Sarah J. Miller
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Discuss how gut structure and function impact choice of feeding route and outcome of feeding.
2. Evaluate patient-specific parameters to determine whether enteral nutrition (EN) is appropriate.
3. Compare clinical efficacy, complications, and costs of EN versus parenteral nutrition (PN).
4. Choose an appropriate method of EN delivery based on patient-specific parameters.
5. Estimate kilocalorie and protein requirements of an enteral feeding candidate and design an EN regimen to meet these.
6. Choose an appropriate category of EN product given patient-specific parameters.
7. Formulate a monitoring plan for an EN patient.
8. Select appropriate medication administration techniques for an EN patient.
KEY CONCEPTS
EN is the preferred route if the gut can be used safely in a patient who cannot meet nutritional requirements by oral intake.
EN is associated with fewer infectious complications than PN.
For patients intolerant of gastric feedings or in whom the risk of aspiration is high, feedings delivered with the tip of the tube past the pylorus into the duodenum or, preferably, the jejunum are preferred.
Standard EN formulas are polymeric formulas; these are appropriate for most patients.
When choosing an EN formula, the patient’s fluid status should dictate the caloric density selected.
Clinical trial data supporting the use of specialty formulas in niche populations typically are unconvincing in terms of patient outcomes.
The role of enteral immunonutrition in clinical practice remains controversial.
GI complications are the most common complications of EN limiting the amount of feeding patients receive.
An important practice to help prevent medication-related occlusion is adequate water flushing of the tube before, between, and after each medication is given through the tube.
Compatibility of medications with an EN formula and, conversely, an EN formula with administered medications is of concern when administering medications through feeding tubes.
Enteral nutrition (EN) is broadly defined as delivery of nutrients via the GI tract. This includes normal oral feeding as well as delivery of nutrients in a liquid form by tube. Sometimes when the term enteral nutrition is used, only tube feedings are included; hence the terms enteral nutrition and tube feedings are often used synonymously. The bulk of this chapter will include information regarding delivery of feedings via tubes. Formulas for EN usually are delivered in the form of commercially prepared liquid preparations, although some products are produced as powders for reconstitution.
It might be expected that EN via tubes would have been used widely before development of parenteral nutrition (PN); however, this was not the case. Modern techniques for enteral access, both placement of the tubes and the materials for making pliable, comfortable tubes, were not developed until the 1960s and 1970s. The National Aeronautics and Space Administration effort in the 1960s led to development of low-residue (monomeric) diets for astronauts. These were adapted for use in sick patients requiring EN. Nonvolitional feedings in patients who cannot meet nutritional requirements by oral intake include EN and PN, which are collectively known as specialized nutrition support (SNS).
Several organizations have issued clinical guidelines on the use of EN. These include the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), the European Society for Clinical Nutrition and Metabolism (ESPEN), and the Canadian team known as Critical Care Nutrition.1–4 A.S.P.E.N. has recently teamed with the Society for Critical Care Medicine (SCCM) to release guidelines for SNS in critically ill patients.5
GI TRACT STRUCTURE AND FUNCTION
Anatomy and Absorptive Function
With normal volitional feeding, food is ingested via the mouth. Here, the process of breaking down complex foodstuffs into simpler forms that can be absorbed by the small bowel begins. Solid food is chewed in the mouth, and enzymes begin digestion. The trigger for release of many enzymes is presence of food in specific regions of the GI tract. Food is swallowed and passes through the esophagus and the esophageal sphincter to the stomach, where additional digestive enzymes and acids further break it down. The stomach also serves a mixing and grinding function.
The food, now in a liquid form known as chyme, passes through the pyloric sphincter into the duodenum, where stomach acid is neutralized. There is wide variation in lengths of the components of the small intestine (i.e., duodenum, jejunum, and ileum) between individuals (Table 101–1). Most absorption of digested carbohydrate and protein occurs within the jejunum. Most fat absorption occurs within the jejunum and ileum. In the small bowel, breakdown of macronutrients (i.e., carbohydrate, protein, and fat) occurs both within the lumen and at the intestinal mucosal membrane surface. The absorptive units on the intestinal mucosal membrane are infoldings known as villi.These villi are made up of epithelial cells called enterocytes. Projections (striations) from these enterocytes called microvilli increase the surface area of the small bowel and make up what is known as the brush-border membrane.
Table 101–1
Digestive enzymes secreted by the pancreas play a role in food breakdown. The pancreas secretes large amounts of sodium bicarbonate that neutralize stomach acid. These substances flow from the pancreas through the pancreatic duct. The pancreatic duct typically joins the hepatic duct to become the common bile duct that empties through the sphincter of Oddi into the duodenum. Bile secreted by the liver does not contain digestive enzymes, but bile salts help to emulsify fat and facilitate fat absorption. Bile flows through bile ducts into the hepatic duct and common bile duct. Bile is stored in the gallbladder until needed in the gut to aid fat digestion, at which time it empties through the cystic duct to the common bile duct to the duodenum. Pathways through which carbohydrate, protein, and fat are digested and absorbed through the small bowel are illustrated in Fig. 101–1.
After absorption in the small bowel, remaining undigested food passes from the ileum through the ileocecal valve to the colon. A major role of the colon is fluid absorption. Some of the water and sodium absorption achieved by the colon is facilitated by short-chain fatty acids (SFCAs) formed from digestion of certain dietary fibers by colonic bacterial enzymes.
FIGURE 101–1. Schematic of carbohydrate, fat, and protein digestion. (From Kumpf VJ, Chessman KH. Enteral nutrition. In: DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 7th ed. New York: McGraw-Hill, 2008:2400.)
Gut Immune Function
In addition to roles in digestion and absorption, the gut plays significant immune roles. The distal small bowel and colon host many bacteria and their endotoxins, and it is important that these organisms not gain access to the internal systems of the body. This function is known globally as the gut barrier function and can be divided into several components.6 Normal flora of the gut comprise one component. The normal flora, particularly some anaerobes, help to prevent overgrowth of potential pathogens. A second component of the gut barrier involves mechanical factors. These include an epithelial mucus gel layer that prevents adherence of bacteria and peristalsis of the small bowel that prevents stasis of bacteria. Gut-associated lymphoid tissue (GALT), prominent in the small bowel, serves as a local immune system. Secretory immunoglobulin A produced at the mucosal surface prevents bacteria from invading the surface. Bile salts and the reticuloendothelial system of the liver are believed to bind bacterial endotoxin and help clear it from the blood should it be absorbed into the portal circulation.
PATIENT SELECTION
In general, if the gut can be used safely in a patient who cannot meet nutritional requirements by oral intake, then EN is the preferred route. If the gut functions, EN is usually preferred over PN. The timing of SNS (either EN or PN) is controversial, but definitive guidelines for these therapies state that SNS should be started when intake has been inadequate for 7 to 14 days or if inadequate oral intake is anticipated to last at least 7 to 14 days.1 Prior nutritional status of the patient should be considered. Previously well-nourished patients can better afford not being fed for longer periods of time than those who are previously poorly nourished. Patients in the intensive care unit (ICU) setting probably benefit from early EN started within 24 to 48 hours of admission to the ICU.3,5 Methods for assessing nutritional status and designing SNS regimens are covered in Chapter 100. In general, non-obese hospitalized patients require 20 to 35 total kcal/kg of body weight/day and 1 to 2 g protein/kg of body weight/day.
