" .

'SIS TI ' I N E W S 8t V I E W S F R C = *

. . VOLUME 5, No. 1 MARCH, 1998

Current Research in Peihneal Dialvsis u .

hematocrits were generally better an ingly equal to those reported for HD. Little effort was initially spent to establish adequacy guidelines or to monitor the dose delivered to the patients. The empha- sis placed on quantitation of delivered dose in HD permeated the thinking of those practicing PD and led to a new, more scientific approach to therapy. It also stimulated research directed at identifying ways to enhance therapy and contain cost. The result of these

to establish policy or guidelines for selection of any therapy. This operational directive demands measure- ment of therapy delivered, monitoring of clinical out- comes, estimation of total cost of care and the correla- tion between each of these parameters. The recent experience with HD proved very helpful in structuring the studies necessary to establish the place of PD in the renal therapeutic armamentarium and to improve out- come. Some examples of concepts generated for HD

of similar terms or units of nt to express dose. The con-

correlates solute removal, m a s (expressed as volume

of distribution of urea or total body water). Despite the limita- tions of this concept and the diffi- culties encountered in estimating V in PD patients, this method of expressing dose allows correla- tion between protein ingestion, BUN and dialysis dose. It also allows comparison with the vast HD data pool as a reference.

Define equivalency between PD and HD in terms of KtN. Much thought has been devoted to establish equivalency between

these two therapies. The Peak Concentra- tion Hypothesis assumes that uremic tox- icity is due to peak rather than time aver- age concentrations of urea. It has served as

. Peritonealdi replacement therapy. The physiologic milestones for the development of this therapy were laid down in the last decades of the 19th century. In 1923, Ganter treated the first urenic patient with PD. However, for approxi- mately 50 years its role was primarily reserved for the &?atment of acute renal failure. The introduction of

APD in tbe Me 1970s revived the interest in PD and resulted in the development of many new modalities of therapy and the creation of a new and sizable industry dedicated to satisfy the growing market for PD. The following two decades can be divided into two distinct periods based on the history of PD re- search and development: a clinical-empiric period and a quantitative-outcome-based pe- r id .

Clinical-empiric Period Several characteristics of

CAPD attracted the attention of patients and clinicians alike. The initial success of this therapy can be attributed to the simplic- ity of the technique, lower cost than hemodialysis (HD), freedomfrommechanicalequipment and asteady physiological state with gradual toxin removal and ultrafiltration. Patients were noted to enjoy a compa- rable or better quality of life than those on HD. Their

Quantitative-outcome-based Period The practice of medicine has been greatly affected by

two decision making concepts: evidenee-based and cost-effectiveness. Certain critical data must be aecu- mulated and correlated with outcome and cost in order

alnutrition are ultiple arad many remain poorly current efforts n two areas: early ention and studies to identifv less obvious etiologies tritional data regularly obtained among PD patients

e being monitored and correlated with multiple variables to identify patients at high risk and to consider early intervention. Early intervention will consist of the simultaneous use of high dialysis nutrition and correction of metabolic acidosij

ye, intra! :toneal

BULK RATE U.S. POSTAGE

ID I IPERMIT NO. 22d

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Current Research in Peritoneal Dialvsis the basis for comparing PD and HD dosing in many studies. Other investiga- tors have applied their own validated models to establish equivalency. Most of the theoretical constructs and the few clinical outcome studies available have suggested similar weekly dose values - K t N > 2.0 or Ccreatinine 2 60 LA .73M2 as adequate for patients for patients un- dergoing PD. Unfortunately, all clinical studies have been performed in patients with significant residual renal function (RRF) and the study design has not al- lowed adequate analysis of the respec- tive contributions of the renal and perito- neal components.

graphic characteristics, comorbid condi- tions and laboratory parameters. The Cox Model and other multivariate analyses have been extensively applied to clinical studies in PD. These analyses have iden- tified many risk factors and predictors of outcome in the PD population and will hopefully lead to better selection of pa- tients and modality of therapy.

A serious effort to provide therapeutic guidelines, based on proven best practices, has been pioneered by the National Kidney Foundation (NKF-Dialysis Out- come Quality Initiatives). Every attempt was made to base as many recommendations as possible on evi- dence rather than general opinion. However, only four of the 32 guidelines are evidence-based, reflect- ing the fact that many of the available studies in the literature are still anecdotal, retrospective and uncon- trolled.

8 Adjust outcome according to demo-

provide therapy; and, 4) Nutritional intervention to reduce morbidity and improve clinical outcome. Frese- nius Medical Care and the Renal Research Institute (RRI) are actively involved in each of these areas of investigation.

