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This is the topic of formulating a nutritional supplement to address the metabolic needs of a critically ill organism.

Previous SAQs on this topic have included the following:

  • Question 7 from the first paper of 2015 (methods of estimating energy expenditure)
  • Question 7.4 from the first paper of 2014 (indirect calorimetry vs. reverse Fick method)
  • Question 25.4 from the second paper of 2010 (indirect calorimetry vs. reverse Fick method)
  • Question 28 from the second paper of 2007 (methods of estimating energy expenditure)

Estimating the resting energy expenditure

There are a few ways of doing this. These are covered extensively in separate chapters dedicated to each method, which are linked below.

  • Predictive equations: One can calculate the likely resting energy expenditure using an empirically derived formula- for example, the Harris-Benedict, the Frankenfield, the Ireton-Jones, or the Fusco. These are obviously only guides, and the numbers they produce may be completely wrong.
  • Reverse Fick method: One can use the PA catheter to calculate the exergy expenditure of the body using the ardiac output, VO2 and DO2. Problem is, this method neglects the energy expenditure of the lungs.
  • Indirect calorimetry: One can measure the energy expenditure of the whole body using the metabolic cart. This is the gold standard. Problem is, the cart tells you how much energy the organism is using, but not how much energy it needs.
  • Cheating: one can crudely estimate that a human organism might need about 25 kcal/kg/day. This is the so-called "ACCP standard" (after the American College of Chest Physicians). The precise estimate is 25-30kcal/kg/day of actual body weight, or 21kcal/kg of ideal body weight.

In brief, please accept this tabulated comparison:

A Comparison of Methods
to Estimate Metabolic Energy Requirements
in Critical Illness
Method Physiology Advantages Limitations
Predictive  Equations
  • Calculation of metabolic requirements made on the basis of empirical experimental data
  • Typically, input information is gender, height, age and weight
  • Specific metabolic abnormalities (eg. burns or sepsis) can be factored in as multipliers
  • Range from complex equations to simple (25cal×kg per day) formulae
  • Cheap
  • Quick
  • Requires no expertise
  • Accurate for many circumstances, particularly straightfrward ICU patients
  • Predict requirements, i.e. useful goals of management
  • Tend to be inaccurate
  • The sicker the patient, the less accurate the predictions
Reverse Fick method
  • Determines oxygen consumption from pulmonary artery catheter:
  • Oxygen utilisation in metabolic processes is correlated to the metabolic rate.
  • Knowing the cardiac output, one can calculate the oxygen consumption of the organism from the arteriovenous oxygen content difference.
  • Accurate - more so than predictive equations
  • Reproduceable
  • Cheaper than the metabolic cart, and more widely available
  • Invasive
  • Does not incorprate the metabolic requirements of the lungs
  • Inaccurate in severe pulmonary pathology, eg. ARDS
Indirect calorimetry
  • Oxygen uptake and CO2 production are monitored by a specialized module attached to the ventilator
  • From the consumption of oxygen, one can estimate the metabolic rate (assuming all oxygen is used to oxidise substrate)
  • The most accurate method of determining energy use
  • Module can integrate with the ventilator

Indications may include:

  • Extremes of obesity
  • Extremes of core body temperature (eg. in hypothermia)
  • Extremes of age
  • Very expensive
  • It makes the assumpation that all oxygen use is for oxidation of substrate
  • It is a complex procedure and it requires special equipment
  • It is a measure of metabolic fuel consumption, not demand.
  • It is not associated with any clinical benefit.
  • Inaccurate at high PEEP
  • Inaccurate with high FiO2
  • Invalid in the presence of circuit leak
  • Difficult to interpret if the ventilator settings keep changing rapidly

Nutritional goals for the critically ill patient

Where indirect calorimetry is not available, ESPEN recommend the use of the 25kcal/kg/day shortcut. There are roughly 200 equations published, and it does not seem to matter which simplified or overcomplicated equation you use to work out how much nutrient your patient requires. The point is, one ought to have an idea of what the daily caloric intake should be. One also ought to have propofol in mind; the oily sedative provides 1.1kcal per 1 ml of infusion, and if you are receiving 20ml/hr of it, you can end up contributing up to 528 calories per day in fatty emulsion.

If one were to be taking this truly seriously, one would not depend on faulty predictive equations, and rather estimate true energy expenditure using indirect calorimetry. The advantage of this method is an improved prediction of energy requirements which can change accurately in step with the changing condition of the critically ill patient. The TICACOS study (Singer et al, 2011) has attempted to quantify the benefit of such an approach. Their treatment group ended up absorbing more calories and protein, but spent longer in the ICU and on the ventilator. The trend towards improved mortality did not reach statistical significance.

Whichever way one estimates the nutritional goal, one should aim to provide at least 50-65% of that goal dose to achieve the benefits of enteral nutrition. This is the dose required to get the various protective benefits, such as the decreased risk of infection and improved return of cognitive function in head injury.

Adjustment of resting energy expenditure to correct for increased demand.

