Plasma Volume Oscillations during Fluid Therapy in Humans.

INTRODUCTION: Oscillations are frequently observed on plasma dilution curves during intravenous fluid therapy. This study aimed to examine how common these oscillations are and what they represent. METHODS: Fourier transforms were used to analyze the residuals obtained during fitting of a volume kinetic model to 269 plasma dilution curves. Oscillating patterns were identified in two-thirds of the fluid infusion experiments. RESULTS: The wave frequency usually had a dominating frequency of 1 h or multiples thereof. The wave amplitudes varied between 1% and 4% of the plasma volume. The "peak-to-peak" amplitudes were then twice as large, which corresponded to blood volume changes of 60-240 mL. A population kinetic analysis of the distribution of infused fluid between body fluid compartments was then applied to search for clues that could explain the oscillations. This analysis showed that amplitudes >1.5% were associated with doubled turnover of fluid in a fast-exchange interstitial fluid compartment and, together with data on plasma albumin, suggested that oscillations might represent bursts of efferent lymph. CONCLUSIONS: Oscillations with very low frequency were often observed on plasma dilution-time curves obtained during fluid therapy. They were associated with fast turnover of interstitial fluid and can possibly have resulted from accelerated lymphatic flow.

Evidence of serial connection between the plasma volume and two interstitial fluid compartments.

BACKGROUND: Kinetic analysis of fluid volume shifts can identify two interstitial fluid compartments with different turnover rates, but how they are connected to the bloodstream is unknown. METHODS: Retrospective data were retrieved from 217 experiments where 1.5 L of Ringer's solution (mean) had been administered by intravenous infusion over 30 min to awake and anesthetized humans (mean age 40 years). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed models software. Possible modes of connection between the two interstitial fluid compartments and the bloodstream were judged by covariance analysis between kinetic rate constants, physiological variables, and time factors. RESULTS: The return flow of already distributed fluid to the plasma via a fast-exchange interstitial compartment was inhibited ongoing infusion of fluid (-38 %), which was probably due to increase of the venous pressure during volume loading. Ongoing infusion also greatly retarded the entrance of fluid to the slow-exchange compartment (-85 %), which suggests that infused Ringer's first had to enter the fast-exchange compartment. A high mean arterial pressure markedly increased the urine output and, to a lesser degree, also the rate of entrance of fluid to the fast-exchange compartment. Moreover, a high blood hemoglobin concentration retarded the rate of entrance of fluid to the fast-exchange compartment. CONCLUSIONS: The fast-exchange but not the slow-exchange interstitial fluid compartment was affected by intravascular events, which suggests that only the fast-exchange compartment is directly connected to the circulating blood.

Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

Anesthesia-induced Lymphatic Dysfunction.

General anesthetics adversely alters the distribution of infused fluid between the plasma compartment and the extravascular space. This maldistribution occurs largely from the effects of anesthetic agents on lymphatic pumping, which can be demonstrated by macroscopic fluid kinetics studies in awake versus anesthetized patients. The magnitude of this effect can be appreciated as follows: a 30% reduction in lymph flow may result in a fivefold increase of fluid-induced volume expansion of the interstitial space relative to plasma volume. Anesthesia-induced lymphatic dysfunction is a key factor why anesthetized patients require greater than expected fluid administration than can be accounted for by blood loss, urine output, and insensible losses. Anesthesia also blunts the transvascular refill response to bleeding, an important compensatory mechanism during hemorrhagic hypovolemia, in part through lymphatic inhibition. Last, this study addresses how catecholamines and hypertonic and hyperoncotic fluids may mobilize interstitial fluid to mitigate anesthesia-induced lymphatic dysfunction.

Blood volume and hemodynamics during treatment of major hemorrhage with Ringer solution, 5% albumin, and 20% albumin: a single-center randomized controlled trial.

BACKGROUND: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery. METHODS: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate. RESULTS: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure. CONCLUSION: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022.

A Slow-Exchange Interstitial Fluid Compartment in Volunteers and Anesthetized Patients: Kinetic Analysis and Physiology.