Indications
Many potential indications for EN exist (Table 101–2). PN was used extensively previously for many of these conditions. Advances in EN technology now allow many patients with these conditions to receive EN. EN is administered in both institutional and home settings.
Contraindications and Precautions
EN should not be used or should be used with extreme caution in certain conditions (Table 101–3). It is possible to use EN in some patients with these conditions depending on severity of illness, location of abnormality, and experience of practitioners delivering care. Controversy surrounds some of these contraindications and precautions. For example, whereas some clinicians deliberately avoid enteral feedings in the hemodynamically unstable patient for fear of worsening intestinal ischemia, others believe that early feeding may facilitate intestinal perfusion and is beneficial.5,7–9 Still others might avoid jejunal feedings in this setting but would proceed with cautious gastric feedings.
Enteral Versus Parenteral Feeding
With the advent of the technique of PN by a large central vein in the late 1960s, this modality of feeding quickly became popular. PN was used originally in patients withinflammatory bowel disease (IBD) or congenital bowel abnormalities but was incorporated quickly into care of other types of patients such as the critically ill. The relative ease of PN administration, along with the perception that critically ill patients had prolonged high-energy expenditures, led to complications of overfeeding. In the United States, where no IV fat emulsion was available commercially for several years during the 1970s, the impact of dextrose overfeeding was observed. Complications included hyperglycemia, carbon dioxide overproduction leading to delays in weaning from mechanical ventilation, and liver abnormalities owing to hepatic steatosis.
Table 101–2 Potential Indications for EN
Table 101–3 Contraindications and Precautions for EN
Severe hemorrhagic pancreatitis
Severe necrotizing pancreatitis
Necrotizing enterocolitis
Diffuse peritonitis
Small bowel obstruction
Paralytic ileus
Severe hemodynamic instability
Enterocutaneous fistulae
Severe diarrhea
Severe malabsorption
Severe GI hemorrhage
Intractable vomiting
As complications of PN became evident, the pendulum began to swing toward EN in the late 1980s and early 1990s as clinical studies were published showing better clinical outcomes with EN compared with PN. Some of the potential advantages of EN over PN are included here. First, EN is expected to preserve the gut barrier function better than PN. This, in turn, could prevent translocation of bacteria and endotoxin from the gut lumen into the lymphatic system and systemic circulation, thus preventing infections. Studies from the same era support that 
EN is associated with fewer infectious complications than PN. EN is cited frequently as having a better overall safety profile than PN. Whereas PN is associated with more severe complications, such as pneumothorax and catheter sepsis, EN is associated with more nuisance complications, such as GI side effects that delay or limit delivery of nutrients. Another major frequently cited advantage of EN over PN is that EN is less expensive. It is true that EN formulas typically are cheaper and less labor intensive to prepare than PN, although some specialty EN formulas approach the cost of PN formulas. However, depending on the method of feeding tube placement, EN costs can mount if the tube must be placed by a radiologist or gastroenterologist rather than a nurse or if the tube must be replaced for some reason.
The arguments in support of EN over PN have been questioned. Part of this questioning relates to the question of whether EN is beneficial compared with PN or whether PN as commonly administered may be detrimental. Overfeeding and hyperglycemia occur easily with PN administration, and the potential harm of hyperglycemia, especially in critical-care populations, has been demonstrated poignantly, although the exact range optimal for glycemic control in the ICU patient remains controversial.10,11 A high-profile study published in 1991 demonstrated in a mildly malnourished perioperative population that there were more infectious complications in patients randomized to receive PN compared with those randomized to receive no SNS; there was no difference in noninfectious complications between the two groups.12
Only in severely malnourished perioperative patients were fewer noninfectious complications seen with PN; in these patients, no difference in infectious complications was seen between groups. Whether EN truly prevents infections and improves clinical outcomes or whether PN is detrimental continues to be debated and is probably dependent on the specific patient population. However, at present, EN is preferred by most experts over PN when the gut is functional. In Europe (more so than in North America), PN is used to supplement EN during the first week of intensive care therapy when EN is not yet being tolerated at full rates.2,13,14 This approach is currently discouraged by the Canadian guidelines and the A.S.P.E.N./SCCM guidelines for SNS in the critically ill patient.3,4 One meta-analysis did indicate that PN may be superior to delayed EN in critical care.15 Data are emerging to indicate that caloric and protein deficits early in the critical care stay are associated with increased morbidity and mortality; one method to prevent such deficits would be to augment EN with PN until full EN is tolerated.13 The Algorithms for Critical-Care Enteral and Parenteral Therapy (ACCEPT) trial showed that use of an evidence-based algorithm for SNS in critical care patients in community and teaching hospitals improved provision of EN and was associated with reduced hospital stay.16
ROUTES OF ACCESS17
There are several access sites for EN (Fig. 101–2). Nasogastric (NG), orogastric (OG), nasoduodenal (ND), and nasojejunal (NJ) routes generally are for short-term use (less than 1 month), whereas gastrostomy, percutaneous endoscopic gastrostomy (PEG), jejunostomy, and percutaneous endoscopic jejunostomy (PEJ) tubes are preferred for longer-term treatment. The esophagostomy/pharyngostomy is used rarely. Both advantages and disadvantages exist for each EN route (Table 101–4).
Gastric Feeding
Gastric feedings are used commonly. They require an intact gag reflex and normal gastric emptying for safety and success. Certain patients, such as those who have suffered head trauma, may not empty their stomachs efficiently and therefore may not be good candidates for gastric feedings. In these patients, it may be impossible to achieve a gastric tube feeding rate to provide adequate nutrients. In addition, pooling of formula in the stomach could increase risk of aspirating feeding formula into the lungs.
The NG route is used most commonly for short-term (less than 1 month) enteral access. The major advantage of this route is that the tube can be placed quickly and inexpensively by the nurse at the bedside.
Gastrostomy tubes, where an incision is made directly through the abdominal wall, are indicated for patients who can tolerate gastric feedings but in whom long-term (greater than 1 month) feedings are anticipated. The most commonly placed gastrostomy tubes are PEG tubes placed endoscopically. Gastrostomy tubes also can be placed laparoscopically or during an open procedure by a surgeon. Placement of a gastrostomy tube either endoscopically or surgically is more expensive than bedside OG or NG placement but does result in placement of a larger bore tube.
An advantage of feeding into the stomach is that the feedings can be delivered either intermittently or continuously.
FIGURE 101–2. Access sites for tube feeding. (From Kumpf VJ, Chessman KH. Enteral nutrition. In DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach, 7th ed, New York: McGraw-Hill, 2008:2403.)
