Nephrol Dial Transplant (1996) 11 [Suppl 2]: 35-38
Original Article
Nephrology
Dialysis
Transplantation
Electrolyte modelling: Sodium. Is dialysate sodium profiling actually
useful?
T. Petitclerc1-2, J. C. Trombert3, B. Coevoet4 and C. Jacobs1
Departments of 'Nephrology and 2Biophysics, CHU Pitie-Salpetriere, Paris, and Hemodialysis Units, 3Evian and
Saint-Quentin, France
4
due to urea rebound which occurs during the first
hours after the end of the session can induce a cellular
Most of the presently available dialysis monitors offer dehydration responsible for urgent thirst reported by
the possibility to set continuously the dialysate sodium some patients [8]. In addition, regular use of high
concentration. Thus the dialysate sodium can be pro- sodium dialysate tends to increase the pool of
filed during the session, either manually, or automatic- exchangeable sodium in the patient, which may be
ally by use of a programmer. The aim of this paper is responsible for long-term morbidity by development
to describe the potential benefits of dialysate sodium of hypertension and severe left heart failure with
profiles and to evaluate whether the clinical imple- pulmonary oedema in susceptible patients [9].
Finally, the dialysate sodium concentration should
mentation of dialysate sodium profile is routinely
be determined only with the aim of preventing longfeasible.
term morbidity due to chronic sodium overload,
because the reduction of dialysate sodium is the only
way of avoiding an increase of the exchangeable
Dialysate sodium profiling: why?
sodium pool. The short-term tolerance to dialysis
in terms of symptomatic hypotension and
treatment,
Symptomatic hypotension and dialysis disequilibrium
disequilibrium
syndrome, should not be the deciding
syndrome are the two most frequent complications
for
the
determination of dialysate sodium,
factor
occurring during haemodialysis sessions. Their pathoare
many other means for decreasing
because
there
physiology is probably multifactorial. An important
intradialytic
morbidity,
especially by using sodium
cause of hypotension is the decrease in blood volume
profiling.
caused by ultrafiltration [1]. Dialysis disequilibrium
syndrome is defined as the occurrence of nausea,
vomiting, headache and cramps, and is mainly due to Dialysate sodium profiling: how?
brain cellular overhydration induced by a fluid shift
into the cells [2]. It is clearly established that preventing
the reduction in plasma osmolality during the dialysis Dialysate sodium profiling allows to modify the profile
session is a major protective factor for occurrence of of plasma osmolality in order to remove the quantity of
dialysis disequilibrium and symptomatic hypotension sodium required for avoiding patient sodium overload
[3], because it avoids or decreases the water inflow without side effects during the dialysis sessions.
into the intracellular compartment during dialysis ses- Decreasing, increasing and alternating sodium profiles
sions and preserves the available amount of interstitial have been proposed.
A decreasing sodium profile allows to linearize the
fluid to compensate for the hypovolaemia. Indeed,
inevitable
reduction in plasma osmolality due to urea
limiting the reduction in extracellular osmolality by
injecting hypertonic saline, or more easily by increasing removal and reduced water inflow into the cells. A
dialysate sodium concentration [4-7], is a very higher level of dialysate sodium concentration during
common and efficient treatment of symptomatic hypo- the early period of the session allows a diffusive sodium
tension and disequilibrium syndrome occurring during influx in order to prevent the rapid decline in plasma
dialysis. However, since the water inflow into the cells osmolality due to the loss of urea and other small
during the sessions has been avoided by increasing molecular weight solutes through the dialyser. During
extracellular sodium concentration, the water outflow the remaining period, when the osmolality reduction
accompanying urea removal is less abrupt, dialysate
Correspondence and offprint requests to: T. Petitclerc, MD, sodium concentration is set at a lower level, increasing
Department of Nephrology, CHU Pitie-Salpetriere, 83 boulevard de sodium removal in order to avoid an increase in the
l'Hopital, F-75651 Paris, France.
exchangeable sodium pool of the patient and an intense
Introduction
© 1996 European Dialysis and Transplant Association-European Renal Association
36
feeling of thirst during the next interdialytic interval.
Indeed, decreasing dialysate sodium profiles generally
yields a decrease in interdialytic weight gain suggesting
an improvement of thirst, or a decrease in occurrence
of hypotension or disequilibrium syndrome in conventional [10] and high efficiency [11] dialysis. The association with a decreasing ultrafiltration profile results in
preserving plasma volume during the phase of lower
sodium dialysate supply, as recently shown by Raja
et al. [12], and can improve the tolerance to dialysis
treatment [13].
