Kinetics and extravascular retention of acetated ringer's solution during isoflurane or propofol anesthesia for thyroid surgery

BACKGROUND: In sheep, isoflurane causes extravascular accumulation of infused crystalloid fluid. The current study evaluates whether isoflurane has a greater tendency than propofol to cause extravascular retention in surgical patients. METHODS: Thirty patients undergoing thyroid surgery lasting for 143 +/- 32 min (mean +/- SD) received an intravenous infusion of 25 ml/kg acetated Ringer's solution over 30 min. Anesthesia was randomized to consist of isoflurane or propofol supplemented by fentanyl. The distribution and elimination of the infused fluid was estimated using volume kinetics based on the fractional dilution of blood hemoglobin over 150 min. Extravascular retention of infused fluid was taken as the difference between the model-predicted elimination and the urinary excretion. The sodium and fluid balances were measured. RESULTS: The fractional plasma dilution increased gradually to approximately 30% during the infusion and thereafter remained at 15-20%. Urinary excretion averaged 11% of the infused volume. Mean arterial pressure was 10 mmHg lower in the isoflurane group (P < 0.001). The excess fluid volumes in the central and peripheral functional body fluid spaces were virtually identical in the groups. The sum of water losses by evaporation and extravascular fluid retention amounted to 2.0 +/- 2.5 ml/min for isoflurane and 2.2 +/- 2.1 ml/min for propofol. The sodium balance refuted that major fluid shifts occurred between the extracellular and intracellular spaces. CONCLUSIONS: The amount of evaporation and extravascular retention of fluid was small during thyroid surgery, irrespective of whether anesthesia was maintained by isoflurane or propofol.     

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

Background: The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia.

Methods: 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.

Results: 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.     

Elimination Rate Constant Describing Clearance of Infused Fluid from Plasma Is Independent of Large Infusion Volumes of 0.9% Saline in Sheep

Background: The purpose of this study was to determine the influence of varying large crystalloid infusion volumes, ranging from a volume that has been safely administered to volunteers to a volume that greatly exceeds a practical volume for studies in normovolemic humans, of rapidly infused 0.9% saline on the elimination rate constant in sheep.

Methods: Six sheep underwent three randomly ordered, 20 min, intravenous infusions of 0.9% saline in volumes of 25 ml/kg, 50 ml/kg and 100 ml/kg. Repeated measurements of arterial plasma dilution were analyzed using the volume kinetic approach to determine the apparent volumes of the central (V1) and peripheral (V2) body fluid spaces, the elimination rate constant (kr) describing clearance from the central fluid space and the rate constant (kt) for the diffusion of fluid between the central and the peripheral fluid spaces. The latter constant was split in to two constants, one describing flow out from the central fluid space and one describing flow into the central fluid space. Urinary output was measured in all sheep.

Results: kr was comparable at each infused volume (38.3 +/- 4.5, 32.2 +/- 4.2, and 36.7 +/- 7.0 ml/min, respectively, in the 25 ml/kg, 50 ml/kg, and 100 ml/kg protocols). However, for the largest infusion, other kinetic parameters were influenced by the magnitude of the infusion. V2 was significantly increased (P < 0.05) and the area under the dilution-time curve divided by the infused volume was 20% lower for the largest infusion (P < 0.03). Although urinary output increased as the infusion volume increased, only 59% of the administered volume had been excreted at 180 min after the 100 ml/kg infusion as compared with approximately 90% after the other two infusions (P < 0.01).     

