Donna M. Kraus, Pharm.D.
Goal: To familiarize students with the differences in nutritional requirements between adults and children with respect to fluids, electrolytes, calories, carbohydrates, proteins, fats and trace elements.
1. Given the age, weight and disease state of a child, calculate the daily maintenance fluids and total daily fluid requirement.
2. List the indications and monitoring parameters (with monitoring frequency) for a child receiving TPN.
3. Given the age, weight and disease state of a child, be able to describe how to initiate and advance TPN with respect to fluids, carbohydrates, protein and fat.
4. Given the age, weight, disease states and TPN order for a pediatric patient, determine if the TPN order is adequate in terms of supplying appropriate calories, protein, fats, electrolytes, minerals, vitamins and trace elements.
5. For both central and peripheral TPN, list the maximum concentration of dextrose that can be used.
6. Explain why neonates and young infants need special amino acid formulations.
7. Discuss the important neonatal issues regarding lipid metabolism and the controversies/complications surrounding its use.
8. List and discuss the common complications of TPN.
9. List the 4 advantages of breast feeding.
10. Discuss the differences in human milk, cow milk and infant formulas with respect to protein, carbohydrates, fats, and mineral content.
11. For each of the following types of infant formulas, list 3 different brand names, how the content differs between types, the rationale of why each type would be used, and the disease state(s) that each would be used in.
a. Cow milk-based infant formulas
b. Soy based infant formulas
c. Therapeutic infant formulas
d. Preterm infant formulas
12. Given a pediatric patient case, be able to appropriately recommend an infant formula and whether or not the infant requires vitamin or mineral supplements.
Chessman KH, Anderson JD. Chapter 135/ Pediatric and Geriatric Nutrition Support in Pharmacotherapy, A Pathophysiologic Approach. 3rd ed. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Appleton & Lange, Stamford, Connecticut, 1997 (pages 2787 - 2797).
Highly Suggested Readings:
Cochran EB, Phelps SJ, Helms RA. Parenteral nutrition in pediatric patients. Clinical Pharmacy Vol 7, May 1988, pp 351 - 66.
McKenzie MW, Bender KJ, Seals AJ. Infant formula products in The Handbook of Nonprescription Drugs, 9th Edition, APhA editors, Washington: APhA 1990 (pages 529 - 561).
Manual of Pediatric Parenteral Nutrition, Kerner JA (editor), 1983, John Wily and Sons Publishers, New York.
Total Parenteral Nutrition, Lebenthal E (editor), 1986, Raven Press, New York.
Marshall LL. Infant formula products. American Pharmacy. Vol NS33, No 10. October 1993:55-60.
ASPEN Board of Directors. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. Journal of Parenteral and Enteral Nutrition 1993:17:1SA - 52SA.
I. Introduction: Adequate nutrition for the proper growth and development of a child requires individualization. The amount and type of fluid, calories, electrolytes, and trace elements are all based on age, weight, nutritional status, and disease state.
II. The total daily fluid requirement of any patient is equal to the normal daily maintenance fluids plus replacement of any fluid deficit plus replacement of any significant abnormal ongoing losses. Two methods to calculate normal maintenance fluids are described below. Normal maintenance fluids provide replacement for normal body functions and for normal losses (for example, insensible water loss, urine output and stool losses). Other factors that may increase the patient's total daily fluid requirements need to be replaced in addition to the normal daily maintenance fluids.
Total daily fluid requirement = Normal Maintenance Fluids + Deficit + Ongoing Abnormal Losses
Total daily fluid requirements may be increased by: 1) increases in insensible water losses due to such factors as fever, hyperventilation, phototherapy, radiant warming, skin breakdown, burns, etc. 2) initial deficits of fluid i.e., dehydration 3) significant ongoing abnormal losses such as diarrhea, vomiting, nasogastric tube losses, high output renal failure, etc.
A. Daily maintenance fluid requirements (i.e., normal maintenance fluids) are those required to maintain normal homeostasis for a 24 hour period. Surface area and body weight are two common methods used for the calculation of maintenance fluids in pediatric patients.
NOTE: Premature infants will have greater daily maintenance fluid requirements then those shown here due to their larger surface area to body weight ratio and thinner skin, both of which significantly increase their insensible water losses from the skin. In fact, preterm infants < 750 grams often require 200 - 250 ml/kg/day to prevent dehydration. Due to their highly specialized needs, calculation of fluid requirements for premature neonates will be considered beyond the scope of this lecture.
1. Daily maintenance fluid requirements calculated by body surface area: For pediatric patients, the amount of daily maintenance fluid required is in the range of 1500 - 1800 ml/m2/day. Usually 1500 ml/m2/day is used. The surface area method is usually used in children > 10 kilograms because a precise measurement of surface area is often difficult in smaller infants.
2. Daily maintenance fluid requirements calculated by body weight
|Weight||Daily maintenance fluid requirements|
|< 2.5 kg||120 ml/kg/day.|
|2.5 - 10 kg||100 ml/kg/day.|
|11 - 20 kg||1000 ml plus 50 ml/kg for every kg over 10 kg.|
|> 20 kg||1500 ml plus 20 ml/kg for every kg over 20 kg.|
|8 kg :||100 ml/kg/day = 800 ml/day|
|15 kg :||1000 ml + (50 ml/kg * 5) = 1000 + 250 = 1250 ml/day|
|27 kg :||1500 ml + (20 ml/kg * 7) = 1500 + 140 = 1640 ml/day|
3. Factors which may increase insensible water loss will increase daily fluid requirements.
a. Estimates of additional insensible water loss (e.g., fever) can be calculated as a percent increase of normal maintenance fluids (e.g. for fever, increase daily fluid by 12% of normal maintenance for every degree Centigrade over 37 degrees).
b. Neonates who receive phototherapy require 20 ml/kg/day additional fluid due to increased insensible water loss.
