Haemodialysis
Online Clearance Monitoring
Assuring the Desired Dose of Dialysis
Contents
1.Foreword
4
2.Dialysis dose
2.1
Standard methods of determination of the dialysis dose
2.1.1 Urea Reduction Ratio (URR)
2.1.2 Kt/V
Clearance K
Effective treatment time t
Urea distribution volume V
2.1.2.1 Determination of Kt/V using blood samples
Formal urea kinetic modelling
Single-pool Kt/V (Daugirdas formula)
Single-pool variable-volume Kt/V
Double-pool Kt/V (dpKt/V) and its approximation:
Equilibrated Kt/V (eKt/V)
2.2
The clinical relevance of dialysis dose
2.3
Recommendations for dialysis dose and the frequency of measurement of delivered dose
5
5
5
5
7
10
11
3.Online Clearance Monitoring – OCM®
3.1
The method of OCM® operation
3.2
OCM® in ONLINEplus Haemodiafiltration treatments
12
12
17
4.Optimisation of dialysis efficiency
4.1
Blood flow
4.2
Dialysis time
4.3
Dialyser (Membrane surface area, low flux/high flux)
4.4
Dialysate flow rate
18
18
19
20
20
5.Measurement of plasma sodium with OCM®
22
6.Frequently Asked Questions about OCM®
24
7.References
26
3
1. Foreword
Online Clearance Monitoring (OCM®) is a standard feature of the Fresenius Medical Care Therapy System 5008
that provides an automatic intradialytic measurement of the effective in-vivo urea clearance K, the total cleared
blood water volume Kt, the delivered dose of dialysis Kt/V and the plasma sodium concentration of the patient.
With the OCM® it is possible to easily monitor these essential parameters without additional costs during regular
ONLINE Haemodiafiltration in either pre- or post-dilution mode, and during haemodialysis treatments.
The OCM® helps physicians and nursing staff to ensure and document on a regular basis that the renal replacement therapy meets the recommended or required quality standards without the need for additional laboratory
tests or expenses.
This user brochure provides clinical and technical background information on the OCM®, describes its operation
and gives recommendations for the application of the OCM®.
4
2. Dialysis dose
Similar to the term “dose”, that defines the specific
Ultrafiltration leads to a very efficient transfer of urea
quantity of a medical product or drug required for the
from the blood into the dialysate, but this does not
treatment of a patient, the dialysis dose can be defined
result in a direct reduction of the urea concentration in
as the quantity of dialysis treatment delivered for a
the blood. This removal of urea is not accounted for in
given period of time. In general the dialysis dose is
the URR method. The greater the UF volume removed
measured by the comparison between the baseline and
during dialysis, the more inaccurate the results of
final concentration of a defined substance in the blood
dialysis dose calculation based on URR (2,3).
of the patient. The more efficient the dialysis session,
the greater the reduction of this given substance is.
2.1.2 Kt/V
In theory, it is possible to determine how efficient any
substance which is present in the blood has been removed during dialysis. Even though different methods
have been developed to measure the dialysis dose,
Clearance
(Manufacturer)
changes in urea concentration are monitored in order
t
V
to determine the dialysis dose in standard practice.
2.1 Standard methods of determination
of the dialysis dose
K x
Dialysis time
(Nephrologist)
Distribution volume
(Patient)
41: The variables of the Kt/V formula
2.1.1 Urea Reduction Ratio (URR)
The formula Kt/V, which is the most commonly used
A simple and commonly-used method of determining
index of the adequacy of the dialysis treatment, is
the dose of dialysis is the calculation of the Urea Reduc-
a mathematical representation involving the blood
tion Ratio (URR). This involves a direct comparison of
volume which has been completely cleared of urea
pre- and postdialytic urea concentrations and shows
during a specified dialysis and the urea distribution
the percentage reduction of the urea concentration
volume of the patient requiring detoxification. 41
during dialysis treatment (1).
URR = 100
( 1 -
Cpost
Cpre
The variables of the Kt/V formula:
)
Cpost: postdialytic urea concentration/Cpre: predialytic urea concentration
Clearance K
As well as being used as a diagnostic parameter in
renal function tests, the term “clearance” is also used
in renal replacement therapy. The primary parameter
In view of the simplicity of the method, URR is frequently
used to determine the volume of blood which has
used to determine the dose of dialysis, despite the fact
been purified during treatment is the effective in-vivo
that the method has an in-built analytical weakness
clearance Keff (mL/min) 42. Clearance is defined as
which may cause inaccurate results. In contrast to other
the (hypothetical) volume of blood which has been
methods, the URR method does not take into account
totally “cleared” of a given substance each minute;
that urea is also removed from the blood by ultrafiltration.
clearance is thus expressed as mL/min.
5
In-vivo must be differentiated from
effects of the corpuscular blood constituents (mainly
in-vitro clearance:
the erythrocytes), the dissolved plasma proteins, and the
adsorption of plasma proteins on the dialysis mem-
In-vitro clearance represents the purely diffusive clearance
brane (the “secondary membrane”) considerably alters
achieved by a dialyser tested under defined conditions
the diffusion properties of the dialysis membrane even
(as specified in standard EN 1283) using standardised
under otherwise comparable circumstances.
aqueous solutions. The EN 1283 standard requires that
measurements be conducted at a predefined dialysis
In-vivo clearance is thus inevitably lower than the stan-
fluid flow rate without any ultrafiltration (that is, without
dardised in-vitro clearance, but does reflect the actual
a convective clearance component). Only on the basis
conditions of the treatment and is thus of central impor-
of these non-patient-specific laboratory measurements
tance for the determination of dialysis efficiency.
is it possible to compare clearance values and thus the
relative efficiency of individual dialysers. In-vitro clearance, i. e. the efficacy of a dialyser under laboratory
conditions, is thus primarily determined by the design
features of the dialyser as well as the membrane characteristics.
K = QB
CB in – CB out
CB in
K = clearance (mL/min), QB = effective blood flow (mL/min), CB in = concentration
of inflowing blood, CB out = concentration of outflowing blood
In-vitro clearances of dialysers, on the other hand, are
measured under the actual dialysis treatment conditions
Effective dialysis time t
involving the patient, generally by means of analysis of
the blood prior to and after passing the dialyser: the term
Effective dialysis time t is the actual duration of diffusive
“whole blood clearance” is thus used in this context.
blood detoxification (time of dialysis fluid flow in the
In-vivo clearances are substantially different from in-vitro
dialyser with the blood pump operating). Interruptions
clearances as, during the dialysis of whole blood, the
to the dialysis treatment for therapeutic or technical
In-vivo Clearance K
influenced by: dialyser, effective
blood (water) flow (considering
haematocrit), ultrafiltration,
recirculation, dialysis fluid flow
42: The dose of dialysis Kt/V is a result of the effective
in-vivo urea clearance K, the effective dialysis time t and
the urea distribution volume V.
6
Effective dialysis time t
sometimes reduced due to alarms
and bypass conditions or premature
termination of the treatment
Urea distribution volume V
dependent on body size and composition,
weight, age and gender of the patient
reasons are considered in the effective dialysis time
The following examples should help explain the
42. The effective dialysis time is, in most cases,
use of the Kt/V concept:
shorter than the total duration of treatment provided.