The ultimate proof of adequacy rests on showing a significant improvement in survival. Recent prospec- tive studies, such as the Canada-USA (CANUSA) study have demonstrated a strong relationship between PD dose and survival. Unfortunately, most patients had considerable RRF, which was measured somewhat infrequently (every 6 months). It is impossible to deter- mine the relative contributions of the renal and perito- neal components to the final outcome. The respective contributions of RRF and PD to survival and the pos- sible equivalency between these two parameters can be best defined by: 1) Prospective, randomized studies with two or more well defined PD doses and frequent measures of RRF; 2) Studies limited to anuric patients with different PD doses; or, 3) Cross-sectional studies of very large populations undergoing PD with various levels of RRF and PD dose. The first type of study is very demanding on the investigators and patients alike. The closest effort to this type of study was the Fresenius PD Randomized Prescription and Clinical Outcome Study. Valuable data regarding progressive loss of RRF have been released, but the final analysis of the first phase of investigation has not been published. Studies limited to anuric patients introduce other con- founding variables such as previous periods of dialysis or transplantation of variable length and may favor certain comorbid conditions known for rapid loss of renal function. The cross-sectional study has several limitations, but can prove powerful if the population is large, the data are extensive and the analysis adequate. Such studies are part of FMC regular CQI efforts. With more than 6,000 patients undergoing PD in our clinics

s type of investigation in HD, such as on of swum a2bumin concentrations as

a powerful predictor of outcome, are we22 known to most. SimiZar ana2ytical methods are beinr app2ied t the PD m I la

Current Research in PD The most significant areas of current PD research

are: 1) Further definition of adequacy through corre- lation of dialysis dose, clinical outcome, RRF, and various biochemical and immunologic parameters; 2) Methods to enhance the dose of PD; 3) More effective, convenient, safe and economic ways to

and a comprehensive data collection system, it is pos- sible to answer many of these questions and identify risk factors that may affect clinical outcome. The fruits of this type of investigation in HD, such as the recog- nition of scrum albumin concentrations as a powerful predictor of outcome, are well known to most. Similar analytical methods are being applied to the PD popula-

J

A better understanding of peritoneal transport and the variables that affect transport rates have made possible the development of more efficient PD modali- ties. We have recently reevaluated the distribution of peritoneal transport rates (PTR) from a very large sample of peritoneal equilibration tests (PET) per- formed in our facilities and analyzed the distribution of body surface area (BSA), weights and heights for more than 40,000 ESRD patients. This information together with clinical data on delivered PD dose accumulated in our PackPD Modeling Program are being used to model the feasibility of providing adequate PD to the USA ESRD population with the available modalities of PD therapy.

In the past, we have evaluated the effects of larger intraperitoneal volumes of dialysate (Vip) and patient position on membrance performance (mass transfer area coefficient or MTAC). These studies culminated in the development of more efficient APD therapy - the PDPlus concept. At present, we continue to inves- tigate methods to enhance the dose of PD by studying the possible advantages of alternate techniques such as high-flow PD using the traditional intermittent tech- nique, tidal or continuous flow. While all these tech- niques have been known for decades, the conclusions of previous investigations have been questioned due to great variability of the results and the lack of control for certain variables not known to affect PTR at the time the studies were conducted. This line of investigation is best suited for the RRI and may well provide the answer to more convenient and efficient PD therapy.

Malnutrition affects a significant proportion of pa- tients undergoing both HD and PD. Malnutrition starts early in the course of uremia. Suboptimal protein ingestion among chronic renal failure patients has been identified when renal function drops to 50% of normal

and is commonly seen at 25% of normal. Aside from the common etiologics for protein malnutri- tion observed in all renal patients, individuals on PD have additional protein losses in their dialysate. The causes of malnutrition are multiple and many remain poorly characterized. Our current efforts are concentrated in two areas: early diagnosis and intervention and studies to identify less obvi- ous etiologies for malnutrition. Nutritional dataregularly obtained among PD patients are being monitored and correlated with multiple variables to identify pa- tients at high risk and to consider early intervention. Early interven- tion will consist of the simulta- neous use of high dialysis dose, intraperitoneal nutrition and cor- rection of metabolic acidosis. This approach may increase the rate of success.

Fresenius Medical Care has a long tradition of inno- vation and precise engineering with a focus on service. Its efforts are exclusively dedicated to the care of renal patients. Our extensive data pool, proven quality im- provement programs and an academic consortium of experienced scientists and clinicians promise a safer and exciting future for PD.

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DZALYSZS TZMES PAGE 3

LeF’ Continuo-rs ,* Blooc Volume Measurement

- - BY CHRISTIAN JOHNER, M.D. Fresenius Medical Care

(EDITOR’S NOTE: The text in this article is from a lecture given by Dr. Johner at the Renal Research Institute’s Evolving Dialysis VI technical seminar held last December in New York City).

Dear Physicians, nurses, technicians and nation- ally acknowledged speakers, that’s the invitation or let’s simply say dear dialysis freaks. I am a dialysis freak as well and one of my main interests, as Dr. Nathan Levin has indicated, is fluid management and therefore I want to discuss blood volume control and measurement.

Now, you may ask why we measure blood volume at all. Is it really necessary? In order to answer this question I would like to focus your interest on one of the biggest problems of dialysis. No, not money; hypoten- sion. I would like to ask how you manage your patients who become hypotensive? How do you care for them?

