TOTAL PARENTERAL NUTRITION

Total parenteral nutrition is a medication used to manage and treat

malnourishment. It is in the nutrition class of drugs. Total parenteral nutrition is
indicated when there is impaired gastrointestinal function and contraindications to
enteral nutrition. Total parenteral nutrition (TPN) is when IV-administered nutrition is
the only source of nutrition the patient is receiving. This activity describes the
indications, action, and contraindications for total parenteral nutrition as a valuable
agent in managing malnourishment and the nonfunctional gastrointestinal system. In
addition, this activity will highlight the mechanism of action, adverse event profile,
and other key factors (e.g., off-label uses, dosing, pharmacodynamics,
pharmacokinetics, monitoring, and relevant interactions) pertinent to members of the
interprofessional team in the management of patients with malnourishment and
nonfunctional gastrointestinal system and related conditions.

Indications

Parenteral nutrition is the intravenous administration of nutrition outside of the

gastrointestinal tract. Total parenteral nutrition (TPN) is when IV-administered
nutrition is the only source of nutrition the patient is receiving. Total parenteral
nutrition is indicated when there is impaired 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. According to Chowdary and Reddy
(2010), TPN has several indications. These include:

 Chronic intestinal obstruction as in intestinal cancer

 Bowel pseudo-obstruction with food intolerance.

 TPN can also be used to rest the bowel in cases of GI fistulas with high flow

 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

 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

The Food and Drug Administration (FDA) regulates parenteral nutrition in the
United States, and the FDA requires statistically significant evidence of the efficacy
and safety of parenteral nutrition products. Consequently, there are
postapproval clinical trial requirements for parenteral nutrition products.

Mechanism of Action

TPN is a mixture of separate components which contain lipid emulsions,

dextrose, amino acids, vitamins, electrolytes, minerals, and trace elements.
Clinicians should adjust TPN composition 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.

 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

o Healthy adult requirements are 0.8 to 1 gm of protein/kg/day.

 This change is 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.
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 vitamin dosing can be according to recommended daily

requirements.

 Electrolytes recommendation per liter of parenteral nutrition:

o Sodium: 100 to 150 mEq

o Magnesium: 8 to 24 mEq

o Calcium: 10 to 20 mEq

o Potassium: 50 to 100 mEq

o 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. Research has shown TNA to be the
standard of care for adult TPN.

The currently used TPN amino acid mixture continues to be incomplete, with only
19 amino acids. 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 greater than or equal to 700 nmol/mL and low less than 400
nmol/mL of glutamine levels in ICU patients showed a statistical correlation with
increased mortality in those patients between 400 to 700 nmol/mL. 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, and patients with
renal failure.

The pharmaceutical perspective of parenteral nutrition and Y site incompatibility:

 Parenteral nutrition (PN) mixtures should be physicochemically and

microbiologically stable. In addition, the preparation of TPN requires analyzing
their composition and any interactions that might occur during preparation,
storage, and administration.

 Hospitalized patients requiring parenteral nutrition (PN) need intravenous

medications. In one study, researchers evaluated the physical compatibility of
various drugs with neonatal total parenteral nutrition (TPN) solution during Y-
site administration. In this study, amiodarone, phenobarbital, and
rifampin formed visible precipitation with neonatal TPN and should not be co-
administered via Y-site injection.

 Clinicians should refer to individual compatibility of drugs with parenteral

nutrition to avoid potential hazards such as crystal formation.

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.

Clinicians can insert a PICC line into the basilic, cephalic, brachial, or median
cubital vein. 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. 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 three
large central veins: femoral, subclavian, or internal jugular. Central venous catheters
are used when administering TPN for several months to years.

An implanted port is a device implanted under the chest's skin with an

attached catheter inserted into the superior vena cava. Implantable ports have been
used when administering TPN for years.

Due to its high osmolarity, total parenteral nutrition is not administered through
a peripheral intravenous catheter (Peripheral Parenteral Nutrition, PPN). 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.

Use in Specific Patient Population

Patients with Hepatic Impairment

Rapid initiation of parenteral nutrition is recommended in moderately or

severely malnourished cirrhotics who cannot be nourished sufficiently by either oral
or enteral route. Parenteral nutrition is recommended in patients with unprotected
airways and encephalopathy (HE) due to the risk of aspiration in these patients. In
patients with liver disease, substantial inter-individual variability exists. Hence, if
available, resting energy expenditure (REE) should be calculated using indirect
calorimetry.

