A good understanding of the metabolic and physiologic changes is necessary to determine fluid, electrolyte, and nutrient requirements.
Fluid, Protein, and Red Blood Cell Losses
Evaporative water losses remain increased until the wound is closed. Even after closure, evaporative losses through the grafted wound are much higher than through normal skin. Increased water intake is essential to compensate for this loss, which can be 2 to 4 L/d. Protein losses from wound exudation and from bleeding persist until wound closure.
The Hypermetabolic-Catabolic State
The host response to a severe burn is an amplification of the fright-flight reaction. The insult (afferent arc) leads to the release of inflammatory cytokines that activate a very abnormal hormonal response led by a marked increase in catecholamines and other hormones (efferent arc) that produce a hypermetabolic-catabolic state (Fig. 100-1 and Table 100-1). Oxygen consumption can double during this period because of the abnormal endocrine environment. Any added central nervous system (CNS) stress such as pain will further amplify the catechol-induced process.
Table 100–1. The Hormonal and Metabolic Response to Burn ||Download (.pdf)
Table 100–1. The Hormonal and Metabolic Response to Burn
The host response to a severe burn.
Hepatic gluconeogenesis is intensely stimulated, and body protein is broken down rapidly to provide amino acids for carbohydrate substrate.6–9 The amino acids are released mainly from muscle as alanine for liver glucose formation and glutamine. Glutamine from muscle is exported in large quantities for use as fuel for the gut, as well as a precursor for the endogenous antioxidant glutathione. As opposed to starvation, where 85% of calories come from fat, protein is not spared for use for fuel, and muscle is lost rapidly.
Optimal nutrition attenuates the process and decreases net protein losses by about 50%, but catabolism still outweighs anabolism because the catabolic hormones predominate and the anabolic hormones, especially growthhormones, are decreased. Morbidity from rapid protein depletion can occur in days to weeks after injury rather than after months, as seen with starvation alone (Fig. 100-2). Oxidants released by the generalized inflammation produce direct cell damage, especially because endogenous antioxidant levels are decreased. The direct cell injury and loss of cellular protein can result in progressive multiple-organ dysfunction.
Daily catabolism following major injury.
The wound or focus of inflammation develops a high blood flow owing to demand for substrate caused by inflammatory mediators that produce local vasodilatation. This blood flow, which steals from the systemic circulation, can lead to a systemic O2 debt. The wound consumes large quantities of energy during the healing process both by inflammatory cells and by fibroblast collagen formation. The wound uses glucose as its primary fuel for ATP but does so in an anaerobic fashion despite oxygen availability. Lactate is returned to the liver to re-form glucose. Gluconeogenesis also employs skeletal muscle amino acids, primarily alanine.
The size of the wound or focus of inflammation corresponds with the magnitude of the stress response. In addition, the wound becomes the preferred consumer of amino acids obtained from muscle until 20% of muscle is lost, at which time both muscle and wound compete equally. With a 30% loss of muscle, the wound now receives less protein substrate than muscle, and poor healing becomes evident as the body attempts to restore lean body mass before a lethal fall10 (Fig. 100-3).
The wound healing rate progressively decreases as the muscle loss increases.
Controlling the Stress Response
It is not necessary that the “stress response” go unchecked. The underlying disease process and the degree and time course of the calorie and protein depletion can be modulated by (1) controlling the source of the stress response and (2) increasing the process of anabolism through nutrition, nutritional adjuvants, and increased muscle activity.
The hypermetabolic-catabolic state is driven by the presence of an injury, infection, or ischemia and resulting inflammation. Therefore, control of the source of the systemic response is critical11 (Table 100-2). Aggressive surgical control of the focus, which is usually devitalized tissue such as burn eschar, is essential to minimize the degree and time course of the response. Both local ischemia and systemic oxygen debt are strong stimuli to continued inflammation and further catechol and cortisol release. The increase in cortisol requirements may not be able to be maintained. Liberal use of analgesics, anxiolytic drugs, and other methods to control psychological stress are required. A relative adrenal insufficiency has been reported with increasing frequency, especially in the elderly burn patient, requiring additional cortisol.12 A controlled β blockade has been shown to decrease the degree of postburn catabolism significantly.13 Optimizing tissue perfusion is essential.
Table 100–2. Controlling the Source of the Stress Response ||Download (.pdf)
Table 100–2. Controlling the Source of the Stress Response
By removing dead tissue, draining infection, and decreasing inflammation and mediator changes in metabolism
By maintaining optimum blood volume thereby avoiding ischemia-induced catechol release
By controlling secondary stresses, e.g., pain, anxiety, which also increase catechol release
It is expected that nutritional support has been started in the early postresuscitation period; however, this support will require adjustment during this period of increasing metabolic activity. The first requirement is an estimation of energy requirements; this is followed by an organized approach to nutrient delivery, tailoring the proportions of carbohydrate, protein, and fat to the individual patient's needs. The use of indirect calorimetry and estimating nutrient needs based on burn size are the most common approaches used.8,11
The nutrition support should begin by the end of the resuscitation period. The enteral route is preferred because nutrient utilization clearly is improved over the parenteral route, and the gut integrity is maintained.11 In general, the caloric requirements for burns of 30% of TBS or greater are 30 to 35 cal/kg per day based on formulas or direct measurements.