B. Fluid deficit is calculated by clinical assessment of dehydration.
Degree of dehydration Clinical Signs Mild Moderate Severe Thirst slight moderate intense Behavior alert, restless irritable to touch, may be lethargic hyperirritable to lethargic, may be comatose Mucous membrane normal dry very dry Tears present +/- absent Eyes normal sunken grossly sunken Skin elasticity (pinch retracts) immediately slowly very slowly > 2 seconds Skin color normal pale mottled or gray Anterior fontanelle normal sunken very sunken Weight loss 3 - 5 % 8 - 10 % 12 - 15 % Fluid deficit 30-50 ml/kg 80-100 ml/kg 120-150 ml/kg
NOTE: If the pediatric patient is hemodynamically stable, 1/2 of the fluid deficit is replaced over the first 8 hours, and the second 1/2 of the fluid deficit is replaced over the next 16 hours.
C. Ongoing losses also need to be replaced. Estimates of sensible fluid losses can usually be easily measured (e.g., NG tube losses, vomiting, etc).
D. Fluid restriction: As in adults, the amount of daily fluids administered to a pediatric patient may need to be restricted. Situations which require fluid restriction include patients with cerebral edema, congestive heart failure, renal failure, SIADH, patent ductus arteriosus, and certain pulmonary disorders. Fluid restriction may be calculated 1) as a percent of maintenance fluids (e.g., 2/3 or 3/4 maintenance) or 2) as insensible loss (300 - 400 ml/m2) plus urine output.
III. Pediatric Total Parenteral Nutrition (TPN)
A. The indications for TPN in children are similar to the indications in adults, i.e., if the G.I. tract cannot be used as a route of administration for nutrition, then parenteral nutrition may be indicated. One big difference vs adults is that due to fewer body stores and a higher caloric daily requirement, children are started on hyperalimentation sooner than adults. Generally, the smaller or younger the child is, the sooner (s)he needs appropriate nutritional intake. Indications:
1. Congenital or acquired anomalies if the G.I. tract: gastroschisis, bowel fistulas, intestinal obstruction, atresias, short gut syndrome.
NOTE: "Short gut syndrome" or "short bowel syndrome" is a condition which is present after a significant amount of intestine has been surgically removed. Often these patients are dependent upon lifetime parenteral nutrition.
2. Chronic or recurrent diarrhea: malabsorption syndrome, inflammatory bowel disease.
3. Preterm infants
4. Malnutrition (i.e. TPN as a supplement in certain diseases in which adequate caloric intake is not being achieved via the oral route: cystic fibrosis, cancer, anorexia nervosa, hypermetabolic states, e.g., burns).
5. Patient who are NPO (or who will be NPO) for sufficient periods of time to cause a significant decrease in caloric intake (e.g., post-operative patients).
B. Pediatric Parenteral Nutrition Practice Guidelines (from the American Society for Parenteral and Enteral Nutrition1):
1. Patients who are candidates for parenteral nutrition support are those requiring nonvolitional feeding who are either already malnourished or are at risk of developing malnutrition.
2. Peripheral parenteral nutrition should be used to provide partial or total nutrition for up to 2 weeks in patients who cannot ingest or absorb oral or enterally delivered nutrients, or when central vein parenteral nutrition is not feasible.
3. Peripheral parenteral nutrition may be used for short-term (less than 2 weeks) maintenance, supplemental nutrition, or repletion nutrition support in some older infants and children who are not fluid restricted.
4. Central intravenous nutrition support should be used in patients who do not tolerate enteral nutrition support or in whom peripheral access is limited, parenteral support will last longer than 2 weeks, nutrient needs cannot be met by peripheral parenteral nutrition, or fluid restriction is required.
C. Monitoring: In order to assure that TPN is meeting the nutritional goals, growth parameters (i.e., weight, height, head circumference) need to be assessed periodically. Monitoring of specific laboratory parameters assures adequate intake and decreases the complications of TPN. (See required reading: Table 108.11, Suggested monitoring schedule during pediatric TPN)
D. Fluid Calculations
1. Initial: The actual volume of TPN (hyperalimentation plus intralipid) to be given is calculated by subtracting the volume of the patient's other necessary fluids (e.g., continuous dopamine infusions, arterial lines, etc.) from the total daily fluid requirement. In patients who are not fluid restricted, who do not have fluid deficits or ongoing abnormal losses, and who do not receive other fluids, TPN is usually started at normal daily maintenance fluids.
2. Advancement of TPN fluid: In order to provide an adequate amount of calories for normal growth and development, the daily total fluid volume will need to exceed the daily normal maintenance fluid requirements.
a. Precautions: Congestive heart failure can easily be produced in a pediatric patient, if fluids are advanced too rapidly or too much fluid is given per day. Daily fluids should be increased according to the following guidelines and patients need to be monitored for signs/symptoms of fluid overload, edema, and CHF.
b. For infants < 10 kg the initial daily fluid volume may be increased (if tolerated) by 10 ml/kg/day until the desired caloric intake is achieved. The maximum amount of fluid (if tolerated) is 200 ml/kg/day.
c. For infants > 10 kg, the initial daily fluid volume may be increased by 10% of the initial volume per day (if tolerated) until the desired caloric intake is achieved. The maximum amount of fluid (if tolerated) is 4000 ml/m2/day).
E. Caloric Requirements: The goal of TPN is to provide adequate calories and nutrients for proper growth and development of the child. Proper growth of the child is determined by maintenance of the child's respective growth percentile for age and gender. For example, if an infant is 75th percentile for height and weight at age 3 months, then the goal is to maintain the 75th percentile for height and weight at older ages (i.e. as the child gets older, (s)he should be following the 75th percentile growth curves).
NOTE: Although controversial, the goal of nutrition in the preterm infant is to achieve a postnatal growth rate equal to the intra-uterine growth rate of a fetus at the same postconceptional age.
1. Caloric requirements per kg are greater in infants compared to children and adults. Children also require more calories per Kg than adults. These increases in caloric requirements are due to increases in cellular growth and physical activity, as well as an increased heat loss (due to the larger surface area per body weight seen in infants and children vs adults).
