Nephrol Dial Transplant (2007) 22: 3553–3560
doi:10.1093/ndt/gfm436
Advance Access publication 23 August 2007
Original Article
Resting energy expenditure and thermal balance during isothermic
and thermoneutral haemodialysis—heat production does not explain
increased body temperature during haemodialysis
Jiřı́ Horáček1, Sylvie Dusilová Sulková2,3, Magdalena Fořtová4, František Lopot4,
Marta Kalousová3, Luboš Sobotka2, Jiřı́ Chaloupka5, Vladimı́r Tesař6, Aleš Žák7 and Tomáš Zima3
1
Department of Internal Medicine II and 2Department of Gerontology and Metabolism, Charles University Prague,
Faculty of Medicine and University Hospital Hradec Králové, Hradec Králové, 3Institute of Clinical Chemistry and
Laboratory Diagnostics, 4Internal Department Strahov, Charles University Prague, 1st Faculty of Medicine and
University Hospital Prague, Prague, 5Department of Occupational Health, Charles University Prague, Faculty of
Medicine and University Hospital Hradec Králové, Hradec Králové, 6Department of Nephrology and 74th Department
of Medicine, Charles University Prague, 1st Faculty of Medicine and University Hospital Prague, Prague, Czech Republic.
Abstract
Background. During routine haemodialysis (HD) body
temperature increases, which contributes to haemodynamic instability. The relative roles of increased heat
production and/or incomplete heat transfer are not
fully elucidated. Concomitant measurement of heat
production and heat transfer may help to assess the
factors determining thermal balance during HD.
Methods. Thirteen stable non-diabetic maintenance
HD patients were investigated during two HD
procedures (isothermic, dT ¼ 0, no change of body
temperature; thermoneutral, dE ¼ 0, no energy transfer
between blood and dialysate), using a blood temperature monitor (BTM) in active mode. Energy transfer,
blood and dialysate temperature, and relative blood
volume change (dBV) were continuously recorded, and
resting energy expenditure (REE; Deltatrac Datex) was
measured repeatedly during each procedure. Fourteen
healthy persons served as controls for REE
comparison.
Results. In isothermic HD, median energy removal was
218 kJ/4 h HD (¼ heat flow 15.1 W). This cooling
correlated with dBV induced by ultrafiltration
(r ¼ 0.731, P < 0.01). There was no difference in dBV
between isothermic (7.7%) and thermoneutral (8.1%)
HD. Predialysis REE was 82.8 W/1.73 m2, not different
from controls. No variation in REE during HD was
observed, except a small and transient increase after
a light meal (5 and 4%). In the time course of REE, no
difference between the procedures was found.
Correspondence and offprint requests to: Prof. Sylvie Dusilová
Sulková, Department of Gerontology and Metabolism, Charles
University Prague, Faculty of Medicine and University Hospital
Hradec Králové, Email: [email protected]
Conclusions. Our findings suggest that stable maintenance HD patients have REE not different from
healthy controls, that HD procedure per se does not
significantly increase REE and that neither isothermic
nor thermoneutral regimen has any influence on
metabolic rate. Therefore, body temperature elevation
during routine HD may rather be due to decreased
heat removal. With the use of BTM in active mode,
body temperature can be kept stable (isothermic HD),
which requires active cooling. This negative energy
transfer is proportional to decrease in blood volume
induced by ultrafiltration.
Keywords: blood temperature monitor; isothermic
haemodialysis; resting energy expenditure; thermal
balance; thermoneutral haemodialysis; ultrafiltration
Introduction
There has been increasing interest in the thermoregulatory processes during haemodialysis (HD) in the
last few years as thermal dysequilibrium is one of the
major deviations from homeostasis during routine HD
procedure, influencing greatly the haemodynamic
stability in response to ultrafiltration [1–5].
Normally, the stability of body temperature is
controlled by equilibrium between heat production
and heat removal from the body. Heat elimination is
mediated by perspiration, convection and radiation;
they are capable of mutual compensation. None of
these three components is directly measurable. On the
other hand, heat production may be estimated using
indirect calorimetry because it corresponds to energy
expenditure.
ß The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please email: [email protected]
3554
HD procedure may affect the steady state between
heat production and heat removal in several ways.
First, there is a heat exchange between blood and
dialysate in haemodialyser. Changes in heat dissipation
from skin surface due to changes in skin perfusion may
also be important. Finally, an increase in metabolic
rate (i.e. increased heat production) during HD has
been suggested.
