Chapter 33. Specialized Nutrition Support

Specialized nutrition support is required to provide either total or partial nutrient supplementation for patients with general undernutrition or other specific nutritional deficiencies. Nutrition support can be provided intravenously (total parenteral nutrition), enterally, or by a combination of both routes.

The decision to provide specialized nutrition support starts with nutrition screening to identify those patients that are malnourished, or those with risk factors that place the patient at risk for nutrition-related problems. The nutrition screen may determine that a more careful nutrition assessment is necessary.1 The assessment should consist of a detailed history, physical examination (including anthropometric measurements), and biochemical parameters to assess the presence of malnutrition as discussed in Chapter 28. It should lead to nutrition risk stratification and specific nutrition therapy recommendations (energy, protein, and micronutrient requirements; route of administration; and treatment goals and monitoring parameters).

The goal of appropriate nutrition therapy is to improve the outcome of a patient’s primary illness, although data supporting this goal are typically lacking. An individual’s requirements for nutrients are initially estimated but cannot be accurately predicted. Therefore, careful monitoring of the nutritional status, including evaluation of growth and developmental parameters, diet history, physical examination, anthropometric measurements, and laboratory determinations, is required at regular intervals in all patients receiving specialized nutritional support. Teams that provide pediatric nutritional support services include physicians, nurse specialists, dietitians, pharmacologists, social workers, and feeding therapists. Such teams are now available at major centers to assist or impart guidance to provide and monitor nutritional support for pediatric patients.

Enteral alimentation provides nutrition via the functioning gastrointestinal tract. It is preferable to intravenous feeding because it is less costly and has far fewer and less serious complications. Nevertheless, proper caution must be exercised to avoid deleterious effects from enteral feeding.

Nutrients can be introduced into the intestinal tract by oral intake or by orogastric, nasogastric, nasoduodenal, esophagostomy, gastrostomy, jejunostomy, or gastrojejunostomy feeding tubes. The route selected depends on patient tolerance and the underlying medical condition necessitating specialized nutritional support. The orogastric route, most commonly employed in preterm infants with immature suck and swallow mechanisms, is useful to provide access for bolus feedings directly into the stomach; the tube usually is removed after each feeding. Nasogastric intubation permits more prolonged feedings, because the tube can be secured and left in position for up to several weeks. Gastrostomy feedings are implemented when the oral and nasal routes cannot be used, when patients have severe neuromuscular problems with dysphagia, or when access for enteral tube feeding is necessary for more than 2 to 3 months.1 Nasoduodenal or jejunostomy tubes are used in patients who may have abnormal gastric emptying or gastroesophageal reflux and aspiration. Additionally, with specially designed tubes and sometimes with the assistance of a gastroenterologist or radiologist, a gastrostomy tube can be converted into a gastrojejunostomy tube to treat these patients. Indications and contraindications for tube feedings are listed in Table 33-1. Tube choice and route selection are two of the most important components in the delivery of enteral nutrition (see Chapter 34).

Once a decision is made to start a patient on tube feedings, a formula must be selected; its strength, rate of infusion, and route of administration determined; and a tube selected. An appropriate formula must be carefully chosen by considering the patient’s age, underlying disease process, and gastrointestinal function. Commonly available formulas in the United States for use in infants are listed in Table 25-1, and those for toddlers and older children are listed in Table 33-2. Human breast milk or special premature formulas can be administered either by bolus or continuous drip to premature infants. Standard infant formulas can be used for those with extraintestinal problems such as lack of oral intake secondary to anoxic brain damage. Similarly, complete formulas can be used in older children who are unable to eat because of coma, severe burns, trauma, or other reasons, or who may benefit from supplemental nutrition infused overnight.

Lactose-free, low-residue, isotonic formulas may be useful in patients with chronic diarrhea. If these are not tolerated, or a patient has deficient intestinal digestive and absorptive function, a semielemental (ie, chemically defined) formula that is specifically designed to meet the nutritional needs of infants [eg, Pregestimil (Mead Johnson), Nutramigen (Mead Johnson), or Alimentum (Ross Laboratories)] or older children [eg, Peptamen (Nestle Nutrition)] can be instituted. Under certain circumstances, including in those patients with severe malabsorption conditions or exquisite protein intolerance, elemental formulas may be required. Most elemental formulas provide protein as free amino acids, adequate long-chain fatty acids to meet essential fatty acid requirements, glucose and glucose polymers, minerals, vitamins, and trace elements. Neocate (SHS North America) is the first elemental formula designed to meet the nutritional needs of infants. Elecare (Ross Laboratories) and Vivonex Pediatric (Novartis Nutrition) are elemental formulas that can be used to meet the specific nutritional requirements of toddlers and children. Note that long-term effects and outcomes have not been investigated for any of these formulas. In the event that formulas are used that have been formulated to meet adult requirements, such as Tolerex or Vivonex Plus (Novartis Nutrition) or Neocate One (SHS North America), mineral and vitamin supplements should be provided (eg, calcium, phosphorus, vitamin D).