Assuming Kt is 20 litres, this means that 20 L of blood
In an observational study, Segura et al. have demon-
have left the dialyser after being cleared of urea. How-
strated that the mean prescribed duration of dialysis
ever, this information does not yet tell us which dialysis
is generally not achieved in practice. Thus, over the
dose the patient has received. In the case of a patient
period of 1 year, the loss of time and therefore of
with a urea distribution volume V of 30 L, a cleared
efficiency per patient was equivalent to that of 7 whole
blood volume of 20 L has quite a different meaning
dialysis sessions (4).
than in the case of a patient with a urea distribution volume of 40 L. If Kt/V is equal to 1, this means that the
volume of blood which has been completely cleared
Urea distribution volume V
of urea in the dialyser is exactly equivalent to the urea
distribution volume of the patient. In a patient with a
The urea distribution volume V is equivalent to the total
distribution volume of 40 L, Kt must be equal to 40 L
body fluid, consisting of the proportion of water in blood
so that the result of the formula Kt/V is also 1. If the Kt
(7 %) as well as the interstitial (31 %) and intracellular
value is only 20 L, the Kt/V value would be 0.5.
volume compartments (60 %). Upon commencement of
dialysis, urea is homogeneously distributed throughout
Even if Kt/V is equal to 1, this does not mean that the
the body; hence, more than 90 % of the urea which
total body fluid or the total urea distribution volume
accumulates in the human body is not present in blood,
of the patient is free of urea, but only that, using the
but in the interstitial and intracellular volume compart-
example above, 40 L blood have left the dialyser after
ments. Thus, only with continuous diffusion of urea
being freed of urea. If Kt/V is 1.0, a urea concentration
from these compartments into the blood and further
of approximately 36 – 37 %, relative to the baseline
transport into the extracorporeal circulation is the
value, remains after dialysis.
largest proportion of urea present in the body made
available for dialysis.
The larger the blood volume (high blood flow rate) which
2.1.2.1 Determination of Kt/V
using blood samples
reaches the dialyser during a treatment session and
the longer the duration of the time-dependent diffusion
There are various methods which can be used to de-
from the interstitial and intercellular compartments into
termine Kt/V in practice. These differ in terms of the
the blood (adequate treatment time), the more efficient
underlying mathematical models used to predict and
the dialysis treatment will be.
determine urea kinetics (in other words, the changes in
the blood urea concentration of the patient over time).
A major advantage of the Kt/V equation is the fact that
Some methods involve very complex calculations and
it takes into account the individual body weight of the
require appropriate software programmes.
dialysis patient. Patients with the same Kt/V are detoxified
to the same extent even if they have markedly different
body weights. Dialysis treatments can thus be compared
in terms of the elimination effect using the Kt/V method.
7
Formal urea kinetic modelling
Single-pool Kt/V (Daugirdas formula)
The most complex, but at the same time most precise
The best alternative to the urea kinetic modelling
method of determination of Kt/V is the so-called for-
method, also based on analysis of blood samples,
mal urea kinetic modelling (5,6). This requires accurate
is provided by the formula for the calculation of Kt/V
measurement of:
developed by J.T. Daugirdas (8).
• urea or BUN (Blood Urea Nitrogen): concentrations
prior to and after the first dialysis session of the week,
Single-pool variable volume Kt/V
and urea or BUN concentrations prior to the second
dialysis session of the week (assuming three treat-
Most widely used at present is the following formula
ments are provided per week)
for calculating Kt/V:
• the body weight of the patient prior to and after the
first dialysis session of the week
• the actual effective treatment time (not the prescribed
Kt/Vsp = -ln (R – 0.008 x t) + (4 – 3.5 x R) x Uf/W
duration of dialysis and not the time from connection to and disconnection from the dialysis machine)
• the effective urea clearance of the dialyser as measured
ln: natural logarithm, R: ratio of postdialytic ÷ predialytic BUN,
t: effective dialysis time in hours, Uf: ultrafiltration volume in litres,
W: weight of the patient after dialysis in kg.
at the dialysis centre (not the value for in-vitro clearance
quoted by the manufacturer).
This mathematical model, which uses the natural logaUrea kinetic modelling is a reproducible method which
rithm to calculate Kt/V, provides sufficiently accurate
not only allows calculation of the dialysis dose Kt/V,
results over the full range of standard Kt/V values (9,10).
but also of the parameter nPCR (normalised Protein
In addition, the Daugirdas formula takes into account
Catabolic Rate), an important marker of the nutritional
the change in patient volume caused by ultrafiltration
status of the patient. Moreover, urea kinetic modelling
and its contribution to convective urea elimination.
allows the exact calculation of the patient-specific urea
distribution volume so that the individual dialysis pre-
The main disadvantage of the urea kinetic modelling
method is the logistical aspect. Some parameters, such
as the effective clearance achieved by a dialyser, are
difficult to measure in clinical practice and the effort
required to obtain and process the necessary data
can be considerable in large dialysis centres.
More recently, a two point urea kinetic model has been
validated which is based on only two measurements
of urea or BUN instead of three, prior to and after the
dialysis session and which supplies precise results
with a marked reduction of logistical effort (7).
8
BUN concentration [mg/dl]
scription can be given on the basis of measured data.
ICV
ECV+
blood
ICV: Intracellular volume
ECV: Extracellular volume
ICV
Equilibrated Kt/V
(eKt/V)
“Rebound”
ECV+
blood
Single pool variable
volume Kt/V (spKt/V)
ICV
ECV+
blood
Time [min]
End of treatment
43: Blood urea nitrogen concentration at the beginning (1), at the end (2)
and 60 minutes after the end (3) of a HD treatment
Double-pool Kt/V (dpKt/V) and its approximation:
with low urea concentrations but having higher rates
equilibrated Kt/V (eKt/V)
of blood perfusion. Organs with low blood perfusion
therefore also constitute a further urea reservoir. In the
As in the case of the other (not discussed here) single-
initial 30 minutes after completion of dialysis, the
pool models, the Daugirdas formula considers the
concentration equilibration again leads to a rebound,
body, for the purposes of mathematical modelling as
thus an increase in blood urea concentration.
a single unified fluid pool, and does not take into
account the differences in rates of urea transfer
The extent of total urea rebound can differ greatly
between the three fluid compartments blood plas-
between individual patients. In a study conducted by
ma, extracellular space and intracellular space. This
Leblanc et al. (15), the mean rebound, the percentage
difference in the transfer rate of urea is described as
increase in postdialytic urea concentration 30 minutes
the double-pool effect.
after dialysis, in comparison with that immediately
after completion of dialysis, was 17 %.
With increasing efficiency of the dialyser, it is possible
that urea is eliminated more rapidly from the blood than
If this rebound effect is taken into account in the cal-
it can diffuse from the cells into the blood. Due to this
culation of the dialysis dose, the resultant Kt/V value is
relative delay of urea movement from cells into blood,
referred to as equilibrated Kt/V (abbreviated to eKt/V).
the intracellular compartment becomes a non-equilib-
On average, equilibrated single-pool Kt/V (eKt/V) is 0.2
rated reservoir for urea, and this aspect is not taken into
lower than non-equilibrated single-pool Kt/V (17,18).
account in the single-pool models for urea kinetics (9,12,13).
