Deaths in preterm infants after infusion of intravenous (IV) lipid emulsions have been reported in the medical literature. Autopsy findings included intravascular fat accumulation in the lungs. Preterm infants and low-birth-weight infants have poor clearance of IV lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion.
Parenteral nutrition: Note: The amount of lipid emulsion needed to prevent essential fatty acid deficiency (EFAD) varies based on age and lipid product; the amount of lipid emulsion (fish oil and plant based) required to prevent EFAD will be higher than the doses of plant based lipid emulsion (eg, Intralipid); use of restrictive dosing protocol with lipid emulsion (fish oil and plant based) may put patients at risk for EFAD (Carey 2019; ESPGHAN [Lapillone 2018]).
Preterm and term neonates: Limited data available: IV: Initial: 1 g/kg/day; increasing by 1 g/kg/day; maximum daily dose: 3 g/kg/day (Deshpande 2020). Studies have evaluated use of lipid emulsion (fish oil and plant based) in neonates with GA range of 23 to 41 weeks and birthweights of 390 to 4,400 g and have shown use is safe and well tolerated (Casson 2020; Rayyan 2012; Repa 2018; Savini 2013; Skouroloakou 2012; Stramara 2020; Tomsits 2010).
Parenteral nutrition: Note: The amount of lipid emulsion needed to prevent essential fatty acid deficiency (EFAD) varies based on age and lipid product; the amount of lipid emulsion (fish oil and plant based) required to prevent EFAD will be higher than the doses of plant based lipid emulsion (eg, Intralipid); use of restrictive dosing protocol with lipid emulsion (fish oil and plant based) may put patients at risk for EFAD (Carey 2019; ESPGHAN [Lapillone 2018]). For patients receiving other lipid emulsion-based medications (eg, propofol), take the lipid content provided from these medications into consideration and reduce dosage as needed to avoid adverse effects such as fat overload syndrome (ASPEN [Mirtallo 2020]).
Infants and Children: IV: Usual reported dose: 2 g/kg/day (Goulet 2010; Ho 2021; Lam 2018;); maximum daily dose: 3 g/kg/day; generally, lipids should account for ~25% to 50% of nonprotein calories (ESPGHAN [Lapillonne 2018]; Goulet 2020; Martindale 2020; Wassef 2021).
Adolescents: Limited data available: IV: Initial: 1 g/kg/day; increase gradually to 2 g/kg/day (Smoflipid prescribing information [Australia 2020]). Note: US labeling for adults has a maximum daily dose of 2.5 g/kg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Monitor liver function closely.
(For additional information see "Lipid emulsion (soybean, medium-chain triglyceride, olive, and fish oils; [SMOF]): Drug information")
Note: For patients receiving other lipid emulsion-based medications (eg, propofol, clevidipine), reduce dosage to avoid fat overload syndrome (ASPEN [Mirtallo 2020]).
Energy/calories: IV: 1 to 2 g/kg/day (ASPEN [Mirtallo 2020]); daily dose may be infused over 12 to 24 hours; maximum daily dose: 2.5 g/kg/day. Note: Lipid injectable emulsion (ILE) should provide 15% to 30% of energy (ASPEN [Mirtallo 2020]) and not exceed 60% of the total daily energy requirements. At the onset of therapy, observe patient for any immediate allergic reactions (eg, dyspnea, cyanosis, fever, pruritus [ASPEN (Mirtallo 2020)]).
Dosage adjustment for increased serum triglycerides: If triglycerides >400 mg/dL, lower dose/infusion rate or stop infusion and advance in smaller increments once triglycerides are <400 mg/dL. Use is contraindicated with triglycerides >1,000 mg/dL (ASPEN [Mirtallo 2020]; Siparsky 2021; manufacturer's labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Emulsion, Intravenous [preservative free]:
SMOFlipid: 20% (100 mL, 250 mL, 500 mL, 1000 mL) [contains egg phospholipids (egg lecithin)]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Emulsion, Intravenous:
SMOFlipid: 20% (100 mL, 250 mL, 500 mL) [contains egg phospholipids (egg lecithin)]
IV: Prior to opening the overwrap, the integrity indicator should be inspected. If the indicator is black, the overwrap is damaged; do not use. Gently invert bag prior to use. Do not use if discolored or if the emulsion contains a precipitate, phase separation, or there are leaks in the bag.
