Pharmacotherapy A Pathophysiologic Approach, 9th Ed.

120. Enteral Nutrition

Vanessa J. Kumpf and Katherine Hammond Chessman


KEY CONCEPTS

 Images The GI tract defends the host from toxins and antigens by both immunologic and nonimmunologic mechanisms, collectively referred to as the gut barrier function. Whenever possible, enteral nutrition (EN) is preferred over parenteral nutrition (PN) because it is as effective, may reduce metabolic and infectious complications, and is less expensive.

 Images Candidates for EN are those with a sufficiently functioning GI tract to allow adequate nutrient absorption who cannot or will not eat and in whom enteral access can be safely obtained.

 Images The most common route for both short- and long-term EN access is directly into the stomach. The method of delivery may be either continuously via an infusion pump, intermittently via a pump or gravity drip, or by gravity or syringe bolus administration.

 Images Patients unable to tolerate feeding directly into the stomach because of impaired gastric motility and for those at high risk of aspiration, feeding tube tip placement into the duodenum or jejunum may be indicated. When feeding into the small bowel, the continuous method of delivery via an infusion pump is required to enhance tolerance.

 Images Selection of the enteral feeding formulation depends on nutritional requirements, the patient’s primary disease state and related complications, and nutrient digestibility and absorption. A standard polymeric formulation will meet the needs of the majority of adults and children.

 Images Measurement of gastric residual volumes can be used to monitor GI tolerance in patients receiving gastric feeding. Although not always reliable, excessive residual volumes may be associated with nausea, abdominal distension, and increased aspiration risk.

 Images Management of diarrhea in patients receiving EN should focus on identification and correction of the most likely cause(s). Tube feeding-related causes include too rapid delivery or advancement, intolerance to the formula composition, and occasionally formula contamination.

 Images Prior to administering medications through a feeding tube, the feeding tube tip location should be verified (stomach or small bowel) and the most suitable dosage form selected. Medications that should not be crushed and administered through a tube include enteric-coated or sustained-release capsules or tablets and sublingual or buccal tablets.

 Images The coadministration of medications with EN can result in alterations in bioavailability and/or changes in the desired pharmacologic effects. Medications known to interact with EN include phenytoin, warfarin, selected antibiotics, antacids, and proton-pump inhibitors.


INTRODUCTION

Enteral nutrition (EN) is defined as the delivery of nutrients by tube or by mouth into the GI tract. This chapter focuses on nutrient delivery through a feeding tube rather than the oral ingestion of food. The terms enteral nutrition and tube feeding are thus used interchangeably in this context. The goal of EN is to provide calories, macronutrients, and micronutrients to those patients who are unable to achieve these requirements from an oral diet. Improvements in enteral access techniques and feeding formulations over the past 20 to 30 years and the recognition of methods to prevent and manage complications have resulted in an increased use of EN across all healthcare settings.

In this chapter, principles and practices related to the successful use of EN support are described. Digestive and absorptive physiology is reviewed, and the beneficial effects of EN are presented. The indications for EN and descriptions of various enteral access and administration methods are also summarized. Characteristics of commercially available enteral feeding formulations are presented, as well as administration and monitoring guidelines. Strategies to prevent and manage complications are discussed, and clinical therapeutic controversies are highlighted. In addition, issues of drug compatibility, drug–nutrient interactions, and drug administration via feeding tubes are discussed. Finally, the effectiveness and pharmacoeconomics of EN in enhancing nutrition and disease outcome goals are reviewed.

GASTROINTESTINAL TRACT PHYSIOLOGY

The GI tract plays a key role in the processing of ingested foods many of which are modifiable by the presence of acute and chronic illnesses.

Digestion and Absorption

Digestion and absorption are GI processes that generate the body’s usable fuels.1,2 Digestion consists of the stepwise conversion of a complex chemical and physical nutrient into a molecular form that is absorbable by the intestinal mucosa. Absorption from the GI tract is a multistep process that includes the transfer of a nutrient across the intestinal cell membrane. The nutrient ultimately reaches the systemic circulation through the portal venous or splanchnic lymphatic systems, provided that the GI or biliary tract does not excrete it. Ingested nutrients are primarily large polymers that cannot be absorbed by the intestinal cell membrane unless they are transformed into an absorbable molecular form. In addition, a coordinated interplay of GI motility and neurohormonal secretion is required to facilitate adequate digestion and absorption.

Nutrient digestion involves the complex coordination of multiple mechanical, enzymatic, and physiochemical processes.1,2 Mechanical dissolution of food occurs by chewing, then mixing and grinding the stomach contents. Food stimulates the secretion of numerous hormones and enzymes from the salivary glands, stomach, liver and biliary system, pancreas, and intestines (see Table 120-1). As food passes along the gut lumen, these hormones modulate GI motility and the secretions from subsequent organs of the digestive system. Nutrient digestion and absorption occurs within the gut lumen and is a specific function of the intestinal cell membrane, which is comprised of fingerlike projections called villi. Each individual villus is made up of epithelial cells called entero-cytes. The enterocyte surface contains special luminal projections called microvilli, which provide an increased surface area that is referred to as the brush-border membrane.

TABLE 120-1 Gastrointestinal Enzymes and Hormones

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The digestion and absorption of carbohydrate, fat, and protein within the small intestine are illustrated in Figure 120-1. Carbohydrates are presented to the small intestine in either a digestible or a nondigestible form. Polysaccharides (starches) and oli-gosaccharides (sucrose and lactose) undergo enzymatic digestion within the small intestine to produce simple sugars. The simple sugars are absorbed via active and passive transport mechanisms and are eventually released into the portal vein. Polysaccharides, such as cellulose complexes and other fiber components, pass undigested to the colon, where they are digested by bacteria and enzymes to form short-chain fatty acids. Absorption of short-chain fatty acids by the colon stimulates sodium and water reabsorption, serves as an energy source, and provides nourishment to the colonic mucosa cells.

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FIGURE 120-1 Schematic of carbohydrate, fat, and protein digestion.

Fat is presented to the small intestine as long-chain triglycerides. Its digestion requires pancreatic enzyme release and formation of mixed bile salt micelles, the end product, which is then absorbed across the intestinal enterocyte. Within the enterocyte, triglycerides are reesterified and packaged into chylomicrons for release into the lymphatic system. Medium-chain triglycerides (MCTs) can be absorbed intact by the mucosal membrane and are acted on by intracellular lipase within the enterocyte to release free fatty acids that pass directly into the portal vein.3

Protein is presented to the small intestine primarily as large polypeptides and to a small extent as free amino acids because of the denaturation of protein within the stomach. Luminal polypeptide digestion generates oligopeptides, which are further hydrolyzed to dipeptides and tripeptides. Absorption of peptides occurs via a peptide transport system; free amino acids are carried via specific amino acid transport systems. The carriers for the peptides are very efficient, whereas absorption of free amino acids appears to be more limited and less efficient.2

Understanding the mechanisms of digestive and absorptive physiology can greatly enhance the rational use of EN during conditions of normal or altered GI anatomy and/or function. Various circumstances may alter the efficacy of nutrient digestion and absorption. For example, the functional immaturity of the neonatal gut may lead to clinical problems associated with inadequate digestion and absorption of EN. These factors, as they relate to successful EN practice, are discussed in detail throughout this chapter.

Gut Host Defense Mechanisms

Images Besides digesting and absorbing nutrients to maintain nutritional health, the GI tract is actively involved in defending the host from toxins and antigens by means of both immunologic and nonimmunologic mechanisms.4 These gut host defense mechanisms are collectively referred to as the gut barrier function. The gut barrier acts to prevent the spread of intraluminal bacteria and endotoxins to systemic organs and tissues. Hydrochloric acid secreted by the stomach kills most of the bacteria ingested with food. Under normal circumstances, a mucus layer coats the intestinal epithelium and thereby alters the adherence of bacteria to the cells of the GI tract but provides a favorable environment for anaerobic bacteria. Anaerobic bacteria, which normally colonize the mucus layer, aid in preventing tissue colonization by potential pathogens. Small bowel peristalsis further prevents bacterial stasis and overgrowth. The gut barrier function is also maintained by the intestinal immune system, known as the gut-associated lymphoid tissue (GALT). GALT regulates the local immune response to antigens within the GI tract. Specific immunoglobulins are secreted to kill the remaining organisms and neutralize any toxins they produce. The liver Kupffer cells help to maintain gut barrier function by clearing the portal blood of gut-derived bacteria and endotoxins. The integrity of gut barrier function may be affected negatively by numerous pathogenic insults, such as physiologic stress and ischemia, and a variety of drugs, including chemotherapeutic agents. The administration of certain probiotics can modify intestinal flora and may have beneficial effects in various disease states and patient populations by positively affecting the maintenance of gut barrier function and intestinal immune function.5,6

INDICATIONS FOR ENTERAL NUTRITION

Images The decision to initiate EN is based on a variety of factors. Suitable candidates are those who cannot or will not eat a sufficient amount to meet nutritional requirements, those who exhibit a sufficient functioning GI tract to allow the absorption of nutrients, and those in whom a method of enteral access can be safely obtained.79 EN may be indicated in a variety of conditions or disease states (Table 120-2). For example, patients who have neurologic disorders, such as a cerebrovascular accident, and have difficulty swallowing often require EN. Patients unable to eat because of conditions such as facial or jaw injuries, lesions of the oral cavity or esophagus, esophageal stricture, or head and neck cancer may also be candidates for EN delivered distal to the affected site. Extreme prematurity necessitates tube feeding because the suck–swallow mechanism has not yet developed sufficiently to allow safe oral intake.

