malnutrition, even if mild, and prolonged post-stressor fasting, intentional or not, can adversely affect

healing, recovery, and overall outcomes after injury or surgery.14–20 In addition, the nutritional needs of

a patient recovering from severe infection, injury, or a major operation are different than those of

nonstressed individuals and aggressive postoperative or postinjury nutritional regimens are associated

with improved outcomes.21 This recognition has led nutrition science to become an integral part of

modern medicine and critical care, and nutritional support to continue to gain ground as primary

therapy in the care of the surgical and critically ill patient.

Table 3-3 Summary of the Daily Requirements of Vitamins, Electrolytes, and Trace

Elements in a per os Diet by Healthy Adults

Subjective Global Assessment

12 Subjective global assessment of a patient’s nutritional status is commonly utilized to assess the

presence and degree of malnutrition in surgical patients. It is one of the few clinical methods that has

been validated as a reproducible method assessing a patient’s nutritional status and has been

consistently associated with clinical outcomes. This global assessment utilizes numerous variables,

including physical examination and anthropometric measurements such as weight, height, and weight

loss history; dietary questionnaires and portion size analyses; along with pertinent past medical history

to classify patients in three distinct categories: class A is assigned to individuals with no evidence of

malnutrition; class B to patients with moderate or indeterminate malnutrition; and class C to patients

with definitive malnutrition. Patients in this last category typically present with recent history of

unintentional weight loss and signs of tissue wasting (temporal and/or extremity most commonly).

While the subjective global assessment can provide coarse information about the severity of

malnutrition, it rarely yields clues pertaining to the underlying etiology (starvation vs. inflammation).

Similar methods of assessing overall nutritional status encompassing dietary history, baseline health,

anthropometric and laboratory measurements have been described and used in certain patient

subpopulations. These include the mini-nutritional assessment, the malnutrition universal screening tool,

the instant nutritional assessment, the geriatric nutritional risk index, among others.

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Anthropometric Measurements and Nutritional Indices

Anthropometric measurements have been used extensively to provide information regarding lean body

mass, total fat stores, and overall nutritional health. Body composition studies aid in determining TBW,

fat, and nitrogen. These anthropometric measurements can be easily performed at the bedside or an

ambulatory setting, and may include an individual’s height and weight (which allow calculation of the

BMI), triceps skinfold, midhumeral circumference, and other body part summations. The BMI is widely

used as a measure of overnutrition (a BMI of 25 to 29.9 suggests overweight status, whereas a BMI

>30 defines obesity). The BMI is calculated from an individual’s height and weight using the formula:

More advanced techniques and measurements include x-ray absorptiometry that allows a more

accurate assessment of total fat and lean body mass. With the exception of the BMI, most

anthropometric measurements are operator dependent, and skill and experience are important in order

to obtain accurate studies.

Nutritional indices provide a means of risk-stratifying and objectively comparing individuals, as well

as to guide nutritional support. The BMI is one of the most commonly utilized nutritional indices. It

provides information on normal, overweight, or obese status. It also provides information on degree of

protein–calorie malnutrition in underweight individuals. Other commonly used indices include the

prognostic nutritional index (PNI), the nutritional risk index (NRI), and the creatinine height index

(CHI).

These are calculated with the following formulas respectively:

Serum Protein Levels. An ideal biochemical marker of malnutrition would be one that is highly

sensitive and specific to nutrition intake. Although a single laboratory biomarker that could effectively

describe a patient’s nutritional status is lacking, numerous freely circulating serum transport proteins

have been used. The most commonly utilized ones are albumin, prealbumin, transferrin, and retinolbinding protein (RBP), each with its own advantages and disadvantages. Many nutrition-unrelated

parameters, most commonly inflammation, dilution secondary to large volume resuscitation, and

chronic liver failure, affect the levels of these serum markers. Although it is customary for markers of

inflammation, usually the C-reactive protein, to be measured with the aforementioned biomarkers (most

commonly prealbumin), little data exist to support this practice.22,23

Albumin. Albumin is a serum protein synthesized in the liver with a long half-life (approximately 20

days) and a relatively large total pool size. Only 5% of total body albumin is produced daily. Its main

function is to carry molecules in the bloodstream and to help maintain intravascular oncotic pressure.

Due to its large pool, long half-life, and relative slow turnover, it has been used as an indirect marker of

protein intake, hepatic synthetic ability, and chronic nutritional status. Unfortunately, it is a negative

acute–phase reactant, decreasing during the acute-phase response, and numerous nutrition-unrelated

factors may affect its levels in either direction (Table 3-4). Albumin is neither a sensitive nor specific

marker for malnutrition, as patients with even severe starvation can have normal levels.24–26 In critical

care, hypoalbuminemia more commonly reflects illness acuity, especially during the acute phase, due to

its function as a negative acute–phase reactant, its redistribution to the interstitial space, and dilution

secondary to large volume resuscitation.27

Prealbumin. Prealbumin, also known as transthyretin or transthyretin-bound prealbumin, similar to

albumin, is a visceral protein synthesized in its majority by the liver, and to a smaller extent by the

choroid plexus in the central nervous system. Its name prealbumin was originally given because it ran

faster than albumin on electrophoretic gels. Its main function is to transport thyroxine (T4) and retinol

(vitamin A) in the bloodstream. As a visceral protein, it is a small part of the total body protein pool,

which includes serum and intracellular proteins. Consequently, it is similarly affected by many of the

same factors that affect serum albumin concentrations. The main advantage of prealbumin over albumin

