7. Nutrition Intervention

In a well-nourished adult in steady state, total nitrogen intake will equal nitrogen output in urine, stool and skin. This is termed (zero) "nitrogen balance." Nitrogen is assimilated almost exclusively as protein, and, on average, 6.25 g protein is equivalent to 1 g nitrogen. The nitrogen is excreted predominantly as urea in the urine, but stool and skin losses account for about 2-3 g daily. If a 70 kg man consumes 1 g protein/kg (= 70 g protein or 11.2 g N), then about 8-9 g of nitrogen can be expected in the urine, assuming nitrogen balance. In the steady state, ingestion of more nitrogen will merely result in excretion of more nitrogen in the urine. In growing children or in malnourished adults, the nutritional goal is a positive nitrogen balance, meaning that body tissue is being formed in excess of what is being broken down (i.e., there is net growth).

Nitrogen balance studies have shown that well-nourished adults can maintain nitrogen balance when given as little as 0.5 g/kg protein intake, if energy requirements are met or exceeded. It is important that the protein supplied be of high quality; it should include all essential amino acids and a balanced mix of nonessential amino acids. Malnourished, septic, injured or burned patients will require more protein, in the order of 1.5-2.0 g/kg daily. Pregnant patients should also be given 1.5 g/kg protein daily. It is less clear that patients with conditions associated with protein loss, such as nephrotic syndrome and protein-losing enteropathy, benefit from extra protein intake.

Basal energy requirements in healthy subjects are accurately predicted by the Harris-Benedict equation:
Males: Energy (kcal/d) = 66 + (13.75 x W) + (5.00 x H) - (6.78 x A)
Females: Energy (kcal/d) = 655 + (9.56 x W) + (1.85 x H) - (4.68 x A)
where W = weight in kg, H = height in cm and A = age in years.

Basal energy requirements, as predicted by these equations, increase in the presence of fever (13% per ºC), sepsis or injury (up to 20-30%), and burns (up to 100%). Modest physical activity usually requires about 30% above basal requirements.

The options for refeeding include oral refeeding, tube feeding and total parenteral nutrition. An assessment by a dietitian regarding current food intake and food preferences is essential. It may well be possible by determining food preferences to provide a well-balanced, nutritionally complete diet. In addition, supplements of high-calorie, high-protein foods such as milkshakes or commercially prepared liquid formula diets may allow for adequate intake. If the patient will not or cannot eat, however, nutritional intervention may be indicated. Examples of patients who will not eat include those with anorexia due to tumor or chemotherapy, and those with anorexia nervosa. Such patients generally have a normal or near-normal nonobstructed bowel, and can be fed enterally. Patients who cannot eat because of severe gastrointestinal illness include those with bowel obstruction or ileus. If nutritional intervention is required in these patients, parenteral (intravenous) nutrition will be necessary.

Enteral nutrition generally refers to nutrition provided through a tube that has been inserted into the gastrointestinal tract. Usually the tube is a fine-bore (10 French [3.3 mm] or less) Silastic^® or polyurethane tube placed via the nose into the stomach, duodenum or jejunum. When long-term feeding is required, it is often preferable for cosmetic and comfort reasons to perform a gastrostomy, which can now be done endoscopically or radiologically with only local anesthetic and mild sedation. If pulmonary aspiration is a potential problem, the tube should be placed into the jejunum.

A multitude of commercial enteral formulas are available for infusion. The formulas have been traditionally divided into polymeric, oligomeric and modular. Polymeric formulas (also called defined formula diets) provide nitrogen as whole protein, often casein, egg white solids or soy protein. Carbohydrate is provided as corn syrup, maltodextrins or glucose oligosaccharides, with sucrose added for sweetness in oral formulas. Fat is usually provided as soy oil, although corn oil and safflower oil may be used. Medium-chain triglycerides (MCT oil) are rarely used. Protein may be provided as milk (usually dry or skim), with lactose as a major carbohydrate. These formulas are contraindicated in patients with lactose intolerance.

Oligomeric formulas (also called elemental diets) provide nitrogen as oligopeptides from partially hydrolyzed whole protein or as crystalline amino acids. Carbohydrate tends to be provided as glucose oligosaccharides or glucose. Fat is usually present in small quantities, enough to meet the requirement for linoleic acid (an essential fatty acid), which is about 2-4% of total calories. MCT oil is added to some formulas. The oligomeric diets were formulated to require minimal digestion by the gastrointestinal tract, with little necessity for bile and pancreatic secretions, and minimal "work" by the enterocyte in terms of brush-border enzyme activity or re-esterification. Hence, these diets have been commercially promoted as ideal for patients with decreased bile output (cholestasis), pancreatic insufficiency and short bowel. However, there is little evidence that these diets are superior to polymeric diets, except with pancreatic insufficiency. Crohn's disease is another condition in which elemental diets may be superior to polymeric diets, although this too remains controversial. Furthermore, since the diet is "predigested," osmolality is high. Finally, the high cost of these diets (often 5 to 10 times that of polymeric diets) rarely justifies their use except in patients with severe pancreatic disease or possibly Crohn's disease.

