Total parenteral nutrition (TPN) is a method of feeding that bypasses the gastrointestinal tract. It involves delivering a nutritionally complete solution directly into a vein, typically through a central venous catheter. This method is used when a person cannot obtain adequate nutrition through oral intake or enteral feeding (feeding through the gastrointestinal tract).

TPN provides all the necessary nutrients, including carbohydrates, proteins, fats, vitamins, minerals, and electrolytes, in the correct proportions required by the body. It's often used in patients who are unable to eat or digest food properly due to conditions such as gastrointestinal disorders, severe burns, major surgeries, or certain cancers.

Total Parenteral Nutrition (TPN) is the administration of food supplements via routes other than the enteral route. It is used commonly in critically ill patients and those with extensive gastrointestinal surgery or diseases such as Crohn's disease or ulcerative colitis.

Indications of Total parenteral nutrition (TPN):

• Nutritional supplementation:
  • Nutritional supplementation with products like Kabiven and Perikabiven is crucial for adult patients who can't get enough nutrition through eating or through tubes in their stomach.
  • These products provide calories, protein, electrolytes, and essential fatty acids directly into the bloodstream when oral or tube feeding isn't possible, is not enough, or isn't safe.
  • They can help prevent deficiencies and support the body's needs, especially during times of illness or surgery.
  • Limitations of use:
    • However, these products aren't suitable for babies under 2 years old, including premature infants, because they don't have all the nutrients these young ones need.
• Guideline recommendations:
  • Guidelines from organizations like the American Society for Parenteral and Enteral Nutrition (ASPEN) and the Society of Critical Care Medicine (SCCM) recommend using parenteral nutrition in certain situations.
  • For example, it's helpful for people with serious malnutrition before or after surgery, those with severe digestive disorders like Crohn's disease, or critically ill patients who can't eat for a long time.
  • In intensive care units, if patients can't get enough nutrition through tubes into the stomach, they might need parenteral nutrition.
  • However, it's important to start it early in those who are at high risk for nutrition problems or who are very malnourished.
  • After about a week or so, if patients still can't get enough nutrition through tubes, parenteral nutrition might be considered, but it's best to use individualized solutions rather than fixed ones because they don't seem to make a big difference in patient outcomes.

Total parenteral nutrition (TPN) Dose in Adults

TPN for Nutritional supplementation:

Fixed-combination solutions:

• Nutritional supplementation through intravenous (IV) therapy involves using fixed-combination solutions tailored to each patient's needs.
• These solutions contain a set mix of amino acids, dextrose (a form of sugar), lipids (fats), and electrolytes.
• The dosage should be customized based on the patient's condition.
• Infusion should continue for as long as necessary, adjusting for severe fluid, electrolyte, or acid-base imbalances before starting.
• Always refer to guidelines, such as those from the American Society for Parenteral and Enteral Nutrition, for more detailed information.

Two commonly used products are Kabiven and Perikabiven:

• Kabiven (for central line use only): Administer at a rate of 19 to 38 mL per kilogram per day over 12 to 24 hours, with a maximum daily dose of 40 mL per kilogram per day.
• Perikabiven (for peripheral or central line): Infuse at a rate of 27 to 40 mL per kilogram per day over 12 to 24 hours, with a maximum daily dose of 40 mL per kilogram per day.

• TPN dosage adjustment for increased serum triglycerides:
  • If serum triglyceride levels rise above 400 mg/dL, stop the infusion and monitor the patient.
  • Once triglycerides drop below 400 mg/dL, restart at a lower rate and increase gradually.
  • However, these products should not be used if triglyceride levels exceed 1,000 mg/dL.
• Equations and recommendations for use when designing patient-specific parenteral nutrition :
  • To calculate the total calories needed for a patient, you can use the Harris-Benedict equation or adjust based on stress levels.
  • The equation includes factors like actual body weight, height, age, activity level, and stress factors such as illness or injury severity.
  • This helps tailor the nutritional support to the patient's energy needs.
  • The stress level determines the calorie requirement per kilogram per day, ranging from 20 to 35 kcal/kg/day, depending on the severity of the condition.

