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Update on the Critical Care Management of Severe Burns

Kevin R. Kasten, Amy T. Makley and Richard J. Kagan J Intensive Care Med 2011 26: 223 DOI: 10.1177/0885066610390869 The online version of this article can be found at: http://jic.sagepub.com/content/26/4/223

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Update on the Critical Care Management of Severe Burns

Kevin R. Kasten, MD1, Amy T. Makley, MD1, and Richard J. Kagan, MD, FACS1,2

Journal of Intensive Care Medicine 26(4) 223-236 The Author(s) 2011 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0885066610390869 http://jicm.sagepub.com

Abstract Care of the severely injured patient with burn requires correct diagnosis, appropriately tailored resuscitation, and definitive surgical management to reduce morbidity and mortality. Currently, mortality rates related to severe burn injuries continue to steadily decline due to the standardization of a multidisciplinary approach instituted at tertiary health care centers. Prompt and accurate diagnoses of burn wounds utilizing Lund-Browder diagrams allow for appropriate operative and nonoperative management. Coupled with diagnostic improvements, advances in resuscitation strategies involving rates, volumes, and fluid types have yielded demonstrable benefits related to all aspects of burn care. More recently, identification of comorbid conditions such as inhalation injury and malnutrition have produced appropriate protocols that aid the healing process in severely injured patients with burn. As more patients survive larger burn injuries, the early diagnosis and successful treatment of secondary and tertiary complications are becoming commonplace. While advances in this area are exciting, much work to elucidate immune pathways, diagnostic tests, and effective treatment regimens still remain. This review will provide an update on the critical care management of severe burns, touching on accurate diagnosis, resuscitation, and acute management of this difficult patient population. Keywords burn, ICU, resuscitation, inhalation, sepsis, nutrition
Received January 8, 2010, Received Revised February 19, 2010. Submitted March 25, 2010.

Introduction
Burn injuries account for 500 000 medical visits annually, of which 40 000 require hospitalization.1 A total of 67% of reported burns in the United States involve less than 10% total body surface area (TBSA) with a mortality rate under 0.5%. Proper diagnosis and treatment by emergency room physicians and general practitioners is vital for good long term outcomes.1-4 In those patients requiring hospitalization, appropriate resuscitation, nutritional support, and early surgical treatment can minimize morbidity and mortality rates,5 especially when treatment occurs in one of the 125 hospitals with specialized burn centers.1 The evolution of burn management in the context of specialized care in dedicated treatment centers has led not only to an overall decrease in burn-related mortality, but also to a marked increase in the LA50 (mean extent of burn associated with 50% mortality) for burn injuries from 40% to >90% TBSA (Figure 1).6-9 Whether treating a burned individual as inpatient or outpatient, appropriate knowledge of burn shock and resuscitation, nutrition requirements, and wound care will aid the clinician in the management of the patient.

Evaluation of the Burn Wound

The skin is composed of 2 distinct layers and provides protection against fluid loss, mechanical damage, and infection. The epidermis consists of keratinocytes, melanocytes, and Langerhans cells, while the dermis consists of structural proteins and cells responsible for tensile strength.10 Blood vessels, hair follicles, and sweat glands are rooted in the dermis. Preservation of these dermal structures following superficial injury is responsible for the regeneration of epidermal cells required for primary healing.11 The depth and extent of injury depend on the mechanism of burn and duration of exposure to the heat source. Scald burns are associated with a robust pro-inflammatory response leading

1 2

Department of Surgery, University of Cincinnati, Cincinnati, OH, USA Shriners Hospitals for Children-Cincinnati, OH, USA

Corresponding Author: Richard J. Kagan, Shriners Hospitals for Children, University of Cincinnati College of Medicine, 3229 Burnet Avenue, Cincinnati, OH 45229, USA Email: rkagan@shrinenet.org

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Figure 1. Schematic view of increased LA50 over time. A representation of the developments in burn care over the past 70 years that have allowed for a steady increase in total body surface area (TBSA) burn size from which 50% of patients will survive.

to increased systemic complications,12 while flame burns are often associated with an increased incidence of inhalation injury, an independent risk factor for mortality.5,11 Chemical burns involve prolonged tissue damage even after removal of the inciting agent, and in the case of hydrofluoric acid, can produce life-threatening electrolyte abnormalities. Electrical burns require close evaluation for cardiac abnormalities and compartment syndrome due to muscle necrosis. Regardless of mechanism, outcomes are directly influenced by burn depth, % TBSA involvement, patient age, and the ability of the treating clinician to properly assess and manage all aspects of the burn injury. First-degree burns are characterized by erythematous changes, lack of blistering, and significant pain. Wounds blanch easily on examination and heal within 2 to 3 days following desquamation of dead cells. Scarring is rare and these injuries should not be included in the estimate of burn size.11 Superficial partial-thickness burns involve the entire epidermis, typically forming fluid-containing blisters at the dermal-epidermal junction. Wounds are erythematous, wetappearing, painful, and blanch with pressure. As the deeper dermis is left undamaged, wounds heal within 2 weeks without the need for skin grafting.11 Superficial and deep partialthickness burns merit distinction because deep partialthickness burns behave clinically like third-degree burns. Deep partial thickness burns blister, but the blister base will have a mottled pink and white appearance due to partially damaged blood vessels. These wounds do not easily blanch and are less painful than superficial burns due to concomitant nerve injury. Some burn surgeons advocate initial monitoring of these areas for up to 14 days to allow wound demarcation, resulting in

fewer operations and less-extensive grafting. Rarely, wounds heal without surgical intervention, but remain at risk for developing hypertrophic burn scars and/or contractures.11 Full-thickness, or third-degree, burns are defined by complete involvement of all skin layers and require definitive surgical management. These wounds are white, cherry red, brown or black in color, and do not blanch with pressure. They are typically insensate from superficial nerve injury. The calculated % TBSA is an independent risk factor correlating with length of hospital stay and mortality5; however, the extent of burn injury is overestimated by up to 75% of initial care providers.13 Incorrect wound extent calculation leads to over-resuscitation, inappropriate transfer to burn centers, and poor use of limited resources.14 Burn diagrams, the rule of nines, and using the palm and fingers of the patients hand to estimate 1% of normal body surface area are methods for burn size estimation.15 The rule of nines is a rough estimation of adult body surface area which often overestimates burn size in children, supporting the need for age-specific body surface area charts such as the Lund Browder diagram.16 (Figure 2). Newer methods to calculate burn surface area using computerized imaging, 2- and 3-dimensional graphics, and body contour reproductions are currently being researched to improve accuracy in initial wound assessment.17

Early Management and Resuscitation of Burn Injuries

Approximately 10% of burns present with additional traumatic injuries, so all patients should be evaluated and managed using

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Figure 2. Shriners Hospitals for Children Burn Diagram (Lund-Browder). This adaptation of the Lund-Browder diagram is utilized in our hospital for estimation of depth and extent of burn in the acute patient.