Experts recommend parenteral nutrition admixtures and lipid emulsions for neonates and infants be protected from light as soon as possible after preparation and through infusion (ASPEN [Robinson 2021]). Administer by IV infusion through a 1.2-micron in-line filter via peripheral line or central venous line using DEHP-free administration sets and lines. May be simultaneously infused with amino acid dextrose mixtures by means of Y-connector located near infusion site (flow rates of each solution should be controlled separately by infusion pumps). When administered with dextrose and amino acids, the choice of a central or peripheral infusion depends on the osmolarity of the final infusate (osmolarity ≥900 mOsm/L must be infused through a central vein). All lipid emulsion infusions should be filtered whether part of an admixture or infused separately using a 1.2-micron in-line filter only (ASPEN [Worthington 2021]; ISMP 2016). To prevent air embolism, use a nonvented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible bags in series, fully evacuate residual gas in the bag prior to administration, do not pressurize the flexible bag to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the bag runs dry. Change tubing after each infusion.
Pediatric: In reported experience, infusions have been over 24 hours in neonates, and over 12 to 24 hours in older pediatric patients. The maximum rate of infusion suggested: Neonates: 0.125 g/kg/hour, and in infants and children: 0.15 g/kg/hour (Biesboer 2016; Smoflipid prescribing information [Australia 2020]). In adult patients, an initial rate of 0.5 mL/minute for the first 15 to 30 minutes is recommended; if tolerated, may gradually increase to a maximum rate of 0.5 mL/kg/hour. A rapid infusion of Smoflipid leading to fat overload syndrome has been reported in the literature (Hojsak 2014).
IV: Administer by IV infusion through a 1.2-micron in-line filter via peripheral line or central venous infusion using DEHP-free administration sets and lines. Initial rate of infusion should be 0.5 mL/minute for the first 15 to 30 minutes; gradually increase until reaching the required rate after 30 minutes as tolerated. Do not exceed a rate of 0.5 mL/kg/hour. May be simultaneously infused with amino acid and dextrose mixtures by means of Y-connector located near infusion site (flow rates of each solution should be controlled separately by infusion pumps) and infused through a 1.2-micron in-line filter (Worthington 2021). When administered with dextrose and amino acids, the choice of a central or peripheral infusion depends on the osmolarity of the final infusate (osmolarity ≥900 mOsm/L must be infused through a central vein). All lipid emulsion infusions should be filtered whether part of an admixture or infused separately using a 1.2-micron in-line filter only (ISMP 2016; Worthington 2021). To prevent air embolism, use a nonvented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible bags in series, fully evacuate residual gas in the bag prior to administration, do not pressurize the flexible bag to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the bag runs dry.
Store at 20°C to 25°C (68°F to 77°F). Store in overpouch until ready for use; once removed from overpouch, use immediately. If not used immediately, the manufacturer suggests storing at 2°C to 8°C (35.6°F to 46.4°F) for no longer than 24 hours; after removal from refrigeration, the emulsion should be infused within 24 hours. Do not freeze. Avoid excessive heat.
Source of calories and essential fatty acids for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated (FDA approved in adults).
Lipid injectable emulsion may be confused with intravenous iron if abbreviated. If abbreviated, use intravenous lipid emulsion (ILE) to avoid confusion (ASPEN 2018; ASPEN [Mirtallo 2020]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Hypertension (3%), tachycardia (≤1%), thrombophlebitis (≤1%)
Central nervous system: Dizziness (≤1%), headache (≤1%)
Dermatologic: Pruritus (≤1%), skin rash (≤1%)
Endocrine & metabolic: Hyperglycemia (5%), increased serum triglycerides (3%), increased gamma-glutamyl transferase (≤1%)
Gastrointestinal: Nausea (9%), vomiting (7%), abdominal pain (4%), flatulence (4%), dyspepsia (2%), cholestasis (≤1%), diarrhea (≤1%), dysgeusia (≤1%)
Genitourinary: Urinary tract infection (2%)
Hematologic & oncologic: Anemia (2%), C-reactive protein increased (≤1%), leukocytosis (≤1%)
Hepatic: Abnormal hepatic function tests (≤1%), increased serum alkaline phosphatase (≤1%)
Local: Catheter infection (2%), sepsis (2%)
Respiratory: Dyspnea (≤1%), pneumonia (≤1%)
Miscellaneous: Fever (4%)
<1%, postmarketing, and/or case reports: Infection
Hypersensitivity to fish, egg, soybean, or any other component of the formulation; severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentrations >1,000 mg/dL). Note: Although the manufacturer's labeling lists hypersensitivity to peanut protein as a contraindication, the product does not contain peanut protein. However, a low risk of cross-reactivity between soy and peanuts may exist.
