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Pediatric Parenteral Nutrition

The therapeutic goal of PN in infants and children is both to maintain nutrition status and to achieve balanced somatic growth; in premature infants, the goal is to mimic intrauterine growth.

General Indications for Use: PN is the provision of required nutrients by the intravenous route to replenish, optimize, or maintain nutritional status.

Specific Indications
PN of all required nutrients (total parenteral nutrition) is indicated in patients for whom it is expected that it would be impossible or dangerous to enterally administer nutrition. PN in combination with enteral nutrition is indicated in patients who are expected to be unable to meet their nutritional needs by the enteral route alone within 5 days. Peripheral PN is indicated only for partial nutritional supplementation or as bridge therapy for patients awaiting central venous access.
1.  Patients with an inability to absorb nutrients via the gastrointestinal tract, which may include the following: Severe diarrhea, short bowel syndrome, developmental anomalies of the GI tract, inflammatory bowel disease, cystic fibrosis, or anatomic or functional loss of GI integrity
2.   Severe malnutrition
3.   Severe catabolic states, such as burns, trauma, or sepsis
4.  Patients undergoing high dose chemotherapy, radiation, and bone marrow transplantation
5.   Patients whose clinical condition may necessitate complete bowel rest (eg, necrotizing enterocolitis, pancreatitis, GI fistulas, or recent GI surgery)
6.   Intensive care low-birth-weight infants
7.   Neonatal asphyxia
8.   Meconium ileus
9.   Respiratory distress syndrome (RDS)

Nutritional Assessment
Nutritional screening may be done on admission by dietitian to identify patients who are malnourished or at risk of malnutrition. Patients identified through the screening process as being at risk should receive a complete nutritional assessment which may include anthropometric measurements, diet history, laboratory values, and physical exam. As many as 44% of hospitalized pediatric patients are malnourished and require nutritional therapy. The type of nutritional support indicated depends on the underlying disease, the degree of gastrointestinal function, and the severity of malnutrition. Acutely malnourished patients have an increased risk for serious infection, postoperative complications, and death. Indicators of acute protein-calorie malnutrition include low weight for height, low serum albumin, lymphopenia, decreased body fat folds, and decreased arm muscle area.

Nutritional Requirements
Energy requirements vary based on age. The following table provides an estimate for caloric and protein requirements at various ages for normal subjects.
Daily Caloric and Protein Requirements for Pediatric Patients
Age
kcal/kg/day
Protein g/kg/day
Preterm neonate
90 to 120
3 to 4
Term infant <1 year
85 to 105
2 to 3
1 to 7 years
75 to 90
1.5 to 3
7 to 10 years
50 to 75
1.5 to 3
11 to 12 years
50 to 75
0.8 to 2.5
>12 to 18 years
30 to 50
0.8 to 2.5
Patients who are severely malnourished or markedly catabolic may require higher levels to achieve catch-up growth or meet increased requirements. Patients who are well-nourished and/or inactive may require less.
During parenteral nutrition, 10% to 16% of calories should be in the form of amino acids to achieve optimal benefit (~3 to 4 g/kg/day in preterm infants, 2 to 3 g/kg/day in infants, 1.5 to 3 g/kg/day in children (1 to 10 years), and 0.8 to 2.5 g/kg/day in adolescents). Exceptions include patients with renal or hepatic failure (where less protein is indicated), or in the treatment of severe trauma, head injury, or sepsis (where more protein may be indicated).

PN ORDERING
Fluid Intake
The patient should be given a total volume of fluid reasonable for his/her age and cardiovascular status. It is generally safe to start with the fluid maintenance level of 1,500 mL/m 2/day in children >10 kg or use the Holliday-Segar weight-based method in children >2 weeks. The fluid requirements in preterm infants are extremely variable due to much greater insensible water losses from radiant warmers and bili-lights. While the standard fluid maintenance of 100 mL/kg/day may be sufficient for term infants, intakes of up to 150 mL/kg/day may be necessary in the very low birth weight infants. Be sure to consider significant fluid intake from medications or other IV fluids and enteral diets in planning the fluids available for PN.