Hence, on completion of a dialysis treatment, the intra-
In order to obtain an exact value for equilibrated Kt/V,
cellular urea concentration is greater than in blood
the BUN concentration should ideally be measured 30
plasma, and the diffusion of urea from cells into blood
minutes after completion of dialysis, but this is, un-
nevertheless continues for approximately 30 – 60
fortunately, not practicable in routine practices of out-
minutes after the end of treatment43. This phenom-
patient haemodialysis centres. In order to overcome
enon is called urea rebound (14,15). If this intracellular
this problem, various formulae have been developed
urea pool is large on completion of dialysis and is not
which, after a third blood (urea) sample has been taken
taken into account, the effective dialysis dose Kt/V will
during the dialysis session (usually after 70 minutes
be overestimated. This effect is particularly marked if
dialysis), allow the postdialytic equilibrated urea con-
high performance dialysers are used in combination
centration to be approximatively calculated (16,19). The
with a short duration of dialysis (16).
additional effort required to obtain a third blood (urea)
sample has meant that this method has not been
In addition to the relative delay of transfer of urea
widely accepted.
between the various body compartments, the marked
differences in blood perfusion of organs also contribute
Daugirdas has also developed a formula which allows
to the rebound effect. It should be borne in mind that
the results of calculation of single-pool Kt/V to be extra-
70 % of total body water, and thus also urea, is present
polated to equilibrated Kt/V (20). Formula 1 ( artKt/V) is
in body organs with a relatively low blood perfusion,
applicable if an arterial postdialytic urea value from
such as skin and muscles at rest. As these urea-rich
an arterio-venous access is available, while formula 2
organs have only a relatively low blood flow, their con-
( venKt/V) should be used if a mixed venous urea value
tribution to the total plasma urea which reaches the
from a veno-venous access is available:
extracorporeal circulation is less than that of organs
9
In 2002, Port et al. published an observational study
(1) equilibrated or eKt/V = artKt/Vsp – (0.6 x artKt/Vsp/T) + 0.03
(2) equilibrated or eKt/V = venKt/Vsp – (0.47 x venKt/Vsp/T) + 0.02
of major importance on the effect of delivered dialysis
dose on the risk of mortality (31).
T: dialysis treatment time in hours, t: dialysis time in minutes
In this retrospective study, the data for 45.967 US paThe key advantage of these formulae is that only two
tients who had commenced chronic haemodialysis
blood samples are required for the calculation of the
therapy between April 1997 and December 1998 were
equilibrated Kt/V.
examined 44.
single-pool Kt/V (spKt/V) values and equilibrated Kt/V
values (eKt/V) relative to the duration of treatment.
Table 1: Ratio of single-pool Kt/V (spKt/V) and equilibrated Kt/V (eKt/V)
as a function of treatment time (t)
eKt/V
spKTt/V
1.0
1.1
1.2
1.3
1.4
1.5
1.6
2.0 hrs
0.73
0.80
0.87
0.94
1.01
1.08
1.15
2.5 hrs
0.79
0.87
0.94
1.02
1.09
1.17
1.25
3.0 hrs
0.83
0.91
0.99
1.07
1.15
1.23
1.31
3.5 hrs
0.86
0.94
1.02
1.11
1.19
1.27
1.36
4.0 hrs
0.88
0.97
1.05
1.14
1.22
1.31
1.39
4.5 hrs
0.90
0.98
1.07
1.16
1.24
1.33
1.42
5.0 hrs
0.91
1.00
1.09
1.17
1.26
1.35
1.44
Annual adjusted death rates [%]
The following table shows the relationship between
Dose Category
Size of circle reflects number of patients per group
*
*
*
*
Small BMI < 23.2 kg/m
Medium BMI 23.2 – 27.8 kg/m 2
Large BMI > 27.8 kg/m 2
2
*
*
*
Small
*
*
Medium
Large
* p<0.05 compared to next lower URR group
44: Dialysis dose and body mass index are strongly associated with survival
in haemodialysis patients. Retrospective analysis of data from 45.967 US
hemodialysis patients starting dialysis during April 1997 through December
1998 (adapted from (31)).
In order to not mask the relationship between mortality
2.2 The clinical relevance of the
dialysis dose
risk and dialysis dose by the separate risk factor “body
weight of the patient”, patients were initially sorted into
three body weight groups – small, medium and large.
If dialysis dose is determined, it is possible to prescribe
The relationship between mortality risk and dialysis
and subsequently monitor the dialysis treatment on the
dose was then analysed separately for each of these
basis of clinical parameters. A significant correlation
body weight groups. The result was confirmed over
between the average delivered dialysis dose and patient
the whole range of dialysis doses analysed: the higher
mortality rates has been demonstrated in many clinical
the delivered dialysis dose, the lower the rate of patient
studies (1,21–29). All these studies reiterate the fact that
mortality. This study also showed that there is no specific
the higher the delivered dose of dialysis, the lower the
maximum dose above which no further decrease in
patient mortality rates.
patient mortality can be achieved. This means that during
each dialysis treatment, it is advisable to deliver the
The NCDS study (30) was the first long-term study which
highest dialysis dose possible.
investigated the correlation between dialysis dose and
10
therapeutic outcome. The results not only demonstrated
Other clinical aspects, such as the erythropoietin (EPO)
a statistical relationship between urea elimination and
requirement, can also be influenced by the dialysis dose
mortality, but also allowed Gotch & Sargent to develop
Kt/V. In a study published in 2001, the EPO require-
the urea kinetic modelling method and define the Kt/V.
ment of two patient groups with different Kt/V values
was compared (32). Measured haematocrit was identi-
consensus on best practices and dialysis adequacy
cal, at 35 ± 1.5 %, in the two investigated groups, A
amongst the European nephrological community (67).
and B, although group A received dialysis at a low Kt/V
<1.2 and group B received dialysis at a high Kt/V >1.4
The respective recommendations regarding dia-
45. While group A (Kt/V<1.2) had an EPO requirement
lysis dose are specified as follows:
of 183 ± 95 U/kg/week, patient group B with its high
Kt/V (>1.4) required only 86 ± 33 U/kg/week. This
• The delivered dialysis dose should be regularly
study shows that if a sufficiently high dialysis dose is
measured and monitored – at least monthly using a delivered, this can have a positive effect on the overall
standardised method
clinical condition of the patient, which, in turn, is re-
• The delivered dialysis dose should be expressed as
flected in a reduction of the EPO requirement.
equilibrated Kt/V (eKt/V) or as single-pool Kt/V (spKt/V)
• The minimum dose per session on a thrice-weekly
EPO dose [U/kg/week]
schedule should be eKt/V ≥ 1.20 (spKt/V ~ 1.4)
Group A
Hct: 35%
The EBPG for Haemodialysis are considered to be the
reference guidelines in Europe and have been adopGroup B
Hct: 35%
ted or taken as the basis for the preparation of national
guidelines.
It has become one of the main aims of haemodialysis
EPO dose
treatment, particularly in the US, to deliver a high Kt/V
45: The influence of a high Kt/V on the weekly EPO-dose (adapted from (32)).
dialysis dose. In the US, the average delivered Kt/V
dialysis dose continuously increased in the period 1986
to 1999 from 0.9 to today’s figure of greater than 1.4.
2.3 Recommendations for dialysis dose
and the frequency of measurement of
delivered dose
The prescription of an adequate Kt/V not only represents the mathematically standardised specification of
a verifiable therapy goal, but is a quality criterion for
As a general rule, it is the task of the treating nephro-
dialysis therapy itself because of the frequently descri-
logist, to prescribe the form and dose of dialysis treat-
bed direct correlation between dialysis dose and patient
ment, taking into account the specific clinical factors
mortality (1, 21 – 29). The regular measurement of delivered
of the individual patient.