Canadian labeling: Additional contraindications (not in US labeling): Severe hepatic insufficiency; severe blood coagulation disorders; severe renal insufficiency without access to hemofiltration or dialysis; acute shock; acute pulmonary edema; hyperhydration; decompensated cardiac insufficiency; unstable conditions (eg, severe post-traumatic conditions, uncompensated diabetes mellitus, acute MI, CVA, embolism, metabolic acidosis, severe sepsis, hypotonic dehydration)
Concerns related to adverse effects:
• Fat overload syndrome: Although rare, a reduced or limited ability to metabolize lipids accompanied by prolonged plasma clearance resulting in a sudden deterioration in the patient's condition accompanied by fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, liver fatty infiltration (hepatomegaly), deteriorating liver function, and CNS (eg, coma) may occur; usually reversible upon discontinuation.
• Hepatic effects: Although the exact etiology is unknown and likely multifactorial, parenteral nutrition associated liver disease (PNALD) has been reported in patients receiving parenteral nutrition for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis, fibrosis and cirrhosis, possibly leading to hepatic failure; cholecystitis and cholelithiasis have also been observed. Consider discontinuation or dose reduction in patients who develop abnormal LFTs.
• Hypersensitivity: Contains soybean oil, fish oil, and egg phospholipids; hypersensitivity reactions may occur. Cross sensitivity has been observed between soybean and peanut. Discontinue use immediately if a reaction occurs and treat appropriately.
• Hypertriglyceridemia: Impaired lipid metabolism with hypertriglyceridemia may occur in conditions such as inherited lipid disorders, obesity, diabetes mellitus, and metabolic syndrome. Obtain baseline serum triglycerides before initiating therapy, at the time of each dosage increase, and regularly throughout treatment. In adults with triglycerides >400 mg/dL, reduce the dose and monitor triglycerides.
• Refeeding syndrome: Refeeding severely undernourished patients with parenteral nutrition may result in the refeeding syndrome (eg, intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic); thiamine deficiency and fluid retention may also develop. Carefully monitor severely undernourished patients and slowly increase their nutrient intakes, while avoiding overfeeding.
Disease-related concerns:
• Anemia: The use of fat emulsion has been associated with anemia likely due to hemodilution (Zellner 1967). Use with caution in patients with anemia.
• Bleeding disorders: Use with caution in patients with bleeding disorders.
• Fat embolism: Use with caution in patients who may be at danger for fat embolism.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Pancreatitis: Use with caution in patients with pancreatitis without hyperlipidemia.
• Renal impairment: Use with caution in patients with renal impairment; may contain aluminum, which may accumulate following prolonged administration in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
Special populations:
• Elderly: Energy expenditure and requirements may be lower in elderly patients.
• Pediatric [US Boxed Warning]: Deaths in preterm infants following administration of fat emulsion have been reported; autopsy findings included intravascular fat accumulation in the lungs. Premature infants, low-birth-weight infants, and small-for-gestational-age infants clear intravenous fat emulsion poorly and have increased free fatty acid plasma levels following fat emulsion infusion. The safe and effective use in pediatric patients, including preterm infants, has not been established.
Dosage form specific issues:
• Aluminum: May contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal impairment. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register 2002). See manufacturer's labeling.
