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.

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.

Serum Creatinine Levels and Nephrocheck® Values With and Without Correction for Urine Dilution-A Multicenter Observational Study.

BACKGROUND: The Nephrocheck® test is a single-use cartridge designed to measure the concentrations of two novel cell-cycle arrest biomarkers of acute kidney injury, namely tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). Correlations of serum creatine values and TIMP-2 and IGFBP7 with and without correction for urine dilution have not been previously undertaken in patients undergoing major abdominal surgery. We hypothesized that the Nephrocheck® values would be significantly different with and without correction for urine dilution in patients with elevated creatinine values post major abdominal surgery. METHODS: We performed a post hoc analysis of serum and urine specimens sampled preoperatively and postoperatively in 72 patients undergoing major abdominal surgery. Thirty samples were measured from patients with the greatest decrease and the greatest increase in postoperative serum creatinine values. Urine was analyzed with the Nephrocheck to predict the risk of acute kidney injury (AKIRisk™). We then examined the relationship between serum creatinine and the urinary excretion of TIMP-2 and IGFBP7 as measured by the Nephrocheck test. The AKIRisk between the groups with and without correction for urine dilution was assessed. RESULTS: The median perioperative change in serum creatinine in the two groups was -19% and +57%, respectively. The uncorrected median baseline AKIRisk decreased from 0.70 (25th-75th percentiles, 0.09-1.98) to 0.35 (0.19-0.57) (mg/L)2 in the first group and rose from 0.57 (0.22-1.53) to 0.85 (0.67-2.20) (mg/L)2 in the second group. However, when corrected for the squared urine dilution, the AKIRisk™ in patients with postoperative increases in serum creatinine was not indicative of kidney injury; the corrected AKIRisk was 8.0 (3.2-11.7) µg2/mmol2 before surgery vs.6.9 (5.3-11.0) µg2/mmol2 after the surgery (P = 0.69). CONCLUSION: In the setting of major abdominal surgery, after correction of TIMP-2 and IGFBP7 for urine dilution, the Nephrocheck AKIRisk scores were significantly different from the uncorrected values. These finding imply that the AKIRisk index is a function of urine flow in addition to an increased release of the biomarkers.

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.

Can perioperative hemodilution be monitored with non-invasive measurement of blood hemoglobin?

BACKGROUND: Trends in non-invasive measurements of blood hemoglobin (Hb) may be useful for identifying the need for transfusion in the perioperative period. METHODS: Crystalloid fluid (5-20 mL/kg) was administered intravenously or by mouth to 30 volunteers and 33 surgical patients in five non-randomized clinical studies where Hb was measured on 915 occasions by non-invasive (Radical-7™) and invasive methodology. The hemodilution curves were compared by volume kinetic analysis and linear regression, with the slope and scattering of the data as key outcome measures. RESULTS: The slope was 1.0, indicating unity between the two modes of measuring Hb when crystalloid fluid was infused in volunteers; however, only 40-45% of the variability in the non-invasive Hb could be explained by the invasive Hb. Patients undergoing major surgery, who showed the most pronounced hemodilution (median 24 g/L); non-invasive Hb explained 72% of the variability but indicated only half the magnitude of the invasive Hb changes (slope 0.48, P < 0.001 versus the volunteers). Simulations based on volume kinetic parameters from the volunteers showed 25% less plasma volume expansion after infusion when based on non-invasive as compared to invasive Hb, while no difference was found during infusion. CONCLUSIONS: In volunteers the non-invasive Hb had good accuracy (low bias) but poor precision. In surgical patients the non-invasive Hb had good precision but systematically underestimated the hemodilution. Despite severe limitations, the non-invasive technology can be used to follow Hb trends during surgery if supported by occasional invasive measurements to assure acceptable quality of the hemodilution curve. TRIAL REGISTRATIONS: ControlledTrials.gov NCT01195025, NCT01062776, NCT01458678, NCT03848507, and NCT01360333 on September 3, 2010, February 4, 2010, October 25, 2011, February 20, 2019, and May 25, 2011, respectively.

