Volume Kinetic Analysis Research Articles

Non-invasive monitoring of blood haemoglobin for analysis of fluid volume kinetics

A commercially available pulse oximeter that reports blood haemoglobin (Hb) concentration is evaluated. This study considers whether this device can provide serial Hb data that would be sufficiently reliable for volume kinetic analysis of infusion fluids. Forty infusions of 5 or 10 ml/kg of acetated Ringer's solution were given over 15 min in 10 healthy volunteers. Hb was measured on 17 different occasions over 120 min using the Radical 7 pulse oximeter and compared with the result of invasive blood sampling (control). A one-volume kinetic model was applied to each data series. The pulse oximeter also reported the perfusion index (PI). The median deviation between the 680 invasive and non-invasive Hb samples (the accuracy) was 1.6% and the absolute median deviation (precision) was 4.6%. Between-subject factors explained half of the variation in the difference between non-invasive vs. invasive sampling. Ten of the 40 non-invasive series of Hb values were discarded from kinetic analysis due to poor quality. The remaining 30 series showed a smaller distribution volume for the infused fluid when kinetic analysis was based on the non-invasive method (3.0 vs. 5.3l; P<0.001). This was due to co-variance with the PI, which exaggerated the decrease in Hb caused by the infusions. The non-invasive method might provide useful kinetic data at the group level, but individual curves deviated too much from the invasive data to be reliable. Non-invasive measurement of the Hb concentration during volume loading could not provide useful kinetic data for individuals.

Label-Free Photonic Crystal Biosensor Integrated Microfluidic Chip for Determination of Kinetic Reaction Rate Constants

We demonstrate a photonic crystal integrated microfluidic chip that is compatible with a 384-well microplate format for measuring kinetic reaction rate constants in high-throughput biomolecular interaction screening applications. The device enables low volume kinetic analysis of protein-protein interactions with low flow latency, and control of five analyte flow channels with a single control point. The structure is fabricated with a replica molding process that produces the submicron photonic crystal structure simultaneously with the micrometer-scale fluid channel structure. The device significantly reduces the kinetic assay time required compared with a conventional biosensor microplate in which reagents reach the active detection surface by diffusion. Using the photonic crystal sensor fluid network system, we demonstrate determination of the kinetic association/dissociation rate constants between immobilized ligands and analytes in the flow stream, using the heparin/lactoferrin system as an example.

Arteriovenous Differences in Plasma Dilution and the Distribution Kinetics of Lactated Ringer′s Solution

Conventional concept suggests that infused crystalloid fluid is first distributed in the plasma volume and then, since the capillary permeability for fluid is very high, almost instantly equilibrates with the extracellular fluid space. We challenge whether this view is consistent with findings based on volume kinetic analysis. Fifteen volunteers received an IV infusion of 15 mL/kg of lactated Ringer's solution during 10 min. Simultaneous arterial and venous blood hemoglobin (Hgb) samples were obtained and Hgb concentrations measured. The arteriovenous (AV) difference in Hgb dilution in the forearm was determined and a volume kinetic model was fitted to the series of Hgb concentrations in arterial and venous blood. The AV difference in plasma dilution was only positive during the infusion and for 2.5 min thereafter, which represents the period of net flow of fluid from plasma to tissue. Kinetic analysis showed that volume expansion of the peripheral fluid space began to decrease 14 min (arterial blood) and 20 min (venous blood) after the infusion ended. Distribution of lactated Ringer's solution apparently occurs much faster in the forearm than in the body as a whole. Therefore, the AV difference in the arm does not accurately reflect the distribution of Ringer's solutions or whole-body changes in plasma volume. The relatively slow whole-body distribution of lactated Ringer's solution, which boosts the plasma volume expansion during and for up to 30 min after an infusion, is probably governed by a joint effect of capillary permeability and differences in tissue perfusion between body regions.

