Daniel Schneditz

Compartment effects in hemodialysis.

Compartment effects in hemodialysis are important because they reduce the efficiency of removal of the compartmentalized solute during dialysis. The dialyzer can only remove those waste products that are presented to it, and then only in proportion to the concentration of the solute in the blood. Classically a two‐compartment system has been modeled, with the compartments arranged in series. Because modeling suggests that the sequestered compartment is larger than the accessible compartment, an assumption has been made that the sequestered compartment is the intracellular space. For urea and other solutes that move easily across many cell membranes, compartmentalization may be flow related, that is, related to sequestration in organs (muscle, skin, bone). Although mathematically urea rebound and mass balance can be described with either model, the flow‐related model best explains data showing that urea rebound after dialysis is increased during ultrafiltration, diminished during high cardiac output states, and also reduced during exercise. Whether compartmentalization is increased in vasoconstricted intensive care unit patients receiving acute dialysis remains an open question.

Cardiovascular and respiratory systems : modeling, analysis, and control

Preface 1. The cardiovascular system under an ergometric workload 2. Respiratory modeling 3. Cardio-Respiratory Modeling 4. Blood volume and the venous system 5. Future directions Appendix A. Supplemental calculations B. A Nonlinear feedback law C. Retarded functional differential equations: Basic theory Bibliography Index.

Temperature and Thermal Balance in Hemodialysis

The analysis of thermal balance and temperature in hemodialysis patients reveals both striking similarities and important differences to urea kinetics. Both urea and thermal energy need to be removed during hemodialysis, however, for different reasons. Urea accumulates between hemodialysis treatments, whereas thermal energy accumulates within hemodialysis treatments. Urea concentration is ideally reduced by approximately 70% during a treatment, whereas temperature is ideally kept constant by removing up to 50% of resting energy expenditure because heat dissipation from the body surface is obstructed as a result of ultrafiltration‐induced hypovolemia. Extracorporeal heat removal is controlled by several factors. Dialysate and patient temperatures play the main role. Low body temperatures are not uncommon with hemodialysis patients, so that dialysate temperatures less than 36°C are often required to maintain reasonable temperature gradients. Another important role is played by extracorporeal blood flow. At the same temperature gradient, heat transfer by extracorporeal blood flow used with high‐efficiency dialysis is approximately six times more efficient than the dissipation of heat across the body surface. And, last but not least, the venous section of the extracorporeal circulation provides constant cooling of approximately 10u2003W. Almost all dialysis treatments provide extracorporeal cooling, even those using dialysate at 37°C. Therefore it is probably better to define the thermal aspects of hemodialysis with regard to the physiologic effects on the patient. Since thermoregulation responds to changes in body temperature, treatments should be characterized as isothermic, hypothermic, and hyperthermic.

Bilirubin Kinetic Modeling for Quantification of Extracorporeal Liver Support

Background/Aim: To provide a measure of treatment dose for extracorporeal liver support (ELS). Methods: The kinetics of conjugated bilirubin were described by a two-compartment model (Vc, Vp) with central elimination (K) and constant generation rate (G). The transfer of solute between compartments was modeled by intercompartmental clearance (Kpc). The central compartment (Vc) was assumed as a constant fraction of total volume (Vc = 0.3*Vt). Results: Eight patients were studied during 35 treatments lasting 6 h each. The average K, Vt, Kpc, G, and mass of conjugated bilirubin removed were 18.6 ± 3.9 ml/min, 9.1 ± 3.8 liters, 103 ± 108 ml/min, 0.33 ± 0.15 mg/min, and 641 ± 275 mg, respectively. The reduction ratio (48 ± 10%) measured as the change in post- to pre-treatment concentrations underestimated the modeled fraction of bilirubin mass removed (54 ± 13%) essentially because of significant conjugated bilirubin appearance during treatments. Conclusions: Kinetic analysis provides an improved measure of treatment dose as generation, distribution, and elimination of conjugated bilirubin are jointly considered.

Access recirculation in a native fistula in spite of a seemingly adequate access flow

True access recirculation (AR) measured by ultrasound dilution technique is usually absent in well-working shunts. It occurs with low access flows (Qa). High access flow rates are assumed to prevent AR. Two major exceptions to these rules are known: presence of intra-access strictures and inadvertently reversed blood lines. We present an additional exception in which true access recirculation occurred in a native arteriovenous (AV) fistula with correct placement of bloodlines. Surprisingly, access blood flow exceeded pump blood flow (Qb) almost threefold. The situation was clarified by a magnetic resonance angiogram showing a collateral forming a functional loop. This loop led to true access recirculation in one branch, although overall blood flow through both branches appeared to be adequate. The different findings in this shunt over time give insight into the often complex pathophysiology of native fistulae. This case proves that seemingly adequate access flow does not necessarily prevent access recirculation in native AV fistulae. We suggest monitoring both access flow and recirculation in hemodialysis accesses on a regular basis.

