Indirect calorimetry: methodology, instruments and

clinical application
Eduardo E. Moreira da Rocha, Valéria Girard F. Alves and
Rosana Barcellos V. da Fonseca

Purpose of review Abbreviations

This review aims to identify the basic methods for accurately FiO2 fractional inspired oxygen
ICU intensive care unit
measuring a patient’s energy expenditure in clinical nutrition M metabolic energy expenditure
practice by indirect calorimetry, and the impact upon a MCHO endogenous metabolism of carbohydrate
MLip endogenous metabolism of lipid
disease state of applying the results obtained. MProt endogenous metabolism of protein
Recent findings MREE measured resting energy expenditure
MW production of metabolic water
The open-circuit method is the most widely used in the PAEE physical activity energy expenditure
majority of classical instruments for measuring energy REE resting energy expenditure
RMR resting metabolic rate
consumption. Advances in gas exchange measurement TDEE total daily energy expenditure
have made this technique readily and precisely available at VO 2 oxygen consumption
VCO2 carbon dioxide production
the bedside. Nevertheless, it is important to understand its uN2 urinary nitrogen
intricate primary methodology for safe and correct
application. The stress and activity factors should be
carefully and specifically applied, and the respiratory ß 2006 Lippincott Williams & Wilkins
1363-1950
quotient abandoned, for tailoring a patient’s daily nutrition
regimens. Caloric expenditure measured by indirect
calorimetry coupled with the doubly labeled water
Introduction
technique introduced the concept of physical activity One of the most important aspects of nutrition support is
energy expenditure, which added to resting energy based on the ability to determine and/or estimate with
expenditure results in total daily energy expenditure. greatest accuracy a patient’s energy expenditure. A dis-
Compact modular and handheld devices have been ease state, critical or not, may have marked effects on
introduced into the market, together with similar technology nutritional status. Consequently, it is essential to avoid
for evaluating exercise energy expenditure, making complications related to the inadequate delivery of nutri-
utilization easier, safer and precise. In the critically ill tion support, in particular of calories in excess [1

,2–4,
population, which is exposed to medical and surgical 5

,6,7,8

,9

].
interventions, indirect calorimetry has greatly changed the
practice of caloric administration, significantly reducing the Monitoring of the patient’s physiologic and metabolic
total daily amount. responses to illness and their nutritional needs is an
Summary important clinical feature [3]. The analysis of substrate
In conclusion, one has to be careful when choosing devices, oxidation and utilization depends on intricate method-
and understanding and clinically applying the results ology, because correct assumptions must be made based
obtained by indirect calorimetry, bearing in mind that on the metabolic calculations [6,10–16]. Consequently,
measured resting energy expenditure should be the daily evaluation of resting energy expenditure (REE) is
caloric goal in order to diminish clinical morbidity. equally indispensable for the provision of the correct
daily nutritional requirements, in order to avoid hyper/
Keywords hypo-caloric and hyper/hypo-protein feeding, any of
carbon dioxide production, energy expenditure, indirect which will lead to increased morbidity and mortality,
calorimetry, oxygen consumption, respiratory quotient, in particular in the critically ill patient population
stress/activity factors, total daily energy expenditure [1

,2,4,5

,7,9

,14–21].

Curr Opin Clin Nutr Metab Care 9:247–256. ß 2006 Lippincott Williams & Wilkins.
NUTROCLIN, Clı́nica São Vicente/Gávea, Rio de Janeiro, Brazil
Correspondence to Dr Eduardo E. Moreira da Rocha, Rua Paulo César de Andrade,
450/401 Laranjeiras, Rio de Janeiro, Brazil 22221-090
Tel: +55 21 2265 5558; fax: +55 21 2285 5896;
e-mail: edurocha46@globo.com
Current Opinion in Clinical Nutrition and Metabolic Care 2006, 9:247–256
Recent advances in gas exchange evaluation technologies
have made assessment of oxygen consumption (VO2 ) and
carbon dioxide production (VCO2 ) promptly available on a
continuous basis and at the bedside. A synthesis of the
recent scientific data on these specific measurements sup-
ports the use of serial determinations of metabolic changes
for monitoring the patient’s nutritional status [3,22].
247

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 248 Pharmaceutical aspects, devices and techniques
The gold standard for indirect calorimetry measurements
in clinical practice should be the most precise, reliable and
safe instrument. As the use of indirect calorimetry is
becoming increasingly widespread, it is necessary to mas-
ter its methodological basis, as well as its theoretical and
practical limitations [1

,2,4,6,7,9

,16,20,21,23,24].
The use of indirect calorimetry is fundamental for the
clinical application of the measurement of REE in normal
individuals and for guiding daily nutrition support as a
whole, in critical illnesses such as major trauma and
sepsis, for the healthy or sick obese patient, and even
for establishing new or re-evaluating estimative caloric
expenditure formulae. Therefore the proper imple-
mentation of a multidisciplinary protocol for metabolic
monitoring as part of the global nutritional assessment
should contribute to improving outcomes as well as to
more cost-effective patient care [1

,2–4,6,7,9

,22].
With the above principles related to indirect calorimetry
in mind, this review will concentrate briefly on the basic
rationale for the utilization of the correct methodology
and the metabolic calculations; it will then discuss the
most widely used and well established instruments,
related technology, and the most current and safe clinical
applications of this technique.
Methodology
Indirect calorimetry is the quantification of REE, which
is the major constituent of total daily energy expendi-
ture (TDEE). It is based on the non-invasive measure-
ment of VO2 , the greater component of REE, and VCO2
[1

,2–4,5

,6,7,8

,14,15]. These primary parameters are
derived precisely by the application of gas dynamics
physics, for the correct measurement of inspired and
expired gas concentrations and volumes [6,10,11].
Basic principle and rationale
The methodology for the performance of indirect calori-
metry in clinical practice is summarized in Table 1. A
Table 1 Caloric expenditure measurement by indirect calorimetry
(1) Measurement
– Expired gas fractions (O2/CO2) (mmHg)
– In a respiratory and metabolic steady state (‘metabolic
equilibrium’: coefficient of variation for VO2 and VCO2 must
be < 5% for five consecutive minutes) [4,9,16,20,21,24–26]
(2) Techniques:
– Closed circuit: spirometer attached to a kymograph for O2
and soda lime for CO2 expired gas fractions (e.g. Tissot
gasometer – out of use and off the market) [6,10]
– Open circuit:
(a) Bock/Margaria mixing chamber and bottle respectively [6]
(b) Douglas bag (50–250 liter capacity)
(c) Lacoste bag (7–8 liter capacity)
(d) Deltatrac II: measures VO2 and VCO2
Adapted from [1

