| 1. |
- Hahn, Robert G., et al.
(författare)
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Biomarkers of endothelial injury in plasma are dependent on kidney function
- 2019
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Ingår i: Clinical hemorheology and microcirculation. - : IOS PRESS. - 1386-0291 .- 1875-8622. ; 72:2, s. 161-168
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Injury (shedding) of the endothelial glycocalyx layer, which alters local blood flow and microvascular permeability, is assessed by measuring components of this layer in circulating blood. The influence of renal function on their concentrations is unknown. METHODS: Plasma and urine concentrations of three shedding products (syndecan-1, hyaluronic acid, and heparan sulfate) and creatinine were measured over 5 hours in 15 healthy volunteers and 15 postoperative patients; this guaranteed a spread of kidney functions. Renal clearances were calculated. RESULTS: Low renal clearances of syndecan-1 (mean 3.5 mL/min) and hyaluronic acid (0.8 mL/min) correlated inversely with the 6-fold variability in the plasma concentrations of these substances (r = -0 . 45 and-0.49). Low creatinine clearance correlated inversely (r = -0.60) and plasma creatinine directly (r = 0.52) with the two-fold variability in heparan sulfate, which was the only shedding substance that also correlated with C-reactive protein (r= 0.51) and, therefore, showed higher concentrations after surgery. CONCLUSIONS: The present explorative study suggests that a 6-fold variability in the plasma concentrations of three commonly measured endothelial shedding products can be understood by the kidneys ability to excrete them. This finding has implications when interpreting results of studies where shedding is assessed.
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| 2. |
- Hahn, Robert G., et al.
(författare)
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Elevated Plasma Concentrations of Syndecan-1 Do Not Correlate With Increased Capillary Leakage of 20% Albumin
- 2021
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Ingår i: Anesthesia and Analgesia. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-2999 .- 1526-7598. ; 132:3, s. 856-865
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Tidskriftsartikel (refereegranskat)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 (10)logarithm 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.
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| 3. |
- Hahn, Robert G., et al.
(författare)
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Fluid volume kinetics of 20% albumin
- 2019
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Ingår i: British Journal of Clinical Pharmacology. - : WILEY. - 0306-5251 .- 1365-2125. ; 85:6, s. 1303-1311
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Tidskriftsartikel (refereegranskat)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 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 steady-state 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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| 4. |
- Hahn, Robert G., et al.
(författare)
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Plasma concentrations of syndecan-1 are dependent on kidney function
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:6, s. 809-815
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Hasselgren, Emma, et al.
(författare)
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Long Intravascular Persistence of 20% Albumin in Postoperative Patients
- 2019
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Ingår i: Anesthesia and Analgesia. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-2999 .- 1526-7598. ; 129:5, s. 1232-1239
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Zdolsek, Joachim, et al.
(författare)
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Recruitment of efferent lymph during infusion of 20% albumin
- 2023
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Ingår i: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 148
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intravenous infusion of hyper-oncotic 20 % albumin expands the plasma volume by approximately twice the infused volume. We investigated whether the recruited fluid stems from accelerated flow of efferent lymph, which would add protein to the plasma, or from reversed transcapillary solvent filtration, where the solvent is expected to be low in protein.Methods: We analyzed data from 27 intravenous infusions of 20 % albumin (3 mL/kg; approximately 200 mL) over 30 min given to 27 volunteers and patients. Twelve of the volunteers were also given a 5 % solution and served as controls. The pattern of blood hemoglobin, colloid osmotic pressure, and the plasma concentrations of two immunoglobulins (IgG and IgM) were studied over 5 h.Results: A decrease of the difference between the plasma colloid osmotic pressure and plasma albumin occurred during the infusions and was almost four times greater for 5 % albumin than for 20 % albumin at 40 min (P < 0.0036), which indicates that non-albumin protein enriched the plasma when 20 % was infused. Moreover, the difference between the infusion-derived dilution of the blood plasma based on hemoglobin and the two im-munoglobulins amounted to-1.9 % (-6 to +0.2) for 20 % albumin and to-4.4 % (25th-75th percentile range -8.5 to +0.2) during experiments with 5 % albumin (P < 0.001). This supports that the plasma was enriched by immunoglobulins, probably via the lymph, when 20 % was infused.Conclusions: Between half and two-thirds of the extravascular fluid that was recruited during infusion of 20 % albumin in humans consisted of protein-containing fluid consistent with efferent lymph.
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| 7. |
- Zdolsek, Markus, et al.
