macronutrients used in PN formulations are available in various concentrations from
manufacturers. Sterile water for injection is 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 PN formulation.
PN formulations may be prepared in one of two ways, a dextrose–amino acid (2-
in-1) mixture in which IV fat emulsion (IVFE) is administered separately as a
piggybacked infusion or a total nutrient admixture (TNA or 3-in-1) in which the
dextrose, amino acids, and IVFE are combined in solution in the same bag. Premixed
PN solutions are also available commercially in different percentages of dextrose
and amino acid preparations. Premixed PN solutions are sterile products that have a
longer shelf life; however, these formulations limit the ability to customize the final
product to meet individual patient needs.
Errors have occurred in preparing and managing this complex therapy, resulting in
patient harm and death. A responsibility of the pharmacist is to ensure safe, accurate,
and sterile preparation of the PN formulation. Guidelines for safe practices have
been developed for situations in which inconsistent practices have the potential to
cause harm. Pharmaceutical problem areas that are addressed in the Safe Practices
for Parenteral Nutrition Formulations are compounding, formulas, labeling, stability,
and filtering of PN formulations.
PN is a costly therapy. Costs associated with PN therapy include not only the
admixture but also the expense of obtaining venous access, laboratory monitoring,
and treatment of complications of therapy. Because of the cost and complexity of PN
therapy, its use should be scrutinized and reserved for patients who will benefit from
Dextrose in water is the most common carbohydrate for IV use. It is available
commercially in concentrations ranging from 2.5% to 70%. Dextrose solutions are
mixed with other components of the PN formulation and diluted to various final
concentrations with sterile water for injection. Dextrose in its hydrated form
provides 3.4 kcal/g, compared with dietary carbohydrate which provides 4 kcal/g.
Another carbohydrate energy substrate is glycerol, a sugar alcohol with a caloric
density of 4.3 kcal/g. It is available as a premixed PN formulation (3% glycerol with
3% AAs) for administration as PPN. Because of the dilute concentrations of this
premixed formulation, large volumes are generally necessary to meet caloric
Lipid or intravenous fat emulsion (IVFE) is the most calorically dense macronutrient
for infusion and a source of essential fatty acids (FA). The optimal composition of
IVFE has been a focus of clinical debate because of the potential to influence immune
function, inflammatory response, and liver function. This has prompted research into
the development of new lipid formulations (structured lipids) in which part of the n-6
polyunsaturated fatty acids (PUFA) has been replaced by less bioactive FAs, such
as coconut oil (rich in medium chain saturated FA), olive oil (rich in n-9
monounsaturated FA oleic acid), or fish oil (rich in n-3 polyunsaturated FA)—
challenging the traditional soybean oil and soybean/safflower oil emulsions (n-6
13 While structured IVFEs have been used for years outside of the United States,
the US Food and Drug Administration has recently approved an IVFE formulated
with a 4:1 combination of olive oil and soybean oil
14 and another IVFE formulation
containing soybean oil, medium-chain triglycerides (MCT), olive oil and fish oil.
The traditional IVFEs are available commercially as 10% (1.1 kcal/mL), 20%
(2.0 kcal/mL), and 30% (3.0 kcal/mL) concentrations. While each gram of fat
provides 9 kcal, the caloric density of the IVFE is increased slightly because of the
glycerol within the IVFE such that each milliliter of 10% IVFE provides 1.1 kcals,
and each milliliter of 20% and 30% IVFE provides 2.0 kcal/mL and 3.0 kcal/mL
respectively. Other components of the IVFE include glycerol to make the formulation
isotonic, egg phospholipid as an emulsifier, vitamin K, and sodium hydroxide to
adjust the final pH. The 10% and 20% IVFEs may be administered concurrently (IV
piggyback) with dextrose/amino acid solutions or mixed with dextrose and amino
acids within the PN formulation. The 30% IVFE is used exclusively for compounding
formulations that combine dextrose, amino acids, and lipid in the same container.
