Parenteral Nutrition Formulations Flashcards
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%
