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
What has been suggested as a strategy to reduce immunosuppression complications in critically ill patients receiving PN?
Withholding or limiting soy-based ILE for the first week of PN - recommendation based primarily on research from only 1 study
When can hypertriglyceridemia occur with PN?
With dextrose overfeeding or with rapid administration rates of ILE (>0.11 gm/kg/hour)
What complications may result from hyperlipidemia?
May impair immune response, alter pulmonary hemodynamics, increase risk of pancreatitis
What amount should ILE intake be restricted to?
<30% of total energy, or 1gm/kg/day
What are the ASPEN recommendations regarding serum triglyceride levels and the appropriate response?
Serum TG >400 mg/dL should be avoided when infusing ILE, and the ILE dose should be reduced or discontinued if this level of hypertriglyceridemia occurs
Why should the dose of ILE be reduced or discontinued in the mechanically ventilated patient receiving Propofol?
Because Propofol is supplied as a 10% ILE
Is ILE considered safe for use in pancreatitis without hypertriglyceridemia?
Yes
What condition is rare unless serum TG levels exceed 1000 mg/dL?
Pancreatitis due to ILE-induced hyperlipidemia
What happens when protein administration is excessive?
The metabolic demand of disposing of the byproducts of protein metabolism increases
Why are patients with hepatic or renal disease prone to developing azotemia?
Because their ability to metabolize and eliminate urea is impaired
What can cause prerenal azotemia?
Dehydration, excess protein, and/or inadequate energy from nonprotein sources
Should protein be restricted in critically ill patients with AKI?
Not if they are receiving CRRT or HD, especially in the setting of malnutrition
If a patient has excessive fluid losses, should fluid and electrolyte replacement be added to the PN formulation or provided separately?
Separately
What parameters should be monitored, and with what frequency, to help identify and prevent metabolic complications in a patient initiating PN?
Before PN is initiated, should evaluate patient’s vital signs, I/O, and physical exam data to determine their fluid status. Complete metabolic panel including phos and magnesium. PN may be administered slowly and titrated to goal over a period of days to prevent hyperglycemia. BG levels monitored at least every 6 hours until patient is euglycemic
What situations may complicate provision of adequate vitamin intake in the PN?
Conditions that increase requirements, such as sepsis, trauma, or recovery following surgery
Why can identifying vitamin deficiency or toxicity be difficult?
Serum vitamin concentrations do not always directly correlate with body stores and clinical symptoms are often nonspecific
Why do patients receiving both PN and warfarin therapy require close monitoring?
Because the vitamin K (150 mcg) included in the 13-vitamin preparation interacts with warfarin and can result in therapeutic failure
Patients with a history of prolonged poor dietary intake or alcohol abuse are at risk for what deficiency?
Thiamin
What amount of additional supplemental thiamin and folic acid is recommended (beyond what is provided in the PN multivitamin preparation) for the initial 5-7 days of PN therapy for patients with a history of prolonged poor dietary intake?
50-100 mg thiamin
1 mg folic acid
In what population has vitamin A toxicity been reported in those patients receiving PN?
Renal failure
What needs to be considered regarding vitamin addition to PN solution for home infusion?
PN is compounded in a batch fashion for the home setting. Several vitamins are known to undergo substantial degradation after addition to the PN formula. In the home setting, the patient or caregiver must perform the task of adding vitamins to the PN formulation prior to administration
ASPEN advice to help clinicians cope with parenteral multivitamin product shortages:
Reserve a supply of IV multivitamins for those patients receiving solely PN
Use oral or enteral MVI whenever possible
Do not stockpile parenteral MVI
Do not use pediatric IV multivitamin for adults
Ration use by reducing the dose by 50% or by giving 1 dose 3 times/week when all options to obtain IV MVI have been exhausted
Administer individual thiamin, ascorbic acid, pyridoxine, and folic acid daily if IV MVI are no longer available
Under what circumstances could trace element deficiency occur (also name specific situations)?
When intake is insufficient or utilization or excretion is increased over a prolonged period. Patient with high intestinal output may become zinc deficient. Cardiomyopathy caused by selenium deficiency has been reported in patients receiving long-term PN without selenium supplementation
True or False: Available parenteral multi-trace element preparations may be lacking in actual requirements in patients receiving PN
False. May exceed actual requirements
Why should clinicians consider reducing manganese and copper dosing in patients with hepatobiliary disease?