Concordance of absolute and relative plasma volume changes in routine hemodialysis

Central hematocrit (H) measurements are currently used to track the degree of ultrafiltration‐induced hemoconcentration with the aim to detect and prevent excessive intravascular fluid depletion during hemodialysis (HD). Failure to maintain hemodynamic stability is commonly attributed to the misinterpretation of H caused by an unaccountable increase in Fcells, the ratio of whole‐body hematocrit to H. It was the aim to examine Fcells under everyday conditions in a group of stable HD patients. Absolute plasma volume (Vp) and H were concomitantly measured during routine HD in the extracorporeal system in hourly intervals by noninvasive and continuous technology (CritLine‐Instrument‐III) and indocyanine green dye dilution to derive relative plasma volumes from Vp and H (RPVp, RPVH), respectively, and to calculate Fcells. Thirteen patients were studied during two midweek treatments (nu2009=u200926). Both absolute Vp (Pu2009<u20090.05) and relative plasma volumes RPVH (Pu2009<u20090.001) decreased during HD. Vp at any time point was positively correlated to RPVH (ru2009=u20090.52). Moreover, relative plasma volumes RPVH and RPVp determined by independent techniques were identical and showed negligible bias (−0.2%) but considerable limits of agreement (−15.6% to +15.3%). Fcells was stable and in the range of 0.9u2009±u20090.05 throughout HD and not different from the value assumed at the beginning of HD. Although Fcells remains constant in patients on routine dialysis and relative plasma volumes (RPVH and RPVp) determined by independent techniques are therefore comparable, the variability of experimental conditions during dialysis and the limited accuracy of absolute volume measurements using available technology continues to complicate the ultrafiltration control problem.

Quick measurement of hematocrit and erythrocyte sedimentation-rate by means of a density tracking method.

SummaryAn instrument to track the sedimentation properties of red blood cells quickly and automatically and to evaluate the hematocrit as well as the plasma density of a blood sample in the same operation is described. Erythrocyte-sedimentation basically is due to the density difference between the red blood cells and the plasma and the new method makes use of the mechanical-oscillator-technique, where the resonant frequency of the bending-type oscillations of a U-shaped glass tube is related to the density of the fluid with which the tube is filled. The oscillating U-tube is part of a sedimentation-tube of special dimensions and particular spatial orientation. The tube is tilted at 60°, the tip of the U-tube being raised above the horizontal plane. Filling the sedimentation-tube with anticoagulated blood first permits recording of the density of the homogeneous suspension. Then, after a few minutes, the onset of erythrocyte-sedimentation produces a decrease in recorded density. The final value is related to the density of the supernatant plasma-fluid. Hematocrit, blood and plasma density of the undiluted blood sample as well as the sedimentation-rate of the anticoagulated sample are automatically calculated from the recorded sedimentation-curve. The particular arrangement of the tilted sedimentation-tube facilitates a determination of the maximum sedimentation-rate within 15 min at most.

Noninvasive Assessment of Vascular Function

Impaired arterial compliance contributing to increased blood pressure and cardiac workload is well accepted as a major factor in cardiovascular disease. Information on local arterial compliance is obtained when analyzing the deformation of selected arterial segments under stress. A more global measure of arterial compliance is obtained by analyzing the arterial pulse by so-called pulse wave analysis. The arterial pulse, even when measured locally, carries characteristic information from the whole arterial system because of reflection of waves at distinct sites of the arterial system. Pulse wave velocity and the transfer function for pulse transmission is obtained from the combined measurement of arterial pulses at proximal and distal measuring points. Both pulse wave velocity and transfer function importantly, but not exclusively, depend on arterial compliance. The reconstruction of the aortic pulse from peripheral pulse measurements using a population-based transfer function finally provides information on central effects of reduced arterial compliance and increased peripheral resistance which may help in the diagnosis and treatment of vascular disease.

On-Line Identification of Hemodynamic Variables by Dilution of Ultrapure Dialysate During Hemodialysis

The removal of fluid during hemodialysis (HD) affecting both blood volume and cardiac output (CO) is one of the main causes for intradialytic hypotension. Information on hemodynamic variables obtained during HD may help to detect and to prevent this risk. It was the aim to develop a technique and a model for simple bedside identification of these variables. The 4008H HDF dialysis machine (Fresenius Medical Care, Bad Homburg, Germany) has the capability to inject defined volumes of ultrapure dialysate at correct temperatures into the extracorporeal bloodline at the relatively slow rate of 150 mL/min, which can be used for the purpose of indicator dilution measurements. However, the classic bolus approach to calculate CO fails in the setting of long and slow infusions. Dilution curves were therefore analyzed by a two-compartment model where the exchange between central (V1) and peripheral (V2) compartments was determined by systemic blood flow (qsys). A blood volume monitor (BVM, Fresenius Medical Care, Bad Homburg, Germany) was used for on-line measurement of changes in blood water concentration (BWC) caused by the dilution. Extracted dilution curves were then used to fit the two-compartment model to the experimental data. The model produced plausible parameters where qsys determined in two patients and for repeated measurements (7.6±0.6 L/min) was close to CO obtained by the reference technique (7.1±1.6 L/min). The system has the potential for complete automatization when equipped with appropriate control inputs to the BVM and to the HDF-module of the HD machine.

Extracorporeal Sensing Techniques

Many physiologic variables have been measured in the extracorporeal circulation by experimental systems but only a few systems have reached technical maturity for everyday application. Variables relating to cardiovascular function, which today can be measured in the extracorporeal system, are pressure, temperature, and measures of blood composition such as hematocrit, hemoglobin, and total protein concentration. While the measurement of blood composition and temperature is well established, and while the use of extracorporeal pressure information awaits further analysis for robust application, recent interest focused on continuous measurement of plasma sodium concentration which is believed to be of major importance for optimal blood treatment. However, problems with a simple, reliable, and continuous measurement of plasma sodium for everyday use have not yet been resolved. As can be seen from the growing interest in isothermic or isonatremic treatment modes which turns away from constant and profiled treatment modes without feedback control, the treatment goal is now to provide stable conditions within the patient so as to minimize interference with intrinsic physiological control mechanisms. This, however, requires valid and reliable measurement of the specific patient variables of interest.