Epidemiology

The most recent edition of the American Burn Association’s National Burn Repository includes a comprehensive analysis of data from acute burn admissions within the United States that were collected between 1998 and 2007. Pediatric burn patients account for almost one third of the total projected volume. Burn-related trauma is the second leading cause of accidental death in children between 1 and 4 years of age and remains the third leading cause of accidental death in individuals younger than age 18 years, exceeded only by motor vehicle accidents and drowning. Approximately 70% of pediatric burns up to the age of 4 years old are the result of scald injuries, whereas flame burns are the most common pattern among children 5 years of age and older (American Burn Association, 2007). In general, younger children are at higher risk for sustaining burn injuries, and abuse or neglect may account for as much as 15% to 20% of these cases (Tucker, 1986; Sheridan et al., 1997a).

The mortality previously associated with severe burn trauma has been significantly reduced since the 1980s. Current survival expectations associated with management of burn wounds may be attributed to improved access to emergency medical care and targeted resuscitation, advanced ventilation modalities and a more comprehensive understanding of the pathophysiology of inhalation injury, rigorous infection control practices, enhanced nutritional support, early burn wound excision and grafting, and the attenuation of the hypermetabolic response (Herndon and Spies, 2001). The development of evidence-based practice guidelines and multidisciplinary care models available at regional burn care centers have aided these efforts. Long-term outcomes have subsequently improved, and pediatric burn survivors are able to report a satisfying quality of life as measured by several psychometric tools (Sheridan et al., 2000; Baker et al., 2007, 2008).

Burn-wound assessment

Injury depth, size, and location are the three components that contribute to the overall severity of burn wounds and are the direct results of exposure to thermal, chemical, electrical, ultraviolet, and radiologic sources. Regardless of the medium, the protective functions of the skin are impaired or destroyed. Burn wounds are dynamic, in that dermal changes evolve over time with damage extending to adjacent or deeper tissues (Palmieri and Greenhalgh, 2002).

The traditional classification of burn depth (first through fourth degrees) has been supplanted by the use of more comprehensive terminology to include the superficial, partial-thickness, and full-thickness categories, although there remains considerable overlap between these designations (Table 31-1). First-degree (superficial) burns are restricted to the epidermis and generally heal quickly without scarring, pigmentation changes, or contractures. Sunburn is the most common example and is associated with erythema, mild pain, and possible minor blistering (Fig. 31-1, A). Second-degree (partial-thickness) burns involve the epidermis and variable portions of underlying dermal structures and are further categorized as superficial or deep partial-thickness injuries, with different implications for the progression of tissue damage and the level of anticipated care. A superficial partial-thickness burn poses minimal risk of scar formation, because the dermal structures (e.g., nail beds, hair follicles, sebaceous glands, and nerves) are largely unaffected, allowing for injuries to heal within 2 weeks (Fig. 31-1, B). In contrast, deep partial-thickness injuries disrupt portions of the dermal matrix, and epithelial regeneration is commonly associated with scar formation. Pain may not be severe, despite extensive injury, which probably reflects variable degrees of nerve dysfunction or loss. Many of these wounds require excision and grafting in order to heal properly (Fig. 31-1, C). Full-thickness burns (formerly third-degree burns) are characterized by deep-tissue destruction where the necrotic debris adheres tightly to the dermal-matrix remnant as a thick, waxy layer of eschar (Fig. 31-1, D). In the absence of normal regenerative capabilities, wound healing can only occur by prolonged peripheral granulation and contraction, with a significantly increased incidence of infection and debilitating scar formation. Surgical intervention is required to reestablish normal barrier functions and prevent infectious sequelae (Sheridan, 2002). Even with early excision and grafting, hypertophic scarring persists years after the original injury. Fourth-degree burns are full-thickness burns with extensions beyond the fascia and include the destruction of gross muscle mass or the disruption of major joint-capsule integrity (Fig. 31-1, E). Injuries of this type are often a precursor to surgical amputation.

TABLE 31-1 Burn Injury Characteristics

Modified from de Campo T, Aldrete JA: The anesthetic management of the severely burned patient, Int Care Med 7:55, 1981.

