Patients with severe extensive burns may experience multiple nutrient losses leading to a combination of energy depletion that may last for weeks. Especially in patients with severe burns the hypermetabolic state is more pronounced and lasts longer than in other traumas. The first manifestation of all traumatization processes is the stress response. The trauma leads to a hypermetabolic state due to the increased neuroendocrine activity of the body and the mobilization of nutrient reserves to provide the body with the additional demand for energy.1 The body’s reserves of carbohydrates, which are the most basic form of energy, are easily and rapidly depleted. The body’s energy needs are then met with proteins and fats, which are directly oxidized, and proteins, which provide the necessary intermediates for the production of glucose. However, if protein is used as an energy-producing substance, it is likely to lead to a massive catabolism of lean body tissue, especially muscle.2 After the acute phase of trauma, a hypercatabolic state persists in the burn victim despite the waning of the adrenergic response.1 Prolonged hypercatabolism of proteins as well as the loss of lean body mass may lead to dysfunction and even death. Hypercatabolism is more complex in the later stages of burn injury, but the depletion of nutrients from the burn wound becomes an important factor in the persistence of a hypercatabolic state. Burn wounds cause high energy demand through several pathways: one of the most dramatic increases in metabolism in burn patients is high vapor water loss, a unique outcome of thermal burns.3 Skin breakdown in burn injuries results in a reduction in the function of the skin’s anti-evaporative barrier. In burned patients, vapor water loss may be 10-12 times higher than the normal rate of loss.4 Water evaporation is an energy-consuming physiological process that typically requires 0.6 kcal/g of water. Total vapor water loss is in equal proportion to the size of the burn. In patients with extensive burns water loss is typically 2.5-4.0 L per day, which requires a daily energy expenditure of 1440-2300 kcal.5 Steam water loss is usually greatest in the first week after burn injury. On the burned body surface, the loss of skin protection also increases nutrient loss. Frequently, large amounts of nitrogen, minerals and trace elements can be detected in the exudate. The skin also acts as an antibacterial protective barrier. After thermal burns this protective barrier disappears and the accumulation of bacteria in the wound and subsequent infection directly increases nutrient loss. Energy expenditure is also increased as host defense mechanisms increase. Macrophages are part of the body’s inflammatory response and are able to ingest and kill bacteria. Reticuloendothelial macrophage activity increases oxygen consumption and energy expenditure after cauterization. The toxic effects of bacterial invasion increase energy expenditure even more. Toxins released in the inflammatory response may elevate body temperature, and fever also brings about thermal energy expenditure. If the virulence of the bacteria exceeds the body’s defenses, the burned patient is susceptible to the development of sepsis. In burn patients, sepsis greatly increases energy requirements.6 During the first few days of a burn injury, the healing process of the burn wound has already begun, although catabolism and nutrient loss are still very significant. Increased synthesis of blood and other tissues composed of proteins often occurs in the early stages after a burn injury. However, all of these physiological processes may exacerbate the limitation of energy intake due to the stress response and the conversion of tissue synthesis to protein composition. The significance and persistence of energy depletion after a burn are directly related to the depth and size of the burn. Cope found that metabolic rate increased by approximately 130-140% from normal when the burn covered more than 20% of the entire body surface area, and increased to 160% when the burn covered more than 65% of the body surface area. He also found that the higher the value of body surface area covered by the burn, the longer the high metabolic rate lasted. Davies and Liljedahl found that during the first 2 weeks after a burn injury, the metabolic rate would increase by 150% over normal at 25% burn area. At 50%, the metabolic rate increased to more than 200%, and 170% over normal metabolic rate was sustained for at least 7 days. The depth of the burn also affects the metabolic process. Rapid epithelial regeneration in partially burned patients rapidly restores the skin’s vapor barrier, thereby reducing the risk of sepsis, as well as eliminating the increased metabolic demands of wound granulation. In contrast, in patients with