Intelligent hemodialysis: Toys or tools?

Stewart LAMBIE,1 Graham WARWICK2

1Department of Renal Medicine, Raigmore Hospital, NHS Highland, Inverness, UK; 2Department ofNephrology, Leicester General Hospital, Leicester, UK

AbstractHemodialysis technology has advanced significantly in recent years, with a variety of new techni-

ques for optimizing treatment now available. It remains to be seen which of these techniques prove

to be of significant benefit and which are useful only within the confines of research projects. Some

of the recent developments in technology are examined here.

Key words: Hemodialysis, monitoring, vascular access, blood volume, adequacy

INTRODUCTION

Hemodialysis therapy is an excellent example of the use

of medical technology to sustain life from previously fatal

diseases.1 However, the treatment regimes are remarkablycrude and empirical. With older and more frail patients

starting renal replacement therapy, many patients experi-

ence problems (e.g., intradialytic symptoms, failure of

vascular access) for which further technological advances

may be able to offer solutions.

In this article, we present a narrative review of the

techniques and evidence of effectiveness for:

� access flow monitoring;

� blood volume monitoring; and

� ionic dialysance to measure urea clearance.

ACCESS FLOW MONITORING

The early prediction that vascular access would be the

Achilles’ heel of hemodialysis has proved to be depress-

ingly accurate. There is significant patient morbidity and

costs associated with problems relating to vascular access.

It is widely accepted that a native arteriovenous fistula(AVF) provides the best long-term access for dialysis but

the use of AVF among prevalent hemodialysis varies from

91% in Japan to 68% in the United Kingdom and only

31% in the United States. The low prevalence in the

United States reflects the high historical use of arteriove-

nous grafts (AVG), although this is changing. Arteriove-

nous grafts are more prone to thrombosis than AVF andthis has prompted interest in methods of monitoring

access devices to try to predict and prevent thrombosis.

The U.S. DOQI guidelines2 recommend monitoring of

vascular access by clinical assessment and a surveillance

program based on pressure or flow measurements with

diagnostic testing, followed by angioplasty or surgery if

there is evidence of a developing stenosis.

Surveillance can be carried out by measuring changesin static or dynamic venous pressure or by changes in

access flow. This article will only consider flow measure-

ments as recommended by the recently published Euro-

pean Best Practice Guidelines.3 A number of methods are

available for measuring flow in a vascular access device

(Table 1).

The technique that has been most widely used is based

on changes in ultrasound transit time through a columnof blood in the dialysis tubing.4 The rate of transmission

of the ultrasound wave through a medium is dependent

on the density of that medium. In blood, this is governed

by the hematocrit and the protein concentration. Changes

in the density induced by a saline bolus cause a change in

ultrasound transmission rate proportional to the dilution.

This technique is analogous to indicator dilution methods

used for many years for measurement of flow.This technique can be used to measure both recircu-

lation of blood in an access device and the total accessCorrespondence to: S. Lambie.E-mail: stewart.lambie@haht.scot.nhs.uk

Hemodialysis International 2007; 11:S34–S38

r 2007 The Authors. Journal compilation r 2007 International Society for HemodialysisS34

flow (Qa) during dialysis (Figure 1). Two ultrasound

transmitters/receivers are clipped to the tubing taking

blood to and from the patient. With the conventional

setup, a bolus of saline is introduced into the return (‘‘ve-nous’’) line, which causes a change in the transmission

rate vs. time curve in the sensor. If there is no recircula-

tion, none of the saline bolus is drawn back to the ‘‘ar-

terial’’ needle and there is no signal at the second sensor.

If there is recirculation, the ratio of the integrated areas

under the curve gives a measure of the percentage recir-

culation. However, this is an insensitive way of detecting

imminent access failure as recirculation only occurswhere the pump speed is greater than the access flow,

by which time the access device is nearly failed.

By creating artificial recirculation by reversing the inlet

and outlet lines from the patient to the dialyzer, a measure

of Qa can be obtained. The saline bolus mixes completely

with the blood flowing in the access. At higher Qa, less of

the saline will be recirculated to the dialyzer. The ratio of

the signal at the 2 sensors can be used to measure theblood flow in the access device.

This technique for measuring access flow has been wellvalidated and is reproducible. However, care must be

taken in AVF where there are multiple collateral vessels

between needles. Hemodynamic changes during dialysis

with falling systemic blood pressure will also lead to

changes in access flow.

The rationale for systematic surveillance of vascular

access is based on 2 premises:

1. Serial measurement of access blood flow accurately

predicts future thrombosis.2. Prophylactic and timely intervention by angioplasty

(or surgery) can prolong the life of the vascular access

and result in fewer procedures and morbid events

and decrease costs.

