History of Tube Feeding An Anthology of Advances in Enteral Tube Feeding Formulations Sheila M. Campbell, PhD, RD Ross Products Division, Abbott Laboratories, Worthington, Ohio ABSTRACT: This article summarizes several major advances in tube feeding formulas marketed in the United States. It traces the progress in tube feeding formulas, starting with blenderized formulas to commercially available intact-nutrient formulas and culminating in the introduction of the concept of immunonutrition. The impact of packaging is also described.
milk, commercial pepsin, sodium bicarbonate, sodium chloride, and dextrose, fortified with fish liver oil, thiamin chloride, nicotinic acid, and vitamin C; and finally to (3) the development of proprietary, fixed-nutrient, commercial formulas that began to appear in the late 1960s and early 1970s (Figure 1).
Blenderized Foods Before the wide availability of commercial enteral feeding products, blenderized formulas made from hospital food were often used.3 Healthy people eat table food without much concern about its microbial quality. Patients requiring tube feeding, however, are often immunocompromised and therefore vulnerable to poor outcomes that have been associated with receiving contaminated formulas.4 Susceptible patient populations include: ● neonates ● the elderly ● patients who are immunocompromised because of: - critical illness or injury - malnutrition - cancer - antineoplastic or other therapies - human immunodeficiency virus/AIDS5 Poor outcomes from feeding microbially contaminated formulas include the following: ● diarrhea ● gastrointestinal (GI) colonization ● pneumonia ● infection ● prolonged length of hospital stay 6 –12 ● mortality Aside from their high microbial load, homemade or institutionally prepared blenderized feedings have been found to be unsatisfactory because of their uncertain nutrition composition, poor homogeneity, and high viscosity that impedes flow through feeding tubes.13–17 Fortunately, technology continued to advance. As a result, the number of commercially available enteral formulas has increased from ⬍3 dozen in 197418 to ⬎200 in 198919 and to ⬎350 in 2006 (personal communication with Patricia Cadwallader, MPH, Marketing Director-Medical Nutri-
The United States market for medical nutrition products will surpass $1 billon in 2006.1 Tube feeding has come a long way since its humble beginning. The advancements in tube feeding formulations reflect the influences of cooking and growth in the sciences of food, food technology, nutrition, and medicine. This article traces evolutionary steps that enteral formulas have passed through since the modern history of American tube feeding began. Because of its notoriety, the initiating event in the history of modern enteral feeding in the US could be said to be the nutrition support President Garfield received after he was shot in 1881 by assassin James Guiteau. President Garfield survived for 79 days. He was given rectal feedings of whiskey and partially hydrolyzed (referred to as protonized) beef and beef broth every 4 hours for most of that time. Considering that (1) nutrient absorption in the colon is limited, (2) the nutrition quality of the solution was poor, and (3) the President had sepsis, it is not surprising that he had lost 80 pounds by the time of his death.2 Tube feeding formulas, devices, and techniques have improved since that time. In her article, Harkness3 provides a review of the evolution of early enteral formulations from (1) mixtures of milk, raw milk, and lactose; to (2) solutions of acidified skim
Correspondence: Sheila M. Campbell, PhD, RD, 275 Longfellow Ave, Worthington, OH 43085. Electronic mail may be sent to
[email protected]. 0884-5336/06/2104-0411$03.00/0 Nutrition in Clinical Practice 21:411–415, August 2006 Copyright © 2006 American Society for Parenteral and Enteral Nutrition
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Figure 1. Timeline of significant events in the progress of enteral formulas in the United States.2
tion, Ross Products Division, Abbott Laboratories [retired]).