deep, full-layer burns, complete wound coverage can only be achieved by waiting until sufficient wound granulation tissue has been grafted. More energy intake and a longer process are required to achieve complete skin coverage in patients with full-layer burns due to the loss of more water, increased risk of infection, and additional demand for granulation tissue. The underlying reasons for the persistent hypermetabolic state of the burn patient and the role of the relationship between the various factors that increase energy expenditure are not yet fully understood. In conclusion, the energy expenditure of the body in burn patients may return to normal only after the burn surface has been completely closed and after the wound has nearly completely healed. Nutrient depletion During the first 30 days after burn injury, total energy expenditure in patients with moderate and severe burns is estimated to exceed that of normal subjects by a factor of 1.5-2. The loss of nutrients over such a long period of time may have an extremely detrimental effect on the tissues of the body, thus requiring the intake of more nutrients and energy than a normal diet. Glucose has been implicated in most studies of hypermetabolic outcomes in patients with severe burns as increasing the rate of total oxygen consumption as well as alterations in glucose metabolism. “Diabetoid trauma” occurs due to increased insulin resistance in peripheral tissues in anticipation of excessive glucose production by the liver. Insulin-mediated glucose utilization in peripheral tissues during the first few days after burn injury plays an important role in post-burn hypermetabolism. In contrast, glucose uptake in the burn wound is non-insulin dependent and has an accelerated rate. Overproduction of glucose by the liver is a very important part in the treatment of thermal burns. This importance is demonstrated by the continued secretion of excess glycogen and cortisol. The most important reason why the body tends to remain in a hyperglycemic state during the first few weeks after a burn8 is that it limits the rate of glucose infusion. Even in the case of overdose, glucose infusion does not completely inhibit increased glucose isomerization. The resulting infusion of glucose at a maximum rate of 5-7 mg/min gradually did not result in significant hyperglycemia. Excess glucose (e.g., more glucose than is utilized as an energy substrate) may lead to the development of fatty liver to varying degrees. Thus, the amount and rate of glucose infusion should be strictly controlled and managed. Protein Protein depletion can be fatal to burns. A rapid reduction in lean body tissue tends to occur after a burn injury, the extent of which correlates with the severity of the burn injury.13 The rate of endogenous protein catabolism is then three times the normal rate and persists for a considerable period of time. Protein catabolism generally occurs in skeletal muscle cells, which release alanine and other amino acids to the liver for conversion to glucose to meet increasing energy needs.14 In the acute state of burn stress, some of the body’s protein can be conserved by providing dietary carbohydrates and other sources of energy.15 In patients with moderate and severe burns, the nitrogen balance is usually negative for the first month after burn injury. month there is usually a negative nitrogen balance. Nitrogen loss is particularly significant during the first week. Studies in this period have shown a urinary nitrogen excretion of 20-45 grams per day. In large samples of cases the negative nitrogen balance gradually decreases as the recovery time increases.16 This is demonstrated by the good agreement between the wound healing and the recovery phase of the organism. The amount of protein catabolism following a burn is a good indicator of the severity of the burn.Davies found that patients with moderate burns (burns on about 30% of the body surface area) catabolize 150 g of body protein per day (approximately 600 kcal.). . Plasma proteins are also lost at the surface of the burn wound, with approximately 2.5-5 grams of protein per 100 milliliters of exudate, resulting in exudate proteins of up to 300-400 grams per day. Losses due to catabolic proteins remain high during wound repair, when the physiological process of synthesizing proteins begins to accelerate. Fat is metabolically intolerant of carbohydrates in the early post-burn period, and fat mobilization provides the main source.17 Throughout the post-burn catabolic and anabolic processes, endogenous lipolysis accelerates in moderately burned patients resulting in significant fat loss. At this time endogenous fat loss is lower than protein loss in terms of body weight composition, but calorie production from fat is much higher than calorie production from