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Annu. Rev. Med. 1991.42:549-565. Downloaded from www.annualreviews.org Access provided by Michigan State University Library on 01/23/15. For personal use only.

PARENTERAL AND ENTERAL NUTRITION Harry M. Shizgal, M.D., F.R.C.S.(C.), F.A.C.S. Department of Surgery, McGill University and Royal Victoria Hospital, Montreal, Canada H3A IAI KEY

WORDS:

malnutrition, protein sparing, nutritional assessment

ABSTRACT

Stress and starvation, especially when complicated by sepsis, will give rise to a rapid erosion of the cellular mass, which significantly affects morbidity and mortality. The best clinical evaluation of the nutritional state is obtained from the medical history and the physical examination. In the patient who cannot eat a balanced diet, specialized nutritional support, in the form of either enteral or parenteral nutrition, is required to prevent malnutrition in the normally nourished, or to correct the nutritional state in the malnourished.

INTRODUCTION Maintaining an optimal state of nutrition and health requires the intake of a complete diet, including both macro- and micronutrients. This is best accomplished by the oral route, but many patients either cannot or should not use their gastrointestinal (GI) tract, or cannot maintain an adequate oral intake because of anorexia and/or dysfunction of the gastrointestinal tract. This is especially true of patients with severe infections or burns, and those recovering from acute trauma and major surgical procedures who are also hypermetabolic, with increased energy and nitrogen require­ ments. To meet their nutrient requirements, specialized nutritional therapy must be instituted as either parenteral or enteral feeding. 549 0066-4219/91/0401-0549$02.00

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STRESS AND STARVATION With either total or partial starvation, endogenous sources must supply the required energy and amino acids. During the initial days of total starvation, the resting, nonstressed, normally nourished 70-kg man breaks down approximately 75 g/day of protein, primarily from skeletal muscle, and 160 g/day of adipose tissue, which provides 1800 calories/day (1). The body stores of carbohydrate, in the form of musele and hepatic glycogen, are minimal, consisting of 150 and 75 g respectivcly, and are depleted within the first 24-48 h of starvation. Subsequently, there is total reliance on triglycerides from adipose tissue and on amino acids from body protein. As a labile pool of body protein is unavailable, all of the protein, which is broken down, serves either a structural or functional role. The skeletal muscles are the major source of this protein, but some visceral protein is also degraded. The 75 g of protein broken down each day are equivalent to 12 g of nitrogen or 300 g of body cell mass. The body cell mass represents the total mass of living, metabolically active cells of the body. In the absence of a catabolic stress, an adaptive process occurs, and the daily nitrogen loss decreases from 12 to 3-5 gjday by the fourth week of starvation, reducing the loss of body cell mass from 300 to 125 gjday. The cumulative loss of body cell mass in the normally nourished 70-kg man during the initial four weeks of total starvation is 5.7 kg, which represents 38% of the skeletal muscle mass or 23% of the body cell mass. A loss of 50-60% of the body cell mass is probably incompatible with survival. Cross-sectional tissue trauma (regardless of the etiology) andjor sepsis increase the requirement for both energy and amino acids in direct pro­ portion to the severity of the trauma. Furthermore, in contrast to the unstressed starved individual, adaptation, with its consequent gradual decrease in gluconeogenesis from protein, does not occur. Following an uncomplicated operation of moderate severity, the daily nitrogen loss ranges from 10 to 15 g/day (2). When injury is complicated by sepsis, the nitrogen loss may increase to 15-25 g/day. With severe injury and sepsis (e.g. major thermal burns), it may rise to 35-40 gjday. With a negative nitrogen balance of 30 gjday there is a 5.3-kg loss of body cell mass by one week; by 2. 5 weeks, over 50% of the body cell mass is lost. The rapid erosion of the cellular mass that may occur with starvation and injury, especially when complicated by sepsis, impacts significantly on morbidity and mortality. The loss of skeletal muscle impairs the ability to cough and clear pulmonary secretions, which leads eventually to pul­ monary infection. Malnutrition is also associated with impaired wound healing, a decreased resistance to infection, and impaired synthesis of many important acute phase proteins.

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NUTRITIONAL ASSESSMENT

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The assessment of the nutritional state is important both in determining the need for and in measuring the response to specialized nutritional therapy. The medical history and physical examination provide the best clinical evaluation of the nutritional status (3). In addition, a number of biochemical and anthropometric variables have been used in an attempt to obtain a quantitative measure of the nutritional state, based on the observation that these variables correlate with the nutritional state. History

The patient's medical history can provide an excellent qualitative evalu­ ation of the nutritional state. The following aspects are important: (a) the magnitude and duration of recent weight changes and whether they were voluntary or involuntary; (b) the presence of diarrhea, which may result in significant protein loss; (c) chronic diseases such as diabetes mellitus, pancreatitis, inflammatory bowel disease, or malabsorption; (d) food allergies and intolerances; (e) surgical resection of the bowel and/or acces­ sory organs of the GI tract such as the pancreas; (/) medications that influence the GI tract; (g) difficulty with chewing and swallowing; (h) generalized muscle weakness with a decreased work capacity. Physical Examination

The diagnosis of frank malnutrition is usually obvious, especially when there is severe wasting of both the subcutaneous fat and skeletal muscle (marasmus), or when the patient presents with the bloated edematous appearance of kwashiorkor. Less severe malnutrition, however, is often difficult to detect by physical examination, especially in the obese and in the patient with generalized fluid retention. Circulating Serum Proteins

