The acute metabolic response to burn injury significantly alters carbohydrate metabolism and demands. Glucose/carbohydrate metabolism presents the burn physician with a rather vexing conundrum. On the one hand, failure to provide adequate carbohydrates results in additional compensatory protein catabolism. ^, On the other hand, the human body has a finite capacity for glucose oxidation. Multiple studies have demonstrated a limit to the amount of carbohydrate calories a burn patient can assimilate—approximately 5 g/kg per day in adults and 7 g/kg per day in children. ^, Providing glucose in excess of these limits will result in increasing hyperglycemia with resultant lactic acidosis ( Fig. 22.4 ).

Oxidative decarboxylation of pyruvate is a pivotal step in the overall oxidative metabolism of carbohydrates and fats. Overwhelmingly high levels of glucose may lead to lactate production, even in the presence of oxygen.

CoA , Coenzyme A; NAD ⁺ , nicotinamide adenine dinucleotide; NADH , nicotinamide adenine dinucleotide plus hydrogen.

(From Gore DC, Ferrando A, Barnett J, et al. Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients. J Trauma. 2000;49:673-677.)

Current guidelines typically recommend providing 50% to 60% of calories as carbohydrates in the setting of trauma or burn injury. However, as previously mentioned, large thermal injury induces massive global energy expenditure. Therefore providing 50% to 60% of calories as carbohydrates in the context of a nutritional therapy that meets the patient’s required caloric needs often results in doses of carbohydrates well in excess of the recommended limits. ^{, , ,} Administration of carbohydrates in excess of the patient’s capacity for glucose oxidation only results in increasing degrees of hyperglycemia, glucosuria, and hypertriglyceridemia. In such cases the patient’s nutritional demands simply reach a point where they exceed that patient’s metabolic capacity.

There is no simple, clinically vetted solution to this challenge. A reasonable approach to this dilemma is to start by titrating enteral formula delivery up to a rate that delivers 5 to 7 g/kg per day of carbohydrates and then provide all further calories in the form of protein supplementation. Unfortunately, this typically results in a protein load that (also) exceeds the body’s capacity for metabolizing.

Although lipids are critical to effective homeostasis and wound healing, the amount of fat required to prevent essential fatty acid deficiency is remarkably small in patients with intact fat stores. Excess fat administration, on the other hand, can cause significant harm. The hypermetabolic response to thermal trauma upregulates lipolysis of circulating lipids. This surfeit of circulating free fatty acids is countered by increased hepatic esterification, with close to 70% of the free fatty acids accumulating in the liver. To minimize hepatic steatosis, the percentage of dietary calories from fat should be limited and carefully monitored. Multiple studies have demonstrated improved outcomes with lower-fat nutrition therapy in burn patients. Fat content should comprise 3% to 15% of total calories. Patients receiving total parenteral nutrition (TPN) for a short period of time (e.g., less than 10–14 days) can generally be spared lipid infusion. In those requiring sustained TPN, 0.5 to 1 g/kg given one to two times per week is sufficient. It should be noted that nondietary fat calories need to be taken into consideration as well (the fat content of a 1% propofol solution is equivalent to that found in a 10% intralipid emulsion).

It should also be noted that the preceding discussion of the role of fat alimentation in nutritional therapy reflects literature that largely predates the application of alternative fat sources (e.g., fish oil, olive oil, borage oil, etc.). In the United States, the current standard of care for both enteral and parenteral fat administration features significant components of fats that have been shown to affect inflammation. Omega-3 fatty acids are perhaps the most well-known antiinflammatory fats. ^, One 2018 study of 92 patients with large thermal injury found significant decreases in rates of sepsis, septic shock, and pyloric dysfunction in patients receiving omega-3 supplementation versus those who were not. A 2022 meta-analysis, however, found no benefit to omega-3 supplementation in burn patients with regard to ventilator days, length of stay, mortality, gastrointestinal complications, or infectious complications. Current research also is undecided on the role of omega-6 fatty acids. Some studies have shown that increased intake of omega-6 or precursors (arachidonic acid or linoleic acid) does not lead to an increase in inflammatory markers. ^, Other studies have shown that increased intake of omega-6 may inhibit the antiinflammatory effects of omega-3 fatty acids, thereby indirectly contributing to more inflammation. Taken together, these studies illustrate a need for further investigation to fully elucidate the role and interactions between fatty acids and their derivatives and inflammation. ^,

Alternative fat sources have become the standard of care in Europe where intravenous fat emulsions (IVFE) have been used for over a decade. The United States has lagged behind its European counterparts but has begun to approve more and more of these formulas. Omegaven (Fresenius Kabi), SMOFlipid (Fresenius Kabi), and Clinolipid (Baxter) are three of the most recently approved IVFEs. However, more often than not, these supplements continue to be nonformulary, and they can be difficult to obtain. Although there are still insufficient data to declare these alternatives superior to the standard of care, the threshold for warranting further study has certainly been met. ^, As our understanding of the unique advantages and disadvantages of different fat sources matures, a reexamination of the role of fat alimentation in burn nutrition is sure to come due.