During routine HD, dialysis solution temperature is
constant and no information about the real energy
transfer is available. However, using a BTM device
(Blood Temperature Monitor, Fresenius, Bad
Homburg, Germany) the extracorporeal energy transfer during HD can be monitored, which offers a unique
opportunity to quantify the heat loss. Moreover,
the simultaneous registration of extracorporeal
energy transfer together with the measurement of
resting energy expenditure (REE) might provide more
information about the thermoregulatory processes
during HD.
The BTM works in active or passive mode. During
HD, two special sensors continuously measure the
blood temperature both in arterial and venous extracorporeal lines and this process is highly standardized
and precise. In passive mode, the energy transfer is
only registered. In active mode, the dialysate temperature is continuously adjusted on the ‘biofeedback’
principle. This biofeedback allows to keep a pre-set
body temperature (regimen T) or to reach a pre-set
energy transfer (regimen E), respectively [1,3,5].
In this study, both energy production and energy
transfer were studied during two distinct thermal
regimens of HD (isothermic HD and thermoneutral
HD). Isothermic HD (dT ¼ 0) keeps a stable body
temperature. Thermoneutral HD (dE ¼ 0) means no
thermal transfer in the dialyser.
Our assumption was that if measured REE increased
during both settings, then HD itself would be
responsible for increased heat production and
its accumulation during HD. If a change in REE
occurred in one setting only, it would be related to the
respective thermal balance, not to HD procedure itself
(e.g. a change in REE in response to the change in
body temperature). If REE remained stable in both
thermal HD regimes, then thermal balance would be
dependent on extracorporeal heat flow.
We were also interested in possible relationship
between thermal balance and relative blood volume
changes (dBV) in response to ultrafiltration, as Rosales
et al. [6] and Schneditz et al. [7] have previously
described a close link between these variables.
An accessory aim of the study was to compare the
REE in our patients with a control group because of
equivocal data on REE in dialysed patients in the
literature.
Subjects and methods
Thirteen chronic HD patients (7 men and 6 women; aged
59.8 13.5 years, length of HD treatment 3.4 2.2 years)
J. Horáček et al.
Table 1. Baseline characteristics of haemodialysis patients (n ¼ 13)
Variable
Unit
Body weight (BW)
Body surface area
Albumin
Prealbumin
Haematocrit
kg
m2
g/l
g/l
%
Reference range Median IQR
NA
NA
32–45
0.20–0.36
37–47 (F)
42–52 (M)
Urea
mmol/l 2.0–6.7 (F)
2.8–8.0 (M)
Ultrafiltration (UF) ml/HD NA
UF as%BW
%
NA
78
1.96
36.0
0.30
32.9
72–87
1.82–2.03
34.5–38.0
0.25–0.41
29.6–34.4
23.0
20.2–28.4
2600
3.0
1550–2700
2.2–3.3
The patients were evaluated twice (before isothermic and thermoneutral HD) within 1 week and the average value of these two
measurements was used for median and interquartile range (IQR)
calculations.
M, males; F, females.
were studied prospectively (Table 1). The patients were
clinically stable, with no signs of inflammation or heart
failure. No patients with diabetes mellitus, or those treated
with glucocorticoids, thyroid hormones or b-blockers were
included. The control group of healthy subjects consisted of
4 men and 10 women with an average age of 41.3 20.5
years. All subjects were informed about the study procedure
and its aim, and expressed their informed consent.
Patients were observed during two HD procedures with
different thermal balance, i.e. during isothermic (‘cool’) and
thermoneutral (‘warm’) HD. Isothermic HD has been
defined as dT ¼ 0, i.e. body temperature remained constant
during HD because the excess heat produced during HD was
convected out of the body (the energy balance of the
procedure was negative). In contrast, thermoneutral HD
has been defined as dE ¼ 0, i.e. no energy is lost in the
extracorporal circuit and body temperature increases [1,2].
Both thermal regimens were continuously kept under control
by BTM module (Fresenius, Bad Homburg, Germany) in
active regimen, with HD monitor 4008S.