Advanced Burn Life Support protocols.11 Burn wounds are initially washed with tepid water18 following removal of the heat source. Chemical burns are copiously irrigated for a minimum of 15 minutes. Ice or iced water increases tissue damage and is contraindicated due to the risk of hypothermia in patients sustaining extensive burns.19,20 Electrical injuries mandate tailored evaluation given the propensity for compartment syndrome, cardiac dysrhythmias, muscle necrosis, and multiorgan system involvement.21 Approximately 60% to

70% of burns seen in emergency departments involve less than 10% TBSA and are treated with minor debridement, oral hydration, topical wound care, and outpatient follow-up.22 Patients who fail outpatient therapy or require supplemental nutrition or hydration need continued care as inpatients. In such cases, the optimal treatment and management of large or complicated burn injuries is in a high volume center.11,23 Current American Burn Association (ABA) guidelines recommend the transfer of patients meeting specific criteria, including patients

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Table 1. Estimated Fluid Resuscitation Requirements for a 12 Year Old Child with 25% Total Body Surface Area Scald Burns. Hourly fluid administration is guided by the response to treatmenta Shriners HospitalCincinnati First 8 Hours 3550 cc/LR 443.8 cc/h
a

Parkland Formula First 8 Hours 2500 cc/LR 312.5 cc/h Second 16 Hours 2500 cc/LR 156.3 cc/h

Modified Brooke Formula First 8 hours 1250 cc/LR 156.3 cc/h Second 16 Hours 1250 cc/LR 78.1 cc/h

Second 16 Hours 3550 cc/LR 221.9 cc/hr

Initial vital signs in the ER include a weight of 50 kg, height of 145 cm, heart rate of 130 bpm, blood pressure of 90/45, and respiratory rate of 23 with an oxygen saturation of 94% on room air. The following are indicated resuscitation regimens, all titrated based on the patients urine output.

at extremes of age, large burns, or burns involving critical anatomy. Prior to transfer, wounds should be covered with clean, dry material or nonadherent gauze.24 The use of wet dressings should be avoided to prevent development of hypothermia in patients with large burn wounds.23 Tetanus prophylaxis, appropriate pain control, and placement of a urinary catheter in patients being actively resuscitated are all necessary prior to transport.

Burn Resuscitation
Delay in resuscitation increases mortality following severe burn injury.5 Intravenous access can be obtained peripherally with small burns but requires central placement for most burns greater than 20% TBSA. Balanced crystalloid infusion should begin after intravenous access is gained, customarily using the Parkland or modified Brooke formulas as initial guidance. The Parkland formula was developed in the 1970s by Baxter and Shires who discovered that resuscitating with a higher volume in the first 8 hours improved cardiac output.25 Pruitt et al altered the original Brooke formula to demonstrate that a lower volume of fluid achieves the same endpoints of resuscitation as the Parkland formula.25 The modified Brooke formula calls for 2 mL/kg per %TBSA burn of balanced salt solution over the first 24 hours following injury, while the Parkland formula recommends 4 mL/kg per %TBSA burn. Although both formulas call for the subsequent titration of fluid rates, in a comparative analysis the Parkland formula more often resulted in over-resuscitation and was an independent risk factor for mortality.26 However, a separate comparative study found no clinical differences in outcomes between patients resuscitated using these 2 formulas.27 Consensus fluid resuscitation by standardized formula has not been reached.25 At our institution, resuscitation includes the administration of estimated basal fluid requirements in addition to the replacement of extensive fluid losses secondary to burn injury (Table 1). Regardless of the resuscitation formula used, all rely on accurate assessment of extent and depth of burn and prompt tailoring of the infusion rate to the individual patient. Resuscitation should be titrated to clinical endpoints including urine output (30-50 mL per hour in adults and 0.5-1 mL per kg per hour in children26) and hemodynamic parameters.25 Evaluation of hemodynamic parameters customarily involves cardiac monitoring, continuous pulse oximetry, and invasive or noninvasive blood pressure measurement.

Swan-Ganz catheters have fallen out of favor in the management of ICU patients but may be helpful in monitoring the resuscitation of the acute burn patient. Newer products such as the NICO (Philips Respironics) and Vigileo Monitor (Edwards Lifesciences) allow measurement of cardiac output and other systemic parameters in patients with burn via end-tidal carbon dioxide and an arterial line, respectively.28,29 Noninvasive methods of cardiac output measurement include esophageal Doppler and pulse contour cardiac output, both demonstrating results comparable to invasive techniques.30 To help avoid the complications of inadequate or excessive resuscitation, current research is examining the utility and efficacy of closed-loop autonomous resuscitation.31 Historically, initial resuscitation formulas called for the use of albumin during the first 24 hours following injury as an adjunct to crystalloid.25 This was advocated because serum protein levels decrease rapidly after burn injury, sometimes resulting in crystalloid resuscitation failure.32 In fact, patients receiving colloid as part of their resuscitation require less crystalloid and total fluid compared to resuscitation with crystalloid only.33 However, recent evidence demonstrates colloid resuscitation does not affect mortality and is more expensive than crystalloid solutions.34 The theoretical reduction in complications and mortality from colloid use has not been proven in prospective human trials and is only used in patients unresponsive to resuscitation with crystalloid.