FIGURE 31-1 Depth of thermal injury. A, Patient with sunburn of the lower extremity (superficial or first-degree burn with associated blister on anterior tibial surface). B, Partial-thickness injury of the hand (superficial second-degree burn). C, Partial-thickness injury extending beyond subcutaneous layers (deep second-degree burn). D, Full-thickness (third-degree) burn. E, Full-thickness injury with extensive tissue loss (fourth-degree burn).

Reassessments of burn-wound size and depth are necessary, because injuries have the potential to evolve from their initial presentation (dermal dysfunction worsens and affects a broader and deeper area than originally observed). Therapeutic fluid administration, nutritional requirements, and prognostic determinations are dependent on the physician’s ability to perform consistent serial evaluations and can be influenced to varying degrees by a clinician’s experience and subjectivity. Several methods have been developed to minimize potential inaccuracies and include laser Doppler, thermography, vital dye fluorescence, and video angiography (Mandal, 2006; McGill et al., 2007; Monstrey et al., 2008). These techniques are used to identify viable tissue by documenting the presence of adequate vascular flow to the site of injury.

Estimates of dermal involvement are recorded as a percentage of total body surface area (TBSA), and several clinometric instruments are available (Wachtel et al., 2000; Jose et al., 2004). Each method seeks to balance ease of use with consistent assessments among different care providers. The Lund-Browder diagram remains a commonly used tool, because it addresses the differences observed with patient size and body proportions in relation to growth (Fig. 31-2) (Lund and Browder, 1994). It has been adapted for the evaluation of pediatric patients. The “rule of nines” is well-suited for a rapid field-estimate of burn injuries to facilitate prehospital management and identify criteria for transfer to a regional burn center. This technique has also been modified to appropriately account for the alterations in body proportions observed with infants, small children, and the morbidly obese (Livingston and Lee, 2000; Smith et al., 2005). Pediatric burn patients have also been evaluated using the palmar method, in which the size of the patient’s palm represents the equivalent of 1% TBSA (Sheridan et al., 1995b; Rossiter et al., 1996). Complex burn wounds often have highly irregular distributions across multiple body segments, introducing additional inaccuracies to surface-area assessments. Newer techniques have been pioneered to improve the precision and reproducibility of clinician assessments. They include a flexible single-use nomogram that can be applied directly to the patient’s wound sites and an advanced graphics software platform that creates a three-dimensional virtual display (Neuwalder et al., 2002; Dirnberger et al., 2003; Malic et al., 2007).

FIGURE 31-2 Comparison of the Rules of Nines and the Lund-Browder burn diagrams. A, The Rule of Nines is applicable to most adult burn patients. B, The Lund-Browder charts improve the accuracy of burn estimates for infants and young children, because body-surface area values correlate well with the patient’s age.

(Modified from Orgill DP: Excision and skin grafting of thermal burns, N Engl J Med 360:893, 2009.)

Burns are further classified by their overall severity (minor, moderate, or major) as defined by the American Burn Association and the American College of Surgeons Committee on Trauma (Table 31-2). These parameters may serve as useful indicators of the anticipated degree of physiologic derangement, but their prognostic value has not been validated.

TABLE 31-2 Burn Wound Severity

TBSA, Total body surface area (%).

Modified from the American Burn Association: Guidelines for service standards and severity classifications in the treatment of burn injury, Am Coll Surg Bull 69:24, 1984.

Pathophysiology

An evidence-based, multidisciplinary approach directed by a pediatric specialist is the most effective way to minimize mortality and improve long-term, functional outcomes among pediatric burn-trauma victims (Thombs et al., 2006; Gore et al., 2007). The spectrum of burn-related physiologic abnormalities includes, but is not limited to, loss of thermal insulation and antimicrobial barriers, distortions of airway anatomy and pulmonary derangements, fluctuating intravascular volumes and the need for individualized fluid replacement, hypermetabolism accompanied by grossly elevated caloric needs, septicemia, altered responses to common anesthetic agents, and a prolonged inflammatory response to systemic trauma. Most patients benefit from the capabilities of a regional burn unit to deal with these complex pathophysiologic changes, and the American Burn Association has forwarded selection criteria to facilitate referrals (Box 31-1).

