Chapter 15: PN Formulations Flashcards
What is the amount of kcal/kg provided in dextrose? (Most commonly used carbohydrate in PN).
3.4 kcal/kg
What is the amount of kcal/kg provided by glycerol? What is glycerol?
4.3 kcal/kg
Sugar-alcohol; less frequently used CHO energy substrate.
What is the amount of kcal/kg of crystalline amino acids in PN formulations?
Yield 4.0 kcal/kg, when oxidized for energy.
AA products are generally assumed to be 16% N (6.25 g AA = 1 g N)
What are some differences between standard and concentrated AA formulations?
The acetate content is higher in the more concentrated products than in standard stock concentrations.
Chloride salts may be used to balance the chloride:acetate ratio in the final PN formulation to avoid iatrogenic acid-base disturbances.
What are the 3 ILE formulations used for PN?
- 2 formulations are composed solely of LCTs; which are 100% soybean oil-based formulations
- 50:50 blend of safflower oil and soybean oil (but has been out of stock due to safflower oil shortages)
What is Smoflipid? What is the composition, benefits?
“Smof” refers to the type of oils
- S: oybean oil
- M: CTs
- O: live oil
- F: ish oil
This ILE contains: 30% soybean oil, 30% MCTs, 25% olive oil, and 15% fish oil, and is available as a 20% solution.
Contraindicated in patients with a known hypersensitivity to soybean, fish, egg, or peanut protein
Essential acid concentration is lower than the traditional soybean oil-based ILEs
Benefit: Contains a vary of oils, while reducing the amounts and detrimetrial effects of w-6 FAs
What is the amount of kcal/kg for fat in PN formulations?
9 kcal/kg
**ASPEN/SCCM Recommendation**
What is the recommendation regarding w-6 FAs in critically ill patients receiving PN?
**ASPEN/SCCM Recommendation**
Suggests that clinicians either withhold soybean oil-based ILE or limit it to a maximum of 100 grams (often divided into 2 doses) during the first week following initiation of PN, if the patient is at risk for EFAD.
What are the preferred forms of calcium and magnesium for use in PN formulations? Why?
- Calcium gluconate
- Magnesium sulfate
Less likely to produce physiochemical incompatibilities compared to calcium chloride, calcium gluceptate, and magnesium chloride.
What are 5 commonly used trace elements in PN formulations?
- Zinc
- Copper
- Chromium
- Manganese
- Selenium
**ASPEN Recommendation**
What types of trace elements products be used for PN formulations?
**ASPEN Recommendation**
When multiple-element products are inappropriate, single-element products should be used to meet individual patient needs.
**ASPEN Recommendation**
What are the specific recommendations ASPEN has made to commercially available multi-trace element products?
**ASPEN Recommendation**
Products need to undergo significant modifications:
- Decreasing copper (to 0.3 from 0.5 mg/d)
- Decreasing manganese (to 55 mcg/d)
- Manufacturing a product without chromium (or a maximum of 1 mcg/d)
- Including selenium in all products at a higher dose of 60 to 100 mcg/d)
What is the only iron approved for addition to PN?
Iron dextran; should only be considered for dextrose-AA formulations, because ILE formulations are disrupted by iron.
What are the benefits of glutamine?
AA found in the human body; has a role in intestinal integrity, immune function, and protein synthesis during stress states.
(TRUE/FALSE)
Glutamine can be added to PN formulations and is recommended for critically-ill patients.
FALSE.
No FDA-approved IV form of glutamine is commercially available in the US for admixture in PN formulations, because of poor solubility and stability and compatibility limitations.
Parenteral glutamine supplementation is no longer recommended for adult critically-ill patients because recent literature indicates either a lack of infectious or morality benefit.
What is carnitine?
A quaternary amine necessary for proper transport and metabolism of long-chain FAs into the matrix of the mitochrondria for beta-oxidation.
(TRUE/FALSE)
IV L-carnitine is commercially available to be added to PN formulations for the treatment of carnitine deficiency or those who are at risk for deficiency, such as neonates/infants.
TRUE.
Only IV L-carnitine can be added to PN, there are no other carnitine formulations available.
