Download TPN-II-REquirement and Components

Professor T. Najjar
PHCL-474
Dept of clinical pharmacy
PART II
TPN: Energy Requirements \ Venous Access \ Formulation
LECTURE I
I)
Estimation of requirements
 Estimation of Energy Expenditure

An important aspect of patient evaluation is estimating energy expenditure. Many
predictive equations for estimating expenditure have been described in the literature.

The traditional method of assessing energy expenditure is to first calculate basal energy
expenditure (BEE), which is the amount of energy (kilocalories (kcal) needed to support
basic metabolic functions in a state of complete rest, shortly after awakening, and after a
12-hour fast.

BEE is most commonly calculated using the Harris-Benedict equations. 2) Alternatively,
BEE can be estimated at 20 to 25 kcal/kg per day.

Resting energy expenditure (REE) is the energy expended in the post-absorptive state (2
hours after a meal) and is approximately 10% greater than BEE.

Determination of BEE or REE does not include additional energy needed for stress or
activity. The Harris-Benedict equation can be modified to include stress and physical
activity factors, or these variables can be estimated at 30 to 35 kcal/kg per day for
moderate stress and up to 45 kcal/kg per day for severe stress as in the following table.

Table: Estimation of energy expenditure
Basal Energy Expenditure (BEE}
Harris-Benedict Equations
BEE-men (kcal/day) = 66.47 + 13.75 W + 5.0 H - 6.76 A .
BEE-women (kcal/day) = 655.10 + 9.56 W + 1.85 H
or "
20-25 kcal/kg/day
Total Energy Expenditure (TEE)
TEE (kcal/day) = BEE x Stress factor x
________________________________________________
Stress or Injury Factors (%increase above BEE)
Major surgery 10-20, Infection 20 , Fracture 20-40, Trauma 40-60"
Sepsis 60, Burns 60-100
Activity Factors (% increase above BEE)
Confined to bed 20
Out of bed
30
or
No stress 28 Kcal/kg/day, mild stress 30 Kcal/kg/day , moderate stress 35
Kcal/kg/day , severe, stress 40 Kcal/kg/day.
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Professor T. Najjar

PHCL-474
Dept of clinical pharmacy
Table: Estimation of protein requirement
U.S.RDA
0.8 g/kg/day
Hospitalized patient-minor stress
1.0-1.2 g/kg/day
Moderate stress
1.2-1.5 g/kg/day
Sever stress
1.5-2.0 g/kg/day
____________________________________________________________________
RDA = recommended dietary allowance.

Energy expenditure can be determined more accurately by indirect calorimetry that uses
an analytical machine to measure the patient's breathing or respiratory gas exchange.

The computerized machine (often termed a "metabolic cart") measures the amount of
oxygen consumed and the carbon dioxide produced when standard testing conditions are
maintained. Through a series of equations it determines the energy expenditure, including
stress, for that point in time and then extrapolates it for 24 hours. The determination is
often termed "measured energy expenditure" (MEE).

Because the measurement usually is conducted while the patient is at rest, activity is not
included in the energy expenditure assessment.

This method has been used as a research tool for more than 20 years. However, today,
this technology is considered the gold standard for energy expenditure determination and
is especially valuable in the energy assessment of critically ill patients. It is also readily
available to many clinicians.

Estimation of Protein Goals

Estimation of protein needs also must be included in nutritional assessment, where it
calculated based on body weight, degree of stress, and disease state.

The RDA for the United States is 0.8 g/kg per day.

Hospitalized patients with minimal stress who are well nourished need 1.0 to 1.2 g/kg per
day for maintenance of lean body mass.

The requirement for protein intake may be as high as 2.0 g/kg per day for a patient in a
hyper-metabolic, hyper-catabolic state secondary to trauma or bums.

In addition, patients with renal or hepatic dysfunction may require a decrease in protein
intake as a result of altered metabolism.
II)
Venous Access Sites

When parenteral nutrition is necessary, the type of venous access must be selected.
Parenteral nutrient formulations may be administered via peripheral veins or central
veins, depending on the:
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Professor T. Najjar

PHCL-474
Dept of clinical pharmacy
1) anticipated duration of parenteral nutrition therapy, 2) degree of malnutrition/nutrient
requirements, and 3) availability of venous access.

Peripheral

Peripheral administration may be considered: 1) when parenteral nutrition is expected to
be necessary for <10 days and 2) the patient has fairly low energy and protein needs
because of minimal stress.

In addition, candidates for peripheral parenteral nutrition: 1) must have good peripheral
venous access, and 2) be able to tolerate large volumes of fluids, because of the limited
osmolaltities (<1 kcal/ml) the patient can tolerate through this route..