The hepatobiliary disease impairs excretion
What are the ASPEN suggestions when facing a parenteral multi-trace element shortage?
Reducing doses in half
Limiting the frequency of administration to 3x/week
Using oral/enteral route when feasible
Withholding multi-trace elements for the first month of PN therapy in newly initiated adult patients who are not critically ill and do not have preexisting deficits
What is the time frame after initiation of nutrition support when refeeding syndrome is a risk?
During the first 2-5 days after the start of nutrition support
In periods of prolonged starvation, how does the body adapt?
By deriving energy from fat (ketone production), reducing energy expenditure, decreasing insulin secretion, and utilizing intracellular minerals and electrolytes
How can complications of refeeding syndrome be minimized when providing PN to a nutritionally depleted patient?
Scenario: Patient w/ h/o gastric cancer s/p partial gastrectomy and small bowel resection. NG output 1250 ml/day w/ SBO. BMI 20, UBW 75 kg, currently 66 kg. Shows evidence of moderate muscle and fat wasting with slight edema
Start nutrition slowly by providing half of the goal energy requirements (~15 kcal/kg/day) on the first day of PN. First bag should contain about 1000 kcal. Start at goal protein dose (1.2-1.5 g/kg/day). Dextrose and fat should comprise the rest of the formulation (dextrose not to exceed 200 gm/day). Slowly advance to goal over the next 2-5 days while monitoring electrolytes daily (Na, K+, Phos, Mg). Administer vitamins and trace elements daily
Aside from refeeding syndrome, what other conditions may cause refeeding hypophosphatemia?
Cellular phosphate redistribution, poor phosphate intake, or renal tubular phosphate loss
What are the 3 types of hepatobiliary disorders associated with PN therapy?
Steatosis (hepatic fat accumulation), cholestasis, and gallbladder sludge/stones
The term PN-induced liver disease has been replaced with which two interchangeable terms?
PN-associated liver disease (PNALD) and intestinal failure-associated liver disease
How does steatosis typically present?
Modest elevations of serum aminotransferase (aka transaminase) concentrations that occur within 2 weeks of PN therapy, and concentrations may return to normal even when PN is continued. Most patients are asymptomatic
What does steatosis seem to be a complication of during PN therapy?
Complication of overfeeding. Has probably decreased in prevalence over the years as estimates of PN energy requirements have been lowered
What may steatosis progress to?
May progress to fibrosis or cirrhosis in patients receiving long-term PN
What is PN-associated cholestasis (PNAC)?
A condition of impaired secretion of bile or frank biliary obstruction that occurs predominantly in children, but may occur in adult patients receiving long-term PN
How does PNAC typically present?
Elevated alkaline phosphatase, GGT, and direct bilirubin with or without jaundice.
What is the prime indicator for cholestasis?
A direct bilirubin >2 mg/dL
Why is PNAC considered a serious complication?
It may progress to cirrhosis and liver failure
What may gallbladder stasis during PN therapy progress to?
The development of gallstones or gallbladder sludge with subsequent cholecystitis
Rather than being related to PN infusion itself, what is gallbladder stasis during PN therapy more related to?
The lack of enteral stimulation which results in decreased cholecystokinin release and impaired bile flow and gallbladder contractility. Duration of PN therapy seems to correlate with the development of biliary sludge
What is acalculous cholecystitis?
Biliary sludge progressing to acute cholecystitis in the absence of gallstones
The risk for and severity of liver disease increases or decreases as the duration of PN usage lengthens?
Increases
What are risk factors for PNALD that are unrelated to the PN therapy itself?
Bacterial and fungal infections (associated with cholestasis)
Sepsis (likely causes liver inflammation due to release of proinflammatory cytokines) and recurrent central line-associated bloodstream infections
SIBO
Massive intestinal resection
Small bowel remnant <50 cm in length
What is the development of steatosis during PN administration primarily related to?
Excessive energy intake, promotes hepatic fat deposition by stimulating insulin release, which in turn promotes lipogenesis and inhibits fatty acid oxidation
What complications may arise from dextrose-based PN that contains little or no fat?