Kt/V is thus an important aspect of medical quality
assurance. To date, however, the need to extensively
A very comprehensive collection of recommendations
sample urea concentrations, and the associated
for the prescription of dialysis was first provided by the
logistical and financial requirements, has made it
US National Kidney Foundation (NKF) in their guide-
difficult to conduct close monitoring of dose or even
lines on adequate haemodialysis treatment. The DOQI
to measure delivered dose in each session. As an auto-
guidelines were published in 1997 and subsequently
mated procedure, which is not based on a urea/blood
updated as the K/DOQI guidelines (Kidney Disease
sampling method, the Online Clearance Monitoring
Outcomes Quality Initiative) in 2000 (33). The European
(OCM®) has made it possible to measure dialysis dose
Best Practice Guidelines for Haemodialysis (EBPG Part1)
easily without additional expenses during on-going
were introduced in 2002 and represent the current
dialysis treatments at every session.
11
3. Online Clearance Monitoring – OCM®
concentration essentially determines the total conductivity of the dialysis fluid.
Although the small, positively-charged sodium ion differs from the non-charged and larger urea molecule,
both particles exhibit comparable in-vitro and in-vivo
diffusion characteristics across a synthetic dialysis
membrane, i. e. their specific diffusion coefficient is
almost identical at 37°C (Na+: 1.94 x 10 – 5 cm2/s,
Urea: 2.20 x 10 – 5 cm2/s46 (34) ). Under real dialysis
conditions, the difference in clearance is even smaller
than the difference of diffusion coefficients since the
OCM® screen during a HDF treatment
clearance is limited by blood and dialysate flow rates
and not by the diffusion process across the dialyser
The Online Clearance Monitoring (OCM®) is a stan-
membrane.
dard feature integrated in the Fresenius Medical Care
lytic measurement of the delivered dialysis dose Kt/V,
the effective in-vivo urea clearance, the accumulated
cleared plasma volume Kt and the plasma sodium
concentration of the patient. OCM® can be applied
during regular ONLINEplus haemodiafiltration treatments in pre or post dilution mode as well as during
standard haemodialysis.
aqueous solutions
Electrolyte clearance [ml/min]
5008 Therapy System. It provides automatic intradia-
Coefficients of diffusion at 37°C
[cm2/s]
Na+
Urea
1.94 x 10-5
2.20 x 10-5
Urea clearance [ml/min]
46: OCM® is based on the equivalence of electrolyte and urea clearance
(adapted from (34)) The dialysis dose determined by the Online Clearance
Monitoring (OCM®) is equivalent to a single-pool Kt/V
(spKt/V).
By means of indirect determination of ion concentrations in the haemodialysis solution (measurement of
conductivity at the inflow and outflow of the dialyser) it
3.1 The method of OCM operation
®
is technically possible to determine the diffusion profile
of sodium ions across the dialysis membrane and thus
To achieve the objective of developing a low cost
calculate the dialysance or ionic clearance (D). On the
method of monitoring clearance, it was necessary to
basis of the dialysance of sodium ions, the “diffusibi-
move away from the cost-intensive concept of enzy-
lity” of urea through the membrane (permeability) and
matic urea analysis. In searching for an alternative, a
thus urea clearance can be determined (35) .
substance was considered which is present in large
12
quantities in the dialysis fluid and where changes in
For accurate measurement of sodium dialysance,
concentrations can be measured by the sensors in-
conductivity sensor cells have been installed in the
stalled within the dialysis machine – namely ionised
inflow and outflow lines of the dialyser to measure the
sodium. Sodium ions represent the largest proportion
conductivity of the dialysis fluid (prior to the dialyser)
of freely mobile electrolytes in the dialysis fluid and their
and in the dialysate (after the dialyser) (36).
Blood outflow
Fistula
Dialysis fluid inflow
Cb out
This short-term increase in the conductivity of the dia-
Cd in Conductivity cell “in”
Dialyser
Cb in
Blood pump
Cd out
reduced by diffusion of a portion of the sodium ions
across the dialysis membrane into the blood of the
QD
QB
lysis fluid prior to entering the dialyser is subsequently
Conductivity cell “out”
patient during the passage through the dialyser. The
dynamic input conductivity signal (pulse) at the dialyser
inflow is continuously monitored by the conductivity
Blood inflow
sensor installed at that position: the signal at the outflow
Dialysate outflow
47: The diagram shows the location of the 2 conductivity cells of the OCM®
of the dialyser is registered by an equivalent sensor
positioned there. The relative areas under the curves
for the two recorded conductivity signals reflect the
In order to achieve a detectable diffusion of sodium
diffusion of sodium ions across the dialyser membrane.
ions across the membrane, the otherwise moderate
The lower the value of outflow conductivity compared
diffusion gradient of sodium between the blood and
to inflow conductivity, the greater the amount of sodium
dialysis fluid sides of the dialyser must be temporarily
that has diffused from the haemodialysis solution into
increased.
the blood compartment as a result of the diffusion
gradient or, in other words, the more permeable the
For this purpose, the dialysis machine induces a short
dialysis membrane for sodium is (45).
term pulse to increase (or decrease) the sodium concentration in the dialysis fluid, thereby resulting in an
As urea – as postulated above – has a diffusion profile
increase in diffusion of sodium ions into the blood
similar to that of the sodium ion, urea clearance can be
compartment or in the reverse direction48. Assu-
determined (using appropriate correction factors) irre-
ming that the conductivity pulse does not exceed the
spective of the actual concentration of urea in the blood.
specified conductivity limits, alternate pulses increase
and decrease conductivity to ensure that the sodium
Steil et al. were able to demonstrate in 1993 that the
balance remains as neutral as possible (37 – 44).
dialysance is directly proportional to urea clearance (35).
They showed how closely measured ionic clearance
correlates with measured urea clearance. In a validation
Inlet/Outlet conductivity
[mS/cm]
study conducted in 2001, Kuhlmann et al. produced
clinical evidence that dialysance also correlates with
urea clearance in-vivo, and that it can be determined
Rec.
accurately within a very low analytical error range of
only ± 5 % by the OCM®49 (39). As a comparison: the
analytical error for the determination of urea in the
Dialysis Time [secs]
laboratory is approx. ± 7 %. In both of the above-mentioned investigations, it was possible to demonstrate
Inlet conductivity
Outlet conductivity
Recirculation
48: Online Clearance Monitoring is operating with a short-term dynamic
conductivity pulse
that the correlation between electrolyte clearance and
the clearance values for urea determined using standard methods is almost ideal. The majority of results
lie, with sufficient precision, on the line of identity and
the correlation value r is close to the ideal value of 1
(if all values for ionic clearance and laboratory data
13
clearance were exactly identical, all results would be
ports recirculating sodium ions to the dialyser which,
on the ideal line). The majority of values are within an
depending on the concentration in the blood, will diffuse
error range of only ± 5 – 6 %.
back into the dialysate. Consequently this results in a
less favourable ratio of the areas under the conductivity
Through further improvements of the Online Clearance
curves, and thus to a reduction in clearance equivalent
Monitoring® method, Goldau et al. reported in a further
to the contribution made by recirculation. Although it is
series of analysis in 2002 an improved level of precision
not possible to produce actual figures for recirculation
of below the 5 % error limit (45).
from the OCM®, the effect is taken into account in the
calculation of effective in-vivo clearance.
