Current Strategies in Surgical Nutrition
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Nutritional Support in the Injured Patient
Charles W. Van Way III, MD*
Damage to the body triggers the stress response, which is characteriz'ed by hypermetabolism, impaired protein synthesis, and catabolism. The net effect is to mobilize the body's resources to meet the demands of healing. Muscle and visceral protein are broken down for energy, and there is a negative nitrogen balance. Mild stress can be tolerated for several days without ill effects. Moderate to severe stress causes nutritional depletion, which can depress essential visceral proteins, impair the immune system, blunt the inflammatory response, and interfere with wound healing. The differences between trauma and other causes of stress are a matter of degree. The postoperative patient rarely shows hypermetabolism more than 25% above normal if no infection is present. Patients with multiple blunt injuries, major abdominal injuries, or central nervous system (eNS) injury typically have 50% hypermetabolism, and patients with major burns may show 100% hypermetabolism. Nutritional support is essential to the therapy of major injuries. This review will outline the body's response to trauma, propose a strategy for nutritional support of the patient with burns or major injury, and discuss current controversies in trauma nutrition. The underlying hypothesis is that nutrition, if given appropriately and early, can significantly reduce complications and improve recovery.
THE STRESS RESPONSE The effect of stress on metabolism is best understood in terms of energy expenditure. Most of the body's energy stores are in fat and muscle. During fasting, glycogen is broken down to glucose, but available glycogen is depleted within 24 hours. Afterward, fat is broken down for energy, but fat is converted to fatty acids, not to carbohydrate, and the brain, blood, *Professor of Surgery. University of Missouri-Kansas City, and Program Director of Surgery, St. Luke's Hospital, Kansas City, Missouri
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CHARLES W. VAN WAY
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and bone marrow must have glucose as a source of energy. Glucose can be generated from amino acids obtained by breaking down protein. Because the biggest reservoir of protein is muscle, fasting induces breakdown of muscle protein. H • 32 With starvation, the body eventually adapts by using ketone bodies for energy. But the responses to stress are not the same as those to starvation. Glucose requirements are much greater during acute stress, and adaptation may not occur. In any case, the object of treatment is to prevent starvation, not to facilitate it. 17 The stress response begins in the CNS and involves the sympathetic nervous system, hormones, cytokines, and acute-phase proteins. The three "catabolic" hormones are cortisol, glucagon, and catecholamines. 6 • 7,12.36.37 Cortisol The stress reaction is the principal cause for ACTH release from the pituitary. This hormone stimulates the secretion of cortisol and other steroids from the adrenal glands. Steroids increase gluconeogenesis, promote glucose release, accelerate muscle breakdown, and enhance protein synthesis in the liver. Glucagon Glucagon enhances gluconeogenesis, indirectly promoting protein breakdown and increasing nitrogen excretion. Release of glucagon during stress is probably secondary to sympathetic nervous system activity. Catecholamines Activation of the sympathetic nervous system causes the adrenal medulla to release epinephrine and norepinephrine. Hyperglycemia is produced by actions of epinephrine on the liver, pancreas, and muscle. Free fatty acids are released from the fat stores. The metabolic rate rises. Insulin, Growth Hormone, and Thyroid Hormones Insulin is an anabolic hormone. A high ratio of insulin to glucagon (IIG ratio) favors protein synthesis. During stress, insulin and glucagon are both elevated, but the IIG ratio drops. Because the levels of cortisol and glucagon are always high with stress, the amount of insulin released is important in restoring the anabolic-catabolic balance. Growth hormone promotes protein synthesis and is elevated in stress. Thyroid hormones have a reciprocal relation to the catecholamines and are lowered in stress. 12. 36 Cytokines A number of peptides are produced by lymphocytes, macrophages, and other cells. First known as lymphokines, then as cytokines, these substances are now known more generally as peptide regulatory factors. They are a family of proteins produced by cells that have their chief effects on other cells. Many of the cytokines have significant systemic effects. The malaise of viral disease, for example, appears to be mediated by cytokines, probably the interleukins. The major groups of cytokines are interleukins, tumor necrosis factors,
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NUTRITIONAL SUPPORT IN THE INJURED PATIENT
interferons, and colony-stimulating factors. A number of other factors have been found that do not fit into these categories. Discussion of the cytokines is beyond the scope of this review but can be found elsewhere. 2 , 7, 13, 16. 24, 25, 28 Metabolic Changes During Stress The starved patient loses approximately 75 gm of muscle protein per day, or about 200 to 300 gm of muscle tissue. The stressed patient loses considerably more. With 60% hypermetabolism, 250 gm of muscle protein may be used up per day, or 750 to 1000 gm of muscle mass. The changes produced by stress are summarized in Figure 1. 11, 32 Glucose utilization determines gluconeogenesis, which in turn appears to necessitate muscle breakdown. The CNS, the hematopoietic system, the immune system, inflammatory cells, and granulation tissue utilize glucose as their primary source of energy. All of these tissues are involved in the response to injury. The stress reaction increases glucose utilization out of proportion to total energy expenditure: an increase in energy expenditure of 50% may be associated with a twofold to fourfold increase in protein breakdown. As stress increases, nitrogen excretion rises much faster than energy expenditure, from a normal of 6 to 8 gm/day to 30 to 40 gm/day.