Development of steatosis. Excess carbs deposit in the liver as fat. Dextrose-based PN may result in EFAD which may lead to impaired lipoprotein formation and triglyceride secretion, resulting in steatosis
A balanced PN formulation should provide __ to __% of nonprotein energy as carbohydrate and __ to __% as fat
70-85% of nonprotein energy as carbohydrate
15-30% as fat
The carbohydrate content of PN should not exceed __ gm/kg/day in adults
7 gm/kg
High levels of what trace element exposure may lead to the development of cholestasis?
Aluminum
How might phytosterols contribute to biliary sludge and stones?
They are inefficiently metabolized to bile acids by the liver and may impair bile flow
High omega-6 fatty acid content of soybean oil-based ILEs may contribute to what kind of complications?
May potentially initiate or worsen inflammatory states and can have immunosuppressive effects
What has shown promising effects in reversing PNALD in pediatric patients?
Using fish oil-based ILE, primarily composed of omega-3 fatty acids and containing no phytosterols when used in place of a soybean oil-based ILE
Chronic cholestasis and severe PNALD were strongly associated with ILE intake greater than __ gm/kg/day in patients receiving long-term PN
> 1 gm/kg
What has carnitine supplementation to PN been shown to accomplish?
Helps mobilize hepatic fat stores and prevent steatosis in neonates receiving PN
Why is choline not a component of PN formulations?
It is assumed that endogenous synthesis is possible from methionine contained in the crystalline amino acid solution. Also an injectable choline preparation is not commercially available
List PN modification strategies to manage PN associated liver complications
Decreasing dextrose
Decreasing ILE (<1 gm/kg)
Providing a balance of dextrose and ILE
Cyclic PN infusion
List ways to prevent/treat bacterial overgrowth that may contribute to PN associated liver complications
Use enteral antibiotics, such as metronidazole, neomycin, doxycycline, ciprofloxacin, or rifaximin
In CIPO patients, consider agents to enhance motility such as metoclopramide or erythromycin
List strategies to manage PN associated liver complications
Rule out non-PN etiologies for liver problems such as hepatotoxic medications, herbal supplements, biliary obstruction, hepatitis, sepsis
Consider PN modifications
Maximize enteral intake
Prevent/treat bacterial overgrowth
Pharmacotherapy
Consider intestinal transplantation for patients with PN failure
How can a PN formulation be modified to minimize and manage the development of cholestasis in an adult patient requiring long-term PN?
Could reduce the frequency of ILE from daily to twice weekly and increase dextrose proportionally to account for decrease in energy from lipid
Trial of stopping ILE for 1-2 weeks
Shorten the infusion cycle
Avoid overfeeding
Efforts to minimize the risk of infection
Why should oral and enteral nutrition be optimized whenever feasible in the long-term PN patient?
Even small amounts of dietary or enteral intake may promote enterohepatic circulation of bile acids
How may cyclic PN reduce the risk of PNALD, especially in patients who depend on long-term PN?
By reducing liver enzyme and direct bilirubin concentrations when compared with continuous PN infusion
Why are patients receiving PN at risk for negative calcium balance?
Because of limited intake and increased urinary calcium loss
What is the smallest pore size filter that is recommended for total nutrient admixture (TNA)?
1.2 micron
According to recommendations by ASPEN parenteral nutrition safety consensus and the National Advisory Group on Standards and Practice Guidelines for parenteral formulations, the amount of dextrose used in preparation of a PN formulation is required to appear on the label as:
Grams per day (eg, dextrose 250 gm/day)
What is the most commonly used carbohydrate energy substrate in PN?
Dextrose
Amount of kcal per gram from dextrose?
3.4 kcal/gm
What concentrations is dextrose available in?
2.5-70%
Why are higher dextrose concentrations (>10%) generally reserved for central venous administration?
Because of their propensity to cause thrombophlebitis in peripheral veins
Amount of kcal per gm in glycerol (glycerin)?
4.3 kcal/gm
What is the nitrogen content of amino acid products?
