Fat Emulsion (Fish Oil and Plant Based)
(fat e MUL shun fish oyl & plant baste)
- Intravenous Fat Emulsion (Fish-Oil Based)
- Lipid Emulsion (Fish Oil Based)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Smoflipid: 20% (100 mL, 250 mL, 500 mL) [contains egg phospholipids (egg lecithin)]
Brand Names: U.S.
- Caloric Agent
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.
In toxicity secondary to highly lipid soluble substances, exogenous lipids provide an alternative source of binding (Rowlingson 2008), commonly known as the "lipid sink" effect. High lipid partition constant and large volumes of distribution are good predictors of success when using lipid therapy (French 2011). Lipid administration may also affect the heart in a metabolically advantageous way by improving fatty acid transport (Weinberg 2006).
Fatty acids, phospholipids, and glycerol are metabolized by cells to adenosine triphosphate (ATP), carbon dioxide, and water
Use: Labeled Indications
Caloric/fatty acid source: Source of calories, essential fatty acids, and omega-3 fatty acids for adults requiring parenteral nutrition.
Off Label Uses
Serious hemodynamic or other instability secondary to highly lipid soluble substances
Data from a limited number of patients studied and case reports suggest that IV fat emulsion may be beneficial for the treatment of serious hemodynamic or other instability not responsive to standard resuscitation measures (eg, fluids, vasopressors, inotropes) secondary to highly lipid soluble substances including, but not limited to: lipophilic local anesthetics, beta-blockers, calcium channel blockers, tricyclic antidepressants, cocaine, benzonatate, bupropion, lamotrigine, quetiapine, and venlafaxine [Arora 2013], [Carr 2009a], [Carr 2009b], [Castanares-Zapatero 2012], [Cohen 2011], [Dagtekin 2011], [Dix 2011], [Finn 2009], [Foxall 2007], [Franxman 2011], [French 2011], [Geib 2012], [Hillyard 2010], [ Jakkala-Saibaba 2011], [Jovic-Stosic 2011], [Kundu 2013], [ Liang 2011], [Litz 2006], [ Lu 2009], [Montiel 2011], [Oakes 2009], [Rosenblatt 2006], [Sirianni 2008], [Weinberg 2009], [Young 2009]. Additional data may be necessary to further define the role of intravenous fat emulsion in this setting.
Based on the American College of Medical Toxicology (ACMT) Position Statement: Guidance for the Use of Intravenous Lipid Emulsion, the American Society of Regional Anesthesia and Pain Medicine (ASRA), and the American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, IV fat emulsion given for hemodynamic or other instability secondary to local anesthetics and other highly lipid soluble substances may be considered when the patient does not respond to standard resuscitation measures (eg, fluids, vasopressors, inotropes) [ACMT 2016], [Lavonas [AHA] 2016], [Neal [ASRA] 2012]. Additional information is available at http://www.lipidrescue.org.
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)
Caloric/fatty acid source: IV: 1 to 2 g/kg/day; daily dose may be infused over 12 to 24 hours; maximum: 2.5 g/kg/day. Note: Fat emulsion should not exceed 60% of the total daily calories. At the onset of therapy, observe patient for any immediate allergic reactions (eg, dyspnea, cyanosis, fever).
Serious hemodynamic or other instability secondary to highly lipid soluble substances (off-label use): Note: Continue chest compressions during administration (lipid must circulate): 20%: IV: 1.5 mL/kg administered over 1 to 3 minutes, followed immediately by an infusion of 0.25 mL/kg/minute (recommended infusion durations vary; see below); may repeat the bolus as necessary for persistent cardiovascular collapse or if instability re-emerges (ACMT 2016; Lavonas [AHA] 2015; Neal [ASRA] 2012). Suggested maximum dose: 10 mL/kg over the first 30 to 60 minutes (Lavonas [AHA] 2015; Neal [ASRA] 2012).