STRATEGY FOR NUTRITIONAL SUPPORT IN THE INJURED PATIENT The general strategy for nutritional support is simple. Both fat and glucose may be given to satisfY caloric needs. To meet glucose requirements,
Figure 1. Catabolism in the stressed human, Fat is the major source of energy, but the amount of glucose required is large, Significant amounts of protein must be broken down each day to provide it. (Data from Cuthbertson DP: Observations on the disturbance of metabolism associated with injury and sepsis, Q J Med 1:233-244, 1932; and Shaw JMF. Wolfe RR: An integrated analysis of glucose, fat, and protein metabolism in severely injured patients, Ann Surg 209:63-72, 1989,)
Glucose 360 gm 1440 Kcal
CHARLES W. VAN WAY
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at least 40% to 50% of calories must be given as glucose. To maintain protein synthesis, amino acids must be given. The proportion of calories given as protein or amino acids should increase as energy needs rise. Energy Expenditure Energy requirements can be estimated in a variety of ways. The standard method is to calculate the basal energy requirements and then to apply a correction factor that estimates the extent of hypermetabolism. The Harris-Benedict equations are commonly used: BEE (men) = 66.47 BEE (women)
=
+ 13.75(wt in kg) + 5(ht in cm) - 6.76(age)
655
+ 9.6(wt in kg) + 1.7(ht in cm) - 4.7(age)
The Harris-Benedict equations estimate the basal energy expenditure (BEE); the total energy expenditure (TEE) is higher, depending on the degree of stress and the amount of activity: TEE
=
BEE X activity factor X stress factor
where the activity factor = 1.2 for bedridden patients and 1.3 for ambulatory patients, and the stress factor = 1.2 for mild hypermetabolism, 1.5 for moderate hypermetabolism, and 1.8 to 2.5 for severe hypermetabolism. Fick Principle Direct measurement of energy expenditure can be used to determine the extent of the stress reaction. If a Swan-Ganz catheter is in place, oxygen consumption can be calculated by the Fick principle: Oxygen consumption
=
(CaO z - CvO z)
X
Sa0 2
X
1.36
X
Hgb
Sv0 2
X
1.36
X
Hgb
CO
X
10
The oxygen consumption is in milliliters per minute, the cardiac output (CO) is in liters per minute, the arterial and mixed venous saturations are decimal fractions, and the Hgb is in grams per deciliter. These simplified equations ignore the dissolved plasma oxygen, which contributes less than 1% to the oxygen consumption. The oxygen consumption index, which is the oxygen consumption related to body surface area (BSA), is the best single measurement of hypermetabolism. The index is normally 90 to 120 mllmin per m 2 • We derive a hypermetabolism factor by dividing the index by 120, the upper limit of normal. This can be used as a stress factor in the Harris-Benedict equations: Oxygen consumption index
oxygen consumption/BSA
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NUTRITIONAL SUPPORT IN THE INJURED PATIENT
Hypermetabolism factor
= oxygen consumption indexl120
The resting oxygen consumption can be used to calculate the daily energy expenditure by the Weir equation. This equation requires the oxygen consumption, the carbon dioxide production, and the nitrogen output, but the nitrogen output is often ignored: Energy expenditure = 3.9
X
O 2 consumption
+
1.1
X
CO 2 production
If the respiratory quotient (RQ) is assumed to be 0.85 and the necessary conversion factors are applied, the Weir equation can be simplified to: Resting energy expenditure (REE; in kcaVday) 7.02 X O 2 consumption (in mVmin) Resting energy expenditure should be multiplied by the appropriate activity factor (below) to estimate TEE. Differential Oximetry The new technique of differential oximetry also uses the Fick principle and uses the same equations given above. The difference is that the saturations are obtained from instruments rather than blood gas analysis. The arterial saturation is measured from a pulse oximeter, and the mixed venous saturation is measured spectrophotometrically using a modified Swan-Ganz catheter containing a fiberoptic bundle. Cardiac output is obtained using thermodilution. Differential oximetry is well suited to making frequent determinations of oxygen consumption. This is not yet a standard technique, but preliminary studies in our intensive care unit have produced promising results. Metabolic Cart Bedside metabolic analysis measures oxygen consumption and carbon dioxide production by analyzing inspired and expired gas. This method does not require that the respiratory quotient be assumed. From this resting energy expenditure, the TEE can be estimated: TEE = REE
X
activity factor
The activity factor = 1.25 (ambulatory patients), 1.15 (bedridden patients), or 1.1 (ventilator-dependent patients). Obtaining an estimate for the total energy expenditure allows the calculation of caloric balance: Caloric balance = caloric intake - TEE Because the total energy expenditure remains fairly constant from day to day, a measurement on one day can be used on succeeding days, assuming no significant changes in the patient's condition. Caloric balance
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is as reliable as nitrogen balance in assessing the adequacy of nutritional intake. 5. 22 Nitrogen Balance Nitrogen excretion is the end product of protein breakdown for energy. Nitrogen intake minus excretion yields the nitrogen balance. The nitrogen balance technique has practical limitations. Measurement of all nitrogen losses over 24 hours should include stool, wound drainage, and fistula output; outside metabolic research units, this is virtually impossible to achieve. Also, the patient should be on a constant diet for 24 to 48 hours before a measurement period. This is difficult to achieve in the usual clinical setting. Nitrogen balance can be useful, but its shortcomings should be recognized. 19. 21 The 24-hour urine urea nitrogen (UUN) is widely used for nitrogen balance determination. Urine contains significant nonurea nitrogen, for which the UUN must be corrected. We use the following correction factor, which was derived from hypermetabolic patients: Total urinary nitrogen (TUN)
=
UUN/O.80
or TUN
=
UUN
X
1.25
With the TUN as an approximation of the total nitrogen loss, the nitrogen balance can be calculated. A confounding factor in nitrogen balance is the use of blood and blood products, especially albumin. 19 A unit of whole blood or packed cells contains about 11 gm of nitrogen in the hemoglobin. Similarly, 50 gm of albumin contains 8 gm of nitrogen. There is no way of determining how long a given amount of exogenous hemoglobin or albumin will last in the body, except that it will be broken down more rapidly than endogenous protein. The standard practice is to ignore exogenous blood and albumin when calculating nitrogen balance. This appears to be acceptable, at least in the short term. 21 Nitrogen and protein requirements can be calculated from the energy expenditure. 18 Assuming the desired nonprotein calorie-to-nitrogen ratio is 100, then: Grams of nitrogen Grams of protein
=
=
energy expenditure/125
6.25
X
(grams of nitrogen)
Calorie-to-Nitrogen Ratio The term "calorie-to-nitrogen ratio" (C/N) is often used as a shorthand for the relation between protein and calories. A normal C/N is 150 to 250. The ratio in stress is 80 to 125. In using this ratio, both components must increase with increasing stress. To increase the proportion of protein without increasing total calories will result in the protein being broken down for
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energy. Dietitians tend to express the same concept as the percentage of total calories supplied by protein. A normal percentage is 15%. A C/N ratio of 125 is equivalent to 20% of the calories being supplied as protein.
ROUTE OF ADMINISTRATION Enteral feeding is preferable to parenteral feeding, as enteral feeding maintains the integrity of the gut mucosa. Exclusive use of total parenteral nutrition may be associated with a loss of the normal gut mucosal barrier, bacterial translocation, and possibly sepsis. In animal studies, enteral nutrition is associated with lower energy requirements, better maintenance of body weight, and fewer septic episodes. 31 Several investigators8 • 26, 29 have shown the efficacy of enteral nutrition and its general superiority to parenteral feeding in patients who can tolerate either mode of nutrient delivery. The Enteral Strategy The general strategy is to feed early, preferably within 24 hours of injury. As any surgeon knows, feeding the patient immediately after a major injury can be difficult. The patient does not eat readily, may not be conscious, and may be dependent on ventilatory support. Ileus may be present, especially after abdominal surgery. The route of administration, then, depends on the patient's condition and the type and severity of injury. For extremity trauma, the patient may be able to eat, but patients with burns or other injuries interfering with eating may require feeding tubes. Abdominal injuries are a special case, because the injury and the operation combine to produce ileus. The ileus is selective; the stomach and the colon are inactive, but the small bowel often continues to work normally. To exploit this, the catheter jejunostomy has been advocated. 27 This is a small catheter placed into the jejunum just past the ligament of Treitz, advanced 15 cm distally into the small bowel, and brought out proximally through the abdominal wall. Feedings can be started within a few hours of operation. The small catheter will not allow infusion of thick feeding solutions, and a low-viscosity defined-formula diet is best. Significant time is required in building up intestinal tolerance to enteral feedings. Starting with half-strength solution at 50 mllhour, one progresses daily to threequarter strength and then to full strength; then to 70 mllhour, and finally to 100 mllhour. It usually takes about 5 days to advance to delivery of sufficient calories to meet requirements. Needle catheter jejunostomy is a very useful technique. Diarrhea is fairly common but easily treated. Intestinal obstruction from torsion of the bowel about the catheter occurs, as does pneumatosis intestinalis. A few patients, usually those with small-bowel or retroperitoneal injuries, have persistent ileus. The principal limitation of the technique is the long leadin time before full enteral nutrition can be given.