Varies, but for nitrogen balance calculations, amino acid products are generally assumed to be 16% nitrogen
6.25 gm amino acid = 1 gm nitrogen
What are the most frequently used amino acid concentrations used in PN compounding?
8.5%, 10%, and 15%
What concentrations are amino acids available in?
3.5-20%
What is the theory behind modified amino acid formulations marketed for use in renal failure that are composed primarily of essential amino acids?
Theory that nonessential amino acids can be physiologically recycled from urea, whereas essential amino acids must be provided from the diet
Do essential amino acid formulations offer a significant advantage in renal failure?
No
What are the 2 ILE formulations available in the US?
Intralipid and Smoflipid
The 2 ILE formulations available in the US are composed solely of what kind of triglycerides?
Long-chain triglycerides
What are the available concentrations of commercial ILE formulations?
20% and 30%
What is the kcal content of 20% ILE concentrated formula?
2 kcal/ml
What is the kcal content of 30% ILE concentration formula?
2.9-3 kcal/ml, depending on the manufacturer
Are 10% ILE formulations available for PN?
No, currently marketed only in premixed products and products with a lipid emulsion such as Propofol.
What effect does the high phospholipid:triglyceride ratio of 10% ILE have?
Increases the presence of free phospholipids, which interfere with lipoprotein lipase activity, thereby decreasing the lipid clearance rate
Is ILE 30% formula available for direct IV administration?
No. ILE 30% formulation is approved only for the compounding of a 3-in-1 admixture (ie, TNA)
What are the major component fatty acids in the 100% soybean based ILE?
Linoleic acid, oleic acid, palmitic acid, alpha-linolenic acid, stearic acid
Do ILE products using a 50:50 mix of soybean oil and safflower oil contain more or less omega-3 fatty acids than ILE using 100% soybean oil?
Less. Safflower oil contains only a trace of alpha-linoleic acid. Contain half as much omega-3 fatty acid (alpha-linolenic acid) as 100% soybean oil ILE
What led to the development of alternative ILE formulations made from various oil sources?
Concern about the high content of proinflammatory omega-6 polyunsaturated fatty acids (PUFA) in traditional ILE
Describe the general composition of Smoflipid and the percent concentration that is available?
Smof refers to the types of oils in it: soybean oil (30%), medium-chain triglycerides (30%), olive oil (25%), and fish oil (15%). Available as a 20% solution
What is the mean essential fatty acid concentration of Smoflipid?
35 mg/mL linoleic acid
4.5 mg/mL alpha-linolenic
Compared with soybean oil-based ILE, what clinical outcomes has Smoflipid been associated with?
Reduced liver changes and the preservation of antioxidant capacity in pediatric home PN patients, adult intestinal failure long-term PN patients, and critically ill patients
What are the other components of ILE formulations (aside from oils) and their purpose?
Egg phospholipid emulsifier (contributes 15 mmol phosphate per liter)
Glycerin to render the formulation isotonic
Sodium hydroxide to adjust the final pH to a range of 6-9
What rate should the ILE infusion rate not exceed (whether infused separately from amino acids and dextrose or as a TNA)?
Should not exceed 0.11 gm/kg/hour
What are infusion rates >0.11 gm/kg/hour of ILE associated with?
Increased risk of adverse effects such as hypertriglyceridemia, infectious complications, and fat overload syndrome (headaches, seizures, fever, jaundice, hepatosplenomegaly, abdominal pain, respiratory distress, pancytopenia, shock)
The daily dose of ILE should not exceed what % of total energy requirements?
Should not exceed 60% of total energy requirements or 2.5 gm/kg/day
What are the ASPEN/SCCM guidelines regarding soybean oil-based ILE in critical illness?
Suggest clinicians either withhold soybean oil-based ILE or limit it to a maximum of 100 gm (often divided into 2 doses) during the first week following initiation of PN if the patient is at risk for EFAD
Why do many clinicians limit soybean oil-based ILE to 1 gm/kg/day
Because of higher omega-6 fatty acid provision
What is the most dramatic impact seen with the use of ILE rich in omega-3 fatty acids?
Seen in the treatment of pediatric intestinal failure associated liver disease, with more rapid and frequent cholestasis reversal with fish oil-based ILE compared to soybean oil-based ILE
What advantages do olive-oil based fat emulsions (such as Clinolipid) have?
