Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992), pp. 1153-1161

REVIEW ARTICLE

Immunonutrition and Enteral Hyperalimentation of Critically Ill Patients STEPHEN A. McCLAVE, MD, CYNTHIA C. LOWEN, RD, CNSD, and HARVY L. SNIDER, MD

Physicians need to be maximally aggressive in their use of total enteral nutrition (TEN) in the critically ill patient, due to its lower cost, better physiology, and lower complication rate when compared to parenteral therapy. Various components in TEN such as glutamine, arginine, RNA nucleotides, omega-3 fish oils, and fiber, may have important roles in immunonutrition by maintaining gut integrity, stimulating the immune system, and preventing bacterial translocation from the gut. For each patient, the physician must choose the optimal enteral formula for that particular disease or organ failure state to maximize nutrient substrate assimilation and tolerance. Total parenteral nutrition (TPN) should be used only when a true contraindication to enteral feedings exists or as adjunctive therapy when full nutritional requirements cannot be met by TEN alone. KEY WORDS: total enteral nutrition; immunonutrition;enterai feeding.

ENTERAL VERSUS PARENTERAL NUTRITION There is increasing information that total parenteral nutrition may be harmful and immunosuppressing to the critically ill patient. When patients are fed by vein with no luminal gut nutrients, atrophy of the gut develops with increased permeability and loss of gut-associated lymphoid tissue (1, 2). This condition may allow bacteria to translocate across the wall of the gut into the circulation (3). Studies in animals have demonstrated radiolabeled luminally derived bacteria as well as endotoxin to be present in mesenteric lymph nodes, the portal vein, and the systemic circulation (4-6). As bacteria enter the systemic circulation, macrophages are stimulated to release cytokines. These cytokines (interleuken-1, tumor necrosis factor, and interleuken-2) in turn generate the hypermetabolic response seen in sepsis (7-11). Possibly through vasoconstriction, Manuscript received June 18, 1991; revised manuscript received December 30, 1991; accepted January 27, 1992. From the Division of Gastroenterology/Hepatology, Department of Medicine, University of Louisville School of Medicine, and Veterans Affairs Medical Center, Louisville, Kentucky. Address for reprint requests: Dr. Stephen A. McClave, Division of Gastroenterology, Department of Medicine, University of Louisville, Louisville, Kentucky 40292.

thrombosis, and physiologic shunts, the cytokines may produce hypoxia and subsequent organ failure (12-14). Although sepsis may originate from areas other than the gastrointestinal tract, it is important to remember that in critically ill patients who appear septic with negative chest x-ray, negative urine, and no other site of obvious infection, the source may be the gut. While total parenteral nutrition (TPN) may promote the occurrence of this situation, the use of total enteral nutrition (TEN) may prevent this scenario (15-17). There are a number of other reasons why TEN is more beneficial than TPN. There is a tremendous cost differential between these two therapies. The average daily cost of TPN may be as much as five times the expense of TEN (18). The use of TEN has physiologic advantages over TPN (19). TEN stimulates contraction of the gallbladder, reducing the likelihood of bile stasis and gallstone formation. TEN maintains gut-associated lymphoid tissue and stimulates immune function. TEN stimulates the pancreas, avoiding sluggish secretion and functional pancreatic insufficiency. The complication profile is improved with TEN. There are no catheters in the vascular space to lead to thrombosis and

Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992) 0163-2116/92/0800-1153506.50/0 9 1992 Plenum Publishing Corporation

