Plasma atrial natriuretic peptide concentration and renin activity during overhydration with 1.5% glycine solution in conscious sheep

We estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls. Glycine infusions resulted in a four-fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP-stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the “transurethral resection (TUR) syndrome”. The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow-up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration. The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance. © 1994 Wiley-Liss, Inc.     

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.     

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.     

Natriuresis and "dilutional" hyponatremia after infusion of glycine 1.5%

STUDY OBJECTIVE: To challenge the view that the hyponatremia resulting from absorption of glycine 1.5% is attributed to the expansion of the extracellular fluid (ECF) volume, and that the change in serum sodium is therefore widely used to calculate the amount of irrigant absorbed. DESIGN: Retrospective analysis of six studies. SETTING: University-affiliated hospital. MEASUREMENTS: Approximately 1.2 L of glycine 1.5% was infused in 23 volunteers (two studies), 1 L in 10 prostatectomy patients, 2.4 L in 6 sheep, 4 L in 6 other sheep, and 3 L in 9 piglets. The distribution of the irrigant water was estimated from the difference between the measured and the expected serum sodium levels, taking into account the urinary losses of sodium and water. MAIN RESULTS: Between 30% and 50% of the irrigant volume had diffused into the cells 30 minutes after the infusion, and only between 0% and 50% of the fluid remained in the ECF. One hour later, natriuresis accounted for 100% of the residual hyponatremia in the small-volume experiments, and it accounted for approximately 50% in the large-volume experiments. The change in serum sodium could not be used to quantify the small infusion volumes, but the large ones could be quantified fairly accurately if assessed at the very end of the infusion. CONCLUSIONS: Diffusion of water into the cells and natriuresis reduced and prolonged the hyponatremia associated with infusions of glycine 1.5%. This finding makes IV fluid with sodium added a more rational alternative than furosemide in the treatment of fluid overload with this irrigating solution.     

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.     

Glycine toxicity after high-dose i.v. infusion of 1.5% glycine in the mouse

Glycine 1.5% is the most widely used irrigating fluid during endoscopic procedures. To investigate if glycine toxicity is a mechanism promoting a fatal outcome when the solution is absorbed, we administered glycine 200 or 300 ml kg-1 dissolved in sterile water or normal saline, and also normal saline alone, over 60 min by i.v. infusion to 100 mice under methoxyflurane anaesthesia. Survival rates were 29% after 1.5% glycine, 21% after 1.5% glycine in normal saline, 67% after normal saline and 100% in controls. Both solutions containing glycine induced bradycardia and prolongation of the PQ interval and QRS duration, while only 1.5% glycine increased the water content of the myocardium. These results suggest that glycine promotes bradycardia and death, regardless of whether hyponatraemia or hypo-osmolality is present. We conclude that glycine toxicity is an important factor that increases the risk of administration of an irrigating fluid.      

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.     

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 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.     

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.     

Haemodynamics and fluid balance after intravenous infusion of 1.5% glycine in sheep

With the aim of studying the pathophysiological background of the “TUR syndrome”, we gave six conscious ewes an intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min. Isotonic saline infusions served as controls. Central haemodynamics were monitored. The plasma concentrations of protein, K, Na and vasopressin, and plasma osmolality were measured repeatedly for up to 4 h. The urinary excretions of Na, K and osmoles were also followed. Both infusions caused an elevation of the mean arterial pressure. With glycine, the pressure increased from 93 ± 4 to 112 ± 12 mmHg (12.4 ± 0.5 to 14.9 ± 1.6 kPa) (mean ± s.d.). The pulmonary capillary wedge pressure increased from 7±3 to 16±3 mmHg (0.9 ± 0.4 to 2.1 ± 0.4 kPa) and remained slightly elevated. The central venous pressure rose from 2 ± 3 to 11 ± 3 mmHg (0.3 ± 0.4 to 1.5 ± 0.4 kPa) but returned to baseline within 30 min after the infusion. Infusion of glycine resulted in a decrease in the plasma Na concentration from 144 ± 3 to 114 ± 4 mmol/l. The plasma osmolality decreased from 290 ± 2 to 280 ± I mosmol/l, and remained low. There was a median 6-fold increase in plasma vasopressin concentration, while saline did not elicit vasopressin release. Despite the absence of electrolytes in glycine solution, the urinary excretion of sodium amounted to 106 ± 40 mmol. We conclude that i.v. infusion of 1.5% glycine solution in sheep causes a transient circulatory strain and natriuresis. Moreover, a vasopressin-mediated reduction of maximal water excretion contributes to persisting hypoosmolality.     

