Distribution of crystalloid fluid changes with the rate of infusion: a population-based study.

BACKGROUND: Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringer's acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids. METHODS: Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringer's acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects. RESULTS: The micro-constants describing distribution (k12) and elimination (k10) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k21) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V(c)) doubled. CONCLUSION: The return of Ringer's acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid.

Volume kinetics of acetated Ringer's solution during experimental spinal anaesthesia.

BACKGROUND: General anaesthesia lowers the clearance of crystalloid fluid, but the volume kinetics of such fluid throughout the duration of spinal anaesthesia has not been studied. METHODS: Ten female volunteers (mean age 29 years) received an intravenous infusion of 25 ml/kg of acetated Ringer's solution with and without spinal anaesthesia. A volume kinetic model was fitted to serial measurements of the haemoglobin concentration over 240 min based on arterial, cubital vein, and femoral vein blood. The measured urine flow was compared to the model-predicted elimination. RESULTS: The arterial pressure remained stable, although the block reached to Th3-Th5 in half of the volunteers. There were no differences in fluid kinetics between the spinal anaesthesia and the control experiments. The administered volume was well confined to the kinetic system, which consisted of two communicating fluid spaces that were 2.8 l and approximately 7 l in size at baseline. The arteriovenous difference in plasma dilution remained positive for 30 min post-infusion in those having analgesia reaching to Th3-Th5, which differed significantly from low-level analgesia (Th12-L2, P < 0.03) when venous plasma was sampled from the leg. The urinary excretion averaged 1.13 l and 1.01 l for the spinal and control experiments, respectively. Volume kinetics predicted the urinary excretion at 5- to 10-min intervals with an overall bias of 52 ml. CONCLUSION: Acetated Ringer's solution showed the same kinetics during experimental spinal anaesthesia as when the fluid was infused alone. Hence, spinal anaesthesia is not associated with the reduced fluid clearance reported for general anaesthesia.

Monitoring of fluid absorption with nitrous oxide during transurethral resection of the prostate.

BACKGROUND: The fluid absorption that occurs during transurethral resection of the prostate (TURP) can be indicated and quantified by the ethanol method. Recently, nitrous oxide (N(2)O) was tested in animals and volunteers and seemed to be more accurate and safe. The present study compared these two methods in surgical patients. METHODS: Eighty-six TURPs were performed at two hospitals using an irrigating fluid that contained 3% mannitol, 1% ethanol and 0.004% N(2)O (40 ml/l). The ethanol concentration was measured by end-expiratory tests every 10 min. The N(2)O concentration was measured by a flared nasal cannula every second. Fluid absorption was calculated based on a regression equation (ethanol method) from the area under the curve based on the samples where CO(2) >median (N(2)O method). RESULTS: Thirteen patients (15%) absorbed >300 ml of fluid as indicated by the ethanol method. The median volume was 707 ml (range 367-1422). Ethanol yielded higher figures for fluid absorption up to 700-800 ml, whereafter the N(2)O method indicated that the absorption was larger. Over the entire range, the mean difference between the two methods at the end of any 10-min period of TURP was only +45 ml, although the 95% limits of agreement were quite separated (-479 to +569 ml). CONCLUSIONS: The N(2)O method does not require forced breath sampling and was successfully apply clinically. However, there was a dose-dependent difference in result between the ethanol and N(2)O methods, which markedly separated the limits of agreement for a wider range of fluid absorption events.

Nitrous oxide for monitoring fluid absorption in volunteers.

BACKGROUND: We studied whether nitrous oxide (N(2)O) added to a fluid allows the infused volume to be quantified by measuring N(2)O in the expired air during normal breathing. If so, N(2)O might serve as a tracer of fluid absorption during endoscopic surgery. METHODS: Twelve male volunteers received continuous and intermittent i.v. infusions (5-45 min) of fluid containing 40 ml litre(-1) of N(2)O. Breath N(2)O and CO(2) concentrations were measured every second via a flared nasal cannula, a standard nasal cannula, or a Hudson mask. RESULTS: An expression for the amount of infused fluid was obtained by calculating the area under the N(2)O concentration-time curve for samples representative for exhalation (CO(2)>median) and then dividing this area by the median CO(2) for the remaining samples. The N(2)O method then estimated fluid volumes of between 50 and 1400 ml within a 95% prediction interval of +/-200 ml. There were differences of up to 14% in results between the airway devices tested, but the volunteers preferred the flared nasal cannula. N(2)O showed a distinctly higher 3 min variability during intermittent infusion, which could indicate whether fluid absorption is directly intravascular or extravascular. No adverse effects were seen. CONCLUSIONS: N(2)O method does not require forced end-expiratory breath sampling but still predicts an administered fluid volume with high precision. N(2)O variability can probably be used to distinguish immediately between intravascular and perivesical fluid absorption during surgery.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

[Volume kinetics--a new method to control intravenous fluid infusion]. / Volymkinetik--ny metod styra intravenös vätsketillförsel.