Offer advantages over the current polyunsaturated LCT ILE, including decreased peroxidation and a lack of in vitro lymphocyte function inhibition. Found to be clinically safe and well tolerated with a tendency to preserve hepatic function
What is the preferred form of calcium for PN?
Calcium gluconate
What is the preferred form of magnesium for PN?
Magnesium sulfate
Daily parenteral requirement for sodium?
1-2 mEq/kg
Daily parenteral requirement for potassium?
1-2 mEq/kg
Daily parenteral requirements for chloride and acetate?
As needed to maintain acid-base balance
Daily parenteral requirement for calcium?
10-15 mEq
Daily parenteral requirement for magnesium?
8-20 mEq
Daily parenteral requirement for phosphate?
20-40 mmol
Commercially available parenteral sodium salts?
Acetate, chloride, phosphate, bicarbonate, lactate
Commercially available parenteral potassium salts?
Acetate, chloride, phosphate
Commercially available parenteral chloride salts?
Sodium, potassium
Commercially available parenteral calcium salts?
Gluconate, gluceptate, chloride
Commercially available parenteral acetate salts?
Sodium, potassium
Commercially available parenteral magnesium salts?
Sulfate, chloride
Commercially available parenteral phosphate salts?
Sodium, potassium
What form of sodium salt should be avoided in PN mixtures?
Bicarbonate and lactate
What form of calcium should be avoided in PN mixtures?
Calcium chloride
What are the ASPEN recommendations for reducing complications from adult trace element products?
Decrease copper to 0.3-0.5 mg/day
Decrease manganese to 55 mcg/day
Manufacturing a product with no chromium (or max of 1 mcg/day)
Including selenium in all products at a higher dose of 60-100 mcg/day
Trace element contamination in PN formulations be limited to <0.1 mg/day of copper and 40 mcg/day of manganese
Why is no FDA-approved IV form of glutamine commercially available in the US?
Poor solubility and stability and compatibility limitations
Is parenteral glutamine supplementation recommended for adult critically ill patients?
No, recent literature indicates either a lack of infectious and mortality benefit or even higher mortality rates when IV glutamine is compared with placebo
What is carnitine?
A quaternary amine necessary for proper transport and metabolism of long-chain fatty acids in to the matrix of the mitochondria for beta-oxidation
What populations are susceptible to carnitine deficiency?
Neonates and infants
What is the most appropriate strategy to provide calcium to a patient receiving PN in the event of an IV calcium gluconate shortage?
Scenario: Surgical pt requiring central PN has a single-lumen PICC. Lab data: Ca 7.1 (normal 8.5-10.2), Mg 1.4 (normal 1.6-2.2), Phos 1.3 (normal 2.5-4.5), Albumin 2.6 (normal 3.5-5), ionized Ca 2.25 (normal 2-2.5). Because of a national shortage of IV concentrated calcium gluconate, the only available salt form available for use is calcium chloride
Remove calcium from PN formulation and monitor ionized calcium concentrations for evidence of calcium deficiency. If calcium supplementation is necessary, administer calcium chloride separately from the PN formulation, taking care not to infuse IV calcium through the same catheter as the PN formulation. Corrected calcium level for a decreased albumin concentration for this pt is 8.2, but the ionized calcium is normal.
What are the two formats that PN admixtures can be prepared in?
Traditional dextrose-amino acid (2-in-1) formulation
Total nutrient admixture (TNA) system aka 3-in-1 admixture aka all-in-1 admixture
What is a 2-in-1 PN formulation?
Dextrose-amino acid format incorporates the dextrose and amino acid-base solutions along with the prescribed electrolytes, minerals, vitamins, and trace elements in either a single container or multiple containers each day. ILE is administered separately as a piggyback infusion
What is a TNA?
Incorporates dextrose, amino acids, ILE, and the prescribed micronutrients together in the same container for final administration
Which process involves more manipulation: 2-in-1 formulation plus separate ILE or 3-in-1 formulation?
Administering TNA involves less manipulation than administering 2-in-1 formulation with separate ILE, and is therefore less risk of contamination of the system during administration
In what settings may TNA be more cost-effective overall?