Dermal Barrier Disruption

The epidermis is an effective barrier to heat loss, evaporation, and infection; the dermis and its supporting neurovascular structures provide elasticity, flexibility, and the mechanism for epithelial regeneration. Burn trauma induces localized tissue coagulation and microvascular reactions in the underlying dermis that can lead to injury extension (Aggarwal et al., 1994a, 1994b). Protective functions are immediately lost with dermal disruption and result in significantly increased risk of infection and hypothermia. The risk of hypothermia is particularly high in infants and young children because of their disproportionate surface area/body mass ratio; burn patients benefit from aggressive control of ambient temperature and humidity to restrict heat loss and limit the caloric expense of shivering.

The severity of skin damage is a function of temperature and its duration of contact. Burn wounds have three zones of heterogeneous tissue damage, radiating from the epicenter of maximal tissue destruction (Jackson, 1953). The zone of edema and stasis is of particular importance, because it represents affected tissues that are potentially salvageable with supportive care. Successful management helps reduce the final TBSA measurement (Fig. 31-3) (Hettiaratchy and Dziewulski, 2004). During the first 24 to 48 hours, systemic hypotension, acidosis, and developing sepsis contribute to injury extension. These conditions are likely to exacerbate tissue edema, impaired microcirculation, and perfusion deficits. Serial examination is the most prudent method to address the variability of burn-wound progression. Early detection of nonviable areas with subsequent surgical excision and grafting has been consistently demonstrated to decrease morbidity and mortality in this patient population (Ong et al., 2006).

FIGURE 31-3 Zones of thermal injury. Burn injuries create three distinct zones of tissue reaction. The zone of necrosis is caused by tissue-protein denaturation. The zone of injury is associated with edema and reduced blood flow. The extent of this zone is variable, and appropriate burn management may limit its progression to necrosis.

(Modified from Orgill DP: Excision and skin grafting of thermal burns, N Engl J Med 360:893, 2009.)

Respiratory Abnormalities

It is often difficult to definitively distinguish respiratory insufficiency caused by the toxic products of combustion from the pulmonary derangements that are commonly observed with systemic responses to severe burn trauma. Inhalational injury is a term that encompasses both the direct thermal and subsequent inflammatory damage to the upper and lower airways. Several studies have demonstrated that inhalation injury associated with burns increases mortality, although no specific indicators are reliably predictive of the overall degree of pulmonary dysfunction (Shirani et al., 1987; Hollingsed et al., 1993; Ryan et al., 1998; Edelman et al., 2006; Endorf and Gamelli, 2007).

Upper-Airway Effects

Direct-heat injury caused by superheated gas inhalation and toxic smoke exposure may manifest as rapidly progressive edema of the tongue, epiglottis, and aryepiglottic folds (Pruitt et al., 1970). Macroglossia, micrognathia, and tonsillar hypertrophy are common findings in previously healthy children, and the normal presence of these features may further restrict airway patency (Benjamin and Herndon, 2002). Reduced cross-sectional area and increased flow resistance are poorly tolerated by infants and young children because of their elevated baseline minute ventilation, oxygen consumption, and limited endurance of the major respiratory muscle groups (Keens et al., 1978). Large-volume intravenous fluid administration is likely to accelerate oropharyngeal edema and convert a marginal airway into a severely compromised one, with subsequent anatomic distortions that make successful direct laryngoscopy challenging or impossible. Avoiding the “lost airway scenario” in the pediatric burn patient is a critical step during initial management, and the clinician should be guided by serial examinations to avoid airway catastrophe. Early, definitive control of the airway using context-appropriate methods is preferable for patients with evidence of progressive respiratory distress. This principle also applies to other clinical circumstances where the oropharyngeal architecture has been altered (e.g., ingestion of caustic agents such as lye).

