burn patients suffer chronic Vitamin D deficiency. This would imply that oral supplementation would be both necessary and helpful in enhancing Vitamin D levels in burn patients and improving bone metabolism. However, in one study oral Vitamin D supplementation did not improve serum levels in a group of burned children [47]. In addition, treatment of burned children with intravenous administration of the bisphosphonate pamidronate was associated with improved bone mineral content after six months, apparently by reducing the bone resorption in these patients[48]. As a result of this experience, it remains unknown whether vitamin D supplements are effective in burn patients and what the correct dose should be. Since all standard multivitamins contain substantial amounts of vitamin D, that is the only supplementation that is recommended at present.

Zinc is the antioxidant trace mineral that is most often routinely supplemented in burn centers. Zinc plays important roles in collagen cross-linking, wound healing, and immune function, and zinc levels have been shown to be depleted in burn patients due to the combination of urinary losses and exudative losses from wounds [49, 50]. Combined IV supplementation of zinc, selenium, and copper has demonstrated increased tissue levels and has resulted clinically in improved wound healing, decreased pulmonary infections, and diminished length of hospital stay [51–53]. However, this strategy has not been widely adopted outside of Europe; best current recommendation from a U. S. center has been for supplementation of zinc only with 200 mg of enteral zinc sulfate, recognizing that this dose may be associated with significant nausea and may interfere with the absorption of copper [42].

Trace mineral supplementation and its application to burn care is an area ripe for future research.

Application: Calories and macronutrients: The patient described in the case above weighed 85 kg and was 180 cm in height. If Harris-Benedict estimation of REE X 1.2 was used for initial calculation, his initial energy goal was 2 356 kcal/ day. If protein was set at 2 grams/ kg/day, the patient received 170 grams of protein, or 680 protein calories. Lipids should not exceed 350 kcal/day (39 grams) if they were to provide less than 15% of caloric demands. The balance of calories were supplied by carbohydrates, totaling

329 grams or 1 314 kcal (56% of estimated daily energy requirement).

Micronutrients: The patient was also given a daily adult multivitamin in the form of an enteral liquid preparation via nasoenteric tube. Administration of 1000 IU of Vitamin A, 500 mg of Vitamin C, and 220 mg of Zinc Sulfate on a daily basis were considered although none were administered. All micronutrient supplementation was enteral.

Formulations for nutritional support

A variety of nutrient formulations are available for enteral nutrition of burn patients, as well as a number of pre-packaged supplements to standard products. While it is possible to prepare customized enteral formulations, this is extremely expensive and timeconsuming, so clinicians should select a commercially available formula in feeding the patient presented in the case scenario. Parenteral nutrition, conversely, is made as needed from components and is easy to customize. Before beginning either type of nutrition the role of specific nutrients in crit- ically-ill patients should be considered.

Calorie considerations: As discussed previously, estimates of total calories required for nutritional support are often used to guide the infusion rate of enteral or parenteral nutrient solutions. In planning this, however, clinicians should remember than other infusions can contain significant calories. In particular, dextrose-containing intravenous fluids given to provide adequate hydration contain significant calories; a liter of 5% dextrose contains 50 grams of dextrose, or almost 200 kcal. Because burn patients require large amounts of fluid to counteract evaporative losses, this can amount to a significant caloric load in itself. In addition, some medications may be given in dextrose-containing fluids. The sedative agent propofol is becoming increasingly popular in burn care, but propofol is a lipid emulsion that contains 1.1 kcal/mL. Use of these agents commonly leads to significant overfeeding unless these calories are calculated into the total requirements of the patient [54]. Also, because neither of these sources contains any protein, this increases the need to use high-protein nutrition to compensate for the effect of these “empty” calories.

Dietary fat and fatty acids: The potential benefits of low-fat diets have been discussed previously. Most common lipid sources contain mainly omega-6 fatty acids ( -6 FFA’s). These acids are metabolized through synthesis of arachadonic acid, a precursor of pro-inflammatory cytokines. Lipids such as fish oil (FO) contain mostly -3 FFA’s, which are metabolized without creating pro-inflammatory compounds. Diets high in -3 FFA’s have been associated with improved outcomes in a variety of clinical situations [55] and have been specifically recommended for use in patients with acute lung injury, in whom aggravated inflammation is thought to play an important pathophysiologic role [3]. Excessive inflammatory response from a pulmonary source may be an issue in some burn patients and use of diets high in -3 FFA’s may have clinical advantages in this setting [56].