BACKGROUND: Physiological studies suggest that the interstitial space contains 2 fluid compartments, but no analysis has been performed to quantify their sizes and turnover rates. METHODS: Retrospective data were retrieved from 270 experiments where Ringer's solution of between 238 and 2750 mL (mean, 1487 mL) had been administered by intravenous infusion to awake and anesthetized humans (mean age 39 years, 47% females). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed-models software. RESULTS: The kinetic analysis successfully separated 2 interstitial fluid compartments. One equilibrated rapidly with the plasma and the other equilibrated slowly. General anesthesia doubled the rate constants for fluid entering these 2 compartments (from 0.072 to 0.155 and from 0.026 to 0.080 min -1 , respectively). The return flows to the plasma were impeded by intensive fluid therapy; the rate constant for the fast-exchange compartment decreased from 0.251 to 0.050 when the infusion time increased from 15 to 60 minutes, and the rate constant for the slow-exchange compartment decreased from 0.019 to 0.005 when the infused volume increased from 500 to 1500 mL. The slow-exchange compartment became disproportionately expanded when larger fluid volumes were infused and even attained an unphysiologically large size when general anesthesia was added, suggesting that the flow of fluid was restrained and not solely determined by hydrostatic and oncotic forces. The dependence of the slow-exchange compartment on general anesthesia, crystalloid infusion rate, and infusion volume all suggest a causal physiological process. CONCLUSIONS: Kinetic analysis supported that Ringer's solution distributes in 2 interstitial compartments with different turnover times. The slow compartment became dominant when large amounts of fluid were infused and during general anesthesia. These findings may explain why fluid accumulates in peripheral tissues during surgery and why infused fluid can remain in the body for several days after general anesthesia.

Fluid distribution during surgery in the flat recumbent, Trendelenburg, and the reverse Trendelenburg body positions.

BACKGROUND: The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg ("legs up") position, or the reverse Trendelenburg ("head up") position. METHODS: Retrospective data on hemodilution and urine output obtained during and after infusion of 1-2 L of Ringer's solution over 30-60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis. RESULTS: General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia-induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the "legs up" position facilitates lymphatic flow, whereas the "head up" position slows this flow. Both Trendelenburg positions increased swelling of the "third fluid space". CONCLUSIONS: General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body.

Accelerated lymph flow from infusion of crystalloid fluid during general anesthesia.

BACKGROUND: Kinetic analysis of crystalloid fluid yields a central distribution volume (Vc) of the same size as the expected plasma volume (approximately 3 L) except during general anesthesia during which Vc might be only half as large. The present study examined whether this difference is due to influence of the intravascular albumin balance. METHODS: A population volume kinetic analysis according to a three-compartment model was performed based on retrospective data from 160 infusion experiments during which 1-2.5 L of crystalloid fluid had been infused intravenously over 20-30 min. The plasma dilution based on blood hemoglobin (Hb) and plasma albumin (Alb) was measured on 2,408 occasions and the urine output on 454 occasions. One-third of the infusions were performed on anesthetized patients while two-thirds were given to awake healthy volunteers. RESULTS: The Hb-Alb dilution difference was four times greater during general anesthesia than in the awake state (+ 0.024 ± 0.060 versus - 0.008 ± 0.050; mean ± SD; P < 0.001) which shows that more albumin entered the plasma than was lost by capillary leakage. The Hb-Alb dilution difference correlated strongly and positively with the kinetic parameters governing the rate of fluid transfer through the fast-exchange interstitial fluid compartment (k12 and k21) and inversely with the size of Vc. Simulations suggest that approximately 200 mL of fluid might be translocated from the interstitial space to the plasma despite ongoing fluid administration. CONCLUSIONS: Pronounced plasma volume expansion early during general anesthesia is associated with a positive intravascular albumin balance that is due to accelerated lymphatic flow. This phenomenon probably represents adjustment of the body fluid volumes to anesthesia-induced vasodilatation.

Early Childhood Education: Health, Equity, and Economics.

