Continuing Education Activity

Total parenteral nutrition is a medication used in the management and treatment of malnourishment. It is in the nutrition class of drugs. This activity describes the indications, action, and contraindications for total parenteral nutrition as a valuable agent in the management of malnourishment and nonfunctional gastrointestinal system. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional team in the management of patients with malnourishment and nonfunctional gastrointestinal system and related conditions.

Objectives:

• Identify the indications for total parenteral nutrition.
• Describe the potential adverse effects of total parenteral nutrition
• Review the appropriate monitoring of total parenteral nutrition
• Outline interprofessional team strategies for improving care coordination and communication to advance total parenteral nutrition and improve outcomes.

Indications

Parenteral nutrition is the intravenous administration of nutrition outside of the gastrointestinal tract. Total parenteral nutrition (TPN) is when the IV administered nutrition is the only source of nutrition the patient is receiving. Total parenteral nutrition is indicated when there is an inadequate gastrointestinal function and contraindications to enteral nutrition. Enteral diet intake is preferred over parenteral as it is inexpensive and associated with fewer complications such as infection and blood clots but requires a functional GI system.[1]According to Chowdary and Reddy (2010), TPN indications include [2]:

• Chronic intestinal obstruction as in intestinal cancer [3]
• Bowel pseudo-obstruction with food intolerance. 
• TPN can also be used to rest the bowel in cases of GI fistulas with high flow [4]
• When an infant’s gastrointestinal system is immature or has a congenital gastrointestinal malformation
• When there is a post-operative bowel anastomosis leak
• When the patient is unable to maintain nutritional status due to severe diarrhea or vomiting
• Small bowel obstruction
• Hypercatabolic states due to sepsis, polytrauma, and major fractures [5]
• An anticipated period of nothing by mouth (NPO) status greater than seven days as in patients with inflammatory bowel disease exacerbations as well as critically ill patients [6]

Mechanism of Action

TPN is a mixture of separate components which contain lipid emulsions, dextrose, amino acids, vitamins, electrolytes, minerals, and trace elements.[7][8] TPN composition should be adjusted to fulfill individual patients' needs. The main three macronutrients are lipids emulsions, proteins, and dextrose. 

Lipid emulsions:

• It provides calories and prevents fatty acid deficiency. Essential fatty acid deficiency may develop within three weeks of fat-free TPN.[2]
• 25% to 30% of the total calories are in the form of lipids.

Proteins:

• A solution that contains essential and non-essential amino acids except arginine and glutamine
  • Healthy adult requirements are 0.8 to 1 gm of protein/kg/day.
• This change based on the condition of the patient. Critically ill patients require 1.5 gm/kg/day, patients with chronic renal failure are given 0.6 to .0.8 gm/kg/day, and patients with acute hepatic encephalopathy need temporary protein restriction to 0.8 gm/kg/day, patients on hemodialysis need 1.2 to 1.3 gm/kg/day.[2]

Carbohydrate:

• Provided through dextrose monohydrate in a variety of concentrations, most commonly 40,50, and 70%
• Glucose utilization maximum rate is 5 to 7 mg/kg/min.
• Excess carbohydrate supplementation can result in hyperglycemia and hypertriglyceridemia.

Electrolytes, trace elements, and vitamins are micro-nutrients.

• Trace elements and vitamins dosing can be according to recommended daily requirements.
• Electrolytes recommendation per liter of parenteral nutrition:
  • Sodium: 100 to 150 mEq
  • Magnesium: 8 to 24 mEq
  • Calcium: 10 to 20 mEq
  • Potassium: 50 to 100 mEq
  • Phosphorus: 15 to 30 mEq

Total nutrition is an admixture, a 3-in-1 solution of the three macronutrients (dextrose, amino acids, lipid emulsions).

• A 3-in-1 solution and intravenous lipid emulsions) mixed with electrolytes, trace elements, vitamins, and water. Parenteral solution with only dextrose and amino acids with a separate intravenous lipid emulsions infusion, the 2-in-1 solution has also been previously used.[7] Research has shown TNA to be the standard of care for adult TPN.

Currently used TPN amino acid mixture continues to be incomplete with only 19 amino acids.[9] The non-essential amino acid glutamine has been used as a complement to TPN to complete the amino acid content of TPN (Glutamine 8 to 10% in PN is a compliment). Surgical critical care patients have decreased glutamine levels on admission, which continues to decline until the third hospital ICU day. Per a study by Tsuji, both high ≥700 nmol/mL and low  <400 nmol/mL of glutamine levels in ICU patients showed a statistical correlation with increased mortality than those patients with a range between 400 to 700 nmol/mL.[10] Glutamine should serve as a complement to TPN rather than pharmaco-nutrition at supra nutritional doses. Patients who should not receive glutamine complementation above what may be present in basal TPN, as referenced by Heyland et al., include patients in septic shock, hemodynamic instability with increased vasopressor doses, patients with renal failure.[11]

Administration

Total parenteral nutrition administration is through a central venous catheter. A central venous catheter is an access device that terminates in the superior vena cava or the right atrium and is used to administer nutrition, medication, chemotherapy, etc. Establishing this access could be through a peripheral inserted central catheter (PICC), central venous catheter, or an implanted port.[12]

PICC line insertion can be through the basilic, cephalic, brachial, or median cubital vein of the arm. The basilic vein is preferable due to its larger size and superficial location. The catheter courses through the basilic into the axillary vein, to the subclavian vein, to settle in the superior vena cava.[13] PICC lines could be used when TPN is administered for several weeks to months.