Amino Acids
Amino acids may be described as either a "standard" mixture of essential and nonessential amino acids or "specialized" mixtures. Specialized mixtures are intended for use in patients whose physiologic or metabolic needs may not be met with the "standard" amino acid compositions. Examples of specialized solutions include:
TrophAmine, Aminosyn PF, PremaSol
Indicated for use in premature infants and young children due to addition of taurine, L-glutamic acid, L-aspartic acid, increased amounts of histidine, and reduction in amounts of methionine, alanine, phenylalanine, and glycine. Supplementation with a cysteineaadditive has been recommended.
HepatAmine
Indicated for treatment in patients with hepatic encephalopathy due to cirrhosis or hepatitis or in patients with liver disease who are intolerant of standard amino acid   solutions. Contains higher percentage of branched-chain amino acids and a lower percentage of aromatic amino acids than standard mixtures.
NephrAmine, Aminosyn RF
Indicated for use in patients with compromised renal function who are intolerant of standard amino acid solutions. Contains a mixture of essential amino acids and histidine.
aSupplementation is usually provided as a fixed ratio to the amino acid solution: 40 mg of cysteine per gram of amino acid; duration of supplementation is usually for the first year of life, but practice varies widely.
Protein provides 4 kcal per gram.
Amino acid calculations:
% amino acid
=
amino acid (g) per 100 mL
Grams of protein
=
grams of nitrogen x 6.25
% amino acid desired
=
(g amino acid/kg) x weight (kg) x 100
total PN fluid volume (mL)

Dextrose
For central PN, dextrose is usually begun with a 10% to 12.5% solution or a solution providing dextrose at no more than 5 mg/kg/minute (in neonates and premature infants). The concentration is advanced, if tolerated, by 2.5% to 5% per day (2 to 2.5 mg/kg/minute increments in neonates and premature infants) to the desired caloric density, usually 20% to 25% dextrose. Fluid restricted patients often need 30% to 35% dextrose to meet their energy needs. For peripheral PN, 5% to 12.5% dextrose is utilized.
Dextrose provides 3.4 kcal per gram.
Dextrose calculations:
% Dextrose = dextrose (g) per 100 mL
Dextrose infusion rate (mg/kg/minute)
=
rate (mL/h) x % dextrose x 0.166
weight (kg)
% Dextrose desired a
=
desired rate (mg/kg/min) x weight (kg)
0.166 x rate (mL/h)
aDo not use dextrose concentrations <5% due to hypotonicity.

Fat Emulsion (FE)
There are three roles for intravenous fat in parenteral nutrition:
1.   To provide nonprotein calories
2.   To provide essential fatty acids and a "balanced" calorie source
3.   To provide calories in catabolic patients with limited ability to excrete CO2
The FE dosage is increased as tolerated daily. The maximum fat intake is 3.5 g/kg/day and no more than 60% of the total daily caloric intake. It is administered as a continuous infusion over 24 hours or at a rate no greater than 0.15 to 0.17 g/kg/hour via a Y-connector with the dextrose-amino acid IV line. In patients receiving cyclic PN, the FE should be administered over the duration of the PN infusion. The triglyceride concentration should be checked on initiation and then weekly. Triglyceride concentrations should be maintained at <200 mg/dL in neonates, <350 mg/dL in renal patients, and <250 mg/dL in other patients. FE should be used cautiously in neonates with hyperbilirubinemia due to displacement of bilirubin from albumin by the free fatty acids. An increase in free bilirubin may increase the risk of kernicterus. Significant displacement occurs when the free fatty acid to serum albumin molar ratio (FFA/SA) >6. For example, infants with a total bilirubin >8 to 10 mg/dL (assuming an albumin concentration of 2.5 to 3 g/dL) should not receive more parenteral FE than required to meet the essential fatty acid requirement of 0.5 to 1 g/kg/day.
Note: Avoid use of 10% FE in preterm infants because a greater accumulation of plasma lipids occurs due to the greater phospholipid load of the 10% concentration.
Fat emulsion 10% provides 1.1 kcal/mL or 11 kcal/g
Fat emulsion 20% provides 2 kcal/mL or 10 kcal/g
Fat emulsion calculations:
20% FE = 20 g fat per 100 mL = 2 kcal/mL
Desired 20% FE (mL)
=
(% total kcal as fat) x (total kcal)

2 kcal/mL
or as an alternative
Desired 20% FE (mL)
=
FE (g/kg) x weight (kg) x 5 mL/g