Other HD characteristics remained identical in both
regimens: low-flux steam sterilized polysulphone dialyzer
1.6 m2, two G15 dialysis needles, blood flow rate 300 ml/min,
dialysate flow rate 500 ml/min, composition of dialysis
solution: c(Naþ) 140 mmol/l, c(Kþ) 3 mmol/l, c(Ca2þ)
1.75 mmol/l and c(HCO
3 ) 32 mmol/l with no glucose,
duration of HD 4 h, constant ultrafiltration rate and identical
total amount of ultrafiltrate. The interval between measurements was one week (mid-week dialysis), afternoon shift. All
patients had a well-functioning native arteriovenous fistula
(proven by regular assessment of vascular access blood flow
by thermodilution).
REE was measured by indirect calorimetry (metabolic
monitor Deltatrac Datex, Helsinki, Finland) using ventilated
canopy. Patients were completely at rest during the whole
HD procedure, lying supine in a quiet room with a temperature of 248C–258C. The measurement started at least 3 h after
the last meal; however, no specific long-term food intake
limitations were imposed to either control subjects or HD
patients. The first measurement was performed before each
HD, after 30 min of rest in supine position. It was then
repeated 4 times: 10, 70, 110 and 215 min after the start of
HD. The fourth measurement (110 min) followed shortly
Resting energy expenditure and heat removal during haemodialysis
3555
after a light meal (two rolls and non-sweetened tea,
1000 kJ). Thus, REE was measured five times during each
HD session.
In each indirect calorimetry procedure, oxygen consumption (VO2) and CO2 production (VCO2) were registered for
10 min at 1 min intervals after 3 min of adaptation period.
The average of these 10 measurements was taken as the
result. Respiratory quotient (RQ ¼ VCO2/VO2) and resting
energy expenditure (REE; Weir formula) were calculated by
the device [8]. The measured REE values were compared with
the values of basal metabolic rate (BMR) estimated from
Harris–Benedict formula [9].
In HD patients, blood pressure (BP), heart rate (HR)
and respiration rate (RR) were recorded before dialysis
and at 30 min intervals during both procedures. Temperature
in arterial blood line (Tart), venous blood line (Tven) and
dialysate temperature (Tdial) as well as relative changes of
intravascular volume (dBV; Critline; On-line Diagnostics,
Riverdale, USA) [10] were recorded continuously throughout
the study. Temperature in arterial blood line (Tart) measured
by BTM is acceptable representative of mixed body
temperature [1,5], provided the recirculation is measured
and included into calculation, as it was in our practice.
Pre-dialysis blood samples were drawn from inserted
dialysis needle just before starting HD. During HD, samples
were taken from arterial blood line in the 70th min of HD.
Post-dialysis blood samples were taken using slow-flow
method from arterial blood line. The samples were kept on
ice for 30 min, and then centrifuged at 48C at 3000g.
Thereafter, serum was kept at 208C until the laboratory
assays were performed (max. 8 weeks).
Serum urea and albumin concentrations were assayed
using autoanalyser Kodak Ektachem 700XR and haematocrit levels using Critline device. For pre-albumin, immunoturbidimetric assay was used (Tinaquant-Prealbumin,
Roche). To compare the magnitude of biological response
to both procedures, pregnancy-associated plasma protein
A (PAPP-A) was measured by TRACE (Time Resolved
Amplified Cryptate Emission) technology based on nonradiating energy transfer. Commercial kit for PAPP-A
determination (BRAHMS GmbH, Berlin, Germany) contains two different monoclonal antibodies—one is conjugated with europium cryptate and the other with fluorescent
agent XL 665. The antigen (PAPP-A) present in serum
samples is sandwiched between two conjugates. The fluorescent signal measured during the formation of the
antigen–antibody complex by the KRYPTOR analyser
(BRAHMS GmbH, Berlin, Germany) is proportional to
the antigen concentration. Cyclic GMP (cGMP) as a marker
of hydration was determined with competitive EIA using
standard kits (Cayman Chemicals, USA). Concentration
of non-esterified fatty acids (NEFA) was determined using
the enzymatic-colorimetric method (NEFA, Randox
Laboratories, UK); they were selected for their supportive
information about metabolic response during HD.
For statistical analysis, non-parametric tests were
employed, as the assumptions for parametric tests were
not consistently met. Data were expressed as medians
(with 1st and 3rd quartiles). For comparisons between the
control and HD groups, Mann–Whitney test was used.
The two distinct thermodynamic regimens within the HD
group were compared using Wilcoxon test for paired data.