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

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

Elimination rate constant describing clearance of infused fluid from plasma is independent of large infusion volumes of 0.9% saline in sheep

BACKGROUND: The purpose of this study was to determine the influence of varying large crystalloid infusion volumes, ranging from a volume that has been safely administered to volunteers to a volume that greatly exceeds a practical volume for studies in normovolemic humans, of rapidly infused 0.9% saline on the elimination rate constant in sheep. METHODS: Six sheep underwent three randomly ordered, 20 min, intravenous infusions of 0.9% saline in volumes of 25 ml/kg, 50 ml/kg and 100 ml/kg. Repeated measurements of arterial plasma dilution were analyzed using the volume kinetic approach to determine the apparent volumes of the central (V1) and peripheral (V2) body fluid spaces, the elimination rate constant (kr) describing clearance from the central fluid space and the rate constant (kt) for the diffusion of fluid between the central and the peripheral fluid spaces. The latter constant was split in to two constants, one describing flow out from the central fluid space and one describing flow into the central fluid space. Urinary output was measured in all sheep. RESULTS: kr was comparable at each infused volume (38.3 +/- 4.5, 32.2 +/- 4.2, and 36.7 +/- 7.0 ml/min, respectively, in the 25 ml/kg, 50 ml/kg, and 100 ml/kg protocols). However, for the largest infusion, other kinetic parameters were influenced by the magnitude of the infusion. V2 was significantly increased (P < 0.05) and the area under the dilution-time curve divided by the infused volume was 20% lower for the largest infusion (P < 0.03). Although urinary output increased as the infusion volume increased, only 59% of the administered volume had been excreted at 180 min after the 100 ml/kg infusion as compared with approximately 90% after the other two infusions (P < 0.01). CONCLUSIONS: Elimination from the central fluid space of large, rapidly infused volumes of saline solution is independent of infused volume. Larger volumes are apparently cleared from the central fluid space (V1) by expansion of a peripheral volume (V2) as renal excretion fails to increase in proportion to the volume of infused fluid.     

Volume kinetic analysis of the distribution of 0.9% saline in conscious versus isoflurane-anesthetized sheep

BACKGROUND: The distribution and elimination of 0.9% saline given by intravenous infusion has not been compared between the conscious state and during inhalational anesthesia. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Isoflurane but Not Mechanical Ventilation Promotes Extravascular Fluid Accumulation during Crystalloid Volume Loading

Background: 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.

Methods: 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).

Results: 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.     

Volume kinetics of Ringer solution after surgery for hip fracture

PURPOSE: To study the time course of volume changes during and after infusion of Ringer's solution in elderly patients after a standardised trauma. METHODS: The kinetics of 12.5 ml.kg-1 Ringer's solution infused over 30 min were studied in ten patients one day after surgery for hip fracture (mean age, 70 yr) and in an age- and sex-matched control group. Hemodilution, as measured every five minutes for 90 min, was used to calculate the size of the fluid space expanded by the fluid (V) and the elimination rate constant (kr). The baseline fluid balance status in the patients and the controls was compared by bioelectrical impedance analysis. RESULTS: The size of V was 4.1 +/- 0.51 (mean +/- SEM) in the patients and 3.4 +/- 0.21 in the controls (P:NS) while the corresponding results for kr were 85 +/- 12 and 166 +/- 27 ml.min-1, respectively (P < 0.04). Bioelectrical impedance analysis showed that the extracellular fluid space and the total body water volumes did not differ between the two groups. Computer simulations based on the data obtained for V and kr indicate that trauma increases the dilution of the plasma volume and the retention of fluid in response to slow and moderate infusion rates, while these indices of short-term changes in fluid balance remain the same in the two groups during very rapid infusion of Ringer's solution. CONCLUSION: A slower elimination rate increased dilution of plasma and retention of fluid when Ringer's solution was infused in elderly trauma patients.     

Population Volume Kinetics Predicts Retention of 0.9% Saline Infused in Awake and Isoflurane-anesthetized Volunteers

Background: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts.

Methods: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored.

Results: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged.     

Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers

BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.     