Increasing sodium profiles preserve plasma volume
during the last period of dialysis, when total ultrafiltration is high. In fact, the preservation of plasma volume
can be obtained by choosing an ultrafiltration decreasing profile. The use of an increasing sodium profile
allows a lower incidence of cramps compared with a
constant or decreasing profile, probably because of a
decrease in sodium removal. However the use of an
increasing profile aggravates the fall in plasma osmolality during the first part of the session and results in a
higher occurrence of symptomatic hypotension [14].
Consequently, such a profile may be preferred in
patients without hypotension and with frequent muscle
cramps suggesting a decreased exchangeable sodium
pool.
Alternating hyper-/hyponatric dialysate sodium profiles have been proposed to induce an alternating fluid
shift through the cellular membrane, thus improving
the cell depuration by the so-created solvent drag.
Such a profile can result in a lesser occurrence of
disequilibrium syndrome [15,16], perhaps by reducing
the urea concentration difference between intra- and
extracellular compartments during the dialysis session,
thus decreasing the water inflow into the cells and
preserving the plasma volume [17].
A new approach: sodium modelling 'a la carte'
Although many studies have demonstrated a lesser
dialysis morbidity with the use of sodium dialysate
profiles, their results are not free of criticisms. A
sodium profile is often compared with a constant
dialysate sodium concentration set at the low value of
the profile, with the pre- and post-dialytic natraemia
with the two modalities being rarely reported. Under
these conditions, it is not possible to know with
certainty whether the reported improvement in dialysis
morbidity is due to the modification of plasma osmolality profile according to the dialysate sodium profile
or only due to the greater mean value of dialysate
sodium concentration, which tends to preserve plasma
osmolality.
Defining a sodium profile for an individual patient
consists of both the determination of the mean value
of dialysate sodium concentration and the choice of
the profile of variation around its mean value during
the session. The actual problem is that the physician
often tries to solve the latter point before having
precisely answered the former. We propose an original
T. Petitclerc et al.
method for routine implementation of sodium profiling
with an automatic optimization of dialysate sodium
concentration.
Automatic optimization of dialysate sodium
concentration
Since the interdialytic water and sodium load varies
from one patient to another and from one session to
another, it must be corrected individually, according
to dietary prescriptions and patient compliance especially concerning water and salt intakes, by adjusting
both the ultrafiltration and the dialysate sodium. The
ultrafiltration rate is usually adjusted according to the
measured predialytic weight, in order to reach a target
value (i.e. the estimated dry body weight), thus
allowing to accurately remove the water load and
restore the physiological value of total body water.
Likewise, the dialysate sodium concentration should
be adjusted according to the predialytic measured
natraemia, in order to reach a target value (i.e. the
estimated physiological value of natraemia), thus
allowing to accurately remove the sodium load.
However, the precise determination of the optimal
dialysate sodium concentration is much more complex
than that of the ultrafiltration rate. The management
of ultrafiltration is based on an accurate relationship
between the observed variable (interdialytic weight
gain) and the command variable (ultrafiltration rate).
In contrast, when managing dialysate sodium concentration, the observed variable (natraemia) is not linked
to the command variable (dialysate sodium concentration) by a simple relationship. The determination of
this relationship requires the elaboration of mathematical models and the precise assessment of patient's
status at the beginning of the session.
We have recently described a technique based on
kinetic modelling in order to automatically adjust at
each session the dialysate sodium concentration for
each individual patient. In order to avoid the necessity
of an on-line sodium sensor, conductivity measurement
is substituted for sodium measurement, because the
conductivity reflects the concentration of osmotically
active solutes in the dialysate as most likely in the
extracellular fluid. By the means of a dialysate recirculating loop [18] or of a short imposed change in
dialysate conductivity [19], it is possible to determine
the plasma water conductivity of the patient (strongly
correlated to natraemia [18]) merely from conductivity
measurements in the dialysate line. Thus it is possible,
using a specially designed 'biofeedback module'
(Hospal R&D Int, Meyzieu, France) to automatically
adjust the dialysate sodium concentration in order to
target at the end of the session a value for patient's
plasma water conductivity fixed by the physician [18].
By prescribing the desired postdialytic dry weight
and plasma water conductivity, the physician determines for his/her patient the total body water and
sodium pool to be obtained at the end of the session.