Parenteral nutrient formulations for administration via peripheral veins traditionally have
been formulated with relatively low concentrations of dextrose (5 to 10%) and amino
acids (3 to 5%) providing <1 kcal/mL. Therefore, several liters may be needed daily to
meet energy and protein needs. Although dilute with nutrients, the osmolarity of these
formulations is 600 to 900 mOsm/L.

These hypertonic formulations are irritating to peripheral veins, causing thrombophlebitis
and the need for frequent site rotations (at least every 48 to 72 hours), which may quickly
exhaust venous access sites.

The concurrent administration of IV lipids with dextrose/amino acid solutions, or a
formulation mixing dextrose, amino acids, and lipids, 1) provides a method to increase
the caloric density with only a modest increase in osmolarity. 2) In addition, the lipids
may protect the vein against irritation by its diluting effect and by serving as a buffer.

The ability to give peripheral parenteral nutrient formulations may be further improved
by using midline venous access catheters, which are longer and thus allow the end of the
catheter to be placed in a larger vein where greater blood flow can dilute the nutrient
formulation.

Patients with midline catheters: 1) have successfully received peripheral nutrient formulations with osmolarities > 1 ,200 mOsm/L for longer periods without an increase in
thrombophlebitis. 2) These catheters also are advantageous because they are made of a
material that allows them to remain in place for 4 to 6 weeks.

Central

Administration of parenteral nutrient formulations through a central vein is preferred for
patients: 1) whose GI tracts are either nonfunctional or should not be used for more than
7 to 10 days and 2) for patients who have limited peripheral venous access or 3) have
energy and protein needs that cannot be met with peripheral nutrient formulations.

Traditionally, the central venous catheter is placed in the subclavian vein and threaded
3
Professor T. Najjar
PHCL-474
Dept of clinical pharmacy
through the vein so that the tip rests in the upper portion of the superior vena cava (SVC)
just above the right atrium.

A newer catheter technique involves the use of a peripherally inserted central catheter
(PICC) that is inserted in the antecubital vein and advanced until the end of the catheter
reaches the upper SVC.

The internal and external jugular veins also may be used to thread a catheter into the
SVC. However, maintaining a sterile dressing on these sites is more difficult than with
the subclavian approach or PICC.

The SVC is an area of rapid blood flow, which quickly dilutes concentrated parenteral
nutrient formulations and thereby minimizes phlebitis or thrombosis.

Some patients are not candidates for placement of catheters in the SVC and require a
femoral vein insertion with the tip of the catheter in the inferior vena cava. Catheters
placed using this technique may be at greater risk for infection.

Central venous catheters may have single or multiple lumens. The use of multi-lumen
catheters permits the administration of several intravenous therapies through the same IV
site.

Unlike with peripheral veins, the central venous access site does not require rotation of
the site every few days. In fact, some patients requiring parenteral nutrition for months to
years may have permanently placed central venous catheters.

Parenteral nutrient formulations designed for administration through central veins can
provide relatively high concentrations of dextrose (20 to 35%), amino acids (5 to 10%),
and lipids giving a caloric density of > 1 kcal/mL, and an osmolarity of >2,000 mOsm/L.
III)
Components of Parenteral Nutrient Formulations

Parenteral nutrient formulations are very complex mixtures containing carbohydrate,
protein, lipids, water, electrolytes, vitamins, and trace minerals. These admixtures must
be prepared under aseptic conditions as described by the American Society of HealthSystem Pharmacists and U.S. Pharmacopeia standards.

Although parenteral feeding is an important adjuvant therapy for many disease states,
errors have occurred in managing this complex therapy resulting in patient harm and
death. This was brought to public attention in 1994 when the FDA issued a Safety Alert
after two deaths related to errors in compounding parenteral nutrient formulations
occurred.

As a result of this sentinel event and other reported errors, guidelines or safe practices
have been developed for those situations in parenteral nutrition therapy in which
inconsistent practices have potential to cause harm.
4
Professor T. Najjar

PHCL-474
Dept of clinical pharmacy
Pharmaceutical problem areas that are addressed in the safe practice for Parenteral
Nutrition Formulations are: 1) compounding, 2) formulas, 3) labeling, 4) stability, and 5)
filtering of parenteral nutrient formulations. These practice guidelines have become
established as standards of practice for the provision of parenteral nutrition therapy.

The three macronutrients used in parenteral nutrient formulations, carbohydrate, fat, and
protein, are available from various manufacturers. Water, as sterile water for injection, is
also used to dilute the macronutrients to achieve the prescribed final concentrations of
dextrose, amino acids, and lipids, as well as the final volume of the parenteral nutrient
formulation.