,3,4,6,7,10,11,17].
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
normal subject or patient breathes room air, or room air
mixed with oxygen, through a mouth piece with a nose
clip, a canopy hood, and an endotracheal or a tracheost-
omy tube. The mixed expired gas is collected at a known
temperature, during a minimum of 12–30 min, and the
total expired gas volume is recorded simultaneously [27–
30].
The O2 and CO2 gas fractions are measured in the total
expired gas volume by specific gas sensors, and trans-
formed into values for VO2 and VCO2 in ml/min, and
finally into a value for REE in kcal (or kJ)/day
(Table 2) [1,6,10,22,31].
The Haldane transformation based on the relatively
insoluble gas nitrogen (N2) is constant in both inspired
and expired gases, assuming that only O2 and CO2 are
exchanged in the lungs, and the rest of the respiratory
gases (excluding water vapor) have the same volume.
Then, if there is no net nitrogen uptake, the inspired gas
volume can be calculated (Table 2) [1

,6,10,11]. The
determination of fractional inspired CO2 is important
when working with a canopy or hood (flow-through)
system with an airflow of between 20 and 60 l/min, which
can lead to a final error in the VCO2 determination, in the
respiratory quotient and consequently in the REE value
[31].
Metabolic calculations
The evaluation of substrate oxidation from bomb calori-
metry can be performed by the utilization of elaborated
metabolic calculations (arithmetic, algebraic and stoichio-
metric equations) [6,10–16]. Based on the primary caloric
Table 2 Calculation of O2 consumption (VO2) and CO2 pro-
duction (VCO2)
Inspired gases: Expired gases:
F iO2 ¼ PiO2 =BP  47 F eO2 ¼ PeO2 =BP  47
F iCO2 ¼ PiCO2 =BP  47 F eCO2 ¼ PeCO2 =BP  47
F iN2 ¼ 1  F iO2  F iCO2 F eN2 ¼ 1  F eO2  F eCO2
Conversion of Ve and Vi (ATPS) into Ve and Vi (BTPS) (liters/min):
Ve (BTPS) ¼ Ve (ATPS)  CF
V i ðBTPSÞ ¼ V e ðBTPSÞ  F eN2 =F iN2 (Haldane transformation)
[1

,6,10,11]
Calculation of VO2 and VCO2 (liters/min):
VO2 ¼ ðF iO2  V iÞ  ðF eO2  V eÞ
VCO2 ¼ ðF eCO2  V eÞ  ðF iCO2  V iÞ
F iO2 and F eO2 , fractional inspired and expired O2 respectively; F iCO2
and F eCO2 , fractional inspired and expired CO2 respectively; FiN2 and
FeN2, fractional inspired and expired nitrogen respectively (all fractions in
%); PiO2 and PeO2 , partial pressures of inspired and expired O2
respectively; PiCO2 and PeCO2 , partial pressures of inspired and expired
CO2 respectively; BP, barometric pressure at sea level; 47, partial
pressure of water vapor at 378C (all pressures in mmHg); Vi and Ve,
inspired and expired gas volumes respectively; ATPS, ambient tempera-
ture and pressure saturated gas; BTPS, body temperature and pressure
saturated gas; CF, correction factor for 378C (reduction of saturated gas
volumes for those at body temperature: BTPS).
Adapted from [1

,6,10,22,31,32].

values for the metabolism of a mixture of 1 g of carbo-
hydrate, lipid and protein, with the consumption of
x liters of O2 (VO2 ) and the production of y liters of
CO2 (VCO2 ), the amounts of each substrate consumed
can be determined.
Likewise, VO2 and VCO2 can be transformed into energy
expenditure in kcal/day, with a correction for the metab-
olism of protein, by applying the widely used Weir
equation [12]:
M ¼ ð3:941  VO2 Þ þ ð1:106  VCO2 Þ
 ð2:17  uN2 Þ
M ðkcal=minÞ  1440 min=day ¼ REE ðkcal=dayÞ
where M is the metabolic energy expenditure in units of
kcal/min, and uN2 is urinary nitrogen in units of g/day;
VO2 and VCO2 are measured in liters/min. This equation is
better suited for the fasting state; Weir stated that the
error in neglecting the effects of protein metabolism is
1% for each 12.3% of total calories arising from protein,
and thus the above equation can be simplified without
the uN2 factor.
In addition, considering the above principles for substrate
oxidation, the values of VO2 and VCO2 in liters/min can be
used to derive the equations for determining the endoge-
nous metabolism of carbohydrate (MCHO; g/min), lipid
(MLip; g/min) and protein (MProt; g/min), the production
of metabolic water (MW; ml/min), and REE (M; kcal/min)
in the post-absorptive state [6,10,11,13–17]:
MCHO ¼ ð4:12  VCO2 Þ  ð2:91  VO2 Þ
 ð2:42  uN2 Þ
MLip ¼ 1:81  ðVO2  VCO2 Þ  1:68  uN2
MProt ¼ 6:25  uN2
MW ¼ ð0:301  VO2 Þ þ ð0:374  VCO2 Þ
 ð0:589  uN2 Þ
M ¼ ð3:99  VO2 Þ þ ð1:04  VCO2 Þ
þ ð1:78  uN2 Þ
As above, multiplying MCHO, MLip, MProt, MW or M by
1440 min/day gives values in units of of g, ml or kcal/day.
This same methodology can also be applied for the
calculation of energy expenditure in other clinical states,
such as energy excess (for example, lipogenesis or
trauma/sepsis) and energy deficit (for example, ketosis
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Indirect calorimetry da Rocha 249
secondary to diabetes mellitus, decreased energy intake,
or severe carbohydrate restriction) [6,10,11,13].
At the present time, all of the above sequences of
mathematical calculations derived primarily from expired
gas fractions of O2 and CO2 (in Table 2, the Weir
equation, and the equations for MCHO, MLip, MProt, MW
and M in the post-absorptive state) are done automati-
cally, precisely and simultaneously on-line in the new
micro-processing calorimeters.
The concept of total daily energy expenditure
The measured REE (MREE) is almost always processed
‘at rest’ in bedridden hospitalized patients in clinical
situations, and so does not need any adjustment to be
comparable with TDEE, for it aggregates any change in
REE due to metabolic or physical stress in 24 h. The
concept of TDEE was introduced together with the
measurement of caloric expenditure by the double-
labeled water technique [5

,9

,33–35]. This technique
is non-invasive and non-restrictive, which facilitates the
evaluation of TDEE in free-living humans. When associ-
ated with measurements of REE and of the specific
dynamic action of nutrients, it is possible to determine
physical activity energy expenditure (PAEE). This latter
fraction of energy expenditure is an important com-
ponent of TDEE which is not usually measured in the
clinical arena (Fig. 1) [17,33].
Following recovery from a disease process, every indi-
vidual initiates deambulation, and subsequently pro-
gresses to other different daily activities that markedly
change caloric expenditure. Consequently, the MREE
added to the PAEE establishes the TDEE, which
Figure 1 Components of total daily energy expenditure (TDEE)
Components of total daily energy expenditure
double labelled water technique
% 120
PAEE
(10--30%)
100 SDA
(10%) REE
80
60
(60--80%)
40
20
0
Total daily en. exp.
TDEE is constituted by resting energy expenditure (REE), which con-
tributes approximately 70%, plus the specific dynamic action (SDA) of
nutrients and physical activity energy expenditure (PAEE). In younger
individuals, a factor for growth included in the REE also contributes to
TDEE. Adapted from [34], with permission.
 250 Pharmaceutical aspects, devices and techniques
depends on the energy reserve capacity of the physio-
logical systems being adequately and safely met. The
effect of disease on energy metabolism has been mostly
established by studies on REE, although these have not
clarified the influence of disease on energy balance. The
PAEE is the component of TDEE that shows greatest
variability, but it has not been evaluated in the majority of
disease states [33].
Jeukendrup and Wallis [36