Increased carbohydrate (CHO) calories (60% of total) are used to try to control the rate of gluconeogenesis, decreasing proteolysis. Excess CHO, however, is deleterious, leading to hyperglycemia, fat formation, and additional carbon dioxide. Fat calories (30% of total) are also given. Endogenous fat stores are also used. However, fat will not spare protein loss. Excess fat is also deleterious, being a substrate for immunosuppressive mediators.11
Protein requirements are two to three times the recommended daily allowance, 1.5 to 2.0 g/kg of body weight per day. The increased protein intake will decrease the net nitrogen (N) losses. Protein supplements usually are necessary to achieve this intake because tube feedings or regular food is not sufficiently protein-rich. Supplements must contain protein of high biologic value, a standard measure of the percentage of the protein amino acids that can be absorbed and used. Egg albumin has a 91% value compared with casein, which is 56% (Table 100-3).
Table 100–3. Biologic Value of Common Proteins ||Download (.pdf)
Table 100–3. Biologic Value of Common Proteins
|Protein||Percent of N Retained for Protein Synthesis|
Glutamine, the most common circulatory and intracellular amino acid, is depleted rapidly after a burn and needs to be replaced for glutathione synthesis.12 Since glutamine represents over 30% of the amino acid used in catabolism and protein loss exceeds 100 g/d, replacement with 30 to 40 g will attenuate the deficiency state. Soluble glutamine is now available for oral use or via tube feedings (Cambridge Nutraceuticals, Boston, Mass.). Glutamine is also known to stimulate release of human growth hormone, adding to its anticatabolic effects.13
Vitamin and Mineral Requirements
Vitamins and minerals are consumed at a rapid rate and should be given at a dose of 10 times the Recommended Daily Allowance (RDA).11 Well-accepted daily doses include vitamin A, 10,000 to 15,000 units; vitamin C, 1 g; vitamin E, 500 to 1000 IU; selenium 100 μg; carotene 50 mg; and zinc sulfate, 220 mg bid.
Increasing the patient's anabolic activity has been shown to further attenuate net catabolism15,16 during the stress phase and to increase muscle restoration in the recovery phase. Currently, only two agents are available—human growth hormone and the testosterone analog oxandrolone.
This agent has been shown to increase healing rate, muscle mass, nitrogen retention, and survival in burn patients when given parenterally in doses of 5 to 10 times that normally produced (0.8 mg/d).14 The major complication is hyperglycemia.
Oxandrolone, a 17-hydroxyl-17-methyl ester of testosterone, is the anabolic steroid that is approved by the Food and Drug Administration (FDA) for restoration of muscle loss after severe trauma, burns or major surgical procedures, or infections.17 The anabolic effect is primarily on muscle (or lean body mass).15,16
Clinical trials on a variety of burn patient populations from children to the elderly have demonstrated significant decrease in lean mass loss during the catabolic state and a marked increase in the rate of lean mass restoration. Oxandrolone (BTG Pharmaceuticals, Iselin, New Jersey) is the only steroid in which a carbon atom in the phenanthrene nucleus has been replaced by another element, namely, oxygen. This alteration appears to be responsible for its potent anabolic activity—5 to 10 times that of methyl testosterone. In addition, its androgenic effect is considerably less than testosterone, thereby minimizing the complication of excess androgen activity common to other testosterone derivatives. The drug is given orally with 99% bioavailability. It is protein-bound in plasma with a biologic half-life of 9 hours. The compound is excreted unchanged primarily by the kidney with minimal hepatic metabolism and therefore results in minimal to no hepatic toxicity. No significant complications have been reported.
Sepsis is the leading cause of morbidity and mortality during this period. The most common sites of infection in the burn patient are the lungs, the burn wound, and vascular catheters.18 Intraabdominal processes, in particular, cholecystitis, are uncommon but are well recognized as sources of sepsis in critically ill patients.
Appropriate antibiotic dosing is a crucial aspect of management. Because of the hypermetabolic state, as well as the loss of antibiotics from the wound, the burn patient generally requires a larger total antibiotic dose and increased frequency of doses to maintain adequate levels. This increased requirement is well documented for the aminoglycosides. Renal impairment may mandate lower doses. Monitoring antibiotic levels is the only valid approach to the use of systemic antibiotics in major burn patients.
Because of the immunocompromised nature of the burn patient, as well as the use of topical and systemic antibiotics, fungal sepsis—especially caused by Candida albicans—is relatively common. The prodrome is often more subtle than with other microorganisms, with patients appearing more chronically ill and just “not doing well.”
As with any form of sepsis, the removal or control of the septic focus is of primary importance. Débridement should be performed gently to unroof pockets of infection and allow for better local wound and topical antibiotic care. Large excisions often are poorly tolerated during this period because of dissemination of infection and blood loss.18 The approach to infection is summarized in Fig. 100-4.
Approach to the burn patient with sepsis.