Synthetic crystalline amino acids serve as the source of protein and nitrogen (6.25 g
protein = 1 g nitrogen). Nitrogen is the building block of cell structure and is used to
produce enzymes, peptide hormones, as well as structural and serum proteins. When
oxidized for energy protein yields 4 kcal/g. Protein calories have not always been
included in the calculation of energy needs for patients receiving PN formulations.
Ideally, amino acids are used to stimulate protein synthesis and tissue repair and are
not oxidized for energy; however, the human body cannot compartmentalize energy
metabolism in such a manner. Today, conventional wisdom is to include protein
calories in the total calorie calculations. Table 38-1 summarizes available nutrients
Amino acid concentrations of 3.5% to 20% are available commercially and vary
slightly from one product to another in specific amounts of each amino acid,
electrolyte content, and pH. Generally, amino acid (AA) products are characterized
as standard mixtures or specialty mixtures. Standard AA products provide a balanced
mix of essential, nonessential, and semi-essential amino acids, whereas specialty AA
products are modified for specific disease states.
Caloric Density of Intravenous Nutrients
Medium-Chain Triglycerides 8.3
Specialty AA mixtures are available for neonatal patients and for adult patients
with hepatic encephalopathy, renal failure, or critical illness. Specialty AA
formulations designed for patients with hepatic failure contain increased amounts of
branched-chain amino acids (BCAA) and decreased amounts of aromatic amino
acids (AAA) compared to standard AA products. These formulations are thought to
counter the imbalance between AAA and BCAA that can occur in hepatic failure.
Elevations in AAA may lead to altered mental status. There is no evidence to suggest
that formulations enriched with BCAA improve patient outcomes compared with
16–18 Formulas enriched with BCAA should be reserved for
patients with hepatic encephalopathy refractory to standard treatment with luminal
acting antibiotics and lactulose.
16 Specialty amino acid products used in renal failure
are predominantly comprised of essential amino acids.
19 Their use is based upon the
theory that nonessential amino acids can be recycled from urea and essential amino
acids. Indications for renal amino acid formulations are limited.
acids should be used in acute kidney injury.
Modified amino acid formulations are also available for critically ill patients with
hypercatabolic conditions such as trauma or thermal injury. These formulations
contain increased amounts of the BCAAs (leucine, isoleucine, and valine) to address
the increased skeletal muscle catabolism that can be seen in severe metabolic stress.
While these BCAA enriched products may slightly improve nitrogen balance,
improved patient outcomes have not been demonstrated.
various amino acid formulas, see Table 38-2.
Micronutrients are electrolytes, vitamins, and trace minerals needed for metabolism.
These nutrients are available from various manufacturers as either single entities or
in combinations. For example, the trace element zinc is available commercially as a
single trace element product or as a combination product with copper, chromium,
manganese, and selenium. Likewise, electrolytes are available as individual salts or
as a combination product to facilitate admixing. Commercially available vitamins for
PN formulations are generally prescribed as a combination multivitamin regimen,
although some vitamins are available as single additives. It is important to be aware
of the specific products available in each institution to avoid providing inadequate or
excessive amounts of various micronutrients.
Patient Assessment: Population-Based Formulation
abdominal pain and bloating while receiving enteral feedings. Other enteral formulas
peripheral PN formulation is to be started. His weight today is 186 lbs; his height is 70 inches.
Nutrition laboratory panel values are as follows:
Blood urea nitrogen (BUN), 10 mg/dL
White blood cell (WBC) count, 8,800/μL
A.A. is a well-developed, well-nourished man prior to admission. However,
A.A.’s visceral proteins are in low-normal range, indicating he may be at increased
risk for malnutrition. See Chapter 35, Basics of Nutrition and Patient Assessment, for
a more detailed description of evaluation of patients with nutritional deficiencies.
The principles from Chapter 35 will be applied to this and all others cases
throughout this chapter. He has a minimal stress level and his baseline electrolytes
CASE 38-1, QUESTION 2: Calculate calorie and protein goals for A.A. using population estimations.