Table 101–4 Options and Considerations in the Selection of Enteral Access
This is unlike feeding directly into the small bowel, where continuous feedings must be used. Intermittent feedings into the small bowel result in GI intolerance in most patients.
Postpyloric Feedings
For patients intolerant of gastric feedings or in whom the risk of aspiration is high, feedings delivered with the tip of the tube past the pylorus into the duodenum or, preferably, the jejunum are preferred. Feeding in this manner bypasses the problem of poor gastric emptying and adds another barrier (the pyloric sphincter) through which tube feedings must traverse before they are aspirated into the lungs. It should be noted that postpyloric feedings do not preclude the possibility of aspiration. Many patients with this complication are not aspirating tube feeding formula but rather their own nasopharyngeal secretions.
ND and NJ feeding tubes can be placed by trained, experienced nurses at the bedside. Although such placements typically take more time than NG or OG placements, this is still a relatively inexpensive method of placement. However, many institutions have not been able to achieve placements consistently at the bedside. In many institutions, ND or NJ placements are done in the radiology suite by a radiologist using fluoroscopy to visualize tube advancement to the appropriate area. This procedure increases the cost of EN therapy. NJ tubes generally are preferred over ND tubes; placement of the tip of the tube distal to the ligament of Treitz (located near the junction of the duodenum and the jejunum) may reduce risk of aspiration further. Alternatively, during a laparotomy, the surgeon can place an ND or NJ tube.
Patient Encounter, Part 1
A 25-year-old man was involved in a motor-vehicle accident in which he suffered several long bone fractures, a ruptured spleen, and a severe closed-head injury. This 5′, 10″-man was well nourished and weighed 75 kg before the accident. During the first surgery to repair his abdominal injuries, the surgeon placed a feeding jejunostomy tube. Following surgery, the patient was taken to the intensive care unit (ICU), where he was mechanically ventilated and had an intracranial pressure monitor. He initially required significant amounts of vasopressor agents to maintain his blood pressure. The decision was made to delay dealing with the long bone fractures until he was more stable.
What would this patient’s estimated caloric and protein requirements be?
What is the potential advantage of using EN rather than PN in this patient?
Why is a jejunostomy tube a good access route for feeding this patient?
Would it be prudent to start jejunal feedings immediately after the patient is admitted to the ICU following his abdominal surgery?
Surgically placed jejunostomy tubes are an option; similar to surgically placed gastrostomy tubes, they are placed through an incision in the abdominal wall, precluding the need for a tube down the nose or mouth. These tubes frequently are placed during laparotomy following abdominal trauma. Alternatively, jejunal access can be obtained by placing a jejunal extension through a PEG tube; the resulting tube is sometimes referred to as a PEGJ tube or G-J tube. Another option is to place a PEJ tube directly; this is more technically difficult than PEG placement and may not be available in some settings.
METHODS OF DELIVERY
Enteral feedings are delivered by several different methods. Continuous infusion must be used when duodenal or jejunal feedings are administered. For gastric feedings, bolus or intermittent feedings could be administered instead of continuous feedings. Each method has advantages and disadvantages.
In many hospitals, EN is delivered most commonly as a continuous infusion over 24 hours at a constant rate regulated by an infusion pump. A variation of continuous infusion is cyclic feeding, in which a constant rate is maintained by a pump over a certain number of hours daily. This method of administration is used commonly in long-term care or home settings. Often EN is administered overnight, giving the patient “freedom” from the infusion pump during the day, although this may not be practical for patients with high nutritional needs because it may be difficult to increase the rate of feedings while trying to maintain GI tolerance with limited infusions.
Intermittent feedings are used commonly in long-term care or home settings due to easier administration. Patients frequently are started with continuous feedings, transitioned to intermittent feedings given several times a day over about 30 to 45 minutes for each feeding, and eventually changed to bolus feedings, where feeding is administered several times a day over less than 10 minutes per feeding. An advantage of intermittent feedings is that they may be administered by gravity flow adjusted with a roller clamp, although some institutions may use an infusion pump. Bolus feedings preclude the need for an infusion set or pump and can be administered using a 60-mL syringe, although, again, in some circumstances an infusion set and pump may be used. Intermittent and bolus feedings often are given in amounts of 240 to 480 mL per feeding, corresponding to one to two cans (8 oz each) of formula.
EN FORMULAS
A number of EN formulas are marketed commercially. Hospitals and long-term care facilities usually limit formularies of EN formulas, stocking only a limited number of products. A number of factors should be taken into account when devising a formulary.
Polymeric versus Oligomeric Formulas
A major criterion for categorizing EN products is whether they contain more intact (polymeric) macronutrients or their macronutrient ingredients are present in simpler forms (oligomeric). Standard EN formulas are polymeric formulas; these are appropriate for most patients. Oligomeric formulas should be reserved for patients with GI dysfunction.
Polymeric formulas typically have low osmolality of 300 to 500 mOsm/kg. These formulas usually supply essential vitamins and minerals in amounts similar to the Adequate Intakes or Recommended Dietary Allowances (RDA) for these nutrients when the formula is delivered in amounts adequate to meet macronutrient requirements of most patients. Many polymeric formulas are inexpensive relative to oligomeric formulas. Most polymeric formulas are lactose-free and gluten-free, as are most modern tube feeding products. Products designed to be used as oral supplements generally are polymeric and often have sucrose or other simple sugars added to improve taste.
The oligomeric formulas are also known as chemically defined formulas. This class of formulas can be subcategorized based on whether the formula contains all free amino acids (elemental formulas) or peptides (peptide-based) as the protein source. Some formulas contain a combination of free amino acids and small peptides. Actually, dipeptides and tripeptides are absorbed more efficiently than free amino acids. Oligomeric formulas may be better tolerated than polymeric formulas for patients with defects in GI function and may be particularly useful with severe pancreatic dysfunction or significantly decreased GI surface area (e.g., short bowel syndrome).
Oligomeric formulas typically are more expensive than polymeric formulas and have higher osmolality because they contain more osmotically active particles. However, osmolality of these products usually does not exceed 700 mOsm/kg, a value less than that of many oral medications or a regular diet. In the past, there was concern that higher-osmolality EN formulas could cause GI intolerance, particularly diarrhea. This led to dilution of formulas by half or more with water and gradually increasing both the strength and rate of formula administration. This practice is unnecessary and serves only to delay attainment of goal nutritional support. Sometimes enteral feedings are diluted to deliver extra water required by the patient; this practice generally is discouraged because of potential risk of formula contamination. Instead, it is better to give extra water as boluses through the tube. If medications are administered through the feeding tube, generous amounts of water should be used to flush the tube before and after each medication; this practice helps provide extra fluid and prevent problems with occlusion of the tube.