TABLE 120-2 Potential Indications for Enteral Nutrition

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Critically ill patients who are endotracheally intubated for mechanical ventilation represent a large percentage of patients requiring EN. Traditionally, EN in the critically ill population was regarded as supportive care designed to provide nutrients during the period of time the patient was unable to maintain oral dietary intake. Recently, the use of EN has been initiated to modulate the stress response to critical illness and improve patient outcomes. Nutrition guidelines support the initiation of EN in critically ill adults1012 and children13 who are unable to maintain volitional intake. Some of these patients may have reduced gastric emptying caused by sepsis, GI surgery, anesthetic agents, opioid analgesics, and underlying pathology, such as diabetic gastroparesis and burns. However, successful EN can often be achieved by bypassing the stomach and placing the tip of the feeding tube beyond the pylorus into the duodenum, or preferably into the jejunum. Small bowel feeding may also be appropriate for patients with gastric outlet obstruction, those with pancreatitis, those with moderate to severe gastroesophageal reflux, or those with high risk of aspiration.

The only absolute contraindications for EN are distal mechanical intestinal obstruction12 and necrotizing enterocolitis.14 However, conditions such as severe diarrhea, protracted vomiting, enteric fistulas, severe GI hemorrhage, and intestinal dysmotility may result in significant challenges to the successful use of EN.

BENEFITS OF ENTERAL NUTRITION

The importance of maintaining nutrient delivery through the GI tract in patients without a contraindication to its use is well supported. The beneficial effects of EN, specifically in the critically ill patient, are further enhanced if EN is initiated within 24 to 48 hours of admission to an intensive care unit (ICU).10

Enteral Versus Parenteral Nutrition

Clinical studies comparing EN and parenteral nutrition (PN) in the critically ill patient demonstrate a decrease in infectious complications and thus improved outcomes with the use of EN.1519 Infectious complications are less common with EN in part because EN supports the functional integrity of the gut by stimulating bile flow and the release of endogenous trophic agents, such as cholecystokinin, gastrin, and bile salts. Provision of enteral nutrients appears to help maintain the villous height of the intestinal mucosa and support the mass of secretory immunoglobulin A (IgA)-producing immunocytes that comprise the GALT. In the setting of critical illness or injury, adverse changes in gut permeability and gut barrier function that result in increased risk for systemic infection and multiorgan dysfunction syndrome have been noted. By supporting gut integrity, the enteral route of feeding is more likely than the parenteral route to lower the risk of infection and minimize organ failure.10

Critical reviews of available prospective randomized, controlled trials comparing EN with PN in the critically ill adult patient with an intact GI tract suggest a significant reduction in infectious complications associated with EN.10,11 Decreased infectious complications have been documented in patients with abdominal trauma, burns, severe head injury, major surgery, and acute pancreatitis. The reduced infectious complications are primarily the result of a lower incidence of pneumonia and catheter-related bloodstream infections in most of these patient populations and a decrease in abdominal abscess in trauma patients. EN is thus preferred over PN for the feeding of critically ill adult patients requiring specialized nutrition support.10,11 There are no randomized, controlled trials that compare the use of EN and PN in children.13

EN is more physiologic than PN in terms of nutrient utilization and therefore is generally associated with fewer metabolic complications, such as glucose intolerance and elevated insulin requirements.20Enteral formulations contain both complex and simple carbohydrates, which results in slower carbohydrate absorption compared with the simple carbohydrate, dextrose, used in PN. In addition, enteral formulations that contain fiber and/or a high fat content will further slow carbohydrate absorption and decrease any elevation in blood sugar by delaying gastric emptying. This may account for better blood glucose control when carbohydrate is given via the enteral route. An additional physiologic benefit of enteral feeding is that it stimulates bile flow through the biliary tract and thus reduces the risk of developing cholestasis, gallbladder sludge, and gallstones, conditions that have been associated with long-term PN and bowel rest.21 Also, EN avoids the potential infectious and technical complications associated with the placement and use of a central venous access device required for PN. Finally, EN is less costly than PN when all factors are considered.

Early Versus Delayed Initiation

The timing of initiation of EN in the critically ill patient is of clinical significance. Initiating EN in the first 24 to 72 hours following admission appears to attenuate the stress response and may reduce disease severity and infectious complications when compared with the initiation of feedings after 72 hours.10,11 Early EN has also been associated with a decrease in the release of inflammatory cytokines and fewer alterations in gut permeability.22 Clinical studies demonstrating a decrease in infectious complications with the use of EN compared with PN in the critically ill patient initiated feeding within 24 to 48 hours of hospital admission.10,11,15,22,23 The benefits of decreased infectious complications are not apparent when the initiation of EN is delayed. A review of available studies comparing early versus delayed EN in critically ill patients showed a trend toward a reduction in infectious complications with early EN.10,11 In addition, a trend toward reduction in mortality associated with early EN has been noted.10,11,24

In critically ill patients who are hemodynamically unstable, early EN may result in gut ischemia because of poor gut blood flow and increased oxygen demand. Consequently, it is recommended that initiation of EN be delayed until the patient is fluid resuscitated and has an adequate perfusion pressure. Once this goal is achieved, often within 6 hours of hospitalization, the initiation of EN at a low administration rate is considered appropriate, along with clinical monitoring to ensure GI tolerance.25,26 Therefore, early EN (within 24 to 48 hours after hospital admission) is recommended in critically ill adult patients.10,11Although no randomized, controlled trials have assessed early EN in critically ill children, initiation of EN within 48 to 72 hours of admission is common.13 Early initiation of EN is not warranted for the mild to moderately stressed adult patient who is otherwise well nourished. It is reasonable to delay the initiation of EN in these patients until oral intake is inadequate for 7 to 14 days.7 In the mild to moderately stressed adult patient with inadequate oral intake who is malnourished, it is unclear when to initiate EN, but most clinicians would wait no longer than 7 days.

ENTERAL ACCESS

Advances in enteral access techniques have contributed to the expanded use of EN for conditions in which PN had previously been used. In particular, improved methods of achieving jejunal access for feeding have allowed for the use of EN during the early postoperative and postinjury period when gastric motility is typically impaired. As outlined in Table 120-3, various factors influence the selection of enteral access site and device, including anticipated duration of use (short- or long-term) and whether to feed into the stomach or small bowel. Figure 120-2 illustrates the predominant enteral access options.

TABLE 120-3 Options and Considerations in the Selection of Enteral Access

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FIGURE 120-2 Access sites for tube feeding.

Short-Term Access

Images Short-term enteral access is easier to initiate, less invasive, and less costly than the establishment of long-term access.27 The most frequently used routes for short-term enteral access are established by inserting a tube through the nose and passing the tip into the stomach (nasogastric [NG]), duodenum (nasoduodenal), or jejunum (nasojejunal). In general, these tubes are used in the hospitalized patient when the anticipated tube feeding duration is less than 4 to 6 weeks. The orogastric route is generally reserved for patients in whom the nasopharyngeal area is inaccessible or in young infants who are obligate nasal breathers. Because these routes do not require surgical intervention, they are the least invasive. The feeding tube is frequently held in place only by a piece of tape on the nose or face; therefore, it can be inadvertently pulled out relatively easily.

NG tubes vary in diameter size and stiffness. Large-bore (≥14F) rigid NG tubes are used primarily to decompress the stomach but can also be used for feeding. There is a low incidence of clogging with these tubes, and they provide a reliable way to measure gastric residual volumes (GRVs). The major disadvantage associated with the use of these tubes is patient discomfort. Small-bore nasal tubes designed solely for feeding are available in varying lengths (16 to 60 inches [41 to 152 cm]) and diameter sizes (4F to 12F) to accommodate both pediatric (including neonates) and adult patients. The tip of the tube can be placed into the stomach, duodenum, or jejunum. These tubes consist of a lightweight, pliable silicone or polyurethane material that is more comfortable for the patient. A disadvantage of the small-bore tubes is that they may become easily occluded, often as a result of improper medication administration or tube-flushing technique.