Carbohydrate

Dextrose in water is the most common carbohydrate for IV use. It is available
commercially in concentrations ranging from 2.5 to 70%. These dextrose solutions are
mixed with other components of the parenteral nutrient formulation and diluted to various
final concentrations.

For cost-effective inventory control, dextrose usually is purchased from only the
manufacturer and in only a few concentrations (e.g., 10%, 70%). From these
concentrations of dextrose, all parenteral nutrient formulations can be compounded. IV
dextrose is monohydrated and provides 3.4 kcal/g in comparison with dietary
carbohydrate that has a caloric density of 4.0 kcal/g.

Glycerol also is available (as a 3% mixture with 3% amino acids) for administration as a
peripheral parenteral nutrient formulation. Glycerol has a caloric density of 4.3 kcal/g.

Other carbohydrates such as fructose, sorbitol, and invert sugar have been: 1) used
investigationally in parenteral nutrient formulations but 2) are associated with adverse
effects and 3) are not available commercially.

Lipid

Lipid for IV use is supplied as emulsions of either soybean oil or a mixture of soybean
and safflower oils that provide long-chain fatty acids (12 to 24 carbon length). The
soybean oil emulsion is available in three concentrations: 10%, 20% and 30%. The 10%
and 20% IV lipid emulsions may be administered concurrently (IV piggyback) with
dextrose/ amino acid solutions or admixed with dextrose and amino acids.

The 30% IV lipid emulsion is hypotonic and should not be used for IV piggyback
administration. It is used exclusively for compounding formulations that combine
dextrose, amino acids and lipid in the same container.

Although lipid has a caloric density of 9 kcal/g, the caloric density of the IV lipid
5
Professor T. Najjar
PHCL-474
Dept of clinical pharmacy
emulsions is increased by the addition of glycerol and egg phospholipids. These
components are added as emulsifiers and to adjust the osmolarity.

The phospholipids are derived from egg yolks; therefore, IV lipids are contraindicated in
patients with severe egg 'allergies, especially egg yolk allergies.

Medium-chain triglycerides (MCTs) are used investigationally.

MCTs are 6 to 10 carbons in length and provide 8.3 kcal/g. Mixtures of long-chain and
medium-chain triglycerides are being evaluated for potential use in the United States and
already are commercially available in other countries.

Amino Acids

Protein for parenteral administration is available as synthetic amino acids and serves as
the source of nitrogen. Amino acid concentrations of 3.5 to 20% are available
commercially and vary slightly from one product to another in the specific amounts of
each amino acid.

Generally, amino acid products are characterized as "standard" mixtures, which provide a
balanced mix of essential, nonessential, and semiessential amino acids or "specialty
mixtures," which are modified for specific disease states. For example, the specialty
amino acid mixture for use in patients with hepatic failure contains increased amounts of
the branched-chain amino acids, and decreased amounts of the aromatic amino acids.

Protein formulations designed for patients undergoing physiologic stress are
supplemented with branched-chain amino acids, but have normal amounts of the other
amino acids.

Amino acid products for patients experiencing renal failure either have increased
amounts of the essential amino acids or provide only essential amino acids.

Amino acid products designed to meet the needs of neonates are also available. Protein or
amino acids have a caloric density of 4 kcal/g.

Traditionally, protein calories were not always included in the calculation of energy
needs for patients receiving parenteral nutrient formulations. Ideally, protein is used for
tissue repair and not oxidized for energy; however, the human body cannot
compartmentalize energy metabolism this way. Today, the conventional wisdom is to
include the protein calories in these calculations.

The following table summarizes available nutrients and their caloric density.

Micronutrients

Micronutrients are the electrolytes, vitamins, and trace minerals needed for metabolism.
These nutrients are available from various manufacturers as either single entities or in
6
Professor T. Najjar
PHCL-474
Dept of clinical pharmacy
combinations. For example, the trace element zinc is available commercially as a single
trace element product or as a combination product with the other trace elements, copper,
chromium, manganese, and selenium.

It is important to be aware of the specific products available in each institution to avoid
providing inadequate or excessive amounts of various micronutrients.

Table: Caloric density of intravenous nutrients
--------------------------------------------------------------------------------Nutrient
Kcal/g
Kcal/ml
Amino acids
4
0
Amino acids 5%
0.2
Amino acids 10%
0.4
Dextrose
3.4
Dextrose 10%
0.34
Dextrose 50%
1.7
Dextrose 70%
2.38
Fat
10
Fat emulsion 10%
1.1
Fat emulsion 20%
2
Fat emulsion 30%
3
Glycerol
4.3
Glycerol 3%
0.129
Medium-chain triglycerides
8.3
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Professor T. Najjar
PHCL-474
Dept of clinical pharmacy
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