Define 2-in-1 PN formulation.
The traditional dextrose - AA formulation; along with the prescribed electrolytes, minerals, vitamins, and trace elements in either a single container for multiple containers each day.
ILE is administered separately as a piggyback infusion
Define 3-in-1 admixture, aka all-in-1 admixture; TNA.
Incorporates dextrose, AA, ILE and the prescribed micronutrients together in the same container for final administeration.
What is the CDC guideline for hang times of ILE?
Limits hang times of ILE given in the piggyback fashion to a maximum of 12 hours.
Faster infusion rates (4 to 6 hours) predispose susceptible patients to hypertriglyceridemia that could have been lessened by infusing ILE at a slower rate.
What is the CDC guideline for iLE incorporated into a TNA?
Can hang for up to 24 hours.
What is the USP?
A private, non-profit organization recognized by the federal gov. as the official group responsible for setting national standards for drug purity and safety and issues standards on the pharmaceutical compounding of sterile products.
What is Chapter {797}?
Established by USP, that discusses that standards that apply to all sterile dosage forms that are compounded, including PN.
What is a low-risk level for CSPs?
CSPs = Compounded Sterile Preparations
Low risk typically involves a simple, closed-system aseptic transfer
What is a medium-risk for CSPs?
Involves reconstitution of several sterile commercial products for transfer into several small-volume minibags or a large-volume parenteral preparation, such as PN.
What is a high-risk level for CSPs?
Involves the preparation from bulk, nonsterile ingredients or the preparation from sterile ingredients that are exposed to less than the International Org. for Standardization (ISO) Class 5 standards.
A low- or medium- risk product becomes high risk when any added component is high risk; thus a PN formulation with L-glutamine compounded from nonsterile powder becomes a high-risk product.
What are ACDs?
Automated Compounding Devices; developed to streamline the manufacturing sequence for multiple-ingredient preparations, such as PN formulations, by automatically delivering individual components in a predetermined sequence under computerized control.
What are some advantages of ACDs?
- Enhanced accuracy
- PN formulations can be more tailored to individual patient needs
- More efficient process
- Should reinforce proper compounding sequence
- Reduce the likelihood of touch contamination
- Reduces labor and supply costs for institutions that compound many PN formulations daily
What are some double-checks that should still happen if an institution uses an ACDs for PN formulations?
- Independent, double-check of the initial daily ACD set-up should be done using a printed checklist
- PN formulations for: Adults, Peds, Neonates, should be done in separate location or time
- Warning limits should be weight-based and determined by pharmacists’ review to ensure consistency with the needs of the specific patient population.
What is gravimetric analysis?
Can be used as a quality control measure for manual or automated compounded systems, and is a method of quality assurance that can be applied independent of the ACD.
What is refractometry?
Also used to determine whether PN formulations have been compounded properly. The refractive index of dextrose and AAs can be measured with a refractometer and compared to values established for known concentrations of dextrose and AAs in PN base formulations.
Cannot be used with ILE
What are SCAPN products?
Standardized Commercially Available Parenteral Nutrition Formulations
These products have an internal membrane that separates the macronutrients into different chambers of the product and is broken so the components can be mixed just before administeration.
They require the addition of the MVI injection shortly before administeration because vitamins are essential components of PN that are not stable when added more than 24 hours in advance of use.
What is ProcalAmine?
- A SCAPN product
- Glycerol-based products that can be used for short-term PPN administeration
- Contains a final concentration of AA of 3%; glycerol 3% and electrolytes
- Remember glycerol is a sugar-alcohol and can be premixed and steriled in a single bottle w/o undergoing the Mallard rxn
What are some potential advantages of SCAPN products?
- Reduction in costs
- Decreased compounding time
- Less risk for ordering and compounding errors
- Fewer bloodstream infections
- Shelf-stable and heat sterilized, allowing for more time before expiration than compounded PN.
What does stability mean when referring to PN admixtures?
Stability of PN formulations refers to the degradation of nutritional components that changes their original characteristics
Example: Maillard reaction (that occurs between IV dextrose and certain AAs such as lysine, resulting in a brownish discoloration of the final formulation).
