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This is a technique of accurately and non-invasively measuring the consumption of oxygen and the production of CO2 in a living human organism. It requires the use of a "metabolic cart". It's actually a sort of cart, although ventilator-attached modules are also available. Indirect calorimetry can determine the energy requirements of the organism, thereby helping one arrive at a better nutritional regimen for them. Its most effective application is in patients for whom conventional methods of estimating nutritional requirements are inadequate, such as hugely obese patients and patients with severe trauma or burns.

With this technique, one can directly measure the following variables:

• O2 consumption- inspired and expired O2 partial pressures
• CO2 excretion - expired CO2 partial pressure
• Minute volume

From these measured variables one can derive other important values:

• Energy expenditure
• Respiratory quotient

The college has asked about indirect calorimetry in several past paper SAQs, including the following:

Usually, the questions either ask about the generic methods of calculating or measuring energy expenditure (in which case only a superficial knowledge is required) or to explain why the indirect calorimetry measurement is different from the reverse Fick method (spoiler: the latter fails to measure oxygen consumption in the lung).

## Theoretical basis of indirect calorimetry

### Mechanism of indirect calorimetry

A crude diagram tells it best:

In short, the metabolic cart measures the input and the output of a patient's respiratory gas mixture. The nitrogen content of the gas, being essentially inert, is safely ignored.

### The mathematics of indirect calorimetry

One can make the assumption, because in almost every energy-producing reaction oxygen is consumed, that oxygen consumption and CO2 production are proportional to energy expenditure.

In order to approximate these values more exactly, one must use the Weir equation:

This can be abbreviated to represent the Resting Energy Expenditure (REE):

The respiratory quotient is even easier to calculate:

A respiratory quotient should normally be around 0.8. However it is subject to change according to the proportion of different metabolic substrates used in the organism. The RQ from fats is approximately 0.7, from protein is 0.8 and from carbohydrates is 1.0 (i.e. for every molecule of oxygen used, one molecule of CO2 is produced). The relative contribution of  macronutrient groups to the total energy expenditure and their influence on the respiratory quoetient has fascinating implications for the practice of prescribing total parenteral nutrition, and is discussed in greater detail in Chapter 5.3.4 ("Prescription and administration of parenteral nutrition")

The measurement of VO2 and VCO2 are possible because the metabolic cart keeps a vigilant eye on every molecule of gas which is delivered to the patient, and which is exhaled.

That may sound reassuring, but in fact this method is fraught with error.

### Physical limitations of indirect calorimetry

Apart from being an unwieldy and complex apparatus, the metabolic cart can give false readings in the following circumstances:

• Inaccurate gas concentration measurements
• Obviously, an error of measuring FiO2 or EtO2 will lead to a magnified error in the calculations
• Inaccurate volume measurements
• Lets say, there is a leak in the circuit 9eg. around the tube, or through a pneumothorax and out of the chest drain). This leak will steal some gas, and render the measurements of volume inaccurate.
• PEEP will also change the circuit volume, altering the minute volume and changing the values in the equations

### Practical limitations of indirect calorimetry:

The following problems have drawn criticism in the past:

• This is a measure of metabolic fuel consumption, but what we are interested in is actually the metabolic fuel demand. The metabolic cart cannot tell you what the patient needs.
• There appears to be no clinical benefit from the use of the metabolic cart, which makes a farce of its use in the resource-poor busy ICU.

### Pragmatic indications for the use of indirect calorimetry

Well, it all stems from the fact that predictive equations and the Fick method of calorimetry (using the PA catheter) are inaccurate. Particularly, the PA catheter misses out on the oxygen consumption of the lung, which (in critical illness, like ARDS or severe pneumonia) may be massively increased. And the predictive equations have all been arrived at by means of empirical data collection; they collapse into uselessness when confronted with patients which are somehow metabolically unusual.

Some examples come to mind:

• Extremes of obesity
• Extremes of core body temperature (eg. in hypothermia)
• Extremes of age

Thus, it is expected that as patients get more bizarre, so will the need for indirect calorimetry increase. One can envision a nightmarish future where intesivists are expected to calculate the nutritional needs in an ICU population of massively obese supercentenarians all of whom have suffered over 60% BSA burns, and who are subjected to deep hypothermic circulatory arrest.

