The evaluation of the influence of the use of total blood volume measurement during dialysis on the incidence of intradialytic hypotension associated events

Patients on dialysis are unable to manage their fluid and electrolyte balance
due to the loss of kidney function. Establishing the euvolemic state - the so
called *dry weight* - is an important clinical conundrum in every
nephrologist*s daily practice. Dry weight is defined as the lowest tolerable
weight without the development of hypotension-associated symptoms.
Overestimation results in volume overload. Underestimation of dry weight (with
excessive ultrafiltration) results in dialysis-induced hypotension due to
lacking cardiovascular compensatory mechanisms when fluid is withdrawn and
total blood volume (TBV) falls. Intradialytic hypotension is associated with
impaired quality of life and increased cardiovascular morbidity and mortality
(11, 12). Currently used methods to establish dry weight include clinical
assessment, bio-impedance spectroscopy and online relative blood volume
measurements. Each have low sensitivity and specificity. An ideal monitoring
tool should encompass measurement of total blood volume. The gold standard to
establish dry weight is isotope dilution to measure absolute blood volume,
which is not feasible to use in daily practice.
Relative blood volume monitoring is an integrated function in today*s dialysis
machines to measure changes in blood volume during dialysis. Recently, Kron et
al. used this function to measure the total blood volume, using the principle
of indicator-dilution. This is a method to calculate absolute blood volume by
measuring the difference in relative blood volume after administering a known
amount of a substance. In a small cohort study of 45 patients, they identified
an absolute blood volume threshold of 65 millilitres per kilogram dry weight
predicting for intra-dialytic hypotension associated symptoms. They found a
sensitivity and specificity of respectively 87% and 100% for this diagnostic
tool.

The aim of current research is to re-investigate the utility of the
above-described method and to confirm the hypothesis of a critical threshold of
65 ml blood volume per kg dry weight.

This study is designed as a non-blinded randomized controlled trial. The study
population will encompass haemodialysis patients of Haga Ziekenhuis (three
locations: Leyweg, Sportlaan and Zoetermeer) who are eligible to participate.
The baseline frequency of intra-dialytic hypotension associated symptoms will
be assessed with the use of a structured questionnaire during four weeks. The
absolute blood volume will be measured during mid-week haemodialysis session in
two consecutive weeks. Subsequently, patients will be randomly assigned to the
intervention group (adjustment of dry weight based on absolute blood volume) or
control group (clinically assessed dry weight). Thereafter, frequency of
intra-dialytic hypotension associated symptoms will be assessed again during
four weeks, comparing the intervention and control group.

During two mid-week hemodialysis sessions 240 millilitres isotonic ultrapure
dialysate will be infused, which will be ultrafiltrated during the same
hemodialysis session. Since this is exactly the same dialysate fluid as used
during regular dialysis, no adverse events are expected. As in regular
hemodialysis, adverse events associated to hypotension might occur, which is
the subject of this study.


De interventiegroep kan mogelijk een voordeel ervaren van de studie, als de
bevindingen van de andere onderzoekers bewaarheid worden. De additionele
belasting van de studie bestaat uit het 24x beantwoorden van een aantal vragen
volgens een vast format.

In tien patiënten zullen de uitkomsten van de TBV-metingen vergeleken worden
met de gouden standaard door middel van isotopendilutie methode. Hierbij zal
een bolus radioactief gelabeld albumine toegediend worden, waarna het TBV
berekend kan worden uit de dilutie van deze bolus. Dit onderzoek vereist een
extra ziekenhuisbezoek, injectie van radio-actief gelabelde substantie en twee
bloedafnames. Bijwerkingen van humaan radio-actief gelabeld albumine zijn zeer
zeldzaam (0.01% - 0.1%, <0.01% anafylaxie). Derhalve wordt het risico voor
participanten als uiterst gering beschouwd.

The administered bolus to measure total blood volumeis exactly the same
dialysate fluid as used during regular dialysis. The bolus will be
ultrafiltrated during the same hemodialysis session. Therefore, we do not
foresee potential risks or adverse events of the administered bolus.
As in regular hemodialysis, adverse events due to dialysis might occur, which
is the subject of this study.

The intervention consists of the adjustment of the patients* dry weight. Target
weight will only be adjusted in patients with a normalized total blood volume
below 65 ml/kg, regardless the occurrence of intradialytic hypotension
associated adverse events during the baseline period. As the intervention only
targets patients with low blood volume, the risk of developing fluid overload
is considered to be low.

There are no data to predict the effect on total blood volume during dialysis
after adjustment of dry weight. We therefore decided to use a standard
approach by increasing dry weight in the intervention group by 1 kg in patients
with a normalized total blood volume < 65 ml/kg at any time during dialysis.
Dry weight will again be increased by 1.0 kg, if a normalized total blood
volume a < 65ml/kg persists until a normalized total blood volume > 65 ml/kg is
achieved.
For example, a hemodialysis patient of 70kg is supposed to have a blood volume
of 4.55 liters, taking the critical threshold of 65ml/kg normalized blood
volume into account. When having an Hb of 7 mmol/l, 72% of blood volume
comprises of plasma and 28% of blood cells. Plasma contains 8% of solids and
92% of water, corresponding with 3,0 liter of water. While removing fluid
during ultrafiltrating, the plasma will be refilled with interstitial fluid.
The intracellular compartment remains relatively equal. Therefore,
theoretically 1 kg of target weight will distribute to the intravascular and
the interstitial compartment in a ratio of 1:3.
An increase of target weight of 1kg, will result in an increase of 250
milliliters (8%) plasma volume. Assuming that other compartments of blood
volume remain stable, this leads to an increase in total blood of 250cc as well
(5.5% of total blood volume). In conclusion, an increase of 1kg target weight
would theoretically result in 5.5% increase of total blood volume in a 70-kg
person with an Hb of 7 mmol/l.
The adjustment in volume control will be achieved by reduction of the
ultrafiltration with 1 liter. This will not result in a change of osmotic
pressure, and therefore not affecting the fluid shifts between intra- and
extracellular fluid compartments.