W10 Total Parenteral Nutrition (GP)

Question 1

What is Enteral Vs Parenteral nutrition?

Answer 1

Nutrition can be provided through gut (enteral nutrition) or directly into the veins (parenteral nutrition)

Question 2

When is parenteral nutrition required?

Answer 2

• Diseases or conditions that impair food intake, nutrient digestion or absorption (e.g., short bowel syndrome, GI fistulas, bowel obstruction, critically ill patients, and severe acute pancreatitis). To ensure ‘Bowel rest’
  (food does not pass through the bowels)
• Contraindications to enteral nutrition (e.g., intestinal obstruction, peritonitis, intractable vomiting and diarrhea).
• Cancer, eating disorders, critical care situations

Question 3

How can TPN be delivered?

Answer 3

• Provides complete nutrition support to the body (vs partial parenteral nutrition – PPN)
• Used for long-term nutrition needs
• Delivered through a large central vein in the neck or chest (superior vena cava, subclavian vein - Central parenteral nutrition or TPN or hyperalimentation)
• Smaller or peripheral vein in the arm (cephalic, basilic, Median antecubital and antebrachial - Peripheral parenteral
  nutrition
• TPN can be given continuously or can be cyclic

Question 4

What should TPN contain to provide complete nutritional support?

Answer 4

• Carbohydrates
• Lipids (fat)
• Amino acids
• Electrolytes
• Vitamins
• Trace elements
• Other optional components (e.g., insulin)
• Depending on individual variables (age, weight, height, medical condition)

Question 5

Composition- Carbohydrates:

Answer 5

• Carbohydrates: primary source of energy
• Dextrose (D-Glucose) is the maincomponent (rather than fructose, galactose).
• Different concentration available –D(%solution)W
• E.g., D50W indicates a 50% w/v Dextrose in water solution

Question 6

Compostion-Lipids:

Answer 6

• Lipids (fat): primary source of essential fatty acid (linoleic acid – precursor of prostaglandins and important for synthesis of fatty acids related to cell membrane integrity).
• Lipid emulsions are composed of soybean and/or safflower oil, glycerol and egg phospholipid.
• 10-20% emulsions in 100 ml, 200 ml, 250 ml and 500 ml volumes
• They are not provided continuously (to prevent hyperlipidemia)
• Available products (Intralipid®,Lipofundin®)

Question 7

Composition and formulation-amino acids

Answer 7

• Amino acids: used for protein synthesis rather than for energy.
• Mixtures of essential (must be obtained from the diet) and non-essential
  (can be synthesized by the body) synthetic L-amino acids.
• The amino acid L-glutamine is not included due to its instability in solution (L-Glutamic Acid instead)
• Provided as crystalline amino acid solution (Aminosin 15%, Travasol 10%, Novamine 15%, Heptamine 8%)
• Amino acid composition can be tailored based on patient requirements, underlying conditions, and nutritional goals.

Question 8

Composition-electrolytes?

Answer 8

• Electrolytes: Potassium (K), Magnesium (Mg), Calcium (Ca).
• Sodium (Na) present as salts (Sodium Acetate/Chloride)
• Phosphate for normal body functioning (to allow phosphorylation of glucose)
• All-in-one solution is available under the name of Hyperlyte® CR Multi-Electrolyte
  Concentrate

Question 9

Composition-Vitamins?

Answer 9

• Vitamins: Fat-soluble (A, D, E and K) water-soluble (B1-3, B5-7, B9, B12 and
  C) vitamins. Required for the metabolism of carbohydrates, proteins and fats.
• Trace elements
  o Contains zinc (Zn), copper (Cu), manganese (Mn) and chromium (Cr)
  o with or without selenium
  o Multitrace-4/5 or multitrace-4/5 Concentrate are available
  o Peditrace is available for pediatric TPN

Question 10

TPN pharmaceutical challenges:

Answer 10

• Parental formulation of nutrients (solubility)
• Solution stability
  o Sedimentation
  o Coalescence
  o Flocculation (aggregation) -> DLVO (Deryagin, Landau, Verwey, Overbeek)
  o Flotation and sedimentation
• Need for hypertonic solutions for volume limitations - OSMOLARITY
• Practicability, efficacy and safety of long-term of TPN - MULTI-CHAMBER BAGS
• Asepsis during compounding, ready to use preparation and administration -STERILITY

Question 11

Osmolarity

Answer 11

• Body fluids have an osmolarity of about 300 mOsm/l (milliosmole/litre).
• TPN solutions tend are highly concentrated (hypertonic solution).
• The fluid from the surrounding tissue moves into the vein due to osmotic gradient.
• If large amounts of nutrients are supplied into a small vein with a low blood flow, the area can become inflamed, and thrombosis can occur.