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.     

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.     

Glycine solution as an irrigating agent during transurethral prostatic resection. Glycine concentrations in blood plasma

In 17 men undergoing transurethral resection of the prostate (TURP), an isosmotic solution of 2.2% glycine was used for irrigation. The plasma glycine concentration was determined before and immediately after TURP and 2, 6, 24 and 48 hours later. The serum concentrations of sodium, albumin and prostatic acid phosphatase protein (PAP) were used as indicators of fluid absorption. Calculation of the absorbed fluid volume was based on the plasma concentration of glycine, and the disappearance rate of glycine from plasma was estimated. The mean disappearance rate (T 1/2) was 85 min, which was midway between previously observed rates for sorbitol and mannitol. The observed plasma glycine increase after TURP correlated well with fall in serum sodium and rise in serum PAP, with the blood loss during and up to 15 min after TURP, and also with the weight of the resected tissue. The plasma glycine level, highest immediately after TURP, normalized 24-48 hours postoperatively. No signs of ammonia intoxication or marked serum urea increase were seen in these patients, although some had very high plasma glycine values after TURP (mean 10.2, maximum 23 mmol/l) as compared with the preoperative levels (mean 0.2 mmol/l). There was some increase of plasma serine (a normal metabolite of glycine) after TURP. The authors conclude that the irrigating fluid should have a minimal concentration of glycine, near to the level of haemolysis onset, to minimize the plasma dilution effects, including hyponatraemia, and the appearance of metabolites when the irrigating fluid is absorbed.     

PHYSICOCHEMICAL CHANGES DURING HAEMORRHAGE AND FOLLOWING INFUSION

Interstitial fluid pressure (IFP) and plasma colloid osmoticpressure (plasma COP) were measured in dogs following acutehaemorrhage and following the infusion of saline, 10% dextran40 in saline and 3% dextran 40 in lactated Ringer's solution.Exsanguination decreased IFP, plasma COP and total plasma proteinand albumin concentrations, and increased plasma glucose concentrationand osmotic pressure. A massive infusion of physiological salineincreased IFP, and decreased plasma COP and total plasma proteinand albumin concentrations. The volume of saline infused correlatedwith the increase in IFP. When a 10% dextran 40 saline solutionwas used, there was a marked increase in plasma COP but a decreasein IFP. When 3% dextran 40 in lactated Ringer's solution wasinfused, IFP was little affected in the early stage, but graduallyincreased thereafter. Plasma COP increased slightly immediatelyafter infusion, but remained near the pre-exsanguination valuefor at least 3 h.     

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.     

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.     

Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969

BACKGROUND: The purpose of this study was to determine the changes in the plasma concentration of rocuronium and the reversal of its neuromuscular blockade after the intravenous infusion of Org 25969, the novel neuromuscular block-reversal agent, in anesthetized guinea pigs. METHODS: Rocuronium was infused for 1 h at a rate of 12-19 nmol.kg-1.min-1 to produce a steady-state 90% neuromuscular block. After 30 min, a concomitant infusion of either the reversal agent Org 25969 at a rate of 50 nmol.kg-1.min-1 or an infusion of an equivalent volume of saline was started. The time course of plasma concentrations of rocuronium was determined by use of liquid chromatography-mass spectrometry/mass spectrometry. RESULTS: In both treatment groups, a steady-state plasma concentration of rocuronium was obtained after 30 min. In the saline-treated group, the plasma concentration of rocuronium and depth of block remained constant. In the Org 25969 group, neuromuscular block was reversed while the rocuronium infusion was ongoing. Simultaneously, an increase in the total plasma concentration of rocuronium (free and complexed) was observed, even though the infusion rate of rocuronium was not changed. Compared with the saline-treated group, a small increase in the postmortem bladder concentration of rocuronium was detected. CONCLUSIONS: The authors propose that the capture of rocuronium by Org 25969 causes the rapid reversal of neuromuscular block. The reversal can be explained by the rapid transfer of free rocuronium from the effect compartment (neuromuscular junction) to the central compartment, in which it is bound to Org 25969. This explains the increase in total plasma concentration of rocuronium (free and bound to Org 25969).