The serum concentration of a number of circulating proteins is related to both the nutritional state and the incidence of morbidity and mortality, and is therefore often used as a quantitative measure of the nutritional state. The proteins most commonly measured for this purpose include albumin, transferrin, thyroxin-binding prealbumin, and retinol-binding protein. Malnutrition is often, though not always, associated with a decreased concentration of circulating proteins. The albumin concentration is a1Tected by the nutritional state but is also affected by the degree of hydration, blood loss, albumin infusions, renal and hepatic disease, steroid administration, major elective surgery, extensive burns, and a variety of similar traumatic

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events (4). The half-lives of the other visceral proteins are shorter and are therefore believed to be better markers of the adequacy of nutrient provision. Unfortunately, the nutritional state is only one of a number of factors affecting their concentration (5). Elevated concentrations of transferrin may occur with iron deficiency, acute hepatitis, pregnancy, and the use of oral contraceptives, while low concentrations are seen with severe liver disease, serious bacterial infections, and protein-losing states. Generally these variables lack sufficient sensitivity and specificity to be useful in evaluating an individual patient's nutritional state. But because they do correlate with the nutritional state, they are useful in epidemiologic surveys to monitor a population's nutritional state. Immune System

A relationship between the nutritional state and the immune response has been recognized for some time. The incidence of infections is greater in the malnourished, and their response to infection is more severe. Skin testing with delayed antigens has been widely used as a measure of the nutritional state, which is based on the association between the mal­ nourished state and the presence of anergy. However, anergy develops with a variety of other conditions besides malnutrition (6). Similarly, the lymphocyte count is related to the nutritional state, but it is also radically affected by a number of nonnutritional factors, such as sepsis, chemo­ therapeutic agents, and corticosteroids (7). Body Composition

The determination of body composition provides an accurate and precise measure of both nutritional state and the response to nutritional therapy. The earliest measurements utilized a two-compartment model dividing body weight into lean body mass and body fat. The lean body mass �as most commonly determined by underwater weighing, with body fat being the difference between body weight and lean body mass. However, this approach does not provide sufficient information regarding the nutritional state. Nutritional assessment requires a three-compartment model, in which body weight is divided into body fat, extracellular mass, and the body cell mass. This is because malnutrition is characterized by a loss of body cell mass with a reciprocal expansion of the extracellular mass, such that there may be very little change in the lean body mass. The size of the cellular mass can be estimated from total body potassium, since 98% of total body potassium is within the cellular compartment and the intracellular potassium concentration varies within a narrow range. Total-body potassium has been measured with a whole-body counter and

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by a variety of multiple isotope dilution techniques (8, 9). The body cell mass can also be determined by measuring total-body nitrogen by means of neutron activation analysis (10). Recently, whole-body bioelectric impedance was measured to determine body composition. Initially, a relationship was demonstrated between the lean body mass and whole­ body electrical resistance ( 11). More recently a series of relationships were developed permitting the determination of body fat, extracellular mass, and body cell mass from body weight, height, and total-body electrical resistance and reactance (12). Although the measurement is simple and noninvasive, its accuracy remains to be demonstrated.

SPECIALIZED NUTRITIONAL SUPPORT The principal objective of nutritional support is to prevent the development of malnutrition in the normally nourished, or in the malnourished, to correct the nutritional state. Nutritional support is best achieved by having a patient eat a balanced diet. This requires an intact GI tract and a normal appetite. Once it has been established that specialized nutritional support is required, a decision must be made between the GI tract or the intra­ venous route. Enteral Feeding

In the patient with a normally functioning GI tract who cannot or will not eat an adequate diet, enteric tube feeding is indicated. These include patients who are either anorexic or comatose, or those with a variety of lesions of the mouth, esophagus, and at times the stomach. Failure to achieve an adequate dietary intake with enteric tube feeding is generally due to the development of either stasis or diarrhea. Aspiration is one of the most serious complications of enteric tube feeding, and can occur even in the presence of an endotracheal tube with an inflated tracheal balloon. Diarrhea, a not uncommon complication of enteric feeding, may result in serious fluid and electrolyte losses and more importantly may be a source of serious protein loss. There has been increased attention recently to the integrity of the barrier function of the gut mucosa. Loss of barrier function gives rise to increased translocation of bacteria and absorption of endotoxin from the gut lumen. This translocation involves bacterial migration from the gut lumen into mesenteric lymph nodes and the portal bloodstream. The presence of food in the gut is the most important stimulus for intestinal growth. Bowel rest, in contrast, results in villous atrophy with decreased muscosal cellularity. Bowel rest with seven days of total parenteral nutrition significantly affec-

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ted the response to endotoxin in normal volunteers (13). When compared to the controls, who received comparable enteral nutrition, there was an enhancement in the responses of the counter-regulatory hormones, the splanchnic cytokines, and the acute phase response; peripheral amino acid mobilization and lactate production were also enhanced. The presence of ischemic and/or malnourished bowel is associated with increased translo­ cation of both endotoxin and bacteria (14). Septicemia also disrupts the intestinal mucosa, as does cardiovascular instability and hypotension. The loss of the mucosal barrier with enhanced bacterial translocation and endotoxin absorption may in turn result in septicemia and/or macro­ phage activation in the splanchnic bed and liver. A number of recent reports have stressed the importance of specific fuels for the GI tract. Glutamine is the most important fuel for the small intestine, followed in order of preference by ketone bodies and glucose (15). For the colon, the preferred fuels include, in order of preference, butyrate, acetoacetate, glutamine, and glucose. Since glutamine is unstable in solution, it is absent in standard parenteral nutrient solutions, and is present in insufficient amounts in most enteral preparations. Sup­ plementation of enteral preparations with pectin, a fermentable fiber poly­

saccharide, also improves mucosal growth and function. The fermentable fibers are water soluble, low in bulk, and almost totally metabolized by anaerobic bacteria in the colon. The short-chain fatty acids-acetic, propionic, and butyric-produced from these fibers possess significant trophic effects on colonic mucosal growth and function (16). Total Parenteral Nutrition