For variation of repeated measurements during HD,
Friedman test was used, with subsequent Dunnett
or Student–Newman–Keuls (SNK) test for significant
difference between the individual measurements, as
appropriate. Relations between variables were evaluated by
non-parametric correlation analysis (Spearman r).
SigmaStatÕ statistical software package, version 3.1 (Jandel
Corp., San Rafael, USA), was used for calculations, and
P < 0.05 was considered statistically significant.
Results
Thermal balance during thermoneutral and isothermic
haemodialysis
As expected, there was a significant difference in
thermal balance between the HD procedures (Table 2).
During thermoneutral HD, in accord with its definition, there was nearly no heat transfer between blood
and dialysate, and continuous increase in arterial
and venous line temperature was observed. During
isothermic HD, dialysate temperature was continuously decreasing, which was paralleled by venous line
temperature. The thermal balance of the procedure
was clearly negative (218 kJ removed in 4 h; heat
flow 15.1 W). In spite of this, there was a minor
(though statistically significant) increase in arterial
line temperature. While the difference in thermal
balance and in venous line temperature was clearly
apparent from the 30th min of HD, arterial line
temperature (best reflecting core temperature) became
significantly different only after the 210th min. Median
difference in dialysate temperature till the end of both
procedures was 1.98C with a starting dialysate temperature of 36.58C in both settings, and final values of
35.28C and 37.18C in isothermic and thermoneutral
HD, respectively.
Changes in intravascular volume (dBV)
There was no difference between the changes of
intravascular volume (dBV) (8.1 vs 7.7% in
isothermic and thermoneutral HD, respectively, NS)
(Table 2). In isothermic HD, significant correlation
(r ¼ 0.731, P < 0.01) was found between dBV and total
amount of heat removed (Figure 1). In thermoneutral
HD, no clear-cut relationship between dBV and body
temperature increase was found.
Haemodynamic stability
Both in isothermic and thermoneutral settings, blood
pressure (systolic, diastolic and mean) remained stable
and no symptomatic hypotension was observed. Also,
there was no significant difference in the heart rate at
any time point between the procedures, in spite of
a minor (but significant) overall increase during
thermoneutral HD (Table 3).
3556
J. Horáček et al.
Table 2. Thermal parameters and relative decrease in blood volume in the course of isothermic (dT ¼ 0) and thermoneutral (dE ¼ 0) HD
Variable Unit Regimen Haemodialysis
Thermal kJ
energy
removal
dE ¼ 0
8C
dT ¼ 0
Tart
dT ¼ 0
dE ¼ 0
Tven
8C
dT ¼ 0
dE ¼ 0
Decrease %
in blood
volume
dT ¼ 0
dE ¼ 0
Friedman P
Start
30 min
60 min
90 min
120 min
150 min
180 min
210 min
240 min
0
0–0
0
0
36.7
36.6–36.8
36.8
36.4–37.0
36.2
36.0–36.6
36.4
36.3–36.7
0.0
0.0–0.0
0.0
0.0–0.0
14
5–19
4
1–7
36.8
36.6–36.9
36.9
36.5–37.2
36.6
36.3–36.7
37.0
36.6–37.4
1.7
0.9–1.9
1.9
1.0–2.1
31
5–41
3
1–5
36.9
36.7–37.0
36.9
36.6–37.2
36.2
35.7–36.7
36.9
36.5–37.2
1.9
1.2–4.4
2.0
1.7–3.7
57
4–75
3
0–5
36.9
36.7–37.0
36.8
36.6–37.3
36.0
35.6–37.2
36.8
36.6–37.3
3.2
2.3–3.8
3.8
2.9–4.6
81
3–110
3
2–4
36.9
36.7–37.0
37.1
36.6–37.3
35.8
35.5–36.3
37.1
36.5–37.3
4.4
3.1–7.0
5.1
3.9–7.9
115
17–147
2
1–5
36.9
36.7–37.1
37.1
36.7–37.5
36.0
35.3–36.7
37.2
36.8–37.4
4.3
2.3–7.2
5.1
3.8–6.5
143
60–194
3
1–6
36.9
36.8–37.2
37.3
36.9–37.5
35.7
35.1–36.5
37.1
36.9–37.4
5.3
2.2–8.0
5.8
4.3–8.5
173
89–238
3
1–5
36.9
36.8–37.2
37.4
36.9–37.5
35.9
35.3–36.4
37.4
36.8–37.5
5.4
2.8–9.0
6.6
5.6–8.0
218
89–284
2
0–5
36.8
36.7–37.1
37.3
36.9–37.5
35.6
35.3–36.2
37.2
36.7–37.6
8.1
3.8–10.9
7.7
6.5–10.1
<0.001
NS
<0.001
<0.001
<0.05
<0.001
<0.001
<0.001
Decrease in blood volume is expressed as percentage of initial blood volume (measured by Critline device).