Lower-Airway Effects (Smoke-Inhalation Injury)

Lower-airway injury is a clinical diagnosis supported by the presenting history and serial examination. Chest radiographs and bedside pulmonary function tests usually remain normal until infectious complications arise, and then their results often show an underestimation of the severity of lung damage (Lee and O’Connell, 1988; Wittram and Kenny, 1994). Fiberoptic bronchoscopy and bronchoalveolar lavage can be used to document the presence of carbonaceous debris and mucosal sloughing, although the absence of these findings should not preclude the diagnosis (Hunt et al., 1975). Technetium scanning is an assessment of pulmonary vascular endothelium damage represented as abnormal lung/liver uptake ratios of the isotope. In the future, this method may be accepted as a more objective diagnostic tool to detect lung injury in those patients with pulmonary signs and symptoms (but negative chest radiographs or pulmonary function test [PFT] findings), although it will require additional study (Shiau et al., 2003).

Toxicologic analysis of the victims with smoke-inhalation injury has demonstrated exposure to many poisonous aerosols, including carbon monoxide (CO), hydrogen cyanide, various aldehydes, hydrogen chloride, and other aromatic hydrocarbons (e.g., benzene). Even a brief exposure has significant adverse effects on the ciliated respiratory epithelial cells; toxic gases induce separation of cells from basement membranes, leukocyte migration, and exudate formation with severe impairment of the mucociliary-clearance mechanism (Fein et al., 1980). Severe ciliary dysfunction permits the accumulation of cellular debris, secretions, and bacteria. Endobronchial sloughing and edema contribute to small airway narrowing. Diminished flow capacity promotes widespread atelectasis that is magnified by surfactant loss (Herndon et al., 1985). Leukocytes aggregate in the affected lung tissue and release potent inflammatory mediators and other chemotaxins that increase endothelial permeability (Wright and Murphy, 2005). Dyspnea, tachypnea, diffuse rhonchi, and bronchospasm are common clinical signs observed with evolving pulmonary insufficiency and impaired gas exchange in the presence of persistent aerosolized irritants (Table 31-3).

TABLE 31-3 Pulmonary Dysfunction Evolving from Burn Injury

Early resuscitation phase (0-48 hours)	Upper-airway compromise Persistent bronchospasm Conducting-airway obstruction Impaired ciliary clearance Decreased lung and chest-wall compliance
Late resuscitation phase (48+ hours)	Surfactant loss Increased dead space Increased closing volume Decreased functional residual capacity Tracheobronchitis ARDS/pulmonary edema/pneumonia

ARDS, Acute respiratory distress syndrome.

The cascade of endobronchial cell destruction and protracted inflammatory changes predispose the patient to barotrauma (lung injury secondary to elevated ventilatory pressures and air trapping in the smaller airways), significant ventilation-perfusion distortions, and the potential for bacterial infection that leads to bronchopneumonia after several days (Pruitt et al., 1975; Rue et al., 1993). Lower-airway injuries also substantially increase systemic fluid requirements. Paradoxically, efforts to minimize pulmonary edema with fluid restriction increase mortality in these patients because inadequate intravascular volume invariably results in systemic hypoperfusion and multiorgan dysfunction (Ansermino and Hemsley, 2004).

During this period, clinical efforts must focus on the maintenance of effective gas exchange to provide time for the resolution of pulmonary tissue injury. Vigorous pulmonary toilet is needed to clear accumulated endobronchial debris, purulent exudates, mucous plugs, and residual particulates (Demling, 2008). A number of studies have reported that the administration of aerosolized heparin and mucolytics may reduce cast formation and attenuate respiratory failure (Desai et al., 1998; Holt et al., 2008). Ventilation modalities should be selected to minimize barotrauma and reperfusion injury, because elevated peak inspiratory pressures and hyperoxygenation worsen pulmonary insufficiency (Shapiro et al., 1980; Slutsky, 1993). Low-volume, pressure-limited ventilation with permissive hypercapnia (allowing for the deliberate elevation of measured arterial carbon dioxide tension [Paco₂] while maintaining pH greater than 7.25 and an arterial oxygen saturation of hemoglobin [SpO₂] of greater than 90%) is one method that may preserve tissue oxygenation in the presence of severe pulmonary dysfunction and is associated with a reduction in short-term mortality (Hickling et al., 1994; Sheridan et al., 1995a). Other methods (e.g., high-frequency percussive ventilation) have also been used, but outcomes data remain unclear (Rodeberg et al., 1994; Micak et al., 1997; Sheridan et al., 1997b; Cortiella et al., 1999; Silver et al., 2004).