The OCM® determines clearance “online” during the
Blood urea clearance [ml/min]
entire treatment period, i. e. with no time lapse and
at predefined measurement intervals. The number of
measurement cycles to be performed during the treatment can be pre-selected within certain limits (see 5008
Operator’s Manual). In addition, the OCM® is capable
of detecting adjustments to blood and/or dialysate flow
rates within 1 minute and then immediately recalculates
the corresponding new clearance values. This means
Error K: ± 5%
that the effects of any alteration to treatment parameters
on actual clearance can be continuously monitored
Electrolyte clearance OCM ® [ml/min]
49:
Correlation of electrolyte clearance measured by the OCM® and
blood urea clearance
during an ongoing session.
In addition to the urea clearance K, the data for the
current effective dialysis time t are obtained from the
Fresenius Medical Care Therapy System 5008 and are
14
The precision of the conductivity monitoring is deter-
included in the calculation of the dialysis dose. The
mined, among other factors, by the stability of the plasma
effective dialysis time t is defined as the time in which
sodium concentration during measurement. The less
physical dialytic processes between the blood of the
variation in the plasma sodium concentration of the
patient and the dialysis fluid occur. The time of any
patient during the measurement cycle, the more pre-
interruption of treatment for technical or therapeutic
cise the result is. For this reason, the time interval of
reasons and the duration of preparation and reinfusion
conductivity variation is kept as short as possible in
procedures are not included: only the “true” dialysis
the OCM® technique.
time (diffusion time) is taken into account.
With this comparatively short (but still sufficiently long)
On the basis of the two measured parameters – urea
measurement of dialysate conductivity at the dialyser
clearance and effective dialysis time – the OCM®
outflow, not only the sodium dialysance of the dialyser,
calculates the cumulative water volume contained
but also the negative effects of total recirculation (fis-
within the blood K x t (in litres) which has been cleared
tula recirculation plus cardiopulmonary recirculation)
of urea, which is equivalent to that proportion of the
can be determined48. Even after the conductivity pulse
circulating blood from which all urea has been re-
in the dialysate has faded out, recirculating blood trans-
moved during dialysis: K x t = x (L).
In order that the Kt/V value can be determined by division of the result for K x t by the urea distribution
volume V, the operator must enter an appropriate value for the urea distribution volume V of the individual
dialysis patient.
Effective clearance:
accurately known
from OCM® (±6%)
K x
Normally unknown
t
Effective dialysis time:
precisely known from
the 5008
V
V from anthropometric data (Watson,Hume-Weyers ...),large deviations
lead to an approximate Kt/V
V from a previous Urea Kinetic Modelling procedure (DCTool ), leads to
the best results for Kt/V (± 0.1 Kt/V)
V from other methods, e.g. bioimpedance
410: To calculate the Kt/V the OCM® measures K and the 5008 Therapy
System measures the exact effective dialysis time t; the user has to enter the
patient’s V
411: A calculator to estimate the urea distribution volume V according to
anthropometric formulae is integrated in the OCM®
It is not only possible to derive the V of a patient by
calculation, but this parameter can also be precisely
measured. In clinical routine, the bioimpedance
spectroscopy technique or the urea kinetic modelling
The easiest method of estimating urea distribution
method described in section 2 above can be used.
volume V is to use the anthropometric formulae de-
Once this measured value is available, it can be directly
veloped by Watson (48), Hume-Weyers (49) and Mellits-
entered into the data-entry menu of the OCM®: the
Cheek (70), the latter being especially adapted for
information necessary for the anthropometric formulae
children below the age of 16. All formulae can be
(age, gender, etc.) is then, of course, no longer required.
selected in the OCM® menu of the 5008. The Watson
formula calculates the V of a patient on the basis of
The anthropometric formulae allow V to be simply and
body weight, height, age and gender411.
quickly estimated, but the results represent only a standardised mean value for the population as a whole.
Deviations attributable to individual factors, such as an
Male
Vurea = 2.447 - 0.09516 x age + 0.1074 x height + 0.3362 x weight
Female
Vurea = -2.097 + 0.1069 x height + 0.2466 x weight
above-average proportion of fat or muscle tissue, are
not accounted for. In some cases, there may be marked
differences between the value for V calculated using
the Watson formula and the measured value for V.
Kloppenburg et al. have demonstrated, in a compara-
The Hume-Weyers formula requires information on
tive study, that the results for urea distribution volume
body weight, height and the gender of the patient; in-
V calculated using the anthropometric Watson formula
formation on age is not required. For information on the
regularly exceed the measured V of the same patient
Mellits-Cheek formula please refer to the FAQ section.
by 26 % (50). Thus, if the value for V obtained using the
Watson formula is used instead of a measured value
for calculation of Kt/V, the achieved Kt/V is frequently
underestimated.
15
In order to determine an exact value for spKt/V using
urea profile of a haemodialysis patient based on two
the OCM®, it is always preferable to enter the measured
blood samples (pre and postdialytic) using the sing-
urea distribution volume rather than an anthropomet-
le-pool variable volume method (7). Important data
rically-derived V.
relevant to the dialysis and nutritional status of the
patient, such as urea distribution volume, Kt/V and
protein catabolic rate (PCR) are derived from this. The
DCTool programme differs from the standard urea
kinetic programmes in that, instead of calculating theoretical clearance on the basis of blood and dialysate
flow rates, the effective in-vivo clearance – averaged
for the treatment as a whole – as measured by the
OCM® is used for modelling.
For the determination of the urea distribution volume
of a patient using the DCTool, the basic patient data
and information on treatment regimen needs to be
entered. Then one dialysis treatment is selected and
the related main treatment and OCM® data (i. e. the
average effective in-vivo clearance) together with the
412:
pre- and postdialytic urea values from blood samples,
DCTool is a urea kinetic modelling software to precisely calculate
the urea distribution volume of the patient
are entered in the DCTool programme. With this information, the DCTool conducts an urea kinetic analysis
With the software “Dose Calculation Tool” (DCTool),
and determines a precise value for the urea distribution
Fresenius Medical Care provides the OCM® user
volume V; apart from other very interesting dose and
with an uncomplicated and precise instrument for
nutritional parameters. Once this assessed value for V
the accurate calculation of patient-specific urea dis-
is available, it can be entered directly into the OCM®
tribution volume V using treatment and laboratory
template, saved on the PatientCard and is hence avail-
data. The DCTool is a urea kinetic modelling (UKM)
able for subsequent treatments. This enables the OCM®
software programme based on 2 point urea kinetic
to calculate an exact value for spKt/V with an error < 0.1
modelling. The programme determines the weekly
for each routine dialysis session conducted over a lon-
The conventional procedure today
Blood samples (expensive)
Once a month/quarterly
Retrospective
Staff, syringes, lab time, cost and energy
6–8%
Inconvenient
Unpractical and uncommon
Aspects
Kt/V ≥ 1.2... 1.8
Frequency
Control
5008 with OCM ® option
Dialysate; K and t (no additional costs)
In every session
Continuous, online
Effort
None
Accuracy of K
6%
Handling
Automatic
Quality assurance
Standard!
413: OCM® offers many advantages in comparison with the conventional method for the Kt/V measurement
16
ger time period (up to 6 months for stable patients) (66).
