Deaths in preterm infants after infusion of 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.
Nutritional supplementation: IV:
Fixed-combination solutions: Note: Dosage should be individualized based on patient status. These products contain a fixed combination of amino acids, dextrose, lipids, and electrolytes. Continue therapy as long as required based on patient status. Correct severe fluid, electrolyte, or acid-base disorders prior to infusion. Also refer to the American Society for Parenteral and Enteral Nutrition for more detailed information.
Kabiven (central line use only): 19 to 38 mL/kg/day infused over 12 to 24 hours; maximum daily dose: 40 mL/kg/day.
Perikabiven (peripheral or central line): 27 to 40 mL/kg/day infused over 12 to 24 hours; maximum daily dose: 40 mL/kg/day.
Dosage adjustment for increased serum triglycerides: Stop infusion and monitor if triglycerides >400 mg/dL; restart at a lower infusion rate and advance in smaller increments once triglycerides are <400 mg/dL. Use is contraindicated with triglycerides >1,000 mg/dL.
Equations and recommendations for use when designing patient-specific parenteral nutrition :
Total calories: Calculate using Harris-Benedict equation (Harris 1919) (constants and coefficients rounded to the nearest hundredth place) or base on stress level as indicated below:
Harris-Benedict Equation (BEE):
Females: 655.1 + [(9.56 x W) + (1.85 x H) - (4.68 x A)]
Males: 66.47 + [(13.75 x W) + (5 x H) - (6.76 x A)]
W = actual body weight in kg; H = height in cm; A = age in years
To determine total calories needed (based on total energy expenditure [TEE]) use the following equation:
TEE = BEE + [BEE x (Activity Factor - 1)] + [BEE x (Stress Factor - 1)]
Activity factor = 1.2 sedentary, 1.3 normal activity (Long 1979)
Stress factor = 1.3 for sepsis, trauma, stressed, or surgical patients; 1.5 for underweight (to promote weight gain); up to 2 for severe burn patients; 1.5 to 2 for acute renal failure; 1.1 to 1.2 for chronic renal failure (ASPEN [Mueller 2012]; Chessman 2016).
Stress level:
Normal/mild stress level: 20 to 25 kcal/kg/day (Delegge 2007)
Moderate stress level: 25 to 30 kcal/kg/day (Delegge 2007)
Severe stress level: 30 to 35 kcal/kg/day (Delegge 2007)
Pregnant women in second or third trimester: Add an additional 300 kcal/day (ASPEN 2002)
Note: In critically ill patients, the use of indirect calorimetry is suggested to determine energy requirements. If IC is unavailable, may use a published predictive equation or a simple weight-based equation (25 to 50 kcal/kg/day [use dry or usual body weight]). If patient is obese, use 11 to 14 kcal/kg/day (use actual body weight) for BMI of 30 to 50 kg/m2 and 22 to 25 kcal/kg/day for BMI >50 kg/m2. Energy expenditure should be reevaluated more than once per week while optimizing energy and protein intake (SCCM/ASPEN [Taylor 2016]).
Fluid: mL/day = 30 to 40 mL/kg (ASPEN 2002; Mirtallo 2004)
Carbohydrate (dextrose): 45% to 65% of total calories (Chessman 2014); maximum rate: 7 mg/kg/minute (Mattox 2014); Note: Doses rarely exceed 5 mg/kg/minute due to an increased risk of hyperglycemia (ASPEN 2002; Mirtallo 2004).
Protein (amino acids):
Maintenance: 0.8 to 1 g/kg/day (Mirtallo 2004)
Critically ill: 1.2 to 2 g/kg/day
Sepsis: 1.2 to 2 g/kg/day (SCCM/ASPEN [McClave 2016])
Obese (critically ill): BMI 30 to 40 kg/m2: 2 g/kg/day using IBW; BMI >40 kg/m2: 2.5 g/kg/day using IBW (SCCM/ASPEN [McClave 2016])
Burn patients (severe): 1.5 to 2 g/kg/day (SCCM/ASPEN [McClave 2016]); increase protein until significant wound healing achieved (ASPEN 2002)
Solid organ transplant: Perioperative: 1.5 to 2 g/kg/day (ASPEN 2002)
Renal failure:
Acute (severely malnourished or hypercatabolic): 1.5 to 1.8 g/kg/day (ASPEN 2002)
Chronic, with dialysis: 1.2 to 1.3 g/kg/day (ASPEN 2002)
Chronic, without dialysis: 0.6 to 0.8 g/kg/day (ASPEN 2002)
Continuous renal replacement therapy or frequent hemodialysis: ≥1 g/kg/day (up to 2.5 g/kg/day) (ASPEN [Mueller 2012])
Pregnant women in second or third trimester: Add an additional 10 to 14 g/day (ASPEN 2002)
Fat:
Initial: 10% to 35% of total calories (Chessman 2014) (maximum: 60% of total calories or 2.5 g/kg/day) (ASPEN 2002; Mattox 2014). Note: Monitor triglycerides while receiving intralipids.