Oligomeric formulas usually are less palatable than polymeric formulas and are not designed for use as oral supplements. Many of the oligomeric formulas provide some fat calories as medium-chain triglycerides (MCTs), a fat source that is more readily absorbed and metabolized than long-chain triglycerides (LCTs) typically found in polymeric formulas. The MCTs do not require bile salts or pancreatic enzymes for absorption. Some of the elemental formulas contain a low proportion of fat (less than 10% of total calories), which makes them useful in certain situations where fat needs to be restricted. The carbohydrate source in oligomeric formulas is also less complex than in polymeric formulas, consisting of oligosaccharides rather than hydrolyzed starch.
Fiber Content
Another distinguishing factor of enteral formulas is whether or not they contain fiber. Both soluble and insoluble fibers may be included in the formula, with insoluble fiber exerting more effect on gut motility by drawing water into the intestine and decreasing transit time, thus preventing constipation. Soluble fiber can help to lower blood cholesterol levels, regulate blood sugar, and prolong gastric emptying. Cellulose gum is an example source of insoluble fiber. Oat fiber and guar gum provide primarily soluble fiber. Soy fiber provides primarily insoluble fiber but also some soluble fiber and is the most commonly used fiber source in tube feeding products. Fiber has been useful for regulating gut motility in some but not all clinical studies; it certainly can be useful in selected patients.18 Some patients may experience GI discomfort secondary to gas production with introduction of fiber-containing formulas.
Fructooligosaccharides (FOSs) are a form of fiber receiving increasing attention. These pass through the stomach and small bowel undigested and are fermented by colonic bacteria to the SCFAs butyrate, propionate, and acetate. The SCFAs serve as a major fuel source for colonocytes and facilitate water and sodium reabsorption in the colon.19 The FOSs fit in the category called prebiotics that serve as fermentable substrates for the normal flora of the colon. The SCFAs are not added directly to EN products because they would be absorbed completely before reaching the colon; rather FOSs are added, allowing bacterial degradation to form SCFAs.
Caloric Density
Enteral feeding formulas can be categorized based on caloric density. Standard caloric density is 1 to 1.3 kcal/mL. More calorically dense formulas containing 1.5 to 2 kcal/mL are also available and have a higher osmolality. 5 When choosing an EN formula, the patient’s fluid status should dictate the caloric density selected. Fluid-overloaded patients may benefit from more calorically dense formulas. It should be recognized that as caloric content of a formula increases, the amount of free water decreases. For example, whereas 1 kcal/mL formulas contain about 850 mL of free water/L, the 2 kcal/mL formulas contain about 710 mL of free water/L.20
Protein Content
The protein content is an important factor in choosing an EN formula. The standard protein content in EN formulas is up to about 15% of total calories as protein. High-protein formulas containing up to 25% of total calories as protein are available for highly stressed patients with elevated protein needs. So are low-nitrogen formulas containing less than 10% of total calories as protein for use in patients requiring protein restriction. A wide range of protein is available, from about 35 to 85 g/L.
Fat Content
Both MCTs and LCTs are used in tube feeding products. Corn, soy, and safflower oils have been the mainstay sources of fat, providing mainly ω-6 polyunsaturated fatty acids (PUFAs). Some newer EN products contain higher quantities of ω-3 PUFAs from sources such as fish oil (i.e., docosahexenoic acid [DHA] and eicosapentaenoic acid [EPA]). Other formulas contain higher quantities of monounsaturated fatty acids (MUFAs) from canola oil and high-oleic safflower or sunflower oils. The essential fatty acid (EFA) content (mainly linoleic acid) of EN formulas is important because EFA deficiency can be induced if at least 1% to 4% of total calories are not supplied as EFA. MCT oil does not contain any EFA.
Specialty Formulas
Specialty formulas designed for use in specific clinical situations generally are much more expensive than standard polymeric formulas.
Clinical trial data supporting use of these specialty formulas in niche populations typically are unconvincing in terms of patient outcomes.
Stress/Trauma Formulas
Historically, formulas aimed specifically for highly stressed, critically ill patients including those suffering significant trauma and those undergoing major surgical procedures, were enriched with branched-chain amino acids (BCAAs). The rationale for these products was that skeletal muscle BCAAs are preferentially used for energy in critical illness. Provision of BCAAs was hoped to limit breakdown of muscle in these patients. Clinical data failed to support or refute benefit of these formulas unequivocally in terms of clinical outcomes.3
Table 101–5 Selected Enteral Feeding Formulas Marketed for Use in High Stress, Pulmonary Disease, and Trauma
The newer generation of enteral feeding formulas marketed for use in these populations covers a broad spectrum of characteristics (Table 101–5). Whereas some are polymeric, others are oligomeric to address malabsorption that may accompany high stress. Some formulas marketed for use in critical illness are calorically dense (1.5 to 2 kcal/mL) to address fluid restrictions seen in this population, whereas others are less calorically dense. Most products contain generous amounts of protein to address requirements of highly stressed patients (nonprotein kilocalorie to nitrogen ratios typically between 75:1 and 125:1). Many products contain ingredients purported to increase immune function; the term immunonutrition is sometimes attached to these products.
Immune-enhancing ingredients present in some enteral feeding products include arginine, glutamine, ω-3 fatty acids, nucleic acids, and antioxidants. Few products contain all of these (see Table 101–5). Arginine is an important substrate for nitric oxide (NO) synthesis, and small amounts of NO have beneficial effects on immune function under certain conditions.21 Arginine has been purported to have positive influence on lymphocyte and macrophage function.
Glutamine is considered to be conditionally essential in critical illness. This amino acid is a preferred fuel source for enterocytes of the small bowel. Supplementation with glutamine, either parenterally or enterally, may help to maintain the integrity of the gut mucosa. This might prevent translocation of bacteria and endotoxin from the gut lumen into the lymphatic system and systemic circulation, although the importance of translocation in humans remains controversial. The ω-3 fatty acids, primarily from fish oils, are included in many immunonutrition products. The metabolites of ω-6 fatty acids include mediators such as prostaglandins, leukotrienes, and thromboxanes that are primarily proinflammatory and increase coagulation. On the other hand, the mediators produced from ω-3 fatty acids are less proinflammatory and decrease coagulation. Thus ω-3 fatty acids may help preserve the antimicrobial capacity of critically ill patients by downregulating inflammation.18 Limited data support nucleic acids as immunomodulators. Quantities of antioxidants (particularly vitamin C, vitamin E, and β-carotene) higher than those traditionally found in standard enteral formulas are added to some immunonutrition formulas to protect body systems including the immune system from damage by oxygen-free radicals.22 Oxygen-free radicals may be produced in high quantities in the setting of injury or infection.
