ing protein-energy malnutrition, significant weight loss, and micronutrient deficiencies.1 Malnutrition may impair tissue healing and increase the risk of infection. Patients with major burns should receive a high-calorie, high-protein diet, preferably by the enteral route and individualized according to their needs. Beginning enteral feeding immediately or within several hours after hospitalization, as opposed to delaying the start of feeding, may improve clinical outcome.2 In some cases, parenteral nutri- tion may be necessary. However, the combination of parenteral and maximally tolerated enteral nutrition can increase morbidity and mortality relative to enteral feeding alone, possibly because of metabolic abnormalities resulting from overfeeding.3

Deficiencies of zinc, copper, and selenium can occur after burns as a result of increased renal excretion of these minerals, losses through the burned skin, and sloughing of necrotic tis- sue.4-8 The severity of the deficiencies increases with increased burn injury. During the first 7 days following a major burn, as much as 5% to 10% of the total body zinc content and 20% to 40% of the total body copper content can be lost through the skin.9

Zinc and copper both play a role in tissue healing, and the requirements for these nutrients are presumably increased during the healing phase following a burn. One group of investigators observed that the rate of epithelialization appeared to be faster and graft acceptance seemed to be better in burn patients supple- mented with zinc than in those not given zinc.10 In addition, zinc, copper, and selenium each play a role in immune function. Consequently, a deficiency of one or more of these minerals could increase susceptibility to infection following a severe burn.

In studies of patients with major burns, intravenous (IV) administration of zinc, copper, and selenium decreased the inci- dence of pneumonia, reduced the amount of time in intensive

Twenty patients (mean age, 40 years) with burns on a mean of 48% of their body surface were studied for 30 days after injury. Beginning as soon as possible after the burn, they were ran- domly assigned to receive, in double-blind fashion, doses that were higher than standard (406 µmol of zinc, 40.4 µmol of cop- per, and 2.9 µmol of selenium) or standard (100 µmol of zinc, 20 µmol of copper, and 0.4 µmol of selenium) intravenously each day for 8 days. After this, the mean number of infections per patient was 39% lower in the higher group than in the standard group (1.9 vs 3.1;P<.05); this decrease was due to an 80% reduc- tion in the number of episodes of bronchopneumonia. The mean duration of stay in the intensive care unit (ICU), adjusted for the percent of body surface area burned, was 33% less in the intervention group than in the control group (P<.04).11

Twenty-one patients (mean age, 35 years) with burns on a mean of 45% of body surface area were randomly assigned to receive daily IV infusions of trace minerals (37.5 mg of zinc, 3.75 mg of copper, and 375µg of selenium) administered in 250 mL of 0.9% saline over 12 hours or placebo (saline alone). Treatment was started within 12 hours of injury and was continued for 14 days if the burn covered 20% to 60% of body surface area or for 21 days if the burn exceeded 60% of surface area. The mean number of infections per patient during the first 30 days was 42% lower in the active-treatment group than in the placebo group (2.1 vs 3.6;P=.01). This reduction was due primarily to a decrease in the number of pulmonary infections (P=.03). Wound healing was also improved in the active-treatment group, with lower requirements for repeated grafting (P=.02).12

In a pooled analysis of the 2 studies cited above, compared with placebo, active treatment reduced the mean number of infections by 43% (2 vs 3.5 episodes per patient;P<.001), the incidence of pneumonia by 59% (33% vs 80%;P<.001), and the mean duration of stay in the ICU (days per percent of burned body surface area) by 36% (P=.002).13

Burns can result from heat (thermal burns), chemical exposure, or radiation. This article is restricted to a discussion of thermal burns (henceforth called burns), which are catego- rized according to severity. First-degree burns involve only the epidermis, second-degree burns involve the epidermis and portions of the dermis, and third-degree burns (also called full-thickness burns) affect the epidermis and the entire der- mis. Morbidity and mortality are related to the depth and location of the burn, as well as to the percentage of body sur- face area affected. Complications of severe burns may include pneumonia and other infections. Treatment of burns varies

according to severity and may include debridement of dam- aged tissue, topical application of antibiotics, administration of medication to relieve pain, and intravenous fluids to replace fluids lost through the burned skin. Major burns can be life threatening and may require intensive treatment at a special- ized burn center.