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The Parenteral Strategy The major advantage of parenteral nutrition is that one can provide the patient with full nutritional requirements within 12 to 24 hours. If the patient was malnourished before injury, is expected to have intolerance to enteral nutrition, or is to be returned to the operating room frequently, total parenteral nutrition may allow full nutritional support. Our practice is to start questionable patients on a peripheral parenteral nutrition regimen. We use a premixed bag containing 2900 ml, which includes 1000 gm of fat, 60 gm of amino acids, and 240 gm of glucose, together with electrolytes and vitamins. This formula can be given at 120 mllhour to virtually anyone without risk of glucose intolerance. Because it is standardized, the cost is relatively low, about twice that of a definedformula enteral diet. The solution can be given through a central line, if one is in place, or peripherally. The total of 2000 calories and 60 gm of nitrogen is adequate on average but low for a seriously hypermetabolic patient. This regimen is used for 5 to 7 days, by which time the patient usually is on full enteral nutrition or is eating. In the few patients who still require parenteral nutrition, high-nitrogen central total parenteral nutrition is a good interim regimen while enteral tolerance is being achieved. BURNS Burn wounds produce the highest metabolic stress of all injuries. The response produced by a large burn (>50% BSA) approaches the maximum metabolic capacity. Even relatively small burns may evoke a large response. The hypermetabolism cannot be suppressed and must be treated. If the patient is to survive, enough calories and protein must be given to meet the extreme demands. Energy Expenditure in Burns Many factors increase energy expenditure. The skin is the largest organ in the body. Injury to muscle and connective tissue adds to the stress. The inflammatory response occurs over a large area. The immune system is activated. The barrier function of the skin is partially lost, exposing the immune system to a host of exogenous challenges. Heat and water loss is accelerated from burned areas. Evaporative water loss per day is about 25 mllper cent burn, leading to energy loss from evaporation of 15 kcallper cent burn per day. The core temperature rises. Secondary infection and sepsis may further increase metabolic demands. Burns have been felt to be "quantifiable" injuries, in which the severity can be determined by estimating the amount of burned BSA. IO• 23 The familiar "rule of 9s" allows this estimate to be made easily and quickly. Estimation of fluid resuscitation by this principle has proved to be fairly accurate using the formula: Fluid per 1st 24 hours = 4
X
% burn
X
body weight (in kg)
The estimate of energy needs is often made using the same principle.
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NUTRITIONAL SUPPORT IN THE INJURED PATIENT
The multipliers used in the Harris-Benedict equations are commonly based on the burn size: TEE = BEE
X
activity factor
X
stress factor
where the activity factor = 1.2 for bedridden patients and 1.3 for ambulatory patients, and the stress factor = 1.5 for small burns «20%), 1.8 for moderate burns (20% to 50%), and 2.1 for severe burns (>50%). The Curreri formula estimates energy requirements attributable to the burn injury as 40 kcal/per cent burn and calculates basal energy requirements as 25 kcallkg: 1O TEE = 25
X
(weight)
+
40
X
(per cent burn)
Burns exceeding 50% are considered as if they were 50%. Measurement of the patient's energy metabolism with a metabolic cart is probably more accurate than using a formula. 5, 22 Gottschlich and associates l5 found that measuring rather than calculating energy expenditure resulted in a mean caloric requirement of only 2900 kcal, considerably less than would have been predicted by the formulas, Protein Metabolism in Burned Patients A patient with a large burn may lose 30 gm of nitrogen per day. The patient should be put into positive nitrogen balance as quickly as possible. Excess protein is better than just enough to meet needs. l Fat Metabolism in Burned Patients After burn injury, serum levels of free fatty acids and glycerol increase, presumably from the breakdown of adipose tissue. This increase is not associated with increased utilization. In severely hypermetabolic patients, fat may not be as effective in conserving nitrogen as carbohydrates. Fat should supply no more than 20% of the total calories. The same may be said for severely stressed and septic patients; the later stages of sepsis are said to be associated with poor fat utilization.
CONTROVERSIES AND CURRENT ISSUES The Gut Hypothesis and Glutamine Glutamine is important in the maintenance of gut mucosal integrity. The theory is as follows. The gut mucosal barrier is interrupted by shock or trauma. In shock, for example, blood flow to the gut is markedly diminished. The gut mucosa is dependent on glutamine as a source of energy and presumably as a nitrogen donor in protein synthesis. Glutamine is not generally regarded as an essential amino acid, but it does appear to be vital to the mucosal cells of the gut. Maintenance of the gut mucosal barrier to bacteria and bacterial products is impaired by a glutamine-free diet or by not giving oral nutrients at all. 33, 34
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Most parenteral regimens do not contain glutamine. The N-terminal nitrogen of glutamine tends to break off as ammonia, and ammonia in total parenteral nutrition solutions is obviously not desirable. Most commercial amino acid preparations contain glutamic acid, but not glutamine. This limitation of parenteral nutrition may contribute to the superiority of enteral nutrition formulations, which generally contain glutamine. Immunonutrition Much recent work has attempted to modulate the immune system by nutrition. Considering that malnutrition impairs the immune system, nutritional support itself is a general immunomodulator. More specific attention has been directed toward fatty acids, arginine, and nucleic acids. A commercial enteral product, Impact, incorporates all three of these nutrients and is now undergoing clinical trials. 35 Omega-3 Fatty Acids Linoleic acid, which is an essential unsaturated (omega-6) fatty acid, is the precursor for a number of eicosanoids (e.g., prostaglandin E2) that depress the immune system. 20 Substituting omega-3 fatty acids (as in some fish oil) for some of the linoleic acid appears to improve the immune system response. Clinical application has been limited. Gottschlich and coworkers,15 in a study comparing different enteral regimens in burned patients, found that one relatively low in fat calories (20%) and linoleic acid (4%) but containing omega-3 fatty acids (4%) was superior to regimens having more fat but no omega-3 fatty acids. Arginine A semiessential amino acid, argmme is necessary for growth. In humans, provision of arginine in excess of needs has been found to decrease T-suppressor cells, increase T-helper cells, and enhance the lymphocyte response to mitogens. Evidence supports the suggestion that supplying arginine in excess of requirements is beneficial to immune function. 3 . 4 Ribonucleic Acid The nucleic acids are normally synthesized de novo by the body. The turnover of nucleic acids increases markedly in stress, because of the cell synthesis involved in the inflammatory and immune responses. Indirect evidence exists that provision of nucleic acids enhances the immune response. 30 For example, in a study of the response of mice to endotoxin, the provision of RNA reduced bacterial translocation. 34. 35 Branched-chain Amino Acids The use of branched-chain amino acids in managing injury has been based on the observations that muscle breakdown releases large amounts of these substances and that branched-chain amino acids are metabolized primarily in the muscle itself. Providing high levels of branched-chain amino acids therefore may reduce muscle breakdown. The best clinical trial to date, a multicenter trial reported by Cerra et al,9 showed clearly that nitrogen balance was rendered more positive in severely stressed patients
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by the use of a regimen enriched in branched-chain amino acids. However, the data did not show a reduction in nitrogen excretion or in muscle breakdown. Similar clinical trials have been done, with equivocal results. A number of workers have emphasized the use of branched-chain amino acids in stressed patients, and more particularly in the injured patient. The evidence at present is insufficient to recommend this as a general practice, but in the hypermetabolic injured patient, branched-chain amino acids may indeed have merit.