Most of these formulas provide enough protein, calories, water, electrolytes, minerals, vitamins and trace elements in 2 L/day for most "nonstressed" patients. In other words, these diets are "complete." Excess requirements may exist in patients with multiple injuries, major infections or burns.

Modular formulas are those that contain or predominantly contain one kind of nutrient. There are commercially available modules for protein, fat, carbohydrates, vitamins, electrolytes and trace elements. These modules are not required for the majority of patients, and are rarely used. However, they may be used if different nitrogen-to-calorie ratios are indicated for a patient. Examples of this might include burns or protein-losing enteropathy, if more protein is to be given, or liver disease, if less protein is to be given. Modular feeding is time-consuming, since solutions must be mixed by the hospital, and are more expensive than "complete" formulas.

Finally, specialized amino acid solutions have been made for use in special circumstances ^_ for example, liver disease, renal disease and "stress," such as trauma and sepsis. For liver disease, these solutions are composed mostly or exclusively of branched-chain amino acids, whereas for renal disease the solutions are predominantly essential amino acids. In general, these solutions are expensive and their efficacy is controversial.

Complications of enteral feeding may be divided into aspiration, mechanical, gastrointestinal and metabolic. In general, enteral feeding is well tolerated, and provided the complications are known, preventive and/or corrective measures may be undertaken to minimize patient risk.

Aspiration of the infused formula, with development of pneumonia, is a potentially lethal complication of tube feeding. Proper positioning of the tube requires radiographic verification. Risk factors for aspiration include patients on a ventilator and those with gastroesophageal reflux, poor or absent gag reflex, and impaired mentation. To minimize aspiration, it is suggested that patients, when possible, be fed with the head of the bed elevated 20-30º. Gastric contents should initially be checked by aspirating the tube every four to six hours, and if residue is present more than two hours following infusion, it should be temporarily stopped. Unfortunately, the small nasoenteric tubes in current use often collapse when aspirated, so small returns do not guarantee that the stomach is not becoming distended with fluid. Hence, examination for epigastric distention and succussion splash should be done. If there is any concern, an upright (if possible) plain film to assess gastric size may be useful. It has also been suggested that the feeding tube be placed into the small bowel well beyond the pylorus to minimize aspiration in those at risk.

Mechanical problems in patients with nasoenteric tubes include problems in the upper respiratory tract, esophagitis with development of esophageal ulceration and stenosis, tracheoesophageal fistula, and gastric outlet and small bowel obstruction. Upper respiratory problems include pharyngeal irritation, nasal erosions and necrosis, sinusitis and otitis media. These mechanical problems can be largely avoided by the use of soft, small-bore nasoenteric tubes.

Gastrointestinal problems related to nasoenteric feeding are common, occurring in 20-30% of patients. The most frequent complaints are nausea, vomiting, abdominal distention and altered bowel habit. Symptoms may be minimized by feeding at a slow rate with dilute solutions, but these symptoms may be just as common as with full-rate, full-strength solutions. Alternatively, a different enteral solution may be tried. If a lactose-containing solution is being used (generally not recommended for tube feeding), changing to a lactose-free solution is indicated. For constipation, fiber-containing solutions may be tried, although they are often unhelpful. Fiber, however, is a potential energy source for the colon, as previously discussed, and may therefore be important for maintenance of the colonic mucosa. At the present time, fiber-containing solutions are not routinely used.

Metabolic complications include overhydration, dehydration, hyperglycemia (including hyperosmolar nonketotic coma) and electrolyte disturbances. Electrolyte problems include hyponatremia, hyper- and hypokalemia, hyper- and hypophosphatemia and hypomagnesemia. In healthy, reasonably nourished individuals with normal cardiac, liver and renal function, these problems are not common. It is recommended that appropriate blood tests be done at intervals over the first few weeks to check for these potential problems.

Total parenteral nutrition (TPN) involves intravenous administration of all known essential nutrients. This form of therapy is as effective as oral or enteral intake in terms of growth and maintaining body nitrogen. Indications include inability to eat for a minimum of 7 to 10 days with a nonfunctional gut. Total parenteral nutrition is also used for "bowel rest," especially in Crohn's disease, intestinal fistulas and pancreatitis, even if adequate absorption is possible. Several studies suggest, however, that bowel rest is not helpful in Crohn's disease. Furthermore, other studies have shown that elemental diets can be used instead of TPN, except when bowel obstruction is present. In general, if the gut is functional, enteral feeding is preferred since it is safer, cheaper and more physiologic.

7.3.2.1.1 Amino Acids

"Protein" is supplied as synthetic crystalline, L-amino acid solutions; these are commercially available in 7-10% concentrations. Most available amino acid mixtures are devised for patients without special requirements. Solutions with added branched-chain amino acids are available for hepatic failure, and solutions with essential amino acids are available for renal failure.

