Chapter 100. Burns: Inflammation-Infection Phase (Day 7 to Wound Closure)

• This period is characterized by hypermetabolism and sepsis syndrome owing to wound inflammation.
• Adequate nutritional support is critical to attenuate the rate of catabolism.
• Enteral nutrition should begin by 3 days, and 80% of nutritional needs should be met by 7 days.
• Inappropriate use of systemic antibiotics is common during this period because infection is overdiagnosed.
• During this period, wound manipulation and operative procedures must be limited because of wound colonization and hypervascularity.
• Pulmonary complications are the most common cause of mortality during this period; general anesthesia and transport are high-risk periods.
• Anemia is characteristic of this period because of decreased red blood cell production and continued red blood cell losses.
• A close working relationship with the patient is the key to control stress.
• Pain and stress management are major problems often necessitating extensive use of narcotics, sedatives, and antipsychotic drugs.

The interval from day 7 after a burn to wound closure is the most complicated phase of management of a large burn. The systemic effects of burn wound inflammation alter the function of all organ systems and magnify any preexisting organ dysfunction—especially cardiopulmonary dysfunction. There is marked catabolism with loss of body protein, especially from muscle but also from viscera, that can lead to organ dysfunction. The increase in metabolic rate resulting from hormonal response to the inflammatory process leads to a marked increase in O2 consumption and CO2 production. The burn wound is now colonized with bacteria, and wound sepsis is a prominent concern. The hyperdynamic hypermetabolic state makes it increasingly difficult to diagnose wound and lung infection.

Pulmonary problems remain a major cause of morbidity and mortality during this phase.1,2 Respiratory failure and pneumonia surpass burn wound sepsis as causes of mortality. The burn patient is especially prone to pulmonary infection after smoke inhalation. In addition, the hypermetabolic state produces a marked increase in O2 consumption and CO2 production at a time when respiratory function may be seriously impaired by pneumonia, pulmonary edema, or muscle weakness. Burn patients with the combination of inhalation injury and a major body burn have the greatest risk of pneumonia, with a rate approaching 50%. The high incidence is a result of the presence of virulent organisms in the ICU environment and the immunosuppressed state of burn patients. Ciliary action is injured directly by heat and by chemicals in inhaled smoke and often does not regenerate adequately, contributing further to the risk of retention of contaminated secretions and development of pneumonia. Since eradication of an established pneumonia in a burn patient is very difficult, prevention is of primary importance.3

When using antibiotics, it is important to remember that the dosages of most antimicrobials required to obtain adequate levels are much higher in hypermetabolic burn patients.4 If continued intubation is expected for weeks, conversion to a tracheostomy in the first week will greatly assist the clearance of secretions. The tracheostomy should not be placed through burned tissue. If the neck is burned, early excision and grafting are indicated. The tracheostomy can be performed through the skin graft.

The increase in O2 consumption and CO2 production during this period imposes increased demand on the respiratory system relative to that seen in the previous periods.5,6 A 50% to 100% increase in CO2 production will be seen with burns in excess of 50% of total body surface (TBS). In addition, the severe catabolism initiated by the inflammatory response can lead to weakness of the respiratory muscles.

Protection of the lungs against processes that would impair their function is the best form of support. Controlling edema and infection, maintaining nutrition, and providing for adequate rest, as well as respiratory muscle exercise, are key components. CO2 production should be limited by avoiding excess carbohydrate calories and controlling hyperthermia. Partial ventilatory support via a tracheostomy may be useful, especially if recovery is not anticipated for several weeks.

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.

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.

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).

Treatment

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.

Nutrition

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.

Nutrient Mix

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

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).

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.

Use of Anabolic Agents

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.

Human Growth Hormone

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 (Oxandrin)

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.

Infection and Sepsis

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.