It requires less nursing time because it is administered via a single container per day and there is no piggyback ILE to administer. The supply and equipment expenses are lower with TNA because only 1 infusion pump and IV tubing are needed
Why might TNA have possible applications in fluid-restricted patients?
Because ILE 30% is restricted to use in TNA
What is an advantage of TNA in regard to fat clearance?
Fat clearance may be better when ILE is administered over more than 12 hours
Is admixed ILE in TNA more or less stable and more or less prone to separation of lipid components than 2-in-1 with separate ILE?
TNA admixed ILE is less stable and more prone to separation of lipid components
Under what circumstances are TNA formulations more sensitive to destabilization?
When they have greater divalent and monovalent electrolyte concentrations and low concentrations of dextrose and amino acids
Would higher or lower pH formulations be more prone to destabilize the ILE portion of TNA?
Lower pH (more acidic)
Compatibility and solubility of calcium gluconate and sodium/potassium phosphate are more or less in TNA formulations than 2-in-1 formulations?
Less
What characteristic of admixed ILE precludes the use of 0.22 micrometer filters?
Larger particle size. Requires larger pore size filter of 1.2 micrometers (not bacteria-eliminating)
In some situations, dextrose and venous access tolerance may be better or worse with TNA than with 2-in-1 formulations?
Better
TNA is more or less stable over time than dextrose-amino acid PN formulations with separate ILE?
Less
What criteria are important to decrease the risk of thrombophlebitis and damage to peripheral veins in PN is to be administered via a true peripherally inserted catheter (not PICC)?
Osmolarity below 900 mOsm/L
Calcium and potassium concentrations should be kept low (Calcium less than or equal to 5 mEq/L, Potassium less than or equal to 40 mEq/L whenever possible)
ILE given daily to provide adequate energy and decrease osmolarity
What is the desired concentration of dextrose and amino acids in TNA to help prevent lipid destabilization from divalent cations and what are the consequences of these concentrations?
Desired concentration of dextrose in >10%
Desired concentration of amino acids is >4%
May limit the ability to adhere to the osmolarity restrictions of PPN
What does SCAPN stand for?
Standardized Commercially Available Parenteral Nutrition
What formulations and via which parenteral route are SCAPNs available in?
Available for central and peripheral vein administration as dextrose-amino acid (2-in-1) formulations with and without electrolytes and 3-in-1 formulations with electrolytes
In SCAPNs, why is there an internal membrane that must be broken just before administration that separates macronutrients into different chambers of the product?
To prevent a chemical reaction that alters the integrity of the dextrose and amino acids (Maillard reaction)
Why do SCAPNs not have multivitamins already added to them?
Multivitamin injection must be added shortly before administration because vitamins are essential components of PN that are not stable when added more than 24 hours in advance of use
What are the defining features of the SCAPN ProcalAmine?
Glycerol-based product that can be used for short term PPN administration. Final concentration of 3% amino acids, 3% glycerol, and electrolytes. Can be premixed and sterilized in a single bottle w/o undergoing the Maillard reaction because glycerol is a sugar alcohol
What are the general final concentrations of dextrose and amino acids in SCAPN 2-in-1 products for central vein infusion?
Dextrose 10%, 15%, 20% , or 25%
Amino acids 2.75%, 4.25%, 5%
What is the osmolarity of SCAPN 2-in-1 products for central vein infusion?
> 900 mOsm/L
What are the final concentrations of dextrose and amino acids in SCAPN 2-in-1 products for peripheral vein infusion?
Dextrose 5%
Amino acids 2.75%, 3.5%, or 4.25%
What is the osmolarity of SCAPN 2-in-1 products for peripheral vein infusion?
<900 mOsm/L
What is the osmolarity of and concentration of dextrose, amino acids, and lipids of SCAPN 3-in-1 products with electrolytes for central vein administration?
Osmolarity 1060 mOsm/L
Dextrose 9.7%
Amino acids 3.3%
Lipids 3.8%
What is the osmolarity of and concentration of dextrose, amino acids, and lipids of SCAPN 3-in-1 products with electrolytes for peripheral vein administration?
Osmolarity 750 mOsm/L
Dextrose 6.7%
Amino acids 2.4%
Lipids 3.5%
What are potential advantages of SCAPN products?