A.A.’s initial calorie goals are to meet his current energy expenditure needed for
basal metabolism and account for mild stress associated with stroke recovery. A.A.
would fall into the category of “hospitalized patient, mild stress” requiring 20 to 25
kcal/kg/day (see Table 35-3 in Chapter 35, Basics of Nutrition and Patient
Assessment). For this calculation, A.A.’s actual weight of 186 lbs (84.5 kg) should
be used because his metabolism and current energy expenditure have caused a
decrease in body mass. Using usual weight or ideal body weight in patients who have
severe weight loss may result in overfeeding. For A.A., the caloric goal should be
Protein goals are estimated based on weight, degree of stress, and disease state.
Because A.A. has had a stroke and his metabolic stress is mild his protein goal
should be based on the desire to maintain his current protein status. Using the
guidelines provided in Table 35-4 (Chapter 35, Basics of Nutrition and Patient
Assessment), A.A.’s protein dose is 1.0 g/kg/day (range 1.0–1.2), or 85 g/day. As
with energy expenditure, calculations of protein needs are only estimates; the
patient’s clinical course should be monitored and the protein dose adjusted
accordingly. The protein source for PN is synthetic amino acids. Generally, 1 g of
protein is equivalent to 1 g of amino acids. A.A. will need 85 to 101 g/day of amino
In patients with chronic kidney disease, protein intake should be adjusted
according to catabolic rate, renal function, and possible protein losses from
23–25 Patients with compromised renal function may require protein
restriction to delay the progression of renal disease. Protein intake for patients
receiving continuous renal replacement therapy should range between 1.8 and 2.5
23–25 Patients with acute kidney injury who receive hemodialysis may
demonstrate positive nitrogen balance with protein dose of 1.5 g/kg/day.
recommended protein intake for patients who receive maintenance hemodialysis is
27,28 while patients who receive chronic ambulatory peritoneal dialysis
Description Product Name Available Concentrations (%)
acids, some available with electrolytes
Contain essential and nonessential amino
acids with a proportion of branched-chain
amino acids (leucine, isoleucine, valine)
Contain primarily essential amino acids;
RenAmin also contains a complement of
Contain percentages of leucine, isoleucine,
and valine, as well as all essential and
Contain only branched-chain amino acids
(isoleucine, leucine, valine); must be used
c These concentrations are available with or without electrolytes.
New York, NY: McGraw-Hill; 1994:891.
CASE 38-1, QUESTION 3: A.A. has a peripheral IV catheter, and his peripheral access appears to be
adequate. Is he a candidate for using a peripheral PPN formulation?
With good peripheral access, A.A. meets one of the criteria for PPN. Furthermore,
he should be able to tolerate the volume of a PPN formulation necessary to meet his
goals. A common complication (up to 70%) of PPN is thrombophlebitis, which
generally occurs within 72 hours.
5,30 Phlebitis is usually attributed to the acidic pH or
hyperosmolarity of the PN formulation. The osmolarity of typical peripheral
parenteral feedings ranges from 600 to 900 mOsm/L compared with an osmolarity of
280 to 300 mOsm/L of plasma. Osmolarity of a dextrose–amino acid formulation can
be approximated quickly by multiplying the percent dextrose concentration by 50 and
the percent amino acid concentration by 100. Approximately 150 to 200 mOsm/L
should be added to account for the contribution of electrolytes, vitamins, and trace
elements. Although the concurrent administration of fat emulsions decreases
osmolarity, buffers the pH, and improves peripheral vein tolerance, it does not
eliminate the risk of thrombophlebitis.
If PN is anticipated to be a long-term therapy
for A.A., central venous access should be obtained.
CASE 38-1, QUESTION 4: Design a parenteral nutrient base formulation and determine the amounts of
protein goals determined previously.
A.A.’s caloric and protein goals are determined to be approximately 1,900
kcal/day and 85 g protein/day. Giving 85 g of protein per day will provide 340
kcal/day (1 g protein = 4 kcal). Subtracting these protein calories from total desired
calories results in the amount of nonprotein calories needed (to be provided by
carbohydrates and fat). For A.A., this would be 1,900 total calories minus 340
protein calories, or 1,560 nonprotein calories needed. Typically, dextrose should
account for 60% to 70% of nonprotein calories, and lipids would account for the
remaining 30% to 40% of nonprotein calories. Providing A.A. with 1,092 kcal of
dextrose (approximately 321 g of dextrose; 1 g dextrose = 3.4 kcal) will supply 70%
of nonprotein calories as dextrose. The remaining 30% of nonprotein calories will be
provided by lipids at 468 kcal (46.8 g of lipids; 1 g of IV lipids = 10 kcal).