Or to ask another way, what are the pathways to hypotension.

There are several factors. There are factors that are directly related to the treatment itself. For example, if you choose a wrong electrolyte compensation, a wrong temperature or the wrong buffer, this may lead to hypotension. But there is also the blood volume which has been known to cause hypotensive episodes. further- more, there are patient specific factors which are in- volved in the genesis of hypotension.

For example - vascular compliance, the fluid stages, the condition of the heart or the sympathetic nervous system.

Okay, the question may arise: Why should we care about this blood volume when it’s only one of several aspects. Nearly all of these other factors have a great impact on blood volume and therefore we should at least measure it. But how? Fortunately there is a very famous person in this audience who has become re- nowned for blood volume measurements, Daniel Schneditz.

And he became famous for the following reasons: Let’s assume we have a patient with five liters

blood volume at the start of dialysis, by definition 100 percent. And this person has a hematocrit of, for ex- ample, 30 percent. Daniel Schneditz found this can correspond to a sound speed, a velocity of sound inside the sample of 1,573 meters. At the end of the dialysis treatment when ultrafiltration is finished there are, in our example, four liters blood volume remaining. Four liters are 80 percent of five liters so therefore we have arelative bloodvolume of 80percent. Since the number of erythrocytes was kept constant during the treatment, during the ultrafiltration the concentration of erythocrytes has increased and we have a higher hema- tocrit of 37 percent. Due to the increased density of this sample - the sound speed is increased as well and a sound speed of, for example, 1,580 meters per second can be found. Daniel Schneditz gave us the equations which we need to calculate the relative blood volume by measuring the sound speed.

We need for these measurements a curette. This curette is integrated in the arterial part of the extracor- poreal system and the blood passes from bottom to top and an acoustic transmitter sends ultrasonic pulses, sound which is received on the right hand side. By

measuring the transit time were able to determine the sound speed and by that the relative blood volume.

In practice, it may look like the following: We have a standard dialysis system. You may have

a blood temperature monitor and you should definitely have a blood volume monitor. The arterial blood passes the curette, goes right up the blood pump to the dialyzer and back to the patient. Now, one can ask, how precise is such a device? Again we’ve had luck.

Beth Israel Hospital took part in this evaluation study and they found the following: The relative blood volume measured with a BVM is highly correlated to the blood volume which is measured with a reference method. This is our hemoglobin measurement with a photometer and a correlation coefficient of 0.97 was found. They could not find any mean deviation be- tween these two methods. And we have a pretty good standard deviation of only 1.7 percent. And one has to be aware that the photometer, of course, has an error of one percent. , .

(See Figure 1).

a Corn parison

BVM - Opticai Deb-ice

I

‘igure 1

1 * This could be a typical example. Here we have the blood volume curve during typical treatment. These measurements are very close to the reference points measured here with the photometer. You can see there is only a small noise on the signal, at least in compari- sons with optical methods.

Okay, to summarize these technical aspects, it seems this untrasonic technique enables very precise measurement with only low noise on the signal. We could not find disturbances due to osmolarity changes or blood flow changes and we are furthermore able to

e to UF - Boli

I Figure3

measure hematocrit and inhemoglobin and are now quite convinced that this ultrasonic technique is appro- priate for controlling, later on, the blood volume.

Now we have nice blood volume curves, but what should we do with them?

(See Figure 2). How can we interpret them and what are the effects

having an impact on blood volume? There are several of these effects having an impact on the blood volume. The next one is most famous one, probably, ultrafiltra- tion. During the treatment the fluid was removed within four ultrafiltration boli. And during the phases of ultra- filtration, the blood volume dropped rapidly, but after switching off the ultrafiltration the blood volume could

*

b

recover and reach nearly a steady state volume. (See Figure 3). Ultrafiltration has an impact on blood volume.

What else? Food uptake. The patient in Figure 4 has his breakfast and after 20 to 30 minutes the blood was trapped toward the region of the stomach and therefore

Kesponse to Posture Changes

Figure 5

was no longer hernodynamically active creating the drop of blood volume.

Other effects, postural changes. (Figure 5) . Here you can see a treatment where the blood volume states to decrease and the patient began feeling a little bit dizzy. Therefore he moved toward the Trendelenburg

CONTINUED: Page 7

*“-L̂ . ._ PAGE 4 DIALYSIS TIMES

1 Physiologica! DialyDRs : A personal view -

BY HANS-DIETRICH POLASCHEGG, PhD What is physiological dialysis?

Dialysis machines today precisely control param- eters as dialysate sodium and dialysate bicarbonate, dialysate temperature and ultrafiltration according to the prescription of chemical and physical parameters. Physiological dialysis is a concept allowing continu- ous adjustment of treatment parameters intra dialytically with the goal to reduce intra dialytic and inter dialytic morbidity. How is it done?

