Osmotic and Hemodynamic Effects of Hypertonic Glucose During Hemodialysis.

It was the purpose to quantify the hemodynamic effects of a bolus of hypertonic glucose injected into the extracorporeal system in a group of stable and nondiabetic patients during hemodialysis (HD). Glucose and electrolytes were measured in frequent intervals. Arterial blood pressures and heart rates were continuously recorded by noninvasive vascular unloading technique. Beat-to-beat stroke volume, cardiac output, and total peripheral resistance were determined by Modelflow method. Relative blood volumes were continuously measured by ultrasonic and optical means. Eight patients were studied in two treatments. Although arterial pressures and heart rates remained stable, stroke volume and cardiac output transiently increased above (19.2 ± 12.3%) and total peripheral resistance dropped below baseline (18.2 ± 8.6%) by a comparable magnitude. Relative blood volume transiently increased above baseline at 100% (104.9 ± 1.0%). Glucose concentrations were significantly related to relative blood volumes (r = 0.86, p < 0.001). In spite of a substantial increase in blood volume, a bolus of hypertonic glucose does not increase arterial pressures in nondiabetic patients because of concomitant vasodilatation. The relative increase in blood volume quantified by noninvasive HD technology follows the course of glucose and could be used as a surrogate to characterize patients with regard to their glucose metabolism during HD.

Sensitivity of Hematocrit to Osmotic Effects Induced by Changes in Dialysate Conductivity: Implications for Relative Blood Volume Measurement and Control.

Hemodialysis is accompanied by osmotic perturbations with distinct effects on red blood cell, plasma, and blood volumes. A series of in vitro studies was done to analyze the separate effect on cell volume. Whole porcine blood was circulated through an extracorporeal circulation maintaining a constant blood volume. Hemoconcentration was continuously measured by established optical and ultrasonic online techniques. Osmotic perturbation was performed by variation of dialysate conductivity within the clinical range of 13-15 mS/cm. Blood samples were analyzed using a microcentrifuge and a standard cell counter. As dialysate conductivity increased, centrifuge hematocrit (in %) decreased with a slope of -1.91% per unit of conductivity in mS/cm (r2 = 0.98). At the same time, Coulter-Counter hematocrit slightly decreased only by -0.18% (r2 = 0.53), while optical and ultrasonic hematocrit showed a small increase by 0.44% (r2 = 0.97) and 0.69% (r2 = 0.94) per unit of conductivity in mS/cm. The sensitivity to osmotic perturbation is consistent with theory and with specific characteristics of measuring techniques used in this study. The differences, however, need to be considered when comparing measurements obtained by different techniques. Finally, devices used for relative blood volume measurement in hemodialysis should be insensitive to osmosis-induced changes in red blood cell volume.

A simple method for vital staining of elastin in arterial tissue.

Highly diluted solutions of Gentian Violet and Evans Blue were used to visualize the elastin network in viable porcine right common carotid artery (RCCA) preparations. The two simple, alternative methods of staining were applied to proximal, intermediate, and distal sections of RCCA under various experimental conditions. These included the state of the vessel wall soon after excision, under relaxed smooth muscle condition after preconditioning, and during vasoconstriction. Micrographs of arterial rings, sectors, and axial strips show that the RCCA is an artery of the elastic type at the proximal end and of the muscular type at the distal end. While in sections of freshly dissected or KCl-constricted arteries the elastic lamellae show the well-known waviness, those in sections from arteries with relaxed smooth muscle and after preconditioning appear nearly straight. It is hoped that the inexpensive staining tools will contribute to solve conflicting interpretations existing on elastin structures in the arterial wall.

Internal filtration, filtration fraction, and blood flow resistance in high- and low-flux dialyzers.

It was the aim to examine the fluid flow in blood and dialysate compartments of highly permeable hollow fiber dialyzers where internal filtration contributes to solute removal but where excessive filtration bears a risk of cell activation and damage. Flow characteristics of high- (HF) and low-flux (LF) dialyzers were studied in lab-bench experiments using whole bovine blood. Measurements obtained under different operating conditions and under zero net ultrafiltration were compared to theoretical calculations obtained from a mathematical model. Experimental resistances in the blood compartment were within ±2% of those calculated from the model when dialysate was used as a test fluid. With whole blood, the experimental resistances in the blood compartment were only 81.8 ± 2.8% and 83.7 ± 4.3% of those calculated for the LF and HF dialyzer, respectively. Surprisingly, measured blood flow resistance slightly but significantly decreased with increasing flow rate (p < 0.001). Mathematical modeling confirmed this decrease both in LF and HF dialyzers which was accompanied by a concomitant decrease in internal filtration fraction, while overall internal filtration increased. The increase in internal filtration when increasing blood flow is associated with a beneficial reduction in internal filtration fraction. Concerns of increased hemoconcentration when increasing blood flow therefore appear to be unwarranted.