The role of enteral immunonutrition in clinical practice remains controversial. A high-profile expert consensus conference held in 2004 concluded that certain populations, particularly malnourished patients undergoing GI surgery and trauma patients, would benefit from this therapy.23–26 Noteworthy is the fact that this symposium was sponsored by the manufacturer of one of the leading immunonutrition products. Several meta-analyses of the commercial immunonutrition products and/or specific ingredients (e.g., arginine and glutamine) found in these products have been conducted.3,27,28 In general, these analyses have found no benefit in terms of mortality. However, several have concluded that infection rates, length of stay, and length of time on a ventilator may be decreased with these products. More research will be necessary to further delineate which subpopulations will most likely benefit from these therapies. The best timing (initiation and duration) of delivery also needs to be determined. There is some concern that supplementation with arginine may be detrimental in septic patients.3
Pulmonary Formulas
Enteral feeding formulas designed for use in patients with chronic obstructive pulmonary disease or receiving mechanical ventilation contain higher amounts of fat (40% to 55% of total kilocalories) than most formulas. The rationale for high fat content is that burning of fat for energy is associated with less carbon dioxide production compared with burning of carbohydrate. Less carbon dioxide production theoretically would be advantageous in patients with retention of this substance and might facilitate weaning from mechanical ventilation. Since part of the market targeted by the manufacturers of these products comprises mechanically ventilated patients, these products are included in Table 101–5 (e.g., Pulmocare, Nutren Pulmonary, Isosource 1.5 Cal and Oxepa). Carbon dioxide retention owing to carbohydrate administration was a problem previously (particularly with PN) when feeding was overzealous. However, at conservative calorie levels typically administered today, even standard enteral formulas usually can be given without fear of excess carbon dioxide production.
One formula, Oxepa, has been studied specifically in critically ill patients with acute respiratory distress syndrome (ARDS) and acute lung injury.29,30 This high-fat formula contains high quantities of the ω-3 fatty acids (EPA) and γ-linolenic acid (GLA). γ-Linolenic acid is metabolized to a prostaglandin with vasodilatory properties. EPA is converted to prostaglandins and leukotrienes with primarily an antiinflammatory profile. This formula also contains large quantities of antioxidants. Patients receiving this formula required fewer days of mechanical ventilation than patients receiving a high-fat enteral feeding product as a control.26,27 Concern that the high-fat product used as a control could actually be detrimental to patients remains. In a preliminary study Oxepa has also demonstrated benefit in patients with severe sepsis.31
Diabetic Formulas
Similar to pulmonary formulas, formulas designed for the patient with diabetes or stress-induced hyperglycemia are relatively high in fat and low in carbohydrate (Table 101–6). Macronutrient content of these products does not follow the recommendations of the American Diabetes Association for patients with diabetes (lower carbohydrate content and higher fat content than recommended), which could be an issue if used for more than a couple of weeks. These formulas typically contain fiber (primarily soluble) because it plays some role in glycemic control. They also may contain fructose and MUFAs. Data support improved blood sugar control with use of these formulas in patients with diabetes.32 The importance of preventing severe hyperglycemia in various clinical settings including intensive care has been recognized. Therefore, whether or not a diabetic EN formula is chosen, avoidance of overfeeding and maintenance of good glycemic control with insulin or other hypoglycemic medications are important in these populations.
Table 101–6 Selected Enteral Feeding Formulas Marketed for Use in Diabetes and Stress-Induced Hyperglycemia
Renal Formulas
Each major manufacturer of EN products markets more than one specialty formula for use in renal failure (Table 101–7). These products have high caloric density (2 kcal/mL) in light of the need to decrease fluid in this situation. The products vary in amounts of nutrients of interest in renal failure patients such as protein, potassium, phosphorus, and magnesium. Products low in protein (20 to 35 g/L) may be appropriate in chronic renal failure patients not yet receiving dialysis. On the other hand, removal of protein by dialysis, coupled with the hypercatabolic, hypermetabolic condition seen in many acute renal failure patients, makes use of higher-protein formulas (70 to 85 g/L) appropriate in these situations. Potassium, phosphorus, and magnesium contents of EN formulas designed for use in renal failure tend to be lower than standard formulas because these renally excreted electrolytes accumulate during renal failure.
Historically, elemental formulas designed for renal failure were enriched with essential amino acids (EAAs) and contained lesser amounts of nonessential amino acids (NEAAs) than standard formulas. Theoretically, EAAs could combine with urea nitrogen in the synthesis of NEAAs, leading to a decrease in blood urea nitrogen (BUN). The only situation in which such formulas may be appropriate is in patients with chronic renal failure who are not candidates for dialysis. Even in this setting, use of these products should be limited to no more than 2 or 3 weeks owing to the risk of increased serum ammonia levels.1 These EAA-enriched formulas have been supplanted largely by polymeric formulas with protein content similar to standard EN formulas. The main difference between these products and standard EN formulas is reduced potassium, phosphorus, and magnesium concentrations.
Table 101–7 Selected Enteral Feeding Products Designed for Use in Renal Failure
Hepatic Formulas
Specialized formulas for patients with hepatic insufficiency are limited in number. These are enriched with BCAAs while containing a reduced quantity of aromatic amino acids (AAAs) and methionine compared to standard enteral formulas. These changes address the high levels of AAAs and low levels of BCAAs found in the blood of patients with hepatic insufficiency. Theoretically, these products might help patients with hepatic encephalopathy (HE). One of the mechanisms postulated as a cause of HE is the “false neurotransmitter” hypothesis. According to this hypothesis, high levels of AAAs in the blood allow large quantities of these amino acids to cross the blood–brain barrier and form false neurotransmitters, such as octopamine. Administration of high amounts of BCAAs could competitively inhibit some AAAs from crossing the blood–brain barrier, thus decreasing formation of false neurotransmitters. Hepatic formulas have low AAA content and this distinguishes them from the BCAA-enriched formulas historically used in critical illness and stress. Although some data support the use of these specialty products in treatment of moderate to severe HE, improvement in mortality attributable to them has not been consistent.1 Therefore, many institutions and clinicians prefer to use less expensive polymeric enteral formulas containing standard protein sources for patients with hepatic insufficiency. The specialty formulas are recommended only for patients with chronic cirrhosis who cannot ingest 1 g protein/kg/day without becoming encephalopathic.1 An example of a specialized hepatic formula is Hepatic-Aid II, a product supplied as a powder for reconstitution that requires vitamin, mineral, and electrolyte supplementation. A second product is NutriHep, supplied as a liquid formula containing the recommended amounts of key vitamins, minerals, and electrolytes.
Patient Encounter, Part 2
By day 2 postoperatively, the patient’s intracranial pressures were improving and he had been weaned off the vasopressor agents. He was still being mechanically ventilated and was requiring an insulin drip at 2 units/h to keep his blood sugar below 140 mg/dL. He was started on an immune-enhancing enteral formula containing 1.3 kcal/mL and 80 g protein/L; the beginning rate was 40 mL/h to be advanced as tolerated to goal rate over 24 to 36 hours.
What effect would the enteral feeding be expected to have on the patient’s blood sugar?
Is an immune-enhancing formula a good choice for this patient?
Approximately what should be the goal rate for this patient using this enteral formula?