] demonstrated changes in
substrate oxidation, mainly of carbohydrate and fat, during
exercise that were secondary to alterations in the size of the
bicarbonate pool at higher exercise intensities. Fat oxi-
dation during exercise can be influenced by its intensity,
duration and mode, as well as by gender, training and diet.
These authors proposed slightly modified equations for
the calculation of carbohydrate and fat oxidation during
low-intensity and high-intensity exercise.
Haman and co-workers [37

], using a combination of
indirect calorimetry and a stable isotope technique, eval-
uated fuel metabolism in non-acclimatized adult men
exposed to low temperatures. The contributions of
plasma glucose, muscle glycogen, lipids and proteins to
total heat production during shivering compared with
exercise were studied. They concluded that a muscle
producing only heat (shivering) as opposed to significant
movement (exercise), both with similar energy demands,
appears to consume a different fuel mixture; in shivering,
muscle glycogen predominates.
In a sequential post-operative study in Sweden of 38
patients submitted to restorative proctocolectomy, with
an ileal pouch–anal anastomosis for ulcerative colitis,
Öhrström and associates [38] demonstrated that these
patients as a group had REE, working capacity and
recreational activities that were comparable with those
of healthy subjects. Their findings also led to the hypoth-
esis that any absorption of short-chain fatty acids from the
pouch, as an additional contributing energy source, did
not affect the patient’s working capacity.
In active subjects suffering from disease, PAEE is a strong
regulator of TDEE. The balance between PAEE and REE
will vary as influenced by the oxidation of known substrates
and the intensity of the exercise being performed. Both of
these components will determine the clinical changes
in TDEE, and ultimately impact on the disease state
[34,35,36

,37

,38]. Thus the double-labeled water meth-
odology and the measurement of REE by indirect calori-
metry provide powerful investigative tools for the clinical
evaluation of energy balance in sick individuals [34].
Instruments
Classical indirect calorimetry measurements are per-
formed with bulky and expensive equipment that calls
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
for careful calibration. Nevertheless, this technique has
broad clinical application, and is still the gold standard for
the validation of newer modular and compact technology.
Deltatrac
Deltatrac (Datex-Ohmeda, Helsinki, Finland) is an open-
system indirect calorimeter for measurement in both
mechanically ventilated and spontaneously breathing
patients (using a closed canopy). It is considered the
most accurate equipment, and has been validated in
various laboratory and clinical situations. The main
limitation to its use consists of its high cost
( $25 000) [8

,9

,21,23,39,40,41

].
Deltatrac measures caloric needs and estimates substrate
oxidation by continuous measurements of VO2 and VCO2 .
It has a paramagnetic and an infrared gas chamber for
sensing O2 and CO2 respectively, which allows for con-
tinuous and accurate measurements of gas concentration
differences between inspired and expired air, even at
high values of fractional inspired oxygen (FiO2 ) up to
60%, and also a pressure transducer to balance differences
in airway pressure.
Before measurement starts, a 30-min warm-up is necess-
ary, as well as calibration of the pressure against local
barometric pressure measured by a mercury barometer,
and of the gas analyzers using a known standard gas
mixture consisting of 96% O2 and 4% CO2.
Most current devices for indirect calorimetry measure-
ments apply the open-circuit technique, where the
expired gases are collected, the volume or flow of gas
measured, and the inspiratory and expiratory concen-
trations of O2 and CO2 analyzed. In general, one of
the flows is measured, and the other is estimated using
the Haldane transformation (Table 2). Such measure-
ment is influenced by several variables, such as the
effects of humidity, changes in gas composition,
secretions and the dynamic response of the flow sensors.
Deltatrac avoids interference on the flow sensors by
using an air dilution technique whereby the expiratory
gases are diluted in a known, constant flow. The con-
stant-flow generator keeps the output flow of the system
fixed and independent of the amount of expiratory gases
added. The expired gas fractions collected travel to the
mixing chamber, where they are sampled and measured.
The gases are then diluted with room air by the flow
generator, making the total flow through the system (Q)
equal to the flow generator’s output (usually 40 liters/
min). VO2 , VCO2 and the respiratory quotient are then
calculated using the following equations (where FCO2 is
the fractional concentration of carbon dioxide and FO2 is
the fractional concentration of oxygen), for example
for the canopy mode [1