The effect of acetate ringer solution, 6% hydroxyethyl starch saline and 20% mannitol solution on the serum concentration of propofol continuously infused

Changes in serum concentrations of propofol after administration of three different fluids were investigated in 42 scheduled surgical patients. Anesthesia was induced with propofol 2 mg.kg-1 and maintained with constant rate infusion of propofol 6 mg.kg-1.hr-1. After achieving a stable depth of anesthesia, 5 ml.kg-1 of acetate Ringer's solution, 6% hydroxyethyl starch saline solution or 20% mannitol solution was infused in 15 minutes. Blood samples each 2 ml were taken before and 0, 5, 15, 30 and 60 minutes after fluid treatment. We measured hemoglobin and hematocrit of the samples for calculating the dilution rate of the plasma with infusion treatment, and determined the serum concentration of propofol by HPLC-spectrofluorometry. After administration of each fluid, the serum concentrations of propofol decreased significantly to 17 +/- 15, 25 +/- 10 and 35 +/- 8%, respectively (mean +/- SEM). The dilution rate of the plasma from the fractional change in blood hemoglobin increased to 0.08 +/- 0.02, 0.24 +/- 0.03, and 0.36 +/- 0.03, respectively. Administration of mannitol might markedly increase distribution volume of propofol, and this can be attributed to osmotic action of mannitol and resultant expansion of extracellular fluid volume. The results of the present investigation suggest that this pharmacokinetic change decreased the concentration of propofol more significantly in mannitol treatment patients than in Ringer's solution or 6% hydroxyethyl starch saline treatment patients.     

Volume Turnover Kinetics of Fluid Shifts after Hemorrhage, Fluid Infusion, and the Combination of Hemorrhage and Fluid Infusion in Sheep

Background: Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts.

Methods: Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion.

Results: The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments.     

Effects of hypertonic saline (7.5%) on extracellular fluid volumes in healthy volunteers

This study evaluated the effects of 7.5% saline on plasma and other extracellular fluid volumes. After baseline measurements, eight healthy postmenopausal female volunteers received 4 ml.kg-1 of hypertonic saline over 30 min. After the fluid infusion, the volunteers were studied for 60 min. Plasma volume was measured using a dilution of 125-iodine-labelled human albumin. Extracellular water and cardiac output were measured by whole body impedence cardiography. The infused volume was 4 ml.kg-1 (average 260 ml). Plasma volume increased rapidly during the infusion (mean +/- standard deviation, 442 +/- 167 ml). At the end of the 1-h follow-up period, plasma volume had increased by on average 465 ml (SD 83). The increase of extracellular water at the end of infusion and at the end of study was 650 ml (SD 93) and 637 ml (SD 192), respectively. The highest serum sodium recorded in the volunteers was 158 mmol.l-1. The effect of 7.5% saline on plasma volume was rapid and lasted for at least 1 h. Plasma volume remained elevated by more than the infused volume at the end of the study. The increase in plasma and extracellular fluid volumes was partly achieved by mobilizing intracellular water to extracellular compartment.     

Volume turnover kinetics of fluid shifts after hemorrhage, fluid infusion, and the combination of hemorrhage and fluid infusion in sheep

BACKGROUND: Hemorrhage is commonly treated with intravenous infusion of crystalloids. However, the dynamics of fluid shifts between body fluid spaces are not completely known, causing contradictory recommendations regarding timing and volume of fluid infusions. The authors have developed a turnover model that characterizes these fluid shifts. METHODS: Conscious, chronically instrumented sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25 ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/- 1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min followed by infusion as noted above (hemorrhage plus infusion). A two-compartment volume turnover kinetic model containing seven model parameters was fitted to data obtained by repeated sampling of hemoglobin concentration and urinary excretion. RESULTS: The volume turnover model successfully predicted fluid shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/- 1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to prevent hemorrhage-induced depression of cardiac output and diuresis. The model suggested that volume recruitment to the central compartment after hemorrhage was primarily achieved by mechanisms other than volume equilibration between the two model compartments. CONCLUSION: Volume turnover kinetics is a promising tool for explaining fluid shifts between body compartments after perturbations such as hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal output after hemorrhage prevailed regardless of fluid infusion and caused fluid retention, which expanded the tissue compartment.     

