A Slow-Exchange Interstitial Fluid Compartment in Volunteers and Anesthetized Patients: Kinetic Analysis and Physiology.

BACKGROUND: Physiological studies suggest that the interstitial space contains 2 fluid compartments, but no analysis has been performed to quantify their sizes and turnover rates. METHODS: Retrospective data were retrieved from 270 experiments where Ringer's solution of between 238 and 2750 mL (mean, 1487 mL) had been administered by intravenous infusion to awake and anesthetized humans (mean age 39 years, 47% females). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed-models software. RESULTS: The kinetic analysis successfully separated 2 interstitial fluid compartments. One equilibrated rapidly with the plasma and the other equilibrated slowly. General anesthesia doubled the rate constants for fluid entering these 2 compartments (from 0.072 to 0.155 and from 0.026 to 0.080 min -1 , respectively). The return flows to the plasma were impeded by intensive fluid therapy; the rate constant for the fast-exchange compartment decreased from 0.251 to 0.050 when the infusion time increased from 15 to 60 minutes, and the rate constant for the slow-exchange compartment decreased from 0.019 to 0.005 when the infused volume increased from 500 to 1500 mL. The slow-exchange compartment became disproportionately expanded when larger fluid volumes were infused and even attained an unphysiologically large size when general anesthesia was added, suggesting that the flow of fluid was restrained and not solely determined by hydrostatic and oncotic forces. The dependence of the slow-exchange compartment on general anesthesia, crystalloid infusion rate, and infusion volume all suggest a causal physiological process. CONCLUSIONS: Kinetic analysis supported that Ringer's solution distributes in 2 interstitial compartments with different turnover times. The slow compartment became dominant when large amounts of fluid were infused and during general anesthesia. These findings may explain why fluid accumulates in peripheral tissues during surgery and why infused fluid can remain in the body for several days after general anesthesia.

The Effects of Acute and Chronic Inflammation on the Dynamics of Fluid Shift of Ringer's Solution and Hemodynamics during Surgery.

The aim of this study was to investigate the influences of acute and chronic inflammation on the dynamics of fluid shift of Ringer's solution and hemodynamics in patients during surgery. Thirty-seven patients with the American Society of Anesthesiologists (ASA) grades I-II were enrolled and allocated to two study groups according to the type of disease and operation and inflammation, including patients undergoing emergency appendectomy (Acute group, n = 19) and patients undergoing elective cholecystectomy (Chronic group, n = 18). All of the patients were administered 15 mL/kg of Ringer's lactated (LR) solution at a constant rate over 35 min before the induction of anesthesia. Plasma dilution (PD), volume expansion (VE), volume expansion efficiency (VEE), and extravascular volume (EVV) were calculated based on the concentration of hemoglobin within 2 h post-infusion. Heart rate (HR), arterial blood pressure and urine output were also recorded. PD and VE peaked at the end of infusion, while VEE peaked at the beginning of infusion in all of the patients. After infusion, PD, VE and VEE in the Acute group were all higher than those in the Chronic group (p < 0.05). PD and VE were higher during anesthesia or surgery than during awake or non-surgery (p < 0.001). The mean arterial pressure (MAP) and diastolic pressure (DBP) in the Acute group were significantly lower (p < 0.001) and HR was significantly higher (p < 0.001) than in the Chronic group during the study periods. It was suggested that patients with acute inflammation be treated with individualized fluid therapy during surgery.

Kinetics of Ringer's Solution in Extracellular Dehydration and Hemorrhage.

BACKGROUND: Ringer's solution might be used to treat volume depletion (extracellular dehydration) and hemorrhage, but there is no integrated view of how these fluid balance disorders influence the kinetics of the infused volume. METHODS: Acute dehydration (mean 1.7 L) was induced by repeated doses of furosemide (5 mg) in 10 healthy male volunteers, and 0.5 L and 0.9 L of blood was withdrawn in random order on different occasions in another 10 male volunteers, just before administration of Ringer's acetate solution. Infusions performed in the normovolemic state served as controls. Measurements of blood hemoglobin and urinary excretion were used to create volume kinetic profiles that were analyzed using mixed-effects modeling software. RESULTS: Infusions over 15 to 30 min showed a marked distribution phase during which the plasma volume transiently increased by 50% to 75% of the administered volume. Dehydration and hemorrhage accelerated redistribution but retarded the elimination; the half-life of the infused fluid increased from 36 to 51 min (mean) from 1 L of dehydration and to 95 min from 1 L of hemorrhage. Extravascular accumulation decreased with the dehydration volume and increased with the hemorrhage volume.Simulations show that 60% as much Ringer is needed to replace volume depletion amounting to 1 L as compared with hemorrhage over a 2-h period. A continued but slower drip after the initial fluid resuscitation prevents rebound hypovolemia. CONCLUSIONS: Furosemide-induced dehydration and blood withdrawal in normotensive volunteers had modest effects on the Ringer's acetate kinetics. Urinary excretion was inhibited more by hemorrhage than by dehydration.

Understanding volume kinetics.

The distribution and elimination kinetics of the water volume in infusion fluids can be studied by volume kinetics. The approach is a modification of drug pharmacokinetics and uses repeated measurements of blood hemoglobin and urinary excretion as input variables in (usually) a two-compartment model with expandable walls. Study results show that crystalloid fluid has a distribution phase that gives these fluids a plasma volume expansion amounting to 50%-60% of the infused volume as long as the infusion lasts, while the fraction is reduced to 15%-20% within 30 minutes after the infusion ends. Small volumes of crystalloid barely distribute to the interstitium, whereas rapid infusions tend to cause edema. Fluid elimination is very slow during general anesthesia due to the vasodilatation-induced reduction of the arterial pressure, whereas elimination is less affected by hemorrhage. The half-life is twice as long for saline than for Ringer solutions. Elimination is slower in conscious males than conscious females, and high red blood cell and thrombocyte counts retard both distribution and re-distribution. Children have faster turnover than adults. Plasma volume expansions are similar for glucose solutions and Ringer's, but the expansion duration is shorter for glucose. Concentrated urine before and during infusion slows down the elimination of crystalloid fluid. Colloid fluids have no distribution phase, an intravascular persistence half-life of 2-3 hours, and-at least for hydroxyethyl starch-the ability to reduce the effect of subsequently infused crystalloids. Accelerated distribution due to degradation of the endothelial glycocalyx layer has not yet been demonstrated.

Effects of three infusion fluids with different sodium chloride contents on steady-state serum concentrations of bromide in dogs.

Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1  hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1  hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1  hr-1 for 5 hr.