After administration of the initial bolus and continuous infusion, recommendations regarding the continuous infusion vary significantly:
American College of Medical Toxicology: If after the bolus and continuing the infusion for 3 minutes, the patient demonstrates a significant response, the infusion rate may be reduced to 0.025 mL/kg/minute (ie, one-tenth the initial rate). If instability re-emerges, the infusion rate may be increased back to 0.25 mL/kg/minute or the bolus may be repeated (ACMT 2016).
American Heart Association recommendations: Continue infusion for 30 to 60 minutes (Lavonas [AHA] 2015).
American Society of Regional Anesthesia and Pain Medicine: Continue infusion for at least 10 minutes after hemodynamic stability has been restored. Increase the infusion rate to 0.5 mL/kg/minute if hemodynamic instability persists or recurs. (Neal [ASRA] 2012).
Energy expenditure and requirements may be lower in these patients; refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Do not use if discolored (should be homogenous liquid with milky appearance) or if the emulsion contains a precipitate, phase separation, and/or there are leaks in the bag. Inspect the integrity indicator before removing the over pouch; discard the product if the indicator is black. Do not add additives directly to the fat emulsion. When preparing parenteral nutrition admixture, do not add fat emulsion to the TPN container first; destabilization of the lipid emulsion may occur. First transfer dextrose solution to the TPN admixture container; then transfer amino acid injection; then transfer lipid emulsion. Amino acid injection, dextrose injection, and lipid emulsions may be simultaneously transferred to the admixture container; use gentle agitation during admixing to minimize localized concentration effects; may shake bags gently after each addition. Do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP).
IV: Administer by IV infusion 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 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 fat emulsion infusions should be filtered whether part of an admixture or infused separately using a 1.2-micron in-line filter only (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.
Serious hemodynamic or other instability secondary to highly lipid soluble substances (off-label use): Administer initial bolus over 1 to 3 minutes followed by a continuous infusion. Chest compressions should continue during administration if patient is in cardiac arrest. Some experts recommend a decreased infusion rate in patients who respond favorably to the initial bolus and infusion (ACMT 2016); repeat bolus or an increase in the infusion rate may be considered if instability persists or recurs. (ACMT 2016; Lavonas [AHA] 2015; Neal [ASRA] 2012).
Caloric content: 2 kcal/mL
Phosphorus: 15 mmol/L
Fat emulsion should not exceed 60% of the total daily calories.
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.
Vitamin K Antagonists (eg, warfarin): Fat Emulsion (Fish Oil and Plant Based) may diminish the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Elevated plasma lipids may interfere with some laboratory blood tests (eg, hemoglobin, lactate dehydrogenase, bilirubin, oxygen saturation) if blood is sampled before lipids have cleared from the bloodstream. Lipids are normally cleared after 5 to 6 hours once the infusion is stopped.
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
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.
• 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.
• Toxicity secondary to highly lipid soluble substances: Hemodynamic and other instability: Successful resuscitation following the administration of fat emulsion has been reported in animal studies and several human case reports in which cardiovascular toxicity was unresponsive to conventional resuscitation and antidotal measures. Successful resuscitation following the administration of fat emulsion has been reported in pediatric patients (Fuzaylov 2010; Ludot 2008; Shah 2009; Wong 2010). Additional information is available at http://www.lipidrescue.org. Consider use when toxicity secondary to a highly lipid soluble substance is likely and conventional methods are unsuccessful. Continue CPR throughout treatment with lipid emulsion. Consultation with a medical toxicologist or poison control center is highly recommended.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• 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.
• 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.
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 and at least weekly during therapy (or until triglycerides are stable and when changes are made in the amount of fat administered; ASPEN Guidelines 2002); monitor especially closely in patients with pancreatitis or hepatic disease.
Animal reproduction studies have not been conducted. 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). Fat emulsion therapy has been used successfully in the resuscitation of a pregnant female with suspected bupivacaine toxicity (Spence 2007).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe loss of strength and energy, bruising, bleeding, burning or numbness feeling, or injection site irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.