CONCLUSION Nutritional support should be started as soon as possible after injury and should be maintained as long as the patient does not eat. Enteral nutrition is considered to be a better option than parenteral nutrition, aI~d every effort should be made to use the gut. Even partial gut feeding with sufficient parenteral supplementation to meet nutritional requirements appears to be superior to total parenteral nutrition in the injured patient. Although it is difficult to show an unequivocal increase in survival with adequate nutrition, studies have shown that nutritional support decreases complications following major injuries.
REFERENCES 1. Alexander JW, MacMillan BG, Stinnett JD, et al: Beneficial effects of aggressive protein feeding in severely burned children. Ann Surg 192:505-517, 1980 2. Balkwell FR: Interferons. Lancet 1:60-90, 1989 3. Barbul A: Arginine: Biochemistry, physiology, and therapeutic implications. JPEN 6:227, 1986 4. Barbul A: Arginine and immune function. Nutrition 6:53-59, 1990 5. Bartlett RH, Ally PA, Medley T, et al: Nutritional therapy based on positive caloric balance in burn patients. Arch Surg 112:974-980, 1977 6. Baue AE, Gunther B, Hartl W, et al: Altered hormonal activity in severely ill patients after injury or sepsis. Arch Surg 119:1125-1132, 1984 7. Bessey PQ: Metabolic response to critical illness. In Wilmore DW, Brennan MF, Harken AH, et al (eds): Care of the Surgical Patient. New York, Scientific American, 1989, section II, chap 11 8. Bower RH, Talamini MA, Sax HC, et al: Postoperative enteral versus parenteral nutrition: A randomized controlled trial. Arch Surg 121:40, 1986 9. Cerra F, Blackburn G, Hirsch J, et al: The effect of stress level, amino acid formula, and nitrogen dose on nitrogen retention in traumatic and septic stress. Ann Surg 205:282, 1987 10. Curreri WP: Nutritional replacement modalities. J Trauma 19:906-908, 1979 11. Cuthbertson DP: Observations on the disturbance of metabolism by injury to the limbs. Q J Med 1:233-244, 1932 12. Dahn MS, Jacobs LA, Lange MP, et al: Endocrine mediators of metabolism associated with injury and sepsis. JPEN 10:253-257, 1986 13. Dinarello CA, Mier JW: Lymphokines. N Eng! J Med 317:940, 1987 14. Gottschlich MM, Alexander JW: Fat kinetics and recommended dietary intake in burns. JPEN 11:80-85, 1987 15. Gottschlich MM, Jenkins J, Warden GD, et al: Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. JPEN 14:225-236, 1990
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16. Green AR: Peptide regulatory factors: Multifunctional mediators of cellular growth and differentiation. Lancet 1:705-764, 1989 17. Lemoyne M, Jeejeebhoy KN: Total parenteral nutrition in the critically ill patient. Chest 89:571-575, 1986 18. Long CL, Shaffe N, Geiger J, et al: Metabolic response to injury and illness: Estimation of energy and protein needs from indirect calorimetry and nitrogen balance. JPEN 3:452-456, 1979 19. Lundholm K, Bennegard K, Wickstrom I, et al: Is it possible to evaluate the efficacy of amino acid solutions after major surgical procedures or accidental injuries? JPEN 10:2933, 1986 20. Kinsellsa JE, Lokesh B, Boughton S, et al: Dietary polyunsaturated fatty acids and eicosanoids: Potential effects on the modulation of inflammatory and immune cells. Nutrition 6:24-44, 1990 21. Kopple JD: Uses and limitations of the balance technique. JPEN 11:79S-85S, 1987 22. Mancusi-Ungaro HR, Van Way CW, McCool C: Caloric and nitrogen balance as predictors of nutritional outcome in burn injured patients. J Burn Care Rehab (in press) 23. Matsuda T, Kagan RJ, Hanumadass M, et al: The importance of burn wound size in determining the optimal calorie:nitrogen ratio. Surgery 94:562-568, 1983 24. Metcalf 0: Haemopoietic growth factors: 1 and 2. Lancet 1:825-942, 1989 25. Michie HR, Spriggs DR, Manogue KR, et al: Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery 4:280, 1988 26. Moore EE, Jones TN: Benefits of immediate jejunostomy feeding after major abdominal trauma: A prospective randomized study. J Trauma 26:874, 1986 27. Moore EE, Van Way CW: Needle-catheter jejunostomy. In O'Leary JP, Woltering EA (eds): Techniques for Surgeons. New York, John Wiley & Sons, 1985, pp 90-95 28. O'Garra A: Interleukins and the immune system: 1 and 2. Lancet 1:943-959, 1989 29. Peterson VM, Moore EE, Jones TN, et al: TEN versus TPN following major torso injury: Attenuation of hepatic protein reprioritization. Surgery 4: 199, 1988 30. Rudolph FB, Kulkarni AD, Fanslow WC, et al: Role of RNA as a dietary source of pyrimidines and purines in immune function. Nutrition 6:45-52, 1990 31. Saito H, Trocki 0, Alexander JW, et al: The effect of route of nutrient administration on the nutritional state, catabolic hormones, and gut integrity after burn injury. JPEN 11:1-7, 1986 32. Shaw JHF, Wolfe RR: An integrated analysis of glucose, fat, and protein metabolism in severely traumatized patients. Ann Surg 209:63-72, 1989 33. Souba WW, Smith RJ, Wilmore OW: Glutamine metabolism by the intestinal tract. JPEN 9:608, 1985 34. Wells CL, Jechorek RP, Erlandsen SL, et al: The effect of dietary glutamine and dietary RNA on ileal flora, ileal histology, and bacterial translocation in mice. Nutrition 6:7075, 1990 35. Wells CL, Jechorek RP, Laven PT, et al: The effect of a uniquely formulated diet (supplemented with arginine, RNA, and menhaden oil) on ileal flora, ileal histology, and bacterial translocation in mice. Nutrition 6:76-80, 1990 36. Wilmore DW, Aulick LH, Becker RA: Hormones and the Control of Metabolism. In Fischer J (ed): Surgical Nutrition. Boston, Little, Brown, 1983, chap 3 37. Wilmore OW, Orcutt TW, Mason AD, et al: Alterations in hypothalamic function following thermal injury. J Trauma 15:697, 1975
Address reprint requests to Charles W. Van Way III, MD Department of Medical Education St. Luke's Hospital 4400 Wornall Road Kansas City, MO 64111
0039-6109/91 $0.00
+
.20
Nutritional Support in the Injured Patient
Charles W. Van Way III, MD*
Damage to the body triggers the stress response, which is characteriz'ed by hypermetabolism, impaired protein synthesis, and catabolism. The net effect is to mobilize the body's resources to meet the demands of healing. Muscle and visceral protein are broken down for energy, and there is a negative nitrogen balance. Mild stress can be tolerated for several days without ill effects. Moderate to severe stress causes nutritional depletion, which can depress essential visceral proteins, impair the immune system, blunt the inflammatory response, and interfere with wound healing. The differences between trauma and other causes of stress are a matter of degree. The postoperative patient rarely shows hypermetabolism more than 25% above normal if no infection is present. Patients with multiple blunt injuries, major abdominal injuries, or central nervous system (eNS) injury typically have 50% hypermetabolism, and patients with major burns may show 100% hypermetabolism. Nutritional support is essential to the therapy of major injuries. This review will outline the body's response to trauma, propose a strategy for nutritional support of the patient with burns or major injury, and discuss current controversies in trauma nutrition. The underlying hypothesis is that nutrition, if given appropriately and early, can significantly reduce complications and improve recovery.