Physiologically relevant parameters as blood vol- ume changes, electrolyte concentration and body tem- perature are calculated from easy accessible param- eters in the extracorporeal circuit and dialysate. These physiologic parameters are used to gain information about the patient and the treatment. They can be used to modify the treatment parameters manually or auto- matically by feedback control. Why physiological dialysis?

In 1979, when I started in dialysis as a physicist I asked why some 68 dialysis concentrates were listed in the catalogue and got the answer that this is necessary

a %for the individualization of the treatment. I learned about sodium modeling and how the patient’s plasma sodium and intracellular-extracellular fluid balance can be influenced by the proper choice of dialysate sodium or by sodium profiles. This sodium modeling

2 I

during dialysis and, the calculation of plasma electro- lyte concentration. It also became the basis of the on- line clearance measurement system.

measures the thermal energy balance in the extracorpo- real circuit and allows on-line calculation of the core temperature. It became the first commercial device that

At the same time Maggiore made the surprising discovery that the superior hemodynamic stability of hemofiltration was caused by the low tempera- ture of the substitution fluid and that the same effect could be achieved with cold dialysate in hemodialysis. The temperature of the substitution fluid for hemofiltration was not intentionally be- low body temperature. This was rather the result of poor engineering. It is a lesson for engineers that medicine can sometimes even benefit from poor engineering. Coincidentally the “hernofiltration society” decided at this time to change its name to “blood purification society.”

When studying the results of Maggiore, I concluded that not the dialysate temperature is the important parameter but the energy balance. This means the amount of thermal energy transferred between the patient and the extracorporeal circuit and the environment. It is well documented that

i

I .

L - > - - - a - - - I- A:: .lO 7 1 4 .lap

_ . .- . .. -I -141 U 3600 7100 96B60 ( U O O 16000

Tlmm I.8~1

Figure 2 Blood volume changes recorded with Crit-Line monitor. l...Hemodialysis, UFR-800 mUh: 2...Isolated UF. UFR=1200: S...lsolated UF. UFR=1400

body temperature reduction leads to vasoconstric- tion and thus to stabilization of blood pressure while a body temperature increase has the opposite effect.

Ultrafiltration leads to vasoconstriction resulting in the conservation of thermal energy and thus in a

Firmre 1: Intradialytic body temperature changes asfunction of dialysate temperature

program (like urea kinetic programs) requires knowl- edge of the pre dialysis plasma sodium and some idea about the goal.

Next I learned that the tolerance of the dialysate sodium concentration in concentrate is 2 percent and the accuracy of mixing at best 1 percent. The total tolerance of the dialysate is therefore 3 percent or more than +5 mmol/l. Then I found out that the accepted range of plasma sodiumresults is 122 to 138 mmol/l for a reference value of 130 rnmoV1, a range that covers even the extremes of dialysate sodium concentration. The conclusion was (and still is) that with conventional analytical technology it is impossible to individualize sodium therapy. This led, in 1982, to the invention of the electrolyte balancing concept that allows measure- ment of the amount of electrolytes removed or gained

temperature increase during dialysis. To stabilize the body temperature

under this condition, it is necessary to adjust the dialysate temperature to a lower value. This value, however, depends not only on the pre-dialysis temperature but also on the operating conditions of the extracorporeal circuit. If the blood flow is low and/or the patient is heavy, the cooling effect will be low. The opposite is the case when the blood flow is high and/or the patient is lightweight. No wonder that some authors found a body temperature increase even for dialysate temperatures of 34 or 35°C as shown in Figure 1. This also makes the different outcomes regarding blood pressure stabilization understand- able. When I studied the problem, I found the following statement by Burton (1)

Medical Devices Consultant, A-923 1 Kostenberg, Austria. E-mail Pg@compuserve.com: “Yet there seems to be possible a considerable advance in clarity of thought, if in nothing else, by the study of this transfer of heat in the light of the laws so well known to apply to purely physical systems. If these laws are held to be of little application to the living animal body on the score that this is something more than a purely physical system yet the question of how much and of what nature this ‘something more’ may be, cannot be answered until the behavior of the underlying purely physical system is understood. In that sense physiology must start with physics.”

Eventually this led to the development of the blood temperature monitor, again a balancing device that

allows automatic control of a physiologic parameter (body temperature) by feedback control.

Studying physiology mostly from the popular text- book of Guyton, I learned that many intra dialytic symptoms and also inter dialytic hypotension are caused by improper fluid control. At this time volumetric ultrafiltration was already available and it was obvious that the problem was not a mechanical but a medical one. I learned about the early attempts to measure and control blood volume and began to study theoretical concepts resulting in patents describing various physi- cal methods to measure blood volume changes. One describes the use of ultrasound density and fortunately, I found somebody who had already developed the technology that is now integrated into a commercial device. Meanwhile several commercial devices are available on the market and the number of publications is rising. All methods employ a physiological marker substance (hematocrit, hemoglobin, total blood pro- tein) to measure blood volume changes. A universal applicable algorithm to control ultrafiltration with the help of blood volume monitors is not yet available, but the data has largely increased our understanding of the parameters that influence the volume of circulating blood and blood stability. However, there are still more phenomena that are not yet understood.