Early studies suggested that flow measurements accu-

rately predicted thrombosis, particularly in AVG. How-

ever, an analysis of the published studies up to 1998

concluded that there was no convincing evidence that asingle access flow measurement could accurately predict

graft thrombosis or failure.5 McCarley6 reported that an

intensive serial monitoring with ultrasound dilution flow

measurements could improve graft survival compared

with historical data. But this was associated with a 6-fold

increase in intervention by angioplasty. Tessitore7 also

showed similar positive results in native AVF. Absolute

flow measurements of between 500 and 600 mL/min orreductions in flow of 25% to values o1000 mL/min were

proposed as indicators for further imaging of access.

However, more recently, other small randomized stud-

ies8,9 and cohort studies10 have failed to show a benefit of

Qa monitoring and this has led to uncertainty over the

role of flow monitoring. Unfortunately, there is no ade-

quately powered randomized study to guide clinical prac-

tice. As the technology is costly in terms of equipmentpurchasing and time to perform the measurements, this is

badly needed.

BLOOD VOLUME MONITORING

Intradialytic hypotension complicates up to 30% of

hemodialysis sessions. This is uncomfortable and poten-tially dangerous for patients. Many factors contribute to

falls in blood pressure (see Table 2) but a reduction in

intravascular blood volume due to ultrafiltration is an

important factor. The change in blood volume during di-

alysis is the net effect of the ultrafiltration rate and the

plasma refilling rate from the interstitial compartment.

Changes in relative blood volume can be calculated

from changes in the hematocrit or in the protein concen-

Table 1 Methods for measuring vascular access blood flow

Indirect measurementUltrasound velocity dilution (i.e., Transonics, Uxbridge,

UK)Ionic dialysanceThermal dilutionContinuous glucose infusion

Direct measurements of flow by doppler ultrasoundNewer techniques

TranscutaneousIntraaccess flow meters

Figure 1 Device for measuring access blood flow and recir-culation.

Intelligent hemodialysis

Hemodialysis International 2007; 11:S34–S38 S35

tration of the blood. A continuous readout of this can be

displayed by:

� optical methods based on the adsorption and scatter-ing of one or more light wavelengths by erythrocytes

(e.g., Crit-line);

� ultrasound transmission rate, which varies with the

density of the blood, mainly reflecting changes in

protein concentration (e.g., Fresenius blood volume

monitor).

The technique has been used now for many years and

much of the initial work focused on 2 areas. The Crit-linemachine was promoted with the idea that each patient

has a critical blood volume reduction that consistently

predicts a fall in BP independent of other factors, e.g.,

ultrafiltration rate, dialysis time, intradialytic weight

gain.11 However, this is surprising, given the range of

factors that may contribute to intradialytic hypotension

(Table 2).

Lopot et al.12 described a series of relative blood vol-ume vs. time curves that have been used to help the de-

termination of dry weight and to allow manual alteration

of ultrafiltration rate during dialysis. A flat or rising

relative blood volume curve suggests overhydration and

may be an indicator to reduce target weight. A rapidly

decreasing blood volume (48%/hr) suggests excessive

fluid removal and is likely to lead to hypotension. Lopot

suggested that the ideal curve demonstrates a more gentle

reduction in blood volume, with a final decrease of 10%to 15%.

These patterns were used in a pragmatic, multicenter

study to determine the effectiveness of blood volume

monitoring in everyday clinical practice.13 Four hundred

and forty-three patients in 10 North American dialysis

centers were randomized to conventional monitoring or

the use of Crit-line monitoring to guide fluid removal.

The Crit-line group had a significantly higher risk ofnonaccess-related hospitalization (relative risk 1.61) and

of death (standardized mortality rate 0.77 vs. 0.26).

These results were surprising and difficult to explain.

The conventional care arm had a much lower hospital-

ization and mortality rate compared with USRDS data.

This study provided dialysis staff with an algorithm for

manually adjusting the ultrafiltration rate in response to

changes in the blood volume vs. time curve. However, useof this was not mandated and staff could make other

changes at their own discretion.

There are now a number of systems produced by di-

alysis companies that incorporate algorithms linking

blood volume changes to alteration in ultrafiltration rate

and other parameters that are designed to minimize rapid

changes in blood volume. An example is the Fresenius

blood volume monitor (Bad Hamburg, Germany), whichis an optional module. This uses an inline cuvette in the

blood line and ultrasound dilution technology to measure

changes in blood volume. This is automatically linked to

ultrafiltration rate so that blood volume will not fall below

an operator-determined reduction in blood volume (anal-

ogous to the critical blood volume). The initial ultrafil-

tration rate starts at twice the required ultrafiltration to

achieve the desired weight loss in the prescribed time anddeclines to zero by the end of dialysis.