protein. Protein accounts for only 12-22% of daily caloric expenditure, whereas fat supplies 75-90% of energy. During the first 20-30 days after a burn injury, the body’s stored fatty acids (palmitic acid and oils) begin to mobilize, and blood levels rise, even to directly produced cytotoxic levels.18 This suggests that their mobilization exceeds their utilization. Recent studies have suggested that this abnormality is due to running proteins (lipoproteins) limiting the utilization of triglycerides and cholesterol.19 These studies suggest that infusion of exogenous fats in the form of long-chain fatty acids as a source of energy can be limiting. Essential fatty acid deficiency due to rapid utilization in wound healing as well as reduced levels of rapid peroxidation of essential fatty acids to produce prostaglandins. Recent studies have shown that toxic substances and alterations in cellular composition and enzyme function are frequently produced as a result of peroxidative abnormalities 20-30 days after severe burns.20 Enhanced fat mobilization (in excess of fat utilization) and other toxic products allow the essential fatty acids to limit the input of exogenous fat emulsion for the purpose of meeting the caloric needs. Non -caloric Nutrient Shortages As part of the common nutrient profile, although slightly lower than the energy metabolism requirements, burn patients still have relative deficiencies of vitamins and minerals. A number of significant negative mineral and electrolyte balances can occur early in the post-burn period as a result of the general stress response. These losses are more pronounced in severely burned patients. Hormonal changes lead to an increase in potassium loss from cells. In addition, large amounts of potassium can be found on the wound surfaces of burn victims, which may further contribute to the loss of potassium reserves in the body. Substantial urinary calcium loss has also been reported following burns. Extensive and severe burns often exhibit hemolytic anemia, which may lead to a significant loss of hemoglobin. In the early post-burn period, increased urination results in the excretion of minerals and other lean tissue components.Reiss and his colleagues found that urinary magnesium and urinary phosphorus levels were increased in the first 9 days after both moderate and severe burns. And both phosphorus and magnesium balance correlated with nitrogen balance. The degree of loss of these nutrients was related to the severity of the burns.Davies and Fell found that zinc excretion was more than twice as high as normal when the burned area of the burned patient exceeded 33% of the body surface area, and that the rate of excretion would be about five times as high as normal when the burned area was between 34% and 77%. Similarly the more extensive the burn the more nitrogen and potassium is lost. Skeletal muscle holds more than 60% of the body’s zinc and more than 95% of its creatinine. Although the vitamin losses in burn victims are still poorly understood, a high metabolic state increases vitamin conversion as well as tissue utilization of vitamins.Costello et al. reported that a low puisne acid state persisted for 7-14 days during surgical stress after surgery. At the same time a significant accumulation of vitamin C, which is closely related to protein metabolism, was found in the vicinity of the wound. Enhanced conversion of vitamin B12 has also been reported after burns. We have also learned that B vitamins play an important role in cellular energy metabolism, and the body will rapidly become deficient if adequate vitamin B is not provided in the diet. The Dangers of Nutritional Deficiencies Severe burns may result in death due to severe metabolic shock, however this often occurs days or weeks after the burn. Although the definitive mechanism of this type of burn-related death is unknown, most such patients are characterized by persistent negative nutrient balances and progressive weight loss, which manifests itself as a day-to-day process of exhaustion. The most striking feature of this type of burn is the persistent loss of lean body tissue.Cuthbertson found that 100% mortality could be achieved in patients with a loss of lean body mass greater than 30% of total body weight after progressive trauma. Even in patients with moderate burns, significant weight loss can occur in the first week after burn injury.Artz et al. reported an average weight loss of 29.5 Ibs in patients with burns averaging 40% of the total body weight in the first 33 days after burn injury.Boswick found that weight loss could be up to 40 Ibs or more in burned patients in the first 4 weeks. Most of this weight loss was in lean body mass, and Davies found that in burns of more than one-third of the surface area, most of the weight loss came from loss