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McCLAVE ET AL infection (19). Although liver enzyme abnormalities have been reported to occur in up to 40% of those patients on enteral feedings (20), they are less likely to develop with enteral than with parenteral regimens (21). TEN also maintains the integrity of the gut, as evidenced by decreased risk of perforation, increased collagen deposition, and improved healing following surgical gut anastomoses (22-24). IMMUNONUTRITION Immunonutrition is the term being used now to refer to the effects of nutritional hyperalimentation on the immune system. A number of studies have identified those components of enteral and parenteral feeding that have the greatest effect on the immune system. Long-chain fatty acids have been shown to have one of the greatest effects on the immune system. Polyunsaturated fatty acids of the omega-6 variety are derived from the essential fatty acid linoleic acid and are the form found in Intralipid in TPN and Microlipid in TEN. These omega-6 fatty acids may have a significant immunosuppressant effect (2527). Infusion of omega-6 fatty acids increases the production of thromboxane A2, which can cause thrombosis and vasoconstriction. Prostaglandin E 2 (PGE 2) is also increased by omega-6 fatty acid infusion, which can have a direct suppressant effect on delayed cellular-mediated hypersensitivity reactions. PGE 2 inhibits complement synthesis, increases superoxide generation, and may decrease tumorocidal activity. PGE 2 mediates its immunosuppressive effect by increasing suppressor T cell activity. Omega-6 fatty acids also increase the leukotriene LTB4, which leads to neutrophil chemotaxis (25, 26, 28, 29). As a result of this process, if bacteria enter the systemic circulation, inflammation, thrombosis, vasoconstriction, and edema are all stimulated, but the definitive immune surveillance system that would eradicate the organisms is inhibited (29, 30). Polyunsaturated fatty acids of the omega-3 variety are derived from the semiessential fatty acid linolenic acid and is found in fish oils (such as menhaden). Omega-3 fatty acids generate a slightly different variety of prostaglandins and leukotrienes. Infusion of omega-3 fatty acids leads to the increase in prostaglandin E 3 (PGE3) and LTBs, which have similarities to PGE 2 and LTB 4, but are much weaker agents with as little as one tenth of the biological activity and much less immune suppressant effects (29, 31, 32).

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Arginine has been shown to have a significant immunostimulatory effect (33). Arginine has a thymotrophic effect, and its infusion has been shown to maintain or increase the weight of the thymus gland and prevent the thymic atrophy, which can occur following injury. This thymotrophic effect leads to the increased production and release of cytotoxic natural killer and helper T cells (34). Arginine also leads to the increased release of interleukin-2, which by itself, has an antitumor effect (35). Interleukin-2 and tumor necrosis factor are responsible for the initiation and propagation of the metabolic response to injury, stress, and sepsis. Interleukin-2, by itself, may be responsible for transplant allograft rejection, blood transfusion reactions, and antigenantibody complex reactions (8-10). RNA nucleotides have also been shown to have an immunostimulatory effect (36). Enteral diets enriched with RNA derived from yeast have been shown to stimulate the maturation and phenotypic expression of T lymphocytes. When compared to nucleotide-enriched dietary regimens, nucleotidefree diets have been shown to result in decreased interleukin-2 production, decreased delayed cellular-mediated hypersensitivity reactions, decreased allograft rejection, and decreased resistance to infection (37). In comparison to these agents, which have a direct immunostimulatory or immunosuppressing effect, there are a number of agents that indirectly support the immune system by maintaining the integrity of the gut. In the stressed critically ill patient, the gut plays a key role in providing nitrogen and protein precursors for the hepatic synthesis of acute-phase reactants and gluconeogenesis. The gut also provides the first line of defense as an immune barrier to foreign antigens or organisms that pass through the lumin of the gut (38). Any substrate that maintains the integrity of the gut promotes this vital function. Glutamine has been shown to have a significant trophic effect on the gut (38), and in some studies has been shown to prevent bacterial translocation (39). Glutamine may actually be a preferred fuel source for the intestinal tract in times of stress (38). Small chain peptides have also been shown to have a trophic effect on the gut and are most useful in a situation of hypoalbuminemia and gut wall edema (40). The infusion of small-chain peptides results in the most efficient absorption of protein and may actually facilitate the cotransport of other nutrients across an edematous gut wall (40). Pectin is conDigestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