If the postdialytic weight and conductivity of the
patient are set as a constant, the total body water and
Electrolyte modelling: sodium
37
Table 2. Intradialytic morbidity events
the sodium pool also return to a constant value at the
end of each session. Consequently the exact amounts
of water and salt accumulated during the interdialytic
period are removed during the session and thus
the sodium-water balance is truly regulated, avoiding
chronic water-sodium overload. In addition, this biofeedback technique allows an automatic, real-time and
Period A
non-invasive estimation of the normalized dialysis dose Period
B
Kt/V actually delivered to the patient [20].
p
Clinical implementation of sodium profiling
If the dialysate sodium concentration is optimized for
avoiding the risk of sodium overload, it becomes
possible to profile the dialysate sodium concentration
in an attempt to prevent intradialytic morbidity. In
order to obtain a decreasing dialysate sodium profile
with a lower dialysate sodium concentration during
thefinalperiod of the session, the 'biofeedback module'
is programmed for reaching, at two-thirds of the course
of the session, a plasma water conductivity equal to
the final target (programmed by the physician),
increased by 1%.
This 'biofeedback' technique has been performed for
4 months in 16 patients (period B) and compared in a
cross-over study with conventional haemodialysis featuring a constant dialysate sodium (period A) (Fig. 1).
During the control period A (724 sessions), the dialysate conductivity was set to the patient's usual value
(range 14—14.2 mS/cm). During the biofeedback
period B (666 sessions) dialysate conductivity was
automatically determined in order to reach at the end
of the session a plasma water conductivity fixed at
14.2 mS/cm for all the patients. The other parameters
(duration, type of dialyser, blood and dialysate flow
rates etc.) were set as usual for the patients and were
identical for both periods. Clinical parameters of the
patients are shown in Table 1. In spite of a significant
elevation of mean dialysate sodium concentration
during period B (14.40 vs 14.16 mS/cm), no clinically
relevant changes in interdialytic weight gain and predialytic blood pressure were seen. The results in Table 2
show that this technique efficiently reduces intradialytic
morbidity. Thus the percentage of sessions with symptomatic hypotension was 20% with conventional
haemodialysis and only 7% (P< 0.001) with the biofeedback technique. Figure 1 shows the decreasing
profile of dialysate conductivity determined by the
module. The dialysate conductivity decreases on average from 14.6 to 14 mS/cm, corresponding to a change
of dialysate sodium concentration from 144 to
Table 1. Clinical parameters of the patients
Weight loss Mean DC Predialytic BP Postdialytic BP
(mmHg)
(inS/cm) (mmHg)
(kg)
Period A 2.13 + 3.01
Period B 2.32 ±0.97
14.16
14.40
136/76
136/78
DC, dialysate conductivity; BP, blood pressure.
131/75
136/79
No. sessions (%) with:
Symptomatic Headache Nausea
hypotension
147(20%)
50(7%)
< 0.001
14(2%)
6(1%)
NS
Vomiting Cramps
64 (9%) 13 (2%) 25 (3%)
15(2%) 7(1%) 19(3%)
< 0.001 NS
NS
NS, not significant.
14,6
O
13,6
0,2
0,4
0,6
0,8
time (fraction of total duration)
1,0
Fig. 1. Average profile of dialysate conductivity during the control
period A and the biofeedback period B.
138 mmol/1. It should be pointed out that this profile
is the average of all the profiles individually adjusted
by the module at each session during the biofeedback
period B. With the same biofeedback technique Di
Giulio et al. have recently reported a lesser variation
in blood volume by higher plasma refilling rate and an
improvement in cardiovascular stability [21].
Conclusion
The problems related to the determination of the
optimal value of dialysate sodium concentration and
its most effective modification during the dialysis session are still debated. The potential advantages
(improvement of intradialytic morbidity) of a given
dialysis technique (high or low sodium dialysate, constant or profiled sodium dialysate etc.) should always
be compared with potential side effects on interdialytic
morbidity during regular use of any technique, thus
justifying the need for long-term studies.
The rational use of sodium profiles can be useful for
improving intradialytic morbidity while avoiding the
risk of chronic sodium overload, and seems especially
suitable for patients frequently symptomatic with conventional techniques. Probably in the near future, the
routine use of on-line sensors and kinetic modelling
will allow the fully automatic real-time adaptation of
the mean dialysate sodium concentration during the
session, in order to avoid sodium overload and its
long-term side effects, together with a profile of variation around its mean value, in an attempt to improve
intradialytic morbidity.