TPN for pregnant women in the second or third trimester:

• For pregnant women in the second or third trimester, an additional 300 kcal/day should be added to their total calorie intake.

Note:

• In critically ill patients, indirect calorimetry is recommended to determine energy needs.
• If not available, predictive equations or weight-based formulas can be used.
• For obese patients, energy requirements may differ, with 11 to 14 kcal/kg/day for those with a BMI of 30 to 50 kg/m² and 22 to 25 kcal/kg/day for those with a BMI greater than 50 kg/m².
• Fluid: Fluid intake should generally range from 30 to 40 mL/kg/day.
• Carbohydrate (dextrose): Carbohydrates (in the form of dextrose) should make up 45% to 65% of total calories, with a maximum infusion rate of 7 mg/kg/minute. However, it's rare for doses to exceed 5 mg/kg/minute due to the risk of hyperglycemia.

Protein requirements vary based on the patient's condition:

• For maintenance, 0.8 to 1 g/kg/day is recommended.
• Critically ill patients may require higher amounts, ranging from 1.2 to 2 g/kg/day.
• Special considerations apply to specific conditions, such as sepsis, obesity, burns, solid organ transplant, and renal failure.

• Pregnant women in the second or third trimester: Add an additional 10 to 14 g/day:
  • Fat should initially contribute to 10% to 35% of total calories, with a maximum of 60% of total calories or 2.5 g/kg/day.
  • Intravenous lipid infusions are generally safe in adults with pancreatitis if triglyceride levels remain below 400 mg/dL.

Note: For electrolytes, minerals, vitamins, and trace elements, refer to local policies and guidelines from organizations like the American Society for Parenteral and Enteral Nutrition (ASPEN). These should be tailored to meet individual patient needs and may vary based on specific medical conditions.

TPN use in Children:

Refer to adult dosing.

TPN Dose in pregnancy and lactation:

• Severe malnutrition during pregnancy can lead to serious problems for both the mother and the baby, such as birth defects, slow growth in the womb, early birth, and even infant death.
• Pregnant women who are severely malnourished might need extra calories and protein to support a healthy pregnancy.
• In some cases, doctors might recommend using total parenteral nutrition (TPN), where all the nutrients are given directly into a vein, to ensure the mother and baby get the right nutrition.
• However, TPN is usually a last resort for pregnant women who can't keep food down due to nausea and vomiting.
• In those cases, doctors prefer to use feeding tubes that go into the stomach to provide nutrition.

TPN use during breastfeeding:

• The way amino acids, dextrose (a type of sugar), and electrolytes are handled in the body when given through IV therapy is similar to how they're processed from regular food.
• However, the clearance of lipids (fats) can vary depending on the patient's condition.
• Manufacturers of pre-mixed solutions suggest considering the decision to breastfeed while undergoing therapy by weighing the potential risk of exposing the infant to the treatment against the benefits of breastfeeding for the baby and the benefits of the treatment for the mother.
• This decision should be made carefully, considering all factors involved.

TPN Dose adjustment in renal disease:

Kabiven, Perikabiven:

• For Kabiven and Perikabiven, no changes in dosage are needed for patients with kidney problems.
• However, it's crucial to fix any serious fluid or electrolyte imbalances before giving these solutions.
• Close monitoring of electrolyte levels is important, and adjustments in the volume of solution administered may be necessary.
• If a patient has kidney issues or needs frequent dialysis, extra protein may be required.
• In such cases, additional amino acid solutions can be added to the pre-mixed solutions or infused separately to meet the patient's needs.
• This ensures that patients with renal impairment receive appropriate nutritional support while managing their kidney condition.

TPN Dose adjustment in liver disease:

• According to the manufacturer's labeling, there are no specific dosage adjustments recommended for patients with hepatic (liver) impairment when using Kabiven or Perikabiven.