Many low-income and minority children in the United States and globally are at risk of poor educational trajectories and, consequently, diminished life courses, because their households and neighborhoods lack resources to adequately support learning and development prior to formal schooling. This review summarizes evidence on center-based early childhood education (ECE) for three- and four-year-olds as a means of assuring school readiness in cognitive and socioemotional skills. While the details of ECE programs merit further research, it is clear that ECE can benefit children, especially those most disadvantaged, with additional societal benefits and positive long-run economic returns. Universal ECE is not a cure-all, and its success requires ongoing alignment with subsequent education and attention to child household and community conditions. Because resource deprivation is concentrated in low-income and minority communities, publicly funded universal ECE can also be a powerful instrument for the promotion of social equity.

Recruitment of efferent lymph during infusion of 20 % albumin.

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 immunoglobulins 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.

Co-morbidity associated with development of severe COVID-19 before vaccine availability: a retrospective cohort study in the first pandemic year among the middle-aged and elderly in Jönköping county, Sweden.

BACKGROUND: In preparation of future pandemics, it is important to recognise population-level determinants associated with development of severe illness before efficient vaccines and evidence-based therapeutic measures are available. The aim of this study was to identify pre-pandemic diagnoses recorded in a middle-aged and elderly population that were associated with development of severe COVID-19 during the first pandemic year. METHODS: A cohort study design was used. Severe COVID-19 was defined as a course of illness that resulted in hospital admission or death. A retrospective analysis was performed that comprised all individuals aged 39 years and older (N = 189,951) living in Jönköping County, Sweden. All diagnosed morbidity recorded in contacts with health care during the pre-pandemic year 2019 was used to identify which diagnoses that were associated with development of severe COVID-19 in the first pandemic year 2020. The analyses were performed separately for each diagnosis using binary logistic regression with adjustment for sex and age. RESULTS: Severe COVID-19 was suffered by 0.67% (N = 1,280) of the middle-aged and elderly population in the first pandemic year. Individuals previously diagnosed with dementia, cerebral palsy, kidney failure, type 2 diabetes mellitus, hypertension, and obesity were at higher risk of developing severe COVID-19. For patients with Type 2 diabetes mellitus, the odds ratio (OR) was 2.18 (95% confidence interval, 1.92-2.48). Type 1 diabetes mellitus was not associated with increased risk. CONCLUSION: Diagnoses suggesting service provision at long-term healthcare facilities and co-morbidity with components of the metabolic syndrome were associated with an increased risk of developing severe COVID-19 in a middle-aged and elderly population before vaccines were available.

Hypovolemia with peripheral edema: What is wrong?

Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1ß, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.

Near-thermo-neutral electron recombination of titanium oxide ions.

While the dissociative recombination (DR) of ground-state molecular ions with low-energy free electrons is generally known to be exothermic, it has been predicted to be endothermic for a class of transition-metal oxide ions. To understand this unusual case, the electron recombination of titanium oxide ions (TiO+) with electrons has been experimentally investigated using the Cryogenic Storage Ring. In its low radiation field, the TiO+ ions relax internally to low rotational excitation (≲100 K). Under controlled collision energies down to ∼2 meV within the merged electron and ion beam configuration, fragment imaging has been applied to determine the kinetic energy released to Ti and O neutral reaction products. Detailed analysis of the fragment imaging data considering the reactant and product excitation channels reveals an endothermicity for the TiO+ dissociative electron recombination of (+4 ± 10) meV. This result improves the accuracy of the energy balance by a factor of 7 compared to that found indirectly from hitherto known molecular properties. Conversely, the present endothermicity yields improved dissociation energy values for D0(TiO) = (6.824 ± 0.010) eV and D0(TiO+) = (6.832 ± 0.010) eV. All thermochemistry values were compared to new coupled-cluster calculations and found to be in good agreement. Moreover, absolute rate coefficients for the electron recombination of rotationally relaxed ions have been measured, yielding an upper limit of 1 × 10-7 cm3 s-1 for typical conditions of cold astrophysical media. Strong variation of the DR rate with the TiO+ internal excitation is predicted. Furthermore, potential energy curves for TiO+ and TiO have been calculated using a multi-reference configuration interaction method to constrain quantum-dynamical paths driving the observed TiO+ electron recombination.

Predicting fluid responsiveness using esophagus Doppler monitoring and pulse oximetry derived pleth variability index; retrospective analysis of a hemodynamic study.