TPN caloric requirements2
Kcal/kg/day 0 - 1 90 - 120 1 - 7 75 - 90 7 - 12 60 - 75 12 - 18 30 - 60
2. Factors that increase caloric requirements: Similar to adults, certain factors will increase daily caloric requirements in children.
INCREASE IN CALORIC NEED2
Fever 10 - 12 % for each degree > 37o C Cardiac failure 15 - 25 % Major surgery 20 - 30 % Burns up to 100 % Severe sepsis 40 - 50 % Long term growth failure 50 - 100 %
NOTE: Infants with protein calorie malnutrition may require 150 - 175 Kcal/kg/day for growth.
F. Carbohydrates: As in adults, pediatric patients are NOT started on TPN with the highest amount of dextrose required to give adequate calories. Carbohydrates are started at a lower amount and advanced in a stepwise fashion to allow an appropriate response of the pancreas. This stepwise advancement allows the pancreas to adjust to the higher amounts of dextrose given by secreting larger amounts of endogenous insulin. Hyperglycemia, glucosuria and osmotic diuresis are thus prevented. (NOTE: Dextrose = 3.4 Kcal/gram)
1. Carbohydrate intake must be calculated for newborns and the very low birth weight premature infant in terms of gm/kg/day or mg/kg/min.
a. Preterm infants < 1 kg
1. Initial: 3 - 5 mg/kg/minute (Homeostasis)
2. Advance by: 0.5 - 1 mg/kg/minute per day
b. Term newborns and older infants
1. Initial: 7 - 8 mg/kg/minute
2. Advance by: 2 - 4 mg/kg/minute per day
c. Infants: Usual maximum rate of infusion: 18 - 20 mg/kg/minute
d. Children: Usually require 6 - 9 mg/kg/minute
2. Practical guidelines: Recommendations according to percent dextrose: Serum and urine glucose must be monitored as some patients may not tolerate these increases. These patients (usually preterm infants) will require other percent concentrations of dextrose, e.g., 6%, 7% etc.
Patient Age Group
5 % Dextrose
2.5 % Dextrose every
5 % Dextrose
2.5 % Dextrose per day
5 % Dextrose
5 % Dextrose per day
NOTE: Premature and newborn infants are more likely to become hypoglycemic if the dextrose solution is suddenly discontinued. Serum dextrose must be monitored if TPN discontinued. Excess carbohydrates (in comparison to protein and fats) may result in fatty infiltrates of the liver and an increase in pCO2 on blood gas.
3. Maximum dextrose concentrations for infants and children
a. Peripheral: 10%. Concentrations above 10% are associated with an increase in phlebitis and a decreased duration of use of the peripheral line. The peripheral use of 12.5% dextrose containing TPN is discouraged however, 12.5% dextrose containing TPN is sometimes used in patients who require higher calories or who are fluid restricted. Close supervision of the IV site then becomes mandatory (e.g., direct nursing care, ICU care).
b. Central: 20 - 25 %. The rapid dilution of TPN solutions with the larger quantities of blood in central veins, allows for solutions with higher final osmolalities to be used centrally (i.e., higher concentrations of dextrose). Typically, dextrose concentrations up to 20 % are used centrally. TPN with 25 % dextrose is usually reserved for severely malnourished patients. Occasionally, concentrations greater than 25% (i.e. 30 - 35 %) have been used in older infants and children who are severely fluid restricted.
G. Protein Requirements: Pediatric patients require a greater amount of protein per kilogram per day compared to adults. Again, this is due to their increased growth rates.3
Daily amount of parenteral protein to promote nitrogen retention Premature neonates and infants 2.5 - 3 grams/kg/day Greater than 1 year of age 1.5 - 2 grams/kg/day Adolescents & adults 1 - 1.5 grams/kg/day
1. Initiation and Advancement: Similar to carbohydrates, pediatric patients are NOT started at the daily amount of protein to promote nitrogen retention. Again, patients are started on lower amounts of protein and advanced in a stepwise fashion.
a. Neonates: Start with 0.5 - 1 gram/kg/day of protein and advance daily by 0.5 gm/kg/day.
b. Older infants and children: Start with 1 gram/kg/day and advance daily by 0.5 - 1 gm/kg/day.
2. Pediatric essential amino acids: In addition to the amino acids which are considered essential in adults,* cysteine, taurine, tyrosine and histidine are thought to be essential amino acids in neonates and young infants. These 4 amino acids are not synthesized in adequate quantities in neonates and young infants due to their decreased activity of enzymes. Therefore, these amino acids must be provided nutritionally.
* Isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine are considered to be the essential amino acids for all age groups.
For example: decreased activity of hepatic cystathionase results in a decreased production of cysteine with a subsequent decrease in taurine. (see figure 1)3 Hepatic cystathionase is thought to mature at approximately 6 months of age.
3. Pediatric amino acid formulations: (see Table 4)3
Neonates receiving standard adult amino acid formulations were found to have elevated plasma concentrations of methionine, phenylalanine and glycine as well as decreased concentrations of tyrosine, cysteine and taurine compared to normal breast fed infants. Two amino acid formulations have been designed to meet the special amino acid requirements in neonates and young infants. TrophamineR and Aminosyn-PFR contain less methionine, phenylalanine and glycine than adult formulations. Both also contain taurine, tyrosine, and histidine. L- Cysteine HCL must be added at the time of TPN preparation due to its instability in solution for prolonged periods.
NOTE: When using TrophamineR, 40 mg of cysteine HCL is added to the TPN for every one gram of protein. Since cysteine HCL comes as a HCL salt, one mmol of acetate or lactate is added to the TPN for every mmol (160 mg) of cysteine HCL. This acetate or lactate is added to balance the HCL load and prevent a metabolic acidosis which can be produced in premature and young infants. (Remember that bicarbonate results from acetate and lactate via the Kreb's cycle.)