Contraindication to Total parenteral nutrition Include:

• Kabiven and Perikabiven are contraindicated in patients with hypersensitivity to egg, soybean proteins, peanut proteins, corn or corn products, or any component of the formulation.
• They should also not be used in patients with severe hyperlipidemia or severe disorders of lipid metabolism characterized by high triglyceride levels (>1,000 g/dL), inborn errors of amino acid metabolism, cardiopulmonary instability including conditions like pulmonary edema, cardiac insufficiency, heart attack (MI), acidosis, and hemodynamic instability requiring significant vasopressor support, as well as in patients with hemophagocytic syndrome.
• Canadian labeling adds additional contraindications such as severe liver or renal insufficiency (not on dialysis or hemofiltration), severe blood coagulation disorders, uncontrolled hyperglycemia, elevated serum electrolyte levels, and unstable conditions like severe post-traumatic conditions, uncompensated diabetes mellitus, stroke, embolism, metabolic acidosis, severe sepsis, hypotonic dehydration, and hyperosmolar coma.
• According to the American Society for Parenteral and Enteral Nutrition (ASPEN), peripheral parenteral nutrition is not recommended in conditions of significant malnutrition, severe metabolic stress, large nutrient or electrolyte needs, fluid restriction, the need for prolonged parenteral nutrition (i.e., >2 weeks), and renal or liver impairment, with central parenteral nutrition being preferred in these cases.

Warnings/Precautions

Catheter occlusion:

• Catheter occlusion is identified when there's resistance during infusion or when attempting to withdraw blood from the catheter.
• This blockage can stem from either thrombotic (clot-related, most common) or non-thrombotic causes.
• Treatment should be tailored accordingly, addressing the specific underlying cause.

Fat overload syndrome:

• Fat overload syndrome is a rare but serious condition where the body has difficulty processing fats, leading to prolonged clearance of fats from the bloodstream.
• This can cause a sudden decline in the patient's health, with symptoms such as anemia, clotting problems, neurological issues like coma, worsening liver function with enlarged liver (hepatomegaly), fever, high levels of fats in the blood (hyperlipidemia), low white blood cell count (leukopenia), or low platelet count (thrombocytopenia).
• Typically, these symptoms improve once the infusion of fats is stopped.

Hyperglycemia:

• Hyperglycemia is a concern when using Kabiven or Perikabiven, especially in patients with diabetes mellitus or insulin resistance.
• This condition can lead to hyperosmolar syndrome, characterized by high blood sugar levels and increased blood osmolarity.
• Even patients without diabetes may develop hyperglycemia, especially if they're older, have severe illness, or if the solution is infused too quickly.
• It's important to closely monitor the rate of administration and check blood sugar levels regularly.
• In some cases, insulin may be needed to manage blood sugar levels effectively.

Hypersensitivity:

• Hypersensitivity reactions, such as allergic responses, can happen with Kabiven or Perikabiven.
• These reactions may manifest as various symptoms like changes in mental status, difficulty breathing (bronchospasm), bluish discoloration of the skin (cyanosis), flushing, shortness of breath (dyspnea), headache, low blood pressure (hypotension), low oxygen levels in the blood (hypoxia), skin rash, sweating, rapid heart rate (tachycardia), fast breathing (tachypnea), or vomiting.
• If any signs or symptoms of hypersensitivity or allergic reactions occur, it's crucial to stop the infusion immediately and seek medical attention.

Hypertriglyceridemia:

• Hypertriglyceridemia, elevated levels of triglycerides in the blood, can occur in patients with impaired lipid metabolism, such as those with diabetes mellitus, metabolic syndrome, or obesity, or in patients receiving excessive dextrose.
• It's important to closely monitor triglyceride levels.
• If serum triglycerides rise above 400 mg/dL (or exceed 1,000 mg/dL, which is associated with pancreatitis), consider reducing the dose of fixed combination solutions or discontinuing intravenous fat emulsion from the parenteral nutrition regimen.
• Once triglyceride levels drop below 400 mg/dL, intravenous fat emulsion may be reintroduced.
• It's essential to monitor all sources of lipids, dextrose, and medications that could affect their metabolism to manage hypertriglyceridemia effectively.