Also, photodegradation from light exposure, particulary fluorescent light, results in a loss of some vitamins.
What does compatibility mean when referring to PN admixtures?
Compatibility issues with PN formulations generally involve the formation of precipitates.
May be solid (crystalline matter) or liquid (phase separation of oil and water in a TNA).
(TRUE/FALSE)
The distinction between stability and compatibility with ILEs can be difficult to discern, because all emusions are inherently unstable systems that will return to their oil and water components over time.
TRUE.
ILEs clearly have compatibility issues. For example, the addition of trivalent cations such as iron dextran to an ILE results in phase separation of the ILE components.
(TRUE/FALSE)
Medications should not be added to PN formulations unless there is clear evidence fro the literature or standard references to support stability, compatibility and maintenance of pharmacological and therapeutic efficacy that is specific to the nutrient composition in the PN to be dispensed.
TRUE.
(TRUE/FALSE)
ILE consists of an interior oil phase dispersed in an external water phase.
TRUE.
What are some factors that may alter the electrical charge on the fat droplet surface in ILEs?
- Reductions in pH
- Addition of electrolyte salts
What is the most critical factor influencing the pH formulations?
The crystalline AA solution used for compounding
(TRUE/FALSE)
The concentration or amounts of calcium and phosphate ions are directly related to the risk of precipitation.
TRUE.
What are the two forms of calcium that are generally less dissociated salts forms of calcium than the chloride salts?
- Calcium gluconate
- Calcium gluceptate
Less impact on risk of precipitation
Trace element contamination is found in most PN formulation components. What do these include? (6)
- Arsenic
- Aluminum
- Chromium
- Zinc
- Manganese
- Copper
What is the primary route for aluminum elimination in the body to prevent toxicity?
Kidneys remove unbound aluminum from the blood
About 60% of infused aluminum is eliminated in patients with adequate renal function. The remaining is deposited in tissues, like the brain, bones, liver and lungs.
Adult patients at risk for aluminum toxicity include? (3)
- Significant renal dysfunction
- High intake of PN
- Iron deficiency
What size are large-pore filters? Purpose?
5 microm
Adequate for the removal of precipitates (ie: calcium phosphate) and particulate matter (ie: plastic fragments from the bag) from PN formulations.
(TRUE/FALSE)
Filters are a good substitute for good compounding practices indended to prevent precipitate formation.
FALSE.
They are NOT
What is the purpose of 1.2 microm filters, with ILE-containing PN formulations?
Avoid particle shearing and instability that may occur with filters of smaller size
Does not trap larger organisms including C. abicans
With which PN type should 0.22 microm filter be used?
For dextrose-AA PN admixtures // 2-in-1
If a 2-in-1 dextrose-AA admixture is administered with a separate infusion of ILE, what 2 filters would be required?
- 0.22 microm in-line filter for the 2-in-1
- 1.2 microm in-line filter for the ILE
(TRUE/FALSE)
In-line filters should be changed with each new administration of PN?
TRUE
Q 24 hours with TNA and 2-in-1s
Q 10-12 hours for ILE
(TRUE/FALSE)
In-line filters can increase the incidence of occlusion alarms during PN administration.
TRUE.
Should be recognized as a potential sign of a precipitate and should be investigated.
CDC does not endorse the use of in-line filters solely for the purpose of infection control.
How much kcal/mL is provided in 20% ILE? (Think PPN)
2 kcal/mL
How much kcal/mL is provided in 10% ILE? (Think PPN)
1.1 kcal/mL
How much kcal/mL is provided in 30% ILE? (Think PPN)
2.9 - 3 kcal/mL
ILE should not exceed what percentage of calories OR x g/kg/day?
Not exceed 60% of total energy OR
2.5 g/kg/kday
What is the maximum rate of dextrose administration?
3 mg/kg/min
5 mg/kg/min is the maximum amount of dextrose the liver can oxidize
CALCULATION:
A patient weighing 80 kg has estimated requirements of 30 kcal/kg/d and 1.5 g/kg/d. Between 20% and 30% of total energy will be provided as ILE. The volume should be restricted to 1.5 L/d.
- Calculate energy and protein needs.
