Note: Descriptions are shown in the official language in which they were submitted.
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Dialysis Method And Apparatus
Field Of The Invention
This invention relates to a method and apparatus for per--
forming hemodialysis. More particularly, the invention
relates to method and apparatus for performing hemodialy-
sis in which the osmolarity of the dialysis fluid varies,
non-linearly as a function of time during at least a
portion of the total time used for the treatment cycle.
Background Of The Invention
The use of dialysis to treat patients with kidney~ disease
is well-known. The treatment involves the use of an
artificial kidney dialyzer which is a device comprising a
first compartment for the flow of blood to be dialyzed and
a second compartment for the flow of an aqueous dialysis
fluid (or "dialysate" as it is sometimes called). The two
compartments are separated from one another in the device
by a semipermeable membrane suitable for the dialysis
procedure. Such semiperrneable membranes are commercially
available and are made from, for example, regenerated
cuprammonium cellulose or cellulose acetate. The semi-
permeable membranes may be used in kidney dialyzers in theform of sheet, tubing or hollow fibers.
In its broadest aspect, hemodialysis involves withdrawing
blood from a patient and passing that blood through the
blood flow compartment of the artificial kidney while at
the same time passing aqueous dialysis fluid through the
dialysate compartment. As the blood flows through the
dialy~er, impurities such as urea and creatinine are
transported throuyh the semipermeable membrane and are
dissolved in the dialysate. Cleansed blood exiting the
dialy%er is returned to the patient, ~hile the dialysate
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containina the impurities removed from the blood is
recirculated or discarded.
The dialysate comprises an aqueous solution of electro-
lytes which is prepared, either on a batch basis or
continuously, by dissolving the electrolytes in water or
by diluting a concentrated aqueous solution of the
electrolytes (called a "dialysate concentrate") with
water. In either case, the "standard" dialysate customar-
ily usecl to carry out the dialysis treatment has a fixedcomposition which typically comprises about 136 milli-
equivalents per liter (meq./l.) of sodium ion, about
3.5 meq./l.'of calcium ion, about 1.5 meqO/l. of magnesium
ion, about 2.6 meq./l of potassium ionl about
15 106.6 meqO/l. of chloride ion, and about 37 meq/l. of
acetate ion. (In some instances, part or all of the
acetate ion may be replaced by bicarbonate ion).
Since, as is well known, the conductivity of an aqueous
solution of electrolytes is a function of the concentra-
tion of electrolytes dissolved therein, it is possible to
ascertain whether the desired concentration of electro-
lytes is present in the dialysate being supplied to the
dialysate cornpartment by measuring the conductivity of the
-~ 25 dialysate. Thus a hemodialysis system typically comprises
a conductivity cell which is placed in the dialysate line
between the source of dialysate and the inlet to the
dialysate compartment and which continuously monitors the
conductivity of~the entering dialysate. The conductivity
cell has three electrodes uniformly spaced in an epoxy
casing. Two of these electrodes are wired together inter-
nally and exit the cell body at a "common" terminal; the
third of the electrodes exits the cell at a "signal"
terminal. The conductivity cell is part of a conductivity
monitor circuit which is designed to create a small
voltage between the cell's "signal" and "common" terni-
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The amount of the flow of electrons which results fromthis voltage will depend upon the conductivity of the
dialysate solution flowing through the conductivity cell.
In the event the rneasured conductivity of the dialysate is
more than a fixed amount, e.g. 5~, above or below the
desired conductivity, the monitor circuit automatically
sends a signal to its associated logic circuitry which, in
turn, produces an alarm (either audible or visual or both)
indicating that the dialysate conductivity limits have
been exceeded. Since conductivity is also temperature
dependent it is common practice to include a thermistor in
the conductivity circuit. This thermistor, which is
located on t`he inlet side of the conductivity cell,
continuously feeds dialysate temperature information to
the conductivity monitor circuit, thus allowing that
circuit to compensate for any changes in dialysate
temperature. Thus it will be seen that the conductivity
cell measures the dialysate conductivity on a continuous
basis and sounds an alarm if that conductivity deviates
more or less than a fixed amount from a constant
conductivity value.