Infection is the most common complication after the accumulation of denuded endobronchial tissue, small-airway obstruction, persistent edema, and extended intubation intervals (Rue et al., 1995). The incidence has been reported as high as 30% in pediatric burn patients, with infection occurring after the loss of antimicrobial barriers and the onset of generalized immunosuppression that follows severe burn trauma (Fitzpatrick et al., 1994). Fever, mucopurulent secretions, and lobar consolidation documented by chest radiographs support the diagnosis of pneumonia (or tracheobronchitis if no x-ray changes are noted). Bronchoalveolar lavage and brushings may help support the diagnosis (Ramzy et al., 2003; Wood et al., 2003; Goldberg et al., 2008; Malhotra et al., 2008). Culture-guided and Gram-stain–guided antibiotic therapies should be reevaluated often and adjusted to optimize bacteriocidal effects and limit the development of antibiotic resistance.

Tracheostomy for pediatric patients has been advocated as a useful adjunct for airway and ventilatory management, but its application is not without risk (Sellers et al., 1997; Coin et al., 1998; Palmieri et al., 2002). The typical challenges encountered during pediatric direct laryngoscopy are made considerably more difficult in the presence of facial burns and progressive edema. Tracheostomy provides a stable, definitive airway and should be considered when the treatment plan requires multiple transports to and from the operating room or frequent repositioning of the patient for wound care. Improved secretion clearance, dead-space reduction, decreased airway resistance, and facilitation of the weaning process are also perceived benefits of a tracheostomy. However, surgical airways in small children may be associated with a greater incidence of structural abnormalities (e.g., subglottic stenosis and tracheoesophageal fistula), and subsequent life-long restricted tolerance of exercise. The routine use of this technique is not recommended (Calhoun et al., 1988; Desai et al., 1993; Barret et al., 2000).

Carbon-Monoxide Exposure

CO is a by-product of incomplete organic combustion and a persistent toxin of heme-containing species because of its strong binding affinity. Although CO reversibly binds hemoglobin, it does so at approximately 200 times the strength of oxygen, producing a functional anemia. Only a brief exposure is necessary to produce clinical symptoms (Fig. 31-4). A person exposed to 1% CO vapor attains measured carboxyhemoglobin (COHb) levels of 30% within 2 minutes. Severe CO poisoning may occur even without evidence of overt burn trauma, and delayed diagnosis contributes to significant morbidity and mortality after exposure (Cone et al., 2008; Stefanidou et al., 2008). The half-life of CO in a patient breathing room air approaches 200 minutes, but by applying 100% oxygen therapy this time can be reduced to approximately 40 minutes (Weaver et al., 2000). The clinician should always maintain a high index of suspicion for occult CO intoxication.

FIGURE 31-4 Measured blood levels of COHb after CO exposure. COHb accumulates rapidly after minimal exposure to CO. This effect becomes more pronounced with higher inspired concentrations of CO.

(Modified from Stewart RD, et al.: Rapid estimation of carboxyhemoglobin level in fire fighters, JAMA 235:390-392, 1976.)

CO binding of hemoglobin and cytochrome P450 produces a leftward shift of the oxygen-hemoglobin dissociation curve and subsequently interferes with erythrocyte transport and oxygen use within the mitochondria (Fig. 31-5). CO-induced alterations of oxygen delivery and cellular usage have the greatest impact on those organ systems with the highest baseline oxygen requirements (i.e., the brain and heart). Ambient levels of 100 ppm are sufficient to produce acute neurologic symptoms (e.g., agitation, dizziness, lethargy, and seizures) in addition to chest pain, dyspnea, and noncardiogenic pulmonary edema. In animal models, CO has been observed to have direct myocardial depressant properties that are independent from the effects of global hypoxemia (Suner and Jay, 2008). The classically-described cherry-red appearance of patients with CO toxicity is rare and should actually be considered a late sign associated with high mortality (“when you’re cherry red, you’re dead”). Most patients have pallor that reflects the functional anemia previously described.