How can patients benefit from physiological dialy- sis?

The patient will gain from the increased under- standing of the physiological process of hemodialysis in general and more directly from a better understand- ing of the individual variations.

Recently, I spent some time in a clinic doing measurements that included on-line hematocrit and blood volume measurement. Normally, blood volume decreases when ultrafiltration is going on. In one case of a diabetic patient, however, blood volume was

DIALYSIS TZMES PAGE 5

piece of educational material for families, and we’re excited to have it available,” said Susan A. Stark, executive director of the Tri-State Renal Network.

Networks that will distribute quantities for patient requests and new patient packages include the following: Trans Atlantic Renal Council, serving New Jersey, Puerto Rico and the Virgin Islands; ESRD Network Number 4, serving Delaware and Pennsylvania; Southeastern Kidney Council, serving Georgia, North Carolina and South Carolina; ESRD Network of Florida, serving Florida; ESRD Network Number 8, serving Alabama, Mississippi and Tennessee; Tri-State Renal Network, serving Indiana, Kentucky, Ohio and Illinois; Renal Network of the Upper Midwest, serving Michigan, Minne- sota, North Dakota, South Dakota and Wisconsin;

increasing (Figure 2). The cause, as we found out, was that the patient drank much tea at home and came to dialysis with a rather low plasma sodium. This thirst was obviously not caused by excessive salt intake. Further investigation revealed that blood sugar control was poor in this patient which may have an influence. This knowledge can now be used to investigate the cause of thirst with immediate feedback information about any treatment effect from blood volume mea- surement. With electrolyte balancing, however, we could measure the effect more quantitatively.

In another case, blood volume started to decrease at the very beginning of dialysis and followed a straight slope which indicates that the deviation from normal blood volume is small and the patient is possibly under hydrated at the end. Indeed, the patient complained about severe thirst immediately after dialysis (in spite of a dialysate sodium of 142 mmol/l). As a result, the doctor after t ahng to the patient and checking the physical status increased the dry weight of the patient.

Especially in the US many patients are on blood pressure reducing drugs because it is not possible to remove excess fluid within the relative short treatment times common without causing intra dialytic symp- toms. In Zurich, we could show that fluid can be removed faster employing a finding, first published by Bob Steuer and coworkers that patients tend to become symptomatic at a specific hematocrit (the “Crash-Crit”). By controlling UF such, that this hematocrit value is not exceeded, symptoms can be avoided. Ultrafiltration rates were adjusted to a rate higher than the linear rate calculated from time and volume and the ultrafiltration rate was switched off automatically by a home made device connected to a dialysis machine when the hema- tocrit approached the “Crash-Crit.” Can we afford physiological dialysis?

The equipment required for physiological dialysi5 consists of sensors in the extracorporeal circuit and the dialysate path. These sensors are connected to the microprocessor control unit of the dialysis machine.

Conductivity sensors in the dialysate path are usec to measure overall electrolyte balance. Dialysis ma chines used today employ at least one conductivitl sensor for dialysate concentration monitoring. An iden tical second one is added downstream. No disposable! or interventions are required. The system collects dat: automatically and display results on-line andor uses i for feedback control of the dialysate concentration.

Non-invasive, non-disposable temperature sen sors in the extracorporeal circuit are employed to mea sure thermal energy balance. From these data con temperature of the patient is calculated. The result c a be used, e.g., to keep the body temperature of thc patient constant by feedback control of the dialysatc temperature. No disposable or user intervention i

CONTINUED: P a a s

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0 - m L

0 1 2 a 4 - [hl Figure 3: IThe UFR was adjusted 1200mL%, a rate higher than the rate calculated from weight loss divided by dialysis time. UF was switched ofland on by the Crit-Line Monitor at Crash-Crit.

W P ion about rehabilitation

is available The American Association of Kidney Patients

AAKP) and the Life Options Rehabilitation 4dvisory Council (LORAC) are pleased to tnnounce a new joint publication, New Life, New Yope: A Book for Families & Friends of Renal Patients.

New Life, New Hope: A Book for Families & Friends of Renal Patients is designed to help the ‘amilies of patients with end-stage renal disease :ESRD). It provides explanations of treatment :hokes, information about rehabilitation, descrip- :ions of possible life style changes, clarification of he roles of the dialysis team, a briefing on patient’s rights and responsibilities, and a glossary 3f frequently used renal terms. All information is tailored to answer the concerns of family mem- bers. There are profiles of real patients and their families to highlight special sections.

“AAKP was honored to work with LORAC on this project,” said Joseph White, president of AAKP. “The diagnosis of ESRD brings shock not only to the patient, but also to the family members. Through our joint efforts we are able to reach the sometimes forgotten family member who needs information as much as the patient.”