Influence of “Liberal”versus “Restrictive” Intraoperative Fluid Administration on Elimination of a Postoperative Fluid Load

Previously, the authors found "liberal" fluid administration (approximately 3 l Ringer's lactate [RL]) to improve early rehabilitation after laparoscopic cholecystectomy, suggesting functional hypovolemia to be present in patients receiving "restrictive" fluid administration (approximately 1 l RL). Because volume kinetic analysis after a volume load may distinguish between hypovolemic versus normovolemic states, the authors applied volume kinetic analysis after laparoscopic cholecystectomy to explain the difference in outcome between 3 and 1 l RL. In a prospective, nonrandomized trial, the authors studied 20 patients undergoing laparoscopic cholecystectomy. Ten patients received 15 ml/kg RL (group 1) and 10 patients received 40 ml/kg RL (group 2) intraoperatively. All other aspects of perioperative management were standardized. A 12.5-ml/kg RL volume load was infused preoperatively and 4 h postoperatively. The distribution and elimination of the fluid load was estimated using volume kinetic analysis. Patient baseline demographics and intraoperative data did not differ between groups, except for intraoperative RL, having a median of 1,118 ml (range, 900-1,400 ml) in group 1 compared with a median of 2,960 ml (range, 2,000-3,960 ml) in group 2 (P<0.01). There were no significant preoperative versus postoperative differences in the size of the body fluid space expanded by infused fluid (V), whereas the clearance constant kr was higher postoperatively versus preoperatively (P=0.03). The preoperative versus postoperative changes in volume kinetics including V were not different between the two groups. Elimination of an intravenous fluid load was increased after laparoscopic cholecystectomy per se but not influenced by the amount of intraoperative fluid administration.

A single-model solution for volume kinetic analysis of isotonic fluid infusions

Volume kinetics was developed to analyze the distribution and elimination of intravenously given fluid. However, when groups of patients are being compared, the current approach is limited by the need for several models, which yield parameters that cannot be compared. To meet the requirement to handle all patients in a group individually and without pooling, a new all-encompassing model was designed. The aim of this paper was to test whether the new model could be used to analyze all patients in a group. The new model consists of 'rate' and 'amount' parameters instead of 'clearance' and 'dilution' parameters. With this change, a redundant parameter can be taken out, but the biexponential nature is retained. The new parameters are the volume of distribution V1 (ml), the intercompartmental rate constant kt/min and the elimination rate constant kr/min. The success rates of the new and original models in producing results within a set of pre-determined quality requirements were compared using blood dilution data from 10 volunteers challenged with intravenous lactated Ringer's solution. The new model could be used to analyze all 10 cases within the pre-determined criteria, but the original biexponential model failed in 70% of cases. The residuals improved with the new model. The medians (interquartile ranges) were as follows: V1, 4931 ml (4239-6149 ml); kt), 0.0384/min (0.0024-0.1140/min); kr, 0.0140/min (0.0015-0.0043/min). The new model was suited to the analysis of all cases, and is therefore a better approach to study how clinical conditions change the distribution and elimination of infused fluid.

Intravascular Fluid Administration and Hemodynamic Performance During Open Abdominal Surgery

We studied whether central hemodynamics measured by a pulmonary artery catheter can serve as a pharmacodynamic expression of fluid therapy in 10 patients undergoing open abdominal surgery. We examined how closely hemodynamic variables follow plasma dilution, which is an index of plasma volume expansion, during and after an IV infusion of 25 mL/kg of lactated Ringer's solution over 45 min. Pulmonary artery wedge pressure and central venous pressure responded to IV fluid with an increase that correlated with accompanying plasma dilution. Six of 10 patients showed a decrease in cardiac output that was probably secondary to an increase in peripheral vascular resistance (nonresponders), whereas the rest increased cardiac output (responders). Volume kinetic analysis suggested that 54% of the infused fluid resided in the central fluid space at the end of the infusion and 25% at the end of the study in the responders compared with 25% and 3%, respectively, in nonresponders. In conclusion, half of the patients undergoing open abdominal surgery responded to crystalloid fluid with a decrease in cardiac output. Pulmonary artery wedge pressure and central venous pressure responded more consistently to different degrees of plasma dilution, which can be simulated for various fluid regimens using volume kinetics.