不同麻醉下老年患者静脉输注乳酸钠林格氏液的容量动力学

目的 比较不同麻醉下老年患者静脉输注乳酸钠林格氏液容量动力学的差异.方法 择期行上腹部手术老年患者30例,年龄65～79岁,ASA Ⅰ或Ⅱ级,随机分为2组(n=15):单纯全麻组(GA组)和硬膜外复合全麻组(GE组).GE组经T8.9硬膜外穿刺置管,注入2%利多卡因4 ml使阻滞平面达T4,然后硬膜外给予0.25%布比卡因8～10 ml.2组静脉注射咪达唑仑2 mg、芬太尼3μg/kg、异丙酚1.5 mg,kg和琥珀胆碱1.5 mg/kg麻醉诱导,气管内插管后行机械通气.麻醉诱导后2组经30min静脉输注乳酸钠林格氏液30 ml/kg,随后以0.1 ml·kg-1·min-1的速率继续输注60 min.连续监测心率、平均动脉压、中心静脉压、心脏指数、每搏量指数、胸内血容量指数及血管外肺水容量指数;桡动脉采血测定血红蛋白浓度和红细胞压积;记录试验过程中的尿量;应用容量动力学理论和物质守恒定律,计算中央容量稀释率、血浆容量增加、容量扩张效率、外周容量增加和清除率(K).尿量与Kr进行直线相关分析.结果 GA组和GE组乳酸钠林格氏液分布均符合容量动力学二室模型.与GA组比较,GE组中央容量稀释率、血浆容量增加和容量扩张效率升高,尿量和Kr减少(P<0.05),外周容量增加差异无统计学意义(P>0.05).GA组尿量与Kr呈正相关(r=0.551,P<0.05);GE组尿量与K呈正相关(r=0.531,P<0.05).结论 与单纯全麻比较,老年患者硬膜外复合全麻下静脉输注乳酸钠林格氏液的容量扩张效率增强.     

Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia

To examine the mechanism of renal sodium (Na) and potassium (K) retention during insulin infusion, seven healthy volunteers underwent clearance studies without (time control) and with insulin infusion (40 mU bolus, followed by 1 mU/kg/min for 150 min). Maximal free water clearance and fractional lithium clearance (FELi) were used to analyze renal sodium handling. Insulin decreased Na excretion (from 189 +/- 25 to 121 +/- 19 mumol/min, P less than 0.01) and K excretion (from 64 +/- 8 to 19 +/- 1 mumol/min, P less than 0.01), but did not change in glomerular filtration rate. FELi increased from 29.8 +/- 1.9 to 32.3 +/- 1.9% (P less than 0.05), minimal urine osmolality decreased from 59 +/- 3 to 46 +/- 3 mOsm/kg (P less than 0.01), and the diluting segment reabsorption index increased from 88.0 +/- 0.9 to 93.7 +/- 0.9%, P less than 0.01). Insulin also decreased plasma K, from 3.91 +/- 0.08 to 3.28 +/- 0.08 mmol/liter, P less than 0.01. In a third clearance study KCl was infused simultaneously (3.75 mumol/kg/min) to prevent this fall in plasma K. In this study insulin had no effect on Na and K excretion and diluting segment reabsorption, but the rise in FELi remained. In a fourth clearance study NaCl (3.75 mumol/kg/min) instead of KCl was infused together with insulin. This maneuver did not prevent the Na and K retaining effect of insulin, nor any of its effects on renal sodium handling parameters. These data suggest that Na and K retention during insulin infusion are largely secondary to hypokalemia, which causes increased reabsorption in the diluting segment.     