Proteolysis is the metabolic hallmark of the hypermetabolic response to thermal injury. As much as 150 g of skeletal muscle are lost per day in the absence of adequate nutritional support. If not attenuated, ongoing systemic proteolysis leads to immune dysfunction and retarded wound healing. Protein requirements of 1.5 to 2 g/kg per day in burned adults and 2.5 to 4 g/kg per day in burned children are well accepted in clinical practice. However, there are limits to the rate of effective protein assimilation. Increasing protein intake above these values can result in increased urea load and azotemia despite limited additional impact on muscle wasting.

The amino acids alanine, arginine, and glutamine play key roles in wound healing in burn patients. Glutamine plays an important role in the function of enterocytes and lymphocytes, and low plasma glutamine concentrations have been associated with increased bowel permeability and increased rates of infection. Studies in animal models of trauma and shock have shown distinct roles for these particular amino acids in recovering enteral and immunologic competence. Glutamine supplementation and other “immunonutrition” formulas featuring these key amino acids have been associated with decreased incidence of infection, shorter hospital stays, and decreased mortality in the setting of traumatic injury and sepsis. Furthermore, it has been shown that early administration of glutamine is particularly beneficial to burn patients in protecting against organ damage and minimizing the hypermetabolic response. Although the benefits of glutamine supplementation were shown in some smaller trials, more recent large-scale trials have called these conclusions into question. The Reducing Deaths caused by Oxidative Stress (REDOXS) study randomly assigned 1223 critically ill ICU patients on mechanical ventilation with multiorgan failure to receive supplements of glutamine, antioxidants, both, or placebo. The primary outcome measure of 28-day mortality was found to trend higher in the glutamine supplementation groups (32.4% vs 27.2%; P =.05). Furthermore, secondary outcome measures of in-hospital mortality and mortality at 6 months were significantly higher in the glutamine supplementation groups.

Until recently, it was thought that burn patients might show a benefit from glutamine that other critically ill patients do not. In response to this question, The Randomized Trial of Enteral Glutamine for the Treatment of Burn Injuries (RE-ENERGIZE) enrolled 1209 patients with severe burns (mean total body surface area [TBSA] 33%) and randomly assigned patients to receive 0.5 g/kg per day enteral glutamine or placebo. Recently published results did not show any difference in the glutamine supplementation group on the primary outcome measure of time to discharge alive from the hospital or mortality at 6 months . (See further discussion in the section on formulas.)

In addition to serving as a means for systemic delivery of nutrients, enteral nutrition (EN) performs a critical function in supporting the alimentary tract itself. Enteral feeds provide direct high-concentration nutrients (e.g., glutamine, alanine), stimulate enteric blood flow, maintain barrier function by preserving tight-junction integrity, and induce production and release of mucosal immunoglobulin and critical endogenous growth factors. These functions are not replaced with parenteral nutrition (PN). After dietary ingestion, polysaccharides such as fiber and starch undergo bacterial fermentation in the colonic lumen. Bacterial fermentation provides two functions crucial to intestinal health: (1) it supports the normal flora of the gut lumen, which in turn prevents colonization and subsequent infection (e.g., Clostridium difficile ) and (2) it produces acetoacetate, propionate, and butyrate (a short-chain fatty acid). Butyrate appears to be the preferred fuel of colonic mucosa cells and is therefore essential for mucosal integrity. Both animal and human studies show that the presence of enteral feeds (in addition to or in place of PN) is associated with increased mucosal mass, mucosal oxygenation, brush-border enzyme synthesis, and villous height when compared with PN alone. ^, Enteral feeding also has frequently been found to improve clinical outcomes both in terms of gastrointestinal and total patient morbidity and mortality. ^,

For the conscious patient with an intact appetite and swallowing function, direct oral intake is the preferred feeding modality. When prescribing a patient an oral diet, it is essential that the physician continuously monitor for adequate intake. In the acute surgical setting, many factors can lead to inadequate caloric intake, including high-caloric requirements because of injury, decreased appetite associated with injury response, depressed mental status, pain, or any other practical obstacles to eating such as bandages and functional limitations impacting utensil use. Should patients consistently fail to meet their caloric needs with a PO (per os, ie., oral) diet, consideration should be given to supplemental feeds via a nasoenteric tube.

In patients continuing to take food orally, careful monitoring should be maintained to ensure appropriate nutrition. Left unchecked, patients may frequently undereat or take in a disproportionate amount of calories as sugar or fat. A simple nutritional journal listing all foods and liquids consumed is often used to track intake. This journal can be maintained by the nursing staff, patient, and/or family throughout the day, and dietary adjustments can be encouraged as needed. In patients attempting to meet all needs orally (thus avoiding the need for an enteric access tube), supplemental “protein shakes” can be helpful in boosting total protein-caloric input.