Images In general, the stomach is the least expensive and the least labor-intensive access site to use for enteral feeding; however, feeding into the stomach is not always tolerated. Patients with impaired gastric motility may be predisposed to aspiration and pneumonia when feedings are delivered into the stomach. Many critically ill, injured, and postoperative patients exhibit delayed gastric emptying, limiting their ability to tolerate gastric feeding. In addition, patients with diabetic gastroparesis or patients with severe gastroesophageal reflux disease or intractable vomiting are at a higher risk for aspiration of gastric contents, resulting in pneumonia. In these patients, placing the tip of the tube into the duodenum or jejunum (also referred to as transpyloric placement) has been suggested as a method to decrease risk for aspiration.12 Nasoduodenal feeding has been associated with a lower rate of vomiting and ventilator-associated pneumonia when compared to NG feeding.28 However, the evidence to support the difference in aspiration and aspiration pneumonia risk associated with gastric and small bowel feeding is inconclusive. In general, small bowel feeding may be beneficial in patients who do not tolerate gastric feeding and offers an alternative to PN.1013 Nasoenteric feeding tubes can be inserted at the patient’s bedside by trained medical personnel. However, greater skill is required to advance the tip of the feeding tube beyond the pylorus. Several techniques have been described in the literature to help facilitate bedside placement. Variable success rates have been reported with these techniques and are largely dependent on clinician experience. Electromagnetic tube placement devices that can be used at the bedside to guide tip position into the small bowel have been shown to be safe and cost-effective for small bowel feeding tube placement.29,30 Alternatively, a variety of endoscopic and fluoroscopic techniques have been described to insert transpyloric tubes.12,27 Radiographic confirmation of appropriate tip placement should be obtained prior to use for all feeding tubes inserted by bedside techniques.7,8

Long-Term Access

Feeding tubes used for short-term enteral access are usually not optimal for long-term use because of patient discomfort, complications, and mechanical failures that develop over time. Long-term access should generally be considered when EN is anticipated for longer than 4 to 6 weeks. Many techniques can be used to establish long-term enteral access, including laparotomy, laparoscopy, endoscopic and image guidance (e.g., fluoroscopy, ultrasound).12 The ability to perform the various techniques will be somewhat dependent on the expertise and facilities available within each institution. Long-term enteral access options include gastrostomy and jejunostomy tubes.

A gastrostomy is the most common type of long-term enteral access. It eliminates the nasal irritation and discomfort associated with nasoenteric feeding tubes and inadvertent removal is uncommon. In addition, because feeding gastrostomies use large-bore tubes, clogging is less of a problem. The most common technique for placement is the percutaneous endoscopic gastrostomy (PEG). It is minimally invasive and can be performed safely and cost-effectively in an endoscopy suite or at the bedside using conscious sedation and local anesthesia. Young children, however, will usually require general anesthesia for the procedure. Gastrostomy tubes are available in various sizes (12F to 28F; 1 to 4.5 cm shaft lengths), material (e.g., silicone, polyurethane), and have different retention mechanisms. Since smaller-diameter tubes are prone to more frequent occlusion and dysfunction, the larger diameter size is usually preferred. For patient convenience and comfort, a low-profile skin-level gastrostomy device may be placed in 2 to 3 months, once the gastrostomy tract has matured, if this type of device was not placed initially. This “gastric button” consists of a short, silicone, self-retaining conduit with either a mushroom tip or a balloon at the internal end and a one-way valve and small flange at the skin surface. Because this averts the external tube presence, it tends to be preferred in children or ambulatory adults who are receiving intermittent feedings. The exit site of all gastrostomies requires general stoma care to prevent inflammation and infection. Routine replacement of the gastrostomy tube at defined intervals (usually 3 to 6 months) is a standard of practice of many clinicians to prevent failure of the retention mechanism that can occur over time.12

In patients with a functional bowel but impaired gastric motility, pancreatitis, or who otherwise do not tolerate gastric feeding and require long-term enteral access, a jejunostomy may be an appropriate option.27 Various endoscopic and fluoroscopic techniques are available for direct jejunostomy placement. A surgically placed jejunostomy may be an option if the patient requires a laparotomy or laparoscopy for other reasons. For patients who require small bowel feeding with simultaneous gastric decompression, a gastrojejunal tube may be placed utilizing various endoscopic, fluroscopic, and surgical techniques.12,27 Because jejunostomies use smaller-bore tubes, occlusion occurs more commonly than with gastrostomy tubes. Gastrojejunostomy tubes are often replaced every 3 to 6 months to prevent occlusion.

Pharyngostomies and esophagostomies are invasive because the tube is located in the neck and passes through the skin into the pharynx or esophagus, respectively. They are rarely performed because of the high complication rate and extreme difficulty associated with their maintenance care.31 However, they may be used in patients with head and neck malignancies and when placement of a gastrostomy or jejunostomy tube is not possible due to GI obstruction.

There are ethical implications regarding determination of appropriate candidates for long-term feeding tube placement.12,31,32 Because a gastrostomy is relatively easy to place and many patients, families, and nonspecialist clinicians overestimate the benefits of EN, it is prone to inappropriate use. In certain patient populations, such as those with end-stage cancer or advanced dementia, the placement of a gastrostomy is controversial. Artificial nutrition and hydration (ANH) has not been shown to promote the healing of pressure ulcers, increase patient comfort or functional status, or prolong survival when compared to hand feeding in patients with advanced dementia.32 From a clinical standpoint, ANH does not increase a patient’s comfort or improve nutrition parameters of most terminally ill people and can result in medical complications.33 Placement of a feeding tube resulted in a higher 1-year mortality rate in a group of 5,266 nursing home residents with dysphagia.34 Evaluation by a multidisciplinary team is warranted for patients near end of life to establish whether the benefit outweighs the risk of feeding tube placement.8,32

ADMINISTRATION METHODS

EN may be administered by continuous, cyclic (continuous rate over a portion of the day), intermittent (infused over 20 to 60 minutes), or bolus (generally given in 5 to 10 minutes) methods and may be accomplished by syringe, gravity, or pump-controlled techniques. The method of delivery depends on the location of the tip of the feeding tube, the patient’s clinical condition and intestinal function, the environment in which the patient resides, and the patient’s tolerance to the tube feeding.

Continuous

Pump-assisted continuous administration of EN is generally the method of choice for feeding patients who are critically ill, have poor glycemic control, are being fed via jejunostomy tube, or have demonstrated intolerance to intermittent or bolus feeding.9,35 When EN is delivered into the small intestine, the continuous method is preferred because it is associated with enhanced tolerance. The rapid delivery of feeding into the small intestine, especially hyperosmotic formulations, may contribute to abdominal distension, cramping, hyperperistalsis, and diarrhea. Therefore, conversion to intermittent or bolus administration is not recommended for those with jejunostomy tubes.

The delivery system for continuous administration generally includes a feeding reservoir or bag attached to an extension set that is connected to a pump. The delivery system is then attached to the patient’s enteral access tube. Continuous administration may increase nursing time because routine checks are needed, but this disadvantage is offset by the improved tolerance. For adults, target EN administration rates generally range from 50 to 125 mL/h, although higher rates have been used without complications. In infants and children, goal administration rates vary with age and weight and should be sufficient to meet caloric needs while maintaining good GI tolerance. The primary disadvantage to this method of administration is the cost and inconvenience associated with the pump and administration sets. In the home care setting, battery-operated ambulatory enteral pumps are available to allow the patient greater mobility.

Cyclic

A patient who is not eating well during the day because of complaints of fullness and lack of appetite may benefit from a trial of cyclic EN, in which the enteral feeding is administered only at night. In addition, EN administration only overnight will free the patient from the pump during the day and allow for greater mobility. This increased mobility may be particularly useful for the home patient or patient requiring rehabilitation. Because a pump controls the rate of administration, this method may be used in patients with either gastric or small bowel access.

Bolus

The bolus administration of EN is commonly used for patients in long-term care settings who have a gastrostomy. This administration technique involves the delivery of the enteral feeding formulation over 5 to 10 minutes. Essentially, the only equipment needed is a syringe to instill the feeding volume into the tube. Depending on the patient’s nutritional requirements, an instillation volume of 240 to 500 mL is generally used and repeated four to six times daily. From a convenience standpoint, it is generally preferable to adjust the bolus volume in increments of the feeding formulation container size (usually 240 to 250 mL). Bolus volumes given to infants and children vary with age and weight (usually 30 to 240 mL) and should be sufficient to meet the calorie needs of most patients. In neonates, the bolus regimen is usually begun with an every 3-hour schedule; as the child grows, feedings may be given less frequently.36 In patients with duodenal or jejunal access, bolus delivery may result in cramping, nausea, vomiting, aspiration, and diarrhea. Bolus administration also should be avoided in patients with delayed gastric emptying and in patients who are at high risk of aspiration.