Complications of Resuscitation
Delayed or inadequate resuscitation results in poor perfusion to both vital organs and the evolving burn wound itself. This can lead to necrosis of previously viable tissue, along with progression of superficial burns to deeper injuries requiring grafting.35 A recent review of the literature demonstrates that a significant proportion of burn injuries are resuscitated with fluid volumes in excess of that calculated by the Parkland formula, mostly due to the use of bolus therapy (ie, ATLS, PALS).32,36 The development of compartment syndromes in the extremities, torso, or abdomen has been linked to the presence of deep, full-thickness circumferential burns and the volume of fluid infused.37 The systemic inflammatory response associated with larger burns leads to microcirculatory leak, vasodilatation, and decreased cardiac output and contractility.38 Clinical suspicion is supported by findings of delayed capillary refill, cyanosis, paresthesias, and diminished pulses. Compartment pressures

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Kasten et al can be measured by placement of an 18-g needle connected to an arterial pressure transducer under the eschar into the subfascial tissue. Pressures above 30 mm Hg in any compartment are considered diagnostic. Treatment necessitates decompression via escharotomy and/or fasciotomy by experienced practitioners. Escharotomy includes incision along the full length of eschar with extension into viable unburned tissue, typically using electrocautery. Fasciotomies involve the surgical opening of the full length of fascial compartments. In both cases, a tissue bulge is often noted indicating adequate release of compartment pressure. The success of these procedures can be quantified by measuring both prerelease and postrelease pressures using a bedside manometric device. While escharotomies are commonly performed at the bedside using mild sedation, fasciotomies may need to be performed in an operating room under general anesthesia. Due to increased morbidity from withheld, delayed, or incorrectly executed procedures, these procedures should only be performed by experienced practitioners at the time of diagnosis.39 Abdominal distention, oliguria, and difficulties with mechanical ventilation may signal development of an abdominal compartment syndrome (ACS). Abdominal compartment syndrome significantly decreases perfusion to vital organs including the small and large bowel, liver, and kidneys, contributing to the development of multisystem organ failure.25 Early recognition of abdominal hypertension through serial bladder pressure evaluation40 can allow for timely decompressive laparotomy and avoidance of the sequelae caused by prolonged tissue ischemia. Percutaneous drainage with peritoneal dialysis catheters may be an effective alternative to laparotomy, preventing the significantly increased morbidity and mortality related to fluid loss through an open abdomen.

227 action in the respiratory mucosa can lead to an increased incidence of pulmonary infections.48

Diagnosis of Inhalation Injury

Closed-space burns involving steam, combustibles, hot gases or explosions should alert the treating physician to possible airway injury. Inhalation injury may be present without evidence of cutaneous injury. The physical exam should include inspection for soot in the oropharynx, carbonaceous sputum, singed nasal or facial hairs, and face or neck burns. Signs of respiratory distress including wheezing, stridor, tachypnea, or hoarseness, along with altered mental status, agitation, anxiety, or obtundation, are strongly suggestive of inhalation injury. Patients may develop progressive respiratory failure upon completion of resuscitation, so clinical suspicion should remain elevated to allow prompt diagnosis. As noninvasive monitoring of pulse oximetry in patients with burn having inhalation injuries can be misleading, laboratory and invasive studies are helpful diagnostic adjuncts. Arterial blood gas (ABG) analysis may indicate a component of inhalation injury with a PaO2:FiO2 ratio < 300 upon completion of resuscitation.57 Albeit controversial, this ratio has been proposed as an indicator of poor outcome in patients with burn.58-61 The half-life of carbon monoxide (CO) is 240 to 320 minutes, decreasing to 40 to 80 minutes with 100% normobaric oxygen,62 so interpretation of carboxyhemoglobin values should be correlated with elapsed time from injury and oxygen therapy provided. If concerned, blood cyanide levels should be drawn, carefully interpreted, and treatment initiated using amyl nitrate perles, 10% sodium nitrite, and 25% sodium thiosulfate.63,64 Chest x-ray and computed tomography scans are insensitive for inhalation injury diagnosis due to a relatively normal lung and airway appearance early in the clinical course.65,66 Fiberoptic bronchoscopy is the gold standard for diagnosis as direct visualization of the supra- and infraglottic airway allows for quantification of hyperemia, edema, and carbonaceous material. Fiberoptic bronchoscopy can be therapeutic via removal of excess exudate, plugs or casts, and placement of an endotracheal tube (ETT) or nasotracheal tube (NTT).67

Inhalation Injury
The development of pulmonary complications has been attributed to both excessive fluid resuscitation.41 and systemic inflammation resulting in third spacing, accumulation of interstitial edema, and symptoms of ARDS.42 The presence of inhalation injury creates an increased fluid requirement, further complicating the resuscitation and management of a disease process predictive of respiratory failure and increased mortality.5,11,34,43-51 The lower airway, consisting of the tracheobronchial tree and lung parenchyma, is rarely injured by heated dry air due to reflexive vocal cord closure and the evaporative cooling capacity of the upper airway.52,53 Inhaled toxins activate alveolar macrophages, initiating direct cellular damage54 with airway hyperemia visible shortly after injury. Inhalants also induce an inflammatory response in the pulmonary parenchyma with disruption of surfactant synthesis and worsening lung compliance.55 Reactive oxygen species (ROS) are molecules synthesized by phagocytic cells such as macrophages and neutrophils that increase vascular permeability with subsequent extrusion of fluid, increased tissue edema, formation of airway casts, and ultimately airway obstruction.56 Loss of ciliary

Management of Inhalation Injury

With suspected inhalation injury, 100% oxygen should be initiated immediately with the duration of treatment dictated by the patients condition and the return of the carboxyhemoglobin to normal levels, or below 10%.68,69 Vascular carboxyhemoglobin decreases much more rapidly with oxygen therapy than carboxymyoglobin, especially in the context of continued treatment with 100% FiO2. This is postulated to promote tissue washout which may actually increase tissue levels of carbon monoxide.70 Additionally, as cardiac muscle contains myoglobin, tissue washout may possibly contribute to myocardial hypoxia.70 Because of this, we do not advocate sustained high inspiration oxygen concentration in the treatment of CO poisoning once carboxyhemoglobin levels have normalized.