Question 12

Peripheral vs total

Answer 12

• In the TPN, large amounts of nutrients in a hypertonic solution can be supplies in the superior vena cava
• This vein has a larger diameter and a higher blood flow rate which both determine a rapid dilution of the TPN solution
• Osmolarity limits
• Peripheral TPN: <900 mOsm/l
• Central TPN: 1,500-2,800 mOsm/l

Question 13

TPN osmolarity limits

Answer 13

• Each component contribute to the TPN total osmolarity.
• Definition: concentration of a solution expressed as the total number of
  solute particles per liter.
• Dextrose: 5 mOsm/g
• Protein: 10 mOsm/g
• Lipid: negligible contribution
• Vitamins/minerals: 300-400 mOsm/l (conventional value)

Question 14

• Calculating the osmolarity of TPN solutions:
  What is the formula?

Answer 14

Osmolarity (mOsm/l) =
[(grams dextrose/litre)x5] + [(grams amino acid/litre)x10] + [(mEq cations/litre)x2]

Question 15

TPN osmolarity limits:
* When TPN is prescribed, three factors need to be considered:

Answer 15

• TPN route: Osmolarity limits <900 mOsm/l (peripheral TPN) and 1,500-2,800 mOsm/l (central TPN)
• 2-in-1 or 3-in-1 (for pediatric and adults)
• Other fluids (feeding, heparin, medications)

A Peripheral TPN compositions provides a
final concentration of 5% amino acids and 8%
dextrose

Question 16

Sterile conditions:

Answer 16

• Pharmaceutical preparations and instruments and equipment for TPN are
  required to be sterile
• Sterilization is the process by which a product is rendered sterile, i.e., by the destruction or removal of microorganisms.
• Different processes used (via filtration, via steam, via radiation).
• On most cases, terminal sterilization processes when the preparation is sterilized in its final container or packaging.
• Preparation of single components and final composition in sterile conditions
• Prepared in compliance with Good Manufacturing Practice
• High capital cost of compounding equipment (aseptic manufacture)
• The labor- intensive nature of the work, regular inspections and
  maintenance are required
• Sterile conditions are required also when additives are added to the base
  solution components
• Sterile conditions are required when undertaking TPN for a patient in
  hospital or at home

Question 17

Packaging

Answer 17

• Transparent material to allow the contents to be visually inspected for particles before use
• Light-Protected Infusions Bags: protection for light-sensitive solutions including lipids, vitamins, and oncology medications
• It should be effectively sealed to prevent the enclosed medicine becoming contaminated with microorganisms or other contaminants during storage before use.
• Containers should be airtight and tamper evident (where possible)

Question 18

Packaging of TPN: (tubing)

Answer 18

• Integral hanger
• A minimum of two ports:
  o Injection port: add components/drugs in the TPN bags if needed (self-sealing septum for needless additions) -> additives can also filter sterilized before going in the bag
  o Infusion port: used for connecting tubing.
• Filter
• to prevent air bubbles in your tubing
• reduce the potential for patient exposure to
  particulates and pathogens

Question 19

Packaging of TPN: (bags)

Answer 19

• Glass bottles (less common nowadays) (A)
• Semirigid plastic containers: additive port to allow other drugs to be added to them, air equilibration may be required (B).
• Collapsible bags (C) - they collapse under
  atmospheric pressure as the contents are removed from them;
• Air inlet system to equilibrate air pressure between the outside and the inside of the container not required.
• Volume ranges from 100 ml to 1,4,5 liters (pediatric vs adult patient)

Question 20

Materials- what is used? (2)

Answer 20

1. PVC (Polyvinyl Chloride): synthetic polymer of plastic
   o Cons: drugs may become adsorbed onto the plastic (e.g., insulin)
   or react with the plastic (e.g., etoposide).
   o Components (monomers and phthalate plasticizers) can leach out
   of the plastic which may be toxic on long-term exposure.
2. Polyolefin (polymers made from olefins)
   * Less reactive and is now replacing PVC for this reason in infusion bags
3. Ethylene-vinyl-acetate (EVA) foils suited for lipid containing products; however permeable to air and therefore unable to protect the content from oxidation

Question 21

Labelling:
The label of a TPN solution should contain what?

