PN formulations are based on the patient's energy and nutrient requirements. Basic formulas contain protein and nonprotein calories: carbohydrates and fat, along with electrolytes, vitamins, trace elements, and fluid requirements.

Fluid Requirements

Basic fluid requirements for maintenance are 30 to 40 mL/kg/day (Ayers et al., 2020). Factors that may increase fluid needs include significant fluid loss, as occurs with diarrhea or the presence of an enterocutaneous fistula.

Proteins/Amino Acids

Proteins are required for anabolism, that is, for tissue growth and repair and replacement of body cells. Amino acids are the basic units of protein. There are eight essential amino acids needed by adults that must be supplied in the diet: isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. There are also nonessential amino acids; these amino acids can be synthesized by the body and include alanine, aspartic acid, asparagine, glutamic acid, glycine, proline, and serine. Histidine is essential mainly in infants and children (Young & Kim, 2017). Conditionally essential amino acids required in the diet during certain disease states include histidine, cysteine, tyrosine, arginine, and glutamine.

Protein in PN is provided as synthetic crystalline amino acids. They are available in concentrations of 3% to 20%, with and without electrolytes. There are also specialty amino acid formulations that may be used with certain disease states, such as hepatic encephalopathy and renal failure.

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Protein requirements for maintenance of healthy adults is 0.8 to 1 g/kg/day, while critically ill patients require 1.5 to 2 g/kg/day (Ayers et al., 2020).

Carbohydrates

Carbohydrates are the major source for energy and also spare body protein. When glucose is supplied as a nutrient, it is stored temporarily in the liver and muscle as glycogen. When glycogen storage capacity is reached, the excess carbohydrate is stored as fat. Carbohydrate types include dextrose (glucose), fructose, sorbitol and xylitol, and glycerol. There is not a specific requirement for carbohydrates; rather, needs are determined based on estimations of energy requirements. Carbohydrates generally provide about 50% of total calories.

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Carbohydrates provide 3.4 calories per gram. Excessive dextrose intake can lead to increased production of carbon dioxide, which can cause respiratory failure. Hepatic dysfunction may occur from excessive dextrose intake as a result of increased synthesis and fat storage in the liver.

Dextrose is the most commonly used source of carbohydrate in PN solutions and is commercially available in concentrations from 2.5% to 70%. In addition to caloric need, considerations in the amount and concentration of glucose are based on respiratory, cardiac, renal, and fluid volume status.

Dextrose may be administered with amino acids as the only nonprotein source of calories or may be administered in conjunction with lipids. When PN is administered peripherally, the final concentration of dextrose must be 10% or less to prevent vein irritation, including thrombophlebitis. Of note, glycerol is another carbohydrate that is used at times in PN formulas. The rationale for using glycerol is that it may be more protein sparing, inducing less insulin response than dextrose, but the evidence for these benefits is conflicting (Ayers et al., 2020).

INS Standard: PN solutions containing final concentrations exceeding 10% dextrose are administered through a CVAD (Gorski et al., 2021, p. S190).

Fat

Fat is a primary source of heat and energy. Fat provides twice as many energy calories per gram as carbohydrates. When fat is used to supply a portion of calories, less dextrose is required. In patients with glucose intolerance, this may be beneficial.

Fat is essential for the structural integrity of all cell membranes. Linoleic acid and linolenic acid are the only fatty acids essential to humans and are required to prevent essential fatty acid deficiency (EFAD) (Ayers et al., 2020). Signs and symptoms of EFAD include desquamating dermatitis, alopecia, brittle nails, delayed wound healing, thrombocytopenia, decreased immunity, and increased capillary fragility.

When fat or lipids are used as a calorie source in PN, there are fewer problems with glucose homeostasis, carbon dioxide production is lower, and hepatic tolerance to IV feedings may improve. In patients with respiratory failure, the use of fat as a part of the total calories allows for a decrease in glucose calories and therefore may decrease carbon dioxide production.

Lipid Administration

There are a variety of lipid injectable emulsions (ILE). These formulations may include soybean, safflower, olive, and/or fish oils and medium-chain triglycerides in different combinations. ILEs provide 1.1 kcal/mL (10% solution) or 2.0 kcal/mL (20% solution) (Gahart, Nazareno, & Ortega, 2021). Lipids may be administered as a separate infusion, concurrently with the amino acid/dextrose solution via a Y tubing, or as part of a total nutrient admixture (discussed later). Of note, ILE products are isotonic, have a pH between 6 and 9, and can be administered via a peripheral vein. To prevent EFAD, 8% to 10% of the caloric input should be supplied as an ILE to provide adequate amounts of essential fatty acids (Gahart et al., 2021).

NOTE: A 30% ILE is available but is never given by direct IV infusion; rather, it is used by the pharmacy in admixtures (Gahart et al., 2021) (Fig. 12-3).