,8

,14,23,42] (Table 2), and

subsequently transformed in M ¼ REE ¼ energy expen-
diture relative to VO2 and VCO2 (see equation under
M-COVX below).
VCO2 ¼ QðFCO2 Þ
VO2 ¼ ½ðQ=1  FiO2 Þ
½FO2  ðFiO2 ÞðFCO2 Þ
Respiratory quotient ¼ VCO2 =VO2
M-COVX
M-COVX (Datex-Ohmeda) is a modular metabolic
monitoring system that is compact and fully integrated
with other intensive care unit (ICU) monitoring modal-
ities. It measures VO2 and VCO2 on a breath-by-breath
basis. This new technology offers the opportunity to
routinely follow metabolic rate in mechanically venti-
lated patients. The modularity allows the switching of
the module between patients without the need for pre-
calibration, thus being immediately operational when
needed.
M-COVX has a technology which resembles that of
Deltatrac for gas sampling and volume analysis; however,
it uses mathematical integration of flow and time syn-
chronized continuous gas sampling in order to provide the
data in a continuous and non-invasive fashion.
The D-lite+ flow sensor (9.5 ml dead space) is totally
integrated to the gas exchange measurement. This flow
sensor in conjunction with the gas sampler is connected at
the patient’s airway and provides the conduit for the gas
exchange measurement. The flow measurement is based
on the pressure drop across a special proprietary turbulent
flow restrictor. The D-lite can be used with active
humidification or in conjunction with a heat and moisture
exchange (HME) filter.
Inside the gas module, the paramagnetic sensor is used to
measure the O2 curve, and the infrared bench is used for
the CO2 curve. Both measurements are based on the side-
stream principle, and consequently gas concentrations
and flow measurements are not simultaneous. When a gas
sample passes through the D-lite, the flow signal is
recorded with a negligible delay (less than 10 ms), since
the pressure difference propagates to the module through
the spirometry tubing at the speed of sound. In contrast,
it takes approximately 1.5 s for the gas fraction to travel
through the sampling line to the module, where first the
O2 concentration and then the CO2 concentration is
measured. The transport time delay is not constant; it
must compensate for fluctuations in the sample flow,
variations in the pressure at the D-lite and changes in
the gas concentration. In addition, the finite rise times of
the O2 and the CO2 sensors need to be compensated for
by utilizing a de-convolution algorithm.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Indirect calorimetry da Rocha 251
After reconstructing the original waveforms of the gas
concentrations and shifting the curves to match the flow
signal, the final calculations are based on mathematical
integration operation of the product of the flow and each
gas signal. Respiratory quotient is calculated once per
minute and updated to the display with the same time
lag. Energy expenditure cannot be measured directly, but
is calculated from VO2 , VCO2 [both measured in units of
ml/min STPD (standard temperature and pressure dry
gas)] and uN2 (units of g/day) once per minute, applying
the formula [14,15,23]:
Energy expenditure ðkcal=dayÞ
¼ 5:5VO2 þ 1:76VCO2  1:99uN2
McLellan and collaborators [38] compared M-COVX
and Deltatrac II in mechanically ventilated patients,
and found that the difference between the two methods
was clinically insignificant for both VO2 and VCO2 .
Repeated measurements for testing reproducibility
suggested that for VO2 M-COVX performed better than
Deltatrac at high FiO2 (0.7), and for VCO2 Deltatrac was
better at lower FiO2 (0.3 – 0.5). They concluded that
M-COVX could be used with adequate reproducibility
and accuracy for measuring respiratory gas exchange
in ventilated critically ill patients. Donaldson and co-
workers [40] also measured VO2 continuously for 24 h in
27 patients on mechanical ventilation admitted to a
general ICU, and concluded that the average of VO2
data with the M-COVXTM module results in small
errors.
MedGem
The MedGem resting metabolic rate (RMR) analyzer
(HealthTech, Golden, CO, USA) is a handheld device
that contains only an oxygen analyzer for measurement of
VO2 . VCO2 is not measured, and consequently no respir-
atory quotient is derived; a constant respiratory quotient
of 0.85 is assumed.
The oxygen analyzer uses a dual-channel fluorescent
quenching sensor, which is based on the deactivation
of ruthenium cells in the presence of oxygen. It is self-
calibrating and needs minimal operator training for profi-
cient testing. The test time is approx. 10 min [8

,43,
44
,45
,46

,47
,48
,49]. It cannot be used with patients
requiring mechanical ventilation, and is intended as an
ambulatory tool for nutrition specialists in the evaluation
of obesity, diabetes or lifestyle improvement [9

].
In comparison with Deltatrac, the MedGem calorimeter
showed no significant differences in the measurement
of VO2 and RMR in healthy and ambulatory subjects
[43,44
,45
,49]. In a validation study with this handheld
device, Nieman and co-workers [45
] demonstrated that
 252 Pharmaceutical aspects, devices and techniques

there were no significant differences between the
Douglas bag technique and MedGem for measuring
VO2 and RMR in children. On the other hand, when
comparisons were made in healthy women [46

],
cancer patients [47
] and obese healthy adults [48
],
there was a wide variation in the results. Melanson and
associates [48
] demonstrated that the BodyGem gave
significantly higher values for RMR when compared
with the Sensormedics 2900 (SM-2900, Yorba Linda,
CA, USA) indirect calorimeter, and that this increase
was largely due to an increased energy demand
required to hold the BodyGem in position.
Clinical applications
Indirect calorimeters can measure energy expenditure in
both mechanically ventilated and spontaneously breath-
ing patients. For spontaneously breathing patients, a
canopy, facemask or mouthpiece with a nose clip may
be used to capture gas exchange. Measurements in
mechanically ventilated patients must be more accurate,
as opposed to the use of a mouthpiece or nose clip, which
might interfere in the measurement due to anxiety and
hyperventilation [4,24]. This can be minimized by allow-
ing a 5 min acclimation period followed by a 20 min
measurement of REE [3,28,50].
Indications for indirect calorimetry can be divided into
three general categories [4,24]: (a) clinical conditions
that significantly alter REE; (b) when patients fail
to respond to presumed adequate nutrition support;
and (c) in order to individualize and fine-tune the
nutrition support in the ICU. Thus, in several clinical
situations, the predictive equations for estimation of
REE can become inaccurate, and consequently
patients will not benefit from the nutrition support
provided, which may even contribute to an adverse
clinical course [1

,2–4,5

,9

,15,16,18–21,24,51–53].
The accuracy of indirect calorimetry measurements is
dependent on patient, environmental and equipment
variables (Table 3) [4]. Careful attention to technical
factors that can affect the validity of study results is
necessary (Table 4) [4].
It is important to consider the duration of the measure-
ment that is necessary to obtain the most accurate esti-
mate of 24 h energy expenditure. A 15 min measurement
seems to be sufficient to adequately estimate REE with a
4% error [51]. Some studies have demonstrated that a
brief measurement of 5 min, provided that there is a
less than 10% variation between measurements over
each 1 min, is sufficient to give a satisfactory result
[25,54]. McClave and collaborators [25] defined steady
state as a period of five consecutive minutes in which
variations in VO2 and VCO2 are less than 10%. When the
patient achieves this condition, the values obtained can
be used as an accurate representation of the 24 h TDEE,
with no further adjustments, especially in the absence
of fever.
There was a consensus in the literature until these
findings to add a 10% activity factor to the REE of an
ICU patient. Under steady-state conditions, MREE
closely approximates true 24 h energy expenditure,
making the addition of an activity factor unnecessary,
with no need to add patient or nursing care activity, as
was done in the past [4,7,9

,20,25]. The addition of
stress or activity factors would increase the risk of over-
feeding. Recent changes and advances in clinical care
have resulted in re-evaluation of the use of these

Table 3 Recommendations for improving accuracy of indirect calorimetry

Patients have rested in a supine position (in bed or a recliner) for more than 30 minutes before the study to avoid the effects of voluntary
activity on REE.

Patients receiving intermittent feedings, i.e., bolus enteral feeding, cyclic enteral or parenteral nutrition, or meals, are studied approximately
12 hour after the feeding if thermogenesis is to be included in the REE or 4 hours after the feeding if it is not.

The rate and composition of nutrients being infused on a continuous basis are stable for at least 12 hours before and through
the study.

Measurements are made in a quiet, thermoneutral environment.

All sources of supplemental oxygen (i.e., nasal cannulas, masks, or tracheostomy collars) are turned off during routine room air measurements,
if medically feasible.

The fraction of inspired oxygen (F iO2 ) remains constant during the measurement.

The study will be delayed tor 90 minutes if changes are required in ventilatory settings.

The patient has usual patterns of voluntary skeletal muscle activity (movement of the extremities) during the study.

No leaks are present in the sampling system.

All data used to derive REE and RQ are taken from a period of equilibrium or steady state that has been identified according to statistically
defined guidelines.

The patient has not received general anesthesia within 6 to 8 hours before the study.

If the patient is in pain or agitated, analgesics or sedatives will be given at least 30 minutes before the study when clinically possible.
Analgesics and sedatives administered will be documented, and this information will be considered during the interpretation of
the study.

