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Biomedical subjects

L J Garred

Publications and source records attributed to L J Garred.

30 records · Page 2Linked to original sources

Urea kinetic modelling by partial dialysate collection.

Conventional urea kinetic modelling (UKM) has several drawbacks, in particular the complexity of the required calculations and the need for accurate values of parameters which are difficult to measure, such as dialyzer clearance and blood flow. An alternative method of UKM is proposed based on collecting a small fraction of spent dialysate flow for 3 consecutive dialyses. Application of a urea mass balance to the 7 day period permits neglecting changes in body urea stores. Thus no blood sampling is required for most patients. The required calculations are simple and straightforward. The partial dialysate collection (PDC) method was compared to conventional UKM in a 3 patient, 15 week study. Protein catabolic rate (PCR) from PDC was a smooth curve and consistent with dietary estimation for each patient. Conventional UKM gave variable PCR results which were 17-27% higher on average. This discrepancy was attributed to overestimation of dialyzer clearance. PDC was concluded to be more convenient and accurate than conventional UKM and therefore ideal for routine clinical use.

Adult↗

Use of a wedge cuvette in thin layer photometry and its application to oximetry.

A wedge cuvette was constructed by fixing 2 glass plates at a known angle with a spacer at one end. This resulted in a thin layer with thickness varying from 0 to 250 micrometer. By measuring the intensity of a beam of light through the thin layer as a function of distance along the wedge (and thus layer thickness), the absorption coefficient at the light wavelength used could be obtained without a separate measurement of I0, the reference light intensity. In addition, the difficult problem of determining accurate layer thickness as encoutered in conventional thin layer photometry has been avoided. Tests of the wedge cuvette method with Evans Blue and Malachite Green serial dilutions as well as with haemoglobin solutions at several oxygen saturations demonstrate that accuracy of the order of 1% can be obtained. Application of the wedge cuvette in experiments on oxygen uptake by layers of haemoglobin solution are discussed.

Hemoglobins↗

Protein catabolic rate determination from a single measurement of dialyzed urea.

Protein catabolic rate (PCR, in g protein/kg/day) for anuric patients can be accurately determined without blood sampling by equating urea generation over 7 days to the urea dialyzed in the three dialyses of this period as measured by partial dialysate collection (PDC) or with a urea monitor. The feasibility of determining the week's dialyzed urea from measurement of urea dialyzed in a single session, obviating the need to monitor three consecutive dialyses, was examined in a steady-state simulation of 540 anuric patients spanning the full range of dialysis parameters. It was found that the first, midweek, and last dialyses account for nearly constant fractions (37.9, 32.1, and 30.0%, respectively) of the week's urea removal, leading to equations of the form: PCR = CU/BW + 0.17 where U is the grams of urea dialyzed in the first, midweek, or final dialysis of the week, C = 2.45, 2.89, or 3.10, respectively, and BW is the patient's dry weight in kilograms. These equations were tested on 1312 weeks of PDC data gathered in 42 dialysis patients. Using the midweek U resulted in a mean absolute error in PCR < 0.05 g/kg/day when compared to PCR determined using all three of the week's U values.

Aged↗

On-line dialysis quantification in acutely ill patients: preliminary clinical experience with a multipurpose urea sensor monitoring device.

Direct dialysis quantification offers several advantages compared with conventional blood urea kinetic modeling, and monitoring urea concentration in the effluent dialysate with an on-line urea sensor is a practical approach. Such a monitoring device seems desirable in the short-term dialysis setting to optimize and personalize both renal replacement therapy and nutritional support of acutely ill patients. We designed a urea monitoring device consisting of a urea sensor, a multichannel hydraulic circuit, and a PC microcomputer. The sensor determines urea from catalysis of its hydrolysis by urease in liquid solution during neutral conditions. Hydrolysis of urea produces NH4+, and creates an electrical potential difference between two electrodes. Each concentration determination of urea is the average value of 10 measurements; samples are diverted and measured every 7 min. Laboratory calibration of the urea sensor has demonstrated linearity over the range 2-35 mmol/L. Urea monitoring was performed throughout the treatment course, either on the effluent dialysate or ultrafiltrate in seven acutely ill patients treated by either hemofiltration (n=5) or hemodiafiltration (n=2). The slope of the concentration of urea in the effluent over time was used to calculate an index of the dialysis dose delivered (Kt/V), urea mass removal, and protein catabolic rate. In addition, samples of the effluent were drawn every 21 min, and sent to the central laboratory for measurement of urea concentrations using an autoanalyzer. Kt/V values also were calculated with Garred's equation using pre and post session concentrations of urea in blood. Concentrations of urea in the effluent determined by the urea sensor were found to be very close to those obtained from the central laboratory over a wide range of values (3 to 42 mmol/L). In addition, Kt/V values for both hemofiltration and hemodiafiltration, when calculated with concentrations of urea in the effluent obtained by the urea sensor, did not significantly differ from Kt/V values obtained from the laboratory concentrations of urea in the effluent. On-line urea sensor monitoring of the effluent suppresses the cumbersome task of total effluent collection, and the complexity of urea kinetic analysis. The multipurpose prototype described here represents a new, simple, and direct assessment of dialysis dose and protein nutritional status of acutely ill patients, and is suitable for various modalities.

