Chapter outlines

INTRODUCTION

ADMINISTRATION OF PARENTERAL NUTRITION

SELECTION OF MACRONUTRIENTS

• Those in need of PN support for prolonged period.
• Patients requiring peripheral parenteral nutrition (PPN) with significant calorie supplementation but unable to tolerate carbohydrates.
• Critically ill patients, and those with hyperglycemia, diabetes mellitus, and respiratory failure. 

DELIVERING PARENTERAL NUTRITION

1. Routes of nutrient delivery:
   • Peripheral parenteral nutrition vs. central parenteral nutrition.
2. Systems of delivering PN:
   • Multiple bottle system, multichamber-bag PN, or hospital compounded PN.
3. Duration of delivering PN:
   • Continuous infusion of PN vs. cyclic infusion of PN.

1. Routes of nutrient delivery

a. Peripheral parenteral nutrition

1. Requirements of PN for a short period (less than a week). Postoperative patients requiring PN support are the most suitable candidates for PPN.
2. Nutritional needs <1500–1800 kcals per day.
3. Central venous catheter insertion is not possible, carries a high risk, or is contraindicated (e.g., patients with coagulopathy).
4. Sepsis or bacteremia in patients with CPN to avoid central vein catheterization for a few days.

1. In patients with high nutritional requirements (i.e., hypermetabolism, preexisting moderate to severe malnutrition, or high risk of protein depletion), PPN is not suitable, as it cannot provide enough nutrients.
2. Patients who need fluid restriction (oliguric patients and edematous patients due to cardiac, hepatic, or renal failure).
3. Critically ill patients who will not tolerate the high fluid volume of PPN required for providing their increased nutritional needs.
4. If PPN does not allow complete nutritional requirements, PN should be administered centrally.
5. If PN is required for a prolonged period (>2 weeks).

1. Easy and safe venous access.
2. It avoids morbidity and risks of CPN and saves the cost of a central catheter.

1. Larger volume is required to provide even maintenance nutritional requirements.
2. Difficulty in meeting high nutritional requirements (because the volume required to provide the same is prohibitively high in sick patients).
3. The concentration of nutrients in peripheral parenteral nutrition is kept low to prevent thrombophlebitis of peripheral veins. So, a larger volume is required to meet the nutritional needs compared to central parenteral nutrition formulas.

1. Add heparin (1U/ml of total volume) and low-dose hydrocortisone to the PPN formulas [10, 11].
2. Place a glycerine trinitrate transdermal patch on the skin overlying the tip of the IV catheter.
3. Topical NSAID creams and gel may inhibit the local inflammatory response.
4. Limiting the osmolarity of PPN to 600 mOsm/L.
5. Chang peripheral lines every 72–96 hours.

b. Central parenteral nutrition

2. Systems of delivering parenteral nutrition

a. Multiple bottle system

• Frequent manipulations during administering PN through multiple bottle systems carry a greater risk of nosocomial infections.
• Adjustment of different flow rates for different nutrients, adding different minerals and vitamins, and monitoring hyperglycemia, hypertriglyceridemia, and electrolyte disorders in each patient are cumbersome and are not without frequent mistakes.
• Simultaneous administration of various nutrients without maintaining proper proportion carries the risk of physicochemical incompatibilities.
• When costs of disposables and time spent by the nurse for administration of PN are considered, a multiple bottle system is costlier than commercially available multichambered PN formulations [43].

b. Multichamber-bag PN (MCBPN)

• Convenience: The easy, convenient, and most preferred way for the single-line administration of PN. As all nutrients are available in a single container (referred to as premixed, “ready-to-use” commercial bags), it saves time and reduces the workload [44, 45].
• Less infection: Decrease bloodstream infection rates due to less handling during preparation and delivery (reduced connections and reduced need of changing bags) [46–49].
• Safer: Lesser chances of various calculations and compounding human errors and better stability and sterility as manufactured with high standards [44, 45, 50].
• Recommended standard practice: SCCM-ASPEN guidelines (2016) and other literature recommend using standardized commercially available PN formulations compared to compounded PN admixtures when the formulation meets the patient’s metabolic needs [1, 51, 52].
• Lower cost: Cost-saving during preparation, handling, and delivery (requiring fewer bags and tubings and no extra pump for lipid emulsion) [40, 49, 53–55].
• Due to slow continuous infusion, better assimilation, and utilization of nutrients with lesser chances of metabolic complications.
• Storage is more convenient with long shelf life [44].