Enteral Formulas of Relative Modernity Today, enteral tube feeding formulas in the US are designated medical foods. The statutory definition of the term was enacted by the Orphan Drug Amendments of 1988 (P.L. 97– 414). The US Food and Drug Administration (FDA) provides the following definition: “A medical food is prescribed by a physician when a patient has special nutrient needs in order to manage a disease or health condition, and the patient is under the physician’s ongoing care. The label must clearly state that the product is intended to be used to manage a specific medical disorder or condition.”20
Elemental Formulas The first commercially available formulas were elemental. They came on the market in the late 1960s. These formulas were tested by US National Aeronautics and Space Administration (NASA) scientists in an attempt to develop a residue-free formula for use by astronauts.21 The purpose for using these types of formulas during missions was to eliminate the problem of disposing of human waste in outer space. Although NASA rejected these formulas because of their poor flavor and aroma, elemental diets have been useful for patients with maldigestion or impaired absorption.22 To the purist, an elemental formula is one in which the macronutrients are in simple forms so that little or no digestion is needed before absorption. In these formulas, amino acids are the protein source and glucose provides the carbohydrate. There often is no additional fat other than fat-soluble vitamins. Subsequent research showed that these types of elemental formulas can be associated with GI atrophy and poor nitrogen balance.23 Today, most of the modern elemental diets are more correctly called partially hydrolyzed because they are peptide based. In the case of critically ill patients and those with GI dysfunction, peptidebased protein systems are more easily absorbed and tolerated.24 Furthermore, peptides are believed to
stimulate tissue recovery, protein synthesis, and protein nutriture better than intact proteins and free amino acids.24,25 Most modern partially hydrolyzed diets have protein systems that contain peptides and free amino acids. The amino acids are added to: 1. supplement with specific amino acids such as arginine and glutamine26; 2. ensure a balanced amino acid profile, thus ensuring adequate absorption and metabolism of the protein source27; and 3. enhance nitrogen delivery into systemic circulation. Nitrogen delivery is enhanced because peptides and amino acids are transported by independent, noncompeting carriers.25
Intact Nutrient Formulas Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), introduced in 1973, was the first intact-nutrient, lactose-free, ready-to-use adult medical nutrition product promoted in the US. It was an “all-purpose” product, designed for tube feeding and oral supplementation. Because it is flavored and contained sucrose to improve palatability, it was not isotonic. Ensure and the other products in this category were designed to be nutritionally complete. Their caloric distribution is consistent with recommendations for a healthy diet. They were designed to provide all nutrients known at that time to be needed for good nutrition. The next advance came a few years later when Mead Johnson (Evansville, IN) introduced Isocal, now marketed by Novartis (Minneapolis, MN). Isocal is a nutritionally complete, isotonic formula specifically designed for tube feeding. Isotonicity was considered to be an important feature for tube feedings because it may improve tube feeding tolerance (eg, the absence of GI symptoms such as abdominal bloating, nausea, vomiting, and diarrhea). Until 1987, virtually all commercially available formulas were fiber-free. There were a few exceptions: commercial formulas made from blenderized foods. These, however, were still relatively low in fiber. In 1987, the first fiber-fortified formula, Jevity (Ross Products Division, Abbott Laboratories) was launched. It was the only formula on the market at
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Table 1 Characteristics of selected fibers used in tube feedings28 Fiber
Soy fiber Oat fiber (from hulls) Carboxymethylcellulose Guar gum Gum arabic Inulin and FOS
Fermentability
% Insoluble/% Soluble
PF NF NF F F F
94/6 94/6 0/100 40/60 1/99 0/100
F, fermentable; FOS, fructooligosaccharides; NF, nonfermentable; PF, partially fermentable.
that time that was supplemented with 14.4 g of soy fiber/L and fortified with conditionally essential nutrients, carnitine, taurine, and the ultratrace minerals molybdenum, selenium, and chromium. Formulating a product supplemented with fiber represented a considerable technical challenge. Adding water-soluble fiber sources, such as pectin, to liquid formulas increase formula viscosity, interfering with formula flow characteristics and increasing the risk of feeding-tube clogging. On the other hand, insoluble fiber sources, such as soy fiber, can settle to container bottoms and form clumps with other insoluble formula components. These insoluble particles can clog feeding tubes. The first fiber-fortified formulas contained soy fiber, a primarily insoluble fiber source. Because of the problems associated with its use, scientists looked for other fiber sources. Today, there are numerous fiber-supplemented tube feeding products on the market. Many contain fiber systems composed of combinations of soluble and insoluble fibers and are designed to meet recommendations for healthy dietary fiber intake. Table 1 shows a selected list of fibers used in modern fiber-supplemented tube feedings. Some fiber-supplemented formulas contain nondigestible, fermentable carbohydrates as a component of their fiber systems. Nondigestible, fermentable oligosaccharides, such as fructooligosaccharides (FOS), inulin, and resistant starch, provide many of the physiologic benefits of fiber but do not interfere with the physical stability or flow characteristics of tube feeding formulas.29,30 Inulin and FOS are prebiotics. They are preferred fuel for beneficial colonic bacteria, thus supporting the growth of beneficial flora and preventing bacterial overgrowth by pathogenic, opportunistic bacteria (eg, C difficile). A byproduct of their metabolism (or fermentation) by colonic bacteria is the production of short-chain fatty acids (SCFA), preferred fuel for colocytes. Because of these benefits, FOS is said to contribute to digestive tract health.
Disease-Specific Formulas Disease-specific formulas have a modified nutrient composition and are designed for the dietary
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management of some conditions that are amenable to dietary therapy. Currently, there are 4 types of disease-specific formulas on the market: pulmonary, renal, diabetic, and hepatic. Pulmocare (Ross Products Division, Abbott Laboratories), introduced in 1985, was a low-carbohydrate formula designed to help reduce hypercapnia in patients with pulmonary disease. Because the Pulmocare formulation was not patented, other manufacturers quickly introduced their own brands of “pulmonary formulas.” Formulas for use with patients with acute or chronic kidney failure who are not receiving dialysis, and for patients receiving dialysis, entered the market next. Neither of these products was patented, and manufacturers quickly introduced their brands. In 1989, a formula specifically designed for patients with diabetes was commercialized: Glucerna (Ross Products Division, Abbott Laboratories) was the first enteral formula to be patented. The other disease-specific formula that was developed was for liver failure. Liver-disease products were formulated to contain increased levels of branched-chain amino acids and reduced amounts of aromatic amino acids.