The concept of using biofeedback to prevent intradi-

alytic hypotension is taken a step further by the Hemo-

controlTM device (Hospal, Minandola, Italy). This also has

as its input the patient’s blood volume, but the desired

outcome is a trajectory of blood volume change over the

course of the hemodialysis session, the aim being to

produce a smooth blood volume trace, achieving thisby manipulating both the dialysate conductivity and

ultrafiltration rate. Several studies of this technique

have demonstrated a reduction in intradialytic hypo-

tensive episodes.14–16

ONLINE CLEARANCE

Small-molecule clearance on dialysis is known to corre-

late with mortality17 and also to have considerable vari-

ability between dialysis sessions,18 implying that more

Table 2 Factors potentially contributing to intradialytichypotension

Antihypertensive medicationsVasodilatorsUnstable cardiovascular statusFluid volume excessVascular diseaseHypoalbuminemiaIncorrect ultrafiltration rateIncorrect patient target weight assessmentDialysate at body temperature or warmerSevere anemiaHypoxemiaLow dialysate sodium levelLack of vasoconstrictionPostureDecreased cardiac reserveAutonomic dysfunctionIntercurrent illness (e.g., fever)Splanchnic vasodilatation (eating)

Lambie and Warwick

Hemodialysis International 2007; 11:S34–S38S36

frequent online monitoring of urea clearance might beuseful.

One method for achieving this relies on ionic dial-

ysance (which is the value of the dialysance of electrolytes

corrected for ultrafiltration and recirculation) measure-

ments taken at repeated intervals throughout dialysis.

Two conductivity meters are required, monitoring inlet

and outlet dialysate conductivity, or alternatively a single

meter, operating alternately at the inlet and outlet. Thechanges in waste dialysate conductivity in response to

defined perturbations of inlet dialysate conductivity allow

ionic dialysance and plasma conductivity to be calculated.

Because conductivity is related to ion concentration, it is

possible to substitute one for the other in further calcu-

lations. As the transfer characteristics of sodium and urea

are similar, the ionic dialysance reflects the clearance of

urea (corrected for recirculation). This can then be ex-pressed as Kt/V using a value for V entered into the model

by the clinician. Diascan from Hospal and the Online

Clearance Monitor from Fresenius are both based on this

principle.19,20

Measurement of Kt/V with this method has been

shown to correlate closely with urea-based measure-

ments, with less than a 5% absolute difference.21

Furthermore, these methods provide a measurement ofsodium removal during dialysis, as well as a measurement

of plasma conductivity (directly related to plasma sodium

concentration) throughout dialysis. For these techniques,

however, V (patient urea distribution volume) must be

estimated to arrive at Kt/V, introducing a further element

of potential error, as current methods for measuring V are

either cumbersome and impractical on a routine basis,

such as measurement of the volume of distribution ofdeuterium, or they are derived from simple anthropo-

morphic data and are hence less accurate (e.g., the Wat-

son formula).22

A further criticism of conductivity-derived Kt/V mea-

surements is that the brief period of increased dialysate

conductivity may alter plasma conductivity, particularly if

there is a high degree of access recirculation. As the cal-

culation of ionic dialysance from these measurements re-lies on the assumption that plasma conductivity remains

stable during the measurement period, this alteration in

plasma conductivity could have a small but significant

impact on the accuracy of the measurement. Indeed, it

may be sufficient to account for a large proportion of the

5% discrepancy usually found between plasma-based

Kt/V and ionic dialysance-derived Kt/V. A refinement of

the technique using dynamic bolus measurement maycircumvent this problem and increase accuracy still

further.20

CONCLUSION

The techniques described above have all been shown to

achieve their primary aims. We can use online techniques

for monitoring vascular access function, monitoring rel-

ative blood volume changes, and tracking urea clearance.

The translation of these achievements into hard clinicaloutcomes that are beneficial to patients is more difficult to

demonstrate. Biofeedback control systems can reduce int-

radialytic hypotension, but otherwise the evidence is

lacking. On the other hand, these online systems have a

minimal increased cost of consumables, and many of the

systems do not need any increase in nursing time to im-

plement them. Increasing technical sophistication offers

hope of improving the quality of dialysis, reducing intra-dialytic symptoms, and maintaining vascular access. The

challenge for nephrologists and multidisciplinary dialysis

teams is to evaluate the technology more thoroughly

and learn how to use it optimally for the benefit of our

patients.

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