• Lack of flexibility: Changes in composition/proportion of contents are not possible.
• Inappropriate overuse due to easy commercial availability of different formulations with a wide choice.
• Absence of transparent color: Due to the presence of lipids, three in one solution is opaque, which impairs visual inspection of the solution for particulate matter, precipitation, or fungal growth.

C. Hospital compounded PN admixture

3. Duration and mode of delivering parenteral nutrition

a. Continuous parenteral nutrition

b. Cyclic/intermittent parenteral nutrition

DESIGNING PARENTERAL NUTRITION FORMULA

Step 1: Calculate the daily nutritional requirements and convert them into a prescription

Step 2: Choosing the appropriate commercially available formula for the infusion

INITIATION OF PN

• It is essential to evaluate the patient’s nutritional status by careful history, physical examination, and laboratory studies before initiation of PN.
• PN may be initiated in hemodynamically stable patients who can tolerate the fluid volume. Correct electrolyte abnormalities and hyperglycemia before the initiation of PN.
• PN should be initiated slowly (no more than 50% of the calculated requirements on the first day) to avoid adverse effects like hyperglycemia and electrolyte disturbances [66]. PN is increased gradually over 4 to 7 days to achieve the nutrition goal.
• PN may precipitate refeeding syndrome in severely malnourished patients due to rapid fall in potassium, magnesium, and phosphorus levels. So slow initiation and close monitoring of the patient’s electrolytes is necessary to avoid adverse effects on cardiac and respiratory function.

Care of PN mixture

• Store reconstituted PN bags in a refrigerator until 30 min before using.
• Always examine the PN solution before administration to exclude particulate matter, cloudiness, or an oily layer in the bag.
• Follow strict aseptic techniques while connecting and administering PN.
• To administer dextrose/amino acids PN formulations, use an infusion set with an in-built air vent and a 0.22-micron filter [52]. For administering lipids containing PN formulations, use a 1.2 micron - larger sized filter to avoid clogging of the filter.
• Do not use a three-way stopcock as it increases the risk of infection.
• Do not insert a needle for air venting in a PN bag.
• Do not add any medication to the PN bag.
• Do not allow the PN solution to hang for more than 24 hours.
• Do not use the PN line to draw blood for the test, administer medications, or measure central venous pressure.

MONITORING OF PN

• Metabolic status, including hyperglycemia and hypoglycemia.
• Risk of refeeding syndrome or clues of overfeeding.
• Micronutrient deficiency and toxicity.
• Fluid and electrolytes status.
• Catheter-related complications, including sepsis.
• Hepatic and other long-term complications.

• Always obtain a chest X-ray to check catheter placement after insertion.
• Record vital signs at least every 4 hours. Temperature elevation is one of the earliest signs of catheter-related sepsis.
• Patients should be weighed daily at the same time each morning after voiding on the same scale. Weight gain may indicate fluid overload.
• Perform site care and dressing change at least three times weekly or whenever the dressing becomes wet.
• Patients receiving PN should be monitored carefully to detect early signs of complications such as fluid overload, electrolyte imbalances, nutritional problems, or allergic reactions.
• Monitor serum glucose levels every 6 hours initially, then once a day. Watch for the symptoms of hyperglycemia, such as thirst and polyuria. Maintain blood glucose <180 mg/dL [1, 67].
• Monitor renal function, electrolyte levels, liver function, phosphate, calcium, and magnesium daily in the first week of initiating PN. Once the patient is stable, these tests are performed once or twice a week and less frequently in the long term.
• Monitoring response to nutritional therapy. There is no single criterion that can reliably indicate the effectiveness of PN. Improvement in clinical status and visceral protein concentrations (e.g., albumin, prealbumin, and transferrin) are most commonly used to monitor nutritional status. When interpreting visceral protein values, it is essential always to consider the patient’s fluid status, organ function, and presence of infection. If nutritional recovery is inappropriate, a nitrogen balance study may guide changes in amino acid intake. Similarly, if traditional methods of calculating calorie requirements are unsatisfactory, indirect calorimetry is indicated.
• If the patient receiving PN develops fever, chills, or hypotension, its most common cause is a catheter-related bloodstream infection. Therefore, for diagnosis of CRBSI, blood cultures should be drawn immediately before initiating antibiotic therapy.