- Calculate minimum and maximum of kcals from ILE.
- Calculate given stock solutions used by the pharmacy for compounding PN are AA 10%, dextrose 70%, and ILE 20%. PN formulations are manually compounded without an ACD as dextrose-AA formulations.
Page 317 in Textbook.
- Total energy = 2400 kcal/day; Protein = 120 g/d
- Minimum = 480 kcals/d; Maximum = 720 kcals/d.
- AA 10%: 400 kcal/d; 100 g; Dex 70%: 250 mL = 595 kcals; 175 g; 20% ILE 250 mL = 500 kcal/d
400 + 500 +595 = 1495 kcal/day in 1500 mL/day; cannot meet full estimated energy and protein needs given FR.
Other examples on page 316 - 317.
What contributes to metabolic bone disease in PN-dependent patients?
Aluminum toxicity
(TRUE/FALSE)
Hyperglycemia causes a shift of water out of the cells into the extracellular space, resulting in dilution of serum sodium
TRUE; resulting in hypertonic hyponatremia
For every 100 mg/dL increase in serum glucose conc above 100 mg/dL, the serum sodium would be expected to DECREASE by approximately 1.6 mEq/L.
Treatment should consist of correction of the underlying hyperglycemia, and NOT changes in sodium and water administration, as this is not a true sodium or water imbalance.
Define azotemia
an elevation in BUN and serum creatinine levels
(TRUE/FALSE)
If serum TG is above 400 mg/dL, the ILEs should be discontinued.
TRUE.
Provide lipids only to prevent EFAD.
Parenteral nutrition should not exceed X mg/kg/min or X to X kcal/kg/day.
Not exceed 5 mg/kg/min OR 20 to 25 kcal/kg/day
When fibrin builds up inside the vein and causes the vascular access device to adhere to the vessel wall, what is it called?
Mural thrombus
A layer of fibrin that develops around the outside of the CVC (central venous catheter) secondary to aggregation of fibrin from the presence of a CVC within a vein, is?
Fibrin sheath
What is fibrin build up on the CVC tip that will allow for infusion through the CVC, but will inhibit withdrawal of blood?
Fibrin tail/flap
What is a clot within the catheter lumen and is caused by inadequate flushing and blood reflex?
Intraluminal thrombus
0.1N HCl acid is most effective for clearing catheter occlusions due to precipitation of?
Calcium-Phosphate
However, direct infusion of HCl acid into the venous system can be associated with fever, phlebitis, and sepsis
What catheter occlusions is sodium bicarbonate been effective in clearing?
Catheter occlusions due to precipitates associated with meds in the high pH range (tobramycin and phenytoin).
What is 70% ethanol effective in clearing in catheter occlusions?
Dissolve lipid residue
What is the most important contributor to metabolic bone disease?
Negative calcium balance.
Hypocalcemia occurs as a result of decreased calcium intake and/or increased calcium urinary excretion.
Factors that cause:
- Excessive calcium & inadequate phosphorus supplementation
- Excessive protein in PN solutions
- Cyclic PN infusions
- Chronic metabolic acidosis
What is the most appropriate intervention for hypercalcemia?
Protein reduction; specifically protein doses for long-term PN should not exceed 1.5 g/kg/day
(TRUE/FALSE)
Oral or enteral feeding, even in small amounts, is the best approach to preventing cholelithiasis.
TRUE, (gallstones) as it stimulates cholecystokinin secretion, bowel motility and gallbladder emptying.
What is ursodiol?
Used to dissolve gallstones; and shown to improve bile flow
However, it has limited results and is only available in an oral dosage form and its absorption may be limited in patients with intestinal resection.
(TRUE/FALSE)
Supplementation of choline has been shown to prevent cholelithiasis.
FALSE
The role of choline in the pathogenesis of cholelithiasis has not been determined
Acetate is metabolized to what?
Bicarbonate
So excessive use of acetate may precipitate a metabolic alkalosis.
(TRUE/FALSE)
Excess chloride is a common cause of metabolic acidosis.
TRUE
As well as, diarrhea and ARF
(TRUE/FALSE)
Severe hypophosphatemia has been reported to cause respiratory failure and seizures?