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Journal of Intensive Care Medicine 26(4) and mortality compared to individuals treated with conventional modes of ventilation.75-77 Airway pressure release ventilation uses high and low PEEP to provide adequate oxygenation and recruitment of closed alveoli. Benefits include reduced barotrauma, improved oxygenation and ventilation due to improved V:Q matching, and decreased sedation and paralysis requirement. In those patients refractory to conventional ventilation strategies, the use of venovenous extracorporeal oxygenation (ECMO) is an option where available. While nonsurvivors were shown to have greater peak and mean airway pressures prior to onset of extracorporeal life support (ECLS).78 scattered reports throughout the literature show minimal improvement in mortality.79-81 Adjunctive therapies such as aggressive pulmonary toilet, nitric oxide, nebulized heparin, N-acetylcysteine, and/or bronchodilators should be considered. Inhaled nitric oxide provides variable improvement in PaO2:FiO2 ratios and survival in patients responding to treatment.82 Therapy should be discontinued due to futility and cost if a response is not demonstrated between doses of 5 and 20 ppm of nitric oxide within 60 minutes.82 Nebulized heparin and tissue plasminogen activator (TPA) have demonstrated potential efficacy in animal and human studies through breakdown of fibrin deposition associated with inhalation injury, maintenance of alveolar structure, and reduced obstruction.83 Although survival benefit has not clearly been demonstrated with Mucomyst use following pulmonary injury, N-acetylcysteine was noted to decrease leukocytes in bronchoalveolar lavage.84-86 Aerosolized delivery of b2-agonists preferentially causes bronchodilation, attenuation of lung inflammation, and may potentially improve fluid clearance without systemic cardiac activation.87 While corticosteroids demonstrate benefit in most chronic pulmonary diseases, improvement in acute pulmonary inflammation secondary to inhalation injury and ARDS has not been definitively demonstrated.68,88-90 Steroids for inhalation injury should be used with caution until larger prospective studies are completed.

Figure 3. Edema associated with inhalation injury and resuscitation. This photograph depicts facial edema due to severe inhalation injury and burn shock resuscitation in a pediatric burn patient. Nasotracheal intubation was performed early to prevent accidental loss of airway.

Rapid displacement of carboxyhemoglobin through hyperbaric oxygen (HBO) therapy has also been advocated due to the neurologic sequelae related to CO poisoning. Unfortunately, there is a paucity of evidence-based literature for HBO use with regard to triggers for the initiation of therapy, the duration and intensity of therapy, and the clinical benefit of such treatment.71 Additionally, the risk of complication from barotrauma in patients with burn having suspected inhalation injury, combined with the risk of monitoring patients with severe burns inside the chamber, likely outweighs any perceived benefit from this therapy. Further studies are needed to fully address the role of HBO therapy in patients with severe burns and/or inhalation injuries. Continuous pulse oximetry may be accurately utilized once carboxyhemoglobin levels normalize. Inhalation injuries can quickly progress to obstruction, hypoxia, and death, with limited ability to intubate late in the disease course, so timely establishment of a definitive airway is required (Figure 3). Early tracheostomy should be considered in any patient with a projected need for mechanical ventilation longer than 2 weeks. Percutaneous tracheostomy placement in burn patients was associated with lower complication rates and cost compared to open tracheostomy in a small, historically controlled study.72 The question of open versus percutaneous tracheostomy is an important one and requires further exploration through randomized controlled trials. Patients with inhalation injury may require nonstandard methods of ventilation such as volumetric diffusive respiratory (VDR) and airway pressure release ventilation (APRV) modes. Volumetric diffusive respiratory involves progressive accumulation of subtidal breaths and passive exhalation once a set airway pressure is met.73 Increased PaO2, PaO2:FiO2 ratio, and decreased mean airway pressure have been demonstrated using this mode, all without adversely affecting hemodynamics.73,74 This modality may also decrease the incidence of pneumonia

Nutritional Support in Burns

Burns induce a hypermetabolic state that may persist for up to 12 months following injury.91,92 Many metabolic disturbances following burn injuries are related to systemic inflammation and altered hypothalamic function, with resultant increases in temperature setpoint and production of catecholamines (reviewed in93). This leads to increased protein catabolism and lipolysis, culminating in decreased lean body mass, poor wound healing, and weakened host defenses. Most equations often overestimate the energy requirements of patients with burn, with indirect calorimetry remaining the gold standard for calculating resting energy expenditure (REE).94-100 Respiratory quotient is unreliable in evaluating the nutrition status of patients with burn.101 Overfeeding results from excess carbohydrate or fat intake, both detrimental to the critically ill patient with burn. Excess carbohydrate consumption increases CO2 production, fat stores, hepatic dysfunction, hyperglycemia, and

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Kasten et al wound-healing duration.57,93,102 Protein excess does not offset hypercatabolism, and may actually increase it.102 While some studies have demonstrated improved survival and reduced hospital stay with underfeeding of nonburned critically ill patients,102 this strategy is harmful in patients with extensive burn injuries. Appropriate nutrition is required for wound healing, mediation of inflammation, suppression of the hypermetabolic response, and reduction of sepsis-related morbidity and mortality.103 Serum albumin levels are often used to monitor nutrition status in critically ill patients. In the patient with burn, albumin is a poor surrogate for nutritional status as serum concentrations are known to rapidly fall after burn injury. Replacement does not stimulate production of endogenous albumin nor has replacement demonstrated clinical benefits related to pulmonary function, wound healing, gastrointestinal function, or mortality.93 Serial measurement of prealbumin is advocated for long-term monitoring of nutrition as it is a distinct marker for protein synthesis, while the one-time measurement of nutritional markers such as transferrin, carotene, iron, and calcium are unreliable indicators of nutrition status.104 Monitoring of glucose levels remains a central part of nutritional management in patients with burn. Hyperglycemia occurs in most patients with burn regardless of injury severity due to an increased rate of glucose production and impaired tissue glucose extraction.105,106 Modulation of the inflammatory response with tight glucose control produces improved survival, sepsis control, and wound healing.107-109 Interestingly, propranolol also aids in restoration of glycemic control, in addition to reducing peripheral lipolysis and enhancing the immune response to sepsis via mediation of catecholamine release during severe burn injury.110 A retrospective review demonstrated a significant decrease in mortality and healing time for burn patients on beta blockade therapy prior to injury, an effect not seen when beta blockade was initiated in the hospital following injury.111 However, in a prospective, randomized trial, decreased healing time and hospital length of stay was demonstrated after beta blockade initiation following injury.112 Additionally, beta blockade in pediatric patients with burn has been associated with decreased cardiac work, reversal of catabolism, and attenuation of the inflammatory response without an increased risk of infection or sepsis.113-115 These findings support the conclusion that multiple factors play a role in the metabolic response to severe burn trauma and further investigation with randomized controlled trials is required.