Acute Kidney Injury↗

Mathematical modeling of erythropoietin therapy.

A simple mathematical model to describe hemoglobin (Hb) concentration response to recombinant human erythropoietin (EPO) therapy is proposed. The model is based on the assumption that Hb production increases linearly with EPO dose level. The resulting equation contains two patient parameters: 1) S, the proportionality constant between g Hb generated/L blood/wk and IU EPO administered/kg body weight/wk; and 2) tau, the patient erythrocyte lifetime in weeks. The model was applied retrospectively to 67 patients from the Canadian Erythropoietin Study, yielding an average error of 5.5 g/L between 27 measured and predicted Hb value pairs over the 27 week study. The model parameters, S (mean +/- SD = 0.015 +/- 0.005) and tau (14.0 +/- 4.1), varied over an order of magnitude. The model was also used to predict the EPO dose required to reach a target Hb of 110 g/L; the EPO requirements varied from 55 to 742 IU EPO/kg/wk (mean +/- SD = 225 +/- 124). It is recommended, based upon the model results, that EPO therapy be initiated at 3 IU EPO/kg/wk for each g/L difference between target and baseline Hb, with subsequent EPO dose adjustment guided by patient modeling.

Dose-Response Relationship, Drug↗

Reuse of "highly permeable" dialyzers with peroxyacetic acid as sole cleansing and disinfecting agent.

In the past few years, dialyzer reuse has gained increased clinical acceptance. This has been due both to the availability of automated reconditioning machines and powerful chemical cleaning and disinfecting agents. In this study the authors evaluated the effectiveness of a newly available peroxyacetic acid solution (PAS) (Dialox) as the dual cleaning and disinfecting agent in the reuse of highly permeable dialyzers. An in vivo study was conducted with ten patients already involved in our center's reuse program using the Renatron reprocessing machine and PAS at various dilutions. One hundred forty dialyzers of three different brands and membrane types (HF80 used for hemodiafiltration [HDF], Filtral 16 used for hemodialysis [HD], and FH88 used for hemofiltration [HF]) were employed for a total of 1182 treatments, giving an average 8.4 uses per module. Significantly more uses were obtained with the HF80 and Filtral 16 dialyzers (9.7 and 9.4, respectively) than for the FH88 modules used by the HF patients (6.7 uses per module). Compromised cleaning by backfiltration due to the lack of a second dialysate port on the FH88 may be a possible explanation. Greater membrane plugging due to higher ultrafiltration rates in HF may be another factor. Patient variability was found to be another factor in dialyzer reuse. The cleaning effectiveness of various dilutions of PAS was also tested in this study. The number of uses achieved was not found to vary significantly with PAS strength; however, a greater frequency of second or third reprocessing was required with more dilute cleaning solution. The authors found the dilution achieved on the Renatron reprocessing machine using the currently marketed PAS concentrate to be the most cost effective.

Disinfection↗

Simple Kt/V formulas based on urea mass balance theory.

The ratio Kt/V (K is patient clearance, t dialysis time, V urea space) has become the standard measure of dialysis adequacy. In this article simple Kt/V equations are developed theoretically from the urea mass balance equation. Two approximations lead to the most precise equation: [formula: see text] where R is the post to pre dialysis urea ratio, BW/V is the amount of fluid removed during dialysis (delta BW) expressed as a fraction of urea distribution space (V) at dry body weight (BW), and t is dialysis length in hours. A second equation arises with V approximated as 58% of BW. One further approximation leads to a simpler but slightly less precise Kt/V formula: [formula: see text] These and earlier published equations were tested with two sets of data: 1) 49 sessions involving 17 patients on maintenance dialysis and 2) 540 computer simulations spanning all likely values of Kt/V (0.6-1.6), protein catabolic rate (0.6-1.6), interdialytic weight gain (0-4% of BW per day) and dialysis session length (2-4 hr). The most precise formula (upper equation above) had a maximum error of 0.031 and 0.035 Kt/V units for the clinical and simulated data, respectively, whereas the lower equation was slightly less accurate with maximum Kt/V errors of 0.079 and 0.081, respectively. The proposed Kt/V equations are considerably more accurate than previously published formulas.

Computer Simulation↗

Urea kinetic modeling with a prototype urea sensor in the spent dialysate stream.