Studies have shown that neonates receiving TPN utilizing TrophamineR had "normal" amino acid patterns i.e., patterns that were similar to breast fed infants. Significantly greater weight gain and nitrogen balance were seen in infants were given Trophamine compared to adult amino acid formulations. Further studies in neonates comparing Aminosyn-PFR and TrophamineR are needed.
4. Nonprotein calorie to gram nitrogen ratio: If an improper amount of nonprotein calorie to gram nitrogen ratio is given to a patient, (s)he will utilize proteins as a caloric source rather than for anabolic processes (i.e, as building blocks for cell growth). The optimal nonprotein calorie to gram nitrogen ratio in pediatric patients is not well defined. In the past, a nonprotein calorie to gram nitrogen ratio of 150 -200: 1 was suggested for adults. However, it is now realized that the ideal nonprotein calorie to gram nitrogen ratio differs with age and severity of illness. For critically ill infants and children, a nonprotein calorie to gram nitrogen ratio of 240 - 350: 1 has been suggested for proper utilization of amino acids. Remember:
Grams of protein / 6.25 = nitrogen content in grams
5. Caloric density: 4 Kcal/gram. Since it is not optimal to use protein as a caloric source, the protein caloric content of hyperalimentation fluids is generally not calculated.
H. Lipids: Lipids are administered as part of TPN to prevent or reverse an essential fatty acid deficiency and to provide a concentrated iso-osmotic source of calories.
1. Essential fatty acid deficiency:
a. Both linoleic acid and linolenic acid are thought to be essential.
b. The premature infant may develop biochemical evidence of essential fatty acid deficiency in as little as 2 days, due to limited fat stores.
c. Provision of 2 - 4 % of the required total daily calories as IV fat emulsion or approximately 0.5 - 1 gram/kg/day will prevent clinical signs and symptoms of essential fatty acid deficiency.
d. Signs of essential fatty acid deficiency include reduced growth, decreased platelets, impaired wound healing, dry scaly skin and sparse hair.
e. Biochemical evidence of essential fatty acid deficiency includes a triene:tetraene ratio greater than 0.4.
2. Lipid Metabolism:
a. Importance of Vitamin E: Lipid metabolism results in lipid peroxidation and free radical formation. Free radicals can damage cell membranes if Vitamin E is deficient. (Vitamin E acts as a free radical scavenger.) Lipid emulsions do contain a small amount of Vitamin E, however, supplementation with MVI is recommended, especially in infants. In order to prevent peroxidative injury, a vitamin E : polyunsaturated fatty acid (PUFA) ratio of > 0.6 mg/g is needed.
b. Decreased lipoprotein lipase activity: Lipoprotein lipase hydrolyzes fat particles to free fatty acids and monoglycerides. Both premature and term newborns have low lipoprotein lipase activity compared to adults. This results in a reduced lipid clearance rate. Hypertriglyceridemia / hyperlipidemia (fat intolerance) occurs when the rate of infusion of the fat emulsion exceeds the plasma lipid clearance rate. Premature infants, small for gestational age infants (regardless of gestational age) and nutritionally depleted older children are at risk for hypertriglyceridemia. Due to decreased fat clearance, lipid infusions for these patients should be administered over 24 hours.
NOTE: In infants and children, IntralipidR is typically infused over 18 - 24 hours.
c. Decreased metabolism of glycerol and free fatty acids:
Plasma lipid clearance is also decreased in neonates due to their decreased metabolism of free fatty acids and glycerol. Carnitine facilitates the transport of free fatty acids across the mitochondrial membranes to the site of fat oxidation. Premature neonates and newborns have limited carnitine stores which can decrease the proper utilization of free fatty acids.
3. Lipid emulsion dosing guidelines 2,3
Premature or SGA Full term or AGA Older children Initial dose 0.5 gm/kg/day 1 gm/kg/day 1 gm/kg/day Advance by 0.25 gm/kg/day or every other day 0.5 gm/kg/day 0.5 gm/kg/day Maximum dose 3 gm/kg/day 3 - 4 gm/kg/day 2 - 3 gm/kg/day
4. Serum triglycerides should be monitored before every (or every other) increase in lipid emulsion, especially in premature infants and routinely thereafter. If triglyceride levels are less than 200 mg/dl the patient can be maintained on her/his present dose.3
5. Caloric Content: Fats are usually considered to contain 9 kcal/gram. Due to emulsifying agents and other additives, IntralipidR 10% = 1.1 kcal/ml and IntralipidR 20% = 2 kcal/ml. Usually 25 - 40 percent of the total calories are provided by lipids but no more than 60 percent of total calories should be provided by lipids.
6. Hypersensitivity reactions including allergic reactions, fever, chills, shivering, cyanosis, flushing, nausea, vomiting, headache, dizziness, or chest and back pain have been reported due to the egg phospholipids which are used to emulsify fat emulsions. Patients should be monitored for these immediate adverse reactions.
a. Hyperbilirubinemia: Free fatty acids, which displace bilirubin from albumin binding sites, may cause an increase in the concentration of unconjugated bilirubin and increase the risk of kernicterus. Decreased amounts of fat emulsion (0.5 - 1 gm/kg/day i.e., just enough to prevent essential fatty acid deficiency) are usually given to neonates with elevated bilirubin concentrations. These decreased amount of lipids are usually given when total bilirubin concentrations are greater than one-half that required for exchange transfusion.
b. Pulmonary compromise: In patients with pulmonary compromise, lipid emulsions may decrease pulmonary diffusion capacity with a resultant decrease in PO2. These effects were observed when large amounts of fat emulsion were administered over short periods of time. The risk is decreased if lipids are infused over 24 hrs.
c. Heparin stimulates the release of lipoprotein lipase and has been postulated to be effective in reducing serum triglyceride concentrations in neonates receiving lipid emulsions. Further studies are needed before routine use of heparin can be recommended.