The study will be delayed for 3 to 4 hours after hemodialysis.

The study will be delayed 1 hour after painful procedures have been performed.

Routine nursing care or activities involving other health care professionals should be avoided during the study.
REE, resting energy expenditure; RQ, respiratory quotient. Reproduced from [4] (Table 2), with permission.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Table 4 Technical factors that decrease the accuracy of indirect
calorimetry

Mechanical ventilation with F iO2  60

Mechanical ventilation with positive end expiratory pressure
> 12 cm H2O

Hyper-hypoventilation (acute changes altering body CO2 stores)

Leak in the sampling system

Moisture in the system, which can affect the oxygen analyzer

Continuous flow through the system > 0 l/min during exhalation

Inability to collect all expiratory flow

Unstable inspiratory F iO2 (> 0.01)

Leaking chest tube (inability to collect all expired gases)

Bronchopleural fistula (inability to collect all expired gases)

Supplemental oxygen in spontaneously breathing patients

Hemodialysis in progress

Errors in calibration of indirect calorimeter
F iO2 , fractional inspired O2. Reproduced from [4] (Table 3), with
permission.
factors, as the measured value accurately reflects TDEE,
which incorporates the increases in REE caused by
metabolic stress. In fact, the MREE of ventilated patients
equates to the TDEE without any multiplication factors
[9

]. An additional 5% should be added only when the
measurement is made in the post-absorptive state or in
bolus feeding, to account for the thermogenic effect of
food (specific dynamic action) [4,20].
In general, patients who do not achieve the steady state
are clinically unstable and the measured value cannot be
extrapolated for the 24 h TDEE. Their test time should
be prolonged to 60 min, or sometimes 24 h monitoring
might be necessary [25]. In an attempt to reduce the
steady-state period even further, Reeves and associates
[26] compared 4 min and 3 min periods of measurement
with a 5 min steady-state measurement in healthy volun-
teers and ambulatory chronically ill patients. The results
showed a small but acceptable difference in the MREE
values when compared with the 5 min period, and a
greatly increased proportion of subjects who reached
the steady state.
The respiratory quotient (the VCO2 =VO2 ratio) varies from
0.67 (corresponding to ketone body metabolism) in the
fasting state, to a maximum of 1.3, reflecting lipogenesis
derived from glucose or a hyperventilation state, either
spontaneous or due to mechanical ventilation. Values
below 0.67 suggest that there might be a leak in the
gas collection apparatus [4,24]. The respiratory quotient
was used in the past to guide the macronutrient choice of
nutrition support. A respiratory quotient of 0.7 would
reflect exclusively lipid metabolism, one of 0.8 indicated
protein consumption, a value of 0.84 suggested mixed
fuel metabolism and one of 1.0 indicated pure glucose
metabolism [16]. Recent studies, on the other hand, have
shown that the use of the respiratory quotient to guide
the macronutrient choice for nutrition support is
inadequate. In fact, a rise in the respiratory quotient
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Indirect calorimetry da Rocha 253
may reflect intolerance to an excessive amount of feeding
resulting in respiratory distress, especially in patients who
are nutritionally depleted, stressed or hypermetabolic, or
who have chronic obstructive pulmonary disease and a
limited capacity to eliminate CO2 [9

].
McClave and co-workers [33] found in a prospective
study with 263 patients that only 28.4% of overfed
patients showed an elevation of the respiratory quotient
above 1.0, but they all had some degree of ventilation
compromise, demonstrating intolerance to the nutrition
burden. The major benefit of the measurement of the
respiratory quotient would be to validate indirect
calorimetry, determining that it falls within the physio-
logical range [4,9

].
Improvements in medical and nursing care for critically ill
patients, changes in sedation practices and the more
frequent use of inotropic agents have all led to a tendency
towards a decline in the metabolic rates of hospitalized
patients, especially in the ICU. Various studies in
patients on mechanical ventilation have demonstrated
the need for a change in the nutrition support after
indirect calorimetry was performed [18,19,21,52,55].
The common use of sedatives in this population, and
eventually the need for neuromuscular blockade, can
result in a significant reduction in the energy expenditure
even in trauma and/or septic patients [16,55,56].
In obese patients, energy expenditure is highly variable.
The overfeeding of critically ill obese patients may be
particularly detrimental and contribute to a poor clinical
outcome. Great discrepancy is shown in clinically apply-
ing the estimation of energy expenditure in this popu-
lation. The difficulty in determining the caloric needs for
obese individuals makes it advisable to determine their
energy demands adequately using indirect calorimetry, in
order to minimize the adverse effects of underestimations
or overestimations [57–59].
It has been established that overfeeding is deleterious
and could influence the outcome of patients in the ICU.
Conversely, the practice of shortly underfeeding is still
controversial, and the degree to which it is detrimental is
yet to be determined. Nevertheless, it seems reasonable
to adjust caloric supply to energy expenditure as
measured by indirect calorimetry in order to obtain a
balanced administration of calories in the critically ill
patient [3,16,21].
To what extent mechanical ventilation affects VO2 , VCO2
and energy expenditure has been evaluated in a few
studies comparing different ventilation modes [60
],
different levels of positive end-expiratory pressure
[61
] and the influence of respiratory therapy treatment
in the critically ill patient [62]. None of these resulted in
 254 Pharmaceutical aspects, devices and techniques
significant alterations in indirect calorimetry results,
especially when tidal volume remained constant through-
out the measurement
The original work of Harris and Benedict [63] inaugu-
rated the concept of ‘estimative or predictive formulae’
derived from indirect calorimetry to determine the
basal metabolic rate of normal human volunteers. Sub-
sequently, a large body of scientific literature has
appeared based on this primary concept, aimed at the
estimation of caloric expenditure in daily clinical nutri-
tion support practice. Although many new studies have
appeared, and around 138 formulae by 40 different
authors have been published, the similarities and differ-
ences between these methods and the real advantages
offered by the recently introduced formulae remain
unclear [5

].
Indirect calorimetry is fundamental in deriving energy
expenditure predictive formulae; however, the primary
biological, physical, ethnic and environmental variability
within each equation will certainly lead to some degree of
error, with regard to their application in practical nutri-
tion. Thus the clinician has to bear in mind this basic
concept when dealing with healthy, malnourished, over-
weight or obese individuals, as well as critically ill
patients, mainly with sepsis and trauma, when aiming
for the administration of adequate and safe nutrition
support [5

].
Conclusion
In a recent review [5

], the authors showed that it is very
difficult to accurately estimate the RMR/REE of any
healthy or sick individual through predictive equations.
Therefore indirect calorimetry is an important tool for the
attending clinicians and/or the nutrition specialists in
order to adequately establish the energy needs of a
patient with a specific pathological state; that is, to match
estimated requirements to actual energy expenditure
[1