IMMUNONUTRITION AND TOTAL ENTERAL NUTRITION tained in apple sauce, Kaopectate, and some enteral regimens with fermentable fiber, and it has been shown to have a significant trophic effect on the gut (41). Short-chain fatty acids are products of carbohydrate metabolism and may exert their trophic effect more on the colon than the small bowel. Short-chain fatty acids may be the preferred fuel source for the colonic epithelium (42, 43). Studies in inflammatory bowel disease (44) have shown that enemas enriched with short-chain fatty acids improve healing and reduce inflammation through this trophic effect and may actually stimulate water and sodium absorption (45, 46). Whether short-chain fatty acids will ultimately be added to enteral regimens is yet to be seen. These factors in immunonutrition are now being shown in clinical outcome studies to have a significant effect on patient care (47). The Shriner's burn formula is an early precursor to the development of Impact by Sandoz (an enteral regimen fortified with nucleotides and arginine). In the Impact formula, fat makes up less than 33% of the nonprotein calories and is divided equally between omega-3 and omega-6 long-chain fatty acids. Early studies have shown that infusion of the Shriner's burn formula resulted in significantly fewer wound infections, pneumonia, total number of infections, and shorter length of hospitalization, with a trend toward reduced mortality, when compared to those patients receiving Osmolite or Traumacal (47). Two subsequent studies compared the Outcome effects of infusing Impact versus Osmolite (48, 49). Results of these studies seem to concur with this differential reduction in total infections and length of hospitalization using this immunostimulatory regimen. TPN differs from TEN with regard to immunonutrition, in that most of these immunostimulants have either not yet been formulated for intravenous use or have been shown to be unstable in combination with intravenous solutions. TPN also lacks the trophic effect on the intestine seen with the administration of almost any intraluminal nutrient (1). CHOOSING THE ENTERAL ROUTE: INDICATIONS AND CONTRAINDICATIONS

These aspects of immunonutrition indicate that physicians must be much more aggressive in their use of TEN. TPN should only be used as back-up when a true contraindication to TEN exists or the patient's nutritional requirements cannot be met by TEN alone. The only true contraindication to enDigestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

teral feeding is the absence of a gut. Other conditions, however, may make enteral feedings so difficult, that they in fact serve as contraindications, such as multiple perforations of the gut, high output fistulas (particularly if located high in the gastrointestinal tract), and mechanical obstruction of the gut. In the past, other conditions were misinterpreted as contraindications to TEN and often resulted inappropriately in the cessation of enteral feedings. Paralytic or postoperative ileus is no longer a contraindication to enteral feeding. A number of studies have shown that feeding into the small bowel with semielemental small-chain peptide formulas may achieve efficient absorption without peristalsis. Patients leave the recovery room after surgery with enteral regimens infusing into the small bowel (50). When no bowel sounds are present, tolerance is monitored by distension and abdominal discomfort. Following surgical gut anastomosis or repair, the infusion of enteral formulas (in animal studies) promoted healing, collagen deposition, and improved tensile strength of the surgical scar (22-24). Aspiration from gastroesophageal reflux, diarrhea, and high residual volumes from gastric feedings are all situations that indicate potential problems and poor patient tolerance but are not contraindications to continued enteral feeding. These situations simply indicate that modifications or adjustments of the patient management need to be made, such as placing the tube beyond the pylorus into the small bowel, elevating the head of the bed using the reverse Trendelenburg position, or changing the osmolality of the enteral formula. Pancreatitis, inflammatory bowel disease, and preoperative gut sterilization are no longer absolute contraindications to enteral feeding (40). Elemental and semielemental formulas may be infused and efficiently absorbed high in the small bowel and still cause minimal stimulation of the pancreas in certain stages of acute and chronic pancreatitis, put the remainder of the gut at rest in inflammatory bowel disease, and allow sterilization of the colon in the preoperative patient (40, 51, 52). DESIGNING THE ENTERAL REGIMEN

In determining the nutritional requirements, the physician may calculate the amount of nonprotein calories by using the Harris-Benedict predictive formula for resting energy expenditure adjusted by a metabolic injury factor, by using a metabolic indirect 1155