NOTE: Heparin is routinely used in TPN at a final concentration of 1 unit/ml to decrease thrombus formation at the central catheter tip, and to increase the duration of patency of peripheral hyperalimentation lines. (see required text reading)
I. Electrolytes and minerals
1. Requirements: Unless the patient has an electrolyte abnormality, start with the recommended daily amount and adjust according to serum chemistries.
Element Daily requirement (infants and children) Sodium 2 - 4 mEq/kg Potassium 2 - 3 mEq/kg Chloride 2 - 3 mEq/kg Magnesium 0.25 - 0.5 mEq/kg Calcium Gluconate 100 - 500 mg/kg Phosphorus 1 - 2 mmol/kg
Sodium: Premature neonates may require higher daily amounts.
Magnesium: Do not routinely add magnesium in the TPN for infants whose mothers have received therapeutic dose of magnesium (i.e. for tocolysis or prophylaxis against eclampsia). Check magnesium serum concentration first. Magnesium may be added if serum magnesium is not elevated.
Calcium Gluconate: Usually, the higher amounts listed are needed in premature newborns and neonates (300 - 500 mg/kg/day), while the lower amounts are recommended for older infants (200 mg/kg/day) and toddlers (100 mg/kg/day). Older children may require only 1 - 2 grams per day of calcium gluconate.
Phosphorous: Older infants and children will require less phosphorous (0.5 mmol/kg/day) than premature infants and newborns (up to 2 mmol/kg/day).
Potassium phosphate = 0.68 mmol phosphate per mEq
Sodium phosphate = 0.75 mmol phosphate per mEq
2. Calcium and Phosphate Compatibility
Since premature newborns, neonates, and young infants require a greater amount of calcium and phosphorus compared to adults, calcium / phosphate compatibility in hyperalimentation fluid is an important issue. Many times the amount of calcium and phosphorous that these patients require is greater than the solubility and calcium-phosphate can precipitate.
Many factors effect the solubility of calcium with phosphate in hyperalimentation solutions. Specific texts (e.g., Trissel's Handbook on Injectable Drugs) and solubility curves4 are utilized to determine if the amount of calcium and phosphate ordered in a hyperalimentation will precipitate.
2. Calcium and Phosphate Compatibility (continued)
Factors which effect calcium and phosphorous solubility include:
a. Concentration of calcium and phosphorous
b. Salt form of calcium
c. Concentration of amino acids
d. Type of amino acid solution
e. Concentration od dextrose
f. Addition of cysteine (effects pH)
g. Temperature of solution
h. Final pH
J. Vitamin requirements
1. MVI PediatricR provides the American Medical Association Nutrition Advisory Group (AMA-NAG) requirements for infants greater than 10 kg until 11 yrs of age. (See table 7 below) 5
2. Unlike the adult MVIR product, the pediatric product contains Vitamin K.
3. FDA recommendations for MVI PediatricR:
Infants < 1 kg 30 % of a vial (1.5 ml) Infants 1 - 3 kg 65 % of a vial (3.25 ml) Infants > 3 kg - 11 yrs 100% of a vial (5 ml)
4. In premature infants, the above FDA recommendations may not be adequate for certain vitamins (vitamin A and E) and may result in higher serum concentrations of water soluble vitamins (e.g., ascorbic acid).
K. Trace elements requirements: 6
1. Trace elements should be given to premature infants upon initiation of TPN and to term neonates and infants who will receive TPN for > 2 weeks.
2. Copper, zinc, chromium, and manganese available as combination products: EXAMPLES: Trace element content per 1 ml:
PTE-4 Pedtrace Neotrace Zinc 1 mg 0.5 mg 1.5 mg Copper 0.1 mg 0.1 mg 0.1 mg Manganese 25 mcg 25 mcg 25 mcg Chromium 1 mcg 0.85 mcg 0.85 mcg
The usual dose of these products is 0.2 ml/kg/day. Please note the big difference in zinc concentrations in these products. Neotrace has the highest amount of zinc and (just as the name implies) is intended for use in neonates. PTE-4 and Pedtrace have less zinc than neotrace and are intended for use in infants and children whose zinc requirements are less than neonates. If PTE-4 or Pedtrace is used in neonates, additional zinc must be given in order for the neonate to receive the total daily recommended amount. Children > 40 - 50 Kg should use the adult trace element formulations (e.g., Multitrace).
3. Selenium 2 - 3 mcg/kg/day up to daily maximum of 30 - 40 mcg also needs to be added to the TPN.
a. Absorbed from topical povidone iodine solution or ointment, so no need to add to TPN.
b. Thyroid profile monitoring recommended for long term TPN.
a. IV iron dextran is recommended for infants > 2 months of age receiving TPN for > 1 month. Preterm infants < 2 months of age may experience hemolysis after given IV iron dextran.
b. If iron is added to the hyperalimentation daily (controversial) the dose is 0.1 - 0.2 mg/kg/day.
c. For monthly IV replacements of iron: calculate iron needs by the following equation and administer the dose over 3 days. (Maximum daily dose = 25 mg).
Body weight (pounds) x (100 - % Hgb) x 0.3 = mg of elemental iron
6. Disease states which alter trace element requirements:
a. Increased losses: In diarrheal states or excess G.I. fistula losses extra zinc may be needed.
b. Decreased elimination:
1. Cholestasis (obstructive jaundice):
Eliminate copper and manganese from TPN
2. Renal failure:
Eliminate Cr and Se from TPN
NOTE: Some clinicians may eliminate Zn or decrease the daily amount.
L. Complications associated with TPN include infectious, mechanical, metabolic and other problems such as cholestasis and rickets: (see Table 9-27) 6. For further discussion of the complications of TPN see required reading text.
1. Infection: The most common organisms to cause sepsis in TPN patients are Staphylococcus epidermidis and Staph aureus. Other common bacteria include: Streptococcus, gram-negative organisms and Candida. Catheter site infections also occur.