Intermittent

If a patient is experiencing intolerance to bolus administration over 5 to 10 minutes, it may be helpful to administer the prescribed volume over a longer time period, generally 20 to 60 minutes. For this method, the desired volume of feeding formulation is emptied into a reservoir bag or container and administered by an enteral pump or via gravity drip using a roller clamp. The bolus method of administration is more consistent physiologically with normal eating patterns than the continuous method. One study in infants demonstrated that normal gallbladder emptying did not occur with continuous feedings but was present in those infants receiving bolus feedings.37 Thus, those patients who need long-term EN and PN, especially children, may benefit when this approach is used because it may minimize the development of cholestatic liver disease.

INITIATION AND ADVANCEMENT PROTOCOL

Guidelines for the initiation and advancement of enteral feeding formulations vary greatly and are primarily tailored to patient tolerance. The typical recommendation for continuous EN administration for adults is to start at 20 to 50 mL/h and advance by 10 to 25 mL/h every 4 to 8 hours until the desired goal is achieved. For intermittent administration, the typical recommendation is to start with 120 mL every 4 hours and advance by 30 to 60 mL every 8 to 12 hours.8,35 In children, the recommendation for continuous administration is initiation at a rate of 1 to 2 mL/kg per hour (no more than 25 to 30 mL/h) or 2 to 4 mL/kg per bolus (no more than 30 to 90 mL) with advancement by similar amounts every 4 to 24 hours. In premature infants, feedings may be initiated at lower rates usually 10 to 20 mL/kg per day and advanced by similar rates daily. Schedules for progression of tube feeding from initial to target rates are important and may influence tolerance. If the protocol is too conservative, it may take an excessively long period of time to reach nutrient goals. The practice of diluting enteral feeding formulations is not routinely recommended unless necessary to increase fluid intake.8,35 The development of an EN protocol within an institution that outlines initiation and advancement criteria may be a useful strategy to optimize achievement of nutrient goals.10,11 Such a protocol should allow nursing to advance the rate (e.g., 25 mL/h every 4 hours until the goal rate is achieved) based on GI tolerance. Clinical signs of intolerance include abdominal distension, abdominal cramping, high GRVs, aspiration, and diarrhea.

ENTERAL FEEDING FORMULATION SELECTION

Historically, enteral formulas were created to provide essential nutrients. Over the years, enhancements have been made to meet specific patient needs and improve tolerance. For example, nutrient composition has been enhanced by changing the content of the amino acids (e.g., glutamine and arginine), changing the omega-3 polyunsaturated fatty acid content, and adding RNA to enhance immune function and improve therapeutic outcomes. These specific nutrients have been called nutraceuticals or pharmaconutrients because of the intent to use them to modify disease processes and improve clinical outcomes. Currently, enteral feeding formulations are categorized by the FDA as medical foods.8 They are considered components of supportive care and are simply regulated to ensure sanitary manufacture. Unfortunately, they are not subject to rules governing health claims, and promotion of medical foods for therapeutic intent is currently not regulated by the FDA.38

The macronutrient content of enteral formulas (namely, protein, carbohydrate, and fat) varies in nutrient complexity (Table 120-4). Nutrient complexity refers to the amount of hydrolysis and digestion a substrate requires prior to intestinal absorption. Polymeric or intact substrates are of similar molecular form as the foods we eat. Enteral formulas that contain partially hydrolyzed or elemental substrates are characterized as elemental or defined-formula diets. The caloric contribution of each of the macronutrients is as follows: carbohydrates, 4 kcal/g (17 kJ/g); protein, 4 kcal/g (17 kJ/g); and fat, 9 kcal/g (38 kJ/g).

TABLE 120-4 Enteral Formula Nutrient Complexity

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Protein Composition

The essential amino acid content of the protein source determines the quality of the protein, and most commercially available enteral feeding formulations contain proteins of high quality. The form of the protein source in enteral formulas will determine the amount of digestion that is required for absorption within the small bowel. Polymeric or intact protein sources require digestion to smaller peptides and free amino acids before absorption from the GI tract. Therefore, enteral formulation protein sources such as meat, milk, eggs, and caseinates require digestion by hydrochloric acid, specific protein enzymes, and pancreatic proteases. Enteral formulations may also contain protein sources that are partially hydrolyzed to peptides or L-amino acids. As the molecular form of protein is reduced in size, the osmotic load of the enteral formulation is increased. Many commercially available enteral feeding formulations contain combinations of intact and partially hydrolyzed protein sources.

Conditionally Essential Amino Acids

Glutamine and arginine are generally considered nonessential amino acids. However, during periods of high physiologic stress, the need for these nutrients may be increased beyond the body’s synthetic ability; consequently, these amino acids are characterized as conditionally essential. Because they are usually present in low amounts in most enteral feeding formulations, those formulations targeted for the critically ill may be supplemented with glutamine and/or arginine.

Glutamine serves as a key fuel for rapidly dividing cells, including enterocytes, endothelial cells, lymphocytes, and fibroblasts. The primary site of glutamine production is skeletal muscle. During critical illness, the catabolism of skeletal muscle provides an increased glutamine supply, but this may not be enough to meet the high rate of glutamine use by cells of the immune system and other cells involved in recovery and repair. Glutamine depletion may develop, particularly during prolonged periods of metabolic stress. Favorable outcomes have been documented in critically ill patients when enteral formulations have been supplemented with glutamine.10,39,40

Arginine has been added to some immune-modulating enteral formulations in concentrations that range from 4.5 to 14 g/L. However, arginine supplementation remains controversial, especially in patients with sepsis.40,41 Many of the physiologic effects of arginine are mediated by its conversion to nitric oxide, which, in turn, modulates immune function, inflammation, vasodilation, and response to sepsis. Some of these effects may be potentially harmful in the patient with sepsis, especially when higher arginine intakes are used.10,11

Carbohydrate Composition

The carbohydrate component of enteral feeding formulations usually provides the major source of calories. Polymeric or intact enteral formulations contain starches and numerous types of glucose polymers, which require digestion to monosaccharide moieties prior to intestinal absorption (see Fig. 120-1). As the hydrolysis of carbohydrate increases within an enteral formulation, the osmolality of the formulation increases. Simple sugars, such as glucose and galactose, contribute significantly to the osmolality of enteral formulations. Consequently, polymeric entities, rather than elemental sugars, are preferred in enteral formulas. Glucose polymers provide a useful carbohydrate source that is tolerated by most individuals (see Table 120-4). The polymers are large chains that provide minimal osmotic load, yet are absorbed easily in the intestine. The one shortcoming of glucose polymers and oligosaccharides is that they are not as sweet as simple glucose and thus may decrease the palatability of orally consumed products. Finally, almost all commercially available enteral feeding formulations used in adults and older children are lactose-free because disaccharidase production within the gut lumen is reduced during illness and periods of prolonged bowel rest. Additionally, there is a high incidence of lactose intolerance in those of certain ethnic decent: rates range from 5% in white northern Europeans, North Americans, and Australians to over 50% in people from South America, Africa, and Asia.42 By adulthood, 15% of Caucasian, 40% of Asians, 50% to 80% of Hispanics, and 85% of African Americans have lactase deficiency. Infant formulas are available with or without lactose.36

Fat and Fatty Acid Composition

Fat is an important constituent in the diet because it provides a concentrated calorie source and serves as a carrier for fat-soluble vitamins. Sufficient linoleic acid is required to prevent essential fatty acid deficiency and should approximate at least 1% to 3% of total daily calories. The most common sources of fat in enteral feeding formulations are vegetable oils (soy or corn) rich in polyunsaturated fatty acids. The concentration of fat varies between less than 2% and 45% of total calories. High fat content of the diet is associated with delayed gastric emptying. Enteral feeding formulations can also contain fat in the form of MCTs derived from palm kernel or coconut oils. Because MCTs do not contain linoleic acid, enteral formulations that contain MCTs will also have a source of long-chain triglycerides to provide essential fatty acids. Potential advantages of MCTs compared to long-chain triglycerides are that they are more water soluble, undergo rapid hydrolysis, require no pancreatic lipase or bile salts for absorption, and do not require carnitine for transport into the mitochondria, where they are converted to energy. They also do not require chylomicron formation for small bowel enterocyte absorption and are not transported via the lymphatic system.