Values are presented as median (above) with interquartile range (below).
Variation of repeated measurements during HD was analysed by Friedman test (significance is given in the last column). If the variation was
significant, Dunnett test (P < 0.05) was used to identify values significantly different from start.
As expected from definitions of the regimens (dT ¼ 0 vs dE ¼ 0), thermal energy removal and the temperatures were clearly different between
the procedures, reaching significance in 60 min (Wilcoxon test), except Tart where the difference became significant (P < 0.05) in 210 and
240 min only. Conversely, in blood volume changes there was no significant difference between the regimens at any time.
Thermal energy removal, total amount of thermal energy transferred into extracorporeal circuit (measured by BTM module) within the given
time; Tart, arterial blood line temperature; Tven, venous blood line temperature.
Inflammatory marker PAPP-A increased after the start
of dialysis, as expected, and returned to pre-treatment
value. The sharp rise of NEFA in the 70th min was
similar in both procedures, as was the subsequent
decrease. No significant difference between isothermic
and thermoneutral HD was found in any of these
investigated parameters.
Indirect calorimetry (REE and RQ)
Fig. 1. Correlation of intravascular volume decrease (induced by
ultrafiltration and measured by Critline device) and total thermal
energy transferred into extracorporeal circuit (measured by BTM
device) during 4 h of isothermic HD. Spearman (non-parametric)
correlation: r ¼ 0.731; P < 0.01.
Selected biochemical variables
Serum urea concentrations were used for Kt/V
calculations, and dialysis adequacy (eKt/V 1.3 or
more) was confirmed. Blood concentrations of circulating volume marker, cGMP, metalloproteinase
PAPP-A as marker of a complex biological response
to extracorporeal procedure [11] and non-esterified
fatty acids (NEFA) in the course of both procedures
are summarized in Table 4.
There was a significant decrease in cGMP level in
both settings, and in the 70th min this decrease was
relatively greater than that of intravascular volume.
REE values remained stable in the course of both HD
regimens (Table 5) except a small and transient
(though significant) increase after the light meal
(110 min). RQ was slowly but significantly declining
during both HD regimens. However, this decline
was abolished after the carbohydrate meal. Significant
negative correlation (r ¼ 0.451, P < 0.05) was found
between the change in RQ and in NEFA level during
both HD settings.
The values of pre-dialysis REE were generally stable
within the same patient; median difference between
the two measurements (i.e. before isothermic and
thermoneutral HD) was 4.7% (4.1% when expressed
as REE per 1.73 m2). Therefore, the mean of two
pre-dialysis values in every patient was used for
comparison with healthy controls. As summarized in
Table 6, there was no difference in REE between HD
patients and controls (in absolute values, or expressed
in watts per standardized body surface area, or as
percentage of BMR).
Resting energy expenditure and heat removal during haemodialysis
3557
Table 3. Blood pressure (BP) and heart rate (HR) in the course of isothermic (dT ¼ 0) and thermoneutral (dE ¼ 0) HD
Variable
BP systolic
Unit
mmHg
Regimen
dT ¼ 0
dE ¼ 0
BP diastolic
mmHg
dT ¼ 0
dE ¼ 0
HR
min1
dT ¼ 0
dE ¼ 0
Haemodialysis
Friedman P
Start
30 min
120 min
240 min
148
139–170
151
136–166
150
131–157
151
134–181
150
126–172
150
133–174
145
134–157
149
137–177
87
77–92
93
81–103
89
82–95
84
76–107
89
74–92
86
76–96
84
78–97
85
75–103
75
69–80
73
69–78
74
71–81
77
70–81
80
78–88
88
74–93
82
77–87
84
75–92
NS
NS
NS
NS
NS
<0.001
Values are presented as median (above) with interquartile range (below).
Variation of repeated measurements during HD was analysed by Friedman test (significance is given in the last column). If the variation was
significant, Dunnett test (P < 0.05) was used to identify values significantly different from start.