2. Mechanical: One of the many mechanical problems with central TPN is thrombus formation. Urokinase (5,000 units/ml) may be used in children to lyse clots in catheters. When using urokinase to lyse a catheter thrombus, it is important to "treat the clot and not the patient" i.e., urokinase should NOT be injected past the catheter into the patient. The internal volume (ml) of the patient's central catheter must be known and only that same amount of urokinase used. Also, after allowing the urokinase to sit in the catheter and dissolve the clot, the urokinase should be withdrawn from the catheter. It should not be administered systemically to the patient. NOTE: The amount of urokinase that is used in adults to clear a catheter can have systemic effects in small infants if inadvertently administered through the catheter and not drawn back as required.
3. TPN cholestasis can occur in pediatric patients, usually after about 2 weeks of TPN. Premature infants and those receiving > 2.5 gm/kg/day of protein have a higher incidence of liver dysfunction. Other factors which may increase the incidence of TPN cholestasis include: sepsis, fasting (being NPO), and calorie overload. Discontinuation of TPN will usually reverse liver dysfunction. If TPN cannot be discontinued, TPN cholestasis may be managed by the following:
a. Give the appropriate type and amino acids and reduce the amino acid load.
b. Give the appropriate amount of calories (i.e. give an adequate but not an excessive amount).
c. Cyclic hyperalimentation (i.e., cycling the patient off of hyperalimentation for part of the day): Pediatric precautions: Infants more often than older children and adolescents may not be able to tolerate infusion periods less than 12 hours/day. Intolerance is usually due to inability to handle the higher ml/hr rates of fluid volume or nutrients that are given over the shorter period of time (i.e., the total daily amount of fluid and nutrients may be given over < 24 hours time, this results in a higher ml/hour rate).
d. Stimulate the gut with minimal enteral feeds.
M. Heparin: As previously mentioned, heparin 1 unit per ml (final volume) of hyperalimentation solution is often used in the pediatric population, both in central and peripheral TPN. Therapeutic doses of heparin may be approached with extremely high hyperalimentation rates or with frequent heparin flushes. (Maintenance doses of heparin are considered to be 10 - 25 units/kg per hour.) Therefore, a reduction from the usual 1 unit/ml of heparin in the hyperal to 0.5 units/ml may be needed especially in small infants requiring larger volumes of fluid.
IV. Pediatric Enteral Nutrition
A. Breast-feeding: "Breast is best": Mature human milk better meets the nutritional demands of human infants than cow's milk. Human milk is the standard against which all infant formulas are compared. Most commercially available (cow's) milk-based infant formulas are designed to closely approximate human breast milk.
1. Advantages of breast feeding and breast milk: Aside from the differences in protein, fat, carbohydrate and renal solute load (see next page) that exist between human milk and cow's milk, there are several other advantages of breast-feeding and breast milk.7
2. Disadvantages of breast-feeding:
1. Infant nutrition is dependent upon maternal nutrition
2. Possible mastitis (inflammation of the breast)
3. Transfer of drugs and/or pollutants (DDT, PDBs, etc.) to the infant
4. Transfer of viruses (Hepatitis B, CMV, HIV)
5. Transfer of allergen's from maternal diet to infant
1. A gradual weaning of breast-feeding starting after 4 - 6 months of age is typical.
2. Bottle (or cup) feedings are increased over a period of several weeks as breast-feedings are decreased and finally discontinued.
B. Comparison of nutrient composition of human milk, cow's milk and milk based infant formulas.
Table 5 -12: Composition of milk (per 100 kcal)8
1. Protein: Human milk contains a lower amount of protein compared to cow's milk, but is easier to digest.
a. Protein types: There are two major types of proteins that are found in milk.
1. Whey protein contains alpha-lactalbumin, beta-lactoglobulin, lactoferrin, albumin, lysozyme and IgA, IgG and IgM. Whey protein is highly soluble and easier to digest.
2. Casein protein contains a mixture of caseins (alpha, beta, gamma and kappa). Casein is relatively insoluble and forms "tough" curds.
b. Whey: Casein ratio
1. Breast milk 60:40 to 70:30
2. Cow's milk 20:80
3. Milk-based infant formula 60:40
Human milk contains a lower casein content and therefore is more easy to digest, compared to cow's milk. Milk-based infant formulas are made with heat-treated cow's milk proteins which form smaller, softer curds than raw or pasteurized cow's milk.
c. Other protein differences: breast milk vs cow's milk
1. Lactoferrin is found in greater quantities in human milk then cow's milk. Lactoferrin is an iron binding protein found in whey (1/3 saturated with iron). Lactoferrin increases the bioavailability of iron. It also has an inhibitory effect on E. Coli and may offer some protection against enteric infection.
2. Secretory IgA is also found in greater quantities in human milk than cow's milk. As an immunoglobulin, it may offer some local G.I. protection against infection.
3. Lysozyme is found in human milk but not in cow's milk. Lysozyme has bactericidal effects.
d. Protein sources, other than cow's milk protein, may be used for infant formulas. These include vegetable protein (soy) or protein hydrolysate (enzymatic breakdown products of casein or whey which result in reduced antigenicity).
2. Fats: Human milk and cow's milk contain a similar total amount of fat but the type of fats differ.
a. Human milk contains more of the essential fatty acid, linoleic acid, compared to cow's milk. Typical commercial infant formulas contain ever more linoleic acid.
b. Human milk but not cow's milk contains human milk lipase to aid in the digestion of fat.
c. Human milk contains long chain unsaturated fatty acids as well as medium chain fatty acids. Cow's milk contains short and long (primarily saturated) fatty acids. Milk based infant formulas replace butterfat with vegetable oil and special MCT oils to provide highly digestible, unsaturated, medium-chain triglycerides (MCTs).