McCLAVE ET AL calorimetric cart to measure energy expenditure, or by simply taking an average of 25-30 cal/kg/day (from a range of 20-40 cal/kg/day). Protein requirements may be calculated from the urine urea nitrogen, from a nonprotein calorie-nitrogen ratio (130:1 to 150:1), or by taking an average of 1.5 g protein/kg/day (from a range of 0.6-2.0 g/kg/day). In the underweight patient in whom weight gain is desired, 500 extra calories may be added per day to these requirements to result in a 1-1b weight gain per week. As the physician designs the nutritional regimen for the critically ill patient, every effort should be made to use the enteral route. The regimen may need to be modified by decreasing the nonprotein calorie-nitrogen ratio to 100:1 or less in order to give more protein with respect to the nonprotein calories. It is important to avoid overfeeding, as defects in metabolism that occur in the critically ill patient prevent the full utilization of infused substrate, and overfeeding may create added stress (ie, increased metabolic rate) for the patient (53). Overfeeding may lead to azotemia, abnormal liver enzymes, and pulmonary deterioration. The regimen needs to be modified for the presence of any concomitant organ failure and may need to be modified for the specific subset of stress. The ultimate goal of the enteral regimen, however, is to support the metabolic response to injury while maintaining adequate patient tolerance. The route of enteral administration may vary between patients. Some patients may benefit simply by oral supplementation of formula between meals or with meals. Other patients may require tube feeding through a nasogastroduodenal tube, through a percutaneous endoscopically placed tube, or through a surgically placed tube. The initial rate and concentration of the formula depends on the position of the tube in the gastrointestinal tract (19). If a tube is positioned in the stomach, the formula may be started at full concentration with slow advancement of the rate. Volume and gastric emptying determine patient tolerance in this situation. Osmolar receptors in the duodenum control gastric emptying and do not allow the formula to pass into the small bowel until it is isosmotic (54). When the tube is in the jejunum, patient tolerance is determined by the osmolar concentration. Formulas infused into the jejunum may be started at the full final rate, with slow advancement of the concentration (19). To select the enteral regimen that best suits a particular patient, the physician must choose from a variety of factors for the formula that most likely 1156

will result in tolerance and assimilation (55). (Table 1). Caloric density varies between formulas, ranging from 1.0 to 2.0 kcal/cc. In renal, hepatic, and heart failure, it may be desirable to concentrate feeds and select formulas with increased caloric density, thereby avoiding excessive fluid administration. In patients with poor volitional intake who cannot consume a large volume of formula, regimens with a greater number of calories per cubic centimeter may be more beneficial. Osmolality is closely linked to caloric density, with greater caloric density formulas being associated with higher osmolality and greater potential patient intolerance (55). Protein complexity may become an issue in certain disease states. Whenever possible, formulas with intact protein should be utilized, as these have the greatest trophic effect on the gut (56, 57). Any patient, however, with an albumin less than 2.6 g/dl may be assumed to have gut wall edema, and the infusion of formulas fortified with small-chain peptides may result in the greatest degree of absorption (58). In gut disuse with flattened villi and decreased absorptive surface, elemental or semielemental formulas with small-chain peptides and even individual amino acids may be absorbed more efficiently (40). Total protein content is an important factor in some disease states, and high nitrogen formulas with over 20% of the total calories provided as protein may be useful. These formulas may be appropriate in trauma, stress, or burn patients with accelerated protein requirements from wound healing and catabolism (59) or in pulmonary patients where increased protein is desired to stimulate ventilatory drive (60). The fat content of a formula varies from low-fat elemental regimens (useful in short bowel syndrome or patients with ileal resection) to formulas high in fat (which may be useful in sepsis, diabetes, or pulmonary disease where carbohydrate is tolerated poorly). Some formulas substitute medium-chain triglycerides (MCT oil) for long-chain fatty acids (to avoid malassimilation) or for carbohydrate calories (to reduce osmolality). Formulas fortified with immunostimulatory components may be more effective in stress or sepsis. MODIFICATION FOR ORGAN FAILURE AND STRESS SUBSET

The enteral formulation must be modified for various disease states (Tables 2 and 3). Patients with pulmonary disease may tolerate fat better than carbohydrate due to decreased carbon dioxide proDigestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