FIGURE 31-5 Leftward shift of hemoglobin dissociation curve. Accumulating levels of COHb interfere with normal oxygen transport and create a functional anemia with subsequent reduction of tissue oxygen delivery.

(Modified from Fein A, et al.: Pathophysiology and management of complications resulting from fire and the inhaled products of combustion: review of the literature, Crit Care Med 8:94, 1980.)

Standard peripheral oximetry overestimates oxygen saturation in the patient with acute CO intoxication and masks profound hypoxemia (Kao and Nañangas, 2004). Arterial sampling of Pao₂ is also misleading, because this technique quantifies plasma levels of dissolved oxygen rather than actual hemoglobin saturation. COHb may be assayed with blood samples or measured directly with a noninvasive cooximeter (Masimo Rad-57, Masimo Corporation; Irvine, Calif) that measures and compares multiple light wavelengths to identify COHb and methemoglobin levels (Suner and McMurdy, 2009).

Long-term sequelae may manifest as chronic headaches, memory disturbances, learning disabilities, and neuromotor dysfunction in as many as 10% of those patients who experience severe exposure (Ginsberg, 1985). Some studies suggest that CO induces brain-lipid peroxidation and leukocyte-mediated inflammation, which culminate in white matter demyelination or focal necrosis (Wang et al., 2009). Neuropsychiatric effects may appear days to weeks after the initial exposure, and although most patients eventually achieve complete clinical recovery, radiographic evidence of CO-induced changes persist for far longer.

Currently, it is difficult to determine the precise risk of long-term neurologic effects, although some clinicians have advocated the use of hyperbaric oxygen therapy (HBOT) to limit neuropsychiatric changes. There is conflicting evidence pertaining to the efficacy of HBOT, in part because the neurocognitive symptoms may be attributable to several factors other than CO exposure (Chou et al., 2000; Gilmer et al., 2002). The benefits of this treatment remain controversial, and HBOT is often impractical for those patients with severe comorbid injuries.

Cyanide Toxicity

Cyanide inactivates cytochrome oxidase and prevents mitochondrial oxidative phosphorylation, even in the presence of adequate oxygen; therefore, normal cellular aerobic metabolism is altered to an anaerobic state (Geller et al., 2006). Toxicity manifests as supranormal venous oxygen levels with a concurrent metabolic lactic acidosis that does not resolve with oxygen therapy. The patient displays many similar neurologic and cardiovascular symptoms as observed with CO poisoning, and in fact may require treatment for the toxic effects from both vapors. Treatment involves the administration of agents that scavenge intracellular cyanide and promote its conversion to nontoxic metabolites. Sodium thiosulfate donates a sulfur group to cyanide and increases its conversion rate to thiocyanate, which then undergoes renal elimination (Gracia and Shepard, 2004). Nitrites (e.g., amyl nitrite and sodium nitrite) induce methemoglobin, which then interacts with cyanide to release it from cytochrome-oxidase binding sites. Nitrites should be used with caution in children because concurrent methemoglobin and carboxyhemoglobinemias significantly reduce oxygen-carrying capacity (Fidkowski et al., 2009). Hydroxocobalamin combines with cyanide to form nontoxic cyanocobalamin (vitamin B₁₂), and this compound is excreted by the kidneys (Borron et al., 2007).

Additional Injury Mechanisms

Acute dermal necrosis from burn trauma is characterized by protein denaturation, loss of elasticity, and tense contractures of the dermal remnant. The rigid layer of eschar that accompanies circumferential full-thickness burns of the abdomen and thorax may severely restrict diaphragmatic movement and chest-wall expansion, quickly progressing to respiratory failure within the first hours after trauma (Quinby, 1972). Markedly elevated intraabdominal and intrathoracic pressures impair venous return, with subsequent reduction of cardiac output (Demling, 1986). Compressive effects of circumferential burns involving the upper or lower extremities lead to neurovascular compromise and render the limbs nonviable. Abdominothoracic and extremity escharotomies are performed to relieve compartment syndromes and restore effective chest wall compliance and limb perfusion.