Parenteral nutrition is required either when the GI tract should not be used or when, because of GT dysfunction, adequate enteral nutrition cannot be achieved. Total parenteral nutrition (TPN) involves the parenteral administration of an individual's entire nutrient requirement-both the macro- and micronutrients. To administer sufficient calories, one must infuse either a lipid emulsion or a hypertonic glucose solution, which requires a central venous catheter. The peripheral intravenous infusion of a hypocaloric solution of amino acids with either 10% dextrose or a lipid emulsion does not provide sufficient calories to correct a malnourished state, but it usually maintains the body cell mass and prevents further deterioration of the nutritional state. Peripheral Protein Sparing

Blackburn et al (17, 18) first reported significant postoperative protein sparing with the infusion of amino acid solutions, which they attributed to

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the avoidance of glucose-containing solutions. They postulated that a glu­ cose infusion increases plasma insulin, which in turn inhibits lipid mobi­ lization, and thus the body initiates gluconeogenesis from protein to meet the energy requirements. In support of this hypothesis they demonstrated that the postoperative infusion of a 3% amino acid solution abolished the nitrogen loss. They also reported an inverse correlation between nitrogen sparing and both the plasma glucose and insulin concentrations; and they noted that nitrogen sparing was directly related to the plasma free fatty acid and ketone body concentrations. Based on these observations, they recommended the infusion of amino acids and the avoidance of glucose solutions. Numerous other studies have confirmed that the infusion of a hypo­ caloric amino acid solution maintains nitrogen balance following a variety of surgical operations (19, 20). The protein-sparing effect of amino acid infusions was also confirmed by measuring the albumin synthesis rate (21) and by monitoring the change in body composition (22) in patients recuperating from major abdominal surgery. But the data have often not supported the hormonal-substrate interrelations proposed by Blackburn. The protein-sparing effect of amino acids appears to be related to the infused amino acids alone; it is not affected by the additional infusion of either glucose or lipid, nor is it influenced by the degree of endogenous fat mobilization (23-25). The protein-sparing effect of hypocaloric amino acid solutions appears to be inversely related to the magnitude of the catabolic stress-less nitrogen is spared as the magnitude of the trauma increases (26). Increasing the nonprotein caloric intake tends to increase the nitrogen sparing (27). The clinical implication of these observations is that the peripheral infusion of hypocaloric amino acid solutions is ideally suited for the maintenance of the nutritional state, specifically to prevent mal­ nutrition in the starving and moderately stressed patient. Peripheral hypocaloric amino acid infusion is best reserved for patients requiring maintenance of their nutritional status for only a short period of time. Typically these are patients who require some nutritional support but who are not as yet candidates for TPN, for example, the severely malnourished patient who has just undergone corrective surgery and is expected shortly to resume a normal oral intake. Because of preexisting malnutrition and therefore a decreased reserve, this individual cannot tolerate an additional loss of nutritional reserve, especially if a post­ operative complication develops and the resumption of oral intake is further delayed. To achieve protein sparing, amino acids are administered at a rate of 1.5-2.0 g·kg- l·day- I with a solution containing 5% amino acids to which is added either 5 or 10% dextrose. A lipid emulsion may also be infused to increase the caloric intake.

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NUTRIENT REQUIREMENTS

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Protein

For young male adults, a mean intake of 0.61 g·kg-1·day-l for reference protein has been proposed (28). Because the coefficient of variation is 12.5%, the needs of 97.5% of a normally distributed population would be met by an intake that was 25% (two standard deviations) above this mean, or 0.75 g·kg-1·day-l. The requirements for young adult women are simi­ lar when adjusted for body weight. Taking into account the usual pro­ tein in the US diet, the recommended dietary allowance (RDA) is 0.8 g·kg-1·day-l. The protein requirements for the typical 70-kg man and 55-kg women are therefore 56 and 44 g per day, or 9 and 7 g of nitro­ gen per day respectively. For rapidly growing infants and children, the requirements are slightly greater. During the first six months of life the RDA is 2.2 g·kg- l'day-1, which decreases to 1.6 g·kg-1·day- l for infants aged 6 months to 1 year, and 1.2 g'kg-1'day-l between the age of I and 3 years. Protein requirements are probably increased in patients subjected to a catabolic stress (acute trauma, burns, infection, etc.) and in patients with severe protein depletion because of their need to replete wasted tissues. Their requirement is thought to be comparable to the require­ ments of rapidly growing infants and children. The majority of patients receiving TPN will respond appropriately with protein intakes of 1.2-1.5 g·kg-1·day-l (29).