General Guidelines for Initiation and Advancement of PNa
Age
Initiation and
Advancementb
Protein
(g/kg/day)
Dextrose (GIR)
Fat
(g/kg/day)
Premature infant
Initial
1.5 to 3
5 to 7 mg/kg/minute
1 to 2
Daily increase
1
1 to 2.5 mg/kg/minute or 1% to 2.5% increments
0.5 to 1
Goal
3 to 4
8 to 12 mg/kg/minute (max: 14 to 18 mg/kg/minute)
3 to 3.5
Term infant <1   year
Initial
1 to 3
6 to 9 mg/kg/minute
1 to 2
Daily increase
1
1 to 2 mg/kg/minute or 2.5% to 5%   increments
0.5 to 1
Goal
2 to 3
12 mg/kg/minute (max: 14 to 18 mg/kg/minute)
3
Children
1 to 10 years
Initial
1 to 2
10%
1 to 2
Daily increase
1
1 to 2 mg/kg/minute or 5% increments
0.5 to 1
Goal
1.5 to 3
8 to 10 mg/kg/minute
2 to 3
>10 years
Initial
0.8 to 1.5
3.5 mg/kg/minute or 10%
1
Daily increase
1
1 to 2 mg/kg/minute or 5% increments
1
Goal
0.8 to 2.5
5 to 6 mg/kg/minute
1 to 2.5
aRate of advancement may be limited by metabolic tolerance (eg, hyperglycemia, azotemia, hypertriglyceridemia)
bTimely intervention in premature infants is essential with initiation of dextrose as soon as possible after birth, amino acids within the first 12 hours, and fat emulsion within 24 to 48 hours of life.

ELECTROLYTES AND MINERALS
Guideline for Daily Electrolyte and Mineral Requirements
Preterm Neonates
(mEq/kg)
Infants/Children
(mEq/kg)
Adolescents/Children >50 kg
Sodium
2 to 5a
2 to 5
1 to 2 mEq/kg
Potassium
2 to 4
2 to 4
1 to 2 mEq/kg
Calcium gluconateb
2 to 4c
0.5 to 4
10 to 20 mEq/day
Magnesium
0.3 to 0.5
0.3 to 0.5
10 to 30 mEq/day
Phosphateb
1 to 2 mmol/kgc
0.5 to 2 mmol/kg
10 to 40 mmol/day
aPremature infants lose sodium in urine due to the immature resorptive function of kidney and diuretic use. Hyponatremia may lead to poor tissue growth and adverse developmental outcomes. Sodium content in PN may be adjusted to a maximum of 154 mEq/L (NS) to achieve normal sodium serum levels.
bCalcium-phosphate stability in parenteral nutrition solutions is dependent upon the pH of the solution, temperature, and relative concentration of each ion. The pH of the solution is primarily dependent upon the amino acid concentration. The higher the percentage amino acids the lower the pH, the more soluble the calcium and phosphate. Individual commercially available amino acid solutions vary significantly with respect to pH lowering potential and consequent calcium phosphate compatibility. 
cA 1.7:1 calcium to phosphate ratio in PN allows for the highest absolute retention of both minerals and simulates the in utero accretion of calcium and phosphate.

VITAMINS AND TRACE ELEMENTS
Vitamins
A pediatric parenteral multivitamin product is indicated for children <11 years of age and <40 kg. Children (>40 kg or >11 years) of age may receive adult multivitamin formulations.

Trace Element Daily Requirementsa
Preterm Neonates <3 kg
(mcg/kg/day)
Term Neonates 3 to 10 kg
(mcg/kg/day)
Children 10 to 40 kg
(mcg/kg/day)
Adolescents >40 kg
(per day)
Chromiumb
0.05 to 0.2
0.2
0.14 to 0.2
5 to 15 mcg
Copperc
20
20
5 to 20
200 to 500 mcg
Manganesed
1
1
1
40 to 100 mcg
Seleniumb,e
1.5 to 2
2
1 to 2
40 to 60 mcg
Zinc
400
50 to 250
50 to 125
2 to 5 mg
aRecommended intakes of trace elements cannot be achieved through the use of a single pediatric trace element product. Only through the use of individualized trace element products can recommended intakes be achieved.
bReduce dose in patients with renal dysfunction.
cReduce dose by 50% in patients with impaired biliary excretion or cholestatic liver disease.
dOmit in patient with impaired biliary excretion or cholestatic liver disease.
eIndicated for use in long-term parenteral nutrition patients.
These are recommended daily trace element requirements. Additional supplementation may be indicated in clinical conditions resulting in excessive losses. For example, additional zinc may be needed in situations of excessive gastrointestinal losses.

