E. Akcahuseyin

Drug Clearance by Continuous Haemodiafiltration

SummaryWith continuous arteriovenous haemodiafiltration (CAVHD), time-averaged clearance rates are higher than with intermittent haemodialysis. Indeed, drug removal rates may be high enough to warrant dose adjustment. In this study we measured the rate of drug clearance by CAVHD for 7 commonly used antibiotics: cefuroxime, cefotaxime, ceftazidime, imipenem, ciprofloxacin, tobramycin and vancomycin. By combining our data on clearance rates by CAVHD with literature data on drug distribution volumes and nonrenal clearance rates, we developed guidelines for drug dosage in intensive care patients treated by CAVHD. Dose adjustments during CAVHD treatment were deemed necessary for cefuroxime, ceftazidime, tobramycin and vancomycin.

Solute transport in continuous arteriovenous hemodiafiltration: a new mathematical model applied to clinical data.

A mathematical model of continuous arteriovenous hemodiafiltration is presented, by which the diffusive mass transfer coefficient (Kd) for a solute may be calculated from blood, filtrate and dialysate flow rates and solute concentrations. The model was applied to clinical data obtained with 0.6-m2 AN69 capillary dialyzers that had been used for up to 5 days. The diffusive mass transfer coefficient proved to depend on dialysate flow rate. Furthermore, it was related to the membrane index of ultrafiltration, as measured in the clinic, and to the filter resistance to blood flow. Measurement of these filter characteristics allowed a reasonable prediction of solute clearance.

A mathematical model of continuous arterio-venous hemodiafiltration (CAVHD)

Continuous arterio-venous hemodiafiltration (CAVHD) differs from conventional hemofiltration and dialysis by the interaction of convection and diffusion, the use of very low dialysate flow rates and by the deterioration of membrane conditions during the treatment. In order to study the impact of these phenomena on diffusive transport, we developed a mathematical model of the kinetics of CAVHD solute transport from plasma water to dialysate. The model yields an expression of the diffusive mass transfer coefficient, Kd, as a function of blood, filtrate and dialysate flow rates and solute concentrations, which can be measured in the clinical setting. This paper gives a description of the model derivation. Kd is demonstrated to vary depending on dialysate flow and duration of treatment.

Simulation study of the intercompartmental fluid shifts during hemodialysis

Hypotension is the most frequent complication during hemodialysis. An important cause of hypotension is a decrease in the intravascular volume. In addition, a decrease in plasma osmolality may be a contributing factor. Modeling of sodium and ultrafiltration (UF) may help in the understanding of underlying relationships. We therefore simulated, in a mathematical model, the intercompartmental fluid shifts during standard hemodialysis (SHD), diffusive hemodialysis (DHD), and isolated ultrafiltration (IU). We analyzed the relative theoretical effect of hydration status, dialysate sodium concentration, the initial plasma concentrations of sodium and urea, and tissue permeation to solutes on the magnitude and direction of intracellular and intravascular volume changes. This theoretical analysis shows that the transcellular fluid shifts taking place during hemodialysis treatment are, to a great part, due to inhomogeneous distribution of regional blood flow and tissue fluid volumes. During hemodialysis treatment, the cellular fluid shifts in tissue groups with relatively high perfusion and small volume occur from the intra- to the extracellular spaces. However, the fluid shift in tissue groups with a low perfusion and large volume takes place in the opposite direction. The UF volume and rates, and the size of the sodium (Na+) gradient between the dialysate and blood side of the dialyzer membrane are the most important factors influencing the fluid shifts. Higher UF volumes and flow rates cause an increasing decline in the plasma volume in both SHD and IU. High dialysate sodium concentration (150 mEq L(-1)) helps plasma refilling slightly when compared with a normal dialysate sodium concentration (140 mEq L(-1)). However, a high dialysate sodium concentration is associated with a high plasma sodium rebound, which in turn may lead to interdialytic water intake resulting from thirst and may cause increased weight gain and hypertension.

Increase in Blood Volume during Dialysis without Ultrafiltration

Combined dialysis and ultrafiltration leads to more frequent episodes of hypotension than isolated ultrafiltration. It has been suggested that decreased plasma volume preservation could be responsible for this phenomenon. The present study evaluates the effects of diffusive dialysis on the changes in relative blood volume (RBV). Six stable hemodialysis patients, without the need of ultrafiltration, were studied during 10 sessions of diffusive dialysis (bicarbonate) lasting 4 h. RBV was monitored continuously by measurement of hematocrit. During the 1st and 2nd h RBV increased by 2.4 ± 1.4 and 2.5 ± 0.8% respectively, returning to baseline levels at the end of dialysis. No changes in blood pressure or heart rate were noted. We conclude that during diffusive dialysis without ultrafiltration RBV is increased. A decrease in vascular resistance, or changes in regional blood distribution could explain these findings.

An analytical solution to solute transport in continuous arterio-venous hemodiafiltration (CAVHD)

In conventional intermittent hemodialysis, the overall mass transfer coefficient (Kd) of a dialyser is mostly calculated at zero ultrafiltration and at relatively high dialysate flow rates. In continuous arterio-venous hemodiafiltration (CAVHD), the dialysate flow rates are low as comparable to the rates of ultrafiltration flows, making the dialysis treatment as slow as possible. Therefore the overall mass transfer coefficient (Kd) of a CAVHD hemofilter has to be calculated in the presence of ultrafiltration. A mathematical model of CAVHD is presented in order to calculate the diffusive mass transfer coefficient (Kd) for a solute when blood, filtrate and dialysate flow rates and solute concentrations are known. The ultrafiltration volume flux (Jv) is assumed to vary linearly along the axial direction of the hemofilter. The calculated mass transfer coefficient Kd shows that at high values of dialysate flow and low values of ultrafiltration, the overall mass transfer coefficient (Kd) of a CAVHD hemofilter equals mass transfer coefficient (Kd) of a dialyser in conventional intermittent hemodialysis. Also, the calculated mass transfer coefficient Kd shows no significant differences when the ultrafiltration volume flux is assumed to be constant along the length of the hemofilter if no backfiltration occurs in the hemofilter.

Continuous arterio-venous haemodiafiltration: hydraulic and diffusive permeability index of an AN-69 capillary haemofilter

The dependence of uraemic solute clearance on the hydraulic and diffusive permeability index of an AN-69 capillary haemofilter is investigated during the treatment of patients with continuous arterio-venous haemodiafiltration (CAVHD). A mathematical model is presented to calculate solute clearance and the hydraulic and diffusive permeability index parameters from clinical data and to predict the blood flow rate entering the extra-corporeal circuit from the manufacturers specifications and blood viscosity. By measuring the flow rates, the patients mean arterio-venous pressure difference and uraemic solute clearance under different clinical and operational conditions, mathematical model equations are evaluated. During the average survival time of an AN-69 capillary haemofilter of about five days, it is found that both the hydraulic permeability index and the diffusive permeability index decline over treatment time, independent of the haemofilter resistance to blood flow. The measured haemofilter resistance to blood flow is three times higher than the haemofilter resistance predicted from the manufacturers specifications and blood viscosity. Predicting the blood flow rate entering the extra-corporeal circuit from the arterial haematocrit, plasma protein concentration and temperature and the manufacturers specifications is not reliable.