229 injury, placement of a nasoduodenal feeding tube is recommended. Initial timing of enteral nutrition after burn injury is controversial, although most burn clinicians advocate starting feeds within hours of injury unless contraindicated. Studies demonstrating reversal of hypermetabolism, hypercatabolism, and systemic inflammation in burn animals receiving early nutrition have not been replicated in humans, possibly due to the inability to realistically start early enteral feeding within 1 to 2 hours of burn.103 Improvement in clinical measures such as decreased length of stay, infection, and mortality have also not conclusively been shown when compared to later initiation of enteral feeding (>72 hours).100 The risk of adverse events including errors in tube placement, aspiration, and intestinal necrosis underlies arguments to delay initiation of feeding until burn resuscitation has been completed. In a prospective, randomized trial, Gottschlich et al found 4 out of 5 patients who developed an abdominal catastrophe from intestinal necrosis were in the early feeding arm of the study.103 Possible explanations include hypotensive episodes during early burn resuscitation and altered gut perfusion during burn shock, combined with the increased intestinal blood flow demand with feeding.103 Despite some of these concerns, initiation of enteral nutrition upon patient stabilization is considered standard of care. Parenteral nutrition (PN), while a mainstay of therapy for many critically ill patients, is reserved for burn patients unable to tolerate enteral feedings due to severe diarrhea or an organic gastrointestinal problem. Increased complication rates in patients with burn on PN are mostly due to central venous catheter infections. Peripheral parenteral nutrition (PPN) is generally not an option due to inadequate calorie delivery and high risk of peripheral soft tissue damage from extravasation.

Vitamin and Steroid Supplementation

Vitamin A has been shown to aid wound healing following burn injury and is replaced in patients with >20% TBSA burns.120 Vitamin C plays a vital role in collagen synthesis and wound healing, necessitating its supplementation. Wound exudates were found to be the primary site of loss for trace elements,121 suggesting patients with burn may require additional supplementation compared to other critically ill patients. The trace element zinc is necessary for wound healing, and decreased zinc levels in septic patients may be associated with subsequent adverse events.57 For these reasons, zinc supplementation is oftentimes included in enteral nutrition formulas. More studies are needed to determine the role of trace element supplementation in pediatric patients with burn. Negative nitrogen balance is often seen during the first 1 to 2 weeks postburn due to hypercatabolism in burns and loss of lean body mass.100 To combat this, the effectiveness of anabolic agents such as oxandrolone in restoration of lean body mass, improved wound healing, improved nutritional status, and liver function has been studied.57,122 The impact of anabolic steroids on the course of burn disease is controversial. A few small, single center studies have been unable to

Enteral and Parenteral Support

Enteral feeding is the ideal route for caloric and nutrient supplementation in patients with burn. Maintenance of gut integrity is hypothesized to reduce the risk of bacterial translocation and subsequent sepsis.116,117 The role of specialty amino acids, proteins, and fatty acids present in commercial enteral formulations for pediatric patients with burn is controversial as studies have demonstrated mixed results.118,119 If oral caloric intake will be inadequate at 5 to 7 days following

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230 demonstrate any clear benefits, in contrast to a multicenter trial stopped prematurely because of significantly fewer hospital days for patients with severe burn treated with oxandrolone.100,123,124 More studies are needed to clarify this contentious treatment question.

Journal of Intensive Care Medicine 26(4) to delay wound healing due to a direct toxic effect on keratinocytes127 (reviewed in ref 128). To combat this, silverimpregnated dressings such as Acticoat, Aquacel Ag, Mepitel, and Mepilex have been developed to provide antimicrobial coverage, adequate humidity, and decreased trauma, all with less frequent dressing changes. Biosynthetic substitutes like Biobrane are marketed as epidermal substitutes that allow for faster re-epithelialization129; however, their use is limited due to infectious complications. In addition to topical therapies, deep burns are managed with surgical excision and placement of xenograft, allograft, autograft, or cultured skin substitutes (CSS; Figure 4). Skin substitutes and replacements require adequate wound bed preparation to ensure minimal graft loss. Most experienced burn surgeons advocate early wound excision within the first 1 to 7 days following thermal injury to attenuate the systemic inflammatory effects of burns and reduce the risk of sepsis.131-135 In fact, no significant difference in infection or mortality rates was found when burn excision was performed at any point between 2 and 7 days.136 Additionally, in a comparison of adult patients over 30 years of age sustaining greater than 30% TBSA injury, no difference in mortality was seen between excision within the first 72 hours and conservative management with grafting after granulation of the wound bed.137 However, this same study found significantly decreased mortality and length of hospital stay in pediatric patients and adults aged 17 to 30 years who underwent early excision compared to conservative management.137 The appropriate timing for burn wound excision and grafting involves a number of important factors including the age of the patient, extent and depth of burn, comorbidities, hospital resources, and physician preference. It is therefore important that the surgeon always assess the risks and/or benefits of delaying surgical treatment in burn-injured patients. At our institution, a staged approach is often taken for more extensive injuries. The burn wound is excised and bleeding controlled on the first operative day. Donor site harvest and grafting then occurs on the following operative day. This approach allows for more extensive excisions, shorter operating times, better temperature control, and the ability to perform sheet grafting with improved hemostasis. Definitive surgical management requires appropriate topical antimicrobial therapy postoperatively for prevention of graft loss and burn wound infection.