The source of long-chain fat within some enteral formulations has been modified from omega-6 to omega-3 fatty acids in an effort to modulate the inflammatory response in patients with acute respiratory distress syndrome (ARDS), acute lung injury (ALI), and sepsis.43 The omega-6 fatty acids serve as precursors to certain cytokines that are potent inflammatory mediators and also decrease cell-mediated immune response. The omega-6 fatty acids are high in linoleic acid and are derived from vegetable oil, whereas the omega-3 fatty acids, derived from coldwater fish oils, are high in linolenic acid. It has been proposed that if the dietary proportion of omega-3 fatty acids is increased and omega-6 fatty acids is decreased, less inflammation and immunosuppression may occur during metabolic stress due to an alteration in the type and quantity of cytokines produced.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are two fatty acids abundant in human milk, but until recently, they were not contained in commercial infant formulas. Although the role of ARA supplementation is unclear, DHA is important in brain and eye development. In some studies, DHA and ARA supplementation provided benefits to a child’s visual function and/or cognitive and behavioral development.44 The FDA has classified plant-based fatty acid blends of DHA and ARA as generally recognized as safe (GRAS), and most infant formulas, as well as some products for pregnant and lactating women, are supplemented with these fatty acids.

Fiber Content

Fiber, in both soluble and insoluble forms, is added to several adult and pediatric enteral feeding formulations in amounts ranging from 5.9 to 24 g/L. Infant formulas generally do not contain fiber; however, at least one formula intended for use in infants with diarrhea contains soy fiber. Fiber supplementation is common in clinical practice, primarily because fiber-free enteral formulations are implicated as a contributing factor to both diarrhea and constipation. Soluble fiber undergoes bacterial degradation within the colon to produce short-chain fatty acids. Potential benefits of soluble fiber are its trophic effects on the colonic mucosa and promotion of sodium and water absorption within the colon. Insoluble fiber is undigested and may help decrease GI transit time by increasing fecal weight. Fiber supplementation may help regulate bowel function in both normal individuals and those with altered colonic motility. In addition, the resulting short-chain fatty acids are an excellent energy source. Although beneficial effects of fiber supplementation have not been clearly proven in clinical studies, there is experimental evidence that fiber may play an integral role in normal nutrition, and risk is generally minimal.45 Fiber supplementation may be beneficial when long-term EN is required or in patients who experience diarrhea or constipation while receiving a fiber-free enteral formulation. Soluble fiber may also be beneficial in the critically ill patient who is hemodynamically stable and develops diarrhea while receiving EN.10,46 Insoluble fiber should be avoided in all critically ill patients due to case reports of bowel obstruction.10

Osmolality and Renal Solute Load

Osmolality and renal solute load can affect tolerance to enteral feeding formulations. The osmolality of a given enteral formulation is a function of the size and quantity of ionic and molecular particles, primarily related to the protein, carbohydrate, electrolyte, and mineral content within a given volume. The unit of measure of osmolality is milliosmoles per kilogram (mOsm/kg) or millimoles per kilogram (mmol/kg). Iso-osmolar is considered to be ∼300 mOsm/kg (300 mmol/kg). Enteral formulations with greater amounts of partially hydrolyzed or elemental substrates have a higher osmolality than formulations containing polymeric or intact substrate forms. Therefore, formulations that contain sucrose or glucose, dipeptides and tripeptides, and amino acids are generally hyperosmolar. Increased caloric density also increases the osmolality of an enteral formulation. In general, the osmolality of commercially available enteral feeding formulations ranges from 300 to 900 mOsm/kg (300 to 900 mmol/kg). The American Academy of Pediatrics recommends that enteral formulations for use in infants have an osmolality of 450 mOsm/kg (450 mmol/kg) or less.

Symptoms of gastric retention, diarrhea, abdominal distension, nausea, and vomiting have been attributed to enteral formulations having high osmolality based on the assumption that a higher osmolality will draw water into the gut lumen. However, clinical evidence to support the relationship between osmolality and GI tolerance is lacking. The practice of diluting hyperosmolar formulations has not been shown to enhance tolerance and should be discouraged unless dilution is done to increase fluid intake.8 Factors such as concurrent antibiotic therapy, method of enteral feeding administration, and the formulation’s composition are likely to play a greater role in GI tolerance than the osmolality.

The renal solute load is determined by the protein, sodium, potassium, and chloride content of the enteral formulation. Formulations that contain a greater solute load increase the obligatory water loss via the kidney. It is estimated that 40 to 60 mL of water is the minimal amount necessary to excrete 1 g of nitrogen. Those receiving high-protein enteral formulations unable to ingest more water, such as a geriatric patient and a patient with altered mental status, may be at risk for significant dehydration.

CLASSIFICATION OF ENTERAL FEEDING FORMULATIONS

Images Although most patients’ needs can probably be met using three or four different formulations, certain disease states or clinical conditions may warrant the use of a specialty feeding formulation. Development of an evidence-based, effective formulary system should focus on clinically significant characteristics of available formulations and avoid duplicate feeding formulations. Categorizing enteral feeding formulations according to therapeutic class is necessary in developing a formulary system for adults (Table 120-5) and children (Table 120-6).

TABLE 120-5 Adult Enteral Feeding Formulation Classification System

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TABLE 120-6 Pediatric Enteral Feeding Formulation Classification System

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Standard Polymeric

A large number of commercially available enteral feeding formulations fall within the category of a standard polymeric formulation. These formulations are approximately isotonic (300 mOsm/L [300 mmol/L]), provide 1 to 1.2 kcal/mL (4.2 to 5 kJ/mL), and are composed of intact nutrients in a nutritionally balanced mix of carbohydrate, fat, and protein. They are provided with or without dietary fiber. The nonprotein calorie-to-nitrogen ratio of these products is ∼125:1 to 150:1. This ratio is a useful parameter for assessing protein density in relation to calories provided. Certain feeding formulations in this category may be promoted as high nitrogen but fall within standard protein amounts. To maintain their isotonicity, many products within this category are not sweetened, making them unpalatable and generally suited only for tube feeding and not oral supplementation; however, flavored products are available. The nutrient requirements of the majority of adult patients and children older than 1 year receiving EN can generally be met using feeding formulations in this category. Many infant formulas will also fall into this category because they provide 20 to 30 kcal/oz (2.8 to 4.2 kJ/mL).36

High Protein

Enteral feeding formulations with a nonprotein calorie-to-nitrogen ratio less than 125:1 can be categorized as high protein. The lower the ratio, the higher the protein density in relation to calories provided. In patients with high protein requirements, it is generally unacceptable to use a feeding formulation with standard protein amounts because the volume necessary to meet protein requirements will result in excessive calorie intake. Patients who may be candidates for a high-protein feeding formulation are critically ill patients and those with pressure sores, surgical wounds, and high output enterocutaneous fistula. In general, adult patients with estimated protein requirements exceeding 1.5 g/kg per day may benefit from a high-protein formulation. High-protein formulations may also be beneficial in mechanically ventilated patients who are receiving propofol for sedation. The vehicle for propofol is a soybean fat emulsion that contains 1.1 kcal/mL (4.6 kJ/mL). At therapeutic dosages, the use of propofol can significantly contribute to caloric intake, and a high protein formulation may be beneficial in allowing for the provision of protein requirements while minimizing the risk of overfeeding.

High Caloric Density

High caloric density formulations are concentrated to provide less fluid and electrolyte intake in comparison to a standard polymeric formulation. They provide ∼2 kcal/mL (8.4 kJ/mL) and will achieve similar calorie and protein intake as a standard polymeric formulation, using half the volume. High caloric density formulations are often necessary for patients who require fluid and/or electrolyte restriction, such as those with kidney insufficiency or congestive heart failure. Although specialty enteral formulations targeted for acute and chronic kidney failure are also available, many patients with kidney failure can be managed using a product in this category.

Elemental/Peptide Based

Formulations in this category contain protein and/or fat components that are hydrolyzed into smaller, predigested forms. Traditionally, enteral formulations in this category were referred to as elemental and contained a high proportion of protein in the form of free amino acids and a low amount of fat. Although still commercially available, many of the formulations in this category have been reformulated to provide a portion of the protein in the form of dipeptides and tripeptides and fewer free amino acids because dipeptides and tripeptides are more readily absorbed than an equivalent mixture of free amino acids.47 These peptide-based formulations, may be beneficial in patients with impaired digestion or absorption. Peptide-based formulations are generally higher in fat than the older, elemental formulations and use MCTs in varying proportions as the fat source.