Sepsis Produced by Pseudomonas Bacteremia Does Not Alter Plasma Volume Expansion After 0.9% Saline Infusion in Sheep

Clinicians generally consider sepsis to be a state in which fluid is poorly retained within the vasculature and accumulates within the interstitium. We hypothesized that infusion of 0.9% saline in conscious, chronically instrumented sheep with hyperdynamic bacteremic sepsis would be associated with less plasma volume expansion (PVE) and greater interstitial fluid volume expansion than in conscious, nonseptic sheep. Six conscious adult sheep received an IV infusion of 25 mL/kg of 0.9% saline over 20 min (1.25 mL.kg(-1).min(-1)) in a control nonseptic state and during early and late sepsis (4 and 24 h, respectively, after initiation of a standard infusion of live Pseudomonas aeruginosa). The distribution and elimination of infused fluid were studied by mass balance (after measurement of plasma volume using Evans blue dye) and volume kinetic analysis. Mass balance demonstrated no significant differences in the time-course of PVE between control, early sepsis, and late sepsis. At the end of the infusions, which averaged 1050 +/- 125 mL in sheep weighing an average of 42 +/- 5 kg, calculated PVE was 312 +/- 50 mL, 386 +/- 34 mL, and 400 +/- 51, respectively. Volume kinetic analysis was similar in all three protocols. In both nonseptic and septic sheep, infusion of 0.9% saline resulted in similar peak PVE and resolution of PVE over a 3-h interval and similar kinetic parameters. Contrary to clinical impressions and to our hypothesis, the distribution of 0.9% saline in this animal model was not changed by bacteremia produced by infusion of Pseudomonas aeruginosa.

“The Proper Study of Mankind Is Man”*—Rather, Men and Women Undergoing Anesthesia and Surgery

“The Proper Study of Mankind Is Man”*—Rather, Men and Women Undergoing Anesthesia and Surgery

Bolus injection of Ringer's solution and dextran 1 kDa during induction of spinal anesthesia

Arterial hypotension following induction of spinal anesthesia is difficult to prevent with infusion fluids. In a randomized, unblinded and controlled study we evaluated whether a rapid fluid administration planned according to volume kinetic analysis is followed by a more stable blood pressure. Spinal anesthesia was induced in 75 surgical patients, using one of three different fluid regimens: intravenous 'bolus injection' of 5 ml kg(-1) of Ringer's acetate over 3 min, 2 ml kg(-1) of low-molecular weight (1 kDa) dextran over 3 min, or a constant-rate infusion of 15 ml kg(-1) of Ringer's acetate over 40 min (controls). The kinetics of the fluid was studied in five patients in each group and also in eight volunteers. The decrease in mean arterial pressure averaged 28%, 27% and 26%, respectively, and was fully developed 16 min after the induction. The height of the block, but not the fluid programme, correlated with the hypotension. Nausea or near-fainting associated with marked hypotension or bradycardia was recorded in none, five (20%) and two (8%) of the patients, respectively. Both bolus injections were followed by translocation of fluid from the peripheral tissues to the bloodstream, which maintained the plasma dilution at about 10% for at least 30 min until surgery began. A brisk infusion of Ringer's solution or dextran 1 kDa over 3 min was followed by the same decrease in arterial pressure as a longer and 3-5-times larger infusion of Ringer's solution over 40 min during induction of spinal anesthesia.

Volume kinetics of glucose 2.5% solution and insulin resistance after abdominal hysterectomy