BACKGROUND: Fluid therapy during major surgery can be managed by providing repeated bolus infusions until stroke volume no longer increases by ≥ 10%. However, the final bolus in an optimization round increases stroke volume by < 10% and is not necessary. We studied how different cut-off values for the hemodynamic indications given by esophagus Doppler monitoring, as well as augmentation by pulse oximetry, are associated with a higher or smaller chance that stroke volume increases by ≥ 10% (fluid responsiveness) before fluid is infused. METHODS: An esophagus Doppler and a pulse oximeter that displayed the pleth variability index were used to monitor the effects of a bolus infusion in 108 patients undergoing goal-directed fluid therapy during major open abdominal surgery. RESULTS: The analyzed data set comprised 266 bolus infusions. The overall incidence of fluid responsiveness was 44%, but this varied greatly depending on pre-infusion hemodynamics. The likelihood of being fluid-responsive was 30%-38% in the presence of stroke volume > 80 mL, corrected flow time > 360 ms, or pleth variability index < 10%. The likelihood was 21% if stroke volume had decreased by <8% since the previous optimization, which decreased to 0% if combined with stroke volume > 100 mL. By contrast, the likelihood of fluid responsiveness increased to 50%-55% when stroke volume ≤ 50 mL, corrected flow time ≤ 360 ms, or pleth variability index ≥ 10. A decrease in stroke volume by > 8% since the previous optimization was followed by a 58% likelihood of fluid responsiveness that, in combination with any of the other hemodynamic variables, increased to 66%-76%. CONCLUSIONS: Single or combined hemodynamic variables provided by esophagus Doppler monitoring and pulse oximetry derived pleth variability index could help clinicians avoid unnecessary fluid bolus infusions.

Trajectory of plasma syndecan-1 and heparan sulphate during major surgery: A retrospective observational study.

BACKGROUND: Surgical trauma-induced inflammation during major surgery may disrupt endothelial integrity and affect plasma concentrations of glycocalyx constituents, such as syndecan-1 and heparan sulphate. To date, no studies have focused on their perioperative temporal changes. METHODS: As part of a trial, we obtained plasma and urine specimens sampled during the perioperative period in 72 patients undergoing major abdominal surgery. The plasma concentration of syndecan-1 and heparan sulphate was measured on five occasions, from baseline to the second postoperative day. Plasma and urinary creatinine and urinary syndecan-1 concentrations were measured before surgery and on the first postoperative morning. RESULTS: We observed three different temporal patterns of plasma syndecan-1 concentration. Group 1 'low' (64% of patients) showed only minor changes from baseline despite a median heparan sulphate increase of 67% (p < .005). Group 2 'increase' (21% of patients) showed a marked increase in median plasma syndecan-1 from 27 µg/L to 118 µg/L during the first postoperative day (p < .001) with a substantial (+670%; p < .005) increase in median plasma heparan sulphate from 279 to 2196 µg/L. Group 3 'high' (14% of patients) showed a constant elevation of plasma syndecan-1 to >100 µg/L, but low heparan sulphate levels. The plasma C-reactive protein concentration did not differ across the three groups and 90% of colon surgeries occurred in Group 1. Treatment with dexamethasone was similar across the three groups. Surgical blood loss, duration of surgery and liver resection were greatest in Group 2. CONCLUSION: Changes in syndecan-1 and heparan sulphate after surgery appear to show three different patterns, with the greatest increases in those patients with greater blood loss, more liver surgery and longer operations. These observations suggest that increases in syndecan-1 and heparan sulphate reflect the degree of surgical injury.

The kinetics of isotonic and hypertonic resuscitation fluids is dependent on the sizes of the body fluid volumes.