(författare)
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Plasma disappearance rate of albumin when infused as a 20% solution
- 2022
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Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The transcapillary leakage of albumin is increased by inflammation and major surgery, but whether exogenous albumin also disappears faster is unclear. Methods An intravenous infusion of 3 mL/kg of 20% albumin was given over 30 min to 70 subjects consisting of 15 healthy volunteers, 15 post-burn patients, 15 patients who underwent surgery with minor bleeding, 10 who underwent surgery with major bleeding (mean, 1.1 L) and 15 postoperative patients. Blood Hb and plasma albumin were measured on 15 occasions over 5 h. The rate of albumin disappearance from the plasma was quantitated with population kinetic methodology and reported as the half-life (T-1/2). Results No differences were observed for T-1/2 between volunteers, post-burn patients, patients who underwent surgery with minor bleeding and postoperative patients. The T-1/2 averaged 16.2 h, which corresponds to 3.8% of the amount infused per h. Two groups showed plasma concentrations of C-reactive protein of approximately 60 mg/L and still had a similarly long T-1/2 for albumin. By contrast, patients undergoing surgery associated with major hemorrhage had a shorter T-1/2, corresponding to 15% of the infused albumin per h. In addition, our analyses show that the T-1/2 differ greatly depending on whether the calculations consider plasma volume changes and blood losses. Conclusion The disappearance rate of the albumin in 20% preparations was low in volunteers, in patients with moderately severe inflammation, and in postoperative patients.
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| 8. |
- Zdolsek, Markus, et al.
(författare)
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Plasma volume expansion and capillary leakage of 20% albumin in burned patients and volunteers
- 2020
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Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Zdolsek, Markus, et al.
(författare)
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Recruitment of extravascular fluid by hyperoncotic albumin
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 62:9, s. 1255-1260
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough hyperoncotic albumin may be used to recruit oedema, its effectiveness remains unclear. Therefore, this issue was studied during infusion experiments in healthy volunteers. MethodFifteen healthy volunteers (mean age 31years) received an infusion of 3mL/kg of 20% albumin over 30minutes. Their urinary excretion was recorded, and venous blood samples were taken to measure blood haemoglobin (Hb), haematocrit, colloid osmotic pressure as well as plasma albumin and sodium concentrations on 15 occasions over a period of 300minutes. Plasma volume expansion was taken as the inverse of the fluid-induced dilution of venous plasma, as given by the blood Hb concentration. Mass balance calculations were used to estimate the mobilisation of fluid from the tissues. ResultsMaximum plasma volume expansion was reached 20minutes after completing an infusion of 20% albumin. Urinary excretion was effectively increased, and the mobilised fluid from the tissues at 300minutes amounted to 3.41.2mL for each infused mL of 20% albumin, of which 19% was of intracellular origin. The urinary excretion correlated strongly with the amount of recruited fluid (R-2=0.87) and inversely with the plasma volume expansion (R-2=0.53). ConclusionThe infusion of 20% albumin significantly increases the plasma volume by recruiting interstitial fluid. After completing the infusion, there is a delay of 20minutes until maximum plasma dilution is reached, and the duration of the plasma volume expansion lasts far beyond 5hours.
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| 10. |
- Bergek, Christian, et al.
(författare)
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Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid
- 2012
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Ingår i: European Journal of Anaesthesiology. - : Lippincott Williams & Wilkins. - 0265-0215 .- 1365-2346. ; 29:12, s. 586-592
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Tidskriftsartikel (refereegranskat)abstract
- Context: Measurement of blood haemoglobin concentration by pulse oximetry could be of value in determining when erythrocytes should be transfused during surgery, but the effect of infusion fluids on the results is unclear.Objective: To study the effect of crystalloid and colloid fluid on the accuracy (bias) and precision of pulse oximetry haemoglobin estimation to indicate the venous haemoglobin concentration in volunteers.Design: Open interventional crossover study.Setting: Single university hospital.Participants: Ten male volunteers aged 18–28 (mean 22) years.Interventions: Each volunteer underwent three infusion experiments on separate days and in random order. The infusions were Ringer's acetate (20 ml kg−1), hydroxyethyl starch 130/0.4 (10 ml kg−1) and a combination of both.Results: At the end of the infusions of Ringer's acetate, pulse oximetry haemoglobin concentration had decreased more than the true haemoglobin concentration (15 vs. 8%; P < 0.005; n = 10) whereas starch solution decreased pulse oximetry haemoglobin concentration less than true haemoglobin concentration (7 vs. 11%; P < 0.02; n = 20). The same differences were seen when the fluids were infused separately and when they were combined. The overall difference between all 956 pairs of pulse oximetry haemoglobin concentration and true haemoglobin concentrations (the bias) averaged only −0.7 g l−1 whereas the 95% prediction interval was wide, ranging from −24.9 to 23.7 g l−1. In addition to the choice of infusion fluid, the bias was strongly dependent on the volunteer (each factor, P < 0.001).Conclusion: The bias of measuring haemoglobin concentration by pulse oximetry is dependent on whether a crystalloid or a colloid fluid is infused.
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