It is possible to convert this single-pool Kt/V determined
by the OCM® to an eKt/V (≈ double pool Kt/V) using
the formulae provided in section 2.1. Alternatively,
eKt/V values are also shown in the table 1 on page 10.
In order to ensure that the V value is appropriately
updated, it is advisable to repeat urea kinetic modelling calculations with DCTool within the framework of
414:
The OCM® display: The blue line indicates the urea clearance, the
cumulating Kt/V is displayed by the red line, the Goal-Kt/V is visualised as a
green line.
routine laboratory tests every 6 – 12 weeks.
In clinical studies in which 40 treatments and 151 treat-
haemodialysis in the removal of middle molecules. In
ments were analysed, it was shown that the DCTool-
selected European countries, up to 30 – 40 % of the
method provided the optimum value for the urea distri-
dialysis population is treated with ONLINE HDF, the
bution volume of a patient (51,52,66) and that the results
average however being around 10 % (61).
agree well with the total body water measured with
bioimpedance spectroscopy. Several studies have demonstrated clinical advantages of the ONLINE HDF treatment modality such as
The use of the OCM® functionality and DCTool in
an increased dose of dialysis, a reduced risk of ß2-
combination makes it possible to determine the exact
microglobulin-associated amyloidosis (62,63), a positive
value for spKt/V during each routine dialysis.
influence on the treatment of anaemia (64) and im-
proved intradialytic cardiovascular stability (65). The
The parameters relevant to therapy monitoring, includ-
results of two recent studies even demonstrate that
ing the OCM® measurement results, are displayed
patients treated with ONLINE HDF had a significant
in a clear overview with a multi-coloured diagram on
35 % reduction of mortality risk compared to patients
the touch screen of the 5008 Therapy System. The
treated with standard haemodialysis (68,69).
clearance K is displayed during the course of the
treatment as a blue line in the “OCM® diagram” graphic,
The precision of the OCM® clearance measurement
so are the current and absolute values for K, Kt/V or
under ONLINE HDF conditions has been validated
Kt and Goal-Kt/V. In addition, the cumulative Kt/V (red
in-vitro and in clinical experiments by Canaud et al.
line) or Kt (black line) are visualised in relation to the set
(Hôpital Lapeyronie, Montpellier, France; publication in
Kt/V target (green line).
KI pending (71)). In these investigations, an error range
of 6 % for the clearance measurement of the OCM®
system during ONLINEplus HDF was reported.
3.2 OCM in ONLINEplus Haemodiafiltration treatments
®
With the introduction of Online Clearance Monitoring in
ONLINEplus Haemodiafiltration it is possible to easily
ONLINE Haemodiafiltration (HDF) with its numerous
monitor the dose of dialysis during highly efficient,
positive effects on uraemia-related cardiovascular risk
convective treatments. factors, is acknowledged as the most effective dialysis
treatment modality that comes closest to the elimination profile of the natural kidney. In particular, HDF
shows superior clearances in comparison to standard
17
4. Optimisation of dialysis efficiency
The efficiency of each haemodialysis treatment is determined by the following four parameters:
• the effective extracorporeal blood flow
• the actual dialysis time
• the effective urea clearance achieved by the dialyser
• the dialysate flow rate
It is essential to achieve the appropriate balance of these parameters in order to ensure that adequate dialysis treatment is provided and also to ensure that the resources available are economically utilised.
4.1 Blood flow
– under standard conditions of dialysis lead to an
increase in the urea clearance of approximately 15 %.
Dialysate flow 500 mL/min
When prescribing the required blood flow, and par-
Urea clearance [mL/min]
ticularly when increasing blood flow, the individual
vascular access of each patient must be considered.
The fistula blood flow rate (average flow rate in radiocephalic fistula is approximately 500 – 900 mL/min)
should always markedly exceed that of the extracorporeal blood flow rate in the dialyser, otherwise there
is the risk that recirculation, which compromises
efficiency, may be induced. Recirculation occurs when
Blood flow [mL/min]
415: Urea clearance of Fresenius Medical Care FX 60 dialyser at different
blood flow rates
blood that has already been cleared of toxins flows,
counter to the natural direction of flow in the fistula,
out of the venous cannula directly into the arterial
cannula and mixes with non-purified blood. Recirculating blood has only a low toxin load prior to its
The extent of urea clearance achieved during dialysis
repeated passage through the dialyser. As a result,
is determined largely by the effective blood flow rate.
the toxin removal per time unit is reduced and dialysis
Increasing the blood flow rate is thus a very effective
efficiency decreases.
method of increasing dialysis efficiency (53). Figure 15
18
illustrates that in the blood flow rate range 0 – 600
There are, however, various devices available, such as
mL/min, the increase in urea clearance is proportional
the Blood Temperature Monitor (BTM), obtainable
to the increase in blood flow rate. Under the specified
as an optional extra to the 5008 Therapy System,
conditions, e. g. with the Fresenius Medical Care FX 60
which can automatically measure recirculation at a
dialyser, an increase in blood flow rate from 200 mL/min
pre-selected blood flow rate. In case of a signifi-
to 400 mL/min results in an increase in urea clearance
cant drop in the measured clearance values (≥ 20 %)
by 65 %, while an increase in blood flow rate from
during the same treatment or compared to the
150 mL/min to 300 mL/min results in an improvement
previous one stored on the 5008 PatientCard, a
of 82 %. But even moderate increases in blood flow
BTM recirculation measurement can be automati-
rate by 50 mL/min – from 250 mL/min to 300 mL/min
cally initiated by the OCM®.
Since the OCM® conducts the clearance measure-
4.2 Dialysis time
ment on the dialysate side only, the accuracy of K is
not influenced by deviations in the blood flow rate. In
As the dialysis time t is a direct variable in the Kt/V
the case of blood or dialysate flow changes in between
formula, it is important to ensure that a sufficiently long
two subsequent measurements, the OCM® is able to
effective dialysis time is delivered to ensure provision of
account for these changes by using a mathematical
an adequate dialysis dose. It is essential to prescribe
estimate for K under the new conditions.
a sufficiently long treatment time which, by avoiding
all interruptions caused by alarms or other delays,
should, as far as possible, also represent the effective
dialysis time.
The DOQI guidelines, for example, take into account
the discrepancy between prescribed and effective
treatment time, which frequently occurs as a result of
undesirable interruptions in the dialysis treatment, by
recommending prescription of a slightly increased Kt/V
value of 1.3 if a Kt/V of 1.2 is to be achieved (33). In a
study published in 2001, J. Leon et al. investigated the
dialysis prescriptions for 721 dialysis patients (54). They
found that in 15 % of patients the dialysis prescription
was too low to achieve the minimum dose of Kt/V 1.2
as recommended in the DOQI guidelines. They also
concluded that in this patient group, a prolongation
of treatment by up to 30 minutes (depending on
patient) would have resulted in the delivery of an
adequate dialysis dose in 75 % of the cases.
This result shows that even a moderate prolongation
of treatment time can be an essential factor in ensuring delivery of an adequate dialysis dose. Individual
prolongation of treatment time should thus seriously
be taken into consideration, despite the difficulties of
incorporating this in shift schedules and the unwillingness of patients to an increase in the dialysis time.
19
4.3 Dialyser
(Membrane surface area, low flux/high flux)
4.4 Dialysate flow rate
It is the concentration gradient between the blood and
dialysate which mainly determines the diffusion rate
240
during haemodialysis. The larger the flow of fresh, toxin-
free dialysis fluid through the dialyser, the larger the
220
removal of toxins by diffusion is (55).