Immunonutrition Enteral formulas containing 1 or more immuneenhancing nutrients (eg, arginine, glutamine, nucleotides, -3 fatty acids) are known as immune-enhancing tube feeding formulas, or immunonutrition. Impact (Novartis Nutrition) was a unique and controversial formula when it was introduced by Sandoz Nutrition in the early 1990s. Since its introduction, numerous studies have been done. Metaanalyses and consensus guidelines created from these study results suggest that when immunonutrition is used in certain patient populations, it is beneficial in lowering infection rates, reducing infectious complications, and shortening length of stay (LOS).31–33 Patient populations who are said to benefit from immunonutrition include those with31–33 ● trauma/multiple trauma, ● postoperative wound infection, ● cancer requiring surgery (especially abdominal surgery in malnourished patients), ● massive blood infusions, ● malnutrition, and ● acutely ill immunosuppressed patients with APACHE II scores of ⱖ10 –20, suggesting an acutely ill, immunosuppressed state. APACHE stands for Acute Physiology and Chronic Health Evaluation. Points are assigned according to vital signs, chemistry values, measures of oxygenation, organ function, preexisting conditions (eg, congestive heart failure, chronic obstructive pulmonary disease), operative severity, and age. Scores range from 0 to 70. Clinicians may not compute APACHE II scores for each patient, but they do base nutrition support decisions on the severity of the patient’s illness or injury. APACHE II
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scores are often cited in published research reports about nutrition support of patients in intensive care units. Until 1998, the only formulas in this category contained supplemental arginine. Because arginine has a stimulatory effect on the immune system, some experts have expressed concern about using it in enteral feedings for patients with inflammatory conditions such as sepsis and the systemic inflammatory response syndrome.31–35 Oxepa (Ross Products, Abbott Division), a formula supplemented with eicosapentaenoic acid (EPA) and ␥-linolenic acid (GLA) but not supplemented with arginine, entered the market in 1998. It was designed for the dietary management of critically ill patients receiving mechanical ventilation. Reports demonstrate that it is associated with improved clinical outcomes for critically ill patients in the following groups who might benefit from modulation of the inflammatory response: ● Patients requiring mechanical ventilation ● Patients with lung injury, including: - pneumonia - sepsis - chest injury - multiple trauma - burns - shock and hypoperfusion - aspiration or near-drowning - cardiopulmonary bypass - hyperfusion-associated lung injury36 – 42
Packaging Tube feeding packaging may seem a mundane topic. Packaging of tube feeding formulas has, however, made significant changes in the practice of tube feeding. Tube feeding formulas for sole source nutrition are available in 2 basic forms: ● dry powders that must be reconstituted before use, and ● sterile liquid solutions packaged in steel cans, glass containers, or multilaminated (plastic/ foil/paperboard) containers. In the US, formulas packaged in glass are nearly impossible to find today because they are heavy and breakable. They were, however, the first type of closed-feeding system. Closed systems for enteral feeding feature formulas prepackaged by the manufacturer into large-volume administration containers. If they are handled according to manufacturer instructions to prevent microbial contamination, they can hang for 24 – 48 hours at the patient bedside. Before their availability, formulas had to be decanted from their original containers into administration reservoirs for delivery. The entry of largevolume, prefilled enteral feeding systems in the late 1980s simplified the tube feeding process. A number of styles of closed enteral systems are now commercially available. One system features flexible bags that are composed of multilayer films of
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laminated polyethylene or polyvinyl chloride that are reminiscent of bags used for IV solutions. They are impact resistant, easy to transport and handle, and flexible enough to allow easy administration without air intake. They also are relatively difficult to spike for administration; increased handling may increase the chance of microbial contamination of formula, thus reducing safe hang time.26 Semirigid closed systems are available. Because they are not fully collapsible, they generally require air priming. They are fitted with microfilters that prevent entry of airborne microbes and fungi. Semirigid containers are easier to handle than a flexible bag.26 Finally, aseptically sterilized closed systems are available. These containers are laminations of aluminum foil, polyethylene, polypropylene, and paperboard. They resemble “juice box” style tetra-brick containers. The rectangular shape occupies less space than round containers, reducing the amount of storage space needed.26 They require a special “cradle” for hanging at the bedside. Closed systems are particularly desirable compared with conventional feeding systems. Closed systems have been shown to reduce handling, save nursing time, and increase compliance to tube feeding prescriptions.43,44
On the Horizon The completion of the Human Genome Project45 promises to have major effects on tube feedings specifically and nutrition care generally.46,47 Nutrigenomics is “the scientific study of the way specific genes and bioactive food components interact.”47 This new science is expected to affect public health by allowing a personalized approach to nutrition intervention to “pre-empt” chronic and metabolic disease. Furthermore, nutrigenomics can be expected to influence acute nutrition intervention, including tube feeding, by allowing the identification of bioactive food components that will ameliorate the onset, incidence, or progression of acute disease and complicating conditions. We can expect to see a blossoming of disease-, condition-, and genetic-specific formulas.
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