DEVELOPING THE PN GOAL REGIMEN
The purpose of this example is to illustrate the thought process in determining what dextrose and amino acid solution and fat emulsion intake would provide the desired daily fluid calorie and protein goals. The following example utilizes the method of calculating calories from protein, dextrose, and fat. However, some clinicians do not include protein calories since protein is used as a building block for adequate growth and development, rather than a calorie source.
1.   Calculate the fluid, protein, and caloric goals. Example:
Weight = 10 kg
Fluids = 100 mL/kg/day = 1,000 mL
Calories = 100 kcal/kg/day = 1,000 kcal
Protein = 2.5 g/kg/day = 25 g
2.   If fat emulsion (FE) comprises 30% to 35% of the total daily calories, using the above example: 30% of 1,000 kcal = 300 kcal
300 kcal ÷ 2 kcal/mL (20% FE) = 150 mL
3. Calculate percent amino acid solution to achieve goal protein intake. Example:
[25 g (total protein) ÷ 850 mL (total fluid)] x 100 = 2.9%
4.   Determine the calories from protein. Example:
25 g x 4 kcal/g = 100 kcal
5.   To determine the goal dextrose concentration calculate the total daily calories remaining. Example:
1,000 kcal
(total daily calories)
-100 kcal
(daily calories from protein)
-300 kcal
(daily calories from fats)
600 kcal
(total daily calories remaining)
6.   Determine the concentration of dextrose to achieve the total daily calories remaining. Example:
600 kcal ÷ 3.4 kcal/g x [100 ÷ 850 mLa] = 21%
aTotal daily fluids desired minus that from fats.
7.   Calculate the goal dextrose infusion rate (GIR) in mg/kg/minute. Example:
(850 mL ÷ 24 hours) x 21% x 0.166 ÷ 10 kg = 12.3 mg/kg/minute
This patient's goal regimen would be: Dextrose 21%, amino acid 2.9%, 850 mL/day plus fat emulsion 20% 150 mL/day.

Suggested PN Monitoring Guidelines
Suggested Frequency
Parameter
Initial/Hospitalized
Follow-up/Outpatient
Growth
Weight
Daily
Daily to every visit
Height/length
Weekly
Weekly to every visit
Body composition (triceps skinfold, bone age)
Initially
Monthly to annually
Metabolic (Seruma)
Electrolytes
Daily to twice weekly
Weekly to every visit
Magnesium
Daily to weekly
Weekly to every visit
Phosphorus
Daily to weekly
Weekly to every visit
BUN/creatinine
Weekly
Weekly to every visit
Acid-base status
Until stable
As indicated
Prealbumin
Weekly
Weekly to every visit
Glucose
Daily to weekly
Weekly to every visit
Triglyceride
Weekly
Weekly to every visit
Liver function tests
Weekly
Weekly to every visit
Complete blood cell count/differential
Weekly
Weekly to every visit
Platelets, PT/PTT
Weekly
As indicated
Iron indices
As indicated
Biannually to annually
Trace elements
As indicated
Annually
Carnitine
As indicated
As indicated
Folate/vitamin B12
As indicated
As indicated
Ammonia
As indicated
As indicated
Bilirubin, direct
Weekly
As indicated
Clinical Calculations
Fluid balance
Daily
As indicated
Projected vs actual intake
Daily
Weekly to every visit
Calorie/protein intake
Daily
As indicated
Frequency depends on clinical condition
aFor metabolically unstable patients, need to check more frequently
Adapted from: Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. ASPEN board of directors and the clinical guidelines task force. JPEN J Parenter Enteral Nutr. 2002;26(1 Suppl):1-138SA.

Pharmacologic considerations of mixing medications with PN solutions include:
Adsorption — bag, bottle, tubing, filter
pH factors
Blood levels
Temperature
Site of injection/administration
Additives in solution
Flush
Heparin dose
Amino acid-dextrose concentrations

REFERENCES
ASPEN Board of Directors and The Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr. 2002;26(1 Suppl):1-138SA.[PubMed 11841046]

Carney LN, Nepa A, Cohen SS, et al. Parenteral and enteral nutrition support: determining the best way to feed. The A.S.P.E.N Pediatric Nutrition Support Core Curriculum. Corkins MR, Balint J, Bobo E, et al, eds. Silver Spring, MD: American Society of Parenteral and Enteral Nutrition. 2010;433-447.

Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. JPEN J Parenter Enteral Nutr. 2004;28(6):S39-S70.[PubMed 15568296]