A patient with kidney disease is typically on a treatment
schedule in which his blood is dialyzed every third day,
' 25 the duration of the treatment varying on the order of from
about three to about five hours~ At the beginning of a
treatment, the sodium ion level in the patient's blood is
elevated and is in the range of 145~146 meq./liter. In
what is regarded as a standard dialysis treatment, the
patient's blood is dialyzed against the aforementioned,
fixed composition standard dialysate, which has a sodiurn
ion concentration of 136 meq./liter. Tl-le composition of
the dialysate solution, and hence the osmolarity, is ~ept
constallt for the c]uration of the treatment cycle. Thus,
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as illustrated in FIG. l, the sodium ion concentration in
the patient's blood is gradually reduced so that at the
end of the treatment, the blood sodium concentration has
been reduced to a level which is approximately equal to
the dialysate sodium concentration. The osmolarity of
the patient's blood has also been reduced as a result of
the removal therefrom of both ionized and non-ionized
waste products during the dialysis treatment. In the
time prior to his next scheduled treatment, the sodium
ion level in the patient's blood gradually increases so
that just prior to the start of the next treatment, it
has reached the elevated level of 1~5-146 meq.~liter.
The increase- in sodium ion, along with increases in the
concentration of non-ionizable waste products, re~sults in
a corresponding increase in the patient's blood
osmolarity.
It has been observed that patients who are dialyzed after
a lay-off of several days exhibit what is known as
"dialysis disequilibrium syndrome", that is, the patient
suffers from such symptoms as nausea, headache, and
vomitinq. Dialysis disequilibrium syndrome is thought to
be related to the large difference between the total blood
osmolarity of the patient at the outset of the dialysis
-~ 25 treatment compared to the total osmolarity of the
dialysate being used.
It has been proposed in order to alleviate dialysis
disequilibrium syndrome that the sodium ion concentration
3~ in the dialysate be increased which in turn increases the
total dialysate osrnolarity. In one approach, illustrated
in E~IG. 2, "high sodium dialysatc" is used for the
duration of the treatment. The dialysate solution used in
this "lligh sodium dialysate" approach has a sodium ion
concentration of about 155 meq./liter as a result of
which its osmolarity is significantly higher than the
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total blood osmolarity of the patient at the start of the
treatment. It will be understood that this approach does
not involve any change in the osmolarity of the dialysate
during the treatment; the osmolarity of the dialysate is
maintained constant throughout the treatment cycle
although at a level which is higher than the osmolarity
of the aforementioned standard dialysate. While this
approach appears to have enjoyed some success in relieving
dialysis disequilibrium syndrome and does not interfere
with the removal from the blood of such impurities as urea
and creatinine, it su-ffers from the serious disadvantage
that during the dialysis treatment cycle, the sodium ion
level in the` patient's blood increasesl whereas one of the
purposes of dialysis is to reduce such sodium levelsO In
addition, such elevation in blood sodium level tends to
make the patient thirsty, and he desires to drink water to
alleviate that thirst at precisely the time when it is
desired to reduce the patient's body water content via
ultrafiltration during the dialysis procedure.
In a second approach to alleviating the dialysis disequi-
librium syndrome problem, a supplementary aqueous sodium
ion solution (e.g., a solution of sodium chloride in
water) is used in conjunction with the aforementioned
"standard" dialysate solution having a fixed composition.