Wound Care
Improperly managed burn wounds may convert to deeper wounds requiring definitive surgical management. Cleansing and debridement of the wound is accomplished with mild soap and water or with chlorhexadine/normal saline washes. Most burn experts recommend debridement of all blisters larger than 0.5 cm to reduce the risk of bacterial colonization or infection. Burn wounds become colonized in the first few hours with gram-positive bacteria including Staphylococcus aureus and epidermidis and are predominantly colonized with gut flora such as Pseudomonas aeruginosa, Enterobacter cloacae, and Escherichia coli by 5 days. Health care workers must be vigilant in hand washing and maintenance of a clean environment around the wounds for prevention of cross-contamination in these immunocompromised patients. Culture swabs of all wound beds should be obtained upon admission and repeated serially to monitor for changes in colonization. Quantitative cultures of the burn to diagnose wound invasion are best obtained by tissue biopsy, either in the operating room or at bedside. Bacterial colonization of burn wounds does not require systemic antibiotics but should be managed with early debridement and/or excision, together with appropriate topical and/or biologic dressings. Cleansing and debridement is followed by application of a topical antimicrobial agent intended to control colonization, not sterilize the burn wound. Several layers of absorptive gauze and Kerlix cover the wound to decrease evaporative water losses.125 Minor burns can be managed with biologic dressings, silver-coated dressings, or tribiotic ointment covered with nonadherent gauze. Commonly utilized topical agents include silver sulfadiazine (Silvadene), mafenide acetate (Sulfamylon), and silver nitrate. Silvadene continues to demonstrate effective control of burn wound colonization, while remaining inexpensive and easy to apply. However, eschar penetration is minimal and complications related to leukopenia and hemolysis have been reported.126 Mafenide acetate cream (Sulfamylon) is easy to apply but is painful when applied to superficial partialthickness burns. Eschar penetration is greatest with Sulfamylon, making it the topical agent of choice in burns where the eschar will not be excised immediately, or when control of Pseudomonas aeruginosa is required. Metabolic acidosis may occur with use as Sulfamylon is a carbonic anhydrase inhibitor. Silver nitrate 0.5% solution has fallen out of favor due to electrolyte abnormalities and poor tissue penetration but may be used as a reasonably effective agent for treatment of gramnegative or fungal colonization. Aside from complications directly related to topical agents, frequent dressing changes often result in traumatized epithelialization and delayed wound healing. Silvadene has been shown

Sepsis in the Burn Patient

Improvements in resuscitation strategies and supportive care have shifted the underlying cause of morbidity and mortality in patients with burn from burn shock to infection. Unfortunately, sepsis is an independent risk factor of mortality following thermal injury, especially when multiorgan system failure (MOSF) is present.138,139 Open wounds, injured lungs, central venous catheters, and urinary catheters place the patient with burn at constant risk of infection and sepsis. Diagnostic uncertainty due to altered physiology affecting clinical and laboratory parameters complicates therapeutic intervention. Signs

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Figure 4. Burn wounds healed with culture skin substitute (CSS). Shown is the back of a pediatric patient grafted with CSS (outlined by dashed lines) and split-thickness skin autograft. A, At 2 weeks after grafting, the borders of the CSS were discernable but the wound was mostly closed. B, At 10 weeks post-grafting, the healed CSS was pliable and hypopigmented observation of some pigmented foci. Reprinted from Clinics in Dermatology, Volume 23, Dorothy M. Supp, Steven T. Boyce, Engineered skin substitutes: practices and potentials, Pages 403-412, Copyright (2005), with permission from Elsevier.

of sepsis, including elevated temperature, tachycardia, tachypnea, and leukocytosis, may be present in the burned patient without underlying infection. Laboratory markers including peripheral white blood cell (WBC) levels, procalcitonin, C reactive protein, and others have been proposed as early indicators of sepsis in the burn patient, all with mixed results. Absolute values and trends in WBC, neutrophil percentage, and body temperature are unable to predict bloodstream infection in the burn patient.139 Although controversial, use of procalcitonin level has been advocated due to its sensitivity, specificity, and mortality correlation in patients with burn having sepsis.140 However, procalcitonin was reported insufficient as a single diagnostic marker for sepsis in patients with burn141 and inferior to monitoring trends in CRP and platelet count.142 As another marker, decreased Human Leukocyte Antigen DR expression showed an inverse correlation between and mortality in sepsis.143 Continued research is needed to clarify the immune response to sepsis, ultimately aiding in accurate diagnosis of infection. Early markers of infection can alert physicians to initiate treatment of unconfirmed but potentially fatal infections. Breakdown of barrier function following burn injury provides the largest entrance point for infection. Careful attention and documentation by physicians and nursing staff of open wounds, together with weekly or biweekly cultures, can prevent progression of superficial colonization to invasive sepsis. In addition, the topical and surgical therapies enumerated above are first lines of care for the prevention of burn wound infections,

the most serious of which is invasive burn wound sepsis. Pneumonia, while not as common as burn wound infection, occurs in 4.5% of flame-injured patients and is associated with increased days of mechanical ventilation, longer ICU stay, and higher hospital cost.1,144 Aggressive bronchoscopy with BAL confirms the infectious agent, provides antibiotic sensitivity information for quick tailoring of antibiotics, and subsequently decreases ventilator and ICU days.146 Following recently released ABA guidelines for prevention, diagnosis and treatment of pneumonia can reduce the complications related to this disease process.146 Bloodstream and urinary tract infections are of constant concern due to prolonged duration of catheter use.148 Newer technologies have yielded silver-impregnated, chlorhexadine/ silver sulfadiazine coated, and antibiotic-coated catheters targeted to reduce catheter infection.149,150 Unfortunately, the ability of antiseptic/antibiotic impregnated catheters to prevent bloodstream infection was found to have no effect beyond that of a comprehensive education strategy involving proper evaluation and maintenance of indwelling catheters.151 Timing of central access exchange in the patient with burn is determined by the risk of colonization, need for placement through burned versus unburned tissue, and physician preference.152 Prompt removal of all indwelling catheters when no longer warranted provides the best prevention for infection in the patient with burn. Blood and urinary tract infections are treated with removal of the catheter whenever possible and appropriately tailored antibiotic therapy.