(BCCA) The fate of the amino acids absorbed from the GI tract into the circulation following a meal depends on whether they are essential or nonessential. For the majority of essential amino acids (histidine, lysine, methionine, phenylalanine, threonine, tryp­ tophan), the liver is the major source of catabolism and the amount passing into the general circulation is regulated by the liver according to the needs of the body for that particular essential amino acid. In contrast, the BCAA are not taken up by the liver but instead are released into the systemic circulation and are taken up by muscle, kidney, adipose tissue, and the brain. The entry into muscle and also into adipose tissue is facilitated by insulin. During the postabsorptive period, the BCAA account for the majority of amino acids absorbed by muscle, while they account for only 20% of the amino acids needed for muscle protein synthesis. This BCAA excess does not leave the muscle, either intact or in the form of other nitrogenous compounds, and it is therefore most probably used to syn­ thesize the nonessential amino acids required for muscle protein synthesis. Thus the BCAA play an important role in the synthesis of muscle proteins. BRANCHED-CHAIN AMINO ACIDS

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Solutions with a higher concentration of BCAA have been advocated, based on a number of reports suggesting that the BCAA decrease muscle protein degradation and increase synthesis in a dose-dependent fashion. However, a recent workshop on the BCAA in stress and injury (30) concluded that, in vitro, only leucine and not valine and isoleucine sig­ nificantly altered protein synthesis; the in vivo animal data were incon� sistent. However, in septic primates the use of BCAA-enriched solutions lessened the calories required to maintain nitrogen balance. The clinical studies demonstrated a positive effect of the BCAA-enriched solutions only in the most severely ill patients. The workshop concluded that "greater benefits must be demonstrated in man before any widespread application of the use of BCAA formulations, alone or as supplements, can be endorsed." The use of BCAA will continue as a research tool to evaluate amino acid kinetics, protein metabolism, and nitrogen accretion. GLUTAMINE

Glutamine was only recently recognized to possess a number of unique and important properties. For a long time it was considered a nonessential amino acid and its importance overlooked. Almost all mammalian cells in culture require the presence of glutamine in the culture medium for growth and survival. Cell proliferation is maximal when the glutamine concentration is maintained at 0.05 mMjl or above, a con­ centration that approximates the normal plasma glutamine concentration. In spite of considerable efforts by a number of investigators, the high rate of glutamine consumption in replicating cells remains an unexplained phenomenon. Glutamine's important role in a number of metabolic pathways in diverse cell types is nicely summarized by Smith (31). In the kidney it is the most important substrate for renal aminogenesis, a process important to acid-base regulation. In the liver it serves as a gluconeogenic substrate and is an important end product in ammonia trapping. In all cells glu­ tamine is an important nitrogen donor for the synthesis of purines, pyrim­ idines, and amino sugars. Glutamine is the most abundant free amino acid in the plasma and in the intracellular space. It accounts for 60% of the free amino acids in skeletal muscle (which contains half of the body's free amino acid pool), where it stimulates protein synthesis and inhibits protein degradation. In the liver it stimulates glycogen synthesis. Both the plasma and the intracellular glutamine concentrations decline with catabolic stress. On the other hand, the administration of glutamine has been demonstrated to have a marked trophic effect both in humans and in animals. The possibility has been raised that glutamine is an essential nutrient under certain circumstances because of its role in metabolic pathways with essential functions. Glutamine is probably an essential nutrient for rapidly

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dividing cells or cells with large energy-dependent functions such as phago­ cytosis or secretion. It is especially important for the immune system, especially in lymphocytes and macrophages, as both an energy source and an important component of the nucleic acids and other constituents required for cell division (32).

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Carbohydrate

The optimal dietary intake of carbohydrate is not known. In North Amer­ ica, carbohydrate supplies from 30 to 60% of the total caloric intake, with protein supplying 10 to 15% and fat 30 to 55%. However, in some coun­ tries the dietary fat intake is much lower, supplying only 10 to 15% of total caloric intake. The caloric content of human breast milk is 50% fat, 38% carbohydrate, and 12% protein. Plasma glucose concentration is maintained in the starving patient by gluconeogenesis. In the absence of stress, gluconeogenesis is inversely related to plasma insulin and therefore responds to glucose administration. In the stressed patient, gluconeogenesis is stimulated predominantly by elevated glucagon concentration, and as a result the suppressive effect of glucose is diminished. However, this can be overcome with large doses of insulin (33). Even in the severely injured patient, the peripheral uptake of glucose by muscle, fat, and other tissues, can be returned to almost normal with large amounts of insulin. The "insulin resistance" of injury occurs only with lower physiological concentrations of insulin. In contrast, the maximum peripheral uptake of glucose that can be achieved in septic patients is only 50% of normal, even with pharmacological amounts of insulin. Insulin, in addition to stimulating peripheral glucose uptake, also sup­ presses the rate of protein breakdown and peripheral lipolysis, as well as stimulating potassium ion uptake. These properties of insulin remain intact in both acutely stressed and septic patients (34). As a result, the admin­ istration of insulin enables better blood glucose control and suppresses protein breakdown, even in the critically ill and septic patient. Fat

The optimal requirement for fat in terms of calories is not known. The US National Research Council Food and Nutrition Board's Committee on Diet and Health recently recommended (a) that the dietary intake of fat be reduced from its present level of 36% to below 30% of caloric intake, (b) that less than 10% of calories be provided from saturated fatty acids, and (c) that dietary cholesterol be less than 300 mg/day (28). This recom­ mendation is based on the recognized relationship between the amount