Reduction in costs, decreased compounding time, less risk for ordering and compounding errors, and fewer bloodstream infections. Shelf stable and heat sterilized, allowing for more time before expiration than compounded PN
In what settings may SCAPN products be preferred over compounded PN?
In settings where PN is used infrequently or irregularly (rural hospitals or LTC). May be used for first-dose or starter PN, as a backup system, and during after-hour and weekend shifts
In what patient populations may SCAPN products not be appropriate?
Those with increased protein requirements or labile fluid status (obese or critically ill), those with conditions that cause significant electrolyte wasting (eg high output ostomy) or conditions that decrease electrolyte clearance (eg renal insufficiency)
What does the stability of PN formulations mean?
Refers to the degradation of nutritional components that changes their original characteristics. Example: Maillard reaction that occurs between IV dextrose and certain amino acids (lysine).
May also refer to the ability of PN additives (medications) to maintain their chemical integrity and pharmacological activity (photodegradation from light exposure results in loss of some vitamins such as cyanocobalamin, folic acid, phytonadione, pyridoxine, riboflavin, thiamin, retinol)
What does the compatibility of PN formulations mean?
Generally involves the formation of precipitates. Precipitates may be solid (crystalline matter) or liquid (phase separation of oil and water in TNA)
Should medications be added to PN formulations?
Should not unless there is clear evidence from 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
What can happen if the surface charge of the fat droplets in ILE become less negative?
Fat droplets begin to aggregate into larger fat globules (>1 micron in diameter), and the emulsion becomes unstable
Why does an ILE become unstable and unsafe for administration if the fat droplets begin to aggregate into larger fat globules?
Fat globules may lodge in the pulmonary vasculature, compromising respiratory function
What are some factors that may alter the electrical charge on the fat droplet surface in an ILE?
Reductions in pH and the addition of electrolyte salts
What pH range is most favorable for ILE stability?
pH 6-9
Additives to ILE that lower the pH <5 or >10 may cause what?
May irreversibly destabilize or “crack” the emulsion
What happens when an ILE “cracks”?
The oil phase separates from the water phase
Why is a low pH in an ILE especially damaging?
In addition to the effects on the electrical charge, the egg phospholipid emulsifier begins to degrade
How do MCTs improve ILE stability?
MCTs are usually derived from coconut or palm kernel oils and improve ILE stability by displacing LCTs at the droplet surface and by reducing stress on the emulsifier because of the shorter hydrocarbon chain
What is the most critical factor influencing the pH of a PN formulation?
The crystalline amino acid solution used for compounding. The final pH of a PN formulation is generally very near that of the amino acid solution unless the buffering capacity of the amino acids has been overwhelmed by other PN components
Amino acids with a pH range of __ to __ are generally acceptable for use in TNA compounding
pH of 5.8 to 7
The pH of crystalline amino acid solutions ranges from __ to __
5.2 to 7
What does the addition of cysteine hydrochloride to a PN formulation do?
Renders the pH of the final admixture to be less than 5, promoting ILE destabilization
Why would some prescribers request the use of pediatric amino acid products in adult PN patients?
Pediatric amino acid formulations are the only products with taurine, and L-cysteine hydrochloride may be added to an adult PN formulation to increase calcium phosphate solubility (eg, when a patient is eliminating high amounts of calcium in response to foscarnet therapy)
Why should a concentrated dextrose solution not be added directly to ILE?
Because a concentrated dextrose solution has an acidic pH. It should first be combined with the amino acid solution during compounding because the amino acid solution serves as a buffer, and low final concentrations of amino acids (<4%) may not provide adequate buffer capacity to prevent destabilization of TNA
What are the limitations in compounding (3-in-1 vs 2-in-1) when compounding a peripheral PN solution?
Patient scenario: Pt is NPO for 5 days due to mandibular fracture and impending surgery. On hospital day 7, diet advanced to full liquid but found to have partial SBO. PPN is initiated because long-term (>10 days) PN is not anticipated and primary physician does not want a central line placed due to risk of infection
2-in-1 PN formulation with a separate infusion of ILE should be prepared. TNA should be used with extreme caution or not at all as PPN formulations.