Natriuresis and the extracellular volume expansion by hypertonic saline

BACKGROUND: The mechanisms governing the duration of the extracellular fluid volume (ECF) expansion as a result of intravenous infusion of hypertonic saline solution are poorly understood. We hypothesized that the duration is closely related to the sodium excretion. MATERIALS AND METHODS: Six conscious splenectomized ewes with a mean body weight of 30 kg were given an intravenous infusion of 4 ml x kg(-1) of 7.5% saline solution on two occasions, one over a period of 5 min and another over a period of 20 min. Mass balance and volume kinetic calculations of the distribution and elimination of fluid were performed after repeated sampling of the plasma sodium concentration and the urinary excretion of water and sodium during 3 h. RESULTS: On considering the addition of sodium to and its excretion from the body, the plasma sodium concentration indicated a 10% dilution of the extracellular space. The volume expansion decayed at an average rate of 20% of the volume expansion per hour, which, however, varied greatly in the animals, depending on their capacity to excrete sodium. After 1 h, increasing natriuresis promoted translocation of water into the cells, which amounted to 25-35% of the total elimination. Computer simulations indicated that tripled natriuresis (up to approximately 750 mmol l(-1)) would increase the rate of elimination to 45% of the volume expansion per hour. CONCLUSION: The sodium excretion was inversely proportional to the duration of the extracellular volume expansion by 7.5% saline.     

Volume Kinetics of Ringer Solution, Dextran 70, and Hypertonic Saline in Male Volunteers

Background: A knowledge of the distribution of different fluids given by intravenous infusion is basic to the understanding of the effects of fluid therapy. Therefore, a mathematical model was tested to analyze the volume kinetics of three types of fluids.

Methods: The authors infused 25 ml/kg of Ringer acetate solution, 5 ml/kg of 6% dextran 70 in 0.9% NaCl, and 3 ml/kg of 7.5% NaCl over 30 min in 8 male volunteers aged from 25 to 36 years (mean, 31 years) and measured the changes in total hemoglobin, serum albumin, and total blood water over time. The changes were expressed as fractioned dilution and then plotted against time. The curves were fitted to a one-volume and a two-volume model, which allowed an estimation of the size of the body fluid space expanded by the fluid (V) and the elimination rate constant (kr) to be made.

Results: The changes in blood water concentration indicated a mean size of V of 5.9 l (+/- 0.8, SEM) for Ringer's solution, 2.6 (+/- 0.3) l for dextran, and 1.2 (+/- 0.1) l for hypertonic saline. The corresponding values of kr were 94 (+/- 42), 12 (+/- 6), and 30 (+/- 4) ml/min, respectively. Blood hemoglobin indicated a degree of dilution similar to that indicated by blood water. Serum albumin indicated a more pronounced dilution, which resulted in a larger expandable volume and a greater mean square error for the curvefitting. The larger volume obtained for serum albumin can probably be explained by a loss of intravascular albumin into the tissues along with the infused fluid.     

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 (k (r)) 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).     

Intra‐operative colloid administration increases the clearance of a post‐operative fluid load

Background: It is unknown whether an intra‐operative colloid infusion alters the dynamics of a crystalloid load administered post‐operatively. Methods: Ten patients received 12.5 ml/kg of Ringer's lactate over 30 min 1–3 days before and 4 h after laparoscopic cholecystectomy, during which 10 ml/kg of a colloid solution, hydroxyethylstarch (HES 130/0.4), was infused. The total body clearance of the pre‐ and post‐operative test infusions was taken as the ratio between the urinary excretion and the Hb‐derived dilution of venous plasma over 150 min. The plasma clearance of the infused fluid was calculated using volume kinetics based on the plasma dilution alone. The pre‐operative plasma clearance was compared with the post‐operative plasma clearance and patients served as their own control. Results: The urinary excretion averaged 350 ml for the pre‐operative infusion and 612 ml post‐operatively, which corresponds to 46% and 68% of the pre‐ and post‐operative infusions, respectively. The total body clearance of the crystalloid fluid was 30 ml/min before surgery and 124 ml/min after surgery (P<0.01). The plasma clearance, as obtained from the plasma dilution alone, was 28 and 412 ml/min, respectively. The maximal increase in plasma volume was 410 ml pre‐operatively vs. 220 ml post‐operatively. Conclusions: Infusion of a colloid solution in combination with a crystalloid during laparoscopic cholecystectomy increased the plasma clearance of a post‐operative crystalloid infusion.