Dysfunction caused by sepsis or drug interaction Hematopoietic ↓ Red cell mass, anemia
Thrombocytopenia
↑ Fibrin split products
Coagulopathies Thrombocytosis
Coagulopathies
Transfusion reactions
Transfusion-related infection Neurologic Encephalopathy
Seizures
↑ ICP Encephalopathy
Seizures
ICU disorientation Skin ↑ Thermal, fluid, electrolyte loss Contractures and scarring Metabolic ↓ Ionized calcium ↑ Oxygen consumption
↑ CO₂ production
↓ Ionized calcium Pharmacokinetics Altered volume of distribution
Altered protein binding
Altered pharmacokinetics
Altered pharmacodynamics ↑ Opioid/sedative tolerance
Enzyme induction
Altered receptor function
Drug interactions

TNF_α, Tumor necrosis factor-α; GFR, glomerular filtration rate; ICU, intensive care unit.

Modified from Szyfelbein SK, et al.: Burn injuries. In Coté CJ, et al., editors: A practice of anesthesia for infants and children, ed 2, Philadelphia, 1993, Saunders.

The release of tumor necrosis factor-α (TNFα) from cardiac myocytes has been demonstrated to contribute to progressive cardiac contractile dysfunction in several models of trauma, thermal injury, and sepsis (Horton et al., 2004; Niederbichler et al., 2006). TNFα is a well-recognized inflammatory mediator that normally modulates the antimicrobial and metabolic response to tissue injury. In the context of burn trauma, this mediator recruits additional neurohumoral agents that exacerbate organ injury and initiate cellular apoptosis. Interleukins (IL-1β, IL-6, and others) also possess negative inotropic effects and may act synergistically with TNFα to perpetuate postburn myocardial cardiac depression (Maass et al., 2002a, 2002b). Nuclear factor κβ (NFκβ) is a transcription agent involved in the regulation of many of the cytokines and chemokines that contribute to the progression of SIRS. Burn trauma appears to activate myocardial NFκß, which promotes the secretion of TNFα (Maass et al., 2002a). Prolonged hypotension that is resolved with volume replacement may result in reperfusion injury and the formation of oxidized free radicals and lipid peroxidation by-products. These agents exacerbate the tissue damage incurred during the low-flow state (Parihar et al., 2008). Free radical generation is accompanied by impaired antioxidant mechanisms and the up-regulation of inducible nitric oxide synthetase (iNOS). This cascade promotes peripheral vasodilation, enhanced NFκβ release, and production of additional reactive tissue injury mediators such as peroxynitrite (Horton, 2003). Leukotrienes, platelet activation factor, thromboxane A_2, and complement are other factors that potentially modulate burn-induced inflammatory responses. Cellular oxidative stress is an important component of burn-mediated injury with a complex and extensive impact on organ function. Further studies are needed to fully describe the interactions of many neurohumoral mediators detected during the systemic burn response, and their appropriate manipulation may result in therapeutic benefits.

Burn shock is the clinical summation of intravascular fluid deficits and cellular ischemia that is initially characterized by decreased cardiac output, impaired contractility, and hypoperfusion of organ systems. Thermal injury also creates significant alterations in endothelial permeability, resulting in pronounced fluid translocation and generalized edema formation (Warden, 2002). Transcellular electrolyte shifts and the loss of circulating plasma proteins further impair tissue perfusion. Pediatric burn patients possess limited compensatory responses to systemic hypotension and vasoactive infusions (e.g., dopamine or norepinephrine) may be needed to supplement intravenous fluid administration to achieve adequate blood pressure and cardiac output. Resuscitation guidelines have evolved to become goal-oriented rather than formula-driven; current recommendations advocate periodic reassessment and adjustment of individual fluid requirements to restore organ perfusion and tissue oxygenation.

Survivors of the acute injury phase often develop a hyperdynamic circulation that is characterized by marked elevation of cardiac output and lowered peripheral vascular resistance. Hypertension has been observed with increased incidence in patients who have sustained more than 20% TBSA thermal injuries (Falkner et al., 1978). Elevations of plasma renin, aldosterone, and catecholamines have been noted. Untreated hypertension may manifest as seizures, encephalopathy, and ultimately, end-organ dysfunction in up to 7% of pediatric patients with severe burns (Popp et al., 1980). Although desirable, antihypertensive therapy may have adverse side effects in this setting and should be guided by clinically relevant measures of systemic perfusion.