IV lipids are safe in adults with pancreatitis if triglyceride levels <400 mg/dL (ASPEN 2002).
Electrolytes, minerals, vitamins, and trace elements: Refer to local policies and ASPEN guidelines.
Kabiven, Perikabiven: No dosage adjustments necessary for renal impairment. Correct severe fluid or electrolyte imbalances prior to administration. Closely monitor electrolytes and adjust administered volume as necessary. Supplement protein as indicated for patients with acute or chronic renal impairment or those requiring frequent dialysis or CRRT. Additional amino acid solution may be added to the premixed solutions or infused separately.
There is no dosage adjustment provided in the manufacturer's labeling; use with caution.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Emulsion, Intravenous:
Kabiven: (1026 mL,1540 mL, 2053 mL, 2566 mL) [sulfite free; lipid chamber contains egg phospholipids (egg lecithin)]
Perikabiven: (1440 mL,1920 mL, 2400 mL) [sulfite free; lipid chamber contains egg phospholipids (egg lecithin)]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Emulsion, Intravenous:
Olimel 4.4% E: (1000 mL, 1500 mL, 2000 mL) [lipid chamber contains egg phosphatide]
Olimel 5.7% and Olimel 5.7% E: (1000 mL, 1500 mL, 2000 mL) [lipid chamber contains egg phosphatide]
Olimel 7.6% E: (650 mL, 1000 mL, 1500 mL, 2000 mL) [lipid chamber contains egg phosphatide]
PeriOlimel 2.5% E: (1000 mL, 1500 mL, 2000 mL, 2500 mL) [lipid chamber contains egg phosphatide]
SmofKabiven: (986 mL, 1477 mL, 1970 mL, 2463 mL) [contains egg phospholipids]
Parenteral nutrition (PN) may be administered as a continuous 24 hour infusion or as a cyclic infusion (generally, over 8 to 12 hours) in selected stable patients (eg, expected to have a longer course or home infusion) (Kumpf 2006; Stout 2010). ASPEN suggests that PN with an osmolarity up to 900 mOsm/L may be administered peripherally; monitor closely for extravasation (ASPEN [Ayers 2013]; ASPEN [Boullata 2014]). Abrupt discontinuation may cause hypoglycemia; infusion tapering may decrease this risk (Stout 2010).
Kabiven and Perikabiven are fixed combinations of amino acids, dextrose, lipids, and electrolytes and come in several sizes; selection will be based on fluid requirements and duration of infusion. Note: Always check compatibility with parenteral nutrition before simultaneously administering any drug via Y-site (Trissel 1997; Trissel 1999). If patient is receiving ceftriaxone, do not administer ceftriaxone simultaneously via Y-site due to precipitation (Kabiven and Perikabiven contain calcium); if the infusion line is thoroughly flushed between infusions with a compatible fluid, may sequentially administer ceftriaxone and Kabiven or Perikabiven.
Kabiven: Infuse over 12 to 24 hours via central vein only using a 1.2 micron inline filter. Maximum infusion rate: 2.6 mL/kg/hour (corresponds to amino acids 0.09 g/kg/hour; dextrose 0.25 g/kg/hour [rate-limiting component]; lipids 0.1 g/kg/hour). Administer through a dedicated line without any connections. Do not use administration lines and sets containing DEHP (sets containing PVC components have DEHP as a plasticizer). Vein irritation, damage, and/or thrombosis may occur if administered via peripheral vein.
Perikabiven: Infuse over 12 to 24 hours via peripheral or central vein using a 1.2 micron inline filter. Maximum infusion rate: 3.7 mL/kg/hour (corresponds to amino acids 0.09 g/kg/hour; dextrose 0.25 g/kg/hour [rate-limiting component]; lipids 0.13 g/kg/hour). Administer through a dedicated line without any connections. Do not use administration lines and sets containing DEHP (sets containing PVC components have DEHP as a plasticizer).
Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place). Gently aspirate extravasated solution (do NOT flush the line), initiate hyaluronidase antidote, remove needle/cannula, and apply dry cold compresses (Hurst 2004; Reynolds 2014). Elevate extremity.
Hyaluronidase: Intradermal or SubQ: Inject a total of 1 to 1.7 mL (15 units/mL) as 5 separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara 1983; Reynolds 2014; Zenk 1981). May also inject hyaluronidase through the catheter that caused the infiltration (Reynolds 2014).
Alternative to hyaluronidase: Nitroglycerin topical 2% ointment (based on limited data): Apply a 1-inch strip to site of ischemia; may repeat after 8 hours if necessary (Reynolds 2014).
Nutritional supplementation:
Kabiven, Perikabiven: A source of calories, protein, electrolytes, and essential fatty acids for adult patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated; prevention of essential fatty acid deficiency or treatment of negative nitrogen balance in adult patients.
Limitations of use: These fixed-content formulations are not recommended for use in children <2 years of age, including preterm infants, because they do not meet nutritional requirements for this age group.
Guideline recommendations:
According to the American Society for Parenteral and Enteral Nutrition (ASPEN), parenteral nutrition has been shown to be beneficial for perioperative nutrition in patients with moderate to severe malnutrition, acute exacerbations of Crohn disease, GI fistulas, extreme short bowel syndrome, critically ill patients who cannot take in oral feeding for prolonged periods of time, or severe acute necrotizing pancreatitis (ASPEN [Mueller 2012]).
The Society of Critical Care Medicine (SCCM) and ASPEN guidelines for the critically ill patient recommend use as soon as possible after ICU admission in patients with high nutrition risk or those who are severely malnourished, when enteral nutrition is not feasible. Parenteral nutrition may be considered after 7 to 10 days in critically ill patients at either low or high nutrition risk if unable to meet >60% of energy and protein requirements by enteral route alone. The use of standardized (or fixed) commercially available solutions are not recommended because they offer no advantage in clinical outcome of the critically ill patient population (SCCM/ASPEN [Taylor 2016]).
TPN abbreviation should not be used when ordering this medication; had been mistaken for tPA (alteplase)
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Nausea (2% to 15%)
1% to 10%:
Cardiovascular: Hypertension (≤1% to 8%), phlebitis (2%), tachycardia (≤1%), thrombophlebitis (≤1%)
Central nervous system: Dizziness (≤1%), headache (≤1%)
Dermatologic: Pruritus (1% to 2%), eczema (≤1%), skin rash (≤1%)
Endocrine & metabolic: Hyperglycemia (2% to 5%), decreased serum total protein (4%), hypokalemia (4%), increased gamma-glutamyl transferase (2% to 4%), increased serum triglycerides (≤1% to 3%), abnormal alanine aminotransferase (2%), hypoalbuminemia (2%), increased serum glucose (≤1% to 2%), hypocalcemia (1%), hyperkalemia (≤1%), hypernatremia (≤1%), hypertriglyceridemia (≤1%), hypomagnesemia (≤1%)
Gastrointestinal: Vomiting (≤1% to 6%), dysgeusia (≤1%)
Hematologic & oncologic: Decreased hemoglobin (6%), C-reactive protein increased (2%), prolonged prothrombin time (1%)
Hepatic: Increased serum alkaline phosphatase (1% to 2%), increased serum bilirubin (≤1%), jaundice (≤1%), hepatic cirrhosis (<1%)
Renal: Increased blood urea nitrogen (2%)
Miscellaneous: Fever (4% to 9%)
Frequency not defined:
Endocrine & metabolic: Hyperphosphatemia, hypophosphatemia (ASPEN 2002)
Gastrointestinal: Cholecystitis, cholelithiasis
Hepatic: Liver steatosis
Miscellaneous: Fibrosis
<1%, postmarketing, and/or case reports: Abdominal distension, abdominal pain, anaphylaxis, cerebrovascular hemorrhage (subependymal), chest tightness, cholestasis, hepatic disease (parenteral nutrition associated liver disease (PNALD), hypersensitivity reaction, infection, lipid metabolism disorder (fat overload syndrome), transient flushing of face
Kabiven, Perikabiven: Hypersensitivity to egg, soybean proteins, peanut proteins, corn or corn products, or any component of the formulation; severe hyperlipidemia or severe disorders of lipid metabolism with hypertriglyceridemia (serum triglycerides >1,000 mg/dL); inborn errors of amino acid metabolism; cardiopulmonary instability, including pulmonary edema, cardiac insufficiency, myocardial infarction, acidosis, and hemodynamic instability requiring significant vasopressor support; hemophagocytic syndrome.