TERMINATION OF PN

COMPLICATIONS OF PARENTERAL NUTRITION

CATHETER-RELATED BLOODSTREAM INFECTION

• Strict asepsis when handling (connecting/disconnecting) the line.
• Single-lumen central venous catheters should be dedicated solely to the infusion of parenteral nutrition.
• Use of a dedicated lumen on a multiple lumen CVC or a PICC line for administration of PN.
• Use of antibiotic-coated or antibiotic-impregnated catheters.

1. Evaluate the catheter insertion site and culture any drainage.
2. Obtain blood cultures: For diagnosis of CRBSI, blood cultures should be drawn from each lumen of the catheter and two sets of blood cultures from peripheral veins via separate venipuncture sites before initiating antibiotic therapy [73]. Catheter tip cultures cannot be used as a substitute for blood cultures to confirm catheter-related bloodstream infection [74, 75].
3. Begin empiric antibiotic therapy: In uncomplicated patients, it is unnecessary to remove the CVC. Instead, treat CRBSI immediately by administering broad-spectrum antibiotics through the lumen to salvage the catheter. It is unnecessary to remove the CVC in uncomplicated patients and treat CRBSI immediately by administering broad-spectrum antibiotics through lumen for catheter salvage.
4. Remove catheter: Indications of catheter removal are [76]:
   • Tunnel and pocket infections.
   • Clinical deterioration, septic shock, or presence of severe complications such as endocarditis, septic thrombosis, or abscess formations.
   • Repeated positive blood culture besides antibiotic therapy.
   • Although guidewire exchange has a lower risk of technical complications, it is not recommended as an alternative approach to removal.

METABOLIC COMPLICATIONS

A. Hyperglycemia

• Do not overfeed the patient (starting dose less than 20–25 kcal/kg/d).
• Restrict dextrose in PN to 100–150 gm/day initially and administer it slowly (2–3 mg/kg/minute).
• Increase the portion of lipid administration if needed (to supply calories and to limit the required dextrose).
• Consider other sources of IV dextrose such as peritoneal dialysis solution, antibiotic drips, etc.
• Monitor blood glucose closely (every 4–6 hours) and increase insulin doses accordingly. 

B. Hypoglycemia

• Overtreatment of hyperglycemia with the use of insulin via PN, IV infusion, or subcutaneous injection. The risk of hypoglycemia is higher when insulin is administered by drip.
• “Rebound hypoglycemia” after abrupt discontinuation of PN formulations (e.g., cyclic infusion of parenteral nutrition) [65].

• Slow tapering: Before discontinuing of the PN, tapper down infusion at half the rate for 1–2 h to reduce the risk of rebound hypoglycemia.
• If PN infusion needs to be discontinued abruptly, administer dextrose-containing fluid for about 1 or 2 hours to avoid the risk of hypoglycemia.
• When insulin is added to the PN solution, the risk of hypoglycemia is low on abrupt discontinuation of PN.
• As aggressive treatment of hyperglycemia to achieve tight blood glucose control carries the risk of hypoglycemia, a target blood glucose in the range of 140–180 mg/dL is recommended to reduce the incidence of hypoglycemia [82].
• Close monitoring of blood glucose and meticulous adjustment of insulin dosage (avoid higher insulin to dextrose ratio in PN).

C. Refeeding syndrome

• Severe malnutrition, BMI less than 18.5 kg/m2, recent weight loss (>10% within the last 3–6 months), poor or no nutritional intake for more than 5 days.
• Alcoholism abuse, anorexia nervosa, depression, bariatric surgery, bowel resections, malabsorption, insulin, chemotherapy, antacids, or diuretics.
• Low baseline levels of phosphate, potassium, or magnesium.