210
200
Blood flow
QB: 300 mL/min
QD: 500 mL/min
190
180
170
0,6
0,8
1,0
1,2 1,4 1,6 1,8 2,0
Effective dialyser surface [m2]
2,2
2,4
FX-class high flux range
FX-class low flux range
416: Urea clearance of Fresenius Medical Care low and high flux dialysers
as function of the effective surface
In vitro urea clearance FX 60 [mL/min]
Urea clearance [mL/min]
230
QB: 300 mL/min
QD: 500 mL/min
Dialysate flow [mL/min]
The dialyser itself plays an important role in the efficiency of dialysis treatment. The use of a dialyser with
417: Urea clearance of a FX 60 dialyser as function of blood and dialysate
flow. The higher the blood flow the higher is the positive effect of increasing the
dialysis fluid flow on urea clearance
the highest possible urea clearance is required for optimisation of the dialysis treatment. As a representative
In many dialysis centres, a dialysis fluid flow rate of
of other low molecular weight substances, urea is one
500 mL/min is used by default in haemodialysis treat-
of the most important marker substances in dialysis.
ments, although optimal solute clearances would already be achieved at lower dialysis fluid flow rates. As
The urea clearance is not only determined by the active
shown in figure 17, at a dialysate flow rate equal to the
surface area of the membrane, but also by the membrane
blood flow rate, approximately 90 % of the maximum
permeability (high or low flux) and the construction of
solute clearance is already achieved. Thus, much
the dialyser itself. Figure 16 shows the increase in urea
higher dialysis fluid flow rates would not significantly
clearance under the given conditions (blood flow rate:
contribute to increases in clearances and are therefore
300 mL/min, dialysate flow rate: 500 mL/min) in relation
not necessary from an economical point of view.
to an increase in the effective membrane surface area.
Under identical conditions, urea clearance is improved
The 5008 Therapy System offers the AutoFlow func-
by changing from low flux to high flux dialysers. To uti-
tion, which automatically adjusts the dialysis fluid flow
lise a given dialyser to its full capacity, it is important
rate in order to derive an optimal ratio between blood
to consider the relationship between effective surface
flow rate and dialysis fluid flow rate. Any potential effects
area and the achievable blood flow (see instructions
on low molecular (e. g. urea) clearance can however be
for use: re-commended blood flow range).
monitored with OCM®, thus providing another very
meaningful function for further treatment optimisation,
e. g. by means of increased blood flow and/or perform-
ing ONLINE HDF.
20
The prerequisite for an effective dialysis treatment is
an appropriate balance between blood flow rate, dialysate flow rate, treatment time and the dialyser used.
For this purpose, Fresenius Medical Care has developed
appropriate software in the form of the Clearance Calculation Tool (CCT), which makes it possible to compare
the efficacy of Fresenius Medical Care dialysers under
diverse predefined treatment conditions.
418: The CCT Clearance Calculation Tool is a software for the planning of
haemodialysis treatments. CCT allows a clearance estimation of any Fresenius
Medical Care dialyser over the full range of treatment conditions
21
5. Measurement of plasma sodium with the OCM®
In addition to the delivered dialysis dose, the OCM® also
Various studies have demonstrated that restriction of
measures the level of plasma sodium of the patient.
sodium intake has a favourable effect on long term
This information is a useful aid in the appropriate
blood pressure control in dialysis patients; low sodium
therapeutic adjustment of the sodium concentration
content in the dialysate, provided this is tolerated by
of the dialysis fluid to the individual plasma sodium
the patient, can assist in dietary control of sodium in-
level of the patient.
take (57 – 59). Krautzig et al. have demonstrated that with
low sodium intake, it is possible to reduce, or even dis-
In a clinically stable haemodialysis patient, there is
continue, the use of anti-hypertensive medication (60).
physiological equilibrium between the quantity of salt
ingested with the nutrition and the quantity of NaCl
However, if a dialysate with a non-physiological, low
removed during haemodialysis.
sodium concentration is used, this can frequently
trigger intolerance reactions, such as hypotension,
There are two mechanisms of intradialytic removal of
tiredness and cramps.
NaCl: ultrafiltration (UF) and diffusion.
Conversely, the use of a dialysate with a non-physioThe electrolyte composition of the ultrafiltrate removed
logical, high concentration of sodium may improve
for the purposes of dehydration of the patient is very
blood pressure stability during dialysis, but also in-
similar to that of blood plasma, the NaCl concentration
creases the patient’s thirst and results in a subsequent
in the ultrafiltrate varies from patient to patient in the
increase in fluid intake by the patient. This, in its
approximate range 135 – 140 mmol/L. The quantity of
turn, leads to increased overhydration and long-term
NaCl removed during ultrafiltration depends directly on
hypertension in the patient. Figure 20 summarises
the volume of UF removed; the higher the volume of UF,
the advantages and disadvantages of high and low
the greater the quantity of NaCl removed from the patient.
sodium concentrations in the dialysate.
Diffusion is even more effective than ultrafiltration in
the removal of NaCl, though in this case maintenance
of an effective concentration gradient between blood
Chronic effects
Acute effects
+
–
cardiovascular stability
thirst
–
–
–
–
extracellular dehydration
plasma osmolality
disequilibrium
hypotension
Na145
Chronic volume overload
hypertension
–
–
blood pressure control
+
and dialysate sides is required.
If the concentration of NaCl available for free diffusion
in the blood plasma of the patient is higher than in the
dialysis fluid, there is a flow of NaCl from blood into
dialysis fluid; NaCl is removed from the patient. The
opposite can, of course, also occur: if the concentra-
Na138
Na130
419: Acute and chronic effects of different sodium concentrations in the
dialysis fluid
tion of NaCl in the dialysis fluid is higher than in blood
plasma, it diffuses from the dialysis fluid into the blood
and there is dialysis-induced salt-loading.
Individual prescription of the sodium concentration of the
dialysis fluid always requires achieving a compromise
The concentration of sodium in the dialysis fluid thus
between long-term beneficial blood pressure control
determines whether the sodium balance is positive or
(with low dialysis fluid sodium) and the short-term ad-
negative during haemodialysis treatment.
vantage of better cardiovascular stability during treatment (with high dialysis fluid sodium). Hence, when
22
deciding on the optimum concentration of sodium in
factors so that the displayed value for plasma sodium
the dialysis fluid, the nephrologist should consider the
is equivalent to that obtained by means of flame pho-
predialytic plasma sodium, the general status and the
tometry assay.
cardiovascular stability of the patient.