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is its shorter half-life (2 to 3 days) which makes it more sensitive and rapidly adaptable to acute, shortlived changes in nutrient intake. Like albumin, prealbumin is also a negative-phase reactant, with values

decreasing during the acute inflammatory response. Therefore, rising prealbumin levels may reflect

improvement in nutritional status or resolution of the inflammatory condition. Prealbumin is commonly

measured along C-reactive protein, and low levels of the former accompanied by high levels of the

latter are commonly seen in inflammatory conditions, as opposed to malnutrition. While this practice is

not well validated, a better use for prealbumin as a marker of overall nutritional status is to monitor

trends.28,29

Retinol-Binding Protein. The majority of retinol-binding protein (RBP) is present in the bloodstream

in the form of retinol-circulating complex that includes prealbumin, retinol (vitamin A), and RBP. It is

catabolized in the kidneys and its levels may be elevated in end-stage renal failure. RBP is dependent on

vitamin A and zinc, as low levels of these conutrients inhibit mobilization of RBP in the liver.30 Due to

its extremely short half-life (approximately 12 hours) and typically expensive laboratory level

assessment, it is rarely used as a malnutrition marker.

Transferrin. Transferrin has also been identified and used as a nutrition biomarker. It has a half-life

between that of albumin and prealbumin (8 to 10 days) and fairly small total body pool size. However,

because it plays a key role in iron transport, its levels are affected by iron status. Iron deficiency may

lead to increased levels secondary to greater iron absorption. Under these circumstances, it may be a

better marker of total iron-binding capacity, rather than malnutrition.

Nitrogen Balance

Nitrogen balance is another marker for overall nutritional status. It is an indicator of whether protein

intake and catabolism are in balance, and along with trends in prealbumin levels, it is a commonly

employed method to assess progress in patients on nutritional support. Nitrogen balance is calculated

from the amount of nitrogen entering minus the amount leaving the human body over a 24-hour period.

Nitrogen intake is estimated from total protein intake divided by 6.25 (the average nitrogen content of

human protein is approximately 16%). The main route of nitrogen excretion is the urine (90% or more).

Nitrogen is also lost through the skin and stool, but this loss is usually small (<2 g/day), difficult to

measure, and therefore typically accounted for with a constant of 2 in the nitrogen balance equation.

Total urinary nitrogen (TUN) is ideally measured, but is frequently substituted by urine urea nitrogen

(UUN), because it is easier to estimate. In the latter case, an additional 2 to 3 g are typically added to

the output side of the nitrogen balance equation to account for the unmeasured losses. The nitrogen

balance equations are as follows:

Table 3-4 Serum Proteins Used in Nutritional Status Assessment

Nitrogen balance (g/day) = Protein intake/6.25 - (TUN + 2)

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Nitrogen balance (g/day) = Protein intake/6.25 - (UUN + 2 + 3)

A nitrogen balance of –2 to +2 g/day indicates nitrogen equilibrium, and typically represents the

goal in medically indicated nutritional support. More negative balances are managed with increases in

protein intake, while more positive values typically reflect anabolism in recovering patients, or simply

errors in measurement in the acutely ill (a positive nitrogen balance implies anabolism, but bedridden

patients with active inflammation are not anabolic). Achievement of a positive balance has been

associated with improved outcomes in certain critically ill patients.31 Limitations of the nitrogen balance

assessment include false-negative results in overfed patients; long time for the equation to reequilibriate after adjustments in nutritional support; and renal insufficiency and upper gastrointestinal

bleeding may invalidate results (due to incomplete excretion of urea nitrogen and due to excess urea

nitrogen production respectively).

Indirect Calorimetry

Resting energy expenditure can be measured at the bedside with indirect calorimetry. This method,

based on thermodynamic principles, calculates heat produced through the measurement of oxygen

consumed and carbon dioxide exhaled. Patients must be either sedated or able to tolerate a respiration

chamber placed over their heads that allows collection of exhaled air. (A less commonly utilized method

is direct calorimetry, in which the patient is placed inside the calorimeter for measurement.) Intubated

patients must have a fraction of inspired oxygen of <60%, while spontaneously breathing patients must

be on room air. No air leaks (that would allow heat to escape the collection chamber) can be present.

Numerous protocols have been developed to measure resting energy expenditure with as little as 5-

minute testing sessions.32

Metabolic Energy Expenditure

In most cases, energy expenditure is not measured, but estimated, on the basis that all metabolic

activity occurs within the fat-free body mass. Fat-free mass is a function of body weight, height, age,

and gender, and therefore, resting energy expenditure can be predicted quite reliably from these

variables. In obesity, where adipose tissue becomes hypertrophic and hyperplastic, most of these

relationships are preserved, but carry a weaker predictive ability. Several equations that predict basal

energy expenditure, and hence daily caloric requirements, have been developed from the

aforementioned variables, with the Harris–Benedict one being among the most widely used (Table 3-

5).33

Once the basal metabolic rate has been calculated, minor adjustments based on exercise frequency

and intensity can be made for estimation of the daily caloric requirement for an adult to maintain

current weight.33

Table 3-5 The Harris–Benedict Equation and Adjustment Using the Harris–

Benedict Principle

The Mifflin–St. Jeor equation appears to be even more accurate in estimating basal metabolic rate in

healthy individuals

34:

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