There were no statistically significant differences between the regimens (dT ¼ 0 vs dE ¼ 0) in any of the variables at any time of measurement
(Wilcoxon test).
Table 4. Selected biochemical variables in the course of isothermic (dT ¼ 0) and thermoneutral (dE ¼ 0) HD
Variable
CGMP
Unit
pmol/l
Regimen
dT ¼ 0
dE ¼ 0
PAPP-A
mU/l
dT ¼ 0
dE ¼ 0
NEFA
mmol/l
dT ¼ 0
dE ¼ 0
Haemodialysis
before
70th min
after
11.5
6.0–20.7
13.8
5.9–17.4
3.9
3.7–4.6
3.7
3.1–4.5
3.7
2.5–4.2
3.3
3.1–4.0
17.2
15.9–19.8
20.6
15.4–25.0
25.0
18.8–27.0
21.9
18.3–28.6
20.0
15.5–22.7
21.0
16.4–23.9
0.35
0.16–0.55
0.29
0.17–0.53
1.39
0.93–2.42
1.12
1.00–1.67
0.55
0.39–1.01
0.67
0.55–0.79
Friedman P
SNK test
P < 0.05
<0.05
1 vs 2,3
<0.01
1 vs 2,3
<0.01
2 vs 1,3
NS
NS
<0.001
1 vs 2 vs 3
<0.001
1 vs 2 vs 3
Values are corrected to blood volume changes and presented as median (above) with interquartile range (below).
Variation of repeated measurements during HD was analysed by Friedman test. If the variation was significant, Student–Newman–Keuls
(SNK) test was used to identify significant difference (P < 0.05) between the individual measurements (1 ¼ before HD, 2 ¼ in the 70th min,
3 ¼ after HD).
There were no statistically significant differences between the regimens (dT ¼ 0 vs dE ¼ 0) in any of the variables at any time of measurement
(Wilcoxon test).
CGMP, cyclic guanosin monophosphate; PAPP-A, pregnancy-associated plasma protein A; NEFA, non-esterified fatty acids.
Discussion
In our study, heat production together with heat
removal were being monitored in the course of two
different thermal HD regimens. One of the compared
regimens was isothermic HD that, with respect to
thermal balance, makes HD as close as possible to
physiological homeostasis because it prevents the
increase in body temperature. The haemodynamic
benefit of isothermic HD has been proven by
Maggiore et al. [2] in a multicentre study and their
conclusion has generally been accepted but still has
remained underused [12].
In isothermic HD, the energy balance is negative.
In two previous studies a quantitative relationship was
found between ultrafiltration and energy transfer [6,7].
A similar conclusion can be drawn from our data:
(cumulative) heat energy removal correlates well
with (cumulative) decrease in intravascular volume
(Figure 1). Furthermore, in our study ultrafiltration as
well as blood volume decrease were considerably lower
than in published studies, but this correlation was of
3558
J. Horáček et al.
Table 5. Indirect calorimetry in the course of isothermic (dT ¼ 0) and thermoneutral (dE ¼ 0) haemodialysis
Variable
REE
Unit
W
Regimen
dT ¼ 0
dE ¼ 0
REE
% baseline
dT ¼ 0
dE ¼ 0
RQ
1
dT ¼ 0
dE ¼ 0
VCO2
ml/min
dT ¼ 0
dE ¼ 0
VO2
ml/min
dT ¼ 0
dE ¼ 0
Haemodialysis
before
10 min
70 min
110 min
215 min
92.5
81.3–95.8
87.6
85.2–103.6
100
100–100
100
100–100
0.94
0.88–0.98
0.93
0.87–0.95
247
219–277
243
229–253
262
242–280
256
249–310
84.6
81.5–94.1
89.0
81.1–102.7
99
92–100
98
92–100
0.9
0.88–0.96
0.88
0.87–0.92
229
219–255
235
218–260
251
241–279
258
240–305
88.8
85.0–95.0
93.8
80.1–101.6
99
95–104
97
91–106
0.83
0.83–0.87
0.84
0.81–0.85
232
219–242
230
204–258
266
254–287
283
238–303
96.8
90.6–101.6
100.6
84.3–109.1
105
102–111
104
96–117
0.83
0.80–0.86
0.84
0.81–0.88
244
231–261
254
240–271
289
270–309
297
253–328
93.9
85.9–101.3
92.6
81.4–104.9
101
97–109
98
93–108
0.82
0.81–0.87
0.82
0.81–0.89
238
230–250
243
215–260
282
254–306
274
242–315
Friedman P
SNK test
P < 0.05
<0.01
4 vs 1,2,3,5
<0.01
4 vs 1,2,3,5
<0.01
4 vs 1,2,3,5
<0.01
4 vs 1,2,3,5
<0.001
1 vs 3,4,5
<0.01
1,2 vs 3,4,5
NS
NS
<0.01
3 vs 1,2,4,5
<0.01
4 vs 1,2,3,5
<0.05
2,3 vs 1,4,5
Values are presented as median (above) with interquartile range (below)
Variation of repeated measurements during HD was analysed by Friedman test. If the variation was significant, Student–Newman–Keuls
(SNK) test was used to identify significant difference (P < 0.05) between the individual measurements (1 ¼ before HD, 2 ¼ in the 10th min,
3 ¼ in the 70th min, 4 ¼ in the 110th min, i.e. after the light meal, 5 ¼ in the 215th min).