In order to reach family members of newly diagnosed patients effectively, the ESRD Net- works have agreed to a unique partnership with AAKP and the LORAC to distribute New Life, New Hope.

for patients, families and caregivers who are seek- ing

“New Life, New Hope is an excellent resource

ESRD Network Number 12, serving Iowa, Kansas, Missouri and Nebraska; ESRD Network Number 13, serving Arkansas, Louisiana and Oklahoma; Intermountain ESRD Network, serving Arizona, Colorado, Nevada, New Mexico, Utah and Wyo- ming; and the Northwest Renal Network, serving Alaska, Idaho, Montana, Oregon and Washington. Other Networks will have a limited quantity for patient requests.

“It’s wonderful that we can have this collaboration, because Networks are in a unique position to reach patients,” said Sharon Stiles, executive director of the Intermountain ESRD Network.

Before its release, New Life, New Hope, underwent field testing. Eighty-nine patients and their families, from randomly selected dialysis units across the country, evaluated the booklet. The field testing results indicate that the booklet will be useful for family members from a variety of educational levels and ethnic backgrounds. New Life, New Hope, is a particularly appropriate resource for families of patients beginning treatment for ESRD.

Family members of newly diagnosed patients can receive the booklet by contacting their regional Network. If the Network phone number is unknown, please contact either AAKP at (800) 749-AAKP or the Life Options Rehabilitation Resource Center at (800) 468-7777.

AAKP is the voluntary patient organization, which for nearly 30 years, has been dedicated to helping patients and their families deal with the physical,

emotional and social impact of

i kidney iisease. The xograms 3ffered b: 4AKP inform / and - inspire

patients and their families to better understand their condition, adjust more readily to their circumstances and assume more normal, productive lives in their communities.

To learn more about the services of AAKP or to request free educational material for patientdfamily members and renal professionals, please call the national office at (800) 749-AAKP, send an e-mail t AAKPnat@aol.com or visit the web site at www.aakp.org.

Since 1993, the Life Options Rehabilitation Program has been developing, collecting and integrating rehabilitation resources to help patients with kidney disease lead, active productive lives. Fc more information about Life Options Rehabilitation Program activities and free materials for patients an renal professionals, call the Rehabilitation Resource Center at (800) 468-7777, send an e-mail to lifeoptions@medmed.com or visit the Life Options Internet Home Page at www.lifeoptions.org.

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PAGE 6 DIALYSIS TIMES

DIALYSIS EFFICIENCY Causes of Variation in Dialysis Efficiency --

Studies using Ultrasonic Transit Time and Ultrasound Dilution Techni Drcermine

By Warren Shapiro, M.D. I Lev E:evieh I We have noted that KTN and URR may show wide

variations from one measurement to another or may be lower than anticipated. We are often at a loss as to which results to believe. In this serialized article, we will describe patient studies using the HDOI device, (Transonic Systems Inc., Ithaca, New York) a novel instrument which measures dialyzer blood flow and access recirculation, and which may help delineate causes for the variations in the observed KTN or URR.

We studied our hemodialysis patients for the pres- ence of recirculation using the standard two needle, BUN method (1) and the ultrasound dilution method using the HDOI device (1). Blood samples were drawn from the arterial (A) and venous (V) lines after 30 min. of dialysis. The blood pump was then stopped for one min. and another sample taken from the arterial line sampling port with the arterial line clamped above the port (systemic sample (S)). Recirculation (R) was cal- culated as: R (%) (S-A)@-V) X 100. Immediately after obtaining the blood samples, blood flow was restored to the previous level. Recirculation was then measured by utilizing the ultrasound dilution method with the HDOI device. Five ml of 0.9% saline were injectedinto the venous line just proximal to the venous generator-sensor. In the presence of saline, ultrasonic transmission through the blood is altered as sensed by the venous generator-sensor producing a curve. When recirculation is present, a second curve is produced when the saline passes the arterial generator-sensor. The HDOI software is able to calculate the percentage of recirculation by comparing the area under the two curves

We 162 simultaneous measurements of recirculation by BUN and ultrasound dilution methods. Although agood linear correlation was obtained (-0.60, p<O.OOOl), there were 149 occasions when the HDOI device detected 0% recirculation, while the simulta- neously measured recirculation by BUN method ranged ftnm 2.7 to 29.25% Almost identical results were

obtained by Lindsey et a1 ( 5 ) with a device which utilizes magnetic principles for the determination of access recirculation. Thus, it can be seen that the BUN method for determining recirculation is highly inaccu- rate, may result in false positive results and thus should be used with caution, if at all. The ultrasound dilution method, on the other hand, is much easier to use, highly accurate and reproducible and requires no blood han- dling.

As an outgrowth of the above recirculation study, we observed that some patients initially had a very high recirculation, which disappeared after reversal of the blood lines (i.e. the “Ve- nous” line attached to the

reversal was still 7.1 percent in patients with repeat studies even after staff education. This phenomenon may explain variability in the KTN and URR results (if they are calculated on a treatment day when inadvertent line placement has occurred), but more importantly, line misplacement may occur on any day and result in a significant unrecognized decrement in dialysis effi- ciency on that particular day. Should this phenomenon reoccur frequently, in the same patient, it couldresult in underdialysis despite apparently “normal” KTN and or URR values which are obtained on days when line reversal did not occur. The data indicate a heretofore

“Arterial” needle and the “Arterial” line to the “Ve- nous’’ needle) (6). Such in- advertent misplacement of blood lines can lead to mas- sive recirculation and a marked reduction in dialy- sis efficiency.