Protein composition: Glutamine (GLU): In addition to providing high-protein nutrition, the specific composition of the protein provided may be important in providing optimal nutrition to burn patients. The amino acids alanine and glutamine are important “transport” amino acids, elaborated in large quantities from skeletal muscle to supply energy to the liver and to healing wounds[57]. Glutamine performs other important roles, acting as a primary nutrient for gut enterocytes [58] and enhancing production of protective heat shock proteins [59]. Glutamine appears to reduce gut permeability and elaboration of inflammatory mediators and reduces infections in critically-ill patients [60]. Glutamine is almost entirely absent from standard PN solutions, which may partially explain the increased infections observed in association with PN use.

Glutamine may be of particular value to burn and trauma patients. Supplemental glutamine given either enterally [61, 62] or parenterally [63, 64] has been associated with reduced infectious complications and mortality in several small studies in burn patients. Because its effects are best seen when glutamine is given at high doses (≥ 0.25 gm/kg/day, or ≥ 18 gm/day in a 70-kg patient), specific supplementation of enteral formulations with glutamine is necessary to obtain its benefits and this supplementation should be used in addition to the high protein content recommended for all burn patients. Glutamine-containing enteral nutrition is recom-

mended for critically-ill populations, including burns [3], and many burn centers currently use it [23] in spite of the absence of conclusive data to support glutamine supplementation. A multicenter randomized trial to assess the benefits of glutamine supplementation in burns is currently underway.

Arginine (ARG): Arginine is another important amino acid in post-burn metabolism. Arginine stimulates T-lymphocytes and enhances synthesis of nitric oxide, both of which enhance immunity and inflammation [65]. Arginine-enhanced nutrition appears to be of value in reducing infections and improving wound healing, and stabilizing inflammation after burn injury [66]. However, there are reports of increased mortality in septic patients receiving arginine-containing formulas. Burn patients are at risk of this complication, making it difficult to advocate for the routine addition of arginine to the diets of burn patients.

Immune-enhancing diets: Because the potential value of the nutrients reviewed above appeared to be both clinically and commercially significant, few trials of individual compounds have been performed. Instead, they were quickly combined into “immune-enhancing” diets (IED’s) containing GLU, ARG, -3 FFA’s, and other compounds. In one early study, a customized low-fat diet supplemented with-3 FFA’s, histidine, ARG, RNA, and vitamins was associated with reduced infections and mortality in a group of burned children [67]. IED’s have been evaluated subsequently in a variety of clinical settings, with demonstration of reduced infections and hospital stay in some trauma and ICU populations [68, 69], but deleterious or no effects in patients with sepsis or pneumonia [70]. These inconsistent results have been attributed to the pro-inflammatory effects of ARG, which may be beneficial in preventing postoperative infections but harmful to patients with acute lung injury, possibly including burn patients [71].

This confusing experience serves to underscore the imperfect status of our knowledge of nutrition in various disease states, In addition, the rush to create commercially-available “cocktails” for clinical use has further obscured our understanding of the action of each of these specific nutrients. As a result, recommendations for use of these supplements are somewhat contradictory. In some publications standard

multi-component IED’s have been recommended for acutely injured patients, including burn victims, but not for patients with acute lung injury or severe sepsis, for whom -3-enhanced diets are suggested [3]. The benefits of these multi-component IED’s have not been clearly demonstrated in burn patients [72, 73]; some reviews have not recommended IED’s for this group [5, 74]. This appears to be one area of critical care in which data from one patient population CANNOT be safely extrapolated to others. As a result, there is little consistency in the nutritional regimens practiced among burn centers [75]. More conclusive recommendations will require the results of well-designed, large-scale clinical trials.

Parenteral nutrition: One advantage of PN is the ability (or necessity) to prepare customized formulas for each patient daily. Parenteral nutrition relies primarily on concentrated dextrose as an energy source. Protein is provided in the form of amino acids, but because glutamine is not stable in suspension it is almost entirely absent from PN formulations. Lipids can be provided as a soy-based lipid emulsion (Intralipid – Pharmacia/Upjohn). Vitamins, trace elements and some additional medications such as insulin or heparin can also be added. Also, because these solutions are hypertonic, free water can be added which reduces the need for additional dextrose-containing IV infusions. Parenteral formulations must be made by pharmacy professionals under strict sterile guidelines, and require central venous access for delivery.

Clinicians attempting to create the “ideal” PN solution encounter a paradox: data cited above suggests that nutrition should be low in fat, but that means providing most calories as dextrose with attendant problems of hyperglycemia. Supplemental insulin – which can be added directly to PN solutions – is very often necessary to help control blood sugar, but even with aggressive insulin infusions, hyperglycemia can become a critical problem. The challenge of hyperglycemia is addressed in more detail in the section on complications of nutrition.