TRUE
What are the recommended maximum amounts of PN components per clinical guidelines for adults?
- mL/kg/day of Fluid
- g/kg/day of CHOs
- g/kg/day of Fat
- g/kg/day of Protein
30 to 40 ml/kg/day of Fluid
7 g/kg/day of CHOs
2.5 g/kg/day of Fat
2 g/kg/day of Protein
What are some contraindications for PPN?
- Signification malnutrition
- Severe metabolic stress
- Large nutrient or electrolyte needs
- FR
- Greater than 2 weeks need for PN support
- Liver and Renal compromise
What feature of Groshong CVC reduces the risk of catheter occlusion?
A pressure-sensitive three-way valve that restricts blood backflow and air embolism by remaining closed when not in use.
This eliminates the need for heparin flushes to maintain catheter patency, but the CVC should be flushed with NS after med administration or blood aspiration to ensure the valve is in the closed position.
What is Alteplase?
Is the only FDA-approved thrombolytic agent for CVAD occlusion
Alteplase 2 mg in a 2-mL volume is injected into the catheter and allowed to dwell for 30 minutes to 4 hours, then aspiration of solution with a syringe is attempted. The process may be repeated, if necessary.
(TRUE/FALSE)
Use of heparin 100 units/mL is appropriate for the treatment of CVAD occlusions.
FALSE
Heparin is appropriate for catheter FLUSHING
Symptoms of manganese toxicity are associated most commonly with the accumulation of the mineral in which organ?
Brain
Manganese absorption from the GI tract is 6-16% of dietary intake; therefore, when provided through PN there is 100% bioavailability.
Manganese is primarily excreted in the feces via bile
Also, 60-80% of manganese is contained in RBCs.
(TRUE/FALSE)
Hypothyroidism is a secondary cause of osteoporosis.
FALSE
HYPERthyroidism
What is the prime indicator (lab value) for cholestasis?
Serum conjugated (direct) bilirubin
If a patient on long-term PN develops hepatic dysfunction, what two trace elements should be monitored?
Manganese and copper, on a regular basis, and may need to be removed from PN solution if serum levels are elevated
Symptoms of SOB, cough, cyanosis of the face, neck, shoulder, and arms, indicates which device complication?
Superior vena cava syndrome
Define sentinel event.
A patient safety event of an unexpected occurrence involving death or serious physical/physiological injury, or the risk thereof.
Serious injury specifically includes loss of limb OR function.
These are examples of??
- Medication errors
- Wrong-site surgery
- Restraint-related deaths
- Blood transfusion errors
- Preoperative/postop complications
Sentinel events
A scientific basis that focuses on a process that leads to a certain outcome, is?
Process measure
An evaluation of processes or outcomes of care associated with the delivery of clinical services, is?
Clinical measures
Quality measures that emphasize research, proximity, accuracy, and adverse effects in order to result in positive patients outcomes, are?
Accountability
(TRUE/FALSE)
Prophylactic use of antibiotic ointment at the catheter exit site is recommended for preventing catheter-associated sepsis?
What about antibiotic prophylaxis during catheter insertion?
FALSE
Abx ointment only encourages the development of resistant flora and should be avoided
FALSE, abx have not been demonstrated to reduce the incidence.
What are the 3 research recommendations as primary interventions for reducing risks of CVAD-related infections?
- Using the maximal barrier technique during catheter insertion
- Cleansing insertion sites with 2% chlorhexidine preparation
- Education and training of health care personnel
What are 3 signs of a catheter-related bloodstream infection?
- Bacteremia/fungemia with at least 1 positive blood culture
- Clinical manifestations, such as fever
- No apparent source except the catheter
**They often present WITHOUT redness or purulence (pus) at the catheter site
What is Malassezia furfur?
A yeast
Classically associated with superficial infections of the skin and associated structures
Occurs most commonly in premature infants and patients receiving PN containing ILE\
Treatment:
- Antifungal
- D/C ILE
- Removal of the intravascular catheter (especially with non-tunneled catheter infections)
What are these hallmark symptoms of (arm, shoulder or neck swelling, limb, jaw, or ear pain, and dilated collateral veins over the arm, neck, or chest) typically indicate?