Modular solutions that are nutritionally complete offer the opportunity to cater the regimen to meet specific needs. As examples, fat (Microlipid [Sherwood Medical]), protein (Casec [Mead Johnson]), and carbohydrate (Polycose [Ross Laboratories]) can be added to a formula to modify its composition and meet the specific needs of selected patients. Low-residue partially (ie, semielemental) or completely (ie, elemental) digested formulas are useful during the transition from parenteral to enteral alimentation because intestinal enzyme systems atrophy during TPN support. Considerations in choosing an enteral formula include the underlying diagnosis; nutritional status; gastrointestinal function; formula osmolality; protein source and quantity; lipid content and composition; mineral, vitamin, and trace element content; feeding route; lactose (and other carbohydrate) tolerance; fiber content; and cost.

Enteral feedings should be initiated slowly in patients with significant gastrointestinal dysfunction and who are on total parenteral nutrition. Because hypotonic and hypertonic solutions may adversely affect gastric emptying, and using a dilute formula plus parenteral alimentation may compromise fluid status, a full-strength isotonic formula can be started at a slow, continuous rate (1–2 mL/kg/h). As the enteral flow rate is increased, the parenteral infusion rate can be decreased almost equally until full nutritional support by tube feeding is achieved. Tolerance is continuously assessed by monitoring clinical changes such as abdominal distension, intake and output (including diarrhea and vomiting), the amount of residual food in the stomach, gastrointestinal blood loss, and reducing substances and pH of the stool.

Monitoring patients who are on enteral nutrition regimens is important to determine whether the selected regimen meets the nutritional goals for each patient. Additionally, complications can be avoided by reinforcing proper preparation and administration of nutrients as well as assessing metabolic imbalances before they become clinically evident. Common complications include aspiration, diarrhea, nausea, vomiting, dehydration, abdominal distention or cramps, constipation, bacterial contamination of the formula or the upper intestinal tract, nasal or skin ulcers, obstruction or infection of nasal passages, and electrolyte and mineral imbalances. Severe complications such as perforation of the posterior pharynx, esophagus, or cribriform fossa (resulting in intracranial placement of the feeding tube) are rare and generally avoidable by use of proper precautions and techniques.

Parenteral nutritional support should be used for patients who are unable to maintain adequate nutritional status orally or by tube feedings via the gastrointestinal tract.2 Parenteral nutrition is used when the intestinal tract cannot be used at all because of intestinal malformations or other congenital anomalies, gastrointestinal surgery, suspected necrotizing enterocolitis, severe respiratory distress, or other conditions in which the intestinal tract may not be able to assume the role of nutrient digestion and absorption. At times, parenteral nutrition is the only method of supplying nutrition when enteral feedings are not tolerated because of significant vomiting or diarrhea. Supplemental parenteral nutrition is useful when the intestinal tract can assimilate some but not all of the nutrients necessary for normal maintenance and growth. Enteral nutrients stimulate gut hormones and other secretions that may be trophic factors to the intestinal tract and thus may be beneficial where gut regeneration is necessary. Because prolonged use of parenteral nutrition is associated with significant complications as well as expense, careful selection of patients and judicious use of available enteral and parenteral solutions are particularly important.

As in enteral support, patient selection begins with nutritional assessment. This process includes determining the gastrointestinal tract’s ability to absorb sufficient nutrients; if it cannot, then nutrient infusions bypassing the gastrointestinal tract may be required. Indications for parenteral nutritional support are listed in Table 33-3. This list is not meant to be definitive or exhaustive; rather, it provides examples of conditions for which parenteral nutrition has been used with some success. Improved technology, newer formulas, and a better understanding of safe approaches to enteral nutritional support have allowed the replacement of parenteral with either complete or partial enteral support for many of the disorders listed. Each patient should be evaluated individually regarding needs and possible benefits and risks of parenteral versus enteral therapy.