Enteral nutrition: A bewildering array of commercial formulas is available for nutritional support. A selection of these is reviewed in Table 2. Before resorting to any of these, remember that many burn patients who tolerate oral intake may need only supplementation. Early diets using eggs, milk, and other

inexpensive products were successful in many patients [76]. Patients often enjoy good-tasting milkshakes made with these products and powdered supplements (e. g., Instant Breakfast , Nestle), or prepared supplements like Boost (Nestle). These formulations can also be infused into large-bore gastric tubes but are usually too thick for use in small enteral feeding tubes.

Reviewing Table 2 will reveal that the range of available commercial products is limited, restricting our ability to “mix and match” specific components. Based on the information reviewed previously, an “ideal” enteral formula might include the following: high-protein (NPCal:N2 of ≤ 100:1), low fat ( > 15%), a high proportion of -3 FFA’s, and a substantial dose (≥ 0.25 gm/Kg) of glutamine. Regardless, no commercial formula currently exists which combines all of these characteristics, leaving clinicians to select the components they think will be most helpful for particular situations. Complications such as diarrhea may limit the use of some formulas or require the addition of fiber. Cost and availability are also issues. Some of the formulas reviewed are intended for very specialized situations such as renal or respiratory failure. They are not well suited for general use in burn patients and are often far more expensive than “standard” formulas.

Clinicians can try to overcome the limitations of available formulas in two ways. First, formulas can be supplemented with protein, carbohydrates, fats, vitamins, fiber, or other specific components. Glutamine is now available as an additive for enteral nutrition but not for PN. Use of these agents can help make up for specific deficiencies of commercial formulas. Some standard additives are included in Table 3. Second, some units have resorted to use of elemental or semi-elemental diets. These diets contain simple carbohydrates, medium-chain triglycerides, and either free amino acids or short peptides. They require almost no digestion and are ideal for patients with short bowel or other absorptive problems. They can be also supplemented with additional nutrients in patients with the ability to digest them. They are relatively expensive, however, and because of increased osmolarity can be associated with diarrhea.

Application: For the patient presented previously, enteral nutrition was begun using Promote (Ab-

bott), a relatively inexpensive, high-protein formula. Infusion through the enteral tube was begun at 25 mL/hr and increased by 10 mL/hr increments every four hours, with a theoretical target rate of 100 mL hr (2,400 Kcal/day). However, at this time the patient was also receiving approximately 285 mL/ hr of dextrose-containing maintenance IV fluid, which provided approximately 200 kcal/liter, or a total of 1,162 kcal/day. As the tube feedings were increased, this maintenance rate was reduced correspondingly. However, the problem of attempting to provide adequate amounts of fluid and protein while avoiding overfeeding total calories persisted. This required a compromise: tube feedings were increased to 90 mL/hr, plus a free water “flush” of 25 mL/hr, and IV fluid was reduced to 125 mL/hr. This provided 2,760 total calories (600 from intravenous dextrose, 2,160 from tube feedings) and 134 gm protein (1.6 gm/kg/D).

Any of the other “stress” formulas listed in the table would have been reasonable choices for this patient. ARG-supplemented formulas were not selected because of the patient’s inhalation injury. The addition of supplemental glutamine could also be considered, but definitive support for this is pending the results of the ongoing randomized controlled trial. Finally, more free water could have been added to the tube feedings to increase fluid intake, which

would have permitted reduction in IV fluids, but significant intake of oral/enteral free water is often associated with hyponatremia following burn injury.

This example indicates some of the issues which must be considered in providing optimal nourishment to severely burned patients. The value of a team-oriented nutrition protocol in this setting is apparent.

Modulation of hypermetabolism: Burn-related hormonal changes create tremendous problems in nutritional support, but also provide mechanisms by which hypermetabolism can be manipulated and at least partially controlled. Recent studies have suggested that manipulation of the metabolic response to injury can be beneficial in burn patients and other groups; this may become routine in the future. A variety of approaches have been utilized, including beta-blockade with propranolol, low-dose insulin infusions, use of counter-regulatory hormones such as insulin-like growth factor-1 (IGF-1), or anabolic agents such as testosterone and oxandrolone [77]. Use of propranolol appears to ameliorate both the cardiovascular response to acute burn injury, and reduce hypermetabolic muscle wasting during acute burn care [78]. Administration of the synthetic oral androgen oxandrolone has been shown to reduce muscle breakdown, speed rehabilitation, and lead to decreased length of stay in hospitalized patients [79,