For dextrose, a 70% stock solution provides 70 g of dextrose/100 mL. To obtain
321 g of dextrose, 459 mL of the stock solution is needed:
Similarly, the volume necessary to provide 85 g of amino acids with a 10% stock
AA solution is 850 mL. IV lipids at 20% provide 2 kcal/mL or 20 g/100 mL. Using
this stock solution, 234 mL would provide 46.8 g of lipids. The total volume of the
dextrose, AA, and fat solution would be 1,543 mL/day. Additional volume will be
required as electrolytes, vitamins, trace elements, and water are included in the final
CASE 38-1, QUESTION 5: The institution administers PPN using a 3-in-1 system at 100 mL/hr (2,400
Maintenance fluid needs can be estimated using several methods. The simplest
method uses 30 to 35 mL/kg/day as the basis. Another method is to provide 1,500 mL
for the first 20 kg body weight plus an additional 20 mL/kg for actual weight beyond
the initial 20 kg. Both methods provide estimates of fluid needs for basic
maintenance, and additional fluid must be provided for increased losses such as
vomiting, nasogastric (NG) tube output, diarrhea, or large open wounds. A.A.’s fluid
needs are estimated as follows:
The PPN formulation is slightly less than A.A.’s needs of 2,590 mL/day. The PPN
can be increased to 2,600 mL/day to better meet fluid needs. This will also slightly
increase his calorie and protein intake bringing him closer to his goal requirements.
Another option would be to provide any additional fluids via a separate IV line. It is
important to not supply fluids in excess. The extra fluid intake may put patients at risk
for becoming fluid overloaded. Therefore, A.A. should be monitored for signs of
fluid overload, including peripheral edema, shortness of breath, daily intake
exceeding daily output, hyponatremia, and rapidly increasing weight.
Providing a portion of calories as fat may reduce the metabolic consequences of
excessive dextrose administration. The maximal rate of dextrose metabolism in
adults is 5 to 7 mg/kg/minute, or approximately 7 g/kg/day. In doses greater than 7
g/kg/day, dextrose is used inefficiently and converted to fat.
may be associated with respiratory compromise and hepatic dysfunction.
Hyperglycemia, another complication of excessive dextrose infusion, is associated
with electrolyte and acid–base disturbances, osmotic diuresis, increased risk of
infections, and altered phagocyte and complement function. Furthermore, using a
mixed-fuel system allows the administration of a small amount of IVFE daily and
avoids the need for larger boluses of lipid twice weekly to prevent essential fatty
acid deficiency (EFAD). Rapid administration of IVFE has been associated with
alterations in the reticuloendothelial system that are not observed with continuous
administration of small doses.
IVFE should be infused at a rate of less than 0.11
g/kg/hour to prevent adverse effects, which include impaired hepatic, pulmonary,
immune, and platelet function.
11 Administration of essential fatty acids as 1% to 4%
of total caloric intake (e.g., 250 mL of 20% lipid twice a week) is necessary to
The essential fatty acids, linoleic acid and α-linolenic acid, are those that cannot
be synthesized by humans. Of these, linoleic acid appears to be the only one required
by adults. Clinical symptoms of EFAD are dry, thickened, scaly skin, hair loss, poor
wound healing, and thrombocytopenia, which may be observed after a few weeks to
months of lipid-free parenteral feedings.
29 Biochemical evidence of EFAD,
determined by a triene to tetraene ratio of greater than 0.4, may be seen after 1 week
of lipid-free parenteral feedings. The continuous infusion of hypertonic dextrose from
the PN is associated with high circulating concentrations of insulin. Because insulin
promotes lipogenesis rather than lipolysis, linoleic acid cannot be released from
Patient Assessment: Moderate Stress
QUESTION 1: B.B. is a 64-year-old woman who was diagnosed with ovarian cancer 4 years ago. The
cancer was treated with a combination of chemotherapy and external beam radiation
Admission laboratory values are as follows:
Alanine aminotransferase, 31 units/L
Aspartate aminotransferase, 27 units/L
Alkaline phosphatase, 65 units/L
Evaluation of B.B. with an abdominal CT scan shows bowel obstruction with a stricture distal to the
enteritis. Why is B.B. a candidate for PN?