In this approach, standard dialysate is continuously fed
to the dialysate compartment in the usual way, and the
supplementary aqueous sodium ion solution is added at a
linearly decreasing rate for an initial portion of the
treatrnent time and at a constant rate for the remainder of
the treatment time. Thus, the osmolarity of the dialysate
flowing through the dialysate compartment of the dialyzer
is linearly reduced during the initial stages of the
dialysis treatment cycle. As an example of the second
approach, and assuming the patient's tota] blood sodiurn
lcvel at the ou~set of the treatment to bc 145 meq./l.,
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the supplementary aqueous sodium ion solution is added to
the dialysate (136 meq./l. Na~) at an initial rate such
that the dialysate which initially flows through the
dialyzer has a sodium ion concentration of about 155
meq./l. The rate of addition of the supplementary sodium
ion solution to the standard dialysate solution is then
continuously reduced on a linear basis so that, by the end
of an initial portion (e.g., one hour) of the total dialy-
sis treatment cycle time, the overall concentration of
sodium ion in the dialysate has approached the customarily
used level of about 136 meq.~l. At that point, the addi-
tion of the supplementary sodium ion is discontinued (or,
if it is desired to keep the feed line flushed, kept at a
constant, extremely low rate) so that the sodium ion level
]5 in the dialysate for the remainder of the treatment time
is held substantially constant at the customary level of
about 136 meq./l. See FIG. 3. The disadvantages of this
second approach are similar, though perhaps not so severe,
to those encountered with the first described approach.
During the initial stages of the dialysis treatent the
total dialysate osmolarity is undesirably and disadvanta-
geously higher than the patient's total blood osrnolarity.
The patient's blood sodium level rises sharply during the
first thirty minutes of the treatment instead of falling
as is desirable. The patient still experiences thirst and
desires to take in water at exactly the time when his
water content is supposed to be reduced or at least held
constant.
In accordance with the present invention there is provided
an improved method for dialyzing blood. The improved
method helps to alleviate the symptoms of, and the
problems associated with, dialysis disequilibrium syndrome
ancl is characterized by the fact that the osmolarity of
thc dialysate supplied to the dialysate chambcr of an
artificial ~.idney is varied non--linearly as a functior. of
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time during at least a portion of the total time used for
the dialysis treatment cycle. In a specific embodiment of
the improved method, the osmolarity of a standard
dialysate solution is varied by varying the concentration
of sodium ion in the dialysate solution in accordance with
the equation:
y = [Ut-U(t-8)] 100 sin n t + [~(t-8)-~(t-17~1
(- t3 + 12.5t2 - 150t -~ 628.33) + [U(t-17)-U(t-60)]
(-t-~70) + [U(t-60)]10
where y - the concentration of sodium ion in the
dialysate, t is the time in minutes and U is a Unit Step
Function.
O~
A preferred method according to the present invention
employs the standard fixed composition dialysate solution
described earlier herein, and a supplementary aqueous
solution of sodium ion. The supplementary solution
preferably consists of sodium chloride dissolved in water.
A 10% by weight solution of sodium chloride in water has
been found suitable-, although other concentrations of
sodium chloride may be used. Similarly, other ionizable
sodium salts may be used in place of sodium chloride. The
osmolarity of the dialysate flowing through the dialysate
compartment of the dialyzer is varied on a non-linear
basis during the first part of the treatment cycle. The
length of this first part of time during which the
dialysate osmolarity is varied on a non-linear basis may
be, for example, one, two, or three hours. AEter the
first part of the total treatment time has been completed,
the osmolarity of the dialysate is preferably decreased
linearly until it approaches thc osmolarity of standard
dialysate. From that point in time unt:il the treatment is
cornpleted, the osmolarity o~ the dialysate is maintained
substantially constant at its standard level.
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Example I
Following is an example of a dialysis treatment in which
the osmolarity of the dialysate is varied non-linearly
during the first hour of a five-hour treatment and is
maintained substantially constant for the last four
hours. During the first hour of the treatment, the
dialysate supplied to the dialysate chamber of the
dialy~er consists of a mixture of the earlier-described
s~andard dialysate solution having a fixed composition
and a supplementary aqueous solution of 10~ by weight
sodiurn chloride. The osmolarity of the supplied
dialysate is varied by varying the sodium ion
concentration therein. The sodium ion concentration in
the supplied dialysate is varied by changing the amount
of the supplementary solution which is mixed with the
standard dialysate.
