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.

[The peritoneal kinetic study performed with hypertonic glucose permits better evaluation of UF capacity and determination of sieving of sodium]. / Las cinéticas con glucosa hipertónica permiten identificar mejor el fallo de ultrafiltración. ¿Qué aporta el cribado de sodio?

INTRODUCTION: The use of solutions containing hypertonic glucose (3.86%/4.25%) has been postulated as the method of choice for study the peritoneal function, and permits a better evaluation of the ultrafiltration (UF) capacity. OBJECTIVE: The aim of our study was to analyze the UF capacity and its relation with the peritoneal permeability and sieving of sodium, performing the peritoneal kinetic study with hypertonic glucose solutions. PATIENTS AND METHODS: We performed 184 peritoneal kinetic studies with hypertonic glucose solutions in stable patients on peritoneal dialysis (PD), with a mean time on PD of 16 +/- 22 months. We measured the mass transfer coefficient of creatinine (CrMTC), dialysate to plasma ratio of creatinine (D/PCr), UF capacity and sieving of sodium at 60 minutes (difNa60). RESULTS: The mean values were: CrMTC: 9.1 +/- 4.5 ml/min, D/PCr: 0.71 +/- 0.09, UF 759 +/- 233 ml/4 h and difNa60: 4.7 +/- 2.3. The best multivariate model that predicts the UF capacity included: difNa60, CrMTC, age and time on PD (r = 0.57; p > 0.0001). In patients with UF lower than 600 ml/4 h (Percentil 25) the correlation between UF and CrMTC was lost, but remains the correlation with difNa60 (r = 0.48). The patients with previous peritonitis (n = 38) showed no differences in UF, CrMTC or D/Pcr, but the had lower difNa60 (3.7 +/- 2.8 vs. 4.9 +/- 2.1; p = 0.002) than the remaining patients. CONCLUSIONS: The peritoneal kinetic study performed with hypertonic glucose allows to standardize the UF capacity and by determination of sieving of sodium, the early detection of water transport alterations, before the UF capacity and small solutes permeability alteration develops.

Fluid restriction during running increases GI permeability.

The purpose of this study was to determine gastrointestinal (GI) permeability during prolonged treadmill running (60 min at 70 % V.O2max) with and without fluid intake (3 ml/kg body mass/10 min). Twenty runners (11 males, 9 females; age = 22 +/- 3 (SD) yrs; mean V.O2max = 55.7 +/- 5.0 ml/kg/min) completed four experiments: 1) rest, 2) running with no fluid (NF), 3) running with ingestion of a 4 % glucose solution (GLU), and 4) running with ingestion of a water placebo (PLA). To determine GI permeability, subjects also drank a solution containing 5 g sucrose (S), 5 g lactulose (L), and 2 g rhamnose (R) immediately prior to each trial. Gastroduodenal permeability was determined by urinary S excretion, while small intestinal permeability was determined by the L/R excretion ratio. Percent body mass loss (i.e., dehydration) was negligible during rest, GLU and PLA, while NF resulted in a 1.5 % loss of body mass (p < 0.05). Gastroduodenal and intestinal permeability were significantly (p < 0.008) increased in NF compared to rest. There were no other differences in GI permeability. These results indicate that fluid restriction during 1 h of steady-state running increases GI permeability above resting levels.

A randomized controlled trial of the anticatabolic effect of epidural analgesia and hypocaloric glucose.

BACKGROUND AND OBJECTIVES: The goal of the present study was to investigate whether epidural analgesia exerts a protein-sparing effect after colorectal surgery in the presence of hypocaloric glucose supply initiated with surgical skin incision. METHODS: We randomly allocated 10 patients to receive general anesthesia combined with epidural anesthesia with bupivacaine, followed by epidural analgesia using bupivacaine/fentanyl, and 10 patients to receive general anesthesia, followed by patient-controlled analgesia with intravenous morphine. All patients received a 48-hour infusion of glucose 10% from surgical skin incision until the second day after surgery. The glucose infusion rate provided 50% of the patient's resting energy expenditure. Kinetics of protein and glucose metabolism were assessed by a stable-isotope tracer technique (L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose). RESULTS: The rate of appearance of leucine increased in the intravenous-analgesia group (112 +/- 29 to 130 +/- 25 micromol/kg/h) 2 days after surgery, and this increase was more pronounced than in the epidural analgesia group (preoperative 120 +/- 24, postoperative 123 +/- 22 micromol/kg/h, P < .05). Leucine oxidation rate increased in the intravenous analgesia group from 17 +/- 8 to 23 +/- 8 micromol/kg/h and in the epidural group from 17 +/- 6 to 19 +/- 7 micromol/kg/h without the difference between the groups reaching statistical significance (P = .067). Nonoxidative leucine disposal remained unaltered in both groups. No differences in glucose metabolism were seen between the groups. CONCLUSIONS: Epidural analgesia inhibits the increase in whole-body protein breakdown in patients receiving perioperative hypocaloric glucose infusion initiated with surgical skin incision. However, oxidative protein loss, protein synthesis, and glucose metabolism are not affected by epidural analgesia.