IMMUNONUTRITION AND TOTAL ENTERAL NUTRITION TABLE 1. GENERAL FORMULA CATEGORIES Formula Standard Tube only Isocal Osmolite Oral tube Ensure Resource Calorie dense Medium Ensure Plus Sustacal HC High Magnacal Isocal H C N Two Cal HN Protein dense Low calorie* Sustacal Osmolite H N Medium calofiet Sustacal HC Ensure Plus Elemental/semielemental Vivonex TEN Vital H N Criticare H N Short peptide semielemental Peptamen Reabilan Milk-based oral Meritene Sustagen Carnation Instant Fiber enriched Jevity Enrich Sustacal with Fiber

cal/cc

mosm

Protein (g/liter)

Protein (%)

CHO (%)

Fat (%)

Manufacturer

1.06 1.06

300 300

34 37

13 14

50 55

37 31

Mead Johnson Ross

1.06 1.06

450 450

37 37

14 14

55 55

31 31

Ross Sandoz

1.50 1.50

690 650

55 61

15 16

53 50

32 34

Ross Mead Johnson

2.00 2.00 2.00

590 690 700

80 75 84

14 15 17

50 40 43

36 45 40

Sherwood Mead Johnson Ross

1.00 1.06

625 310

61 44

24 17

55 53

21 30

Mead Johnson Ross

1.50 1.50

650 690

60 55

16 15

50 53

34 32

Mead Johnson Ross

1.00 1.00 1.06

630 500 650

38 42 37

15 17 14

82 74 83

3 9 3

Norwich Eaton Ross Mead Johnson

1.00 1.00

260 350

40 31

16 12

51 53

33 35

Clintec O'Brien

.96 1.85 1.06

505 840 677

58 I 11 57

24 24 22

46 68 51

30 8 27

Sandoz Mead Johnson Clintec

1.06 1.10 1.06

310 480 480

44 40 46

16 14 17

54 55 53

30 31 30

Ross Ross Mead Johnson

*Similar formulas include Isocal HN, Ensure HN, Isosource, Isosource HN, Isotein HN. tSimilar formulas include Trauma Cal, Ensure Plus HN, Resource Plus.

duction (61). Protein stimulates ventilatory drive and may or may not be beneficial to the patient with pulmonary disease (60). The use of Pulmocare or Traumacal in these patients may be appropriate in that over 50% of the nonprotein calories are provided as fat. Traumacal has 35% more protein than Pulmocare (83 g/liter versus 62 g/liter) if more protein is required. Patients with hepatic failure may have difficulty tolerating protein, as multiple metabolic products (methylmercaptans, aromatic amino acids, ammonia) contribute to encephalopathy (62). Liver disease patients with ascites and portal hypertension may tolerate fluid volume poorly, and those with cholestasis or alcoholic liver disease may have difficulty tolerating fat (63). In these patients, it may be appropriate to concentrate feeds, watch serum triglycerides closely, and use Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

Hepaticaid, which is fortified with branched-chain amino acids (46% branched-chain amino acids versus 22% in standard formulas). Hepaticaid differs from stress formulas (which are also fortified with branched-chain amino acids) by its negligible methionine levels (less than 1% of the total protein) (64). Patients with renal failure may be markedly catabolic and tolerate protein and fluid volume poorly. In these patients, it is important to concentrate feeds and provide some protein (0.6-0.8 g/kg/ day), but increase the nonprotein calorie-nitrogen ratio high enough to create anabolism. Renal failure formulas such as Amin-Aid or Travesorb Renal contain 100% of the protein as essential amino acids and histidine and are designed to promote the recycling of nitrogen away from urea production to the production of nonessential amino acids. In

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McCLAVE ET AL TABLE 2. SPECIALTYFORMULAS Formula Stress/trauma Stresstein Traumacal Hepatic HepaticAid Travasorb Hepatic Renal Amin-Aid Travasorb Renal Pulmonary Pulmocare TraumaCal Diabetes Glucerna Immunostimulant Impact

cal/cc

mosm

Gm protein (g/liter)

Protein (%)

CHO (%)

Fat (%)