We hypothesized that volume kinetics can be used to predict the rate of infusion of glucose 2.5% solution required to yield any predetermined plasma glucose level and degree of plasma dilution during the postoperative period. In 15 women, mean age 50 yr (range 37-63), 2 days after an abdominal hysterectomy, a volume kinetic analysis was performed on an i.v. infusion of 12.5 ml kg(-1) ( approximately 900 ml) of glucose 2.5% given over 45 min. The insulin resistance was measured by a glucose clamp, and it was compared with daily bioimpedance analyses, which indicated the hydration of the intra/extracellular body fluid spaces. The clearance of glucose was 0.42 litre min(-1) (0.60 litre min(-1) is normal) while the other five parameters in the kinetic model were similar to those obtained in healthy volunteers. Computer simulations indicated that in a 70-kg female, at steady state, the rate of infusion (ml min(-1)) should be three times the allowed increase in plasma glucose (mmol litre(-1)). To maintain a predetermined plasma dilution the corresponding rate factor was 160. The glucose uptake during clamping was 3.9 mg kg(-1) min(-1) (7.0 is normal), which, during the second day after hysterectomy, correlated with the dehydration of the intracellular space (r=0.77; P<0.002) and with the protein catabolism as indicated by the urinary excretion of 3-methylhistidine (r=-0.76, P<0.002). The anaesthetist can prescribe postoperative administration of glucose 2.5% to reach any desired plasma glucose level and dilution by using the two presented nomograms. Insulin resistance correlated with intracellular dehydration and protein catabolism.

The Volume Kinetics of Acetated Ringer???s Solution During Laparoscopic Cholecystectomy

We studied the distribution and elimination of an IV infusion of 20 mL/kg of acetated Ringer's solution (approximately 1500 mL) over 60 min in 12 women undergoing laparoscopic cholecystectomy. A plasma dilution of 4.2% developed during the induction of general anesthesia, even though fluid was withheld. The additional plasma dilution induced by the subsequent volume expansion was slightly larger than expected from previous volunteer experiments and averaged 18%. The diuretic response to intravascular fluid administration was small, and only 20% of the infused fluid had been excreted 4 h later. Volume kinetic analysis showed that the IV fluid expanded a central body fluid space by 3.2 L. The clearance constants for distribution and elimination averaged 115 mL/min and 6.8 mL/min, respectively. These data represent a half-life of the fluid in the patients that is 17 times longer (median, 4.5 h) than the half-life of the plasma dilution (16 min), indicating a strong tendency to the formation of peripheral edema. A nomogram based on the kinetic variables suggests that infusion rates should be relatively rapid early on during surgery but slower later. This strategy creates a constant plasma dilution at any desired level without causing undue peripheral accumulation of fluid.

Distribution and elimination of crystalloid fluid in pre-eclampsia.

Pre-eclampsia (PE) is a disease of pregnancy associated with peripheral oedema and hypovolaemia, but few details are known about how women with PE handle a volume load of crystalloid fluid compared with healthy pregnant women. To study this issue, Ringer's acetate solution (12.5 ml/kg of body weight) was given by intravenous infusion over 30 min to eight women with PE and to eight healthy pregnant women matched with respect to gestational week (mean, 34 weeks). Venous blood was sampled and excreted urine was collected over 90 min to study the time course of the volume expansion by means of volume kinetic analysis. The results show that the size of the central body fluid space expanded by the infused fluid was smaller in PE (mean, 2940 ml compared with 4240 ml respectively; P<0.04), and the clearance constants for distribution (100 ml/min compared with 43 ml/min; P<0.04) and elimination (125 ml/min compared with 36 ml/min; P<0.02) were higher in the women with PE than in the controls. Less excess volume accumulated in the central body fluid space in the presence of PE, whereas the rates of distribution and elimination were higher during and for 15 min after the infusion. It is concluded that Ringer's acetate solution fluid is both distributed and eliminated faster in women with PE than in matched pregnant controls.

Validation of volume kinetic analysis of glucose 2.5% solution given by intravenous infusion

The distribution and elimination of glucose solutions can be analysed by means of a volume kinetic model, but the ability of the model to predict plasma dilution ('model linearity') has not been evaluated. Six male volunteers received four separate infusions of glucose 2.5%: 10 ml kg(-1) and 15 ml kg(-1) over 30 min, and 15 ml kg(-1) and 25 ml kg(-1 )over 60 min. The kinetic model was fitted to measurements of plasma glucose concentration and haemodilution. The mean volume of distribution for the glucose was 9.2 (SEM 0.4) litres while the infused fluid expanded a central body fluid space (V(1)) of 3.1 (0.3) litres. Increasing the amount of infused fluid, but not the infusion rate, resulted in a proportional increase in the area under the curve for plasma glucose and plasma dilution, the only confounder being glycosuria. The bias of computer simulation was slightly increased by rebound hypoglycaemia, which could occur with the highest infusion rates, but the accuracy was almost identical regardless of whether the kinetic parameters from all 24 experiments or from any of the subgroups were used. The volume kinetic model for glucose 2.5% is linear and can therefore be used for computer simulation as long as marked glycosuria does not occur.

