7.2.3Protein Metabolism

Protein/amino acids from skeletal muscle are the major source of fuel in the burned patient, which leads to marked wasting of lean body mass (LBM) within days after injury [1, 56]. Since skeletal muscle has been shown to be responsible for 70–80 % of whole body insulin-stimulated glucose uptake, decreases in muscle mass may significantly contribute to this persistent insulin resistance post-burn [57]. A 10–15 % loss in lean body mass has been shown to be associated with significant increases in infection rate and marked delays in wound healing. The resultant muscle weakness was further shown to prolong mechanical ventilatory requirements, inhibit sufficient cough reflexes, and delay mobilization in protein-malnourished patients, thus markedly contributing to the incidence of mortality in these patients [58]. Persistent protein catabolism may also account for delay in growth frequently observed in our pediatric patient population for up to 2 years post-burn [4].

Various groups suggest that hypermetabolism is a major contributor to poor outcome post-burn and that treatment or alleviation of the hypermetabolic response is beneficial for patient outcomes.

7.3Attenuation of the Hypermetabolic Response

7.3.1Non-Pharmacologic Strategies

7.3.1.1 Nutrition

The primary goal of nutritional support is to provide an adequate energy supply and the nutrients necessary to maintain organ function and survival. Early adequate enteral nutrition alleviates catabolism and improves outcomes [59]. However, overfeeding in form of excess calories and/or protein is associated with hyperglycemia, carbon dioxide retention, fatty infiltration of organs, and azotemia [56]. Therefore, nutrition is an essential component to alleviate hypermetabolism, but too much feeding is detrimental and should not be pursued.

Nutritional Route

The preferred route to administer nutrition is oral/NG or NJ tubers. Enteral nutrition (EN) decreases bacteremia, reduces sepsis, maintains motility of the gut, and preserves “first pass” nutrient supply to the liver [59]. In cases where enteral feeding is not applicable (e.g., prolonged ileus or intolerance to enteral feeding), parenteral nutrition should be used to maintain appropriate macroand micronutrient intake. Parenteral nutrition remains of critical importance in burn patients in whom appropriate dietary support cannot be achieved or in those whose total caloric requirements cannot be fully supplied via enteral nutrition alone.

Initiation of Nutrition

Recently, the initiation of adequate nutrition gained attention and several studies delineated that optimal nutritional support for severely burned patient is best

accomplished by early (within 12 h after injury) initiation [62]. Beside clinical data, there are animal studies showing that early initiation of enteral nutrition can significantly attenuate the post-burn hypermetabolic responses to severe burn outlined above [59]. Patients with severe burn injury can be safely enterally fed in the duodenum or jejunum within 6 h post-burn, whether or not they have total gastroduodenal function [63]. Thus, nasojejunal or nasoduodenal feeding should be administered early.

Amount of Nutrition

As aforementioned, underas well as overfeeding is associated with adverse outcomes. Currently, resting energy requirements of burned patients are commonly estimated using equations that incorporate body mass, age, and gender. The performance of these equations has been compared to actual measured resting energy expenditure, which is obtained through indirect calorimetry.

Validation and agreement analysis of formulas such as the Harris-Benedict, Schofield HW, Curreri, and World Health Organization formulas have shown that, although these formulas are based on patient-specific factors such as age, gender, weight, and burn size, they may significantly overestimate caloric requirements in burn patients, increasing the risk of overfeeding and its subsequent deleterious effects [64, 65]. Recently, the adapted Toronto equation seems to be a better formula to calculate REE, as the calculated results very closely matched the MREEs.

We therefore recommend to measure resting energy expenditure via indirect calorimetry and adjust nutrition to this estimation. A factor of 1.2–1.4 is applied to the results of these formulas accounting for the burn hypermetabolic response.