The evidence reviewed here indicates that dietary inter- ventions and nutritional supplements can play an important role in improving clinical outcomes in burn victims. In addi- tion, honey and potato peels have each been found to be use- ful for topical application in the treatment of burns.

One report on vitamin A levels in the serum of burned patients showed that these serum levels declined significantly after major burns. This decrease may have been due in part to a lack of retinol-binding protein secondary to protein deficiency, because oral vitamin A supplementation did not increase serum vitamin A levels but vitamin A levels returned to normal as soon as the burn victims were able to tolerate a high-protein diet.14,15 In mice, intraperitoneal administration of 3000 IU of vitamin A blunted the decline in cell-mediated immunity that resulted from extensive burn injury.16

In clinical settings, parenteral administration of vitamin A has been shown to reduce the incidence of gastric and duodenal ulcers in patients with major burns or other severe physiologic

Fifty-two patients with burns over 25% of their body surface or other severe physiological stresses (major trauma or major postoperative disturbances) were randomly assigned to receive parenteral water-soluble vitamin A (Aquasol-A, water-miscible vitamin A palmitate) or no vitamin A (control group). The dose was 100 000 IU 2x/d for adults and 50 000 IU 2x/d for children. The dosage was doubled if the serum vitamin A level did not promptly become normal. It was not stated how many days vitamin A was given. The incidence of stress ulceration was sig- nificantly lower in the vitamin A group than in the control group (18% vs 63%;P<.05).15

Debridement of damaged tissue,
topical antibiotics,
analgesics,

Enteral feeding
ASAP after
admission to burn
treatment facility

Nutritionally
support tissue
regeneration &

Apply selected
topical healing
preparations

Depression
Hallucinations
Muscle cramps, tremors
Aminoglycoside
treatment

include antacids, H2 blockers, proton pump inhibitors, or sulcra- fate. While these treatments decrease the incidence of such ulcers, they do not prevent them completely. Combining conventional therapy with short-term, high-dose vitamin A might be more effec- tive for ulcer prophylaxis than either of these treatments alone.

As an antioxidant, vitamin C may decrease the extent of free radical–induced tissue damage following a burn.17 Low plasma vitamin C concentrations have been observed in patients after severe burns.18

In dogs subjected to burns of a hind paw, IV administration of vitamin C (14 mg/kg body weight per hour) decreased micro- vascular leakage of fluid and protein from the burned tissue.19 In guinea pigs subjected to deep dermal burns over 70% of their body surface area, administration of large doses of IV vitamin C (170 mg/kg body weight per day) decreased by 75% the amount of IV fluids needed to prevent hypovolemic shock. Vitamin C appeared to work by minimizing the post-burn increase in capil- lary permeability, thereby decreasing the leakage of plasma into the interstitial space.20 Similar results were seen in guinea pigs subjected to third-degree burns over 70% of their body surface area and treated with IV vitamin C at a dose of 340 mg/kg body weight per day.21 In mice, daily intraperitoneal administration of 25 to 50 mg of vitamin C for 5 days following a full-thickness burn dose-dependently decreased the severity of the burn.22

One practitioner reported that topical application of vita- min C combined with oral or parenteral administration of the vitamin was beneficial for patients with burns. Sixty-two patients with mild, moderate, or severe burns received topical applications of 1% ascorbic acid in normal saline or distilled water or a 2% ascorbic acid ointment in a water-soluble base. Vitamin C was also given orally, intramuscularly, or intrave- nously at a dose of 500 to 2000 mg/day for adults and 300 to 900 mg per day for children. This vitamin C treatment appeared to relieve pain and accelerate healing. In addition, the hoarse- ness and pain resulting from swallowing smoke was alleviated by gargling or spraying the throat with a 1% solution of ascorbic acid in normal saline.23