THE STRESS RESPONSE The effect of stress on metabolism is best understood in terms of energy expenditure. Most of the body's energy stores are in fat and muscle. During fasting, glycogen is broken down to glucose, but available glycogen is depleted within 24 hours. Afterward, fat is broken down for energy, but fat is converted to fatty acids, not to carbohydrate, and the brain, blood, *Professor of Surgery. University of Missouri-Kansas City, and Program Director of Surgery, St. Luke's Hospital, Kansas City, Missouri
Surgical Clinics of North America-Vol. 71, No.3, June 1991
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CHARLES W. VAN WAY
III
and bone marrow must have glucose as a source of energy. Glucose can be generated from amino acids obtained by breaking down protein. Because the biggest reservoir of protein is muscle, fasting induces breakdown of muscle protein. H • 32 With starvation, the body eventually adapts by using ketone bodies for energy. But the responses to stress are not the same as those to starvation. Glucose requirements are much greater during acute stress, and adaptation may not occur. In any case, the object of treatment is to prevent starvation, not to facilitate it. 17 The stress response begins in the CNS and involves the sympathetic nervous system, hormones, cytokines, and acute-phase proteins. The three "catabolic" hormones are cortisol, glucagon, and catecholamines. 6 • 7,12.36.37 Cortisol The stress reaction is the principal cause for ACTH release from the pituitary. This hormone stimulates the secretion of cortisol and other steroids from the adrenal glands. Steroids increase gluconeogenesis, promote glucose release, accelerate muscle breakdown, and enhance protein synthesis in the liver. Glucagon Glucagon enhances gluconeogenesis, indirectly promoting protein breakdown and increasing nitrogen excretion. Release of glucagon during stress is probably secondary to sympathetic nervous system activity. Catecholamines Activation of the sympathetic nervous system causes the adrenal medulla to release epinephrine and norepinephrine. Hyperglycemia is produced by actions of epinephrine on the liver, pancreas, and muscle. Free fatty acids are released from the fat stores. The metabolic rate rises. Insulin, Growth Hormone, and Thyroid Hormones Insulin is an anabolic hormone. A high ratio of insulin to glucagon (IIG ratio) favors protein synthesis. During stress, insulin and glucagon are both elevated, but the IIG ratio drops. Because the levels of cortisol and glucagon are always high with stress, the amount of insulin released is important in restoring the anabolic-catabolic balance. Growth hormone promotes protein synthesis and is elevated in stress. Thyroid hormones have a reciprocal relation to the catecholamines and are lowered in stress. 12. 36 Cytokines A number of peptides are produced by lymphocytes, macrophages, and other cells. First known as lymphokines, then as cytokines, these substances are now known more generally as peptide regulatory factors. They are a family of proteins produced by cells that have their chief effects on other cells. Many of the cytokines have significant systemic effects. The malaise of viral disease, for example, appears to be mediated by cytokines, probably the interleukins. The major groups of cytokines are interleukins, tumor necrosis factors,
539
NUTRITIONAL SUPPORT IN THE INJURED PATIENT
interferons, and colony-stimulating factors. A number of other factors have been found that do not fit into these categories. Discussion of the cytokines is beyond the scope of this review but can be found elsewhere. 2 , 7, 13, 16. 24, 25, 28 Metabolic Changes During Stress The starved patient loses approximately 75 gm of muscle protein per day, or about 200 to 300 gm of muscle tissue. The stressed patient loses considerably more. With 60% hypermetabolism, 250 gm of muscle protein may be used up per day, or 750 to 1000 gm of muscle mass. The changes produced by stress are summarized in Figure 1. 11, 32 Glucose utilization determines gluconeogenesis, which in turn appears to necessitate muscle breakdown. The CNS, the hematopoietic system, the immune system, inflammatory cells, and granulation tissue utilize glucose as their primary source of energy. All of these tissues are involved in the response to injury. The stress reaction increases glucose utilization out of proportion to total energy expenditure: an increase in energy expenditure of 50% may be associated with a twofold to fourfold increase in protein breakdown. As stress increases, nitrogen excretion rises much faster than energy expenditure, from a normal of 6 to 8 gm/day to 30 to 40 gm/day.