,2–4,5

,9

,17,18,20–22,51,52,55]. This becomes of
vital significance when dealing with critically ill patients,
especially those who are obese or malnourished, who are
exposed to marked organ insults, in association with the
use of several different types of drugs and submission to
clinical procedures that greatly alter their metabolic state.
The repeated use of indirect calorimetry in these clinical
situations is imperative in order to determine the effec-
tive REE and to avoid deleterious overfeeding and
clinical nutrition-induced morbidity [2–4,9

,21,22,55].
Caloric expenditure determined by indirect calorimetry
corresponds to an energy ‘use’ instead of energy ‘need’ of
the body. Energy use involves the caloric expenditure
related to the endogenous and exogenous metabolism of
nutrients, independent of other nutrition and metabolic
variables. Therefore MREE in the steady state (Table 1)
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
is a patient-specific caloric reference. Conversely, energy
need is related to the patient’s clinical status and the
route of nutrient administration [40].
Recent advances in the determination of gas exchange
have made VO2 and VCO2 evaluation promptly available at
the bedside in a continuous manner, on-line and/or for
24 h if necessary. It is important to understand the
methodological basis of indirect calorimetry, and its
theoretical and practical limitations. The type of assess-
ment being performed, be it on mechanically ventilating,
spontaneously breathing or exercising subjects, must be
recognized for the correct clinical application of the
measurement results [1

,2–4,9

,51,55].
The measurement of uN2 excretion, together with that of
VO2 and VCO2 , permits the estimation of macronutrient
oxidation, which is important information for tailoring the
nutrition support protocol in malnourished, obese or
critically ill subjects in particular. Nevertheless, it is most
important to be certain that the inherent metabolic
assumptions are fulfilled in the clinical situation being
studied [2,6,10,11,13,16,21,36

].
State-of-the-art current technology for the determination
of energy expenditure is based on the classical instru-
ments for indirect calorimetry, in which the application of
the open-circuit technique is widely present. The Delta-
trac is the instrument for this purpose that has been most
validated in research and clinical nutrition practice, and
can be considered as the gold standard due to its com-
plete, precise and diversified modes for indirect calori-
metry measurement and metabolic evaluation [2,8,9

,
21,23,39,40,41

].
The new compact modular metabolic assessment system
M-COVX is very convenient for the ICU setting, and also
provides complete energy expenditure measurements
and useful metabolic calculations; however, it has to
be integrated to an ICU monitoring system and has an
inherent measurement error of up to 5–6% compared
with Deltatrac [39,40]. Another recent and interesting
handheld device for indirect calorimetry is MedGem,
which has been thoroughly validated in several clinical
instances; however, due to its technical characteristics it
can only be utilized for ambulatory patients or out-
patients, mainly for the purpose of tailoring and moni-
toring weight loss regimens or for follow-up of patients
with wasting diseases on a nutritional replenishing
protocol [8

,43,44
,45
,46

,47
,48
,49].
A recently introduced technology outside the clinical
setting for the measurement of exercise-dependent calo-
ric expenditure, related to PAEE and TDEE, includes
actigraphy, uniaxial accelerometry methods and an
instrument known as the ActiReg. This methodology

has been validated by classical indirect calorimetry
measurements, and opens a whole new field of appli-
cation for physical exercise training, monitoring and
enhancing performance, and as an important research
tool [64,65,66

].
A primary aim when measuring REE is the quantification
of energy use by the body cell mass in order to detect
hypermetabolism or hypometabolism. The assessment of
body composition coupled with REE measurement is of
great diagnostic potential, since it can objectively identify
a true hypometabolic state. A reduction in REE could be
related to real body cell mass consumption, or signal a
markedly deleterious hypometabolic response, probably
secondary to cytopathic hypoxia [2–4,7,21,41

,67]. In
the presence of a hypermetabolic response in the criti-
cally ill patient following a pathophysiological insult, a
major goal is to maintain energy balance [2,9

,16,17].
Indirect calorimetry provides reliable, non-invasive and
precise measurements of REE, which is the largest
constituent of TDEE. Nutrition delivery based on indir-
ect calorimetry determinations is the most accurate, and
protects the patient from under or overfeeding. Never-
theless, since there are a wide variety of primary methods
involving basic physics and chemistry, as well as tech-
niques and equations for the final determination of
energy expenditure, it is imperative to adhere to and
be familiar with known protocols aiming at strict meth-
odology, which is necessary for technical accuracy and
clinically useful results.
In conclusion, a summary of the published data advises
the use of gas exchange evaluation of VO2 and VCO2 in a
sequential manner for assessing metabolic alterations
and for monitoring a patient’s nutritional status. The
measurement of energy expenditure through indirect
calorimetry is instrumental in the modulation of calorie
administration, and MREE should be the caloric target.
The respiratory quotient should be used to confirm test
validity, but the addition of stress or activity factors is
probably unnecessary, and will increase the incidence
of clinical nutrition-related morbidity [2–4,7,9

,18,19,
21,22,33].
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:

of special interest


of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 334).
1 Branson RD, Johannigman JA. The measurement of caloric expenditure. Nutr


Clin Pract 2004; 19:622–636.
An elegant and thorough review of the methodology, instruments, technical
considerations and main factors that interfere in utilization, as well as the practical
application of indirect calorimetry in clinical nutrition.
2 Battezzati A, Vigano R. Indirect calorimetry and nutritional problems in clinical
practice. Acta Diabetol 2001; 38:1–5.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Indirect calorimetry da Rocha 255
3 Headley JM. Indirect calorimetry: a trend toward continuous metabolic
assessment. AACN Clin Issues 2003; 14:155–167.
4 Wooley JA, Sax HS. Indirect calorimetry: applications to practice. Nutr Clin
Pract 2003; 18:434–439.
5 Rocha EEM, Alves VGF, Silva MHN, et al. Can measured resting energy


expenditure be estimated by formulae in daily clinical nutrition practice? Curr
Opin Clin Nutr Metab Care 2005; 8:319–328.
A thorough review of the main clinical variables that interfere in the derivation of
predictive formulae for estimating energy expenditure, from the use of indirect
calorimetry measurements and their adequate and safe application in clinical
nutrition practice.
6 Bursztein S, Elwyn DH, Askanazi J, Kinney JM, editors. Energy metabolism,
indirect calorimetry and nutrition, Baltimore: Williams and Wilkins; 1989.
7 Uehara M, Plank LD, Hill GL. Components of energy expenditure in patients
with severe sepsis and major trauma: a basis for clinical care. Crit Care Med
1999; 27:1295–1302.
8 Stewart CL, Goody CM, Branson R. Comparison of two systems of measuring


energy expenditure. JPEN J Parenter Enteral Nutr 2005; 29:212–217.
A well designed study comparing the handheld indirect calorimeter MedGem and
Deltatrac, with the application of a nicely arranged methodology, showing no
significant difference in RMR measurements between the two devices in sponta-
neously breathing subjects.
9 Holdy KE. Monitoring energy metabolism with indirect calorimetry: instru-