Background and Aims: The extracellular and intracellular fluid volumes (ECV and ICV) vary not only with age, gender, and body weight but also with the habitual intake of water. The present study examines whether the baseline variations in the ECV and ICV change the distribution and elimination of subsequently given infusion fluids. Material and Methods: Twenty healthy male volunteers underwent 50 infusion experiments with crystalloid fluid for which the fluid volume kinetics was calculated based on frequent measurements of the hemodilution using mixed-effects modeling software. The results were compared with the ECV and ICV measured with multifrequency bioimpedance analysis before each infusion started. The fluids were given over 30 minutes and comprised 25 mL/kg Ringer's acetate (N = 20), Ringer's lactate, 5 mL/kg 7.5% saline, and 3 mL/kg 7.5% saline in 6% dextran 70 (these fluids, N = 10). Results: A large ICV was associated with a small extravascular accumulation of infused fluid, which increased the plasma volume expansion and the urinary excretion. With hypertonic fluid, a large ECV greatly accelerated urinary excretion. The body weight did not serve as a covariate in the kinetic models. Albumin was recruited to the plasma during infusion of both types of fluid. The hypertonic fluids served as diuretics. The infused excess sodium and osmolality were distributed over a 35% larger space than the sum of the ECV and ICV. Conclusion: A large ICV reduced the rate of distribution of Ringer's solution, whereas a large ECV accelerated the excretion of hypertonic saline.

Laser Probing of the Rotational Cooling of Molecular Ions by Electron Collisions.

We present state-selected measurements of rotational cooling and excitation rates of CH^{+} molecular ions by inelastic electron collisions. The experiments are carried out at a cryogenic storage ring, making use of a monoenergetic electron beam at matched velocity in combination with state-sensitive laser dissociation of the CH^{+} ions for simultaneous monitoring of the rotational level populations. Employing storage times of up to 600 s, we create conditions where electron-induced cooling to the J=0 ground state dominates over radiative relaxation, allowing for the experimental determination of inelastic electron collision rates to benchmark state-of-the-art theoretical calculations. On a broader scale, our experiments pave the way to probe inelastic electron collisions for a variety of molecular ions relevant in various plasma environments.

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

Preclinical studies in animals and human clinical trials question whether the endothelial glycocalyx layer is a clinically important permeability barrier. Glycocalyx breakdown products in plasma mostly originate from 99.6-99.8% of the endothelial surface not involved in transendothelial passage of water and proteins. Fragment concentrations correlate poorly with in vivo imaging of glycocalyx thickness, and calculations of expected glycocalyx resistance are incompatible with measured hydraulic conductivity values. Increases in plasma breakdown products in rats did not correlate with vascular permeability. Clinically, three studies in humans show inverse correlations between glycocalyx degradation products and the capillary leakage of albumin and fluid.

Plasma disappearance rate of albumin when infused as a 20% solution.

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 (T1/2). RESULTS: No differences were observed for T1/2 between volunteers, post-burn patients, patients who underwent surgery with minor bleeding and postoperative patients. The T1/2 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 T1/2 for albumin. By contrast, patients undergoing surgery associated with major hemorrhage had a shorter T1/2, corresponding to 15% of the infused albumin per h. In addition, our analyses show that the T1/2 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.

Plasma Volume Expansion and Fluid Kinetics of 20% Albumin During General Anesthesia and Surgery Lasting for More Than 5 Hours.

BACKGROUND: Intraoperative administration of crystalloid for plasma volume expansion may be reduced by use of hyperoncotic albumin. However, the degree of plasma volume expansion with administration of 20% albumin is poorly quantitated. We estimated the amount of volume expansion attributable to 20% albumin administration in patients undergoing surgery for more than 5 hours. METHODS: Twenty percent albumin was delivered at 3 mL/kg by intravenous infusion during 30 minutes to 15 patients (mean ± standard deviation [SD] age; 46 ± 15 years) undergoing surgery. Blood samples and urine were collected for 5 hours. Mass balance calculations and volume kinetics were used to estimate plasma volume expansion and capillary leakage of albumin and fluid. RESULTS: Administration of 20% albumin was associated with an increase in plasma volume amounting to 1.7 times the infused volume. After correction for hemorrhage, the median (and 25th to 75th percentiles) intravascular half-life for the administered albumin mass was 20.4 (14.2-34.7) hours. The plasma volume decreased with a half-life of 21.7 (16.1-26.8) hours. Urinary excretion was 3 times greater than the infused volume of albumin, but kinetic analysis suggested that other flows of fluid to and from the plasma occurred more slowly than previously found in volunteers. Hemodynamic support with norepinephrine increased urinary excretion and contracted the plasma volume. CONCLUSIONS: Albumin (20%) increased the plasma volume by 1.7 times the infused volume. Our results do not support that the transcapillary leakage of albumin is accelerated by anesthesia and surgery.