Other warnings/precautions:
• Administration: The too-rapid administration of fat emulsion can cause fluid and/or fat overloading, resulting in dilution of serum electrolyte concentrations, overhydration, congested states, pulmonary edema, impaired pulmonary diffusion capacity, or metabolic acidosis; hourly infusion rate should be as low as possible.
• Appropriate use: Simultaneous infusion of a carbohydrate/amino acid solution is recommended to minimize the risk of metabolic acidosis.
• Three-in-one mixtures: Lipid emulsion in a three-in-one mixture may obscure the presence of a precipitate; follow compounding guidelines, especially for calcium and phosphate additions.
Due to the differences in compositions of the available lipid emulsions, the amount of lipid emulsion to prevent essential fatty acid deficiency (EFAD) will vary by product; the amount of lipid emulsion (fish oil and plant based) (eg, Smoflipid) required to prevent EFAD will be higher than the doses of plant based lipid emulsion (eg, Intralipid); use of restrictive dosing protocols with lipid emulsion (fish oil and plant based) may put patients at risk for EFAD (Carey 2019; ESPGHAN [Lapillone 2018]).
Rapid infusion has been associated with fat overload syndrome in pediatric patients. In a case report, a 2 year old inadvertently received 20 grams (1.75 g/kg) of lipid emulsion (fish oil and plant based) over 30 minutes. The patient developed vomiting, dyspnea, tachypnea, pallor, tachycardia, hypertension, and metabolic acidosis, which was determined to be fat overload syndrome. Treatment included fluids, platelets, albumin, fresh frozen plasma, RBC infusions, and filgrastim; laboratory results slowly returned to normal over a week (Hojsak 2014).
None known.
Vitamin K Antagonists (eg, warfarin): Lipid Emulsion (Fish Oil and Plant Based) may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Caloric content: 2 kcal/mL
Phosphorus: 15 mmol/L
Fat emulsion should not exceed 60% of the total daily calories.
Severe maternal malnutrition may cause adverse events to the fetus/neonate. Indications for fat emulsion therapy in pregnant women are the same as in nonpregnant women. The ASPEN guidelines for parenteral and enteral nutrition state that intravenous fat emulsion may be used safely in pregnant women to provide calories and prevent essential fatty acid deficiency (ASPEN Guidelines 2002).
Monitor for signs and symptoms of infection (including vascular access device complications); fluid and electrolyte status; serum osmolarity; blood glucose; blood counts (including platelets and coagulation parameters); signs and symptoms of essential fatty acid deficiency, fat overload, refeeding syndrome, and/or hypersensitivity reactions.
Monitor hepatic and renal function tests periodically. Monitor triglycerides before initiation of therapy, at least weekly during hospitalization and after changes are made in the amount of lipid emulsion administered; once stable, monitoring frequency may range from weekly to monthly depending on patient clinical status and history; monitor more frequently in patients at risk for hypertriglyceridemia such as premature infants (especially those that are extremely low birthweight); patients receiving high lipid or glucose doses; critically ill patients; patients with sepsis, severe thrombocytopenia, or coagulopathy; pancreatitis or hepatic disease or in patients receiving other lipid emulsion-based medications (eg, propofol) (ASPEN [Mirtallo 2020]; ESPGHAN [Lapillonne 2018]).
Monitor hepatic function (direct bilirubin, ALT/AST, alkaline phosphatase, and gamma-glutamyl transferase) at least weekly during hospitalization and at least every 3 months for patients receiving home parenteral nutrition (Deshpande 2020; ESPGHAN [Lapillonne 2018]).
Fat emulsion is metabolized and utilized as an energy source; provides fatty acids (linoleic acid, oleic acid, caprylic acid, palmitic acid, capric acid, stearic acid, and alpha linolenic acid) and omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) necessary for normal structure and function of cell membranes.
Metabolism: Fatty acids, phospholipids, and glycerol are metabolized by cells to adenosine triphosphate (ATP), carbon dioxide, and water
Excretion: Biliary (phospholipids)
Smoflipid contains 0.163 to 0.225 mg/mL of all-rac-α-tocopherol; take into consideration the amount of α-tocopherol provided by Smoflipid when determining the need for additional supplementation.
Emulsion (SMOFlipid Intravenous)
20% (per mL): $0.12
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