Allen M. Kaufman

Impact of Dialysis Dose and Membrane on Infection-Related Hospitalization and Death: Results of the HEMO Study

Infection is the second most common cause of death among hemodialysis patients. A predefined secondary aim of the HEMO study was to determine if dialysis dose or flux reduced infection-related deaths or hospitalizations. The effects of dialysis dose, dialysis membrane, and other clinical parameters on infection-related deaths and first infection-related hospitalizations were analyzed using Cox regression analysis. Among the 1846 randomized patients (mean age, 58 yr; 56% female; 63% black; 45% with diabetes), there were 871 deaths, of which 201 (23%) were due to infection. There were 1698 infection-related hospitalizations, yielding a 35% annual rate. The likelihood of infection-related death did not differ between patients randomized to a high or standard dose (relative risk [RR], 0.99 [0.75 to 1.31]) or between patients randomized to high-flux or low-flux membranes (RR, 0.85 [0.64 to 1.13]). The relative risk of infection-related death was associated (P < 0.001 for each variable) with age (RR, 1.47 [1.29 to 1.68] per 10 yr); co-morbidity score (RR, 1.46 [1.21 to 1.76]), and serum albumin (RR, 0.19 [0.09 to 0.41] per g/dl). The first infection-related hospitalization was related to the vascular access in 21% of the cases, and non-access-related in 79%. Catheters were present in 32% of all study patients admitted with access-related infection, even though catheters represented only 7.6% of vascular accesses in the study. In conclusion, infection accounted for almost one fourth of deaths. Infection-related deaths were not reduced by higher dose or by high flux dialyzers. In this prospective study, most infection-related hospitalizations were not attributed to vascular access. However, the frequency of access-related, infection-related hospitalizations was disproportionately higher among patients with catheters compared with grafts or fistulas.

Measurement of access flow during hemodialysis using the constant infusion approach.

With reversed placement of blood lines and with a peripheral arteriovenous access, hemodialysis recirculation (R) consists of a local access component, and a central cardiopulmonary component that must be separated for the calculation of access flow (Qac) using indicator dilution principles. With indicator injections that follow constant infusion principles Qac = (1 - RX)/(RX(1 - CPR)) × (Qb, x - UFR), where Qb is the extracorporeal blood flow, where UFR is the ultrafiltration rate, and where the index x indicates reversed placement of blood lines. CPR, the amount of cardiopulmonary recirculation (CPR = Qac/CO) is determined from two recirculation measurements with correct (index x) and with reversed (index x) placement of blood lines CPR = Rn(1 - Rx)/Rx(1 - Rn) × (Qb, x - UFR)/Qb, n. Qac was measured in 11 hemodialysis (HD) patients using a thermodilution device tested in an in vitro set-up based on constant infusion principles. Mean Qac was 1.135 L/min and 1.054 L/min for measurements done early and late in dialysis. The coefficient of variation was ±7.3% and ±8.6%, respectively. Repeated measurements of access flow in HD patients showed good reproducibility (Qac.1 = 1.01*Qac.0, r2 = 0.98), with the regression line not different from the line of identity; however, in vivo results remain to be validated by an independent technique.

Relative underestimation of fluid removal during hemodialysis hypotension measured by whole body bioimpedance.