What calcium phosphate precipitate poses the greatest potential threat for lethal precipitants in PN admixture?
Dibasic calcium phosphate. Virtually insoluble in water, is commonly implicated in reports of significant morbidity and mortality among patients receiving incompatible mixtures
List the factors that increase the risk of calcium phosphate precipitation
Increased calcium concentration
Increased phosphate concentration (including amino acids with phosphorus content)
Calcium chloride salt use (instead of calcium gluconate)
Increased temperature of PN admixture
List the factors that increase calcium phosphate solubility
Increased amino acid concentration
Increased dextrose concentration
Lower pH of the PN admixture
How can lipid destabilization with divalent cation concentrations between 16-20 mEq/L be prevented?
By making the final concentration of monohydrated dextrose >10% and final amino acid concentration >4%
Name a trivalent cation that has a high destabilizing effect on ILE
Fe 3+
How can excess cation (particularly calcium or magnesium) amounts influence lipid destabilization?
Can reduce or neutralize the negative surface charge exerted by the emulsifier, thereby removing the repulsive force and allowing fat particles to combine
Can iron dextran be added to TNA?
No because of instability issues
What factor plays a major role in dictating the solubility of calcium and phosphate in PN?
The pH of the final PN formulation
Does lowering the pH of the PN admixture increase or reduce the likelihood that calcium and phosphate with precipitate?
Reduces
Why are clinicians discouraged from using TNA admixtures in neonatal and pediatric populations?
Relatively large doses of calcium and phosphorus are routinely required in neonatal PN to optimize bone formation. Pediatric amino acid products are formulated at a lower pH. L-cysteine hydrochloride (also considered a semiessental amino acid in premature infants) can be added to further decrease pH and thereby increase calcium and phosphate solubility. The acidic pH creates an unfavorable environment for ILE and may destabilize the final emulsion
At what concentrations of calcium must the risk of metabolic bone disease be considered?
When calcium provision is below 10-15 mEq/day
What circumstances cause adult patients to be at risk for aluminum toxicity?
Significant renal dysfunction
High intake of parenteral products such as PN
Iron deficiency
What size of filters are adequate for the removal of precipitates (calcium phosphate) and particulate matter (plastic fragments) from a PN formulation?
5 micron (relatively large-pore)
What size filters can remove pathogenic microorganisms such as Staphylococcus epidermis, E. coli, and Candida albicans from a PN administration line?
0.22 micron
What is a limitation of filters?
Fat particle sizes (even in the most stable formulations) contain fat droplets in excess of 5 microns. 0.22 micron filters are inappropriate for use with ILE
What filter size is recommended for use with ILE-containing PN formulations?
1.2 microns, to avoid particle shearing and instability that may occur with filters of smaller pore size
What size filter should be used with dextrose-amino acid PN admixtures (2-in-1)?
0.22 micron
How many filters would be required for administration of a 2-in-1 dextrose-amino acid mixture with a separate infusion of ILE?
2 filters: a 0.22 micron in-line filter for the dextrose-amino acid mixture and a 1.2 micron filter for the ILE (infused via a separate vascular access or infused via Y-connector with the filter placed closer to the patient than the 0.22 micron filter)
How often should in-line filters be changed?
With each new administration of PN
- every 24 hours for TNA and dextrose-amino acid formulations
- every 10-12 hours for ILE infused separately
Should PN be kept at room temp or refrigerated?
Refrigerated from the time it is compounded until it is administered
What is the CDC recommended hang-time for ILE (infused separate from dextrose-amino acids)?
12 hours
What is the CDC recommended hang-time for ILE incorporated into a TNA?
Up to 24 hours
Why is the administration and hang-time of TNA/3-in-1 PN formulations extended?
Bacterial growth is inhibited by the reduced pH (pH of 5.6-6) and the increased total osmolarity with the combination of all 3 substrates in 1 container
What is the maximum amount of dextrose the liver can oxidize? What is the usual rate that dextrose is administered at?
Maximum amount the liver can oxidize is 5 mg/kg/min
Usually administered at a maximum rate of 3 mg/kg/min
What percent of dextrose should be used for compounding PN in situations of fluid restriction?
50% or 70%