[Relation between glucose concentrations in cerebrospinal fluid and sensory and motor block during spinal anesthesia with hyperbaric bupivacaine]. / Relación de los niveles de la glucorraquia con el bloqueo sensitivo y motor durante la anestesia raquídea con bupivacaína hiperbara.

OBJECTIVE: To study the relation between cerebrospinal fluid (CSF) glucose levels, the highest level of sensory block, and the duration of motor block after intrathecal injection of 2 mL of hyperbaric bupivacaine. To determine CSF glucose levels upon recovery from motor block. PATIENTS AND METHODS: A prospective study of 34 patients administered a spinal anesthetic in continuous infusion through a 22-gauge catheter. CSF samples were extracted through the catheter 5, 10, 15, 20, 30, 45, and 60 minutes after start of infusion and upon motor recovery. After each extraction the intensity of the motor block was assessed; the intensity of the sensory block was assessed after each extraction up to 20 minutes. RESULTS: Glucose concentrations in CSF tended to decrease from 5 minutes (1027.07 [SD 349.04] mg dL(-1)) until full motor recovery (247.50 [20.39] mg dL(-1)). The probability of finding a motor block at a CSF glucose concentration of 287.5 mg dL(-1) or higher was less than 5%. We identified a positive correlation between the highest level of sensory block and the duration of full motor block (r=0.62, P<0.01) and between CSF glucose levels at the moment of greatest sensory block and upon full motor recovery (r=0.50, P<0.01). CONCLUSIONS: After continuous spinal anesthesia with hyperbaric bupivacaine, glucose concentrations in CSF are directly related to the highest level of sensory block, the course of the blockade, and its reversal.

Relación de los niveles de la glucorraquia con el bloqueo sensitivo y motor durante la anestesia raquídea con bupivacaína hiperbara / Relation between glucose concentrations in cerebrospinal fluid and sensory and motor block during spinal anesthesia with hyperbaric bupivacaine

OBJETIVO: Estudiar la relación de la glucorraquia conel nivel más alto del bloqueo sensitivo y con la duracióndel bloqueo motor después de la administración intratecalde 2 mL de bupivacaína hiperbara. Averiguar lascifras de glucorraquia al finalizar el bloqueo motor.PACIENTES Y MÉTODOS: Estudio prospectivo de 34pacientes bajo anestesia espinal continua con un catéter22 G, a través del cual se extraen muestras de líquidocefalorraquídeo para determinar la glucorraquia a los 5,10, 15, 20, 30, 45, 60 minutos y al final del bloqueomotor. Después de cada extracción se valora el grado delbloqueo motor y durante los primeros 20 minutos elnivel del bloqueo sensitivo.RESULTADOS: Se observa una tendencia descendente delos niveles de glucorraquia desde los 5 minutos (1027,07 ±349,04 mg dL-1), hasta el final del bloqueo motor completo(247,50 ± 20,39 mg dL-1). La probabilidad de no encontrarbloqueo motor con cifras de glucorraquia de 287,5 mgdL-1 o superiores es menor del 5%. Identificamos unacorrelación positiva entre el nivel más alto de bloqueo sensitivoy la duración del bloqueo motor completo (r = 0,62,p < 0,01) y entre las glucorraquias obtenidas en el momentodel nivel más alto de bloqueo sensitivo y al final del bloqueomotor completo (r = 0,50, p <0,01).CONCLUSIÓN: Después de una anestesia espinal continuacon bupivacaína hiperbara, la glucorraquia guardauna relación directa con el nivel más alto de bloqueosensitivo, la evolución y el final del bloqueo motor

OBJECTIVE: To study the relation between cerebrospinalfluid (CSF) glucose levels, the highest level of sensoryblock, and the duration of motor block after intrathecalinjection of 2 mL of hyperbaric bupivacaine. Todetermine CSF glucose levels upon recovery from motorblock.PATIENTS AND METHODS: A prospective study of 34patients administered a spinal anesthetic in continuousinfusion through a 22-gauge catheter. CSF samples wereextracted through the catheter 5, 10, 15, 20, 30, 45, and60 minutes after start of infusion and upon motor recovery.After each extraction the intensity of the motorblock was assessed; the intensity of the sensory blockwas assessed after each extraction up to 20 minutes.RESULTS: Glucose concentrations in CSF tended todecrease from 5 minutes (1027.07 [SD 349.04] mg dL-1)until full motor recovery (247.50 [20.39] mg dL-1). Theprobability not to find a motor block at a CSF glucoseconcentration of 287.5 mg dL-1 or higher was less than5%. We identified a positive correlation between the highestlevel of sensory block and the duration of full motorblock (r=0.62, P<0.01) and between CSF glucose levels atthe moment of greatest sensory block and upon fullmotor recovery (r=0.50, P<0.01).CONCLUSIONS: After continuous spinal anesthesia withhyperbaric bupivacaine, glucose concentrations in CSFare directly related to the highest level of sensory block,the course of the blockade, and its reversal

Evaluation of intraperitoneal pressure and the effect of different osmotic agents on intraperitoneal pressure in children.