MONITORING AND COMPLICATIONS
Although complications of EN generally are considered less serious than those of PN, some complications nevertheless can be dangerous or can lead to impaired delivery of desired nutrient load. Complications of EN can be divided into four categories: GI, technical, infectious, and metabolic. The first three of these categories, along with common causes, are listed in Table 101–8. Patients on EN must be monitored for prevention of complications (Table 101–9). Note that monitoring of many parameters can become less frequent as the patient’s condition stabilizes. Monitoring for efficacy of EN is also important.
GI Complications
GI complications are the most common complications of EN limiting the amount of feeding that patients receive. Although diarrhea frequently is blamed on the tube feeding formula or the method of EN administration, other possible causes of diarrhea usually exist (see Table 101–8). Many of these are related to the fact that, particularly in the inpatient setting, patients receiving EN frequently are some of the sickest patients in the hospital. Along these lines, Clostridium difficile colitis must be considered as a possible cause of diarrhea, especially in patients who have been receiving antimicrobial therapy or proton pump inhibitors.33–36 Antibiotic therapy is a major cause of diarrhea in acutely ill patients, including those receiving EN. A medication-related cause of diarrhea largely overlooked until the early 1990s is the sorbitol content of medications.37 Large quantities of this substance present in many oral liquid medications (often considered the dosage form of choice for administration through a feeding tube) can cause diarrhea. Unfortunately, the sorbitol content of many medications is not listed on their labeling, and some manufacturers state that they frequently reformulate these preparations to contain varying amounts of excipients, such as sorbitol. Determining the cause of the diarrhea is obviously important to know how to address the problem. Whereas C. difficile colitis should be treated with metronidazole or vancomycin, sorbitol-or other medication-induced diarrhea can be addressed by removal of the offending agent. Likewise, diarrhea secondary to malabsorption sometimes can be addressed by changing to an oligomeric EN formula. Antiperistaltic agents such as loperamide may be useful in some cases of diarrhea of noninfectious etiology.
On the other hand, constipation may occur in some patients receiving tube feedings, especially the elderly. Increased provision of fluid or fiber may be useful in attaining bowel regularity. As with diarrhea, constipation may be drug-related, in which case discontinuation or replacement of the offending drug may help alleviate the problem.
Table 101–8 Complications of Tube Feeding
Table 101–9 Suggested Monitoring for EN Patients to Prevent the Development of Complications
Impaired gastric emptying is seen commonly in EN patients receiving gastric feedings and may be associated with nausea and vomiting. Impaired gastric emptying may be related to a disease process (e.g., diabetic gastroparesis or sequelae to head injury) or to drug therapy, most notably narcotics. Gastric residual checks frequently are measured in patients receiving gastric feedings (see Table 101–9). To accomplish such a check, a syringe is attached to the feeding device, and as much liquid as possible is aspirated into the syringe. Much debate is ongoing as to what constitutes a significant gastric aspirate, with numbers between 100 and 500 mL most commonly defended.4,38–40Approaches to the patient with delayed gastric emptying might include changing to an enteral formula containing less fat because dietary fat is associated with slower gastric emptying. Metoclopramide often is given to patients receiving gastric feedings to facilitate gastric emptying. Erythromycin is an alternative medication that may be useful in stimulating gastric motility, although it also can be associated with potentially serious drug–drug interactions. Feedings by a PEG tube may be associated with a decreased risk of aspiration compared to NG feedings.40 Patients with consistently high gastric aspirates are considered to be at higher risk of aspirating feedings into their lungs and should be considered for transition to postpyloric feedings. Postpyloric feedings may help relieve EN-related nausea and vomiting and are preferred for patients without an intact gag reflex. An important practice to help prevent aspiration is elevation of the head of the bed to at least 30 degrees during continuous feedings and during and for 30 to 60 minutes after intermittent and bolus feedings. Adding blue food coloring to tube feeding formulas to help detect aspiration in bronchial or tracheal aspirates has been largely abandoned due to reports of absorption of this supposedly-nonabsorbable substance in patients with sepsis.41
Technical Complications
Technical or mechanical complications are encountered frequently in the EN patient. Tube occlusion most commonly is related to formula occlusion or medication administration through the tube. 
An important practice to help prevent medication-related occlusion is adequate water flushing of the tube before, between, and after each medication is given through the tube. If intermittent feedings are used, water flushing after each feeding is recommended. Tube occlusion can increase cost of EN significantly if the tube has to be removed and replaced. Clearing of the occlusion using water or pancreatic enzymes plus sodium bicarbonate can be attempted, and special devices and kits (e.g., DeClogger) are available for this purpose.42
Tube displacement is a potentially significant complication of EN. This may be seen secondary to an agitated patient pulling at the tube, or in some cases the tip of the tube migrates spontaneously. The danger of this complication arises if the tip of the tube is positioned in the tracheobronchial tree and feeding is delivered to this area, potentially leading to pneumonia, pneumothorax, and other problems. Location of the tip of the feeding tube should be confirmed initially by chest radiograph after placement and before use. For ongoing assessment of tube placement, auscultation and measurement of aspirate pH can be used; debate continues as to the best method of monitoring tube placement.
Endoscopic and surgical feeding tubes can be complicated by erosion of the exit site caused by leakage of gastric or intestinal contents onto the skin. This complication must be addressed by good wound care and repair or replacement of the access device. Similarly, NG, ND, and NJ tubes can be complicated by nasopharyngeal irritation or necrosis. This is one reason why such tubes should be considered for short-term use only.
Infectious Complications
Infectious complications of EN include aspiration pneumonia and infections related to delivery of contaminated EN formula. Aspiration is a complication with GI, mechanical, and infectious implications. Although GI infections owing to contamination of enteral formulas have been reported uncommonly, there is ample opportunity for these formulas to be seeded with organisms during the processes of transferring from the can to the delivery bag with ready-to-use formulas and during the process of reconstitution with powdered formulas. The so-called closed systems of delivery, wherein the formulas come from the manufacturer premixed in a delivery bag, should help to decrease the chance of formula contamination.
Metabolic Complications
Metabolic complications of EN most commonly include disorders of fluid and electrolyte homeostasis and hyperglycemia. More severely ill patients require more frequent monitoring (see Table 101–9). Both dehydration and fluid overload can occur with tube feeding. Careful monitoring of fluid inputs and outputs as well as body weight is important. Dehydration may be due either to excessive fluid losses or inadequate fluid intake. The trend in the BUN-to-serum-creatinine ratio can be useful in helping monitor for this complication; a ratio of greater than about 15:1 may be an indicator of dehydration. Attention should be paid to the free-water content of EN formulas; this information usually is included on product labeling. Free-water content of EN formulas varies from about 65% to 85%, with percentage of free water typically dropping as caloric density of the formula rises. If dehydration develops, switching to a less calorically dense formula or using more water flushes may be appropriate. Fluid overload is reflected by increases in weight, lower extremity edema, and pulmonary rales and particularly may be a problem in patients with renal or cardiac insufficiency. Use of an EN formula that is more calorically dense (i.e., contains less free water) may be helpful, and diuretic therapy may be necessary. Fluid imbalances often are associated with abnormalities of sodium homeostasis that should be addressed in concert with fluid imbalance.