Kinetics of crystalloid fluid in hyperglycemia; an open-label exploratory clinical trial.

BACKGROUND: Infusion with 0.9% saline is a mainstay in the treatment of severe hyperglycemia, but the kinetics of the saline volume in this setting has not been studied. METHODS: An intravenous infusion of 1 L of 0.9% saline over 30 minutes was given on 31 occasions to 17 patients with hyperglycemia due to poorly controlled diabetes (mean age 51 years). A two-volume kinetic model was fitted to serial data on the hemodilution and urinary excretion, using mixed-effects modeling software. RESULTS: Plasma glucose was 36 ± 9 mmol/L on arrival to the hospital. The central volume of distribution (the plasma) was only 2.38 L (mean; 95% confidence interval 1.73-3.04) on the day of admission. Uptake into a remote compartment, believed to be the cells, amounted to 300 mL of the first liter of saline, although only small amounts of insulin were given. Plasma glucose, plasma bicarbonate, urine glucose, and plasma creatinine served as covariates in the kinetic model and mathematically affected the urinary excretion. For example, elimination of the infused fluid tripled from an increase in plasma glucose from 5 to 35 mmol/L and doubled from a reduction in plasma bicarbonate from 24 to 5 mmol/L. CONCLUSIONS: The excretion of 0.9% saline was increased depending on the degree of hyperglycemia. The kinetics was characterized by glucose-accelerated diuresis, and an intracellular uptake that occurred at two thirds the urine flow rate. These data could help to determine appropriate volumes and rates of infusion of crystalloids in hyperglycemia.

Long Intravascular Persistence of 20% Albumin in Postoperative Patients.

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.

Fluid distribution kinetics during cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. METHODS: Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. RESULTS: The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. CONCLUSIONS: The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur.

Fluid distribution kinetics during cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. METHODS: Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. RESULTS: The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. CONCLUSIONS: The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur. .

Preoperative urine-specific gravity and the incidence of complications after hip fracture surgery: A prospective, observational study.

BACKGROUND: Mild to moderately severe dehydration is common in the elderly, but its relationship to surgical outcome is unclear. OBJECTIVES: To study the incidence of dehydration prior to hip fracture surgery and its relationship to postoperative complications. DESIGN: Prospective observational study. SETTING: Operation department and orthopaedic ward at a regional hospital. PATIENTS: Forty-five patients [median (interquartile range) age 78 (75 to 86) years] undergoing acute hip fracture surgery. INTERVENTIONS: A urine sample was taken on admission to the operating theatre. Complications were assessed 2 days postoperatively using a check-list. MAIN OUTCOME MEASURES: Dehydration was considered to be present if the urinary specific gravity was 1.020 or higher, indicating renal water conservation. The number and type of postoperative complications were recorded. RESULTS: Dehydration was present in one third of the patients. Sixty percent of these patients had at least one postoperative complication, whereas the corresponding proportion was 30% in the euhydrated patients (P < 0.01). Only one patient (3%) had more than one complication in the euhydrated group compared with six patients (40%) in the dehydrated group (P < 0.01). Euhydrated patients had a mean of 0.3 postoperative complications per surgery, whereas dehydrated patients scored 1.1 complications (P < 0.015). The higher incidence included confusion, arterial desaturation and cardiovascular events. CONCLUSION: Dehydration before surgery nearly quadrupled the number of postoperative complications after hip fracture repair. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01294930.

Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid.

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), hydroxyethyl starch 130/0.4 (10 ml kg) 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 whereas the 95% prediction interval was wide, ranging from -24.9 to 23.7 g l. 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. TRIAL REGISTRATION: ClinicalTrials identifier: NCT01195025.

Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid.

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), hydroxyethyl starch 130/0.4 (10 ml kg) 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 whereas the 95% prediction interval was wide, ranging from -24.9 to 23.7 g l. 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. Trial registration ClinicalTrials identifier: NCT01195025.