The resting energy expenditure of a critically ill patient is surprisingly similar to that of a normal person. The distinction is the presence of critical illness, and the increase in metabolic requirements resulting from it.

One tends to multiply the REE numbers by the "stress factor" For example, the resting energy expenditure achieved by the use of a predictive equation may be multiplied by 1.2 to factor in a mildly increased level of stress, and by 1.9 to factor in a severe hypercatabolic state.

Daily requirements of macronutrients

Let us say that one has finally arrived at a figure of daily caloric requirements which one is satisfied with. Now, one ought to think about how much of each major macronutrient group one wishes to supply. These issues have relevance to the practice of prescribing TPN, as well as to critical care nutruiitional support in a broader sense.

Carbohydrate (glucose) requirements

Everything runs on carbohydrates. Undersupplementation of carbohydrates is a major trigger in the starvation response, and contributes to protein catabolism. Ergo, one should feed the critically ill patient a reasonable amount of glucose.

How much is "a reasonable amount"? Well.

There is no mandatory daily glucose requirement; or rather, the lower limit of carbohydrate intake which is compatible with life appears to be zero. It is simply not an essential nutrient, and in fact human history abounds with evidence that a lifetime of carbohydrate-free existence is possible. For example, the Inuit people of Greenland have traditionally existed on a diet composed entirely of fat and protein. There were no adverse effects on their longevity or health, apart from those which might be directly associated with living in an icy wasteland and being forced to hunt walrus. In fact, Eugene Du Bois (1928) commented on the "hardiness and freedom from disease of the Eskimo on his very high protein diet", which he contrasted with "the poor condition of the Bengali on his very low protein ration". Without further digression, it is safe to say that glucose is a non-essential nutrient.

However, that does not mean the average middle-aged Western ICU patient with thrive fantastically in the total absence of carbohydrates, nourished only by seal meat and whale fat. We simply do not know the ideal amount of carbohydrate. Cahill et al (1973) suggested that as little as 25g/day may be sufficient for the central nervous system to continue normal function, but this is in normal man and taking advantage of the metabolic adaptation to starvation. It is more difficult to scientifically estimate what is required in critical illness.   LITFL reports that the daily requirement of glucose is approximately 4-5g/kg/day in severely catabolic patients, but the main reference for this is Thomas Ziegler's 2008 NEJM article, which makes no specific dose recommendation (only that 60-70% of the total caloric goals should be met by dextrose).

The 2003 ESPEN guidelines recommend 2g/kg/day of glucose as the minimum amount of carbohydrate requred. Their recommendation is based on Bier et al (1999) - the Report of the IDECG Working Group on lower and upper limits of carbohydrate and fat intake. In this report, Bier et al acknowledge that one does not require glucose to sustain life, but suggest that it would still be nice to have some.

"The Group ...concluded that the theoretical minimum intake of zero should not be recommended as a practical minimum."

According to this report, about 50g/day of glucose is enough to prevent ketosis in the adult. Approximately 100g/day is oxidised irreversibly by the brain, and therefore that (with a 50% bonuse for safety) should be the minimal daily recommended intake. That comes to just over 2g/kg for the average 70kg adult.

So, that is the minimum requirement for carbohydrate in critical illness. Is there a safe maximum? One might base the upper limit of g on the maximum rate of glucose oxidation in the critically ill patient. It is generally believed that this rate is about 4-7mg/kg/min, or 5.7-10g/kg/day (MacDonald et al, 2013). That works out to be about 16.8-29.4g per hour for a 70kg patient, or roughly 90-160mmol/hr. Thus, the maximum daily glucose requirement for this Homo vulgaris should be around 400-700g/day. Any extra glucose will merely hang around and contribute to stress-induced hyperglycaemia, placing the patient in danger of overfeeding. In practice, this generous amount of glucose is rarely matched by TPN prescriptions. Locally, we use 250g in every 24hour bag.

Lipid requirements

Apart from glucose, fatty acids offer a source of metabolic energy substrate, and they are essential for the maintenance of cellular function. Particularly, the fatty acids linoleic acid (omega-6) and α-linoleic acid (omega-3) cannot be synthesized in the body and are therefore essential. Soya bean oil contains large quantities of these essential fatty acids (and is therefore a frequently used constituent of parenteral nutrition). ESPEN suggest that the typical ICU patient requires 9–12 g/day of linoleic acid and 1–3 g/day of α-linoleic acid. Other desirable fatty acids include eicosopentanoic acid and docosahexaenoic acid, which are available in fish oil, and oleic acid, which is available in olive oil.

How much fat is safe and appropriate? Bier et al (1999) in the already quoted IDECG report have recommended that a daily fat intake should be greater than 10% (as this does not meet the daily requirement of essential fatty acids) and less than 65-70% (as this would prevent the theoretical minimum daily carbohydrate intake). Therefore, a middle-ground 30% was recommended as the ideal proportion of daily fat. The mass of the daily lipid requirement is therefore about 1g/kg/day, or 70g for a normal-sized person; a sane range is 0.7-1.5g/kg/day. In the distant past, it was thought that more energy (up to 50% of daily energy requirements) should be provided by lipids; however these days this has been reduced to about 30%, which should maintain a respiratory quotient in the range of 0.85-0.90.