Patients with Renal Impairment

Patients with renal impairment, especially patients with ESRD, are at

increased risk of nutritional disorders. In hospitalized patients with AKI or CKD
requiring medical nutrition therapy, indirect calorimetry should be used to estimate
energy expenditure to guide nutritional therapy and avoid under or overfeeding. In
case of contraindications to ONS and EN, PN(parenteral nutrition) should be started
within three to seven days. To promote positive nitrogen balance in acute kidney
injury, clinicians should adjust protein intake according to catabolic rate, renal
function, and dialysis losses. Common laboratory abnormalities associated with
prolonged RRT include hypophosphatemia, hypokalemia, and hypomagnesemia.
Hence, electrolyte intake in patients should be adjusted by monitoring serum
concentrations. Trace elements should be monitored and supplemented as there are
increased requirements during ESRD, critical illness, and extensive effluent losses
during renal replacement therapy(RRT). Clinicians should give specific attention to
selenium, zinc, and copper.

Breastfeeding Considerations

A literature review suggests that breastfeeding women receiving total

parenteral nutrition have breastfed their infants. In addition, using intravenous amino
acids in parenteral nutrition in postpartum mothers may hasten the onset of lactation
and improve weight gain in breastfed infants.

Pregnancy Considerations

The association between low pre-pregnancy BMI and poor weight gain in
pregnancy with adverse perinatal outcomes has been well described; still,
information regarding the outcome of pregnancy in women on TPN is lacking.
Substantial advancements in TPN technology have now minimized maternal safety
concerns. However, according to the American College of Obstetricians and
Gynecologists (ACOG) guidelines, Clinicians should utilize enteral tube feeding to
provide nutritional support to a pregnant woman, as life-threatening complications
such as sepsis and thromboembolism associated with parenteral nutrition have been
reported. In addition, clinicians can insert peripherally inserted central catheter
(PICC) lines to avoid some complications associated with central lines. However,
PICC lines are still associated with substantial morbidity and should be used only
when enteral feeding is not feasible.

COVID-19 Considerations

Critically ill intubated patients with COVID-19 usually require a prolonged ICU
stay and are prone to significant energy and protein deficits. Therefore, when enteral
nutrition is not possible, there is a need to switch to parenteral nutrition. The
significant change in prescribing PN therapy was from soybean oil-based lipid
injectable emulsions (ILEs) to alternative ILE products with a lower inflammation
profile. In addition, the requirement for multi-chamber-bag PN products increased
during the pandemic. This practice reduced pharmacist and pharmacy technician
time in the sterile compounding area to decrease the use of PPE and divert
resources to other pharmacy responsibilities. For parenteral nutrition, nurses guard
the tubing with a protective layer, a critical consideration from an infection-control
perspective. In addition, for patients with COVID-19, consolidation of timing for
medication administration and parenteral nutrition is recommended. Finally, patients
with COVID-19 are prone to develop hypertriglyceridemia; hence, serum triglyceride
concentrations are obtained at baseline and within 24–48 hours of initiating
parenteral nutrition.

Adverse Effects

The main adverse effects can be metabolic abnormalities, infection risk, or

associated venous access.

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

 Pneumothorax

 Air embolism

 Bleeding

 Venous thrombosis

 Vascular injury

Catheter Site Infections

 Central line-associated bloodstream infection (CLABSI)

 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
  Parenteral-associated cholestasis

Due to safety concerns and the complexity of administration, parenteral nutrition is

considered high risk by the ISMP (Institute for Safe Medication Practice).

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, 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]

Boxed Warning: The FDA has issued a boxed warning for some intravenous fat
emulsions due to the increased risk of death in preterm neonates related to
intravascular fat accumulation in the lungs. Therefore, clinicians must be cautious in
choosing the right TPN therapy for preterm infants according to evidence-based
guidelines.

ASPEN (American Society for Parenteral and Enteral Nutrition) evidence-based

guidelines suggest using a 1.2-micron in-line filter. Although 1.2-micron filters are not
advised for use as standard infection control, these filters are efficacious in
preventing Candida albicans infection in patients receiving parenteral nutrition.

Monitoring

Per the American College of Gastroenterology, the identification of critically ill

patients who can benefit from parenteral nutrition should be made using a validated
scoring system such as Nutrition Risk Screening 2002 (NRS-2002) or Nutrition Risk
in Critically Ill (NUTRIC) score.
Per Maudar 2017, several variables require monitoring while on TPN. Among these
are:

 Intake and output 12-hour charts

 Urine sugar monitoring 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 weekly

The American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines also
offer monitoring guidelines. These include:

 Patients who recently received TPN should be monitored daily until stable.
They require frequent monitoring if metabolic abnormalities are detected or
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 expected.

 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.