Small absolute differences between the plasma sodium
concentration determined by the dialysis machine
Plasma-Na [mmol/l]
using this non-invasive method and the results
of laboratory analysis can be explained by deviations
of the measurement and calibration instruments
Pat 1 (Dial.-Na: 140 mmol/l)
Pat 2 (Dial.-Na: 140 mmol/l)
Pat 3 (Dial.-Na: 142 mmol/l)
Pat 4 (Dial.-Na: 142 mmol/l)
used. Of more clinical relevance, however, is the
change in plasma sodium concentration during dialysis – with its associated effects – relative to predialytic
baseline plasma sodium. Using the data for changes
in plasma sodium over time registered by the dialysis
420:
Example of a plasma sodium profile of 4 HD patients measured
by OCM®
machine, it can be determined whether the patient
is being loaded with sodium from the dialysis fluid
(plasma sodium concentration increase) or whether
too much sodium is being removed from the blood
Figure 20 shows the effects of a haemodialysis treat-
(plasma sodium concentration falls), or whether the
ment on the plasma sodium concentration in individual
sodium concentration of the haemodialysis solution is
patients (mean values for 10 treatments are quoted).
appropriate for the patient (e. g. a tendency to constant plasma sodium concentrations). Online Clearance
While there was little fluctuation in plasma sodium levels
Monitoring (OCM®) can assist to appropriately adjust
in patients 1 and 2 (the dialysis fluid used for both these
the sodium concentration of the haemodialysis solu-
patients had a sodium concentration of 140 mmol/L),
tion during the ongoing treatment.
plasma sodium levels in patients 3 and 4 (here the
specified dialysis fluid sodium concentration was 142
The plasma sodium concentration over time is displayed
mmol/L) increased by 2.5 – 3 mmol/L during dialysis.
as a red line in the UF-Na-Diagram of the 5008. At low
flow conditions (QB ≤ 80 mL/min; QD < 300 mL/min),
the plasma sodium concentration is not displayed. The
How can the OCM® be used for measurement of
accuracy of the value displayed is furthermore strongly
plasma sodium?
affected by the existence of fistula recirculation.
The OCM® determines sodium concentrations at the
dialysate inflow and outflow by monitoring conductivity.
The difference between the two values, in relation to the
dialysate flow rate, shows the rate of flow of sodium
into or out of the patient. Using the value for clearance
as measured by the OCM®, the plasma concentration
of sodium can be calculated. In this way, the OCM®
derives a value for plasma sodium from each clearance
measurement. The result is adjusted using correction
421: The kinetics of the plasma sodium concentration in the course of a HD
treatment can be displayed by the OCM® (red line)
23
6. Frequently Asked Questions about the OCM®
1. Is Kt/V as measured by the OCM® a single-pool or
of a blood flow change between 2 measurements). If an
double-pool Kt/V?
estimated Hct which deviates from the actual Hct of the
patient is entered in the OCM® template, this will have
The Kt/V value determined by the OCM® is a single-pool
little effect on the accuracy of the value for clearance
Kt/V (spKt/V). It is possible to convert the single-pool
calculated by the OCM®. If, for example, the entered
Kt/V determined by the OCM® to an eKt/V (≈ equilibrated
value for Hct is 10 % higher or lower than the actual
or double pool Kt/V) using the formulae provided in
value for Hct, there is only a 2 – 3 % change in the re-
Section 2.1.2.1 Alternatively, eKt/V values are also
sult for clearance. If no value for Hct is entered prior to
shown in the table on page 10.
commencement of treatment, the OCM® automatically
assumes a hypothetical value of 35 %. In case a 5008
2. In a comparison conducted at a dialysis centre, it
Blood Volume Monitor (BVM) is used simultaneously
was observed that the OCM® Kt/V was 10 % lower than
with the OCM®, the continuously measured Hct value can
the Kt/V measured on the blood side: what is the cause
be automatically transferred from the BVM to the OCM®.
of this discrepancy?
4. Why is the clearance measured by the OCM® frequen-
Such a difference is frequently seen if the value for urea
tly lower than clearance measured on the blood side?
distribution volume V used for Kt/V calculation by the
OCM® has been estimated using the Watson formula.
This occurs if a simplified method of whole blood
The anthropometric Watson formula tends to overesti-
clearance measurement is performed on the blood
mate the urea distribution volume in dialysis patients. As
side, where the full blood flow value QB is used
the precisely measured result for K x t determined by
for blood side calculation of clearance, while the
the OCM® is then divided by an incorrectly high value
OCM® correctly uses the effective flow of water
for V, this results in an underestimation of the delivered
contained within the blood (= plasma water + intra-
dialysis dose (Kt/V). This problem can be avoided if the
cellular water). The effective flow of water contained
value for V is determined more precisely using a bioim-
within the blood is equivalent to the effective blood
pedance spectroscopy (BIS) technique or urea kinetic
flow x 0.87. The factor 0.87 takes into account the
modelling (e.g. with the aid of DCTool) – see Section
characteristic composition of human blood. If the
3 – and this value being entered into the OCM® and
effective flow of water contained within the blood is not
stored on the PatientCard for future use.
used for blood side calculation of clearance, there can
be an inappropriate overestimation of urea clearance
3. What is the significance of haematocrit for the calcu-
by up to 25 % compared with the effective clearance
lation of clearance and plasma sodium concentrations?
which is accurately measured by the OCM®.
What alternative is there if no recent value for haematocrit is available for a patient? Could an estimated value
5. Could the accuracy of OCM® measurements be im-
for haematocrit result in an inaccurate result for Kt/V?
paired if equipment is not disinfected between each dialysis treatment?
The haematocrit is required to calculate the effective
24
flow of water contained within the blood (= plasmawa-
In theory, throughout dialysis deposits may occur on
ter + intracellular water) and subsequently the effective
the conductivity sensors of the OCM® just as in any of
Kt/V (Comment: Hct does not have any influence on K,
the other components of the hydraulic system of a
since only dialysate-side quantities are used to deter-
dialysis machine. To avoid this problem, it is mandatory
mine it. Rather, it enters the estimation formula in case
to disinfect the equipment after each dialysis session.
The risk of an inaccurate clearance measurement is
For girls with a height > 110.8 cm:
thus excluded.
V = -10.313 + 0.252 x body weight (kg)
+ 0.154 x height (cm)
6. Does the accuracy of the OCM® depend on the
membrane material used in the dialyser?
In order to obtain a precise value for V in children, a
bioimpedance measurement or urea kinetic modelling
No evidence has been found to date that the accuracy
(e. g. with DCTool) is preferable.
of the clearance measurement by the OCM® is influenced by the type of dialyser membrane used.
9. How does one take into account an amputation
when calculating urea distribution volume?
7. Can OCM® measurement be started during on-going
dialysis treatment?
Urea distribution volume V in amputated dialysis patients should not be estimated using anthropometric
In principle, the OCM® can be started at any time during
formulae (such as the Watson formula), but should be
on-going treatment. If, however, more than 80 minutes
determined by a bioimpedance measurement or urea
have passed since treatment was started without a suc-
kinetic modelling (DCTool).
cessful OCM® measurement performed, the system will
not calculate Kt and Kt/V. It would not be worthwhile ex-
10. Can OCM® also be used during ONLINE HDF?
trapolating backwards, as there may have been marked
changes in clearance since the initiation of treatment.
OCM® can be used during regular ONLINEplus Haemo-
dialfitration treatments in either post- or predilution mode
8. Is it possible to calculate the urea distribution volume
but due to the missing dialysate flow in the dialyser not
of children using the Watson formula?
in ONLINE-HF nor in Single-Needle modes. The Mellits-Cheek formula rather than the Watson formula should be used for anthropometric estimation of
V in children:
For boys with a height < 132.7 cm:
V = -1.927 + 0.465 x body weight (kg)
+ 0.045 x height (cm)
For boys with a height > 132.7 cm:
V = -21.993 + 0.465 x body weight (kg)
+ 0.209 x height (cm)
For girls with a height < 110.8 cm:
V = 0.076 + 0.507 x body weight (kg)
+ 0.013 x height (cm)
25
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