of muscle tissue. In burn patients, there is a continuous loss of protein and other nutrients, and the lack of adequate dietary supplementation not only limits energy supplementation but also impairs the body’s ability to defend itself against microbial infections or other toxic substances. Sepsis remains the most common cause of death in burn patients. Malnutrition is also an important factor in the development of infections because it may affect the integrity of the body’s tissues and cellular immune function. A normal immune response relies on sufficient amounts of antibodies in the body. As with other plasma and tissue proteins, the amount of antibody globulin depends entirely on the adequacy of the amount of dietary protein. In humans and several animal species the production of antibodies may be impaired due to deficiencies in protein and amino acid intake. In addition, vitamins play an important role in the production of antibodies in the blood circulation. Protein and other nutrient deficiencies also limit the quality of tissue repair. Early and complete healing of burn wounds is essential to achieve full recovery in patients with severe burns. Wound healing not only reduces the hypermetabolic state and direct nutrient loss, but also reduces the threat of septic complications. Nutrient deficiencies can delay wound healing. For example, vitamin C and protein deficiencies may inhibit collagen formation. Collagen is the most essential component of the tissue covering deep burn wounds. Deficiencies of some micronutrients, especially zinc, can also delay wound healing. In patients with extensive burns the tissue repair process increases the need for these nutrients. In patients with total skin loss, skin grafts are needed to cover the epithelial tissue. Full recovery is achieved in patients who have undergone early and successful skin grafting. Graft failure as well as difficulty in healing the donor site skin may be related to malnutrition. Goals of Nutritional Therapy The ideal nutritional regimen for burn patients has not been fully defined; however, empirical practice guidelines have been effective in reducing morbidity and mortality. These guidelines are being improved as new information continues to accumulate. The most important and fundamental principle of evil in them remains the reduction of the metabolic rate, including the maintenance of an appropriate ambient temperature (28-31oC), the relief of pain sensations as well as the rapid debridement of necrotic tissues to promote wound healing. The first step in prescribing nutrition is to calculate the caloric expenditure.The Curreri formula is now widely used in estimating the patient’s caloric needs. This formula is based on the patient’s weight to burn ratio of 25′ body weight (Kg) + 40′% (burn area). However, our experience in applying this formula to calculate caloric energy differs significantly compared with the actual caloric energy determined by applying the indirect lateral heat method. Calculation of caloric energy requirements should follow the principle of individualization, which has a large variability among burn patients and can vary considerably even at different stages of burn injury in the same individual. (For example, some patients have a dramatic increase in energy metabolism requirements in the first 2 weeks after burn injury.) Measurement of oxygen consumption and respiratory quotient (RQ) every 2 weeks after burn injury helps to accurately calculate the composition of the caloric expenditure and respiratory quotient, and the respiratory quotient for pure carbohydrates is at 1.0 while that for fats is 0.8. Our scientific data suggests that a more accurate formula for calculating daily caloric requirements would be 1.37 times the basal metabolic rate.22 In the burned patient, as body weight changes, the level of negative nitrogen balance and glucose concentration adjusts accordingly, resulting in a more accurate calculation of daily caloric requirements. In burned patients, the levels of negative nitrogen balance and blood glucose concentration are adjusted accordingly to minimize the possibility of overfeeding and to allow flexibility in adjusting the feeding formula. Scientific studies have shown that the administration of excessive calories from glucose may increase the metabolic rate, which requires increased respiratory activity to eliminate the increased production of carbon dioxide, and more importantly, fatty infiltration of the liver can occur and ultimately lead to varying levels of hepatic dysfunction. When the respiratory quotient of carbohydrate production is equal to 1.0, performing continuous RQ testing will help to prevent overfeeding and its possible secondary complications. The requirement for protein can be easily calculated by its calorie production