Canadian labeling: Additional contraindications (not in US labeling): Note: Contraindications may vary by product; also refer to product labeling: Severe liver or renal insufficiency (not on dialysis or hemofiltration); hepatic coma; severe blood coagulation disorders; uncontrolled hyperglycemia; elevated serum electrolyte levels of any of the included electrolytes; unstable conditions (eg, severe posttraumatic conditions, uncompensated diabetes mellitus, stroke, embolism, metabolic acidosis, severe sepsis, hypotonic dehydration, hyperosmolar coma); hypertriglyceridemia-associated acute pancreatitis.
Note: Contraindications, as recommended by the American Society for Parenteral and Enteral Nutrition (ASPEN), for peripheral parenteral nutrition regardless of formulation (premixed or patient-specific formulations) include significant malnutrition, severe metabolic stress, large nutrient or electrolyte needs, fluid restriction, need for prolonged parenteral nutrition (ie, >2 weeks), and renal or liver impairment. Central parenteral nutrition in these conditions is recommended (ASPEN [Mueller 2012]).
Concerns related to adverse effects:
• Catheter occlusion: Recognized when unable to infuse due to resistance or unable to aspirate blood due to resistance. May be due to thrombotic (most common) or nonthrombotic causes; treat as appropriate (ASPEN [Mueller 2012]).
• Fat overload syndrome: A reduced or limited ability to metabolize lipids accompanied by prolonged plasma clearance may rarely occur. Fat overload syndrome may result in a sudden deterioration in patient condition along with anemia, coagulation disorders, CNS manifestations (eg, coma), deteriorating liver function and hepatomegaly, fever, hyperlipidemia, leukopenia, or thrombocytopenia; usually reversible upon discontinuation.
• Hyperglycemia: Use with caution in patients with diabetes mellitus or insulin resistance. Hyperglycemia and hyperosmolar syndrome may occur with therapy. Hyperglycemia may also occur in patients without diabetes; risk factors include age, severity of illness, and rate of infusion (Clement 2004). Monitor administration rate as well as serum glucose; insulin may be required for optimal glucose control.
• Hypersensitivity: Allergic or hypersensitivity reactions (eg, altered mentation, bronchospasm, cyanosis, flushing, dyspnea, headache, hypotension, hypoxia, rash, sweating, tachycardia, tachypnea, vomiting) may occur; discontinue infusion immediately if signs or symptoms of hypersensitivity or allergic reactions occur.
• Hypertriglyceridemia: May occur in patients with impaired lipid metabolism (eg, diabetes mellitus, metabolic syndrome, obesity) or those being overfed with dextrose; monitor triglycerides closely. Reduce dose of fixed combination solutions or eliminate IV fat emulsion from the parenteral nutrition regimen with serum triglycerides >400 mg/dL (>1,000 mg/dL is associated with pancreatitis); may reinitiate IV fat emulsion when <400 mg/dL. Monitor all sources of lipids, dextrose, and medications that may interfere with their metabolism (ASPEN [Mueller 2012]).
• Infection: Patients requiring parenteral nutrition may be at high risk of infection, including sepsis, due to malnutrition, the underlying disease state, or catheters required for administration. Proper aseptic technique should be followed; monitor for signs of early infection. Diabetic patients are at a greater risk of developing catheter-related infections compared with nondiabetic patients (McMahon 1996). Consider antifungal prophylaxis in patients receiving parenteral nutrition in ICUs with high rates (>5%) of invasive candidiasis (IDSA [Pappas 2016]).
• Parenteral nutrition-associated liver disease: Has been reported in patients receiving parenteral nutrition for extended periods of time, especially preterm infants. Parenteral nutrition-associated liver disease may present as cholestasis or steatohepatitis. Consider discontinuation or dose reduction in patients who develop liver function test abnormalities.
• Refeeding syndrome: Use with caution in patients at risk for refeeding syndrome (eg, severely malnourished). Refeeding syndrome may occur in severely undernourished patients and is due to the intracellular shift of magnesium, phosphorus, and potassium resulting in generalized fatigue, muscle weakness, edema, hemolysis, and cardiac arrhythmia (may result in cardiopulmonary arrest); thiamine deficiency may also develop. In patients at risk, initiate and advance caloric intake slowly (ASPEN [Mueller 2012]).