OBJECTIVES: To establish intraperitoneal pressure (IPP) in a relatively large pediatric study group and to study the effects of a 3.86% glucose solution and a 7.5% icodextrin solution on IPP during a 4-hour dwell. DESIGN: IPP was measured with the patient in a supine position. The intraperitoneal volume (IPV) was 1200 mL/m2 with a 1.36% glucose solution. The influence of dialysis solutions was obtained by performing two 4-hour peritoneal equilibration tests (PETs) with 3.86% glucose and 7.5% icodextrin as test solution, using an IPV of 1200 mL/m2 and dextran 70 as volume marker. IPP was measured at two consecutive time points (t = 0 and t = 240 minutes). Transcapillary ultrafiltration, net ultrafiltration, and marker clearance were calculated. PATIENTS: IPP was established in 30 patients with median age of 4.5 years (range 1.0 - 14.9 years). Influence of dialysis solutions on IPP was studied in 9 children with median age of 4.2 years (range 1.7 - 10.9 years) and median treatment period of 12 months (range 5.6 - 122.3 months). RESULTS: Mean IPP was 12.0 +/- 6.5 cm H2O. Significant relations were found between the change in IPP and transcapillary ultrafiltration and body surface area during the PET with 3.86% glucose. No relations were seen during the PET with icodextrin. CONCLUSIONS: IPP was established in a large pediatric study group and was similar to previously published values of IPP in a small number of patients. Differences in fluid kinetics have different effects on the change in IPP during a 4-hour dwell period.

Effects of vasodilators on peritoneal solute and fluid transport in rat peritoneal dialysis.

The pharmacological manipulation by vasodilators of peritoneal solutes and fluid kinetics was investigated. Rats were dialyzed for 240 minutes with 30 mL 4.25% glucose dialysate containing dextran 70. An angiotensin-converting enzyme inhibitor (captopril), three calcium channel blockers (nicardipine, diltiazem, and verapamil), and an +/-blocker (maxisylite) were administered intraperitoneally at various concentrations. Membrane permeability to urea, glucose, and protein, actual net ultrafiltration rate (UFR), transcapillary ultrafiltration rate (TCUFR), and peritoneal net fluid absorption rate (PNFAR) were measured. All three vasodilators caused a decrease in blood pressure, which, except for moxisylite, was associated with a decrease in net UFR. Captopril and the three calcium antagonists increased PNFAR dose dependently. Captopril increased membrane permeability to small and large molecular solutes, with a consequent decrease in TCUFR. Nicardipine and verapamil increased permeability to urea and glucose but not to protein. Only the latter decreased TCUFR. Diltiazem caused no change in permeability. In conclusion, various vasodilators administered intraperitoneally affect peritoneal solute and fluid transport differently. This should, perhaps, be taken into consideration when working with continuous ambulatory peritoneal dialysis (CAPD) patients to whom antihypertensive drugs are administered in large doses.

Calcium lactate interference in measuring creatinine in peritoneal dialysis fluids by the Jaffé kinetic method.

Creatinine measurements in peritoneal dialysis fluids using the Jaffé method have poor specificity due to interfering substances. We have checked to see if calcium lactate, in addition to glucose, interferes with the Jaffé kinetic measurement. Eight samples were prepared with increasing concentrations of glucose (960-3890 mg/dL) and eight were prepared with the same glucose content plus 7 mg/dL of calcium lactate, all without creatinine; in addition, 96 samples with increasing concentrations of glucose (1500-4000 mg/dL), calcium lactate (3-7.5 mg/dL), and creatinine (0.75-4.5 mg/dL) were prepared. There was a 0.31 +/- 0.13 mg/dL glucose interference on the Jaffé kinetic measurement in the first series, with an exponential trend. Interference was greater with calcium lactate and glucose: 0.50 +/- 0.16 mg/dL with the same trend. Data from the second series confirm the overestimation: 0.54 +/- 0.05 mg/dL (32.6%) with an exponential trend. The interference of glucose, creatinine, and calcium lactate on the Jaffé kinetic measurement was obtained by multi-variate regression. The single effects of glucose2 and glucose are predominant, but both creatinine and calcium lactate have a significant effect. Our study highlights the nonlinear glucose interference on creatinine measurement with the Jaffé kinetic method and the linear interference of both calcium lactate and creatinine.