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and nature of fat ingested, and carcinogenesis, atherosclerotic vascular disease, and the prevalence of obesity and its adverse effects. A number of polyunsaturated fatty acids are essential for growth and the maintenance of health. A diet lacking these fatty acids will provoke an essential fatty acid deficiency, characterized by scaly skin, hair loss, impaired wound healing, and an increased susceptibility to infection. The three most important essential fatty acids are linoleic, linolenic, and arachi­ donic. Although arachidonic is considered an essential fatty acid, it does not need to be supplied in the diet, as most mammalian tissue can convert linoleic to arachidonic. These essential fatty acids are important precursors in the synthetic pathways of many of the prostaglandins. With essential fatty acid deficiency, the concentration of plasma eicosatrienoic acid is elevated while the arachidonic concentration falls; this elevates the ratio of triene (eicosatrienoic) to tetraene (arachidonic) acid. A ratio of 0.4 or greater is indicative of essential fatty acid deficiency. The essential fatty acid requirement in humans has not been clearly defined. A daily intake of linoleic acid ranging from 7.S (2.2% of total caloric intake) to 25 g has been recommended (35, 36). In children and infants, the optimal requirement for linoleic acid is 4% of total caloric intake. Essential fatty acid deficiency is accentuated by the increased meta­ bolic demands associated with growth, and the hypermetabolism following injury, sepsis, or stress. In practice, TPN patients should receive 500 ml of a 10% lipid emulsion two to three times a week, while daily infusions are probably required to correct a deficiency. Energy

The energy requirements of the hospitalized patient on either enteral or parenteral nutrition are not well defined and remain an area of considerable controversy. The total energy requirement is the sum of the resting energy expenditure and the energy required for physical activity and growth. The energy requirement for growth is estimated at 5 kcal/g of tissue gained (37). The most recent RDA for energy is summarized in Figure 1 (28). The higher energy requirement of infants and young children is related to their growth and greater activity, as well as to their body composition since their body cell mass comprises a greater proportion of their body weight. Shortly after the advent of TPN, both calories and amino acids were administered with great enthusiasm. The pendulum is now swinging in the opposite direction (38), based in part on the increased metabolic gas exchange that accompanies large carbohydrate infusions (39). Substituting lipid for carbohydrate decreases metabolic gas exchange and presumably avoids respiratory failure, especially in the patient with a decreased res­ piratory reserve. However, the increased metabolic rate with hypercaloric

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Annu. Rev. Med. 1991.42:549-565. Downloaded from www.annualreviews.org Access provided by Michigan State University Library on 01/23/15. For personal use only.

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Age (years) Figure 1

The Recommended Dietary Allowance (RDA) for daily energy intake (in

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intakes may represent the energy associated with tissue synthesis (40). The energy required for both body protein and body fat synthesis exceeds the energy available when these tissues are hydrolyzed. Peptide bond synthesis requires 29.2 kcal/mole, while hydrolysis of protein yields only 5 kcal/mol. The depleted patient to achieve net tissue synthesis would therefore require an energy intake that exceeds the sum of the resting energy expenditure and the activity-related energy. The increase in metabolic gas exchange occurring with hypercaloric glucose infusions is of the order of 50 to 100%, far less than that seen with the activities of normal living. When compared to bedrest, energy expenditure increases by 40 and 75% with sitting and standing respectively. Walking results in an almost four-fold increase. It is therefore unlikely that hypercaloric glucose feeding would be responsible for respiratory failure. Respiratory muscle atrophy secondary to a catabolic stress and/or starvation is probably a far more important factor in the development of respiratory failure. The infusion of the appropriate substrate to repair the malnourishment, in spite of the associated increase in gas exchange, may be crucial in the ultimate recovery of many of these patients (41). Protein synthesis is directly related to both protein and energy intake. In the malnourished adult on a constant protein intake, nitrogen retention increases as the caloric intake is increased, and with a constant energy intake, increasing protein intake has a similar effect. The efficiency of

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protein retention is greater in the malnourished individual and is inversely related to age; the efficiency decreases with advancing age (42). The relationship between caloric intake and protein retention was determined by body composition (29) and nitrogen balance (43) measurements in malnourished patients receiving TPN. These studies demonstrate that malnutrition is corrected slowly and requires a relatively large caloric intake. A caloric intake of 50 kcal·kg- '·day-' results in a body cell mass increase of 50-100 g·kg-'·day- I . Similar results have been reported in malnourished children. It now appears that a high-protein diet is neither necessary nor desirable (44, 45). The weight gain of malnourished children was significantly related to caloric and not protein intake, provided that the protein intake was above daily requirements. Furthermore the malnourished children recovered more rapidly when they received a high-calorie, normal protein diet, rather than the traditional high-protein diet. The adult recovering from mal­ nutrition is, in many regards, comparable to the growing child.

Lipid versus Carbohydrate Calories

The relative efficacy of lipid and carbohydrate calories remains con­ troversial. Improved dietary protein utilization was observed in healthy young males in whose diet fat was replaced with an equal number of carbohydrate calories (46). In the acutely injured patient, nitrogen excretion was related to resting energy expenditure and inversely related to carbohydrate intake (47). As the carbohydrate intake was increased, nitrogen excretion decreased, reaching a plateau as the calo�ic intake approached the resting energy expenditure. The administration of insulin further improved protein utilization. The additional infusion of a lipid emulsion did not alter nitrogen balance at any level of carbohydrate intake. Similarly, in the patient with extensive burns receiving TPN, there was a deterioration in protein utilization when lipid supplied more than 20% of the nonprotein calories (48). In malnourished patients on TPN, the body cell mass was restored more rapidly when carbohydrate rather than lipid supplied the nonprotein calories (29). Elwyn recently reviewed the relation­ ship between protein synthesis and both energy and amino acid intake, and concluded that under certain circumstances lipid calories are not as efficient as carbohydrate calories (49). In contrast, Jeejeebhoy et al (50) could not detect any difference between the effect of lipid and carbohydrate calories on protein utilization in pati­ ents with inflammatory bowel disease who were receiving TPN. In their 7-day crossover study, patients received TPN with either carbohydrate or a solution in which a lipid emulsion provided 83% of the nonprotein calories. Only during the latter half of the study period was there no