A patient having kidney disease is set up in the usual
fashion for a dialysis treatment. Blood to be dialyzed is
taken from the patient, pumped through a blood dialyzer,
and returned to the patient as usual. An aqueous solution
consisting of 136 meq/l. Na+, 106.6 meq./l. Cl-, 3.5
meq./l. Ca~2, 1.5 meq./l. Mg~2, 2.6 meq./l. K-~, and 37
-~ 25 meq./l. of acetate ion is used as the standard dialysate
of fixed composition. A solution of 10~ by weight of
sodium chloride in water is used as the supplernentary
aqueous sodium ion solution, this solution containing 380
rneq./l. sodium ion. The standard dialysate solution and
the supplementary solution are kept in separate reservoirs
and are pumped to a mixing point on the inlet side of the
dialysate chamber usinq any suitable pumping means. The
standard dialysate is purnped at a rate of 0.5 liters/
minute. The patient to be treated has a total blood
sodiurm level at the start of the treatmeIlt of about 145-
1~6 meq./l. At thc? ouLsct of the treat;nent and for
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approximately three minutes thereafter, the supplementary
solution is added to the standard dialysate at such a rate
that the sodium ion concentration in the mixed dialysate
entering the dialyzer rises to a value of about
155 meq./l. It will be observed that the sodium ion
concer,tration in the mixed dialysate (and, corresponding-
ly, the osmolarity) at this point in the treatment cycle
is considerably in excess of the initial sodium ion
concentration of the patient's blood. Subsequently, the
rate of addition of the supplementary solution is reduced
so that after about 10 minutes from the start of the
treatment, the sodium ion concentration in the mixed
dialysate is about 145 meq./l. At the end of the same ten
minu-te period, the sodium ion level in the patient's blood
has increased to a level of approximately 150 meq./l. It
will be observed that, at this point in the treatment
cycle, the sodium ion level in (and, correspondingly, the
osmolarity of) the mixed dialysate is decreasingl while
the sodium ion concentration of the patient's blood is
increasing. It should further be noted that at this point
in time the sodium level in the mixed dialysate is less
than the sodium ion level in the patient's blood. The
rate of addition of the supplementary solution is then
increased and during the next 6 minutes of the treatment
cycle, the sodium ion concentration in the mixed dialysate
reaches 148 meq./l. while the sodium ion concentration in
the blood reaches a level of 152 meq./l.
As a result of the foregoing procedure, the peak value of
the sodium ion in the blood is minimized during the first
thirty minutes o the treatmerlt. 'rhe time lag between
the increase in sodium ion level in the dialysate and the
subsequ~nt increase in the sodium ion level in the blood
is significant in holding the peak levels of sodium ion
in the blood to a minimum. Subsequently, the rate of
addition of the ,ul)plementary solution is reduced
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gradually and on a linear basis until the sodium ion
concentration in the dialysate supplied to the dialyzer
approaches 136 meq./liter which is the sodium ion concen-
tration in the standard, fixed composition dialysate. At
that time, the addition of the supplementary solution is
substantially discontinued (if desired, the addition of
the supplementary solution may be continued at a neyli-
gible rate in order to keep the feed lines flushed3 and
the sodium ion concentration in the dialysate (and hence
the osmolarity of the dialysate) is held substantially
constant for the remainder of the treatment cycle.
It will be u`nderstood that a variation in the sodium ion
level in the dialysate effects a corresponding va~riation
in the dialysate osmolarity, that is, a higher sodium ion
level produces a higher osmolarity and a lower sodium ion
level produces lower osmolarity. FIG. 4 shows the non-
linear variation of the sodium ion level in the dialysate
during the initial stages of the treatment, the subse-
quent linear decrease in concentration o~ the sodium ionin the dialysate in the intermediate stages of the
treatment, and the constant level of sodium ion in the
dialysate during the final stages of the treatment.
Since the osmolarity is a direct function of the sodium
ion level, the osmolarity of the dialysate likewise
varies non-linearly, then decreases linearly, and
thereafter holds constant for the remainder of the
treatment.
FCP 56