In a randomized controlled trial, IV administration of a large dose of vitamin C improved clinical outcome in patients with extensive burns. Thirty-seven patients with burns over more than 30% of their body surface area who were hospitalized within 2 hours after injury were randomly assigned to receive IV vitamin C (66 mg/kg body weight per hour for 24 hours) or no vitamin C (controls). Lactated Ringers solution (isotonic with blood) was given to maintain stable hemodynamic measurements and ade- quate urine output. Compared with the control group, the vitamin C group required a mean of 45.5% less IV fluid per percent of burn area (P<.01), had significantly less wound edema and significantly less severe respiratory dysfunction, and required significantly fewer days of mechanical ventilation (12.1 days vs 21.3 days;

group than in the control group (47% vs 39%), but this increase may have been due to the greater mean burn size in the former than in the latter (63% vs 53% of body surface area).24

Patients with major burns lose increased amounts of mag- nesium in the urine, as well as from exudation of fluid through the burned skin and from sloughing of necrotic tissue. In addi- tion, magnesium requirements are increased during the healing phase of burns.4,25 In a case report, magnesium deficiency was implicated as the cause of hypokalemia that failed to respond to potassium therapy in a patient with massive burns.26 Many burned patients exhibit psychiatric and physical symptoms that resemble those of magnesium deficiency: Of 8 patients who developed hypomagnesemia after burns, 5 experienced symp- toms such as depression, hallucinations, muscle cramps, or tremors; these symptoms responded to oral or IV administra- tion of magnesium.27

Patients with extensive burns may be treated with amino- glycosides (eg, gentamicin or tobramycin), which can exacerbate magnesium deficiency by increasing urinary magnesium excre- tion.28 These patients may need aggressive magnesium supple- mentation, including IV administration.

Glutamine is considered a nonessential amino acid under normal circumstances. Under conditions of extreme stress (such as major burns), additional amounts are needed to support immune function, increase energy production, and enhance tis- sue repair.29 In a study reported in The Lancet in 1990, the mean plasma glutamine concentration was 58% lower in patients with severe burns than in healthy controls.30 Glutamine deficiency may contribute to the impairment of immune function that occurs after major burns.

In mice, glutamine supplementation prevented the increase in susceptibility to infection following a burn injury.31 In various clinical trials, as described in the paragraphs below, the addition of glutamine to standard enteral or parenteral nutrition mini- mized the degree of immunosuppression, enhanced wound healing, decreased the incidence of septicemia, reduced the duration of hospital stays, and decreased mortality in patients with severe burns.

Forty-eight severely burned patients (total burn surface area, 30% to 75%; full-thickness burn area, 20% to 58%) were randomly assigned to receive, in double-blind fashion, standard enteral nutrition supplemented with glutamine or placebo (gly- cine) at a dose of 0.5 g/kg body weight per day for 14 days. Compared with placebo, glutamine significantly improved vari- ous parameters of cellular immune function, including lympho- cyte transformation ratio, neutrophil phagocytosis index, CD4/ CD8 ratio, and interleukin-2 levels. The mean duration of hospi- tal stay was 16% less in the glutamine group than in the placebo group (46.6 days vs 55.7 days;P<.05).32

Twenty-six patients with severe burns (total burn surface area, 25% to 90%) were randomly assigned to receive, in double- blind fashion, IV glutamine (0.57 g/kg body weight per day) or an isonitrogenous mixed amino acid solution (FreAmine) as a continuous infusion during their stay in the ICU. The incidence of Gram-negative bacteremia was significantly lower in the glu- tamine group than in the FreAmine group (8% vs 43%;P<.04).