The body's handling of fluid given by intravenous infusion can be analysed and simulated by means of volume kinetics, in which pharmacokinetic principles are applied to dilution-time profiles obtained during fluid therapy. In volume kinetics, the emphasis is on the distribution of fluid to body fluid spaces which accordingly become expanded. These spaces do not always correspond to known anatomical or physiological fluid compartments. The time course of the effect of volume fluid distribution to these spaces may be investigated by means of computer-assisted simulation, or a nomogram based on values for volume kinetic variables obtained from infusion experiments.

Volume kinetics of Ringer's solution in hypovolemic volunteers.

BACKGROUND: The amount of Ringer's solution needed to restore normal blood volumes is thought to be three to five times the volume of blood lost. This therapy can be optimized by using a kinetic model that takes accounts for the rates of distribution and elimination of the infused fluid. METHODS: The authors infused 25 ml/kg Ringer's acetate solution into 10 male volunteers who were 23 to 33 yr old (mean, 28 yr) when they were normovolemic and after 450 ml and 900 ml blood had been withdrawn. One-volume and two-volume kinetic models were fitted to the dilution of the total venous hemoglobin and plasma albumin concentrations. RESULTS: Withdrawal of blood resulted in a progressive upward shift of the dilution-time curves of both markers. The two-volume model was statistically justified in 56 of the 60 analyzed data sets. The hemoglobin changes indicated that the body fluid space expanded by the infused fluid had a mean total volume of 10.7 l(+/-0.9 SEM). The elimination rate constant (kr) decreased with the degree of hypovolemia and was 133 ml/min (22 ml/min [SEM]), 100 ml/min (39 ml/min [SEM]), and 34 ml/min (7 ml/min [SEM]), respectively (P < 0.01). Plasma albumin indicated a slightly larger body fluid space expanded by the infused fluid, but kr was less (P < 0.02). Hypovolemia reduced the systolic and diastolic blood pressures by approximately 10 mmHg (P < 0.05). CONCLUSIONS: The dilution of the blood and the retention of infused Ringer's solution in the body increases in the presence of hypovolemia, which can be attributed chiefly to a reduction of the elimination rate constant.

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.

Volume kinetics of Ringer's solution in female volunteers.

The kinetics of crystalloid solutions in humans have not been adequately described previously. Therefore, we measured blood haemoglobin concentration during and for 120 min after i.v. infusion of 25 ml kg-1 of Ringer's acetate solution over 15, 30, 45 and 80 min, and 12.5 ml kg-1 over 30 min in six adult female volunteers. The dilution-time profiles were analysed according to a new kinetic model adapted for fluid spaces. Volume expansion produced by Ringer's solution approached steady state in an exponentially decaying manner when plasma volume had increased by approximately 550 ml. The size of the fluid space expanded by Ringer's solution was only 4.8 litre (95% confidence interval 3.8-5.8 litre) except for the fastest infusion, where it averaged 9.0 litre. The rate of fluid elimination could be predicted as the product of plasma dilution and a constant averaging 95 (95% confidence interval 68-122) ml min-1.

Time course of increased haemodilution in hypotension induced by extradural anaesthesia.

Volume loading with crystalloid solution results in more pronounced haemodilution in patients who develop arterial hypotension during induction of extradural anaesthesia than in those who remain normotensive. The aim of this study was to describe the time course of this increase in haemodilution. Heart rate, systolic arterial pressure and blood haemoglobin concentration were measured every 3 min during the onset of extradural anaesthesia in 22 elderly men undergoing short urological operations. Fluid therapy consisted of 15 ml/kg body weight of Ringer's acetate solution. Patients with a decrease in systolic pressure of > 25% retained 50% (SD 12%) of the infused fluid in the circulation, while the others retained 36 (8%) (P < 0.002). In both groups, arterial hypotension was followed by increased haemodilution after a delay of as much as 15 min. This suggests that, despite volume loading, there is relative hypovolaemia throughout the development of hypotension.