Isoflurane but not mechanical ventilation promotes extravascular fluid accumulation during crystalloid volume loading.

The combination of isoflurane anesthesia and mechanical ventilation reduces urinary output and promotes redistribution of a crystalloid bolus into the extravascular space. The authors hypothesized that mechanical ventilation rather than isoflurane causes this alteration. The fate of a 25-ml/kg, 20-min, 0.9% saline fluid bolus was studied in four different experiments per sheep: while conscious and spontaneously ventilating (CSV), while conscious and mechanically ventilated (CMV), while anesthetized with isoflurane and mechanical ventilated (ISOMV), and while anesthetized with isoflurane and spontaneously ventilating (ISOSV). By calculations based on the indicator dilution and mass balance principles, plasma expansion was similar between protocols. Isoflurane but not mechanical ventilation reduced urinary output and increased interstitial fluid volume (P < 0.001): At 180 min, mean total urinary outputs were 15.6 +/- 2.1 and 15.9 +/- 2.9 ml/kg in the CSV and CMV protocols and 2.7 +/- 0.6 and 3.1 +/- 1.1 ml/kg in the ISOSV and ISOMV protocols, respectively. The net changes in extravascular volume, assumed to be interstitial fluid volume, were 8.6 +/- 3.3 and 8.1 +/- 3.1 ml/kg, and 22.5 +/- 1.5 and 22.1 +/- 1.6 ml/kg in the corresponding protocols. Volume kinetic analysis demonstrated extravascular fluid accumulation associated with isoflurane anesthesia similar to the calculated interstitial accumulation of 20.2 +/- 0.5 and 26.5 +/- 0.3 ml/kg in the ISOSV and ISOMV protocols, respectively. Isoflurane, but not mechanical ventilation, decreased urinary excretion and increased interstitial fluid volume. Volume kinetic analysis indicated "third-space" losses due to isoflurane. Perioperative fluid retention may be associated not only with surgical tissue manipulation, but with anesthesia per se.

Volume kinetic analysis of fluid shifts accompanying intravenous infusions of glucose solution.

Volume kinetics is a mathematical tool for macroscopic (whole-body) evaluation of the distribution and elimination of fluid given by intravenous infusion. Although the kinetic system has mostly been applied to crystalloid fluids, such as Ringer's solution, it has more recently been extended to glucose solution, which is characterized by interdependence between glucose and fluid kinetics. The elimination of glucose, as estimated by a one-compartment open model, serves as the driving force for cellular uptake of glucose and, by virtue of osmosis, of water. Key findings include the observation that the infused fluid, besides being accumulated in the cells, occupies a central body fluid space (V1), which is no larger than 3-4 L, and that the cellular hydration has a much longer time-course than the hydration of V1. This explains the risk of hypovolemia associated with rapid infusion of 5% glucose; the dilution of V1, which is quite substantial owing to the small size of this space at baseline, stimulates a brisk diuresis while the excess water is being "trapped" in the cells along with the glucose. Model linearity has been demonstrated for 2.5% glucose solution and this allows the construction of nomograms for administration of such fluid during surgery and critical illness.

Physiological or Functional Fluid Spaces

Physiological or Functional Fluid Spaces

Volume Kinetic Analysis of the Distribution of 0.9% Saline in Conscious versus Isoflurane-anesthetized Sheep