Burn patients, particularly those suffering from larger burns, frequently prove incapable of eating sufficient quantities to meet their nutritional needs. Direct enteral feeding (“tube feeding”) is the method of choice to supplement or replace oral intake.

Either gastric or small-bowel access tubes can be used for delivering EN. Gastric feeding access allows for direct (trophic) feeding of the gastric mucosa. In the immediate postburn phase of resuscitation, though, gastric dysmotility may be present, posing a significant risk for aspiration and (particularly in children) for vagally mediated cardiac events. Thus we recommend placement of a venting nasogastric or orogastric tube for the duration of initial resuscitation.

Dysmotility does not tend to manifest in the small bowel as rapidly or as profoundly as in the stomach. Feeding using a nasojejunal tube advanced past the ligament of Treitz can be initiated within 6 hours after injury and may help in preempting the onset of starvation-associated ileus. This approach also allows continuous feeding during surgeries and physical therapy sessions. It should be noted that some authorities recommend attempting gastric feeds before resorting to postpyloric feeding, reasoning that gastric feeds may minimize the risk of gastric ileus associated with severe injury.

Nasojejunal feeding may be preferable in some settings because it does not need to be stopped before surgery to prevent aspiration. Contrary to the previously postulated protective effect of the pyloric sphincter, the largest randomized controlled trial and most recent meta-analysis of earlier studies indicate that nasogastric and nasojejunal feeds are associated with comparable rates of pneumonia.

In the past it was thought that monitoring residual stomach volumes via gastric tubes prevented aspiration pneumonia by (1) serving as a marker of enteric feed intolerance and (2) alerting the clinician to gastric distension so that feeds could be held to avert impending reflux and/or aspiration. Large multiinstitutional clinical trials have since shown that larger gastric residual volumes do not actually predict aspiration, and foregoing gastric residual monitoring altogether does not increase the incidence of pneumonia. In these studies, increasing or eliminating the gastric residual volume threshold led to significantly improved nutritional intakes.

As noted earlier, immune dysfunction represents one of the most critical complications of malnutrition in burn patients. In animal and clinical studies, specific nutrients including arginine, omega-3 polyunsaturated fatty acids, glutamine, and nucleotides have been shown to positively modulate the host response with regard to immune function. Biochemically, arginine supplementation is intended to support T lymphocytes and provides a substrate for the generation of nitric oxide. Inclusion of nucleotides nonspecifically enhances immune competence. Long-chain omega-3 fatty acids decrease the production of inflammatory eicosanoids, cytokines, and adhesion molecules. This occurs directly by replacing arachidonic acid as an eicosanoid substrate, inhibiting arachidonic acid metabolism, and giving rise to antiinflammatory resolvins. This indirect effect continues on a transcriptional level with modulation of transcription factors that regulate the expression of inflammatory genes. The antiinflammatory benefits of omega-3 supplementation could be particularly helpful for those with preexisting acute and chronic inflammatory conditions ( Table 22.2 ).

Immune-enhancing formulas consist of nutritional components enriched with arginine, glutamine, nucleotides, and omega-3 fatty acids. Although most formulations are hyperosmolar at full strength, dilution by 25% to 50% to make isotonic and hypotonic formulas, respectively, is initially preferred to minimize the possibility of diarrhea from excess osmotic load and to facilitate absorption.

A myriad of clinical trials of immunoenhancing nutritional therapies have yielded conflicting results. Some early trials showed promise, but more recent investigations have generated concerning results. Perhaps most troublesome, as mentioned previously, the REDOXS trial examined the impact of glutamine supplementation in a large, heterogeneous population of critically ill patients. This trial found patients receiving glutamine supplementation not only exhibited no benefit but, surprisingly, also showed a trend toward increasing mortality compared with subjects treated with standard care. Furthermore, a similar large-scale study of enteral glutamine supplementation in patients with severe burns did not show any decreased hospital length of stay or a 6-month mortality benefit. Naturally, these findings have greatly dampened enthusiasm for glutamine supplementation and highlighted the importance of verifying hypothesized benefits through randomized clinical trials.

The conflicting nature of these results, and a higher number of studies that show potential benefit of immunonutrition in burn patients, highlight the need for further study. Interestingly, studies of serum glutamine levels in broad populations of critically ill patients suggest that not all patients are deficient. In the modern age of individualized medicine, there may be certain patient phenotypes, particularly among patients who are already nutrient deficient (chronically malnourished patients, those with hypercatabolic trauma, and burn patients), in which immunonutrient supplements are of much greater benefit. ^{, ,} Finally, post hoc analysis of the REDOXS data suggests that the majority of the mortality risk associated with glutamine supplementation could be attributed to patients already in multiorgan or renal failure before the initiation of treatment. In light of this fact, it may be prudent to highlight more specific inclusion and exclusion criteria for glutamine supplementation candidates to avoid confounding variables.