ments, interpretation and clinical application. Nutr Clin Pract 2004; 19:447–
454.
This review compares types of current indirect calorimetry instruments, describes
new approaches to the interpretation of MREE, discusses the clinical application of
indirect calorimetry, and re-evaluates energy metabolism in terms of body com-
position, and cellular and organ energy expenditure.
10 Consolazio CF, Johnson RE, Pecora LJ. Physiologic measurements of meta-
bolic functions in man. New York McGraw Hill; 1963. pp. 1–59.
11 Ferrannini E. The theoretical basis of indirect calorimetry: a review. Metab Clin
Exp 1988; 37:287–301.
12 Weir JB. New methods for calculating metabolic rate with special reference to
protein metabolism. J Physiol 1949; 109:1–9.
13 Westenskow DR, Schipke CA, Raymond JL, et al. Calculation of metabolic
expenditure and substrate utilization from gas exchange measurements. JPEN
J Parenter Enteral Nutr 1988; 12:20–24.
14 Takala J, Meriläinen P. Handbook of gas exchange and indirect calorimetry.
Document No. 876710-1. In: Takala J, Meriläinen P, editors. Helsinki: Datex
Division Instrumentarium Corp.; 1991. pp. 1–74.
15 Takala J. Clinical application guide of gas exchange and indirect calorimetry.
Helsinki: Datex-Ohmeda; 2002.
16 Brandi LS, Bertolini R, Calafa M. Indirect calorimetry in critically ill patients:
clinical applications and practical advice. Nutrition 1997; 13:349–358.
17 Rocha EEM. Determination of caloric expenditure in critically ill patients [in
Portuguese]. Clin Bras Terap Intens 2001; 11:1–23.
18 McClave SA, Lowen CC, Kleber MJ, et al. Are patients fed appropriately
according to their caloric requirements? JPEN J Parenter Enteral Nutr 1998;
22:375–381.
19 Alberda C, Snowden L, McCargar L, et al. Energy requirements in critically
ill patients: how close are our estimates? Nutr Clin Pract 2002; 17:38–
42.
20 McClave SA, Snider HL. Use of indirect calorimetry in clinical nutrition. Nutr
Clin Pract 1992; 7:207–221.
21 Reid CL. Nutritional requirements of surgical and critically ill patients: do we
really know what they need? Proc Nutr Soc 2004; 63:467–472.
22 Fonseca RBV, Alves VGF, Rocha EEM, et al. Clinical use of indirect calori-
metry: which factors interferes on the test in critically ill patients? [Abstract in
Portuguese] Rev Bras Nutr Clin 2005; 20 (Suppl. 2):S8.
23 Takala J, Keinänen O, Väisänen P, Kari A. Measurement of gas exchange in
intensive care: laboratory and clinical validation of a new device. Crit Care
Med 1989; 17:1041–1047.
24 Malone AM. Methods of assessing energy expenditure in the intensive care
unit. Nutr Clin Pract 2002; 17:21–28.
25 McClave SA, Spain DA, Skolnick JL, et al. Achievement of steady state
optimizes results when performing indirect calorimetry. JPEN J Parenter
Enteral Nutr 2003; 27:16–20.
26 Reeves MM, Davies PS, Bauer J, Battistutta D. Reducing the time period of
steady state does not affect the accuracy of energy expenditure measure-
ments by indirect calorimetry. J Appl Physiol 2004; 97:130–134.
27 Haugen HA, Melanson EL, Tran ZV, et al. Variability of measured resting
metabolic rate. Am J Clin Nutr 2003; 78:1141–1145.
 256 Pharmaceutical aspects, devices and techniques
28 Grunwald GK, Melanson EL, Forster JE, et al. Comparison of methods for
achieving 24-h energy balance in a whole room indirect calorimeter. Obes
Res 2003; 11:752–759.
29 Forse RA. Comparison of gas exchange measurements with a mouthpiece,
face mask, and ventilated canopy. JPEN J Parenter Enteral Nutr 1993;
17:388–391.
30 Isbell TR, Klesges RC, Meyers AW, et al. Measurement reliability and reactivity
using repeated measurements of resting energy expenditure with a face mask,
mouthpiece and ventilated canopy. JPEN J Parenter Enteral Nutr 1991;
15:165–168.
31 Damask MC, Schwarz Y, Weissman C. Energy measurements and require-
ments of critically ill patients. Crit Care Clin 1987; 3:71–96.
32 Diem K Reduction of saturated gas volumes for those at body temperature
[in Spanish] in Diem K (Ed.) Documenta Geigy: Tablas Cientificas, 6th Edition.
J. R. Geigy SA, Basilea (Suiza), 1965, p. 305.
33 McClave SA, Lowen CC, Kleber MJ, et al. Clinical use of the respiratory
quotient obtained from indirect calorimetry. JPEN J Parenter Enteral Nutr
2003; 27:21–26.
34 Toth MJ. Energy expenditure in wasting diseases: current concepts and
measurement techniques. Curr Opin Clin Nutr Metab Care 1999; 2:445–451.
35 Vinken AG, Bathalon GP, Sawaya AL, et al. Equations for predicting the
energy requirements of healthty adults aged 18–81. Am J Clin Nutr 1999;
69:920–926.
36 Jeukendrup AE, Wallis GA. Measurement of substrate oxidation during


exercise by means of gas exchange measurements. Int J Sports Med
2005; 26 (Suppl. 1):S28–S37.
An excellent publication on the biochemistry of caloric expenditure and related
proposed calculations and equations for substrate oxidation during exercise,
derived from the application of indirect calorimetry, emphasizing fat metabolism.
37 Haman F, Peronnet F, Kenny GP, et al. Partitioning oxidative fuels during cold


exposure in humans: muscle glycogen becomes dominant as shivering
intensifies. J Physiol 2005; 566:247–256.
An original research paper on metabolic rate and fuel oxidation with a nice
methodological design, utilizing indirect calorimetry and comparing fuel selection
in shivering and exercise, demonstrating a striking and challenging different pattern
of use for each situation.
38 Öhrström M, Jansson O, Wohlfart B, Ekelund M. Working capacity and resting
energy expenditure after ileal pouch-anal anastomosis. Br J Surg 2004;
91:618–624.
39 McLellan S, Walsh T, Burdess A, Lee A. Comparison between the Datex-
Ohmeda M-COVX metabolic monitor and the Deltatrac II in mechanically
ventilated patients. Intens Care Med 2002; 28:870–876.
40 Donaldson L, Dodds S, Walsh TS. Clinical evaluation of a continuous oxygen
consumption monitor in mechanically ventilated patients. Anaesthesia 2003;
58:455–460.
41 Krems C, Lürhman PM, Strassburg A, et al. Lower resting metabolic rate in the


elderly may not be entirely due to changes in body composition. Eur J Clin Nutr
2005; 59:255–262.
A large cross-sectional study comparing estimated and measured energy expen-
diture by indirect calorimetry with Deltatrac, and whole-body and organ-specific
composition between healthy young and aging populations, showing that the
decline in RMR with aging cannot be entirely due to changes in body composition.
42 Weissman C, Sardar A, Kemper M. In vitro evaluation of a compact metabolic
measurement instrument. JPEN J Parenter Enteral Nutr 1990; 14:216–221.
43 St-Onge MP, Rubiano F, Jones A Jr, Heymsfield SB. A new hand-held indirect
calorimeter to measure postprandial energy expenditure. Obes Res 2004;
12:704–709.
44 Compher C, Hise M, Sternberg A, Kinosian BP. Comparison between