There were no statistically significant differences between the regimens (dT ¼ 0 vs dE ¼ 0) in any of the variables at any time of measurement
(Wilcoxon test).
REE, resting energy expenditure; RQ, respiratory quotient (VCO2/VO2); VCO2, carbon dioxide production; VO2, oxygen consumption.
Table 6. Indirect calorimetry—comparison of HD patients (n ¼ 13) and control group (n ¼ 14)
Variable
BMR
REE
REE
REE
RQ
VCO2
VO2
Unit
W
W
W/1.73 m2
% of BMR
1
ml/min
ml/min
Control
HD
Median
IQR
Median
IQR
68.5
81.8
82.8
118
0.92
233
235
62.9–84.0
68.4–98.5
75.6–92.7
114–123
0.89–0.93
187–272
206–288
74.6
90.0
82.8
123
0.92
247
259
70.2–79.4
83.2–110.0
75.7–86.4
113–129
0.88–0.94
230–279
248–295
The patients in the HD group were measured twice (before isothermic and thermoneutral HD) within 1 week and the average value of these
two measurements was used for median and interquartile range (IQR) calculations.
There were no statistical differences between controls and HD patients in any of the variables (Mann–Whitney test).
BMR, basal metabolic rate (calculated from Harris–Benedict formula); REE, resting energy expenditure (measured by indirect calorimetry);
RQ, respiratory quotient (VCO2/VO2); VCO2, carbon dioxide production; VO2, oxygen consumption.
similar strength. In our patients, the energy loss per
1% of body weight change corresponded to 5.6% of
measured pre-dialysis REE, which is in perfect agreement with 6% estimation of Rosales et al. [6] despite
considerably lower ultrafiltration volume in our
patients. Also, our heat flow (15 W) is in accord with
Schneditz et al. [7], who observed extracorporeal heat
flow of 20 W (with a mean dBV of 15% in his patients).
According to ‘volume hypothesis’ [1], the accumulation of heat in the body during conventional HD
is a consequence of vasoconstriction, which is a
regulatory haemodynamic response to decreasing
intravascular volume due to ultrafiltration. Vasoconstriction leads to skin hypoperfusion, thus impairing
heat dissipation. In order to prevent the rise in body
temperature, the accumulated heat must be removed in
another way, i.e. by heat transfer from blood into
dialysate in dialyser. As vasoconstriction is presumably
proportional to the loss of circulating volume,
the necessary amount of heat removed is proportional
to the loss of intravascular volume, too. Our findings
are in accord with this ‘volume hypothesis’, and lend
Resting energy expenditure and heat removal during haemodialysis
3559
further support to it in a novel setting, with smaller
changes in intravascular volume, and no important
changes in blood pressure.
Quite recently, van der Sande et al. [13, 14] were
first to show that in isothermic HD some thermal
energy had to be removed (to keep body temperature
constant) even in isovolaemic HD without any
measured cutaneous perfusion changes. They concluded that ‘volume hypothesis’ does not provide full
explanation for heat accumulation during HD, and
more factors, so far poorly understood, may be
involved. In our setting, ultrafiltration was always
used, therefore we cannot comment on this.