Internal filtration in a high-flux dialyzer quantified by mean transit time of an albumin-bound indicator.

Internal filtration in high-flux (HF) dialyzers significantly contributes to convective solute removal of molecules with poor diffusibility, but it is difficult to quantify. The aim of this study was to present the theory and to develop a method for measuring internal filtration and backfiltration in HF dialyzers, which also could be applied to patient studies. In a series of lab-bench experiments, the mean transit times (τd) of indocyanine green (ICG) passing the dialyzer were optically measured under different operating conditions and compared with mean transit times calculated from the known volume of the blood compartment (τV) using a mathematical model. τd was always larger than τV. The relative difference in mean transit times (1 - τV/τd) was related to the average cumulative filtration rate (Qfil). The internal filtration fraction Fb = Qfil/Qb was largely independent of blood flow (Qb) and not different from theoretical predictions obtained from a mathematical model. The dispersion of a nondiffusible indicator such as ICG can be used to quantify the magnitude of internal filtration and backfiltration in HF dialyzers using available technology. This information could be useful for testing the HF dialyzers in everyday situations.

Clearance, distribution volume, and dialyzer mass area transport coefficient of glucose in whole blood.

The extracorporeal transport of glucose was studied to determine the dialyzer mass transfer coefficient K(0)A for glucose in whole blood under conditions of glucose delivery and glucose removal. Glucose was removed from blood or delivered to blood using glucose-free dialysate or dialysate with a glucose concentration of 200 mg/dl (11.1 mmol/L). FX8 dialyzers (Fresenius Medical Care, Bad Homburg, Germany) were studied at constant dialysate flow Q(d) (500 ml/min) and variable blood flows Q(b) (200, 300, and 400 ml/min) under countercurrent flow conditions in a series of laboratory bench studies. Glucose clearance K(d) and glucose distribution volume flow rate Q(e) were determined from glucose mass balance. In 32 studies done with bovine blood at different hematocrit levels glucose was calculated to distribute in plasma water and to be excluded from red cell water when passing the FX8 dialyzer. The dialyzer mass transfer area coefficient K(0)A for glucose computed from Q(e), Q(d), and K(d) was 301.6 ± 45.2 ml/min and not different between modes of glucose delivery or glucose removal but lower than expected from the diffusivity of glucose estimated for aqueous solutions.

Blunted insulinemia using high dialysate glucose concentration during hemodialysis.

The benefit of high glucose concentrations in the dialysate remains under debate. The aim of this study was to analyze and to compare the acute insulin response using a common but high glucose concentration in the dialysate representing a parenteral mode of glucose administration to oral glucose administration in stable and fasting nondiabetic hemodialysis patients during their routine hemodialysis session. Glucose was either given by a standardized oral load (75 g) or using a glucose concentration of 11.1 mmol/L (200 mg/dL) in the dialysate for the duration of an hour. The insulin response per unit glucose stimulus was determined from the slope of paired insulin and glucose concentrations measured in 15-minute intervals using standard techniques. This slope is mathematically equivalent to the insulinogenic index (IG) and has been shown to be independent of extracorporeal clearance by ongoing hemodialysis. In 10 subjects, the IG was 9.3 ± 2.6 U/mol with oral glucose delivery but only one-third of that value (3.0 ± 1.1 U/mol, p < 0.001) when glucose was delivered through the dialysate. Administration of glucose using dialysate thus leads to a blunted insulin response per unit glucose stimulus. This may cause prolonged hyperglycemia which should be avoided in patients treated with hemodialysis.

More may be less: increasing extracorporeal blood flow in an axillary arterio-arterial access decreases effective clearance.

Axillary arterio-arterial graft interposition has been described as a reasonable haemodialysis access in selected patients. In a patient with this unusual access, we measured and calculated effective clearance at different extracorporeal blood flows (Q(b)). Effective clearance increased with increasing blood flow and reached a maximum at a Q(b) of ~200 mL/min but then decreased when Q(b) was increased further. As this type of access typically provides low access flow, one has to be aware that local recirculation will easily occur. Therefore, a Q(b) above access flow has to be avoided since any increase beyond that threshold reduces effective clearance.