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difference in nitrogen balance with the lipid and glucose systems. For the entire period and for the initial four days, nitrogen balance was sig­ nificantly more positive with the glucose system. In both stressed and septic patients, the rate of lipolysis may be as much as three to four times above normal. Fatty acid oxidation is also elevated. This combination of increased lipolysis and fatty acid oxidation can easily accommodate the increased requirement for energy substrate. Since the rate of lipolysis is generally elevated to a much greater extent than fat oxidation, more than 80% of the fatty acids released by lipolysis are reesterified into triglyceride (51). Because of the high rate of fat mobi­ lization in the severely stressed patient, exogenous lipid administration may possibly give rise to hepatic lipid infiltration and should perhaps be avoided, except in cachexic patients without an adequate fat mass. Although the oxidation of endogenous fat can supply all the energy required by the body cell mass to perform its various functions, it may not support the requirements for protein synthesis (52). With complete starvation, there is a gradual wasting away of the body cell mass, as body protein is converted to carbohydrate. Carbohydrate, even in relatively small amounts will provide the energy required for pr otei n synthesis, with a significant reduction in the net loss of body protein. The nitrogen-sparing effect of lipid emulsion in the starving individual can be explained by the glycerol content of the emulsion (53). Micronutrients

In addition to the macronutrients, a complete diet must also include vitamins, macrominerals, and microminerals. A complete review of the requirements for the micronutrients is beyond the scope of this review, but each is reviewed in detail elsewhere (54). The macrominerals include sodium, chloride, potassium, calcium, phos­ phate, and magnesium. The requirements for electrolytes vary widely in individual patients, depending on the volume and composition of fluid loss, and on preexisting deficits. In addition, it is important to remember that an adequate intake of the intracellular electrolytes must be provided when correcting a malnourished state. Rudman et al (55) demonstrated, in malnourished patients receiving TPN, that nitrogen retention will occur only when potassium and phosphate are included in the TPN solution. Nitrogen, phosphorus, and potassium are retained in the proportions 1 g to 0.08 g to 3.1 meq respectively. The microminerals include iron, zinc, copper, selenium, manganese, chromium, and iodine. They are essential nutrients for humans and deficiency states have been identified in patients on long-term TPN. These micronutrients are present as contaminants in varying quantities in infused

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drugs, blood products, and intravenous fluids, including TPN solutions. Commercial preparations of trace elements for addition to TPN solutions became available following the recommendations to the US Food and Drug Administration made by an expert committee of the Nutrition Advis­ ory Group of the American Medical Association. The daily intravenous requirements are described in detail elsewhere (56). Vitamins are an essential dietary component for the normal mainten­ ance, growth, and functioning of celIs. These include both the fat-soluble vitamins (A, D, E, K) and the water-soluble vitamins (C, thiamin, ribo­ flavin, niacin, B-12, folic acid, biotin, pantothenic acid). Because the essen­ tial requirement of vitamins has been well recognized for some time, overt vitamin deficiency states are relatively uncommon. Vitamins also play an important role as essential enzyme cofactors in a number of important metabolic pathways. It is possible that suboptimal enzyme function may exist, before a clinicalIy overt deficiency syndrome develops. This could have unrecognized adverse clinical consequences, such as inefficicnt sub­ strate utilization, poor wound healing, or decreased resistance to infection. At this time, it is difficult to demonstrate a relationship between vitamin malnutrition and clinical outcome. Nevertheless, vitamins should be administered to patients who are receiving TPN or who have not taken anything by mouth for more than five days, because biochemically sig­ nificant evidence of vitamin deficiency may develop in normal individuals within a week or two of vitamin deprivation, and because it is difficult to detect early vitamin deficiency. Excessive administration of some vitamins must be avoided, as a potential for toxicity exists. The vitamin require­ ments were recently reviewed by a variety of committees (28, 57, 58). Literature Cited

1. Cahill, G. F. Jr. 1970. Starvation in man. N. Engl. J. Med. 282: 668-75 2. Kinney, J. M. 1975. Energy require­ ments of the surgical patient. In Manual ofSurgical Nutrition, Committee on pre­ and postoperative care, American Col­ lege of Surgeons, pp. 223-35. Phi­ ladelphia: Saunders 3. Baker, J. P., Dctsky, A. S., Wesson, E. S., Wolman, S. L., Stewart, S., et al. 1982. Nutritional assessment: a com­ parison of clinical judgement and objec­ tive measurement. N. Engl. J. Med. 306: 969-72 4. Forse, R. A., Shizgal, H. M. 1980. Serum albumin and the nutritional status. 1. Parenteral Enteral NUlr. 4: 450-54 5. Roza, A. M., Tuitt, D., Shizga1, H. M. 1984. Transferrin-A poor measure of

nutritional status. 1. Parenteral Enteral 8: 523-28 6. Forse, R. A., Christou, N. V., Meakins, J. L., MacLean, L. D., Shizgal, H. M. 1981. Reliability of skin testing as a mea­ sure of nutritional state. Arch. Surg. 116: 1284-88 7. Forse, R. A., Rompre, c., Crosilla, P., O-Tuitt, D., Rhode, B., Shizgal, H. M. 1985. Reliability of the total lymphocyte count as a parameter of nutrition. Can. 1. Surg. 28: 216-19 8. Moore, F. D., Olsen, K. H., McMurray, J. D., Parker, H. V., Ball, M. R., Boyden, C. M. 1963. The Body Cell Mass and its Nutr.