3. Carbohydrates: Because cow's milk contains less carbohydrates than human milk, supplementation of cow's milk with carbohydrates to make milk-based formulas is necessary.
a. Lactose is the primary carbohydrate for human milk, cow's milk and milk-based infant formulas.
b. Infants are especially prone to lactose intolerance. The activity of the intestinal enzyme lactase is not fully developed until late in fetal life. In addition, infants may have a temporary reduction in lactase with diarrhea or malnutrition. (Lactase, as you recall, is the enzyme which is found in the brush border of the small intestine. Lactase cleaves lactose into galactose and glucose which are then absorbed.) Without lactase, the increased amount of lactose in the intestine creates an osmotic gradient in the colon that results in diarrhea. Excess lactose is also fermented by bacteria in the gut to produce CO2 and lactic acid.
c. Other carbohydrates such as dextrins, maltose, corn syrup solids and sucrose are can also be used in infant formulas (i.e., lactose-free formulas).
4. Renal solute load, osmolality, and caloric content
a. Cow's milk has three times the ash (mineral residue) and protein content as that of human milk. This results in a much higher renal solute load for cow's milk as compared to human milk. As you recall, renal solute load is related to the protein (urea) and mineral content of a formula. The renal solute load represents the total amount of water-soluble substances that must be removed from the body by the kidneys. The renal solute load of human milk = 79 mOsm/l, Cow's milk = 228 mOsm/l.
b. Osmolality is directly related to the mineral and carbohydrate content of a formula. The osmolality of human milk is approximately 300 mOsm/kg. Most formulas intended for use in infants are iso-osmotic. Generally, the higher the caloric content, the higher the osmolality. Infant formulas for preterm infants (24 cal/oz) have osmolalities less than 400 mOsm/kg.
c. Caloric content: Human and cow's milk have 20 kcal/oz. Most infant formulas are either 20 or 24 kcal/oz.
5. Mineral content: Although less in content/ml, both zinc and iron in human milk is more readily absorbed (ie, more bioavailable) than zinc and iron in cow's milk. Infants fed whole cow's milk diets often have iron deficiency anemias due to the decreased bioavailability of iron. The calcium to phosphorus ratio for human milk is 2:1, while for cow's milk it is 1:1.
C. Types and uses of infant formulas
(NOTE: composition is per 100 kcal.)
1. Complete cow milk-based infant formulas9
a. Used for normal term infants
b. Lactose is carbohydrate source
2. Complete soy based infant formulas9
a. Soy protein rather than cow protein
b. Lactose free
c. Used for
1. lactose intolerance or primary lactase deficiency (e.g., galactosemia)
2. milk allergy (NOTE: Protein hydrolysate formulas rather than soy based formulas are preferred for infants with cow milk allergy. About 10% of infants with cow milk allergy will also react to soy protein)
d. For disaccharide intolerance (sucrase deficiency) use Prosobee or Isomil SF
3. Therapeutic Formulas 9 /disease states
a. For fat malabsorption states, such as cystic fibrosis, short bowel syndrome, bile acid deficiency or cholestasis use Portagen or Pregestimil.
b. For general malabsorption states, use Pregestimil.
c. For protein and disaccharide intolerance, use Pregestamil or Nutramigen.
d. For congestive heart failure or when low salt content is needed, use Lonalac (short-term use only, Na = 1 mEq/l), SMA, or Similac 60/40.
e. For chronic renal failure use PM 60/40, SMA
f. For phenylketonuria use Lofenalac
g. For galactosemia use soy based formulas, Nutramigen or meat-based formulas (older infants).
4. Preterm formulas: differences include:
a. Partial substitution of glucose polymers for lactose
b. Increased protein
c. Substitution of long-chain fatty acids with MCT
d. Increased concentrations of vitamin D, calcium and phosphorus to promote bone growth
e. Altered concentrations of iron and vitamin E to prevent hemolytic anemia.
D. Supplemental foods are introduced at 4 to 6 months of age (after the infant has established the ability to swallow non-liquid foods). Introducing foods at this time also allows the infant to develop his/her host defense mechanisms to protect the infant from foreign proteins (i.e., food allergies are less likely to develop). In addition, the continued maturation of kidneys at this time will increase the handling of renal solute loads.
1. Feedings are usually started with iron fortified cereals such as rice. (Oatmeal cereals may follow.)
2. Vegetables, fruits, and pureed meats may also be introduced with cereal.
3. It is important to add one new food at a time and continue for 3 to 4 days before adding another. This allows time to evaluate allergy or sensitivity problems and to identify the food which caused the problem.
4. Iron fortified cereals are usually continued until about 2 years of age as an iron source.
E. Vitamin and mineral supplementation: It is now recommended that all infants receive iron fortified infant formulas. (These are commercially available)
1. General recommendations for supplements in healthy infants10
2. Fluoride supplementation is dependent upon age and concentration of fluoride in the drinking water. 11
NOTE: Fluoride dose is in mg/day.
3. Recommended daily dietary allowances for vitamins and minerals change with age. (See tables 12)
Recently, higher daily calcium requirements have been recommended by the NIH panel on optimal calcium intake.13
F. General Guidelines for Infant Feeding: Remember, introduce one new food at a time and continue for 3 to 4 days before adding another. Evaluate for allergy / hypersensitivity (diarrhea, vomiting, coughing, hives or rash).
1. DO NOT give foods such as nuts, seeds, popcorn, raw vegetables, hot dogs, candy or gum that may cause choking.
2. DO NOT give honey or corn syrup, which have been associated with infant botulism.
3. DO NOT force infant to eat everything, this may lead to overeating.
4. DO NOT give whole, 2% or skim milk under 1 year of age. Only give 2 % or skim milk after 2 years of age.
5. DO NOT add salt or sugar to infant's food.
6. DO NOT feed infant any solids or semi solids before the age of 4 months. Infant is not physically ready to eat solids nor do they need them. Breast milk or iron-fortified infant formula provides all the nutrients a FT infant needs to grow on until 4 - 6 months.
7. DO NOT prop up bottle and leave infant to feed him/her self (this may increase choking, as well as tooth decay and otitis media).
8. DO NOT leave older infant unattended at mealtime.
|Stroking the cheek near the mouth causes the infant to turn the face to that side, open mouth and attempt to suckle (Rooting reflex).||Breast
milk or formula, 6 - 10 feedings per day (21 - 24
Do not give semi-solid foods.