Renal Abnormalities

Acute renal dysfunction occurs in the context of hypoperfusion, intravascular depletion, myoglobin-induced tubular damage, and mechanical obstruction secondary to cast formation by the products of hemolysis (Aikawa et al., 1990). Hyperglycemia is a function of the stress response and may add to intravascular volume depletion by promoting an osmotic diuresis. Efforts to maintain urine output within a recommended range of 1 to 1.5 mL/kg per hour should be confirmed with serial urimeter measurements that demonstrate ongoing evidence of adequate fluid resuscitation. Tubular dysfunction in the form of altered responses to plasma renin and aldosterone may also contribute to renal derangements (Mariano et al., 2008).

Significant interpatient differences concerning the pharmacodynamics and pharmacokinetics of commonly used antibiotics have been reported (Weinbrem, 1999; Kiser et al., 2006; Conil et al., 2007). Alterations of creatinine clearance and glomerular filtration rates impact drug-dosing schedules and effective plasma concentrations, necessitating customized dosing regimens guided by serum plasma levels (Boucher et al., 1992). Antibiotics with nephrotoxic properties are likely to exacerbate renal dysfunction.

Perturbations of extracellular water and macromolecules affect electrolyte composition, and rapid changes of serum sodium, potassium, and calcium concentrations are associated with increased morbidity; serial monitoring and correction of these alterations is an essential component of acute burn management. Elevated levels of stress hormones (e.g., aldosterone, angiotensin, catecholamines, and plasma renin) also contribute to renal dysfunction observed in the early postburn period. Patients with thermal injuries release elevated levels of atrial natriuretic peptide (ANP), which may mitigate the adverse effects of low-flow states by improving renal blood flow and urine output (Onuoha et al., 2000). Animal studies have shown intrarenal redistribution of blood flow with the preservation of inner cortical perfusion. Reductions in urinary chloride and sodium concentration reflect the increased perfusion of the juxtaglomerular nephrons that possess significant salt-retention capacity (Carter and Well, 1975).

Hepatic Abnormalities

Burn-related hepatic dysfunction is a significant contributor to morbidity and mortality. Hepatic blood flow is compromised in the early burn phase secondary to blood loss, large-volume fluid shifts, and compensatory vasoconstriction. The extent of hepatocellular derangement is also influenced by the onset of sepsis, toxic drug interactions, and the potential infectious risks of multiple blood product transfusions. Liver dysfunction is likely modulated by cytokines IL-1β and TNFα, both of which are potent inflammatory mediators (Jeschke et al., 1999). Elevations of serum transaminases, reduced synthesis of constitutive proteins (e.g., albumin, transferrin, and retinol-binding protein), and focal hypertrophy are all clinical markers of evolving hepatic dysfunction (Jeschke et al., 2007a).

Restoration of hepatic blood flow precedes an extended phase of hypermetabolism and initiates a catabolic cascade with adverse systemic effects. Acute phase protein production occurs at the expense of albumin synthesis, and subsequent reductions of the protein binding capacity result in unpredictable drug plasma levels. The acute-phase process may continue for months, prolonging systemic organ dysfunction and delaying efforts to restore lean body mass (Jeschke et al., 2004). The duration and severity of hepatic dysfunction are variable and ultimately dependent on the ability to reconvert the patient’s hepatic function to an anabolic state; this process requires successful wound closure, infection control, and adequate nutritional support.

Metabolic and Gastrointestinal Abnormalities

The severity of burn trauma correlates directly with the anticipated degree of inflammatory and hypermetabolic responses, and these physiologic derangements are associated with increased mortality for those patients who have experienced more than 60% TBSA burn (Jeschke et al., 2007b). Endogenous catecholamines and other stress hormones (e.g., glucagon and glucocorticoids) act synergistically to produce metabolic changes that include a hyperdynamic circulation, sharply elevated basal energy expenditure, and the catabolism of skeletal muscle proteins. Additional clinical findings include refractory tachycardia, increased cardiac output and oxygen consumption, hyperpyrexia, and increased carbon dioxide production (Tredget and Yu, 1992).