Composition of Nutrition (Table 7.1)

At the moment, no ideal nutrition for burn patients exists. There are only recommendations, and we at RTBC recommend the use of a high glucose, high protein/ amino acid, and low-fat nutrition with some unsaturated fatty acids.

We believe that the major energy source for burn patients should be carbohydrates and amino acids thereby sparing protein from oxidation for energy, allowing the protein to be effectively used by the skin and organs. It is estimated that critically ill, burned patients have caloric requirements that far exceed the body’s ability to assimilate glucose, which has been reported to be 5 mg/kg/min or approximately 7 g/kg/day (2,240 kcal for an 80 kg man) [66, 67]. However, providing a limited amount of dietary fat diminishes the need for carbohydrates and ameliorates glucose tolerance.

Although the hypermetabolic response to severe burns stimulates lipolysis, the extent to which lipids can be utilized for energy is limited. Thus, fat should comprise less than 25 % of nonprotein calories [68]. Recently, several studies were conducted on the composition of administered fat which showed that the composition of fat is more important than the quantity. Most common lipid sources contain omega-6 polyunsaturated fatty acids such as linoleic acid, which are metabolized

to arachidonic acid, a precursor of proinflammatory molecules such as prostaglandin E2 [2, 66]. Omega-3 fatty acids are metabolized without producing proinflammatory compounds. Diets high in omega-3 fatty acids have been associated with an improved inflammatory response, improved outcomes, and reduced incidences of hyperglycemia [69].

Proteolysis is another hallmark of the hypermetabolic response after severe burn injury, and protein loss can exceed 150 g/day [56]. Increased protein catabolism leads to compromised organ function, decreased wound healing, immunoincompetence, and loss of LBM [56]. Evidence suggests that providing a larger protein replacement pool is helpful after severe burn injury [70, 71]. While research has shown that healthy individuals require approximately 1 g/kg/day of protein intake [27, 72–74], in vivo kinetic studies on oxidation rates of amino acids have shown that utilization rates in burned patients are at least 50 % higher than those in healthy, fasting individuals [70, 71]. Thus, at least 1.5–2.0 g/kg/day protein should be given to burn patients. However, supplementation with higher amounts of protein needs to be evaluated carefully as they may fail to yield improvements in muscle protein synthesis or LBM and may serve only to elevate urea production.

Amino acids supplementation was and is controversially discussed, especially alanine and glutamine. Both are important transport amino acids to supply energy to the liver and skin to increase healing mechanisms and metabolic needs [27, 75, 76].

Glutamine also serves as a primary fuel for enterocytes and lymphocytes maintaining small bowel integrity, preserving gut-associated immune function, and limiting intestinal permeability following acute injury [77, 78]. Glutamine is quickly depleted post-burn from serum and muscle [77, 78]; however, this depletion mainly occurs intracellularly, and it is very difficult to deliver glutamine effectively to the cells. Small studies in burn patients indicated that glutamine supplementation decreased incidence of infection, length of stay, and mortality [77, 78]. Therefore, there is a signal that glutamine supplemental maybe associated with beneficial effects. A current multicenter trial (REDOX) is addressing the answer, and the results are expected over the next 4–5 years. The literature on alanine is even sparser, and at this time, there is no evidence to administer or not administer alanine. Furthermore, there are no signals whether or not to supplement branched-chain amino acids which improve nitrogen balance [79].

Other important components affected by burns are vitamins, micronutrients, and trace elements [80] Table 7.2. Decreased levels of vitamins A, C, D, E, iron, copper, zinc, and selenium have been implicated in wound healing deficiencies and immune dysfunction after severe burn injury [80, 81]. Vitamin A replacement is particularly important for wound healing and epithelial growth. Vitamin C is paramount for the synthesis and cross-linking of collagen post-burn, and burn patients often require up to 20 times the recommended daily allowance [81, 82]. Vitamin D levels are low in burned children, and adequate vitamin D status is likely essential for attenuating further loss of bone minerals post-burn [81, 82].