Manufacturer

1.2 1.5

910 490

70 83

23 22

57 40

20 38

Sandoz Mead Johnson

1.2 1.1

560 600

44 29

15 10

57 78

28 12

Kendall McGaw Clintec

1.9 1.4

700 590

19 23

4 7

75 81

21 12

Kendall McGaw Clintec

1.5 1.5

520 490

63 83

17 22

28 40

55 38

Ross Mead Johnson

1.0

375

42

17

33

50

Ross

1.0

375

56

22

53

25

Sandoz

critically ill patients, however, this recycling does not occur, and thus these formulas are not recommended (65). Osmolite or Isocal with low phosphorus and potassium concentration, or Magnacal with high caloric density may be more appropriate in these patients. Patients with cardiac disease tolerate all three substrates well and only in the presence of congestive heart failure do they tolerate fluid volume poorly. Monitoring fluid and electrolytes in

these patients is important while providing a standard formula such as Osmolite or Isocal. Four distinct subsets of stress exist: starvation, fight/flight/fright, wound healing, and sepsis (66). A single patient may actually pass through each of the four subsets within a single hospitalization, and the enteral formulation must be adjusted differently for each of the subsets. Simple starvation would occur in a patient with cancer cachexia awaiting surgery

TABLE 3. MODIFICATIONSFOR DISEASESTATES Condition Standard Hypoalbuminemic form of protein--calorie malnutrition Marasmic form of protein-calorie malnutrition Gastrointestinal disease Gut disuse, short bowel, gut wall edema Stress Starvation Fight/flight Wound healing

Nonprotein (cal/kg)

Protein (g/kg)

CHO:FAT

Suggested formula

Rationale

25 20-25

1.0 1.5-1.8

60:40 60:40

30-35

1.2-1.5

60:40

25-30

1.8

60:40

Peptamen, Reabilan, Vital HN

Small peptides (with MCT oil) to enhance absorption

30-35 20 30-35

1.0 1.0-1.5 1.5-2.0

60:40 50:50 60:40

20-25

1.5-1.8

40:60

Liver disease

30-35

0.8-1.2

60:40

Standard feeding Feed cautiously through ebb stage Increase protein, carbohydrate for granulation Reduce carbohydrate for insulin resistance Provide branch chain amino acids

Congestive heart failure

25-30

1.2-1.5

60:40

Pulmonary disease

30-35

1.2-1.8

40:60

Osmolite, Isocal Reabilan, Peptamen Stresstein, Impact, Osmolite HN, Replete Pulmocare, Glucerna, Impact Hepatic Aid, Travasorb Hepatic Magnacal, Two Cal HN, Isocal HCN Pulmocare, Traumacal

Renal disease Nondialysis

30-35

0.6-0.8

60:40

Dialysis Diabetes

30-35 25-30

1.0-1.5 1.0-1.5

60:40 40:60

Osmolite, Suplena, Magnacal Osmolite, Isocal Glucerna, Pulmocare

Increase calories while reducing protein Provide protein and calorie needs Decreased carbohydrate feeding

Sepsis

1 158

Osmolite, Isocal Standard feeding Osmolite HN, Isocal HN, Increase protein, decrease Peptamen, Reabilan HN nonprotein calorie-N ratio Osmolite, Isocal Promote weight gain, increase calories and protein