Catheter-related central venous THROMBOSIS
What is the most common metabolic complication associated with PN?
Hyperglycemia
Cholestasis has been associated with ILE doses greater than __ gm/kg/day in adult patients receiving long term PN
1 gm/kg/day
ASPEN recommended phosphorus dose for PN formulation?
20-40 mmol/day
What is calcium supplementation in PN limited by?
Limited by calcium’s physical compatibility with phosphorus
How can excessive vitamin D be detrimental to the bone?
Excessive vitamin D can suppress parathyroid hormone and promote bone resorption
How does stress-associated hyperglycemia develop?
As a result of insulin resistance, increased gluconeogenesis, and suppressed insulin secretion
What is the ASPEN recommended target BG concentration in adult hospitalized patients?
140-180 mg/dL
What conditions has excessive carbohydrate administration been associated with?
Hyperglycemia, hepatic steatosis, and increased carbon dioxide production
In acutely ill patients, carbohydrate administration should not exceed a rate of:
4-5 mg/kg/min or 20-25 kcal/kg/day
When would the delivery of ~100 gm dextrose be warranted?
If the patient has a low BMI or poor glucose control
How often should capillary blood glucose concentrations be monitored in patients receiving short-acting subcutaneous insulin?
Every 6-8 hours
What is a common initial insulin regimen in PN?
0.05 to 0.1 units per gram of dextrose
0.15 to 0.2 units per gram of dextrose if patient is already hyperglycemic
What kind of insulin should be added to the PN formulation?
Regular insulin
What clinical outcomes is hyperglycemia associated with?
Increased risk of infection
Poor wound healing
Inability to gain weight
How can PN-associated hypoglycemia occur?
Excess insulin administration via the PN solution, IV infusion, or subcutaneous injection
What are treatment methods for PN-associated hypoglycemia?
Initiation of a 10% dextrose infusion, administration of an ampule of 50% dextrose, and/or stopping any source of insulin administration. Can also consider oral carbohydrate (glucose gel or chewable tablets) in mild hypoglycemia in patients who can tolerate it
What has been associated with rebound hypoglycemia?
Abrupt discontinuation of PN
How can the risk of rebound hypoglycemia be reduced?
1- to 2-hour taper down of the infusion, or half the infusion rate
What should be done if a PN solution must be discontinued quickly?
A dextrose-containing fluid should be infused for 1 to 2 hours following PN discontinuation to avoid a possible rebound hypoglycemia
ILE-free PN may result in what deficiency?
Essential fatty acid deficiency (EFAD)
What are clinical manifestations of EFAD?
Scaly dermatitis
Alopecia
Hepatomegaly
Thrombocytopenia
Fatty liver
Anemia
After what length of time receiving an ILE-free PN can EFAD occur?
Within 1-3 weeks in adults receiving ILE-free PN
Adult requirements for linoleic acid are met through exogenous sources or endogenously through the lipolysis of adipose tissue, but what can happen when hypertonic dextrose is infused?
Insulin is secreted and lipolysis is reduced, necessitating an exogenous source of fat provision
To prevent EFAD, what percent of daily energy requirements should be derived from linoleic acid and linolenic acid?
1-2% from linoleic acid
0.5% from linolenic acid
What is the infusion goal of 10% and 20% soy-based ILE administration to prevent EFAD?
500 ml of 10% soy-based ILE administered over 8-10 hours twice a week OR
250 ml of 20% soy-based ILE administered over 8-10 hours twice a week OR
500 ml of a 20% soy-based ILE given once a week
What needs to be considered (regarding preventing EFAD) when using an alternative oil-based ILE (such as those containing MCTs, olive oil, fish oil)?
A greater amount of ILE is required to meet essential fatty acid requirements because these non-soy based products contain lower quantities of linoleic and linolenic acid
How has linoleic acid (aka omega-6) been postulated to suppress the immune response?
By activating the arachidonic pathway
How is it suggested that certain long-chain fatty acids may impair immune function?
By interfering with phagocytosis and chemotaxis and may increase the patient’s risk of infection