ratio of at least 20%. Whole proteins (enteral nutrition) are more effective than crystalline amino acids. Standard formulations of crystalline amino acid solvents should be given when parenteral nutrition is required, whereas high concentrations of branched-chain amino acid solvents show no significant benefit. The adequacy of protein supplementation can be measured by measuring the nitrogen balance, e.g., if the negative nitrogen balance exceeds 5 g per day, protein intake should be increased to reach 25% of total calories.16 Protein intake above 25% may also pose a risk of nitrogen retention and multiple complications in intermediary metabolism. Fat emulsions given by parenteral or enteral routes can replace the loss of essential fatty acids rather than just calories. Twice weekly fat emulsions (500 ml) can maintain normal plasma arachidonic acid concentrations. Linoleic acid capsules can also help prevent essential fatty acid depletion. Adequate replenishment of water-soluble vitamins can be achieved by either oral or parenteral nutrition. Because of the difficulty in accurately estimating requirements, the current recommendations for the entire B vitamins and vitamin C for burn patients are three times the recommended daily allowance (RDA) for normal subjects. Vitamin B12 supplementation should be by intramuscular injection once a week or given by the parenteral route of nutrition. Micronutrients (zinc 4 mg, magnesium 0.04 mg, copper 1.2 mg, and chromium 12 mg) are available centrally by various routes. Phosphorus (20 mmol) and sodium and potassium should be supplied daily in adequate amounts. Fat-soluble vitamins (A and D) should be supplied twice the RDA daily. Vitamin K should be supplemented with 5mg twice weekly. Sodium and potassium intake needs to be varied immediately according to the individual burn patient’s condition, so it is difficult to establish a clear and fixed baseline recommendation. Specific intakes are based on blood levels, urinary excretion, and exudation from the wound. In burn patients, the use of continuous diuretics may result in relative water retention and consequent hyponatremia, requiring a certain amount of sodium supplementation. Excess nutrient supply requires a choice of whether to be provided by enteral or parenteral nutrition. There are advantages and disadvantages to each of these approaches, and an individualized design should be used for stressed patients with a high catabolic state. Enteral nutrition should be the first option unless the gastrointestinal tract is unable to function properly. Complications of enteral nutrition occur less frequently and are less severe than those of parenteral nutrition. For absorption and utilization of most nutrients, enteral nutrition is better utilized than parenteral nutrition. Peristalsis of the small intestine is almost always impaired in burn patients, but slow gastric peristalsis occurs first in burn victims. The major complication of enteral nutrition is gastric dilatation and the resulting aspiration pneumonia. These complications can be effectively overcome by placing a fine-diameter duodenal feeding tube and adjusting the rate with a 24-hour infusion pump. Complications due to gastric dilatation can be avoided by performing gastric suction during gastrointestinal nutrition. In patients with extensive severe burns, parenteral nutrition can be used to meet a variety of nutritional needs, but it is usually performed only as an adjunctive therapy. In general, the gastrointestinal tract provides about half of the nutrients and the remaining half can be provided by peripheral or central venous nutrition. Intravenous catheters can have serious complications, the most serious being sepsis. Catheter sepsis can be effectively prevented by replacing the catheter every 72 hours. However, other infectious complications such as phlebitis and endocarditis may occur more frequently than with normal parenteral nutrition. Infections can occur with either vena cava or peripheral venous cannulation, and septicemic phlebitis and non-septicemic phlebitis occur more frequently with superior vena cava cannulation. CONCLUSIONS Hypermetabolic and protein wasting syndromes manifest more severely and last longer after burns compared to surgery. This requires nutritional therapy to minimize the multiple complications of malnutrition. The goal of nutritional support today is to supply daily calories at 1.37-1.7 times the basal metabolic rate or a higher proportion of protein. Fat emulsions are supplemented twice a week to replenish essential fatty acids. Vitamins, minerals and trace elements should be supplemented routinely. The current recommended amounts are based on research done 10 years ago and need to be adjusted as knowledge of metabolic abnormalities in burn patients rapidly expands.