Evidence to support the use of elemental or peptide-based formulations is limited, and their routine use is generally not recommended. Patients who do not tolerate standard, intact nutrient formulations as a result of malabsorption or short bowel syndrome might be candidates for a trial of a peptide-based formulation. In addition, elemental or peptide-based products that have higher percentages of MCTs and small amounts of long-chain triglycerides may be beneficial for patients with severe pancreatic insufficiency, such as chronic pancreatitis and cystic fibrosis; severe abnormalities of the intestinal mucosa, such as untreated celiac disease; biliary tract disease, such as biliary atresia or severe cholestasis; or chylothorax.

Disease Specific

Newer enteral feeding formulations have been designed to meet unique nutrient requirements and manage metabolic abnormalities associated with specific disease states. Conditions for which specialized enteral feeding formulations exist include kidney and liver failure, lung disease, including ARDS, diabetes mellitus, wound healing, and metabolic stress. Specialized enteral formulations designed to modulate the inflammatory response in patients with severe metabolic stress have been referred to as immune-modulating formulations or immunonutrition. These specialized formulations are supplemented with nutrients such as glutamine, arginine, branched-chain amino acids, nucleotides, and omega-3 polyunsaturated fatty acids, as a result of their potential role in regulating immune function; guidelines for their use in critically ill patients have been published.10,11,48 Positive results have been reported in patients undergoing major elective GI surgery and major cancer surgery of the head and neck, patients with severe trauma or burns, and critically ill patients on mechanical ventilation. Multiple meta-analyses have shown that the use of immune-modulating enteral formulations in these select patient populations is associated with significant reductions in infectious complications, hospital length of stay, and duration of mechanical ventilation.49,50 However, use of immune-modulating formulations has been associated with increased mortality in patients with preexisting severe sepsis and should therefore not be used or used with caution in these patients and in those who become septic while receiving these products.10Because of the lack of evidence to support their use, immune-modulating formulations are not currently recommended for use in children.13


Clinical Controversy…

Although there appears to be a role for immune-modulating enteral formulations in critically ill patients, the optimal pharmaconutrient composition and type of critically ill patient most likely to benefit are unclear. Available literature has been criticized for the heterogeneity of studies, including a wide range of patient populations and a variety of enteral formulations. The specific effects and optimal dose of individual nutrient components contained in immune-modulating enteral formulations also remain unclear. Caution is suggested in patients with severe sepsis due to arginine content, but available evidence is conflicting.

In patients with ARDS, improved outcomes from using a low carbohydrate formulation supplemented with specific fatty acids (eicosapentaenoic acid and γ-linolenic acid) and antioxidants have been documented.43,51 When compared with a high fat formulation, the specialized diet was associated with fewer days of ventilatory support, fewer ICU days, and fewer new organ failures. Consequently, it is recommended that this specialized formulation be used for patients with ARDS and severe ALI.10,11,48

There are no disease-specific enteral products currently marketed for use in infants or children younger than 10 years of age. The use of modular supplements may be necessary in children with special nutrition needs (see Modular Products below).

Oral Supplements

In general, oral supplements are not intended for tube feeding but to enhance an oral diet. They are sweetened to improve taste and therefore are hypertonic (∼450 to 700 mOsm/kg [∼450 to 700 mmol/kg]). Osmolality is generally not a problem in the patient with a functioning GI tract. However, in the tube-fed patient, a sweetened product is unnecessary and may contribute to GI intolerance, particularly diarrhea. Powder supplements that are mixed with milk should be avoided in lactose-intolerant patients. In addition to liquid supplements, puddings, gelatins, bars, and milkshake-like supplements are available.

Modular Products

A module is a powder or liquid form of a nutrient (e.g., protein, carbohydrate, and fat) that is used to supplement nutrition intake when the diet or commercially available enteral formulation does not fully meet a patient’s needs.36,52Alternatively, formulations available in powder or concentrate can be mixed with less water than needed for the standard dilution to deliver more nutrients in less volume. Infant formulas generally are concentrated beyond their standard concentration in this way. The mixing process required for modular components increases the potential for bacterial contamination and incorrect preparation. Contamination is a particular concern with the use of blenders and reconstitution of powders.8,53 Human milk fortifiers are available for supplementation of human milk so that it meets the needs of a premature infant. Human milk fortifiers add calories, protein, and minerals and have been shown to improve nutritional outcomes in human milk-fed premature infants.36,5457

Rehydration

Oral rehydration formulations are useful in maintaining hydration or treating dehydration in adult and pediatric patients with high GI output. Such formulations are available commercially in powder or liquid form or can be extemporaneously compounded. They can be administered orally or given via a feeding tube. The glucose content of oral rehydration solutions is important because it stimulates active transport systems, which, in turn, stimulate passive sodium and water uptake simultaneously with the glucose. Therefore, oral or enteral administration of rehydration solutions may decrease fecal water loss and generate a positive electrolyte balance.58,59

FORMULARY AND DELIVERY SYSTEM CONSIDERATIONS

For an institution’s formulary considerations, generally no more than one product is necessary per category of enteral feeding formulation, and it may be possible to omit certain categories based on the specific patient population within a given institution. Additional selection criteria include container size and type, liquid or powder form, shelf life, ease of use, and cost.

Most enteral products are available as ready-to-use, prepackaged liquids, and a few are available in the powdered state and require reconstitution prior to use. Advantages of ready-to-use liquid formulations are convenience and lower susceptibility to microbiologic contamination. One disadvantage is that more storage space is required. The ease or convenience of a ready-to-use liquid is especially important for self-care patients, the disabled, and those who have difficulty reading or following printed instructions. Ready-to-use liquid enteral formulations are generally available in rigid plastic containers, cans, or closed, ready-to-hang bags. Bolus administration of EN is usually achieved using formulas available in cans. However, when formula from a can is used for continuous or cyclic administration, it must first be poured into a bag or bottle to allow for administration via a pump. This “open system” has a higher risk of microbial contamination than closed, ready-to-hang containers. The use of a powder formula is also considered an open delivery system.

Contaminated enteral feeding formulations are a potential source of infectious complications.8,58 The GI tract may serve as a portal of entry for bacteria into the systemic circulation, especially in patients who are receiving multiple antibiotics, have undergone a surgical procedure, are immunosuppressed, or have GI tract stasis from a variety of causes. The contamination of enteral feeding formulations is associated with a lack of attention to proper handling techniques, inability to disinfect preparation equipment, and nonsterile or contaminated tube-feeding additives. Unlike liquid formulations, powdered products are not guaranteed by the manufacturer to be sterile because of the inability to properly sterilize the powder without destruction of some of its components. Contamination of milk powder and consequently powdered infant formulas with Enterobacter sakazakii (Cronobacter species) has been reported.53 Contamination of one infant formula with E. sakazakii at the manufacturing site was implicated in the death of an infant in a neonatal ICU, prompting FDA warnings regarding the use of powdered formulations in premature neonates and other immunocompromised infants. Because powder formulations require reconstitution, often in a blender that is difficult to sterilize, they are also more susceptible to contamination at the time of preparation. To minimize contamination risk, stringent handling procedures should be followed during all stages of enteral feeding preparation and delivery. The closed-system containers supply a ready-to-hang, prefilled, sterile supply of formula in volumes of 1 to 1.5 L. Most but not all enteral formulations intended for use in adults and some pediatric formulations are available in the closed-administration system. The closed-administration system also offers the advantage of not requiring refrigeration and allowing hang times beyond 24 to 36 hours, whereas the conventional open-delivery system necessitates hang times of generally 4 to 8 hours.

COMPLICATIONS AND MONITORING

The majority of complications associated with EN are metabolic, GI, and mechanical. The early detection and management of potential complications is necessary to allow for the successful use of EN. In addition, measures to avoid complications should be incorporated into the management of all patients receiving EN (Table 120-7).

TABLE 120-7 Suggested Monitoring for Patients on Enteral Nutrition

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Metabolic Complications

Metabolic complications associated with EN are similar to those associated with PN, but the incidence tends to be lower. EN is associated with a lower incidence of hyperglycemia than PN.20,60 Complications related to hydration and electrolyte imbalance and altered glucose control are observed more frequently in critically ill patients, especially those with underlying organ dysfunction. The micronutrient and water contents within enteral feeding formulations are in fixed amounts intended to meet recommended dietary allowances for the average person. Consequently, the frequency of clinical and laboratory assessment to monitor hydration, electrolyte, organ function, and glucose control adequately for a patient who is critically ill is greater than for a stable patient or patients residing in rehabilitation units or at home. Patients receiving long-term EN at home may require laboratory monitoring only every 2 to 3 months, depending on their clinical status. Besides macronutrient content, it is important to evaluate the actual content of water and micronutrients provided by the enteral formulation, especially in critically ill patients at high risk of metabolic complications. Supplemental fluid, electrolytes, and minerals may be required in some patients. Conversely, for patients who have fluid retention or increased serum electrolytes, the enteral formulation may need to be changed to one that is more concentrated or provides less of a particular nutrient.