Infection:

• Patients who need parenteral nutrition are often at increased risk of infection, including potentially life-threatening conditions like sepsis.
• This risk can stem from malnutrition, underlying health conditions, or the catheters used for administering the nutrition.
• It's crucial to strictly adhere to sterile techniques to prevent infections and watch for early signs of infection.
• Diabetic patients, in particular, face a higher risk of catheter-related infections compared to non-diabetic patients.
• In intensive care units with high rates of invasive candidiasis (more than 5%), antifungal prophylaxis should be considered for patients receiving parenteral nutrition to reduce the risk of fungal infections, as recommended by the Infectious Diseases Society of America (IDSA).

Parenteral nutrition-associated liver disease:

• Parenteral nutrition-associated liver disease (PNALD) is a known complication in patients, particularly preterm infants, who receive prolonged parenteral nutrition.
• This condition can manifest as cholestasis (impaired bile flow) or steatohepatitis (inflammation and fatty degeneration of the liver).
• If patients develop abnormalities in liver function tests, such as elevated liver enzymes, it's important to consider discontinuing or reducing the dose of parenteral nutrition to mitigate further liver damage.
• Monitoring liver function closely and adjusting nutrition support accordingly can help prevent or manage PNALD effectively.

Refeeding syndrome:

• When using Kabiven or Perikabiven, caution is advised in patients at risk for refeeding syndrome, especially those who are severely malnourished.
• Refeeding syndrome can occur in these patients due to shifts of magnesium, phosphorus, and potassium within cells, leading to symptoms like fatigue, muscle weakness, swelling (edema), breakdown of red blood cells (hemolysis), and abnormal heart rhythms (arrhythmias), which can be life-threatening.
• Thiamine deficiency may also develop as a result.
• To mitigate the risk, it's important to start and increase caloric intake slowly in patients at risk for refeeding syndrome, as recommended by the American Society for Parenteral and Enteral Nutrition (ASPEN).
• This cautious approach helps to prevent or minimize the complications associated with refeeding syndrome.

Hepatic impairment:

• Patients with hepatic impairment should be treated cautiously when using Kabiven or Perikabiven.
• Hepatobiliary disorders such as cholecystitis, cholelithiasis, cholestasis, cirrhosis, hepatic steatosis, fibrosis, and even hepatic failure may occur, even in patients without pre-existing liver disease.
• If hepatobiliary complications arise during treatment, several strategies can be considered, including reducing the dextrose or intravenous fat emulsion component, maintaining a balance between dextrose and intravenous fat emulsion, or cycling parenteral nutrition.
• Additionally, amino acid therapy may lead to increased blood ammonia levels and hyperammonemia, so patients should be assessed for hepatic insufficiency or potential inborn errors of amino acid metabolism.
• Monitoring and appropriate management are crucial to ensure the safety and efficacy of parenteral nutrition in patients with hepatic impairment.

Renal impairment:

• Patients with renal impairment should use Kabiven or Perikabiven with caution.
• These patients are at increased risk of electrolyte and fluid volume imbalances when receiving parenteral nutrition.
• It's important to closely monitor electrolyte levels and fluid status in such patients to prevent complications.

Monitoring Parameter:

• Serum Triglycerides: Check baseline levels, with each dose change, and regularly during therapy.
• Fluid and Electrolytes: Monitor regularly to prevent imbalances.
• Blood Glucose: Check regularly, especially in diabetic patients.
• Serum Osmolarity: Assess periodically to ensure proper fluid balance.
• Hepatic and Kidney Function: Monitor liver and kidney health regularly.
• Blood Ammonia: Evaluate levels, especially in patients with liver issues.
• Blood Count: Check regularly, including platelets and coagulation factors.
• Fluid Status: Closely monitor in patients with heart failure, renal impairment, or pulmonary edema.
• Signs and Symptoms of Infection: Watch for any signs of infection, especially catheter-related.
• Hypersensitivity Reactions: Be alert for allergic reactions during therapy.
• Essential Fatty Acid Deficiency: Look out for symptoms and address promptly if suspected.
• Fat Overload Syndrome: Monitor for signs and manage appropriately.
• Refeeding Syndrome: Be cautious, especially in severely malnourished patients.