PN should be considered when the patient’s nutrient intake has been inadequate for
7 days or longer and the GI tract is not functioning. B.B. has eaten little in the past
week, and her 5% decrease in weight is a concern. Furthermore, her weight has
decreased by more than 10% during the past 6 months, which is considered a severe
weight loss. B.B. is not expected to resume oral intake because her radiation enteritis
is being managed conservatively with bowel rest.
Assessment of weight loss should include evaluation of hydration status,
especially because B.B.’s vomiting and minimal oral intake for the past week place
her at risk of dehydration. Loss of lean body mass is probably less than that reflected
by the decrease in weight. In addition, B.B.’s admission serum albumin concentration
is low at 3.1 g/dL. Her hydration status should be considered when evaluating this
visceral protein, since B.B.’s serum albumin concentration will probably decrease
further after she is rehydrated. Because B.B.’s GI tract is not functioning, PN is
indicated. For a list of the most common primary diagnoses for the use of PN in
hospitalized patients, see Table 38-3.
CASE 38-2, QUESTION 2: What type of malnutrition does B.B. have?
B.B. exhibits some loss of fat and muscle, as well as depletion of visceral
proteins. She has components of both marasmus and kwashiorkor malnutrition;
therefore, she would be considered to have mixed protein-calorie malnutrition (see
Chapter 35, Basics of Nutrition and Patient Assessment).
Most Common Primary Diagnoses for TPN in Adult Hospitalized Patients
Intestinal or peritoneal adhesions with obstruction
JPEN J Parenter Enteral Nutr. 2013;37:56–67.
CASE 38-2, QUESTION 3: Members of the medical team are anxious to have B.B. gain weight and are
B.B. may be at risk of refeeding syndrome. Chronic malnutrition may lead to
intracellular depletion of phosphorus, potassium, and magnesium that may not be
evident when measuring serum electrolyte concentrations. Refeeding syndrome may
occur as phosphorus, potassium, and magnesium shift from the extracellular space
into the cells upon consumption of concentrated sources of calories. Carbohydrate
calories are converted to glucose which triggers the secretion of insulin, which in
turn, facilitates the uptake of glucose, water, phosphorus, and other intracellular
electrolytes. This phenomenon was first reported in World War II when chronically
malnourished survivors were given normal food and liquid diets. Complications
coinciding with refeeding these individuals included hypertension, cardiac
insufficiency, seizures, coma, and death. These complications were reported later in
the 1970s and 1980s, with the introduction of PN in chronically ill, essentially
starved hospitalized patients. Knowing a patient’s history of weight loss and diet
will help to assess the risk of refeeding syndrome. Specialized nutrition support
should be initiated and advanced slowly for “at risk” patients, along with close
monitoring to avoid serious electrolyte abnormalities and the cardiovascular
To minimize the risk of refeeding syndrome in B.B., all electrolyte abnormalities
must be corrected before nutrition support is initiated. Because B.B.’s electrolytes
are within normal range, no baseline adjustments are necessary. Nutrition should then
be implemented slowly and vitamins administered routinely. Laboratory values
including phosphorus, potassium, magnesium, and glucose should be monitored at
least daily for the first week.
Overfeeding should be avoided in all patients, especially those with respiratory
concerns (i.e., mechanically ventilated, chronic obstructive airway disease).
Overfeeding with carbohydrates is particularly detrimental because of the amount of
carbon dioxide produced relative to the amount of oxygen consumed. This results in
carbon dioxide retention that may lead to alterations in acid–base balance. Complete
oxidation of carbohydrate is demonstrated at dextrose infusions of 4 to 5
mg/kg/minute (20–25 kcal/kg/day). Infusions exceeding this rate increase carbon
Comments
Post a Comment
اكتب تعليق حول الموضوع