Hypokalemia, hypomagnesemia, and hypophosphatemia are some of the most common electrolyte abnormalities in sick, hospitalized patients. These can occur in the context of the so-called refeeding syndrome. This syndrome occurs in chronically malnourished patients when aggressively started on a feeding regime. Although more classically associated with PN, refeeding syndrome can occur with aggressive EN. Careful monitoring of these electrolytes, coupled with a feeding regimen increased gradually to goal rate over a period of several days to a week, should help protect the at-risk patient from this potentially harmful complication. Hypokalemia and hypomagnesemia also may be associated with excessive losses through the GI tract or urine and may be associated with various medication therapies, including diuretics. Repletion of these conditions may be accomplished enterally in the nonsymptomatic patient or parenterally if the patient is symptomatic or the abnormality is severe. Enteral repletion with magnesium and phosphate can be associated with diarrhea. Hyperkalemia, hypermagnesemia, and hyperphosphatemia are encountered less commonly and usually are associated with renal insufficiency and decreased excretion. Hyperkalemia also is associated with several medications, including potassium-sparing diuretics and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
Although hyperglycemia is less common with EN than with PN, it can occur. Many severely ill patients (e.g., septic, highly stressed) receiving EN have a metabolic milieu promoting hyperglycemia. In addition, many patients have preexisting or undiagnosed diabetes mellitus. For the ICU patient with hyperglycemia receiving continuous EN, an IV insulin drip may be the most effective way to achieve good glycemic control. Administration of scheduled intermediate or long-acting insulin is preferred over sliding-scale insulin alone in patients requiring insulin after they have been stabilized on their enteral feeding regimen.43,44 Administration of a higher-fat, lower-carbohydrate EN formula may be useful in selected patients.
Monitoring for Efficacy/Outcome Evaluation
The most useful physical measurement of efficacy of EN in the long-term patient is typically body weight. Depending on the clinical situation, the goal may be weight gain, weight maintenance, or weight loss. Whereas day-to-day fluctuations in weight generally reflect fluid changes, week-to-week variations are more useful in determining if caloric provision is appropriate.
The amount of EN actually administered is often less than the amount ordered owing to interruptions in therapy caused by carrying out of procedures and other daily activities, especially in hospitalized patients. It is imperative to monitor volume of feedings actually received and to make adjustments in rates or amounts of EN as necessary.
Biochemical markers may help the SNS practitioner interpret adequacy of the EN therapy. Albumin frequently is measured as part of standard metabolic lab panels. Its long half-life renders this visceral protein less useful for making decisions regarding adequacy of the nutritional prescription over the short term. Prealbumin, with a much shorter half-life that is expected to increase more rapidly in the setting of sufficient calorie and protein provision, has become the major biochemical monitoring parameter used to determine efficacy of SNS. However, in the acute phase of illness characterized by a proinflammatory state, proteins known as acute-phase reactants are preferentially synthesized. One of these acute-phase reactants measured clinically is C-reactive protein (CRP). In some patients with significant illness, prealbumin may not rise, even though the patients are receiving the appropriate EN regimen, until CRP begins to fall. Collection of urine to measure nitrogen balance can help analyze adequacy of caloric and protein provision but must be performed with care to obtain reliable information.
In patients with wounds (e.g., decubitus ulcers), a goal of nutritional therapy is to help facilitate wound healing. Therefore, monitoring the status of the wound becomes part of the ongoing nutritional assessment. In debilitated patients, particularly those on long-term EN, measures of functional status such as grip strength and ability to perform activities of daily living become important parts of the assessment of nutritional adequacy.
MEDICATION ADMINISTRATION IN PATIENTS RECEIVING EN
Medication Administration Through Feeding Tubes
If a patient receiving EN is alert and can swallow oral medications, then, medications should be given by mouth. However, many patients are not able to receive medications by this route, and the feeding tube may be considered as a route of delivery. Although used widely, the effects of medication administration through feeding tubes on the delivery of both the drug and the EN formula nutrients have been inadequately studied, and important questions remain unanswered.45
Compatibility of medication with an EN formula and, conversely, an EN formula with administered medication is of concern when administering medications through feeding tubes. An important technical complication of EN is tube occlusion, related most commonly to medication administration. Not only must compatibility of the medication and the EN formula be considered, but interactions between these components and the feeding tube itself must be considered. Since either medication or EN formula or some combination thereof can physically stick to the tube itself, strict protocols for flushing the tube before, between, and after administration of medications are important.5The best fluid for flushing feeding tubes is warm water. Carbonated beverages and fruit juices are no longer recommended and should be avoided because sugar in these products may stick to the surface of the feeding tube. Between 10 and 30 mL of water should be used as a flush before and after any medication administration through a feeding tube. Medications should be administered one at a time sequentially rather than being mixed together for simultaneous administration down the tube; about 5 mL of water should be used as a flush between each medication. This should help prevent interactions between drugs within the feeding tube itself that could lead to tube occlusion.
Different dosage forms present unique challenges for administration through feeding tubes. Certain solid dosage forms should not be crushed because crushing would significantly alter release characteristics.46 For example, controlled-release, extended-release, and sustained-release preparations should not be crushed; crushing allows a quicker release of more drug initially than the original dosage form was designed to deliver. Sublingual dosage forms should not be crushed. Enteric-coated dosage forms generally are designed to protect acid-labile medications from stomach acid; when these dosage forms reach the small bowel with its higher pH, the drug then is released into an environment in which it is more stable. Alternatively, enteric-coated dosage forms protect the stomach from medications that could cause irritation. Thus, crushing of the enteric coating for delivery down a gastric feeding tube defeats the purpose of the dosage form and could lead to decreased efficacy or increased adverse events.
Medications available commercially as compressed tablets can be crushed for administration through feeding tubes. After such a tablet is crushed into a fine powder, it should be mixed with 10 to 30 mL of fluid (usually warm water) for administration. A powdered dosage form inside a hard-gelatin capsule similarly can be poured out and mixed with water for administration through feeding tubes. Soft-gelatin capsules can be dissolved in warm water for administration. Some enteric-coated and delayed-release microencapsulated products can be opened, and the individually-coated particles can be administered through the tube without crushing if the tube has a large enough diameter.
If a liquid dosage form of a medication exists, it would seem rational to use this dosage form for administration through a feeding tube. Although this may decrease the potential for tube clogging, it may in some instances decrease tolerability of medication administration. As mentioned above, sorbitol is an excipient found in many liquid medications in amounts sufficient to cause diarrhea. If diarrhea secondary to sorbitol in a liquid medication is suspected, contact with the manufacturer to ascertain sorbitol content may be necessary.