Vit D, Fe & Fl Rx may be recommended for breast fed infants.
No vitamin/mineral Rx needed for FT with iron fortified infant formula.
Plain water 3 - 4 ounces/day in very hot weather OK if tolerated.
|4 - 5 months||Infant is able to hold neck steady and sit with support. Can begin to draw in lower lip as spoon is removed.||Breast
milk or formula, 4 - 6 feedings per day (24 - 32
Vitamin/mineral Rx if indicated.
May start spoon feedings of Fe fortified dry infant cereal mixed with formula or breast milk to a thin consistency. Start with 1 Tablespoon of rice cereal at 1 feeding for 4 - 5 days. Gradually offer other single grain cereals and slowly increase to 3 - 4 Tablespoons per day.
|7 months||Infant can reach and grasp for objects. Jaw begins to use up and down movement.||Breast
milk or formula, 4 - 5 feedings per day (24 - 32
Vitamin/mineral Rx if indicated.
Fe fortified cereal: > 4 Tablespoons/day Vegetables/fruit: Start with 1 Tablespoon strained plain vegetables such as green beans, peas or carrots. Do not feed from jar, can cause bacterial growth. Put anticipated feeding in bowl. Feed from bowl. Cover remaining food in jar and refrigerate Do not add salt. Gradually add 1 Tablespoon plain strained fruit such as applesauce, apricots, peaches or pears. Slowly increase serving size to 4 - 5 Tablespoons/day.
Teething foods: Offer toast strips, unsalted crackers, zwieback, teething biscuits.
|8 - 9 months||Infant can sit alone without support. Baby is learning to chew. Important to offer foods that encourage chewing.||Breast
milk or formula, 3 - 4 feedings per day (24 - 32
Vitamin/mineral Rx if indicated.
Fe fortified cereal: > 4 Tablespoons/day Vegetables: > 4 Tablespoons/day
Fruit: > 4 Tablespoons/day
Chewing foods: toast strips, zwieback, unsalted crackers.
Protein Foods: Offer well cooked, strained or ground lean beef, pork, chicken, turkey, liver, cheese, cottage cheese, or egg yolk. Do not give egg whites until 12 months of age due to high chance of allergic reactions. Do not add seasoning. Remove all bones before straining. May use plain meat baby jar food (not mixed vegetables and meat dinners). Start with 1 Tablespoon and increase to 2 Tablespoons/day.
Juice: Give Vit C containing juice in a cup. Be sure to give fruit juice. Juice is more nutritious than fruit drink, fruit punch, pop or koolaid. Dilute 1 part juice with 2 parts water at first. Start with 1 - 2 ounces & increase to 2 - 6 ounces according to appetite. Do not give fruit juice by bottle especially at naptime. Fruit sugar can cause decay. Do not give citrus juices until 1 year of age due to high chance of allergic symptoms.
Finger foods: Give soft pieces of food such as toast strips, soft peeled fruit pieces, soft cooked vegetable pieces, cooked macaroni or noodles, milk cheese cubes or strips.
|10 - 12 months||Infant is able to hold a cup with help and try to feed self. Baby likes to play with food more than eat it. Expect a smaller and more picky appetite as infant's growth rate slows at 1 year of age.||Breast
milk or formula, 3 - 4 feedings per day (24 - 32
ounces/day). Offer some from a cup.
Vitamin/mineral Rx if indicated.
Fe fortified cereal: 1/4 cup/day Vegetables:soft cooked 1/4 - 1/2 cup/day
Fruit and fruit juice: 1/2 - 3/4 cup/day
Bread or toast: 1 - 2 slices/day.
Protein Foods: 2 - 4 Tablespoons/day. The infant's meal pattern should be similar to that of the rest of the family with 3 meals and 2 snacks.
1. ASPEN Board of Directors. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. Journal of Parenteral and Enteral Nutrition 1993:17:1SA - 52SA.
2. Manual of Pediatric Parenteral Nutrition, Kerner JA (editor), 1983, John Wily and Sons Publishers, New York.
3. Cochran EB, Phelps SJ, Helms RA. Parenteral nutrition in pediatric patients. Clinical Pharmacy Vol 7, May 1988, pp 351 - 66.
4. Fitgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Trophamine. Am J Hosp Pharm 1986;43:88-93.
5. Total Parenteral Nutrition, Lebenthal E (editor), 1986, Raven Press, New York.
6. Heyman MB. "Enteral and Parenteral Nutrition" in Rudolph's Pediatrics 19th edition. Rudolph AM, ed., 1991 Appleton & Lange, East Norwalk, Conn.
7. Wilson JT. "Prevalence and Advantage of Breast Feeding" in Drugs in Breast Milk. ADIS press 1981.
8. Hambidge KM, Krebs NF. "Normal Childhood Nutrition and Its Disorders" in Current Pediatric Diagnosis and Treatment 10th edition Hathaway WE, Groothius JR, Hay WW Paisley (editors), Appleton & Lange, East Norwalk, Conn, 1991.
9. Nichols BL. "Infant Feeding Practice" in Nutrition During Infancy Tsang RC, Nichols BL (editors), Hanley & Belfus, Inc, Philadelphia 1988.
10. McKenzie MW, Bender KJ, Seals AJ. "Infant Formula Products" in The Handbook of Nonprescription Drugs, 9th Edition, APhA editors, Washington: APhA 1990.
11. Committee on Nutrition. Fluoride supplementation for children: interim policy recommendations. American Academy of Pediatric News 1995;11(2):18.
12. Johnson KB (ed). The Harriet Lane Handbook, 13th edition, Mosby Year Book, St. Louis Mo, 1993.
13. NIH Consensus Developmental Panel on Optimal Calcium Intake. Optimal Calcium Intake. JAMA 1994;272:1942-8.
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|The University of Illinois at Chicago||Last modified: Dec 19, 1997|