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12. Tschop J, Martignoni A, Reid MD, et al. Differential immunological phenotypes are exhibited after scald and flame burns. Shock. 2009;31(2):157-163. 13. Cone JB. Whats new in general surgery: burns and metabolism. J Am Coll Surg. 2005;200(4):607-615. 14. Collis N, Smith G, Fenton OM. Accuracy of burn size estimation and subsequent fluid resuscitation prior to arrival at the yorkshire regional burns unit. A three year retrospective study. Burns. 1999; 25(4):345-351. 15. Perry RJ, Moore CA, Morgan BD, Plummer DL. Determining the approximate area of a burn: an inconsistency investigated and reevaluated. BMJ. 1996;312(7042):1338. 16. Wachtel TL, Berry CC, Wachtel EE, Frank HA. The inter-rater reliability of estimating the size of burns from various burn area chart drawings. Burns. 2000;26(2):156-170. 17. Neuwalder JM, Sampson C, Breuing KH, Orgill DP. A review of computer-aided body surface area determination: Sage ii and epris 3d burn vision. J Burn Care Rehabil. 2002;23(1):55-59; discussion 54. 18. Cuttle L, Pearn J, McMillan JR, Kimble RM. A review of first aid treatments for burn injuries. Burns. 2009;35(6):768-775. 19. Sawada Y, Urushidate S, Yotsuyanagi T, Ishita K. Is prolonged and excessive cooling of a scalded wound effective? Burns. 1997;23(1):55-58. 20. Ofeigsson OJ, Mitchell R, Patrick RS. Observations on the cold water treatment of cutaneous burns. J Pathol. 1972;108(2): 145-150. 21. Koumbourlis AC. Electrical injuries. Crit Care Med. 2002;30 (11 suppl):S424-S430. 22. Latenser BA, Miller SF, Bessey PQ, et al. National burn repository 2006: a ten-year review. J Burn Care Res. 2007;28(5): 635-658. 23. Latenser BA. Critical care of the burn patient: the first 48 hours. Crit Care Med. 2009;37(10):2819-2826. 24. Armour AD, Billmire DA. Pediatric thermal injury: acute care and reconstruction update. Plast Reconstr Surg. 2009;124 (1 suppl):117e-127e. 25. Pruitt, BA Jr. Fluid and Electrolyte Replacement in the Burned Patient. Surg Clin N Am 1978; (58):1291-1312. 26. Chung KK, Wolf SE, Cancio LC, et al. Resuscitation of severely burned military casualties: fluid begets more fluid. J Trauma. 2009;67(2):231-237; discussion 237. 27. Cancio LC, Chavez S, Alvarado-Ortega M, et al. Predicting increased fluid requirements during the resuscitation of thermally injured patients. J Trauma. 2004;56(2):404-413; discussion 413404. 28. Reid RD, Jayamaha J. The use of a cardiac output monitor to guide the initial fluid resuscitation in a patient with burns. Emerg Med J. 2007;24(5):e32. 29. Jaffe MB. Partial CO2 rebreathing cardiac outputoperating principles of the nico system. J Clin Monit Comput. 1999;15(6): 387-401. 30. Berton C, Cholley B. Equipment review: new techniques for cardiac output measurementoesophageal doppler, fick principle using carbon dioxide, and pulse contour analysis. Crit Care. 2002;6(3):216-221.

Conclusion
Dedication and research over the past 5 decades has produced an enviable reduction in mortality for burn-injured patients treated in the United States. With appropriate and tailored resuscitation regimens, early enteral nutrition, quick and effective management of the burn wound with topical and surgical therapies, the severely injured burn patient can not only survive but experience minimal short and long-term morbidities. Success in these areas involves a multidisciplinary team trained in current state-of-the-art interventions and therapies, with ultimate goal of restoring function and allowing psychosocial reintegration. Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Funding
The author(s) received no financial support for the research and/or authorship of this article.

References
1. National Burn Repository 2009 Report: Dataset 5.0 American Burn Association, Chicago, IL http://www.ameriburn.org/ 2009NBRAnnualReport.pdf. 2. Wibbenmeyer LA, Amelon MJ, Torner JC, et al. Populationbased assessment of burn injury in southern iowa: Identification of children and young-adult at-risk groups and behaviors. J Burn Care Rehabil. 2003;24(4):192-202. 3. Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective estimates of the probability of death from burn injuries. N Engl J Med. 1998;338(6):362-366. 4. DeKoning EP, Hakenewerth A, Platts-Mills TF, Tintinalli JE. Epidemiology of burn injuries presenting to north carolina emergency departments in 2006-2007. Burns. 2009;35(6):776-782. 5. Wolf SE, Rose JK, Desai MH, Mileski JP, Barrow RE, Herndon DN. Mortality determinants in massive pediatric burns. An analysis of 103 children with > or 80% tbsa burns (> or 70% full-thickness). Ann Surg. 1997;225(5):554-565; discussion 565-559. 6. Esselman PC. Burn rehabilitation: an overview. Arch Phys Med Rehabil. 2007;88(12 suppl 2):S3-S6. 7. Harrington DT. Burn injuries and burn care. Med Health R I. 2009;92(5):179-180. 8. Mann R, Heimbach D. Prognosis and treatment of burns. West J Med. 1996;165(4):215-220. 9. McGwin G Jr, Cross JM, Ford JW, Rue LW 3rd. Long-term trends in mortality according to age among adult burn patients. J Burn Care Rehabil. 2003;24(1):21-25. 10. Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev. 2006;19(2):403-434. 11. Grunwald TB, Garner WL. Acute burns. Plast Reconstr Surg. 2008;121(5):311e-319e.