Gastrointestinal Complications

Images The GI complications associated with tube feeding include nausea, vomiting, abdominal distension, cramping, aspiration, diarrhea, and constipation. GRV refers to the volume of contents in the stomach and is measured by using a syringe and aspirating from a large-bore NG or gastrostomy tube. For patients receiving tube feeding into the stomach, GRV is widely used to assess tolerance. Although not well documented, patients with high GRVs may be at higher risk of vomiting and/or aspiration. The frequency of measuring GRV generally varies between 4 and 8 hours, and most institutions follow a protocol that directs the frequency of monitoring and at what volume and for how long to hold feedings.61 In critically ill patients receiving gastric feeding, GRVs should be measured every 4 hours.10

If high GRVs occur, the response is often to hold the next scheduled bolus or stop or decrease the rate if feeding is continuous. However, frequent interruptions in EN delivery can adversely affect the attainment of nutrition outcome goals. Because GRV is an unreliable measure of EN tolerance, symptoms such as abdominal distension, fullness, bloating, and discomfort are generally more reliable indicators of EN intolerance and should be assessed frequently. A trend toward increased GRV is generally more important than one isolated high measurement. Generally, in the absence of other signs of intolerance, EN should not be held when the GRV is less than 500 mL.10 If symptoms are present, and GRVs are elevated, a decrease in the tube-feeding rate or discontinuation may be warranted. Measures to reduce aspiration risk should be implemented when GRVs are consistently elevated, including elevating the head of the patient’s bed to a 30° to 45° angle and consideration of postpyloric continuous feeding. In addition, it may be beneficial to initiate a prokinetic agent such as metoclopramide or erythromycin to increase the gastric emptying rate.10,62,63 Other interventions include minimizing the use of narcotics, sedatives, or other agents that may delay gastric emptying and correcting underlying fluid imbalance and electrolyte disturbances that can impair GI motility.64 Unless GRVs are excessive (greater than 500 mL in adults), they should generally be reinstilled (refed) through the tube to minimize nutrient, fluid, and electrolyte losses.8,65

Aspiration pneumonia is considered the most serious complication associated with tube feeding and is potentially life-threatening. Although aspiration is a fairly common event for critically ill patients receiving tube feeding, progression to aspiration pneumonia is difficult to predict. Risk factors for aspiration include a previous aspiration episode, decreased consciousness, neuromuscular disease, structural airway or GI tract abnormalities, endotracheal intubation, vomiting, persistently high GRVs, and prolonged supine positioning.65 Identification of these risk factors, along with close monitoring of GRV, is recommended for all critically ill patients receiving tube feeding. Historically, blue food coloring had been added to enteral formulations in an attempt to detect aspiration. However, because of its low sensitivity for detection and association with several serious adverse events, including death, the addition of blue food dye to enteral formulations is no longer advised.10,66 There are currently no reliable methods available to detect aspiration in enterally fed patients.10,67


Clinical Controversy…

Some clinicians use low-dose ‘trickle’ or trophic EN (10 to 20 mL/h) early in the course of critical illness to maintain gut integrity and function while decreasing risk of GI complications. However, the necessary volume of EN required to maintain intestinal integrity remains unknown. There is some evidence that providing initial trophic EN in mechanically ventilated patients with acute respiratory failure results in similar clinical outcomes to those of full energy EN with fewer episodes of GI intolerance.

Diarrhea develops in 20% to 70% of patients receiving EN. Because of the lack of a standard definition and the number of contributing factors, the true incidence is unknown.20,35 When monitoring for diarrhea, stool frequency, consistency, and volume should be evaluated, and previous bowel habits should be considered. Diarrhea has been defined as more than three liquid stools daily or a stool volume of more than 250 to 500 mL/day (10 to 25 mL/kg per day in children) for at least two consecutive days.20 Therefore, the occurrence of one or two loose stools does not constitute diarrhea or require intervention.

Images Diarrhea in patients receiving tube feeding may be caused by a number of factors, and management should be directed at identifying and correcting the most likely cause(s). Tube feeding-related factors that may contribute to diarrhea include too rapid delivery or advancement of formula, intolerance to the formula composition, administration of large volumes of feeding into the small bowel, and formula contamination. Thus, measures to prevent or manage diarrhea related directly to the tube feeding should address these potential causes.20,58,64 If diarrhea occurs when using a fiber-free formulation, consider switching to a fiber-containing formulation. If using a high-fat formulation, it may be beneficial to switch to a formulation lower in fat or having a proportion of the fat supplied as MCTs. Finally, it is important to assess the risk of bacterial contamination of the formula and take steps to minimize any potential risk factors. Once infectious etiologies have been excluded, severe diarrhea may require pharmacologic treatment with loperamide, diphenoxylate/atropine, or opioids.

Drug therapy, particularly the use of broad-spectrum antibiotics, is a common cause of diarrhea that is unrelated to tube feeding. Sorbitol, used as a sweetening agent in many liquid formulations to enhance palatability, is an osmotic laxative that can cause diarrhea. In addition, many drugs available in a liquid form are hyperosmolar, which may contribute to diarrhea, especially when these medications are not diluted properly before administration. Because many patients receiving tube feeding also receive medications in a liquid form, all medications should be evaluated for their potential contribution. Infectious causes, such as antibiotic-induced bacterial overgrowth by Clostridium difficile or other intestinal flora, need to be considered when diarrhea develops. Malabsorption, secondary to the underlying disease state or condition, may also cause diarrhea.

Mechanical Complications

Mechanical complications of EN are those associated with the feeding tube, including tube occlusion or malposition, and nasopulmonary intubation. Feeding tube occlusion usually results from the improper administration of medications and/or flushing technique. Kinking of the tube also may cause occlusion. The tube should be flushed with at least 30 mL of water before and after administering any medication. The recommended volume used in children is generally less than 30 mL and depends on the size of the tube. The frequency of flushing should be at least every 8 hours during continuous feeding and before and after each intermittent feeding. If tube occlusion occurs, an attempt to irrigate the tube with warm water should be made. Other fluids such as colas and cranberry juice have been used to irrigate occluded tubes but have not been shown to be any better than warm water. Some success in reestablishing patency has been shown with the use of pancreatic enzymes mixed in sodium bicarbonate.68 Declogging devices that are specifically designed to unclog feeding tubes are available. They have been designed to either mechanically break through or remove the occlusion or provide an applicator and syringe prefilled with pancreatic enzymes and various powders targeted to restore patency.

Inadvertent nasoenteric tube removal or displacement has been reported in ∼40% of patients receiving EN.69 An agitated or confused patient may pull at the feeding tube and cause its removal or malposition. Measures to decrease agitation and confusion should be attempted. Various manipulations done to the patient may also cause malposition. Securing the tube with tape may be helpful, as well as marking the tube with permanent ink at the exit site to assess for position change. A recently developed nasal bridle that uses a magnetic retrieval system has proven to be a simple and effective method for securing nasoenteric feeding tubes and preventing accidental removal.69

When a feeding tube is inserted nasally or orally, there is a risk that the tube may inadvertently enter the tracheobronchial tree. The risk may be higher in patients who have an impaired cough or gag reflex and when a stylet is used for tube insertion. Proper positioning of the tube should always be confirmed by radiography prior to feeding initiation and routinely reassessed to avoid inadvertent administration of enteral formula into the lung.

Other Complications

Infectious complications of feeding tube placement include sinusitis (with nasoenteric placement), exit site-related infections (e.g., cellulitis, subcutaneous abscess, and necrotizing fasciitis), and intraabdominal infections (e.g., peritonitis and abscess). Leaking and bleeding around the exit site can also occur.12,31 Formation of excessive granulation tissue around the exit site is often the cause of leaking and bleeding and can be managed by applying silver nitrate.

A unique complication of tube feedings in children, especially in the first year of life, is the development of feeding disorders as a consequence of oral hypersensitivity, poor oral/motor skills, and food aversion. In these children, transitioning from tube to oral nutrition is often difficult and protracted. The involvement of an occupational or speech therapist, behavioral psychologist, or other trained individual, as well as perseverance by the family, often is necessary to improve oral intake. Avoidance of a strict nothing by mouth (NPO) status, if possible, and oral stimulation programs for those children who must remain NPO are recommended to avoid this complication.70

DRUG DELIVERY VIA FEEDING TUBE

Using enteral feeding tubes to deliver drugs is a common practice and offers an alternative for patients unable to take drugs by the oral route. However, in addition to tube occlusion, effects on drug bioavailability and other potential interactions need to be considered when using this route. Medications have been given as a concomitant bolus administration via the feeding tube or admixed with the enteral feeding formulation.