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1 g of fat = 9 kcal Use of fat for a portion of the calories in the PN solution will allow for a decrease in dextrose and may improve glucose management in stress states.

Lipid-containing solutions are known to leach di(2-ethylhexyl) phthalate (DEHP), a known toxin, from bags and tubing made of PVC; therefore, they are administered through DEHP-free administration sets. Non-DEHP administration sets are available with most commercially available ILEs. Lipids are always filtered with a 1.2-micron filter (Worthington et al., 2021). Lipids may be supplied in glass containers or special non-polyvinyl chloride (non-PVC) bags (see Fig. 12-1).

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For the first 15 to 30 minutes, the ILE should be infused slowly. Always follow the manufacturer's directions. For example, the initial rate of a 20% ILEs in adults should be 0.5 mL/min or 0.1 g of fat/min for the first 15 to 30 minutes; if there are no untoward effects, the rate can be increased to the required rate (Gahart et al., 2021).

INS Standard: Administration sets used to administer lipid-based infusates should be free of DEHP (Gorski et al., 2021, p. S124).

Electrolytes

Electrolytes may be given either in a premixed PN formula or adjusted based on the patient's status. Standard ranges for parenteral electrolytes assume normal organ function and normal losses. Electrolytes are available in several salt forms and are added or adjusted based on the patient's metabolic status. For example, potassium may be given as potassium chloride, potassium phosphate, or potassium acetate salt. The electrolytes included in PN solutions include sodium, potassium, magnesium, calcium, chloride, acetate, and phosphate (see Chapter 3 for a review of the physiological roles of electrolytes).

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Serum potassium levels must be closely monitored during PN administration. Patients with impaired renal function are at risk for hyperkalemia and generally require a decreased amount of potassium.

Standard daily requirements for electrolytes included in PN solutions include:

• Sodium: 1 to 2 mEq/kg
• Potassium: 1 to 2 mEq/kg
• Phosphate: 20 to 40 mmol
• Magnesium: 8 to 20 mEq
• Calcium: 10 to 15 mEq
• Chloride/acetate: As needed based on acid-base status (Patel, 2017)

Vitamins

Vitamins are necessary for growth and maintenance, as well as for multiple metabolic processes. Vitamins cannot be synthesized by the body and must be provided in the diet. Both fat-soluble and water-soluble vitamins are included in commercially available multivitamin products. Fat-soluble vitamins are vitamins A, D, E, and K. Water-soluble vitamins include vitamin C and the B complex vitamins: Thiamine (B₁), riboflavin (B₂), niacin (B₃), pantothenic acid (B₅), pyridoxine (B₆), biotin (B₇), folic acid (B₉), and cyanocobalamin (B₁₂). Vitamin supplements are added to the PN formulation.

Trace Elements

Trace elements are micronutrients found in the body in minute amounts. Basic requirements are very small, measured in milligrams. Each trace element is a single chemical and has an associated deficiency state. The functions of trace elements are often synergistic. Trace elements may be provided in the PN solution as a multi-trace element combination or as single-element products. Trace elements commonly used in PN solutions include:

• Zinc: RNA, DNA, and protein synthesis; important to wound healing
• Copper: Works with iron to form red blood cells
• Chromium: Potentiates insulin reactions
• Manganese: Antioxidant protection; involved in enzyme reactions; carbohydrate synthesis
• Selenium: Catalyst in an important antioxidant pathway (Ayers et al., 2020).

NOTE: Iron is not routinely included as a component in the PN solution. Most often, it is administered as a separate infusion when needed. Iron dextran is approved for addition to PN solutions, but it can be used only in PN solutions without fat emulsions (Ayers et al., 2020).

Medication Administration With Parenteral Nutrition

PN solutions are complex with the potential for physicochemical interactions associated with drug-nutrient combinations. Potential interactions between drugs and the nutrients in the solution include physical changes such as precipitation, altered viscosity of the solution, changes in consistency, clumping or curdling of the solution, and loss of drug activity or toxicity (Ayers et al., 2020). Medications that are generally compatible with and may be added to PN include regular human insulin, unfractionated heparin, and histamine receptor agonists (e.g., famotidine) (Ayers et al., 2020). Histamine receptor agonists are used to decrease gastric acid secretion and reduce risk for stress ulcers.

Hyperglycemia is a complication of PN caused by the high concentration of glucose in the PN solutions and altered glucose metabolism associated with stress and disease. Insulin aids in adequate metabolism of carbohydrates. It is chemically stable in PN and is often added to the solution. However, insulin can be adsorbed into the plastic solution container, the administration set, and the filter, so doses often need to be increased until blood glucose control is achieved (adsorption is addressed in Chapters 5 and 10).

