunteers or postoperative patients. B, Urinary concentration of creatinine before the infusion started. C, Infusing the same amount of albumin but dispersed in different volumes of fluid. D, Combined effect of 2 covariates for k ₁₀ on the predicted urinary excretion. E, Rate of absorption of fluid in all subjects (thin lines) and as the mean rate (thick line). F, Predictive check of the kinetic model. The parameter values shown in Table 2 were used for the simulations. In subplots A–D, 1 or 2 covariates values were changed as indicated