Over a one year period, we studied patients in our hemodialysis unit for the presence of inadvertent line reversal by using the HDOI device. Patients were ran- domly screened throughout the year for the presence of recirculation. Patients found to have recirculation were immediately tested a second time after the arte- rial and venous lines were

INCIDENCE OF INADVERTENT REVERSAL OF HEMODIALYSIS LINES BEFORE AND AFTER CREATION OF AN ACCESS

DIAGRAM

STUDY PERIOD 1 2 3 4 FIRST STUDY (BEFORE DIAGRAM)

# OF PATIENTS I 60 1 9 I 21 I 17 # OF STUDIES I 60 1 9 [ 21 I 17 # OF REVERSED LINES 11 2 2 2

% 18.3 22.2 9.5 11.8

REPEAT STUDY AFTER DIAGRAM # OF PATIENTS # OF STUDIES # OF REVERSED LINES

5 16.1 7.1 7.1

Table

reversed. If the recirculation disappeared after line reversal, the patient was said to have had misplacement of the blood lines. After testing, a diagram of the arterio-venous access was made for all patients, the nursing staff informed and the diagram placed in the chart for future reference. All new patients and patients previously studied (and thus with diagrams in their charts) were re-studied quarterly for the presence of recirculation.

Progress on RRI RRI has just about concluded its negotiations with a number of

academic centers and with scientists and clinical researchers in other facilities or institutions. Individuals will be members of the Research Board of RRI. At present, RRI is interested in blaod volume monitoring, temperature regulation on line clearance mea- surement, on line bioimpedance, a new vascular access, methods for measuring access flow, polymer application in uremia treat- ment, cardiovascular function, and a number of clinical trials, etc.

More news will be reported in subsequent issue of Dialysis Times.

As shown in Table I, the incidence of inadverteht line reversal was sig- nificant in newly studies patients and, although lower in those restudied, it remained a potential important cause of underdialysis. Since recirculation ranged from 8-40 percent when. the blood lines were inadvertently re- versed, even an incidence of line reversal of 5 percent, (the lowest percentage recorded in our study) may result in important decrements in dialysis efficiency. In the last quar- ter, the incidence of inadvertent line

unrecognized problem which may occur in other dialy- sis units (not just ours) and is of practical importance for quality assurance.

The HDOI device appears to be extremely useful in assessing proper access cannulation. The latter finding may be very important because if appears to be quite common, may account for unsuspected underdialysis and should easily be rectified once its existence is identified.

References 1.4 DOQI clinical practice guidelines. Vascular ac-

cess, anemia of chronic renal failure. Am J Kidney Dis 3O:Suppl3 S166,1997

2. Shapiro W, Gurevich L: The e&ct of arterial needle size on dialyzer blood flow as measured by ultrasound dilution. JASN 7:1419, 1996.

3. Lindsey R Burbarzk J, BruggerJ, BradBeldG, Kram R, MalikP, BlakeP: Adeviceandamethodforrapidand accurate measurement of access recirculation during hemodialysis. Kidney Int 49: 1152-1160,1996.

4. Shapiro W, Gurevich L: Inadvertent reversal of hemdialysis lines - A possible cause of decreased hemodialyzer eflciency. JASN 8: 172A, 1997.

DZALYSZS TZMES PAGE 7

A personal view of

Continuous Blood Volume * Measuremen

g * * - I - >- Physiological =k*-KONmVU€D:Ffom Puue 3 position so that the fluidin the legs could be better

Dialysis CONT/NU€D:From Paae 5 required for this procedure.

For these two methods only the initial investment for the equipment is necessary. Both methods offer additional information for quality control in dialysis that may already pay for the initial investment: Electro- lyte balancing is the basis for on-line, non-invasive measurement of effective clearance and thermal en- ergy balancing allows automatic, non-invasive mea- surement of recirculation.

Blood volume measurement still requires special disposables but no user intervention. Some devices used for blood volume measurement can also be used for blood access evaluation.

Compared to other costs of ESRD treatment, the equipment and running costs of physiological dialysis are negligible. With the current payment system, how- ever, there is no financial motivation to employ these methods. Treatment costs are fixed and independent of morbidity outcomes. Morbidity increases the profit not for the dialysis unit but for the medical system at large. Intra and inter dialytic symptoms require application of drugs and use of additional disposables that can be charged extra. Also, the doctor’s efforts can be charged. Indications that this is indeed an important contribution to income are the numerous “billing” programs avail- able on the market. When the payment system is converted to capitation payment, providers will be motivated to reduce overall cost and the cost of morbid- ity and intra dialytic intervention will be evaluated and taken into account. Furthermore, when competition between dialysis units increases and patients learn that they have choices, morbidity figures published by dialysis units may become important for commercial success.