Twenty years ago Monteon et al. [15] demonstrated
no important difference in energy expenditure between healthy subjects and stable patients undergoing
maintenance HD. Their results were later supplemented with reports of increased REE precipitated
by inflammation [16, 17] or accentuated hyperparathyroidism [18], but also of decreased expenditure
in simple (non-inflammatory) malnutrition [19]; all
these measurements were performed on non-dialysis
days. Pre-dialysis REE in our patients did not vary
on repeated measurement within 1 week, and it was
not different from healthy controls (though our
control group was not pair-matched). Our patients
had no symptoms/signs of inflammation/infection or
malnutrition.
There are scarce data on time course of REE during
HD and we have found no (full-text) report comparing
different thermal HD regimens in this aspect. Ikizler
et al. [20] described an increased REE in the course of
HD, but the inflammatory status of patients was not
reported, their dialysis solution contained 11 mmol/l
glucose, and also in other aspects their method was
different from ours.
Also, studies comparing pre- and post-dialysis values
of measured REE are scarce. An abstract by Lange
et al. from 1995 was cited in [1] suggesting an average
increase in REE by 8.6% (but with a high SD of
8.8%) during ‘cool’ HD, while during ‘warm’ HD it
was 12.4% (SD 9.7%). These results are difficult to
discuss as no full-text paper on these patients, with
other important methodological data, has since
appeared. Van der Sande et al. [13] found no change
in REE before and after isothermic and thermoneutral
HD (in both regimens with or without ultrafiltration).
Our study gives further support to their measurements,
providing original data on REE not only before and
after, but also during the course of HD. However, this
stability does not preclude mild changes in REE when
more intensive cooling is applied, as observed by
Rokyta et al. [21] in their critically ill patients.
In our setting, HD was standard ‘low-flux’ procedure, using standard dialysis solution, where endotoxin
concentrations were kept below the safety values
recommended by European pharmacopoeia. There
was no difference between isothermic and thermoneutral HD in serum PAPP-A levels, indicating that
thermal balance does not influence the biological
response to dialysis.
Our secondary (though rather surprising) finding
was continuously decreasing RQ in the course of both
HD regimens. Ikizler et al. [20] described a similar
trend, while van der Sande et al. [13] found no
difference in RQ before vs after HD. Our finding
may tentatively be explained by corresponding variations in NEFA concentrations and/or metabolism.
Preferential NEFA oxidation decreases RQ, while
glucose oxidation has the opposite effect. In the first
hour of both HD regimens an increase in NEFA levels
was found, followed by a decline but not to the
baseline values. Theoretically, we might ascribe the
initial rise of NEFA to heparin (2000 U administered
at the beginning of HD), a well-known activator of
lipoprotein lipase. More importantly, NEFA may also
be mobilized by fasting during HD, possibly aggravated by glucose loss into dialysate. This hypothesis
would be supported by their decline following a light
(carbohydrate-containing) meal. While NEFA levels
were decreasing after the light meal, the observed
decline in RQ was stopped, and RQ then remained
stable in spite of a temporary increase in oxygen
consumption and REE. Also, there was a correlation
between the changes in NEFA levels and in RQ during
HD. We have found no data on NEFA dynamics
during HD in the available literature.
We are also not aware of any study describing the
changes of vasoactive hormones during isothermic and
thermoneutral HD. The sharp (and expected) decrease
in cGMP, corresponding to the loss of circulating fluid
volume, was not different between isothermic and
thermoneutral HD, indicating no important difference
in the fluid shifts between these procedures.
In conclusion, our findings suggest that stablemaintenance HD patients have REE not different
from healthy controls, that HD procedure per se does
not significantly increase REE and that neither
isothermic nor thermoneutral regimen has any influence on metabolic rate. Therefore, body temperature
elevation during routine HD may rather be due to
decreased heat removal. With the use of BTM in active
mode, body temperature can be kept stable (isothermic
HD), which requires active cooling. This negative
energy transfer is proportional to decrease in blood
volume induced by ultrafiltration.
Acknowledgements. This study was supported by the research
projects ‘MZO 0021620819’ and ‘MZO 00179906’, Czech Republic.
We are grateful to Dr Jirina Soukupova for her valuable laboratory
work, to Ing. Petr Moucka for his technical support and consultations and to Dr Jan Blaha for recruitment of patients.
Conflict of interest statement. None declared.
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Received for publication: 13.2.07
Accepted in revised form: 11.6.07