Restrict fluid administration Reduce carbohydrate to decrease COz

Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

IMMUNONUTRITION AND TOTAL ENTERAL NUTRITION and is characterized by low insulin levels, orderly catabolism, and a switch to ketone metabolism (66, 67). In this setting, all substrates are tolerated well and a standard 1 cal/cc isotonic formula (such as Isocal or Osmolite) is appropriate. The subset fight/ flight/fright occurs in a patient undergoing surgery or recently sustaining trauma or burns. This subset is characterized by increased catecholamine and cortisol secretion, low insulin levels with insulin resistance, and often ileus (66). Although there is tremendous energy expenditure and protein catabolism, multiple metabolic defects exist making it difficult to meet the patient's requirements (53). Fluid resuscitation with moderate protein provision and a low nonprotein calorie-nitrogen ratio is appropriate in these patients. Small-chain peptide formulas such as Reabilan or Peptamen may be infused at full strength directly into the small bowel even in the face of ileus (40, 50). As the acutely injured or postoperative patient begins to heal, he passes from the ebb phase to the flow phase of injury and enters the stress subset of wound healing (66). A subtle change in the hormonal milieu from alpha- to beta-adrenergic catecholamine release allows insulin levels to rise (66, 68). Because granulation tissue is an obligate glucose consumer, enteral feedings in this subset need to have increased carbohydrate despite the persistence of an insulin resistance (69). Elevated urine urea nitrogen may indicate catabolism of skeletal muscle following injury, accelerated protein requirements, and depletion of branch chain amino acids. In this situation, stress formulas fortified with branched-chain amino acids (such as Stresstin or Traumacal) or standard formulas fortified with protein (Osmolite HN or Isocal HN) may be beneficial (59). Another alternative for this subset would be the immunostimulatory formula Impact (which is also fortified with protein). If at any point in the hospital course the patient develops infection, he may enter the fourth stress subset of sepsis. Here the production and release of acute-phase reactants and white blood cells create even greater demand for protein. Insulin levels are still increased, but an even greater insulin resistance exists compared to that seen in the previous subsets (66, 70). In these patients, the enteral formulation may need to be adjusted to decrease the carbohydrate-fat ratio for the nonprotein calories. Switching to Pulmocare or the diabetic formula Glucerna, where at least 50% of the nonprotein calories are provided as fat, may be appropriate. Increasing the percentage of fat caloDigestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

ties may overload the reticuloendothelial system or potentially suppress immune function with omega-6 long-chain fatty acids. This may be avoided by using formulas in which a large portion of the fat calories are provided as medium-chain triglycerides (Peptamen) or as omega-3 fatty acids (Impact). Fiber residue may be a factor for consideration in some patients (71). Patients who have pancreatitis, inflammatory bowel disease, or who are undergoing gut sterilization prior to surgery, may require a fiber-free, low-residue regimen such as the elemental or small-chain peptide formulas. Assuming adequate tolerance, the infusion of these formulas should result in negligible stool output. Patients receiving standard enteral formulas may or may not have regular bowel movements. Bowel regularity and the formation of solid stool may be promoted by switching to fiber-enriched formulas (such as Enrich or Jevity). Most often, adjustments in the enteral regimen for different patient conditions and specific disease subsets are made by switching from standard formulas to specialty formulas designed for that situation. It is important to realize that the same adjustments can be made simply by taking a standard formula and adding modules for the appropriate substrate. Powdered modules such as Polycose (providing 30 cal of carbohydrate per tablespoon) or Casec (providing 4 g of protein per tablespoon) may be added to a standard formula such as Osmolite or Isocal. Likewise, fat may be added in the form of Microlipid (4.5 cal of omega-6 long-chain fatty acids per cubic centimeter), menhaden fish oil, or MCT oil (providing 8 cal of medium-chain triglycerides per cubic centimeter). Although MCT oil does not provide essential fatty acids, it may be most appropriate as a calorie source in patients with maldigestion, malabsorption, or short bowel syndrome. CONCLUSIONS Whenever possible, physicians should choose the enteral rather than the parenteral route for the nutritional management of the critically ill patient. TPN suppresses the immune system and may promote sepsis, the hypermetabolic response to injury, and subsequent organ failure. TEN, in comparison, is more physiologic, less costly, and may have fewer complications. TEN stimulates the immune system, may reduce the hypermetabolic response to injury, and may decrease the likelihood of sepsis, hypoxemia, and organ failure. TEN may be finely 1159

McCLAVE ET AL a d j u s t e d to m a x i m i z e s u b s t r a t e u t i l i z a t i o n a n d patient tolerance in any disease subset. T P N should b e u s e d o n l y i n the r a r e c a s e s w h e r e a c o n t r a i n d i c a t i o n to e n t e r a l f e e d i n g e x i s t s o r w h e n total p r o t e i n a n d c a l o r i e n e e d s c a n n o t b e m e t b y the e n t e r a l r o u t e exclusively.

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Immunonutrition and enteral hyperalimentation of critically ill patients.

Physicians need to be maximally aggressive in their use of total enteral nutrition (TEN) in the critically ill patient, due to its lower cost, better ...
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