ASPEN Recommendations (ASPEN [Mueller 2012])

• Baseline and Daily:
  • Weight (2 to 3 times per week in stable patients)
  • Intake and Output (daily in stable patients unless assessed by physical exam)
• Baseline and Weekly:
  • Complete Blood Count (CBC) with differential
  • Prothrombin Time (PT)/International Normalized Ratio (INR), Partial Thromboplastin Time (PTT)
  • Serum Triglycerides (measure on day 1 of initiation)
  • Transferrin or Prealbumin
  • Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST), Alkaline Phosphatase, Total Bilirubin (measure on day 1 of initiation; monthly in stable patients)
• 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) (measure 3 times daily upon initiation)
  • Blood Urea Nitrogen (BUN), Creatinine
  • Serum Glucose (measure 3 times daily upon initiation)
• As Needed:
  • Capillary Glucose (measure 3 times daily in critically ill patients until consistently <150 mg/dL)
  • Nitrogen Balance

Note: In patients on long-term parenteral nutrition, consider annual bone mineral density testing, periodic monitoring for iron deficiency, and biannual assessment of serum levels of trace elements.

How to administer TPN?

• Continuous or Cyclic Infusion: PN can be given as a continuous 24-hour infusion or as a cyclic infusion over 8 to 12 hours for selected stable patients, especially those expected to have a longer course or home infusion.
• Peripheral Administration: PN with an osmolarity up to 900 mOsm/L may be given peripherally, but close monitoring for extravasation is essential.
• Hypoglycemia Risk: Abrupt discontinuation of PN may lead to hypoglycemia; tapering the infusion can help reduce this risk.

Kabiven and Perikabiven Administration

• Composition: These solutions contain amino acids, dextrose, lipids, and electrolytes and are available in various sizes based on fluid requirements and infusion duration.
• Compatibility: Always check compatibility with other medications before administering simultaneously via Y-site.
• Kabiven: Infuse over 12 to 24 hours via central vein only, using a 1.2 micron inline filter. Maximum infusion rate and specific components detailed.
• Perikabiven: Can be infused over 12 to 24 hours via peripheral or central vein, using a 1.2 micron inline filter. Maximum infusion rate and specific components detailed.

Extravasation Management

• Precaution: PN is a vesicant, so proper needle or catheter placement is crucial to avoid extravasation.
• If Extravasation Occurs: Stop infusion immediately, disconnect, aspirate extravasated solution, initiate hyaluronidase antidote, apply cold compresses, and elevate extremity.
• Hyaluronidase Administration: Inject as directed into the area of extravasation.
• Alternative Treatment: Nitroglycerin topical 2% ointment may be used based on limited data.

This comprehensive approach to PN administration and management of extravasation ensures patient safety and optimal therapy delivery.

MOA of TPN:

• Parenteral nutrition is a solution that combines amino acids, dextrose (a form of sugar), lipids (fats), and electrolytes to provide essential nutrients to patients who are unable to take in food orally or through a feeding tube.
• This combination ensures that patients receive all the necessary building blocks, energy, and essential nutrients they need to support their bodily functions and promote healing when oral or enteral nutrition is not feasible.

International Brand Names of TPN:

• Kabiven
• Perikabiven 
• Olimel;
• Olimel E;
• PeriOlimel;
• SmofKabiven
• Smofkabiven Electrolyta Free Amino Acids

TPN Brands in Pakistan:

Brands in Pakistan will be updated later.