## Practical use of indirect calorimetry in the ICU

### Rationale for the use of indirect calorimetry

• Oxygen consumption and CO2 production are proportional to energy expenditure.
• Resting energy expenditure (REE) can therefore be approximated from the measurement of O2 consumption and CO2 excretion, using the Weir equation
• The REE can be compared to the known energy value of the nutritional intake; thus one can decide whether the patient is receiving enough nutrition, too much or too little.
• The respiratory quotient can be calculated, which is an estimate of metabolic substrate use (the RQ for fats is 0.7, for protein is 0.8 and for carbohydrates is 1.0).
• This helps to determine the proportion of metabolic substrates used for energy production.
• In turn, this can be used to fine-tune the nutritional supplement mixture.

### Arguments in support of indirect calorimetry

• Predictive equations are frequently inaccurate.
• Some patient groups (eg. the hyper-obese, trauma and burns patients) are particularly opaque to equation-based nutritional assessment.
• Experts suggest that "Indirect calorimetry is considered the gold standard to measure energy requirement and cannot be replaced by assumptions based on weight, height, sex, age, or minute ventilation"(Guttormsen, Pitchard, et al - 2014).
• ESPEN and ESICM are in favour of developing a easy-to-implement calorimeter for routine clinical use.

### Advantages of indirect calorimetry over other methods

• The "gold standard" - see abovementioned European expert opinion.
• Non-invasive (especially compared to a PA catheter)
• Not prone to underestimating the energy expenditure (eg. the PA catheter ignores the oxygen consumption in the lung itself)
• Does not depend on predictive equations or fudge factors; therefore it is a faithful representation of (aerobic) metabolism.

### Limitations of indirect calorimetry

Theoretical sources of error:

• Errors of gas partial pressure measurement
• most oxygen sensors, eg. the Clark electrode, become inaccurate at high partial pressures of O2
• Errors of volume measurement -introduced by circuit leak, pneumothorax (with bubbling drain) and PEEP which distorts the circuit volume.

Practical difficulties:

• Urinary nitrogen, which is required for the Weir equation, requires a 24-hour urinary collection.
• The metabolic cart is expensive and cumbersome to implement.
• The use of this device requires special training.
• Even if you had infinte money and special training, good luck finding a vendor: according to a 2014 review, "Sale of Deltatrac II was discontinued 8 years ago and very few working units still remain."
• Use in children is complicated by leaky uncuffed tubes
• Useless in HFOV, as there is no minute volume.
• Difficult to implement in the context of ECMO.

Pragmatic arguments against routine use:

• Indirect calorimetry measures the consumption of metabolic substrates; it is powerless to predict the requirement for them, which is what one actually wants to know.
• Inaccurate results will fool you into underfeeding or overfeeding your patient, in the false belief that this method is more accurate than predictive equations.
• Thus far, there has been no mortality benefit from its use.

### References

LITFL has an excellent summary dedicated to indirect calorimetry. I stole a couple of their references.

Holdy, Kalman E. "Monitoring energy metabolism with indirect calorimetry: instruments, interpretation, and clinical application." Nutrition in Clinical Practice 19.5 (2004): 447-454.

Flancbaum, Louis, et al. "Comparison of indirect calorimetry, the Fick method, and prediction equations in estimating the energy requirements of critically ill patients." The American journal of clinical nutrition 69.3 (1999): 461-466.

Weir, JB de V. "New methods for calculating metabolic rate with special reference to protein metabolism." The Journal of physiology 109.1-2 (1949): 1.

McClave, Stephen A., Robert G. Martindale, and Laszlo Kiraly. "The use of indirect calorimetry in the intensive care unit." Current Opinion in Clinical Nutrition & Metabolic Care 16.2 (2013): 202-208.

Lev, Shaul, Jonathan Cohen, and Pierre Singer. "Indirect calorimetry measurements in the ventilated critically ill patient: facts and controversies—the heat is on." Critical care clinics 26.4 (2010): e1-e9.

Fraipont, Vincent, and Jean-Charles Preiser. "Energy Estimation and Measurement in Critically Ill Patients." Journal of Parenteral and Enteral Nutrition 37.6 (2013): 705-713.

Pichard, Claude, Taku Oshima, and Mette M. Berger. "Energy deficit is clinically relevant for critically ill patients: yes." Intensive care medicine 41.2 (2015): 335-338.

Casaer, Michael P., and Greet Van den Berghe. "Nutrition in the acute phase of critical illness." New England Journal of Medicine 370.13 (2014): 1227-1236.

Guttormsen, Anne Berit, and Claude Pichard. "Determining energy requirements in the ICU." Current Opinion in Clinical Nutrition & Metabolic Care 17.2 (2014): 171-176.