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position in Heallh and Disease. Phi­ ladelphia: Saunders 9. Shizgal, H. M., Spanier, A. H., Humes,

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J., Wood, C. D. 1977. Indirect measure­ ment of total exchangeable potassium. Am. J. Physiol. 233(3): F2S3-60 Cohn, S. H., Dombrowski, C. S. 1971. Measurement of total-body calcium, sodium, chloride, nitrogen, and phos­ phorus in man by in vivo neutron acti­ vation analysis. J. Nucl. Med. 12: 499-

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chuk, W. W., Lykken, G. L. 1985. Assessment of fat free mass using bio­ electrical impedance measurements of the human body. Am. J. Clin. Nutr. 41: 810-17 12. Shizgal, H. M. 1990. Validation of the measurement of body composition from whole body bioelectric impedance. Infusionstherapie 17(Suppl. 3): 67-74 13. Fong, Y., Marano, M. A., Barher, A., He, W., Moldawer, L. L., et al. 1989. Total parenteral nutrition and bowel rest modify the metabolic response to endotoxin in humans. Ann. Surg. 210: 449-57 14. Alverdy, J. C., Aoys, E., Moss, G. S. 1988. Total parenteral nutrition pro­

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gut. Surgery 104:185-90 15. Rombeau, J. L. 1990. Advances in entcral nutrition. Can. J. Gastroenterol. 4(Supl. A); 26A-29A 16. Kipke, S. A., Fox, A. D., Berman, J. M., Settle, R. G., Rombeau, J. L. 1989. Stimulation of intestinal mucosal growth with intracolonic infusion of short-chain fatty acid irrigation. J. Par­ enteral Enteral Nutr. 13: 109-16 17. Blackburn, G. L., Flatt, J. P., Clowes, G. H. A. Jr., O'Donnell, T. F., lIensle, T. E. 1973. Protein sparing therapy during periods of starvation with sepsis or trauma. Ann. Surg. 177: 588-94 18. Blackburn, G. L., Flatt,1. P., Clowes, G. H. A. Jr., O'Donnell, T. 1973. Peripheral amino acid feeding with isotonic amino acid solutions. Am. J. Surg. 125: 447-54 19. Hoover, H. C., Grant,J. P., Gorschboth, c., Ketcham, A. S. 1975. Nitrogen-spar­ ing intravenous fluids in postoperative patients. N. Engl. J. Med. 293: 172-75 20. Elwyn, D. H., Gump, F. E., lies, M., Long, C. L., Kinney, J. M. 1978. Protein and energy sparing of glucose added in hypocaloric amounts to peripheral infusions of amino acids. Metabolism 27: 325-31 21. Skillman, J. J., Rosenoer, V. M., Smith, P. C., Fang, M. S. 1976. Improved albu­ min synthesis in postoperative patients by amino acid infusion. N. Engl. J. Med.

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H. 1979. The effect of nitrogen-sparing intravenously administered fluids on postoperative body composition. Sur­ gery 85: 496-503 Freeman, J. B., Stegink, L. D., Wittine, M. F., Danny, M. M., Thompson, R. G. 1977. Lack of correlation between nitrogen balance and serum insulin levels during protein sparing with and without dextrose. Gastroenterology 73: 31-36 Rowlands, B. J., Clark, R. G. 1978. Post­ operative amino acid infusions: an appraisal. Br. J. Surg. 65: 384--89 Greenberg, G. R., Marliss, E. R., And­ erson, H., Langer, B., Spence, W., et al. 1976. Protein-sparing therapy in post­ operative patients. Effects of added hypocaloric glucose and lipid. N. Engl. J. Med. 294:1411-16 Ching, N., Mills, C. J., Grossi, C., Angers,J. W., Iham, G., et al. 1979. The absence of protein sparing effects utiliz­ ing crystalline amino acids in stressed patients. Ann. Surg. 190; 565-70 Young, G. A., Hill, G. L. 1980. A con­ trolled study of protein sparing therapy after excision of the rectum. Ann. Surg. 192; 183-91 Recommended Dietary Allowances, A Rcport of the Food and Nutrition Board, Commission on Life Sciences, National Research Council. Washing­ ton: Natl. Acad. Press, 1989. 10th ed. Shizgal, H. M., Forse, R. A. 1980. Pro­ tein and caloric requirements with total parenteral nutrition. Ann. Surg. 192: 562-69 Brennan, M. F., Cerra, F., Daly, J. M., Fischer, 1. E., Moldawar, L. L., et al. 1986. Report of a research workshop; Branch-chain amino acids in stress and injury. J. Parenteral Enteral Nutr. 10:

446-52 31. Smith, R. J. 1990. Glutamine meta­

bolism and its physiologic importance. J. Parenteral Enteral Nutr. 14: 4OS-44S 32. Newsholme, E. A., Newsholme, P., Curi, R. 1987. The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns. Biochem. Soc. Symp. 54: 145-61 33. Shangraw, R. E., Jahoor, F., Miyoshi, R., Neff, W. W., Stuart, C. A., et al. 1989. Differentiation between septic and postburn insulin resistance. Metabolism 38:983-89 34. Jahoor, F., Shangraw, R. E., Miyoshi, H., Wallfish, H., Herndon, D. H., Wolfe, R. R. 1989. Role of insulin and glucose oxidation in mediating the protein catabolism of burns and sepsis. Am. J. Physiol. 257: E323-31