The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia. Six adult sheep received an intravenous infusion of 25 ml/kg of 0.9% saline over 20 min in the conscious state and also during isoflurane anesthesia and mechanical ventilation. The distribution and elimination of infused fluid were studied by volume kinetics based on serial analysis of hemoglobin dilution in arterial blood and by mass balance that incorporated volume calculations derived from volume kinetic analysis and measurements of urinary volumes. The mass balance calculations indicated only minor differences in the time course of plasma volume expansion between the conscious and anesthetized states. However, isoflurane anesthesia markedly reduced urinary volume (median, 9 vs. 863 ml; P < 0.03). In conscious sheep, the central and peripheral volume expansion predicted by volume kinetics agreed well with the calculations based on mass balance. However, during isoflurane anesthesia and mechanical ventilation, calculation using volume kinetic analysis of the variable kr, an elimination factor that, in conscious humans and sheep, is closely related to urinary excretion, represented both urinary excretion and peripheral accumulation of fluid. This suggests that the previous assumption that kr approximates urinary excretion of infused fluid requires modification, i.e., kr simply reflects net fluid movement out of plasma. In both conscious and anesthetized, mechanically ventilated sheep, infusion of 0.9% saline resulted in minimal expansion of plasma volume over a 3-h interval. In conscious sheep, infused 0.9% saline was rapidly eliminated from the plasma volume by urinary excretion; in contrast, the combination of isoflurane anesthesia and mechanical ventilation reduced urinary excretion and promoted peripheral accumulation of fluid.

Volume kinetics of intravenous fluid therapy in the prehospital setting.

To study the volume effect of isotonic and hypertonic crystalloid fluid during ambulance transports after mild trauma, a prospective case-control study was initiated, using the ambulance and helicopter transport system in Stockholm. The hemodilution resulting from intravenous infusion of 1.0 L of Ringer's acetate solution (n = 7) or 250 ml of 7.5% sodium chloride (n = 3) over 30 minutes (min) was measured every 10 min during 1 hour when fluid therapy was instituted at the scene of an accident, or on arrival at the hospital. The dilution was studied by volume kinetic analysis and compared to that of matched, healthy controls who received the same fluid in hospital. The hemodilution at the end of the infusions averaged 7.7% in the trauma patients and 9.1% in the controls, but the dilution was better maintained after trauma. The kinetic analysis showed that the size of the body fluid space expanded by Ringer's solution was 4.6 L and 3.8 L for the trauma and the control patients, respectively, while hypertonic saline expanded a slightly larger space. For both fluids, trauma reduced the elimination rate constant by approximately 30%. Mild trauma prolonged the intravascular persistence of isotonic and hypertonic crystalloid fluid as compared to a control group.

Stability of the interstitial matrix after crystalloid fluid loading studied by volume kinetic analysis

To investigate if fluid therapy changes the prerequisites for the development of oedema, four i.v. infusions of Ringer's solution 25 ml kg-1 were given over 15 or 30 min in a randomized crossover study to 10 healthy male volunteers, aged 28-40 (mean 31) yr. Blood haemoglobin concentration, measured every 5 min for 90 min, and urinary excretion were used as input data for volume kinetic analysis. The results showed that the elimination rate constant (kr) was higher when another infusion had been given earlier on the same day (208 vs 140 ml min-1; P < 0.002) and the size of V1 was larger during the 15-min infusions (4.7 vs 3.2 litre; P < 0.02). However, the size of V2 and the rate constant for the exchange of fluid between V1 and V2 were similar during all infusions. We conclude that a fluid challenge makes elimination of further infused fluid more effective but does not change compliance with volume expansion in healthy volunteers.

Urinary excretion as an input variable in volume kinetic analysis of Ringer's solution

The disposition of fluid given by i.v. infusion can be studied by fitting one-volume and two-volume kinetic models to the fractioned dilution of blood haemoglobin and serum albumin concentrations over time. However, the two-volume model is sometimes associated with a high standard error in estimating the size of the secondary (peripheral) body fluid space, V2. To examine if a fixed elimination rate constant (kr) determined by urinary excretion can be used to make the model more stable, we infused Ringer's acetate 25 ml kg-1 over 30 min in 15 male volunteers (mean age 35 yr). A fixed kr increased the total residual error when curve-fitting was applied according to the one-volume model. The two-volume model was improved when there was a strong within-patient covariance between kr and V2 (r2 < or = -0.98). The size of V2 was 10 litre when the fixed and model-generated values of kr agreed fully.