The insertion of central venous catheters can be through one of the large three central veins: femoral vein, subclavian vein, and internal jugular vein. Central venous catheters are used when administering TPN for several months to years.[14]

An implanted port is a device that is implanted under the skin in the chest with an attached catheter inserted into the superior vena cava. Implantable ports are used when administering TPN for years.[14]

Total parenteral nutrition is not administered through a peripheral intravenous catheter (Peripheral Parenteral Nutrition, PPN) because it has high osmolarity. PPN osmolarity needs to be less than 900 mOsm. The lower concentration necessitates larger volume feedings, and high-fat content is necessary. High osmolarity irritates peripheral veins; hence TPN is given through central venous access. PPN is used to provide additional nutrition to patients with functional gut and enteral feedings.

Adverse Effects

The main adverse effects can be due to metabolic abnormalities, infection risk, or venous access associated.

Venous access: It is associated with the insertion of the central line catheter. 

• Pneumothorax
• Air embolism
• Bleeding
• Venous thrombosis
• Vascular injury [15][2]

Catheter site infections:

• Bloodstream infection, known as sepsis
• Local skin infection at insertion or exit site

Metabolic abnormalities:

• Refeeding syndrome in chronic alcoholic patients, and in patients who have nothing-by-mouth status (NPO) for more than 7 to 10 days
• Hyperglycemia
• Sudden discontinuation can lead to hypoglycemia. Hypoglycemia is correctable with 50% dextrose. 
• Serum electrolyte abnormalities
• Wernicke’s encephalopathy [16][2]
• Parenteral associated cholestasis cholestasis

Contraindications

According to Maudar (2017), TPN is generally contraindicated in the following conditions:

• Infants with less than 8 cm of the small bowel
• Irreversibly decerebrate patients
• Patients with critical cardiovascular instability or metabolic instabilities. Such instabilities require correction before administering intravenous nutrition. 
• When gastrointestinal feeding is possible
• When the nutritional status is good and, only short-term TPN is needed
• The lack of a therapeutic goal, as TPN should not be used to prolong life when death is unescapable.[5]

Monitoring

Per Maudar 2017, several variables require monitoring while on TPN[5]:

• Intake and output 12-hour charts
• Urine sugar estimate every 8 hours
• Serum electrolytes: daily sodium, potassium, bicarbonate, calcium, and chloride values
• Serum creatinine and blood urea daily values
• Serum protein levels twice daily
• Liver function tests twice daily

The American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines include[17]:

• Patients who recently received TPN should be monitored daily until stable. They require more frequent monitoring if metabolic abnormalities are detected or if the patient has a risk of refeeding syndrome. Refeeding syndrome can occur in severely malnourished and cachectic individuals when feeding is reintroduced and can lead to severe electrolyte instabilities. Refeeding syndrome can correlate with hypophosphatemia, respiratory distress, rhabdomyolysis, and acute kidney injury. Prevention of refeeding syndrome is critical and achievable with a slower initial infusion of TPN than would be exected.[18]
• Unstable and critically ill patients should be monitored daily until stable.
• Stable hospital patients with no formulation changes for one week should be monitored every 2 to 7 days.
• Stable hospital, home, or long-term care setting patients with no formulation changes for one week should be monitored every 1 to 4 weeks if clinically stable.

Toxicity

Generally, the toxicity of TPN is related to the individual toxicity of its components. Increased caloric amounts due to TPN glucose and lipid excess can lead to hepatic toxicity; this risk can decrease by using decreased glucose content and greater lipid content. A glucose infusion rate greater than 5 mg/Kg/min can result in fatty liver; this is because increase glucose in the blood induces hepatic lipogenesis, and increased glucose levels trigger increased insulin levels leading to more lipogenesis.[19] This effect is preventable by decreased dextrose dosage to under 5 g/kg day, less than 5mg/kg min, cyclic PN for 8 hours as it decreases hyper-insulin, and substituting 30% of dextrose energy with lipids.

Parenteral nutrition supplementation rather than total parenteral nutrition is harmful to pediatric patients in the pediatric intensive care unit (PICU). Parenteral nutrition supplementation should be withheld in the first week in the PICU independent of age or nutritional status; this is because amino acids in the PN suppress the autophagy process needed for cellular damage removal. Excess amino acids a shuttled to urea production. Increased urea levels can pose harm to the kidney and liver.[20]

Long term usage of TPN ranging from weeks to months can be associated with the rare complication of manganese toxicity. Manganese exposure via TPN is characterized by high bioavailability due to bypassing the GI tract regulatory mechanisms. This high concentration of manganese over time leads to its deposition in the liver, brain, and bone. However, the brain is most likely to be affected as manganese will deposit and affect the globus pallidus and striatum of the basal ganglia. Manganese preferentially affects dopaminergic neurons in the basal ganglia resulting in extrapyramidal symptoms that present in a similar way to  Parkinson disease. Idiopathic Parkinson disease can be differentiated based on the location of neurons affected, i.e., in the substantia nigra.[21]

Enhancing Healthcare Team Outcomes

Managing the administration of TPN need s a well-coordinated health care team with an interprofessional approach.

The team includes:

• Clinician
• Pharmacist
• Dietician
• Nutrition nurse specialist

The clinician determines the treatment and the form of needed nutrition. The clinician coordinates care with the patient's primary health care team.

The pharmacist provides sterile parenteral nutrition. The pharmacists' advice on the stability of the compound and any drug/nutrient interactions that may arise.

The dietician assesses the nutritional status of the patient, calculates the daily requirement, and designs the feeding regiment.

The nutrition nurse specialist supervises catheters and tube care. They are the patient's advocate and trains the patient/caretaker to manage the tubes at home.

Extended staff includes: social workers, occupational therapists, and wound management nurses.[22]