Concomitant Drug Administration

Images Concomitant administration of medications with enteral feedings requires awareness of certain limitations. Medications delivered directly into the stomach allow for the normal process of drug dissolution. Medications delivered into the small bowel may result in alterations of drug dissolution because the stomach is bypassed. In addition, therapeutic effect designed to occur within the stomach, such as with antacids and sucralfate, may be influenced by the feeding tube route. Because many drugs are best absorbed in the fasting state, they should be administered on an empty stomach whenever possible. Patients on bolus gastric feeding may receive medications appropriately spaced between the feedings, but patients on continuous feeding will require interruption for drug administration.

Selecting the proper medication dosage form for coadministration with the tube feeding is another important consideration. Medications in sublingual form, sustained-release capsules or tablets, and enteric-coated tablets should not be crushed and therefore should not be administered via enteral feeding tubes.8,68 Solid dosage forms that are appropriate to crush should be prepared as a very fine powder and mixed with 15 to 30 mL of water or other appropriate solvent before administering through the tube. In addition, many capsules may be opened and the contents administered in the same manner. Pellets contained inside microencapsulated dosage forms should generally not be crushed. It may be acceptable to administer intact pellets through feeding tubes, provided that the pellets are small enough and drug absorption is not compromised.69,71,72 To avoid the need to crush a solid dosage form and mix with water, liquid dosage forms are used commonly for administration through feeding tubes. However, the risk of GI intolerance should be considered because of the hyperosmolality of many liquid formulations and possible sorbitol content.68,71 Although the use of a liquid dosage preparation may be more convenient than a solid dosage form, it may not be the best choice if GI intolerance is an issue.

As previously mentioned, adherence to the proper flushing technique is necessary to prevent occlusion when administering medication through a feeding tube. At least 15 mL of water should be given before and after each medication administration to clear the drug through the tube and help get the drug into the stomach.8 If more than one medication is scheduled for a given time, each should be administered separately, and the tube should be flushed with 5 to 15 mL of water between them.8,68 Flush volume will be less for children but generally should be at least 5 mL to ensure adequate flushing of the tube.8


Clinical Controversy…

The source of water used to flush the feeding tube and maintain patient hydration via the feeding tube is controversial. Tap water is adequate for the otherwise healthy, immunocompetent patient. However, the acute or chronically ill patient receiving EN may be at higher risk from exposure to nonsterile tap water and may benefit from the use of purified water. Nosocomial infections from contaminated tap water sources have been reported in critically ill patients. The use of purified water for tube-feeding flushes in at-risk patients has been recommended by some clinicians.

Admixture of Drugs with Enteral Feeding

Mixing liquid medications with certain enteral feeding formulations is associated with several types of physical incompatibilities, including granulation, gel formation, separation, and precipitation.68,71 Not only can these physical incompatibilities inhibit drug absorption, but gel formation potentially may clog small-bore feeding tubes. Physical incompatibility with medications is more common in formulations that contain intact protein than in those with hydrolyzed protein. Also, medication and enteral formula incompatibilities are more common with the use of acidic pharmaceutical syrups. The most prudent recommendation is to avoid the routine admixture whenever possible, especially for nonaqueous preparations and syrups. In the clinical setting, exceptions do exist, such as adding electrolyte injections of potassium or sodium to enteral formulas to assist in maintaining or repleting electrolytes.

Drug–Nutrient Interactions

Images The most significant drug–nutrient interactions that can occur during continuous enteral feeding are those in which the bioavailability of the drug is reduced, and the desired pharmacologic effect is not achieved (Table 120-8). Unfortunately, limited clinical studies are available to document the extent of this problem with enteral feeding. Most of the observations are anecdotal case reports involving few patients. One of the most well-documented interactions is between phenytoin and enteral feeding. Phenytoin serum concentrations may decrease by 50% to 75% when phenytoin is given concomitantly with EN, possibly as a result of the binding of phenytoin to calcium caseinates or protein hydrolysates in the enteral formulation. Patients typically require higher than normal phenytoin doses while receiving EN.68,71 The patient’s clinical response and phenytoin serum concentrations should be monitored closely if phenytoin is given enterally during continuous enteral feeding and after its discontinuation.

TABLE 120-8 Medications with Special Considerations for Enteral Feeding Tube Administration

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Decreased bioavailability of certain antibiotics, particularly quinolones, has been documented when coadministered with enteral feeding due to complexation with multivalent cations such as calcium, magnesium, and iron contained in the feeding.68,71 Although the practice of holding tube feeding for 30 minutes before and 30 minutes after quinolone administration has been recommended, it has not been shown to improve drug absorption. Another option is to increase the quinolone dose when given concurrently with EN. There is evidence to suggest that ciprofloxacin absorption is significantly decreased when given via a jejunostomy tube, so this practice should be avoided, if possible.68

Warfarin resistance has been documented during enteral feeding, possibly as a consequence of decreased absorption or the antagonist effects of vitamin K. Before 1980, it was thought that the content of vitamin K (up to 1,330 mcg/1,000 kcal [or 317 mcg/1,000 kJ] of enteral feeding formula) was contributing to the pharmacologic interaction with warfarin. Subsequently, the vitamin K content within formulas intended for use in adults was reduced to less than 200 mcg/1,000 kcal (or 48 mcg/1,000 kJ). However, warfarin resistance continues to be reported, and a warfarin dosage increase may be required in patients receiving EN.68,73 The International Normalized Ratio should be closely monitored in patients receiving both warfarin and enteral feedings. Conversely, when EN is discontinued, a reduction in warfarin dose may be required.


Desired Outcomes

Desired outcome goals of EN are to promote an adequate nutritional state in adults and to promote growth and development of infants and children. Assessing the outcome of EN includes monitoring objective measures of body composition, protein and energy balance, and subjective outcome for physiologic muscle function and wound healing. In addition to optimizing nutrition, the goal of EN is to reduce disease-related morbidity and mortality. Measures of disease-related morbidity include length of hospital stay, infectious complications, and the patient’s sense of well-being. Such clinical outcome goals are extremely difficult to document with the use of EN, in part because other factors, such as age, underlying comorbidities, extent of injury, immunocompetence, and end-organ complications, also affect disease outcome. The successful use of EN can minimize the need for PN in patients unable to meet nutrient requirements with an oral diet. Ultimately, no disease process can improve with prolonged starvation and malnutrition.

PERSONALIZED PHARMACOTHERAPY

A nutrition care plan that incorporates nutrition assessment and therapy goals should be developed for all EN patients. The EN goals are individualized to each patient and based on meeting estimated fluid, calorie, protein, and micronutrient requirements. The desired end point should be included in the care plan. The end point may be resolution of a disease or condition that impairs ability to eat, such as a critically ill trauma patient who is expected to transition back to an oral diet. EN may be considered a lifelong therapy for those with a permanent impairment that restricts or limits eating, such as gastroparesis. Selection of appropriate enteral access device should be individualized based on anticipated duration of therapy, expected tolerance to gastric or jejunal feeding, and patient lifestyle preferences. For example, a low-profile gastrostomy tube may be a good option for active adult or pediatric patients who do not want the presence of an external tube. The method of EN administration should be individualized based on route of enteral access and patient tolerance. A patient with a gastrostomy tube who does not tolerate bolus feedings may do better when switched to slower, intermittent feedings. A patient with a jejunostomy tube may prefer nocturnal feeding to continuous, around-the-clock feeding. A target weight should be established for each patient and energy content from the EN regimen adjusted as needed to safely achieve target weight (i.e., no more than 1 to 2 pound [∼0.45 to 0.9 kg] per week weight gain or loss). EN may be used to supplement an oral diet when oral intake is inadequate and should be modified as needed based on changes in tolerance to the diet. A monitoring plan should be developed for each patient to identify potential complications and assess response to therapy.

CLINICAL BOTTOM LINE

Identifying appropriate candidates for EN and designing a personalized EN regimen and monitoring plan is a complex process that is often under-appreciated. A.S.P.E.N. has identified safety issues related to the administration and management of EN and created practice recommendations based on evidence-based research and expert opinion.9 Evidence-based practice guidelines for the provision and assessment of nutrition support therapy, including EN, are also available for the adult critically ill patient.10 All healthcare professionals should be knowledgeable in EN therapy because it is provided to a diverse patient population across various healthcare settings. A multidisciplinary approach, either as a formal nutrition support service or as a team of caregivers within the practice setting, is recommended to optimize patient outcomes.

ABBREVIATIONS

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