Parenteral nutrition may be infused via peripheral veins in patients with good venous access who require short-term (ie, < 2 weeks) support and no fluid restriction. The maximum recommended concentration through a peripheral vein is 12.5% dextrose; this reduces the risk of thrombophlebitis, which occurs when the osmolality of the solution exceeds 900 mOsm/kg. Patients in whom caloric needs cannot be met by the peripheral venous route require a central venous catheter for nutrient infusion. The dextrose concentration then can be raised to 20% to 30% (ie, 2000–3000 mOsm/kg) or greater when infused through a central line placed appropriately, usually by an experienced pediatric surgeon, into the right atrium or superior or inferior vena cava. Percutaneous intravenous central catheters (“PICC lines”) are also utilized for long-term venous access including parenteral nutrition.

After placement of a central line, the physician must always document the correct location of the catheter tip by radiography before initiating the parenteral nutrition infusion. The catheter tip should be located just proximal to the junction of the superior vena cava and right atrium. Infusion of the solution through an improperly placed catheter can be dangerous to the patient. Complications that have been associated with catheter insertion include pneumothorax, hemothorax, hydrothorax, arterial puncture, myocardial perforation, catheter embolism, air embolism, cardiac arrhythmias, cardiac tamponade, and thrombosis of the jugular or vertebral vein or in the central nervous system because of catheter malposition.

The goal of the parenteral nutritional regimen is to provide the necessary fluid and nutrients either alone or in combination with enteral nutrition for maintenance or replenishment of normal nutritional status. In children, “normal” nutritional support includes nutrients for growth. Calculations therefore must be made to infuse adequate fluid, energy, fat, protein, electrolytes, minerals, vitamins, and trace elements to meet each patient’s requirements. Estimates of nutrient needs are based on oral intakes, balance studies, and accepted standards. Fluid and energy requirements are calculated for weight and age. Energy is supplied by glucose and emulsified lipid. Specific considerations for each component utilized in parenteral solutions are discussed in the following sections.

Glucose

Glucose, in the form of a dextrose monohydrate, provides 3.4 kcal/g of dextrose and can be infused safely through a central line in concentrations up to 35 g/dL (35% dextrose solution). The usual starting dose of dextrose to maintain a normal blood glucose concentration is 5 mg/kg/min. The dose can be increased as tolerated to 15 to 20 mg/kg/min; tolerance is judged by the absence of glycosuria and hyperglycemia. As noted earlier, the maximum recommended dextrose concentration administered via a peripheral vein is 12.5%. Premature infants often are unable to metabolize glucose at even relatively low doses and may require lower amounts and slower increases of dextrose infusions. If glucose intolerance appears in a previously stable patient, infection and sepsis must be considered; insulin may be required in selected patients to control glucose intolerance. The initial dose of insulin (usually 0.5–1.0 unit per 10 g of dextrose in solution) may be difficult to predict accurately because the insulin binds variably to the bottle and tubing. The goal should be to have no glucose or only trace amounts in the urine, although the serum glucose concentrations may still be as high as 150 mg/dL. It may be beneficial to avoid prolonged hyperglycemia in critically ill children, but this needs to be balanced with the avoidance of hypoglycemia.

Parenteral nutrient infusion containing a large concentration of dextrose cannot be discontinued abruptly unless another source of glucose (enteral or intravenous) is assured. High plasma insulin levels persist for 15 to 30 minutes after cessation of the glucose infusion and can lead to hypoglycemia. Problems with hypoglycemia on cessation of parenteral glucose infusions are routinely prevented by gradual tapering of the infusion rate.

Lipid

Lipid emulsions in a 10% solution (1.1 kcal/mL) or a 20% solution (2 kcal/mL) are composed of triglycerides stabilized with egg phospholipids and isotonically balanced with glycerol. They provide a concentrated calorie source with relatively low osmolality. At least 0.25 gm/kg/d of linoleic acid should be given to preterm infants (0.1gm/kg/d to older infants and children) to prevent essential fatty acid deficiency.1 The maximum recommended amount of intravenous lipid administered daily is 2.5 to 3.0 g/kg/d in adults and up to 4 g/kg/d in neonates, infants, and children. Usually, 25% to 40% of the infused calories are provided by lipids. Tolerance should be assessed by occasionally monitoring serum triglyceride concentration 4 to 8 hours after completing the lipid infusion. If the serum triglyceride level is greater than 250 mg/dL in infants and 400mg/dL in older children, the lipid infusion rate should be reduced. Side effects of lipid emulsion include allergic reactions (particularly in persons allergic to eggs), metallic taste, hepatomegaly, splenomegaly, transiently elevated serum transaminase (alanine aminotransferase, aspartate aminotransferase) concentrations, and hyperlipidemia resulting in decreased oxygenation and displacement of unconjugated bilirubin from albumin-binding sites. These last two effects are important considerations in neonates who may have pulmonary disease or indirect hyperbilirubinemia. The fat overload syndrome, which is characterized by jaundice, fever, leukocytosis, bleeding secondary to a coagulopathy, focal seizures, and possibly shock, occurs with extreme hyperlipidemia and has been reported in infants receiving lipid dosages of 4 g/kg/d or greater. Stable infants on a lipid infusion regimen may develop the fat overload syndrome in conjunction with an acquired viral or bacterial infection.