STRATEGY FOR NUTRITIONAL SUPPORT IN THE INJURED PATIENT The general strategy for nutritional support is simple. Both fat and glucose may be given to satisfY caloric needs. To meet glucose requirements,
Figure 1. Catabolism in the stressed human, Fat is the major source of energy, but the amount of glucose required is large, Significant amounts of protein must be broken down each day to provide it. (Data from Cuthbertson DP: Observations on the disturbance of metabolism associated with injury and sepsis, Q J Med 1:233-244, 1932; and Shaw JMF. Wolfe RR: An integrated analysis of glucose, fat, and protein metabolism in severely injured patients, Ann Surg 209:63-72, 1989,)
Glucose 360 gm 1440 Kcal
CHARLES W. VAN WAY
540
III
at least 40% to 50% of calories must be given as glucose. To maintain protein synthesis, amino acids must be given. The proportion of calories given as protein or amino acids should increase as energy needs rise. Energy Expenditure Energy requirements can be estimated in a variety of ways. The standard method is to calculate the basal energy requirements and then to apply a correction factor that estimates the extent of hypermetabolism. The Harris-Benedict equations are commonly used: BEE (men) = 66.47 BEE (women)
=
+ 13.75(wt in kg) + 5(ht in cm) - 6.76(age)
655
+ 9.6(wt in kg) + 1.7(ht in cm) - 4.7(age)
The Harris-Benedict equations estimate the basal energy expenditure (BEE); the total energy expenditure (TEE) is higher, depending on the degree of stress and the amount of activity: TEE
=
BEE X activity factor X stress factor
where the activity factor = 1.2 for bedridden patients and 1.3 for ambulatory patients, and the stress factor = 1.2 for mild hypermetabolism, 1.5 for moderate hypermetabolism, and 1.8 to 2.5 for severe hypermetabolism. Fick Principle Direct measurement of energy expenditure can be used to determine the extent of the stress reaction. If a Swan-Ganz catheter is in place, oxygen consumption can be calculated by the Fick principle: Oxygen consumption
=
(CaO z - CvO z)
X
Sa0 2
X
1.36
X
Hgb
Sv0 2
X
1.36
X
Hgb
CO
X
10
The oxygen consumption is in milliliters per minute, the cardiac output (CO) is in liters per minute, the arterial and mixed venous saturations are decimal fractions, and the Hgb is in grams per deciliter. These simplified equations ignore the dissolved plasma oxygen, which contributes less than 1% to the oxygen consumption. The oxygen consumption index, which is the oxygen consumption related to body surface area (BSA), is the best single measurement of hypermetabolism. The index is normally 90 to 120 mllmin per m 2 • We derive a hypermetabolism factor by dividing the index by 120, the upper limit of normal. This can be used as a stress factor in the Harris-Benedict equations: Oxygen consumption index
oxygen consumption/BSA
541
NUTRITIONAL SUPPORT IN THE INJURED PATIENT
Hypermetabolism factor
= oxygen consumption indexl120
The resting oxygen consumption can be used to calculate the daily energy expenditure by the Weir equation. This equation requires the oxygen consumption, the carbon dioxide production, and the nitrogen output, but the nitrogen output is often ignored: Energy expenditure = 3.9
X
O 2 consumption
+
1.1
X
CO 2 production
If the respiratory quotient (RQ) is assumed to be 0.85 and the necessary conversion factors are applied, the Weir equation can be simplified to: Resting energy expenditure (REE; in kcaVday) 7.02 X O 2 consumption (in mVmin) Resting energy expenditure should be multiplied by the appropriate activity factor (below) to estimate TEE. Differential Oximetry The new technique of differential oximetry also uses the Fick principle and uses the same equations given above. The difference is that the saturations are obtained from instruments rather than blood gas analysis. The arterial saturation is measured from a pulse oximeter, and the mixed venous saturation is measured spectrophotometrically using a modified Swan-Ganz catheter containing a fiberoptic bundle. Cardiac output is obtained using thermodilution. Differential oximetry is well suited to making frequent determinations of oxygen consumption. This is not yet a standard technique, but preliminary studies in our intensive care unit have produced promising results. Metabolic Cart Bedside metabolic analysis measures oxygen consumption and carbon dioxide production by analyzing inspired and expired gas. This method does not require that the respiratory quotient be assumed. From this resting energy expenditure, the TEE can be estimated: TEE = REE
X
activity factor
The activity factor = 1.25 (ambulatory patients), 1.15 (bedridden patients), or 1.1 (ventilator-dependent patients). Obtaining an estimate for the total energy expenditure allows the calculation of caloric balance: Caloric balance = caloric intake - TEE Because the total energy expenditure remains fairly constant from day to day, a measurement on one day can be used on succeeding days, assuming no significant changes in the patient's condition. Caloric balance
542
CHARLES W. VAN WAY
III
is as reliable as nitrogen balance in assessing the adequacy of nutritional intake. 5. 22 Nitrogen Balance Nitrogen excretion is the end product of protein breakdown for energy. Nitrogen intake minus excretion yields the nitrogen balance. The nitrogen balance technique has practical limitations. Measurement of all nitrogen losses over 24 hours should include stool, wound drainage, and fistula output; outside metabolic research units, this is virtually impossible to achieve. Also, the patient should be on a constant diet for 24 to 48 hours before a measurement period. This is difficult to achieve in the usual clinical setting. Nitrogen balance can be useful, but its shortcomings should be recognized. 19. 21 The 24-hour urine urea nitrogen (UUN) is widely used for nitrogen balance determination. Urine contains significant nonurea nitrogen, for which the UUN must be corrected. We use the following correction factor, which was derived from hypermetabolic patients: Total urinary nitrogen (TUN)
=
UUN/O.80
or TUN
=
UUN
X
1.25
With the TUN as an approximation of the total nitrogen loss, the nitrogen balance can be calculated. A confounding factor in nitrogen balance is the use of blood and blood products, especially albumin. 19 A unit of whole blood or packed cells contains about 11 gm of nitrogen in the hemoglobin. Similarly, 50 gm of albumin contains 8 gm of nitrogen. There is no way of determining how long a given amount of exogenous hemoglobin or albumin will last in the body, except that it will be broken down more rapidly than endogenous protein. The standard practice is to ignore exogenous blood and albumin when calculating nitrogen balance. This appears to be acceptable, at least in the short term. 21 Nitrogen and protein requirements can be calculated from the energy expenditure. 18 Assuming the desired nonprotein calorie-to-nitrogen ratio is 100, then: Grams of nitrogen Grams of protein
=
=
energy expenditure/125
6.25
X
(grams of nitrogen)
Calorie-to-Nitrogen Ratio The term "calorie-to-nitrogen ratio" (C/N) is often used as a shorthand for the relation between protein and calories. A normal C/N is 150 to 250. The ratio in stress is 80 to 125. In using this ratio, both components must increase with increasing stress. To increase the proportion of protein without increasing total calories will result in the protein being broken down for
NUTRITIONAL SUPPORT IN THE INJURED PATIENT
543
energy. Dietitians tend to express the same concept as the percentage of total calories supplied by protein. A normal percentage is 15%. A C/N ratio of 125 is equivalent to 20% of the calories being supplied as protein.