The authors have previously demonstrated the feasibility and accuracy of urea kinetic modeling (UKM) based on monitoring urea concentration in the spent dialysate stream (SDS) throughout the hemodialysis (HD) session. They describe here a prototype urea sensor for this purpose and initial experience with HD patients. The sensor is based on ammonium ion and reference electrodes housed in a cell through which the entire SDS passes. The two electrode tips are bathed in urease solution on one side of a dialysis membrane; the SDS flows along the adjacent side. Urea diffusing across the membrane from the SDS is converted by the urease into ammonium ion, which is measured by the electrode pair. For evaluation, the prototype flowthrough urea sensor was installed in the SDS of a Cobe Centry 3 HD machine for 36 HD sessions. Independent measurement demonstrated a linear relationship between mv output of the sensor and logarithm of SDS urea concentration. The use of SDS urea concentration time profiles obtained with this sensor to obtain accurate values of patient protein catabolic rate (PCR) and KT/V is illustrated. Incorporation of urea sensors such as this prototype into HD machines, will permit complete automation of UKM in the near future.

Dialysis Solutions↗

Simple equations for protein catabolic rate determination from pre dialysis and post dialysis blood urea nitrogen.

Several simple equations exist for Kt/V determination from pre dialysis (Cpre) and post dialysis (Cpost) blood urea. However, comparable equations have not been available for calculation of protein catabolic rate (PCR), an essential parameter for assessing patient status. Three simple formulas for PCR determination were developed from the urea mass balance equation for an anuric patient in protein steady state receiving thrice weekly dialysis. The simplest formula, PCR = 0.0076 [Kt/V] [Cpre + Cpost] + 0.17 relates PCR (in g protein/kg/day) to Kt/V and pre and post dialysis blood urea nitrogen measurements (in mg urea nitrogen/dl) for the midweek session. When tested for 540 simulated patients spanning a range of Kt/V (0.6-1.6); PCR (0.6-1.6 g/kg/day); dialysis duration t (2-4 hrs) and interdialytic weight gain expressed as a percentage of dry body weight gained daily (0-4%), this equation yielded a maximum error of less than +/- 5%, within the accuracy generally required for clinical needs. A more accurate formula, [formula: see text] where Clm is the logarithmic mean of Cpre and Cpost, gave maximum errors in PCR estimation for the same 540 simulated patients of less than +/- 0.6%. Both formulas require a precise value of Kt/V. The equation below incorporates a very accurate simple Kt/V equation recently published by the authors, allowing PCR to be expressed in terms of Cpre, the ratio of Cpost to Cpre (R), the ratio of session ultrafiltration volume (delta BW) to urea distribution volume (V), and dialysis time (t, in min). [formula: see text] This equation was accurate to within a maximum error of +/- 1% for the simulated patient group. These equations allow simple and accurate patient PCR determination, and should be used in conjunction with a simple formula for accurate Kt/V determination to guide end-stage renal failure patient therapy.

Blood Urea Nitrogen↗

Direct determination of blood recirculation rate in hemodialysis by a conductivity method.

Blood recirculation is one of the key factors of decreasing dialysis efficiency. Determination of recirculation rate (R) is necessary to optimize effective dialysis delivery and to monitor vascular access function. R can be directly measured by a conductivity method in paired filtration dialysis (PFD), a double-compartment hemodiafiltration system that permits direct access to plasma water via the ultrafiltration stream. Measurement of R, in this system, involves the first of two conductivity sensors integrated in a urea monitor (UMS, BelIco-Sorin, Mirandola, Italy), and two saline injections. The rise in conductivity (deltaC1) induced by a 2.7 ml bolus of hypertonic saline 20% (mg/dl) in the arterial line serves for calibration, and is followed by an equivalent injection into the venous line, giving rise to deltaC2. The ratio deltaC2/deltaC1 equals R. A comparison between R values obtained with this method and with the low-flow technique in 31 chronic dialysis patients during 138 PFD sessions is reported. Mean R+/-SD by the conductivity method was 5.1+/-2.0 and 5.7+/-2.0% after 65 and 155 minutes of PFD (correlation coefficient, r = 0.75), whereas it was 6.4+/-4.9% and 5.5+/-4.6% after 30 sec of low blood pump flow for urea and creatinine markers, respectively (r = 0.35). After 120 sec of low flow, mean R increased to 9.0+/-5.1 and 8.8+/-4.6% for urea and creatinine, respectively (r = 0.45). Considerable discrepancies were found in R values measured simultaneously with the two blood markers. Statistically significant differences were found between the two measurement modalities (blood-side and conductivity); the correlation coefficients (r) varied between 0.28 and 0.41. The observed differences in mean R results do not seem considerable from a clinical perspective. The best agreement between blood-side and conductivity R measurements was obtained with Rcreat after 30 sec of low flow. Overall, a wider distribution was found in R values from blood-side determinations, most likely consequent to variability in the dosing method. The conductivity method appears more accurate and simple in assessing total R, and can be readily automated and integrated into the dialysis machine. The authors, therefore, recommend evaluation of R using methods not based on chemical blood concentration values.

Adult↗