Protein requirements

According to the cognoscenti, daily protein requirements range from 1.5-2.0g/kg/day. Why not more? Well; the addition of extra protein beyond this dose does not result in an increase of protein uptake by the tissues of burns patients, and they are generally held to be the most protein-hungry of all ICU demographic groups.

What is the upper limit of protein supplementation? The IDECG Report mentions studies administering 4g/kg/day to experimental subjects (but no reference is given). Moreover, athletes and weightlifters in training routinely take up to 8g/kg/day with no apparent ill effects, and one may again recall the indigenous populations of carb-poor areas who subsist on high-protein diets for the duration of their lives. However, for the majority of critically ill patients, the administration of excess enteric protein is probably not going to be consequence-free. It may give rise to diarrhoea and enteric microorganism overgrowth, if it is not absorbed. If it is absorbed, then the use of protein catabolism for energy will result in the deamination of amino acids, and therefore the liberation of ammonia. The urea cycle will either function normally (and produce a massive amount of urea) or not function normally (and produce an excessive amount of ammonia). In either case, the consequence is an encephalopathy. The patient receiving TPN is harmed even more by protein hyperalimentation, as they tend to receive their parenteral "protein" as a 10% w/v amino acid slurry. The dissolved acids present as hydrochlorides (eg. lysine hydrochloride), and the consequence of overusing them is a normal anion gap metabolic acidosis.

The ideal carbohydrate:fat ratio

How does one decide, how much carbohydrate lipid and protein one's patient needs? Well. Certain basic facts must be remembered about the daily human physiological requirements.

  • Carbohydrate is the preferred energy substrate of most tissues
  • Lipid is the preferred energy substrate of some (few) tissues
  • Amino acids should not be used for fuel under conventional circumstances, but the breakdown and synethesis of protein contributes to the overall energy requirement. The critically ill patient is in a stressed state and will have altered (increased) amino acid requirements.

The college answer to Question 7 from the first paper of 2015  quoted a carbohydrate:fat ratio of 70:30. This is again based in the nutritional recommendations made by IDECG. Those are generic, and apply equally well (or badly) to the healthy as well as the sick. How do you know your patient is benefiting maximally from this ratio? Is there any method to determine the ideal ratio for any given patient, ad individualise their nutrition?

One such method may be indirect calorimetry.  As it offers a measurement of the respiratory quotient, it could be the ideal means of calculating the carbohydrate:fat ratio.  The theoretical range for the RQ is from 0.67 to 1.30; RQ for fat is 0.70, for protein is 0.80 and for carbohydrate is 1.00. These values were obtained by Graham Lusk in 1924, in a famous and often-quoted paper. There, a table is presented to demonstrate the change in the non-protein respiratory quotient, which is reproduced below with some cosmetic modification:

Lusk Table for Non-Protein Respiratory Quotient
Respiratory Quotient (RQ) Infused carbohydrate ratio (%) Infused lipid ratio (%)
0.70 0% 100%
0.75 15% 85%
0.80 33% 67%
0.85 50% 50%
0.90 67% 33%
0.95 85% 15%
1.0 100% 0%
     

"Measurement of the overall cumulative RQ should theoretically reflect the percentage use of each substrate at the cellular level", McClave et al (2003) suggested. The measured indirect calorimetry data can be used with the table offered above, provided it is modified to reflect the oxygen cost of protein catabolism. This formula is given as follows:

\(NPRQ = {VCO_2 - (4.0 \times UUN) \over VO_2 - (5.9 \times UUN) }\)

- where UUN is the urinary urea nitrogen, which can be obtained from a 24-hr urinary specimen collection.

The theoretical ideal RQ for a person on a "typical Western diet" should be around 0.85-0.90 (McClave et al, 1992). Basically, if the person is underfed, the RQ slips lower (as more fats and proteins are catabolised instead of carbohydrates). Alternatively, the person who is gaining weight does not catabolise any fats or proteins, but rather burns carbohydrate and creates more tissue fat by lipogenesis, and thus the RQ increases to 1.00 or above. Guenst et al (1994) found the RQ well above 1.0 in patients receiving excess carbohydrate nutrition (in fact, some were receiving up to 140% of their predicted requirement). Unfortunately, the 2003 study by Stephen McClave was unable to put the RQ to good use as a measure of nutritional substrate use. The investigators were forced to recommend against any attempt to finely adjust the carbohydrate:fat ratio of their patients on the basis of their NPRQ. These days, most people rely on McClave's earlier work, and aim for a respiratory quotient of  around 0.90 by using a 70:30 mixture of fat and carbohydrate. Of course, it is impossible to dictate what your patient is going to do with those substrates  -their metabolism and the prevailing hormonal milieu may force them to lay down more fat in their liver, or to ignore the infused nutrients and cannibalise structural protein, or to build more tumours, or whatever else. All you can do is supply enough of everything (and not too much) and hope for the best.

References

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