Answer 21

• patient’s name
• day of administration
• rate and duration of infusion [ml/hr]
• a detailed composition (concentration and dose of components in well
  defined units)
• Strength
• lot identification
• Instruction for use
• Expiration date.
• Storage conditions. Usually stable up to 24 hours, refrigeration storage

Question 22

Preparation and packaging:
* Multi-bottle PN system (bottle of single
components in parallel)

Answer 22

-> parallel infusion of energy (carbohydrate)
together with amino acids for protein synthesis to be controlled
Preparation and packaging

• Keeping in consideration different physicochemical interactions
  (incompatibilities)
• Limited stability
• Hang time= number of hours a bag can hang at room temperature until is considered unsafe
• better parallel infusion of carbohydrate and amino acids

Question 23

Preparation and packaging: Combination approach:

Answer 23

• PN admixtures containing amino acids, glucose, and electrolytes have been produced commercially in concentrated aqueous solutions (large volume bag)
• Infused in parallel with a bottle of lipid a lipid emulsion prepared in 100 to 250 ml bags or glass bottles (milky in appearance)
  -> better parallel infusion of carbohydrate
  and amino acids
• AKA 2-in-1 approach when intravenous fat emulsion and dextrose/amino acid solution are administered on separate lines

Question 24

Latest development- 3-in-1 approach or total nutrition admixture

Answer 24

• Combine both the aqueous and lipid phases as mentioned above.
• The all-in-one solutions may offer more convenience of administration and a potential cost savings.
• However, decrease the mixture stability
  through relatively higher divalent and monovalent cations and increased concentrations of phosphate and calcium
• the available products has relatively lower
  than recommended concentrations of macronutrients

Question 25

Multi-chamber bag system

Answer 25

• Each macro-nutrients in separated from the other in its own compartment
• New multilayered bag materials allowed steam sterilization and extended microbial stability
• Protective wrapping with air-tight plastic foils contributes to the extended shelf life through excluding oxidation by ambient air.
• Ready for use, the seal between the chambers has to be broken mechanically and the components are then mixed together in a closed bag system (asepsis).

Question 26

Preparation of TPN bags

Answer 26

• Premade PN bags vs hospital pharmacy compounded bags
• Individualized PN solutions (patient-dependent and paediatric applications)
• Mixing order is important
  1) Dextrose in water bag
  2) Amino acids
  3) Lipids
  4) Electrolytes (phosphate is generally added first, while calcium is added near the end)
  5) Trace and vitamins

Question 27

TPN Complications

Answer 27

• There is a risk of serious infection associated with central lines
• Sterile solutions
• TPN requires clean and sterile environment
• TPN solution is mixed daily under sterile conditions.
• External tubing (from the TPN bag to the catheter) should be changes everyday and dressings should be replaced every 2 days to keep them sterile
• Watch out for any signs of infection (redness, swelling, fever, drainage or pain)
• If infection occurs, interruption of the nutrition, antibiotics, and exchange of lines is required.

Question 28

Complications

Answer 28

• Another cause of infection: GI tract not in use -> atrophy and gut bacteria can translocate into the circulatory system and increase risk of infection.
• May cause mild to severe liver dysfunction, including liver failure.
• Specific adjustments of the parenteral nutrition to a patient’s specific needs.
• Requires daily monitoring of individual’s parameters (glucose levels, weight, urine output, electrolytes and waste products in the blood (plasma urea)) in the hospital.
• Once stabilization is reached, the TPN can be used at home under certain conditions (weekly monitoring) and proper patient and caregiver education

Question 29

TPN discontinuation
When can this take place?

Answer 29

• It takes place when patient can satisfy 75% of caloric and protein needs with oral intake or enteral feeding
• Gradually reduce the infusion rate (halved for 1 hours, halved again the next hours and then discontinued).
• This helps preventing rebound hypoglycaemia from hyperinsulinemia