ROUTE OF ADMINISTRATION Enteral feeding is preferable to parenteral feeding, as enteral feeding maintains the integrity of the gut mucosa. Exclusive use of total parenteral nutrition may be associated with a loss of the normal gut mucosal barrier, bacterial translocation, and possibly sepsis. In animal studies, enteral nutrition is associated with lower energy requirements, better maintenance of body weight, and fewer septic episodes. 31 Several investigators8 • 26, 29 have shown the efficacy of enteral nutrition and its general superiority to parenteral feeding in patients who can tolerate either mode of nutrient delivery. The Enteral Strategy The general strategy is to feed early, preferably within 24 hours of injury. As any surgeon knows, feeding the patient immediately after a major injury can be difficult. The patient does not eat readily, may not be conscious, and may be dependent on ventilatory support. Ileus may be present, especially after abdominal surgery. The route of administration, then, depends on the patient's condition and the type and severity of injury. For extremity trauma, the patient may be able to eat, but patients with burns or other injuries interfering with eating may require feeding tubes. Abdominal injuries are a special case, because the injury and the operation combine to produce ileus. The ileus is selective; the stomach and the colon are inactive, but the small bowel often continues to work normally. To exploit this, the catheter jejunostomy has been advocated. 27 This is a small catheter placed into the jejunum just past the ligament of Treitz, advanced 15 cm distally into the small bowel, and brought out proximally through the abdominal wall. Feedings can be started within a few hours of operation. The small catheter will not allow infusion of thick feeding solutions, and a low-viscosity defined-formula diet is best. Significant time is required in building up intestinal tolerance to enteral feedings. Starting with half-strength solution at 50 mllhour, one progresses daily to threequarter strength and then to full strength; then to 70 mllhour, and finally to 100 mllhour. It usually takes about 5 days to advance to delivery of sufficient calories to meet requirements. Needle catheter jejunostomy is a very useful technique. Diarrhea is fairly common but easily treated. Intestinal obstruction from torsion of the bowel about the catheter occurs, as does pneumatosis intestinalis. A few patients, usually those with small-bowel or retroperitoneal injuries, have persistent ileus. The principal limitation of the technique is the long leadin time before full enteral nutrition can be given.
544
CHARLES W. VAN WAY
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The Parenteral Strategy The major advantage of parenteral nutrition is that one can provide the patient with full nutritional requirements within 12 to 24 hours. If the patient was malnourished before injury, is expected to have intolerance to enteral nutrition, or is to be returned to the operating room frequently, total parenteral nutrition may allow full nutritional support. Our practice is to start questionable patients on a peripheral parenteral nutrition regimen. We use a premixed bag containing 2900 ml, which includes 1000 gm of fat, 60 gm of amino acids, and 240 gm of glucose, together with electrolytes and vitamins. This formula can be given at 120 mllhour to virtually anyone without risk of glucose intolerance. Because it is standardized, the cost is relatively low, about twice that of a definedformula enteral diet. The solution can be given through a central line, if one is in place, or peripherally. The total of 2000 calories and 60 gm of nitrogen is adequate on average but low for a seriously hypermetabolic patient. This regimen is used for 5 to 7 days, by which time the patient usually is on full enteral nutrition or is eating. In the few patients who still require parenteral nutrition, high-nitrogen central total parenteral nutrition is a good interim regimen while enteral tolerance is being achieved. BURNS Burn wounds produce the highest metabolic stress of all injuries. The response produced by a large burn (>50% BSA) approaches the maximum metabolic capacity. Even relatively small burns may evoke a large response. The hypermetabolism cannot be suppressed and must be treated. If the patient is to survive, enough calories and protein must be given to meet the extreme demands. Energy Expenditure in Burns Many factors increase energy expenditure. The skin is the largest organ in the body. Injury to muscle and connective tissue adds to the stress. The inflammatory response occurs over a large area. The immune system is activated. The barrier function of the skin is partially lost, exposing the immune system to a host of exogenous challenges. Heat and water loss is accelerated from burned areas. Evaporative water loss per day is about 25 mllper cent burn, leading to energy loss from evaporation of 15 kcallper cent burn per day. The core temperature rises. Secondary infection and sepsis may further increase metabolic demands. Burns have been felt to be "quantifiable" injuries, in which the severity can be determined by estimating the amount of burned BSA. IO• 23 The familiar "rule of 9s" allows this estimate to be made easily and quickly. Estimation of fluid resuscitation by this principle has proved to be fairly accurate using the formula: Fluid per 1st 24 hours = 4
X
% burn
X
body weight (in kg)
The estimate of energy needs is often made using the same principle.
545
NUTRITIONAL SUPPORT IN THE INJURED PATIENT
The multipliers used in the Harris-Benedict equations are commonly based on the burn size: TEE = BEE
X
activity factor
X
stress factor
where the activity factor = 1.2 for bedridden patients and 1.3 for ambulatory patients, and the stress factor = 1.5 for small burns «20%), 1.8 for moderate burns (20% to 50%), and 2.1 for severe burns (>50%). The Curreri formula estimates energy requirements attributable to the burn injury as 40 kcal/per cent burn and calculates basal energy requirements as 25 kcallkg: 1O TEE = 25
X
(weight)
+
40
X
(per cent burn)
Burns exceeding 50% are considered as if they were 50%. Measurement of the patient's energy metabolism with a metabolic cart is probably more accurate than using a formula. 5, 22 Gottschlich and associates l5 found that measuring rather than calculating energy expenditure resulted in a mean caloric requirement of only 2900 kcal, considerably less than would have been predicted by the formulas, Protein Metabolism in Burned Patients A patient with a large burn may lose 30 gm of nitrogen per day. The patient should be put into positive nitrogen balance as quickly as possible. Excess protein is better than just enough to meet needs. l Fat Metabolism in Burned Patients After burn injury, serum levels of free fatty acids and glycerol increase, presumably from the breakdown of adipose tissue. This increase is not associated with increased utilization. In severely hypermetabolic patients, fat may not be as effective in conserving nitrogen as carbohydrates. Fat should supply no more than 20% of the total calories. The same may be said for severely stressed and septic patients; the later stages of sepsis are said to be associated with poor fat utilization.