38
References
1. Lins LE, Hedenborg G, Jacobson SH, Samuelson K, Tedner B,
Zetterholm UB, Ljungqvist O. Blood pressure reduction during
hemodialysis correlates to intradialytic changes is plasma
volume. Clin Nephrol 1992; 37: 308-313
2. Arieff AI. Dialysis disequilibrium syndrome: current concepts
on pathogenesis and prevention. Kidney Int 1994; 45: 629-635
3. Rodrigo F, Shideman J, McHugh R, Buselmeier T,
Kjellstrand C. Osmolality changes during hemodialysis: natural
history, clinical correlations, and influence of dialysate glucose
and intravenous mannitol. Ann Int Med 1977; 86: 554-561
4. Van Stone JC, Bauer J, Carey J. The effect of dialysate sodium
concentration on body fluid distribution during hemodialysis.
Trans Am Soc Artif Intern Organs 1980; 26: 383-386
5. Port FK, Johnson WJ, Klass DW. Prevention of dialysis disequilibrium syndrome by use of high sodium concentration in the
dialysate. Kidney Int 1973; 3: 327-333
6. Henrich WL, Woodard TD, McPhaul JJ. The chronic efficacy
and safety of high sodium dialysate: double-blind,' crossover
study. Am J Kidney Dis 1982; 2: 349-353
7. Cybulsky AVE, Matni A, Hollomby DJ. Effects of high sodium
dialysate during maintenance hemodialysis. Nephron 1985; 41:
57-61
8. Wilkinson R, Barber SG, Robson V. Cramps, thirst and hypertension in hemodialysis patients—the influence of dialysate
sodium concentration. Clin Nephrol 1977; 7: 101-105
9. Robson M, Oren A, Ravid M. Dialysate sodium concentration,
hypertension, and pulmonary edema in hemodialysis patients.
Dial Transplant 1978; 7: 678-679
10. Sadowski RH, Allred EN, Jabs K. Sodium modeling ameliorates
intradialytic and interdialytic symptoms in young hemodialysis
patients. / Am Soc Nephrol 1993; 4: 1192-1198
11. Acchiardo SR, Hayden AJ. Is Na + modeling necessary in high
flux dialysis? Trans Am Soc Artif Intern Organs 1991; 37:
M135-M137
T. Petitclerc et al.
12. Raja RM, Po CL. Plasma refilling during hemodialysis with
decreasing ultrafiltration. Influence of dialysate sodium. ASAIO
J 1994; 40: M423-M425
13. Perschel WT, R6ckel A, Klinke B, Reinhardt B, Behnken LJ,
Abdelhamid S, Fiegel P, Walb D. Variation of ultrafiltration
and dialysate sodium. Beneficial effects on vascular stability in
diabetic dialysis patients. In: Baldamus CA, Mion C, Shaldon S,
eds. Improvements in Dialysis Therapy. Contrib. Nephrol,
Karger, Basel, 1989: 74: 176-181
14. Raja R, Kramer M, Barber K, Chen S. Sequential changes in
dialysate sodium during hemodialysis. Trans Am Soc Artif Intern
Organs 1983; 29: 649-651
15. Martin-Malo A, Perez R, Gomez J, Burdiel LG, Andres E,
Castillo D, Moreno E, Aljama P. Sequential hypertonic dialysis.
Nephron 1985; 40: 458-462
16. Maeda K, Kawaguchi S, Kobayashi S, Niwa T, Kobayashi K,
Saito A, Iyoda S, Ohta K. Cell-wash dialysis (CWD). Trans Am
Soc Artif Intern Organs 1980; 26: 213-218
17. Kouw PM, Olthof CG, Gruteke P, de Vries PMJM, Meijer JH,
Oe PL, Schneider H, Donker AJM. Influence of high and low
sodium dialysis on blood volume preservation. Nephrol Dial
Transplant 1991; 6: 876-880
18. Petitclerc T, Hamani A, Jacobs C. Optimization of sodium
balance during hemodialysis by routine implementation of kinetic modelling: technical aspects and preliminary clinical study.
Blood Purif 1992; 10: 309-316
19. Petitclerc T, Goux N, Reynier AL, Bene B. A model for noninvasive estimation of in-vivo dialyzer performances and patient's
conductivity during hemodialysis. Int J Artif Organs 1993;
16: 585-591
20. Petitclerc T, Bene B, Jacobs C, Jaudon MC, Goux N. Noninvasive monitoring of effective dialysis dose delivered to the
haemodialysis patient. Nephrol Dial Transplant 1995; 10:212-216
21. Di Giulio S, Meschini L, de Paolis P, Cherubini C, Friggi A,
Rosa M, Stortoni F. Improved cardiovascular stability with
biofeedback module for automatic prescription of electrolyte
transport during hemodialysis (abstract). Blood Purif 1994;
12: 174-175