There is a human requirement for linoleic acid, which is a precursor of arachidonic acid, which is in turn a precursor of prostaglandins. Linoleic acid, an essential fatty acid, cannot be produced by humans. It has been recommended that this be supplied as 4% or more of total caloric intake. Commercial fat solutions consist of soybean or safflower oil, emulsified with egg phospholipid, and made isotonic at 300 mOsmol/L with added glycerol. Commercially available fat emulsions are available at concentrations of 10% or 20%.

Glucose is the preferred carbohydrate for intravenous use. Glucose is widely available in concentrations from 5-70%. The osmolality of these solutions may be markedly hyperosmolar up to about 2,500 mOsmol/L.

Once the initial 100 g of glucose is provided for use in the brain, renal medulla and red blood cells, glucose and fat are equally effective in preserving body nitrogen after an equilibration period of four to five days. Glucose is very inexpensive as an energy source, but requires insulin for uptake into cells, and hyperglycemia can be a problem when large amounts of glucose are utilized. The high osmolality of glucose solutions means that only dilute solutions can be used in peripheral veins, and if glucose is used as a major energy source, a large central vein is necessary to prevent thrombosis. Furthermore, glucose has a respiratory quotient (R.Q. = CO₂ produced/O₂ consumed) of 1.0, meaning that large amounts of carbon dioxide may be produced. Finally, glucose infusion leads to catecholamine release and increased metabolic rate, further increasing CO₂ production. These changes may be deleterious for patients being weaned from ventilators, or with borderline respiratory function.

Lipid solutions offer the benefit of being iso-osmolar, containing linoleic acid and having a lower respiratory quotient of 0.7, with less carbon dioxide production. Drawbacks include somewhat higher cost compared to glucose, and poor tolerance in patients with hyperlipidemia.

7.3.2.2.1 Central

The most flexible way to deliver total parenteral nutrition is through a large central vein, usually the superior vena cava, via either the internal jugular or subclavian approach. With the large flow through the superior vena cava, solution osmolality is not of great concern, and thrombosis of this vessel is rare.

Ten percent amino acid solutions approach 1,000 mOsmol/L, and 50% dextrose solutions are over 2,500 mOsmol/L, while intravenous fat solutions are, as mentioned, iso-osmolar at about 300 mOsmol/L. Therefore, fat must become the major caloric source in a system that infuses total parenteral nutrition into a peripheral vein. There is a minimum requirement of a 1:1 ratio of amino acid/dextrose solution to the lipid solution. The typical peripheral total parenteral nutrition regimen will consist of 1 L of 5% amino acid/10% dextrose solution, Y-connected to 1.5 L of 10% lipid. This provides 50 g "protein," 350 kcal as glucose and 1,650 kcal as lipid, with the final osmolality over 600 mOsmol/L. Because of this hypertonicity, it is still necessary to rotate the catheter site every 48 hours to prevent phlebitis.

Complications of total parenteral nutrition may be divided into local and systemic. Local problems relate to the catheter site, and in the case of central lines involve all the complications of central catheters, including inadvertent arterial catheterization with bleeding, pneumothorax, hemothorax and inadvertent infusion of solutions into the pleural cavity. The complication of pneumothorax is much more common with subclavian insertion than with internal jugular insertion, meaning that internal jugular insertion is a safer technique, overall. Air embolism may occur at the time of insertion or any time thereafter with a central line. Catheter embolization may occur, and as mentioned, thrombosis has been reported, particularly with the use of stiff catheters. For long-term use, Silastic^® catheters are preferred. It is essential that catheter placement be done by persons with considerable experience to minimize these complications.

Systemic complications include sepsis, metabolic problems and bone disease. Bacteremia or fungemia occurs in 3-7% of patients given total parenteral nutrition, and this appears to arise predominantly from the hub where the catheter joins the intravenous tubing. Catheters are always inserted in a strictly aseptic manner, with personnel fully gowned and gloved. Metabolic problems include hyperglycemia, which can be treated by reducing the amount of glucose given in the solutions, hypertriglyceridemia when excess calories and/or excess lipid is given, and alterations in electrolytes. In particular, total parenteral nutrition causes anabolism with increased intracellular water, so that potassium and phosphate are driven into cells, leading to possible hypokalemia and hypophosphatemia. These complications are very uncommon if adequate amounts of these electrolytes are provided and careful monitoring is performed. Liver disease remains a frustrating complication of total parenteral nutrition and occurs in up to 90% of cases, but in most cases the changes are restricted to enzyme elevations. In general, mild elevations in AST and alkaline phosphatase occur in the second week, with occasional elevations in bilirubin occurring later. Liver biopsy may show mild cholestasis. Overfeeding, particularly with glucose calories, may result in steatosis; this can be treated by reducing total calories and glucose. Rarely, long-term TPN (extending over years) may result in cirrhosis without a well-defined cause.