Newer lipid solutions composed of fish oils (Omegaven), which contain omega-3 fatty acids, may reduce inflammatory responses (such as tumor necrosis factor-α) to a variety of stimuli compared to traditional vegetable oil–based lipid emulsions. These solutions are not available for general use in the United States where they are currently under investigation. In Europe, fish oil–derived lipid emulsion for intravenous administration is available commercially. In some clinical scenarios, these lipid emulsions may reduce morbidity and mortality.3 Promising data suggest that they may be particularly beneficial for reversal or prevention of parenteral nutrition–associated liver disease in infants and children.4

Protein

Protein requirements are estimated from studies of fetal nitrogen accumulation (mean nitrogen retention of 320 mg/kg/d or of 2 g/kg/d protein) or by analysis of breast-fed–infant data. Current guidelines suggest giving premature and term infants a minimum of 1.5 g/kg/d of protein to prevent a negative nitrogen balance, with a maximum of 4 g/kg/day in preterm infants and 3.5 g/kg/day in term infants.1 Increasing the nonprotein calories above a minimum of 50 to 60 kcal/kg/d appears to enhance the efficiency of protein accretion in a growing infant. The amount of protein necessary to attain positive nitrogen balance declines with age, so by adulthood, the amount of protein required is 0.6 to 0.8 g/kg/d.

Most currently available amino acid solutions are not made specifically for infants and children. Newer formulations (TrophAmine [Kendall-McGaw], Aminosyn PF [Abbott Laboratories]) yield a plasma amino acid pattern resembling that seen in breast-fed infants; they possibly are preferable to the standard solutions now in general use. Addition of cysteine and other amino acids that may be essential for neonates is being considered, although evidence to support their routine use is not conclusive.

Special amino acid formulas for patients with renal or hepatic failure or sepsis also are available. However, because of their expense and lack of proven benefit in children, these solutions should not be used until their efficacy is demonstrated.

Electrolytes and Minerals

Electrolyte and mineral requirements can be met by using the guidelines listed in Table 33-4 and adjusting them as indicated for losses from vomiting, diarrhea, and also from nasogastric suction, gastrostomy, ileostomy, colostomy, or fistula outputs. Potassium, magnesium, and phosphorus should be monitored especially carefully when parenteral nutrition is given to a severely undernourished patient because, as the patient becomes anabolic, there is a flux of these minerals into cells (refeeding syndrome). Symptoms of hypophosphatemia, hypokalemia, and hypomagnesemia can be severe and life threatening in these patients (see Chapter 29). Potassium may be added to the solution as the acetate salt. Acetate is metabolized to bicarbonate and can be adjusted as desired to achieve acid-base equilibrium.

Precipitation of calcium phosphate in solution presents a problem in the supply of calcium and phosphorus to premature and term neonates, infants, and young children. Current solutions often do not contain adequate amounts to meet the patient’s metabolic requirements for both minerals, so infants who are on long-term parenteral nutrition have a high prevalence of bone demineralization, rickets, and fractures. Recent studies also suggest that the ratio of calcium to phosphorus should be approximately 1.3:1 to 1.7:1.1 High concentrations of calcium and phosphorus should not be infused by peripheral vein because of the risk of the potentially caustic solution infiltrating into the soft tissues. Oral supplementation may be beneficial for selected patients.

Vitamins and Trace Elements

All 13 vitamins are available in a single solution to meet the guidelines established for intravenous vitamin infusions (Table 33-5). The multivitamin preparation solution is available in a 5-mL vial. The dose for children weighing more than 3 kg is 5 mL/day. Additional vitamin D (25,000 IU intramuscularly per month) may be necessary to prevent rickets in infants receiving long-term total parenteral nutrition. In the past, extra water-soluble vitamins have been available as an additive for intravenous solutions, and these may be necessary for patients with excess losses, such as those undergoing hemodialysis or peritoneal dialysis.