• Cardiovascular: Fluid overload, congestive heart failure, arrhythmias, bradycardia/tachycardia, and hypotension.
• Respiratory: Respiratory failure, pulmonary edema, hypoventilation, and failure to wean from the ventilator.
• Neurological: Paraesthesia, ataxia, delirium, Wernicke’s encephalopathy.
• Musculoskeletal: Weakness, fatigue, myalgias, and rhabdomyolysis.
• Miscellaneous: Abdominal pain, constipation, vomiting, anemia, metabolic acidosis.

• Search and recognize high-risk patients for refeeding syndrome.
• Order baseline laboratory tests to assess potassium, magnesium, and phosphorus status before initiating nutrition support.
• Prophylactic administration of adequate electrolytes (even if blood levels are in the low-normal range), vitamin (thiamine, water, and fat-soluble), and micronutrient (Zn, Fe, Se) in “standard” maintenance doses, concurrently with the nutrition support. An approximate daily dose of electrolytes supplementation suggested is 1–1.5 mEq/kg potassium, 0.2–0.4 mEq/kg magnesium, and 0.3–0.6 mmol/kg phosphate. If values of electrolytes are severely low, it is recommended to delay the initiation of nutrition support until the electrolyte imbalances are corrected.
• The recommended dose of thiamine is 100 mg per day, to be administered before initiating dextrose-containing IV fluids and to be given for a period of 5–7 days or longer.
• Start refeeding gradually and cautiously in a stepwise manner to avoid excessive nutritional replenishment and limit the resultant risk of refeeding syndrome. First, start caloric supplementation in low dose (no more than 50% of energy requirements [NICE guidelines] or 100–150 gm of dextrose or 10–20 kcal/kg for the first 24 hours [ASPEN guidelines 2020]) and increase the dose slowly (advance by 33% of a goal every 1 to 2 days).
• Careful administration of sodium and fluids to avoid fluid overload.
• Close clinical and laboratory indices monitoring. Measure vital signs every 4 hours on the first day and maintain daily weight and intake output chart. Monitor serum potassium, magnesium, and phosphorus every 12 hours for the first three days.
• If overt symptoms and abnormal electrolyte values, curtail nutritional supplementation. In patients with refeeding hypophosphatemia, reduce energy intake temporarily or restrict it for 48 hours and gradually increase subsequently. Reduce fluid intake if edema or congestive heart failure and replace electrolytes aggressively according to the serum electrolyte levels. 

D. Hepatic abnormalities

• Excessive energy intake or overfeeding.
• Glucose overload or excessive carbohydrate administration.
• Excess administration of lipid >1 gm/kg/d.
• Administration of soybean oil-based lipid emulsion.
• Continuous infusion of PN.
• Lack of enteral stimulation.
• Carnitine and choline deficiency.

• Avoiding excessive calorie administration: Avoid administration of >25 to 30 kcal/kg calories to reduce the risk of steatosis or fat deposition in the liver.
• Avoiding excessive carbohydrate administration: Avoid administration of >5 mg/kg/min/d carbohydrate to prevent PNALD/IFALD [96].
• Appropriate carbohydrates to lipids ratio: PN solution should contain about 70–85% carbohydrates and 15–30% lipids to provide nonprotein energy [106].
• Restrict the dose of soybean-based lipid emulsions (<1 gm/kg body weight/d) to treat children with PNALD [21, 107].
• Change the composition of lipid emulsions: Supplementation (partial or complete) of omega-3-fatty acids enriched fish oil to soybean-based lipid emulsions (with the reduced n6/n3 ratio) is recommended to prevent and treat PNALD [103, 108–110].
• Prefer cyclic PN instead of continuous PN: Cyclic PN (9 for 12 to 16 hours) allows time for the mobilization of fats during the non-administration period of PN [105]. Therefore, a switch to cyclic PN infusion helps stabilize or improve impaired liver function [64, 65, 111].
• Early oral or enteral nutrition: Even small amounts of oral or enteral nutrition (EN) stimulates enterohepatic circulation of bile acids and reduce the risk for PNALD.

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