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NUTRITION 35. Collins, F. D., Sinclair, A. I., Royles, I. P., Coats, D. A., Maynard, A. I., Leonard, R. F. 1971. Plasma lipids in human linoleic acid deficiency. Nutr. Metab. 1 3: 150-67 36. Ieejeebhoy, K. N., Zohrab, W. I., Langer, B., Phillips, M. T., Kuksis, A., Anderson, G. H. 1973. Total parcntcral nutrition at home for 23 months, with­ out complications and good rehabili­ tation. Gastroenterology 65: 811-20 37. Roberts, S. B., Young, V. R. 1988. Energy costs of fat and protein depo­ sition in the human infant. Am. J. Clin. Nutr. 4S: 951-55 38. Kinney, J. M. 1990. Barnyard bio­ chemistry. J. Parenteral Enteral Nutr. 14: 1485-1565

39. Elwyn, D. H., Kinney, I. M., Malay­ appa, J., et a!. 1979. Influence of increas­ ing carbohydrate intake on glucose kin­ etics in injured patients. Ann. Surg. 190: 117-27 40. Roza, A., Forse, R. A., Coughlin, M., Shizgal, H. M. 1984. The effect of total parenteral nutrition (TPN) on gas ex­ change. Surg. Forum 25: 85-90 41. Kelly, S. M., Roza, A., Field, S., Cough­ lin, M., Shizgal, H. M., Macklem, P. T. 1984. Inspiratory muscle strength and body composition in patients receiving total parenteral nutrition. Am. Rev. Resp. Dis. 130: 33-37 42. Shizgal, H. M., Martin, M., Gimmon, Z. 1 991 . The effect of age on the caloric requirement of the malnourished. Am.J. C/in. Nutr. In press 43. Elwyn, D. H., Gump, F. E., Munro, H. M., Iles, M., Kinney, J. M. 1979. Changes in nitrogen balance of depleted patients with increasing infusions of glu­ cose. J. C/in. Nutr. 32: 1597-1611 44. Kerr, D., Ashworth, A., Picou, D., Poulter, N., Seakins, A., et a!. 1973. Accelerated recovery from infant mal­ nutrition with high calorie feeding. In Endocrine Aspects of Malnutrition, ed. L. E. Gardner, P. Amacher, p. 467. Santa Ynez, Calif: Kroc Found. 45. Ashworth, A., Bell, R., James, W. P. T., Waterlow, J. C. 1968. Calorie require­ ments of children recovering from pro­ tein-calorie malnutrition. Lancet 2: 6008 46. Richadson, D. P., Wayler, A. H., Scrim­ shaw, N_ So, Young, V. R. 1979. Quan-

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titative effect of isoenergetic exchange of fat for carbohydrate on dietary protein utilization in healthy young men. Am. J. Clin. Nutr. 32: 2217-26 47. Long, I. M., Wilmore, D. W., Mason, A. D., Pruitt, B. A. 1977. Effect of carbo­ hydrate and fat intake on nitrogen excretion during total intravenous feed­ ing. Ann. Surg. 185: 417-22 48. Long, 1. M., Wilmore, D. W., Mason, A. D., Pruitt, B. A. 1974. Fat carbo­ hydrate interaction: Nitrogen sparing effect of varying caloric sources for total intravenous feeding.. Surg. Forum 25: 61-63

49. Elwyn, D. H. 1990. New concepts in nitrogen balance. Can. J. Gastroenterol. 4(Suppl. A): 9A-12A 50. leejeebhoy, K. N., Anderson, G. H., Nakhooda, A. F., Greenberg, G. R., Sanderson, I., Marliss, E. B. 1976. Meta­ bolic studies in total parenteral nutrition with lipid in man. J. C/in. Invest. 57: 125-36 51. Wolfe, R. R., Herndon, D. N., Jahoor, F., Miyoshi, H., Wolfe, M. H. 1987. Effect of severe burn injury on substrate cycling by glucose and fatty acids. N. Engl.J. Afed 317:403-8 52. Moore, F. D. 1980. Energy and the maintenance of the body cell mass. J. Parenteral Enteral Nutr. 4: 228-60 53. Brennan, M. F., Fitzpatrick, G. F., Cohen, K. H., Moore, F. D. 1975. Gly­ cerol: major contributor to the short term protein sparing effect of fat emul­ sions in normal man. Ann. Surg. 182: 386-94

54. Brown, M. L., ed. 1990. Present Knowl­ edge in Nutrition. Washington, DC: Int. Life Sci. Inst. Nutr. Found. 55. Rudman, D., Millikan, W. J., Rich­ ardson, T. I., et a!. 1975. Elemental bal­ ances during intravenous hyperalimen­ tation of underweight adult subject. J. c/in. Invest. 55: 94-104 56. Shils, M. E. 1988. Enteral (tube) and parenteral nutrition support. See Ref. 58, pp. 1023-66 57. Food and Agricultural Organization/ World Health Organization. 1989. Report of a Joint FAO/ WHO Expert Com­ mittee. FAO Food and Nutr. Ser. 23.

Rome: FAO 58. Shils, M. F., Young, V. R., ed. 1988. Modern Nutrition in Health and Disease.

Philadelphia: Lea & Febiger. 7th ed.

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Parenteral and enteral nutrition.

Stress and starvation, especially when complicated by sepsis, will give rise to a rapid erosion of the cellular mass, which significantly affects morb...
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