Unfractionated heparin may be added to the PN solution to improve the clearance of fat emulsions from the bloodstream (Ayers et al., 2020). However, unfractionated heparin is not compatible with total nutrient admixture (TNA) formulations (discussed later).

INS Standard: Medications are not added to or coinfused with the PN solution/emulsion before or during infusion without consultation with a pharmacist regarding compatibility and stability (Gorski et al., 2021, p. S190).

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Always consult with the pharmacist or check current information about drug compatibility with PN solutions. Medications are never “piggybacked” directly into PN solutions. Only regular insulin is appropriate for IV administration.

Parenteral Nutrition Compounding

PN solutions must be prepared and stored safety and accurately according to regulations established by the United States Pharmacopeia (USP) <797> entitled Pharmaceutical Compounding: Sterile Preparations (Ayers et al., 2020). It is the responsibility of the dispensing pharmacist to ensure that PN is prepared, labeled, controlled, stored, dispensed, and distributed properly. Compounding of an accurate solution that is free of microbial and particulate matter is essential to the process. PN solutions are prepared in compounding rooms that must meet certain conditions, and pharmacy personnel must wear protective equipment such as gloves, masks, and hair/shoe covers during the compounding process.

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The USP Chapter <797> Pharmaceutical Compounding: Sterile Preparations (2008) details the procedures and requirements for compounding sterile preparations and sets standards that are applicable to all practice settings in which sterile preparations are compounded. These standards have been widely adopted, are enforced by many state boards of pharmacy, and may be used by accreditation organizations (e.g., The Joint Commission) in surveys. The standards are currently undergoing revision at the time of the publication of this book.

Peripheral Parenteral Nutrition

Peripheral parenteral nutrition (PPN) is used to nourish patients who either already are malnourished or have the potential for developing malnutrition and who are not candidates for enteral nutrition. Patients who are candidates for PPN must meet the criteria of (1) good peripheral venous access and (2) able to tolerate large volumes of fluid, 2.5 to 3 L/day. PPN is considered controversial; some believe that the risks of PPN outweigh the benefits because candidates for this therapy have minor nutritional deficits (Ayers et al., 2020). Administration of PPN should be limited to less than 14 days.

PPN is limited to solutions with an osmolarity below 900 mOsm/L, and the final dextrose concentration for a peripheral infusion should not exceed 10% due to the increased risk for phlebitis and extravasation (Gorski et al., 2021; Worthington et al., 2017).

Advantage of PPN

1.Avoids insertion and maintenance of a CVAD.

Disadvantages/Limitations of PPN

1.Contraindications include significant malnutrition, compromised renal/hepatic status.

2.Cannot be used in volume-restricted patients because higher volumes of solution are needed to provide adequate calories.

3.Risk for phlebitis due to high solution osmolarity.

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Assess for an appropriate peripheral catheter for delivery of PPN. Some may consider a midline catheter for PPN as the tip is in a larger blood vessel, allowing for better dilution of the PPN. However, the risk of phlebitis is not eliminated with a midline catheter, and there is no current research documenting the efficacy of midline catheters with PPN (Worthington et al., 2017). Hyperosmolar infusates should not be infused via midline catheters due to risk of severe endothelial damage (Ryder et al., 2020).

INS Standard: The use of midline catheters for peripheral PN has not been studied; the location of midline catheters in a deeper vein may mask early signs of phlebitis. Do not use midline catheters for continuous vesicant therapy, PN, or solutions with extremes of pH or osmolarity. Recognize the increased risk for phlebitis with PPN; weigh the risks versus benefits for PPN administration (Gorski et al., 2021, p. S190).

Parenteral Nutrition via a Central Vein

PN via central vein (previously called total parenteral nutrition [TPN]) is used to provide nutrients at greater concentrations and fluid volumes than is possible with PPN. Central vascular access can be maintained for prolonged periods (weeks to years) with a variety of catheters (e.g., peripherally inserted central catheter [PICC]; see Chapter 8). The PN formula may be administered with the lipids mixed together with dextrose/amino acid components (total nutrient admixture [TNA]), or the lipids may be administered as a separate intermittent infusion. Centrally delivered PN involves both advantages and disadvantages.

Advantages

• Dextrose solution of 20% to 70% can be administered as a calorie source.
• May be used for patients with long-term or even life-long needs for PN.
• Caloric and nutrient needs can be met.
• Provides calories; restores nitrogen balance; and replaces essential vitamins, electrolytes, and minerals.
• Promotes tissue synthesis, wound healing, and normal metabolic function.
• Is nutritionally complete.

Disadvantages

• Requires placement of a CVAD.
• May cause metabolic complications, including glucose intolerance, hepatobiliary complications, electrolyte imbalances, and EFAD.
• Potential complications related to CVADs (see Chapter 9).