Medgem and Deltatrac resting metabolic rate measurements. Eur J Clin Nutr
2005; 59:1136–1141.
An interesting clinical trial in patients on home nutrition support validating Med-
Gem against Deltatrac, and concluding that the former has an acceptable degree
of reproducibility; however, the values obtained are lower than the traditional ones.
45 Nieman DC, Austin MD, Chilcote SM, Benezra L. Validation of a new handheld

device for measuring resting metabolic rate and oxygen consumption in
children. Int J Sport Nutr Exerc Metab 2005; 15:186–194.
An important study in children aged 11  0.2 years evaluating MedGem as
opposed to the Douglas bag technique and showing a good correlation, and
no significant difference in values of VO2 and RMR between the two devices.
46 Alam DS, Hulshof PJ, Roordink D, et al. Validity and reproducibility of resting


metabolic rate measurements in rural Bangladeshi women: comparison of
measurements obtained by Medgem and by Deltatrac device. Eur J Clin Nutr
2005; 59:651–657.
Detailed rural field research on a group of 37 non-pregnant women showing that
the MedGem VO2 and RMR readings were neither valid nor reproducible when
matched to those of Deltatrac; nevertheless, the FAO/WHO/UNU BMR-prediction
equations showed good estimation of BMR.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
47 Reeves MM, Capra S, Bauer J, et al. Clinical accuracy of the MedGem indirect

calorimeter for measuring resting energy expenditure in cancer patients. Eur J
Clin Nutr 2005; 59:603–610.
A cross-sectional clinical validation study evaluating the performance of MedGem
in comparison with traditional indirect calorimetry, that showed poor clinical
accuracy by limits of agreement between the two instruments in both cancer
patients or healthy subjects.
48 Melanson EL, Coelho LB, Tran ZV, et al. Validation of the BodyGem hand-held

calorimeter. Int J Obes Relat Metab Disord 2004; 28:1479–1484.
A study on 41 healthy subjects for the validation of the BodyGem calorimeter
which only displays RMR, in contrast with classical indirect calorimetry, concluding
that the former device gives significantly higher values than the latter, probably due
to the increased energy demand of holding the BodyGem in position.
49 Nieman DC, Trone GA, Austin MD. A new handheld device for measuring
resting metabolic rate and oxygen consumption. J Am Dietet Assoc 2003;
103:588–592.
50 Kobar S, Francis CC, Mawhinney S, Sharp T. Effect of acclimation on resting
energy expenditure measurements. Nutr Clin Pract 2003; 18:417–421.
51 Van Lanschott JJB, Feenestra BWA, Vermeij CG, et al. Calculation versus
measurements of total energy expenditure. Crit Care Med 1986; 14:981–985.
52 Barak N, Wall-Alonso E, Sitrin MD. Which patients are likely to benefit from
indirect calorimetry measurement? [abstract]. JPEN J Parenter Enteral Nutr
2004; 28:S16–S17.
53 Petros S, Engelmann L. Enteral nutrition delivery and energy expenditure in
medical intensive care patients. Clin Nutr 2005; [Epub ahead of print]
54 Frankenfield DC, Sarson Y, Blosser SA, et al. Validation of a 5-min steady
state indirect calorimetry protocol for resting energy expenditure in critically ill
patients. J Am Coll Nutr 1996; 15:397–402.
55 Alves VGF, Rocha EEM, Silva MHN, et al. Indirect calorimetry: a practical
approach in intensive care [Abstract]. Clin Nutr 2004; 23:853.
56 McCall M, Jeejeebhoy K, Pencharz P, Moulton R. Effect of neuromuscular
blockade on energy expenditures in patients with severe head injury. JPEN J
Parenter Enteral Nutr 2003; 27:27–35.
57 Dickerson RN. Specialized nutrition support in the hospitalized obese patient.
Nutr Clin Pract 2004; 19:245–254.
58 Ireton-Jones CS, Francis C. Obesity: nutrition support practice and applica-
tion to critical care. Nutr Clin Pract 1995; 10:144–149.
59 Alves VGF, Rocha EEM, Silva MHN, et al. Assessment of the caloric
expenditure of mechanically ventilated obese patients: comparison of indirect
calorimetry with formulae [Abstract]. Clin Nutr 2004; 23:798.
60 Uyar M, Demirag K, Olgun E, et al. Comparison of oxygen cost of breathing

between pressure-support ventilation and airway pressure release ventilation.
Anaesth Intensive Care 2005; 33:218–222.
A prospective, randomized, crossover study in the ICU comparing pressure-
support ventilation and airway pressure release ventilation modes, in sponta-
neously breathing patients after long-term mechanical ventilation, showing similar
results for the oxygen cost of breathing and other metabolic variables for both
ventilation modes.
61 Castanon-Gonzalez JA, Satue-Rodriguez J, Camacho-Juarez JS, et al. Effects

of different positive end expiratory pressure levels on resting energy expen-
diture measured by indirect calorimeter in patients with pressure-controlled
ventilation [in Spanish]. Gac Méd Méx 2004; 140:583–588.
A prospective comparative study which demonstrates that different levels of
positive end expiratory pressure do not affect REE, although the respiratory
quotient is not accurate.
62 Berney S, Denehy L. The effect of physiotherapy treatment on oxygen
consumption and haemodynamics in patients who are critically ill. Aust J
Physiother 2003; 49:99–105.
63 Harris JA, Benedict FG. A biometric study of basal metabolism in man.
.Publication 279. Washington, DC: Carnegie Institute of Washington; 1919
64 Moran DS, Heled Y, Gonzalez RR. Metabolic rate monitoring and energy
expenditure prediction using a novel actigraphy. Med Sci Monit 2004;
10:MT117–MT120.
65 Kumahara H, Schultz Y, Ayabe M, et al. The use of uniaxial accelerometry for
the assessment of physical-activity-related energy expenditure: a validation
study against whole-body indirect calorimetry. Br J Nutr 2004; 91:235–243.
66 Hustvedt B-E, Christophersen A, Johnsen LR, et al. Description and validation


of the ActiReg1: a novel instrument to measure physical activity and energy
expenditure. Br J Nutr 2004; 92:1001–1008.
A thorough and nicely designed validation by traditional indirect calorimetry and the
double-labeled water technique in healthy volunteers of an instrument to measure
physical activity and energy expenditure, analyzing the limits of agreement between
the results, and confirming the effective and practical usefulness of the testing device.
67 Rocha EEM. Is there an application for indirect calorimetry in nutritional
assessment? [in Portuguese]. Rev Bras Nutr Clin 1998; 13:90–100.