Introduction of physiological dialysis into clinical practice is no longer a technical problem but a problem of knowledge and mentality in the ranks of medical personnel. For those dialysis organizations that want to employ physiological dialysis as a means to become more competitive, training of medical personnel will be crucial.

I am confident that a payment system that moti- vates providers to reduce patient morbidity will result in the widespread use of physiological dialysis. For the skeptics I would like to quote frommy experience in the early 1980s: At this time I was head of R&D at Frese- nius, Germany, and we had developed the 2008 dialysis machine, the first successful commercial device em- ploying volumetric ultr&iltration control. The estab- lished US companies at this time all told us that there is no need for this technology in the U.S. In 1994 I met Ben Lipps who immediately recognized the value of the device and I got the opportunity to demonstrate the machine personally in the U.S. The reader is familiar with the further development of the company in the U.S.

nose in the ‘&*try looking into the future will recognize the opportunities offered by new technolo- gies and prepare for it.

/

1. Burton AC. The application of the theory of heat flow to the study of energy metabolism. J. Nutrition 1934: 7:497-533.

mobilized. This Trendelenburg pos&on stabilized the relative blood volume for 10 to 20 minutes but once again the blood volume began to decrease. The patient became hypotensive and saline had to be administered.

Okay, final curve (Figure 6). What can we learn from such a curve? We see a treatment with nearly no blood volume reduction despite ultrafiltration. The

m.

The Guyton Concept

I Figure 6

steady state value is only three percent below the initial volume. What does this mean? This patient was sup- posed to be fluid overloaded. Therefore we should take a look at the famous Guyton curve. The Guyton curve gives us the relationship between blood volume and excess cellular water or excess cellular volume.

Let’s assume we have a healthy person with an excess of cellular volume of 15 liters, then four-and- one-half of these 15 liters are distributed in the vascular compartment and the remaining ten-and-one half liters are in the interstitial compartment. Let’s imagine now that we are able to switch off the kidneys of this person. If this patient starts drinking and some of this additional fluid is distributed in the vascular compartment and the remaining one is in the interstitial compartment so we go upward. But the storage capacity of the vascular compartment is, of course, limited and therefore if the patient continues drinking all additional fluid is di- rectly shifted to the interstitial space and we are reach- ing aplateau. During dialysis, of course, it would go the opposite way.

In this particular treatment there was areduction of excess cellular water due to ultrdiltration, but no significant reduction of blood volume. This means the patient probably was above his dry point. Most likely this patient was still fluid overloaded at the end of the treatment. But if you are considering blood volume as a market you only ever have to consider the steady state volume. Do you emember, though, the graph with the high ultrafiltration boli. There was no further change of excess cellular volume even though the blood volume increased. This is the steady state value that must be taken into account.

We have seen a long list of effects having an impact on blood volume like ultrafiltration rate and volume, the fluid or dry weight status, food and fluid uptake, posture changes and there are more like osmo- larity and temperature. You may ask how to care for all these effects? It would be nice if you have something automatical which is caring about all of these effect automatically.

This automatical something could be a control algorithm. (See Figures 7 and 8).Such an algorithm should know that patients may stand high ultrafiltration rates at the start of treatment and low ulQafiltration rates at the end. The algorithm also should be aware that very low blood volumes should be avoided and if the blood volumes drops into the red region (on the chart)

-

the ultrdi hould be switched off. There is another thing I would like to demonstrate

with Figure 8. This is a high variability in response to ultrafiltration. This is one in the same patient only this was two days later and we have a totally different response to the ultrafiltration despite having nearly the same ultrafiltration volume.

So what’s the benefit of such an-algorithm? First with a control algorithm the reduction of relative blood volume is seven or eight percent and that’s smaller than the reduction of blood volume if you are using standard that mean a constant ultrafiltration rate. The chart shows a reduction of about 11 percent, but most important is the clinical relevance of such an algorithm. And you can see that it was possible in this particular study to reduce the number of symptoms by two-thirds. to me that is impressive.

I have shown that the ultrasonic technique enables you to obtain very precise blood volume measurements and if you have control algorithms you are further able to reduce the number of symptoms. This, of course, is just a starting point for further development. We have to improve these algorithms and we have to individual- ize them as well.

- - -.- ..B +?

Figure 7 I

I Figure8

1 In the next issue o Dialysis Times...

We’ll have more lectures from the Evolving Dialysis VI Seminar that was held in New York City in Decem- ber.

I’ I

PAGE8 . DIALYSIS TIMES

NEW TECHNOLOGY FOR CLINICAL PRACTICE

DATE: May 15,1998

Cambridge, Mass. Fresenius Medical Care

Blood Volume Monitor lood Temperature Monitor

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HOSTED BY= Dr. J. Michael Lazarus, M.D. - Medical Director Fresenius Medical Care North America Dr. Nathan W. Levin, M.D. - Medical and Research Director Renal Research Institute

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