Disease-related concerns:
• Hepatic impairment: Use caution in patients with hepatic impairment. Hepatobiliary disorders (eg, cholecystitis, cholelithiasis, cholestasis, cirrhosis, hepatic steatosis, fibrosis) may occur in patients without liver disease and may lead to hepatic failure. If hepatobiliary complications occur during treatment, among other strategies for treatment, consider reducing dextrose or IV fat emulsion component, providing a balance between dextrose and IV fat emulsion, or cycling parenteral nutrition (ASPEN [Mueller 2012]). Increased blood ammonia and hyperammonemia may occur with amino acid therapy; evaluate patients for hepatic insufficiency or an unknown inborn error of amino acid metabolism.
• Renal impairment: Use with caution in patients with renal impairment; risk of electrolyte and fluid volume imbalance may be increased.
Dosage form specific issues:
• Aluminum: Kabiven, Perikabiven: May contain aluminum; toxic aluminum concentrations may be seen with prolonged use or renal dysfunction. 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 in patients with renal dysfunction (including premature infants); tissue loading may occur at lower doses.
Other warnings/precautions:
• Abrupt withdrawal: If TPN is discontinued abruptly, rebound hypoglycemia may occur. Infuse dextrose 10% at same rate and monitor capillary blood glucose for hypoglycemia at 30 minutes to 1 hour after TPN is discontinued. To reduce the risk of rebound hypoglycemia in susceptible patients (eg, patients requiring large doses of insulin), taper down the infusion rate for 1 to 2 hours or half the infusion rate (ASPEN [Mueller 2012]).
Special populations:
• Pediatric: Kabiven, Perikabiven: [US Boxed Warning]: Deaths in preterm infants following IV administration of lipid emulsion have been reported; intravascular fat accumulation in the lungs has been observed on autopsy. Preterm and low birth weight infants clear IV lipid emulsions poorly and have increased free fatty acid plasma concentrations following lipid emulsion infusion.
Severe malnutrition is associated with adverse pregnancy outcomes, including congenital malformations, intrauterine growth restriction, preterm delivery, perinatal mortality, and low birth weight infants. Indications for special nutrition support are the same in pregnant women as in nonpregnant patients. Additional calories and protein may be required (ASPEN 2002). Long-term use of TPN throughout pregnancy has been noted in case reports (Buchholz 2015).
In women with nausea and vomiting of pregnancy, total parenteral nutrition should be used as a last option for any woman who cannot maintain her weight because of vomiting; enteral nutrition is preferred (ACOG 189 2018).
Amino acid, dextrose, and electrolyte disposition is the same as supplied by ordinary food; lipid clearance is dependent on clinical status. According to the manufacturer of the premixed solution, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Serum triglycerides (baseline, with each dose change, and regularly during therapy), fluid and electrolytes, blood glucose, serum osmolarity, hepatic and kidney function, blood ammonia, blood count (including platelets and coagulation factors). Fluid status should be closely monitored in patients with heart failure, renal impairment, or pulmonary edema. Signs and symptoms of infection (especially catheter-related infection), hypersensitivity reactions, essential fatty acid deficiency, fat overload syndrome, refeeding syndrome.
ASPEN recommendations (ASPEN [Mueller 2012]):
At baseline and daily: Weight (in stable patients, 2 to 3 times per week); intake and output (in stable patients, daily unless fluid status assessed by physical exam)
At baseline and weekly: CBC with differential; PT/INR, PTT; serum triglycerides (upon initiation also measure on day 1); transferrin or prealbumin; ALT/AST, alkaline phosphatase, total bilirubin (also measure on day 1; in stable patients, these may be measured monthly)
At baseline and 1 to 2 times per week in stable patients/daily in critically-ill patients: Electrolytes (sodium, potassium, chloride, carbon dioxide, magnesium, calcium, phosphorus) (upon initiation, 3 times daily); BUN, creatinine; serum glucose (upon initiation, 3 times daily)
As needed: Capillary glucose (in critically ill patients, measure 3 times daily until consistently <150 mg/dL); nitrogen balance
Note: In patients receiving long-term parenteral nutrition, obtain bone mineral density testing annually, monitor for iron deficiency periodically, and monitor serum levels of trace elements biannually.
Combination of amino acids, dextrose, lipids, and electrolytes to provide parenteral nutrition.
Emulsion (Kabiven Intravenous)
3.3-9.8-3.9-0.7% (per mL): $0.04
Emulsion (Perikabiven Intravenous)
2.4-6.8-3.5-0.5% (per mL): $0.03
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