Another potential problem with administration of liquid medications through feeding tubes is high osmolality of some of these products. Dilution of hypertonic medications with 30 to 60 mL of water (depending on osmolality of the medication and dosage volume of the undiluted medication) or administration of smaller dosages more frequently may help prevent diarrhea. Although administration of IV medications through feeding tubes sometimes may be entertained, these dosage forms frequently are hypertonic and contain excipients that can be problematic when given via the GI tract.
It is generally not recommended to mix medications directly into the EN formula because of concerns that physical incompatibilities between the medications and the formula might lead to tube occlusion. There is some evidence that polymeric formulas are more likely to demonstrate physical incompatibility with medications compared with monomeric formulas, although most of the work in this area has used casein or caseinate-based formulas, and other proteins may act differently.45 Limited data currently available indicate that acidic syrups and elixirs may be most harmful, causing physical incompatibility when admixed with EN formulas. This incompatibility may be due to changes in the protein structure after exposure to acid or alcohol.45
It would seem logical that medications considered being absorbed to a greater extent in the fasted state either should be given between feedings on an intermittent feeding schedule or the feedings should be held before and after medication administration. However, results of one provocative study with the antihypertensive medication hydralazine indicated that continuous feeding into the stomach resulted in a situation mimicking fasting in terms of rate of gastric emptying and drug absorption.45 This issue deserves further study.
The location of the tip of the feeding tube is important when considering medication administration down a feeding tube. This is particularly true if the medication acts locally in the GI tract itself. For example, sucralfate and antacids act locally in the stomach. Therefore, administration of these medications through a duodenal or jejunal tube is not logical. Likewise, for medications such as itraconazole that require acid for best absorption, administration directly into the duodenum or jejunum would be expected to result in suboptimal absorption. Absorption of drugs when administered directly into the small bowel, especially the jejunum, is a topic where more research would be useful.
Problem Medications
Phenytoin
Certain medications present specific challenges when administered through feeding tubes. The medication studied most thoroughly is phenytoin. Most studies have shown significant decreases in phenytoin absorption when the medication was administered enterally to patients receiving EN. Several mechanisms have been proposed for this apparent interaction. Many institutions have adopted a policy of holding tube feedings for 1 or 2 hours before and after administration of phenytoin to decrease the interaction, although some EN patients subjected to this routine still will require relatively high dosages of phenytoin to achieve therapeutic serum concentrations. Holding the feeding around medication administration can make meeting nutritional requirements difficult with continuous feedings, especially if the phenytoin is administered several times daily. Diligent monitoring of phenytoin serum concentrations is necessary for the patient on EN receiving this medication. In some cases, use of IV phenytoin or another anticonvulsant medication may be prudent.
Warfarin
EN formulas contain vitamin K, which can antagonize the pharmacologic activity of warfarin. Vitamin K content of EN formulas generally has been adjusted down over the past several decades, resulting in products today that contain amounts of vitamin K unlikely to affect anticoagulation by warfarin significantly. However, inadequate warfarin anticoagulation in EN patients receiving formulas containing minimal vitamin K has been reported. There is some thought that a component of certain tube feedings, perhaps protein, may bind warfarin and result in suboptimal activity of the drug. A recent small study indicated a better response in terms of the International Normalized Ratio (INR) when feedings were held for one hour before and after warfarin administration compared to administration of the drug without holding the feedings.47 When tube feedings are started, changed, or discontinued, the INR should be monitored closely.
Patient Encounter, Part 3
After a week in the ICU, the patient was transferred to a stepdown unit and was switched to a standard polymeric EN formula. He required 3 weeks of inpatient care owing to complications from his injuries, including seizures and a wound infection. He eventually was transferred to a rehabilitation facility still requiring EN.
How should the patient be monitored for adequacy of his EN regimen?
Outline a monitoring plan for tolerance of the EN regimen in the ICU, stepdown unit, and rehabilitation facility.
Discuss work-up of the patient if diarrhea occurs while he is receiving tube feedings.
If the patient requires phenytoin for his seizures, how should this medication be administered?
Fluoroquinolones
Absorption of antimicrobial agents such as fluoroquinolones and tetracyclines that can be bound by divalent and trivalent cations potentially could be compromised by administration with EN formulas containing these cations. The fluoroquinolones (e.g., levofloxacin and ciprofloxacin) have been best studied in this regard, and results of studies are not consistent.48,49 Some institutions hold tube feedings for 30 to 60 minutes or more before and after enteral dosages of fluoroquinolones. Because ciprofloxacin absorption has been shown to be decreased with jejunal administration, this drug probably should not be given by jejunal tube.49
SUMMARY AND CONCLUSION
EN is an important method of feeding patients who cannot or should not eat enough to meet their nutrient requirements for a prolonged time. When the GI tract can be used safely, EN is preferred over PN. Various types of enteral access devices are available. Whereas tubes inserted through the nose often are adequate for patients expected to receive EN for a short time, more permanent devices (endoscopically or surgically placed) are preferred for longer-term patients. Choice of whether to feed into the stomach or postpylorically is patient-specific. Although numerous EN formulas are available commercially, many products are very similar, making a limited formulary feasible. Data supporting many of the specialized types of EN formulas are limited. Although complications of EN tend to be less serious than those of PN, the adverse effects encountered can be significant, and diligent ongoing monitoring is necessary. Although medications can be administered through feeding tubes, various factors must be taken into account in each individual patient to ensure that this practice is prudent.
Patient Care and Monitoring
1. Assess the patient’s condition to estimate the amount of time he or she is expected to be unable to eat adequately to meet nutritional requirements. If inadequate intake has occurred or is anticipated for 7 to 14 days, start SNS. The threshold for starting SNS is lower for previously malnourished patients than for previously well-nourished patients. Also, critically ill patients should generally be started on EN within 24 to 48 hours of ICU admission.
2. Assess whether the GI tract is functional. If not, then PN is the first SNS therapy of choice. If the GI tract is functional and no contraindication to EN exists, then EN is the SNS therapy of choice.
3. Does the patient have any condition precluding gastric feeding? If so, then postpyloric feeding should be started.
4. Choose the appropriate type of enteral access device based on the expected duration of SNS.
5. Choose an appropriate feeding formula based on patient-specific factors. This necessitates assessing nutritional requirements. Standard polymeric formulas are appropriate for the majority of patients.
6. Choose the method of feeding administration (e.g., intermittent or continuous) based on the type of feeding access (i.e., gastric versus postpyloric) and other patient factors. For example, in a patient with a gastric access, starting with or later transitioning to intermittent feedings may be preferred if it is anticipated that the patient still receiving these feedings will be discharged to a long-term care facility or to home.
7. Develop a plan to include monitoring at appropriate intervals for metabolic, GI, technical, and infectious complications.
8. Start the tube feeding at full strength and at a low rate, and increase the rate as tolerated to the goal that will meet the patient’s nutritional requirements.
9. Develop a monitoring plan for adequacy of the nutritional regimen.
10. If the patient is to be discharged to home on EN, educate the patient or caregiver on
• Enteral access device care
• Feeding delivery
• Troubleshooting
• Complications to observe for (e.g., fluid overload, dehydration)
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
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