Practice Criteria for PN

• PN is delivered through a CVAD as defined by the catheter tip located in the superior vena cava at or near the cavoatrial junction.
• Verification of the catheter tip placement must be obtained before use of the catheter.
• The central line bundle interventions are followed during CVAD insertion (see Chapter 2).

Total Nutrient Admixtures (Three-in-One Admixtures)

TNAs are PN solutions containing dextrose, amino acids, and fat emulsions in one large solution container. TNAs are often referred to as “all-in-one solutions” or “three-in-one solutions” (3-in-1 solutions). The solution is compounded in the pharmacy and is usually milky-white and opaque, although a faint yellow hue may be evident with the addition of vitamins. “Multichamber bags” may be used in home infusion. This is defined as a container designed to promote extended stability of the PN formulation by separating some components (e.g., IV fat emulsion) from the rest of the formulation. It consists of two or more chambers separated by a seal or tubing that is clamped (Fig. 12-4). At the time of administration, the seal or clamp is opened to allow the contents of the chambers to mix and create an admixture.

TNA solutions offer some important advantages, including the following:

• All components compounded aseptically in the pharmacy
• Less manipulation during administration and less risk of contamination (compared to administering lipids as a separate infusion)
• Less nursing time required
• Less supply and equipment expense (e.g., one infusion pump and administration set)
• Better dextrose tolerance in some cases
• May be more cost-effective
• Improved fat clearance when administered over more than 12 hours (Ayers et al., 2020)

Disadvantages may include less solution stability and risk for separation of lipids, difficulty in visualizing precipitate or particulate matter in the solution, more risk for drug-nutrient incompatibilities, and increased risk for catheter occlusion over time (Ayers et al., 2020).

Total nutrient admixtures must be administered through a 1.2-micron filter because of the risk of particulate matter (Fig. 12-5). The stability of TNA is affected by many factors, including admixture contents, storage time and conditions, addition of non-nutrient drugs, pH of the solution, and variability in temperature.

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Examine the TNA solution for signs of instability before hanging the bag and periodically throughout administration. These solutions may “crack” as the oil separates. Instead of a uniformly white appearance, yellow oil streaks appear throughout the container, or an oil layer appears at the top of the container. It is not safe to administer a TNA with such an appearance. Causes for this phenomenon include: Reduced pH, which is not favorable for stability of the lipid component in the TNA Addition of electrolyte salts (Ayers et al., 2020)

Cyclic Parenteral Nutrition

For patients requiring long-term PN support, cyclic PN is widely used. Cyclic PN is defined as administering the PN solution over a reduced time frame (e.g., 8 to 16 hours) instead of as a 24-hour continuous infusion. Cyclic PN is indicated for patients who have been stable on continuous PN and require long-term PN; for those receiving home PN (HPN); and for patients who can handle total infusion volume in a shortened time period.

Patients are transitioned to cyclic PN once they are stable on a 24-hour continuous infusion. The hourly rate of PN infusion is increased as the number of infusion hours is decreased. Typically the infusion is shortened by 4 to 6 hours per day until the desired cycle time is met (Ayers et al., 2020). Because of the increased fluid volume and increased glucose delivery over less time, the patient is monitored carefully for signs of fluid volume excess and hyperglycemia. Symptoms of excess fluid administration should be monitored, such as weight gain resulting in edema or infusion-related shortness of breath. If too much fluid is administered during the cyclic period, the time frame is extended.

Cyclic PN administration requires twice as many central line manipulations as continuous PN because of the initiation of the infusion and the discontinuation of the infusion every 24 hours. This increases the risk of introducing bacteria into the internal catheter lumen and thus the risk of a bloodstream infection. Attention to aseptic technique with every catheter access is critically important.

Advantages

1.Allows for more physiological hormonal response and appetite stimulation because of periods of time without infusion

2.Reduces risk for serum liver enzyme and conjugated bilirubin concentrations when compared to continuous PN (Ayers et al., 2020)

3.For patients on long-term PN, improved quality of life by encouraging normal daytime activities and enhances psychological well-being; patient does not need to carry around an infusion pump 24 hours/day; usually run over nighttime hours for home-care patients

Disadvantages

1.Patients must be observed for symptoms of hypoglycemia, hyperglycemia, dehydration, excessive fluid administration, and infection associated with central-line manipulation.

2.Patients require monitoring for hyperglycemia, which can develop during the peak flow rate.

3.There is also a risk for hypoglycemia generally during the 30 to 60 minutes after cyclic PN discontinuation. Blood glucose levels should be checked whenever the patient displays symptoms of nausea, tremors, sweating, anxiety, or lethargy. Tapering the infusion rate for 1 to 2 hours at the end of the infusion may be needed.

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Cyclic PN is usually used for patients requiring long-term PN. The patient's cardiovascular status must be able to accommodate higher infusion rates during the infusion period.