CONTROVERSIES AND CURRENT ISSUES The Gut Hypothesis and Glutamine Glutamine is important in the maintenance of gut mucosal integrity. The theory is as follows. The gut mucosal barrier is interrupted by shock or trauma. In shock, for example, blood flow to the gut is markedly diminished. The gut mucosa is dependent on glutamine as a source of energy and presumably as a nitrogen donor in protein synthesis. Glutamine is not generally regarded as an essential amino acid, but it does appear to be vital to the mucosal cells of the gut. Maintenance of the gut mucosal barrier to bacteria and bacterial products is impaired by a glutamine-free diet or by not giving oral nutrients at all. 33, 34
546
CHARLES W. VAN WAY
III
Most parenteral regimens do not contain glutamine. The N-terminal nitrogen of glutamine tends to break off as ammonia, and ammonia in total parenteral nutrition solutions is obviously not desirable. Most commercial amino acid preparations contain glutamic acid, but not glutamine. This limitation of parenteral nutrition may contribute to the superiority of enteral nutrition formulations, which generally contain glutamine. Immunonutrition Much recent work has attempted to modulate the immune system by nutrition. Considering that malnutrition impairs the immune system, nutritional support itself is a general immunomodulator. More specific attention has been directed toward fatty acids, arginine, and nucleic acids. A commercial enteral product, Impact, incorporates all three of these nutrients and is now undergoing clinical trials. 35 Omega-3 Fatty Acids Linoleic acid, which is an essential unsaturated (omega-6) fatty acid, is the precursor for a number of eicosanoids (e.g., prostaglandin E2) that depress the immune system. 20 Substituting omega-3 fatty acids (as in some fish oil) for some of the linoleic acid appears to improve the immune system response. Clinical application has been limited. Gottschlich and coworkers,15 in a study comparing different enteral regimens in burned patients, found that one relatively low in fat calories (20%) and linoleic acid (4%) but containing omega-3 fatty acids (4%) was superior to regimens having more fat but no omega-3 fatty acids. Arginine A semiessential amino acid, argmme is necessary for growth. In humans, provision of arginine in excess of needs has been found to decrease T-suppressor cells, increase T-helper cells, and enhance the lymphocyte response to mitogens. Evidence supports the suggestion that supplying arginine in excess of requirements is beneficial to immune function. 3 . 4 Ribonucleic Acid The nucleic acids are normally synthesized de novo by the body. The turnover of nucleic acids increases markedly in stress, because of the cell synthesis involved in the inflammatory and immune responses. Indirect evidence exists that provision of nucleic acids enhances the immune response. 30 For example, in a study of the response of mice to endotoxin, the provision of RNA reduced bacterial translocation. 34. 35 Branched-chain Amino Acids The use of branched-chain amino acids in managing injury has been based on the observations that muscle breakdown releases large amounts of these substances and that branched-chain amino acids are metabolized primarily in the muscle itself. Providing high levels of branched-chain amino acids therefore may reduce muscle breakdown. The best clinical trial to date, a multicenter trial reported by Cerra et al,9 showed clearly that nitrogen balance was rendered more positive in severely stressed patients
NUTRITIONAL SUPPORT IN THE INJURED PATIENT
547
by the use of a regimen enriched in branched-chain amino acids. However, the data did not show a reduction in nitrogen excretion or in muscle breakdown. Similar clinical trials have been done, with equivocal results. A number of workers have emphasized the use of branched-chain amino acids in stressed patients, and more particularly in the injured patient. The evidence at present is insufficient to recommend this as a general practice, but in the hypermetabolic injured patient, branched-chain amino acids may indeed have merit.
CONCLUSION Nutritional support should be started as soon as possible after injury and should be maintained as long as the patient does not eat. Enteral nutrition is considered to be a better option than parenteral nutrition, aI~d every effort should be made to use the gut. Even partial gut feeding with sufficient parenteral supplementation to meet nutritional requirements appears to be superior to total parenteral nutrition in the injured patient. Although it is difficult to show an unequivocal increase in survival with adequate nutrition, studies have shown that nutritional support decreases complications following major injuries.
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16. Green AR: Peptide regulatory factors: Multifunctional mediators of cellular growth and differentiation. Lancet 1:705-764, 1989 17. Lemoyne M, Jeejeebhoy KN: Total parenteral nutrition in the critically ill patient. Chest 89:571-575, 1986 18. Long CL, Shaffe N, Geiger J, et al: Metabolic response to injury and illness: Estimation of energy and protein needs from indirect calorimetry and nitrogen balance. JPEN 3:452-456, 1979 19. Lundholm K, Bennegard K, Wickstrom I, et al: Is it possible to evaluate the efficacy of amino acid solutions after major surgical procedures or accidental injuries? JPEN 10:2933, 1986 20. Kinsellsa JE, Lokesh B, Boughton S, et al: Dietary polyunsaturated fatty acids and eicosanoids: Potential effects on the modulation of inflammatory and immune cells. Nutrition 6:24-44, 1990 21. Kopple JD: Uses and limitations of the balance technique. JPEN 11:79S-85S, 1987 22. Mancusi-Ungaro HR, Van Way CW, McCool C: Caloric and nitrogen balance as predictors of nutritional outcome in burn injured patients. J Burn Care Rehab (in press) 23. Matsuda T, Kagan RJ, Hanumadass M, et al: The importance of burn wound size in determining the optimal calorie:nitrogen ratio. Surgery 94:562-568, 1983 24. Metcalf 0: Haemopoietic growth factors: 1 and 2. Lancet 1:825-942, 1989 25. Michie HR, Spriggs DR, Manogue KR, et al: Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery 4:280, 1988 26. Moore EE, Jones TN: Benefits of immediate jejunostomy feeding after major abdominal trauma: A prospective randomized study. J Trauma 26:874, 1986 27. Moore EE, Van Way CW: Needle-catheter jejunostomy. In O'Leary JP, Woltering EA (eds): Techniques for Surgeons. New York, John Wiley & Sons, 1985, pp 90-95 28. O'Garra A: Interleukins and the immune system: 1 and 2. Lancet 1:943-959, 1989 29. Peterson VM, Moore EE, Jones TN, et al: TEN versus TPN following major torso injury: Attenuation of hepatic protein reprioritization. Surgery 4: 199, 1988 30. Rudolph FB, Kulkarni AD, Fanslow WC, et al: Role of RNA as a dietary source of pyrimidines and purines in immune function. Nutrition 6:45-52, 1990 31. Saito H, Trocki 0, Alexander JW, et al: The effect of route of nutrient administration on the nutritional state, catabolic hormones, and gut integrity after burn injury. JPEN 11:1-7, 1986 32. Shaw JHF, Wolfe RR: An integrated analysis of glucose, fat, and protein metabolism in severely traumatized patients. Ann Surg 209:63-72, 1989 33. Souba WW, Smith RJ, Wilmore OW: Glutamine metabolism by the intestinal tract. JPEN 9:608, 1985 34. Wells CL, Jechorek RP, Erlandsen SL, et al: The effect of dietary glutamine and dietary RNA on ileal flora, ileal histology, and bacterial translocation in mice. Nutrition 6:7075, 1990 35. Wells CL, Jechorek RP, Laven PT, et al: The effect of a uniquely formulated diet (supplemented with arginine, RNA, and menhaden oil) on ileal flora, ileal histology, and bacterial translocation in mice. Nutrition 6:76-80, 1990 36. Wilmore DW, Aulick LH, Becker RA: Hormones and the Control of Metabolism. In Fischer J (ed): Surgical Nutrition. Boston, Little, Brown, 1983, chap 3 37. Wilmore OW, Orcutt TW, Mason AD, et al: Alterations in hypothalamic function following thermal injury. J Trauma 15:697, 1975
Address reprint requests to Charles W. Van Way III, MD Department of Medical Education St. Luke's Hospital 4400 Wornall Road Kansas City, MO 64111