Optimal use of glucose polymer (icodextrin) in peritoneal dialysis.

The osmotic effectiveness of glucose polymer is now well established. The relative inertness of this macromolecular compound has been the key factor in its success as the first "colloid" osmotic agent in clinical use. In its present form, it produces sustained ultrafiltration for up to 12 hours, and a daily overnight use would obviate the need for hypertonic exchanges, especially 3.86% glucose. In addition, it could be used in automated peritoneal dialysis regimes to enhance ultrafiltration and solute clearance during the daytime. Preliminary reports also indicate that it is beneficial in diabetic patients and in some patients who have lost ultrafiltration. The new "bimodal" formulations look promising, with the potential to replace all the currently used hyperosmolar exchanges with physiological solutions. Although systemic accumulation of glucose polymer breakdown products occurs, it reaches steady-state levels quickly (within two weeks) and remains stable throughout the duration of polymer use. In the long-term study, these levels of maltose and oligosaccharides over three-and-a-half years represent the longest exposure of these substances in uremic patients without any clinical or metabolic adverse effects and provide an important evidence of safety. Future work based on studies that are ongoing suggest that a family of physiological solutions ("bimodal" preparations in iso-osmolar combination) could be available, and the individual's dialysis prescription could be tailored to take into account the ultrafiltration, metabolic needs, as well as the long-term viability of the membrane. Glucose polymer will be a key component of such solutions.

[Failure to thrive in young children--disorders of carbohydrate absorption?]. / Gedeihstörungen bei Kleinkindern--Störungen der Kohlehydratresorption?

We examined 31 formerly hypotrophic newborn children (birth weight < 5th Kyank percentile) with failure to grow in infancy (weight < 3th Prader percentile). The rates of digestion and absorption of carbohydrates were determined by segmental perfusion of the small intestine and compared to the results of 21 patients with florid coeliac disease. Despite the normal structure of the mucous membrane of the small intestine, the rates of absorption of glucose in 14 formerly hypotrophic children and, additionally, in 12 and 10 of these children, respectively, the rates of hydrolysis of lactose and sucrose were nearly as low as in patients with florid coeliac disease. The reduced absorption and digestion of carbohydrates, respectively, could be a cause of subsequent failure to grow in some of the hypotrophic newborn children.

[Carbohydrates in parenteral nutrition solutions in pediatrics--a critical evaluation]. / Kohlenhydrate in parenteralen Nährlösungen für die Pädiatrie--eine kritische Bewertung.

Application of carbohydrates in pediatric infusion therapy has recently been limited to glucose and xylitol. Fructose and sorbitol, which formerly had been used widely as energy sources in parenteral nutrition, have meanwhile been banned in order to prevent fatal complications in patients with undiscovered hereditary disturbances in fructose metabolism. The aim of this review is to focus the attention on potential side effects and limitations of glucose administration in pediatric infusion therapy. With special regard to total parenteral nutrition in preterm infants, sufficient glucose conversion to N-acetylneuraminic acid and other carbohydrate building blocks of glycoproteins and gangliosides is to be placed in question. This might have consequences for normal brain development and can be considered a challenge for future research work in this field.

Retention of glucose in oral fluid at different sites in the mouth.

Using glucose as a marker, a detailed study of retention at 5 different sites in the mouth of 1 subject and a less detailed examination of 4 selected sites in the mouths of 10 other subjects revealed site-specific differential patterns of oral retention (or clearance). These patterns seemed independent of sometimes large, absolute day-to-day variations in oral retention which occur in all subjects but appeared to vary somewhat between subjects, probably reflecting slight differences in the anatomy and physiology of the individual mouth. In general, the patterns resembled those recently derived from studies of other oral phenomena such as rates of diffusion out of plaque, fluoride uptake by mineral and hydrogen ion concentrations in plaque. They will dictate the concentrations and thereby influence the activity of all extraneous substances in different regions of the oral cavity and may relate to the site-specific patterns of oral disease.

Prolonged intraperitoneal dwell decreases ultrafiltration coefficient in rabbits.

In rabbits undergoing peritoneal dialysis, hypertonic (6% dextrose) dialysis solution increased the net ultrafiltration rate (UF) from 233 to 462 microL/kg/min, which was not proportional to the increment in the osmotic gradient, so the ultrafiltration coefficient decreased. As intraperitoneal dwell of hypertonic dialysate was prolonged, the gross and net UFs and ultrafiltration coefficients decreased, and the UF per dextrose absorption declined. The decrement in UF was multifactorial, including a component of fluid and solute stagnation, increasing the distance over which osmotic forces must exert their effects. Excessively hypertonic dialysis fluid should be used only briefly to achieve ultrafiltration efficiently and to avoid the high dextrose loading.