Whole body bioimpedance is considered helpful in monitoring the removal of excess body water by ultrafiltration in hemodialysis patients. In this study, the cumulative, estimated decrease in extracellular volume (Vest) modeled from whole body bioimpedance data was compared with measured volume (Vmeas) removed by ultrafiltration (UFR = 1.01 ± 0.31 L/hr) in 12 patients during 36 high efficiency hemodialysis treatments. In the mean, estimated (Vest=3.0 ± 1.4 L) and measured volumes (Vmeas=3.4 ± 1.1 L) correlated linearly: Vest = 1.05 x Vmeas − 0.60, r2 = 0.68. Patients developed hypotension in half the treatments. Except for a larger decrease in systolic blood pressures in hypotensive (34 ± 24 mmHg) vs. stable (14 ± 15 mmHg) treatments, patient and treatment characteristics were not different between groups. However, at the end of hemodialysis, the difference Vest − Vmeas was − 0.8 ± 0.9 L in hypotensive, and only 0.1 ± 0.4 L in stable patients (p < 0.05). The difference between Vest and Vmeas can be explained by a predominant removal of excess body water from central body compartments such as the trunk and the central blood volume during hypotension. These compartments are not adequately measured by whole body bioimpedance techniques. However, this information could be helpful in identifying patients with delayed peripheral fluid removal that may occur when either target weight is too low or UFR rates are too high.

In vivo verification of an automatic noninvasive system for real time Kt evaluation.

It is generally accepted that morbidity and mortality of hemodialysis patients is related to dialysis quantitation. Currently available methods for the quantitation of dialysis require blood sampling or a continuous measurement of changes in urea concentration during treatment. These maneuvers are time consuming and expensive, and are generally performed, at most, once per month. The authors introduce an on-line, automated method for measurement of dialyzer electrolyte clearance comparable to urea clearance by using dialysate conductivity sensors placed pre and post dialyzer, and measuring conductivity at three different pre dialyzer levels. Conditions that reduce clearance, such as recirculation or fiber clotting, are automatically taken into account so that the method measures effective clearance rather than dialyzer clearance. In vitro and in vivo studies validate the method. Results are immediately available and can be used to address problems such as improper needle placement and access recirculation. In addition, repetitive electrolyte clearance data can serve to enhance quality assurance programs with respect to verifying the function of reused or new dialyzers. Appropriate algorithms can be used to calculate delivered Kt/V.

Clinical Experience with Heat Sterilization for Reprocessing Dialyzers

Use of heat sterilization for dialysis reprocessing offers significant advantages over chemical germicides. Polysulfone dialyzers (Fresenius 60M or 80M) can be sterilized by heating to 105 degrees C for 20 hr, thus permitting clinical trials of this method. One hundred eighty patients received 9,000 treatments. Pyrogenic reactions, sepsis, and subjective symptoms have not occurred. In vitro clearances (Qb 500 ml/min, Qd 800 ml/min) at baseline and after 2-8 uses did not differ (340 +/- 29 vs. 352 +/- 4 ml/min, respectively). KoA determined in vivo did not decrease (baseline 709 +/- 131 vs. 7th use 632 +/- 50 ml/min). Kt/V for urea was not different in 18 patients treated with heat sterilized dialyzers over 6 months when compared with a baseline period with formaldehyde sterilized dialyzers (1.37 +/- 0.12 vs. 1.32 +/- 0.11 at similar time and blood flows). Mean use number was 7.4 (dialyzers limited to 11 uses). Of discarded dialyzers, 44% failed a bedside integrity test (blood side pressurized at > 400 mmHg for 1 min), 36% failed automated fiber bundle or pressure holding tests, 8% had a blood leak, and 12% reached 11 uses. Clinical blood leaks occur in < 0.5% of treatments. Heat sterilization is a safe and effective method of dialysis reprocessing, but quality control of the process is essential. Based on initial clinical experience, heat sterilization of dialyzers for reuse is a promising alternative to chemical disinfection.

Dynamics Of Plasma Volume During Ultrafiltration Treatment

An open, two compartment model is developed to describe the response of plasma volume to the removal of protein-free ultrafiltrate from the intravascular space of hemodialysis patients. It is assumed that refilling from the extravascular compartment includes a small but definite amount of protein (c,,+ g). Protein refilling increases the colloid-osmotic capacity of the plasma compartment and leads to enhanced plasma volume recovery. Model parameters such as plasma and extravascular fluid volume which can be obtained by fitting to experimental data could be of interest to estimate the excess of body-water in hemodialysis patients.