Several trace elements have been associated with documented deficiency states in humans. Four are routinely provided in parenteral nutrition solutions: (1) zinc, (2) copper, (3) chromium, and (4) manganese (Table 33-6). Normal excretion routes for trace elements must be considered in assessing a patient’s requirements. Extra zinc may be needed in diarrheal states. Conversely, copper and manganese should be limited or totally withheld when cholestasis is present because they are both excreted mainly in bile. Copper levels should be monitored frequently in the presence of cholestasis and titrated to maintain normal serum levels. Selenium supplementation also may be necessary for patients on prolonged (ie, > 6 weeks) total parenteral nutrition with no enteral intake, but excess selenium should be avoided because it can also cause significant toxicity. Selenium, chromium, and molybdenum should not be administered to patients with renal failure. Iron is provided enterally if possible or by intravenous bolus infusion of iron dextran solutions as indicated. Intramuscular injections of iron should be avoided because of complications of pain, pigmented staining of skin, and difficulties in managing allergic reactions. The addition of iron to routine parenteral nutrition solutions is controversial because it may lead to sensitization and allergic reactions, and it is incompatible with lipid preparations. Additionally, prolonged intravenous iron administration may predispose patients to iron overload, gram-negative septicemia, or oxidant injury, especially in premature infants. Additional molybdenum and iodide may be useful to prevent deficiency states in patients receiving prolonged total parenteral nutrition, although adequate iodide appears to be provided by topical agents that are used routinely for catheter and wound care. Fluoride may be important in children with developing teeth who take no oral fluid containing fluoride, even though no data support this recommendation.

Other Additives

A variety of medications can be added safely to parenteral nutrition regimens. The compatibility of each drug with a specific solution should be confirmed before it is added to the solution. Common additives include heparin, H2-receptor antagonists (cimetidine, ranitidine), and antibiotics that are compatible with the solution. These can be infused in “piggyback” fashion so that the parenteral nutrient infusion does not have to be discontinued. Many pharmacologic agents precipitate in parenteral nutrient solutions and therefore cannot be infused into the same venous line as the total parenteral nutrition solution.

Careful clinical observation, laboratory assessment, and catheter technique can prevent complications that are usually associated with parenteral nutrition regimens. A pediatric nutritional support team, including a parenteral-nutrition nurse specialist designated specifically to care for these patients, has been shown to improve outcome and minimize complication rates. Complications are divided into 3 main categories: (1) infectious, (2) metabolic, and (3) mechanical (Table 33-7). Mechanical complications are discussed in Chapter 34. The most common and potentially serious complications are sepsis (1–5% of patients), usually with Staphylococcus, Streptococcus, gram-negative organisms, and Candida species; catheter thrombosis; and metabolic problems because of deficiencies (eg, refeeding syndrome), excesses, or imbalance of nutrients. This increased risk of sepsis requires that patients with a central line and fever be treated presumptively for infection.

Long-term parenteral nutrition may lead to hepatobiliary disorders, including cholestasis or fibrosis, and skeletal demineralization. Early initiation of enteral supplementation may help to prevent the development or progression of these problems. Use of a fish oil–based lipid emulsion may be beneficial in children with cholestasis on chronic total parenteral nutrition. Chronic use of loop diuretics and acid-base abnormalities especially predispose those infants receiving total parenteral nutrition to cholelithiasis and bone mineral loss. Increased experience with prolonged parenteral nutritional support may reveal other unrecognized nutrient deficiencies or parenteral nutrition–associated toxicities such as aluminum accumulation. Diminished renal function in patients on total parenteral nutrition for 4 years or longer also has recently been reported; further studies are pending to determine the significance of this observation. Another often overlooked problem with both enteral and parenteral nutritional support in infants and children is acquisition of oral feeding skills. Infants and toddlers acquire these skills at specific ages, so if the child has oral feeding entirely withheld, later acquisition of feeding skills is very challenging. Allowing a child to swallow even small amounts of water, breast milk, and/or formula several times a day or to eat and chew minimal amounts of food at developmentally appropriate times may either minimize or avoid problems with later acquisition of feeding skills.

Careful observation and reassessment are paramount to the successful implementation of parenteral nutrition regimens. Proper monitoring is necessary to detect or prevent complications and to assess the efficacy and appropriateness of the solution being infused. Clinical monitoring will determine whether mechanical or infectious problems are likely to occur. Biochemical abnormalities can be uncovered by appropriate laboratory assessment before they become clinically significant. Suggested guidelines are listed in Table 33-8. The frequency of monitoring will depend on the clinical status of each patient. Close monitoring of all patients on parenteral nutrition regimens is essential to assure optimal nutritional support and minimize complications.