Downloaded from jic.sagepub.com at CAPES on August 7, 2011

Kasten et al
31. Salinas J, Drew G, Gallagher J, et al. Closed-loop and decisionassist resuscitation of burn patients. J Trauma. 2008;64 (4 suppl):S321-332. 32. Warden GD. Burn shock resuscitation. World J Surg. 1992;16(1): 16-23. 33. Goodwin CW, Dorethy J, Lam V, Pruitt BA Jr. Randomized trial of efficacy of crystalloid and colloid resuscitation on hemodynamic response and lung water following thermal injury. Ann Surg. 1983;197(5):520-531. 34. Alderson P, Bunn F, Lefebvre C, et al. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2004;(4):CD001208. 35. Nisanci M, Eski M, Sahin I, Ilgan S, Isik S. Saving the zone of stasis in burns with activated protein C: an experimental study in rats. Burns. 2010;36(3):397-402. 36. Dulhunty JM, Boots RJ, Rudd MJ, Muller MJ, Lipman J. Increased fluid resuscitation can lead to adverse outcomes in major-burn injured patients, but low mortality is achievable. Burns. 2008;34(8):1090-1097. 37. Ivy ME, Atweh NA, Palmer J, Possenti PP, Pineau M, DAiuto M. Intra-abdominal hypertension and abdominal compartment syndrome in burn patients. J Trauma. 2000;49(3):387-391. 38. Tricklebank S. Modern trends in fluid therapy for burns. Burns. 2009;35(6):757-767. 39. Brown RL, Greenhalgh DG, Kagan RJ, Warden GD. The adequacy of limb escharotomies-fasciotomies after referral to a major burn center. J Trauma. 1994;37(6):916-920. 40. Hershberger RC, Hunt JL, Arnoldo BD, Purdue GF. Abdominal compartment syndrome in the severely burned patient. J Burn Care Res. 2007;28(5):708-714. 41. Klein MB, Hayden D, Elson C, et al. The association between fluid administration and outcome following major burn: A multicenter study. Ann Surg. 2007;245(4):622-628. 42. Steinvall I, Bak Z, Sjoberg F. Acute respiratory distress syndrome is as important as inhalation injury for the development of respiratory dysfunction in major burns. Burns. 2008;34(4): 441-451. 43. Maybauer DM, Maybauer MO, Traber DL. Resuscitation with hypertonic saline in burn shock and sepsis. Crit Care Med. 2006;34(6):1849-1850. 44. Herndon DN, Thompson PB, Traber DL. Pulmonary injury in burned patients. Crit Care Clin. 1985;1(1):79-96. 45. Shirani KZ, Pruitt BA Jr, Mason AD Jr. The influence of inhalation injury and pneumonia on burn mortality. Ann Surg. 1987; 205(1):82-87. 46. Palmieri TL, Warner P, Mlcak RP, et al. Inhalation injury in children: a 10 year experience at shriners hospitals for children. J Burn Care Res. 2009;30(1):206-208. 47. Craft B, Kagan RJ. Current management of burns. Medical Update for Psychiatrists. 1998;3(2):53-57. 48. Hanumadass ML, Kagan RJ, and Matsuda T. Management of Pediatric Burns. In Vidyasagar, D and Sarnaik AP, ed. Neonatal and Pediatric Intensive Care. PSG Publishing Co. Littleton, MA; 1985:215-226. 49. McAuliffe PF and Mozingo DW. Inhalation Injury and Ventilator Management. In: Soper NJ, Saffle JR, eds. Problems in General

233
Surgery: Thermal Injuries. Philadelphia, PA: Lippincott, Williams and Wilkins; 2002;20:97-105. Robb BW and Kagan RJ: Outpatient and Emergency Department Management of Thermal Injuries. Probl Gen Surg. 2003;7-15. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1334-1349. Pruitt BA Jr, Erickson DR, Morris A. Progressive pulmonary insufficiency and other pulmonary complications of thermal injury. J Trauma. 1975;15(5):369-379. Moritz AR, Henriques FC. Studies of thermal injury II: the relative importance of time and surface temperature in the causation of cutaneous burns. Am J Pathol. 1947;23(5):695-720. Miller K, Chang A. Acute inhalation injury. Emerg Med Clin North Am. 2003;21(2):533-557. Nieman GF, Clark WR Jr, Wax SD, Webb SR. The effect of smoke inhalation on pulmonary surfactant. Ann Surg. 1980; 191(2):171-181. Herndon DN, Traber LD, Linares H, et al. Etiology of the pulmonary pathophysiology associated with inhalation injury. Resuscitation. 1986;14(1-2):43-59. Mak G AS, Kagan R. Pediatric burns. In: Wheeler D WH, Shanley T, ed. Pediatric Critical Care Medicine. Springer-Verlag; 2007:15971606. Gauglitz GG, Finnerty CC, Herndon DN, Mlcak RP, Jeschke MG. Mak G, Allen S, and Kagan RJ: Pediatric Burns. In: Wheeler D, Wong H, Shandley T, eds. Pediatric Critical Care Medicine: Basic Science and Clinical Evidence. London, UK: SpringerVerlag; 2007;1597-1606. Gonzalez-Castro A, Llorca J, Buron J, Suberviola B, Vallejo A, Minambres E. Evaluation of the oxygenation ratio as long-term prognostic marker after lung transplantation. Transplant Proc. 2007;39(7):2422-2424. Krafft P, Fridrich P, Pernerstorfer T, et al. The acute respiratory distress syndrome: definitions, severity and clinical outcome. An analysis of 101 clinical investigations. Intensive Care Med. 1996;22(6):519-529. Yilmaz M, Iscimen R, Keegan MT, et al. Six-month survival of patients with acute lung injury: prospective cohort study. Crit Care Med. 2007;35(10):2303-2307. Weaver LK, Howe S, Hopkins R, Chan KJ. Carboxyhemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure. Chest. 2000;117(3):801-808. Baud FJ, Barriot P, Toffis V, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med. 1991; 325(25):1761-1766. Barillo DJ. Diagnosis and treatment of cyanide toxicity. J Burn Care Res. 2009;30(1):148-152. Reske A, Bak Z, Samuelsson A, Morales O, Seiwerts M, Sjoberg F. Computed tomographya possible aid in the diagnosis of smoke inhalation injury? Acta Anaesthesiol Scand. 2005;49(2): 257-260. Wittram C, Kenny JB. The admission chest radiograph after acute inhalation injury and burns. Br J Radiol. 1994;67(800):751-754. Nugent N and Herndon D. Diagnosis and Treatment of Inhalation Injury. In: Herndon, ed. Total Burn Care. Saunders; Philadelphia, PA; 2007.

50. 51. 52.

53.

54. 55.

56.

57.

58.

59.

60.

61.

62.

63.

64. 65.

66. 67.

Downloaded from jic.sagepub.com at CAPES on August 7, 2011

234
68. Rabinowitz PM, Siegel MD. Acute inhalation injury. Clin Chest Med. 2002;23(4):707-715. 69. Ernst A, Zibrak JD. Carbon monoxide poisoning. N Engl J Med. 1998;339(22):1603-1608. 70. Erupaka K, Bruce EN, Bruce MC. Prediction of extravascular burden of carbon monoxide (co) in the human heart. Ann Biomed Eng. 2010;38(2):403-438. 71. Kealey GP. Carbon monoxide toxicity. J Burn Care Res. 2009; 30(1):146-147. 72. Gravvanis AI, Tsoutsos DA, Iconomou TG, Papadopoulos SG. Percutaneous versus conventional tracheostomy in burned patients with inhalation injury. World J Surg. 2005;29(12): 1571-1575. 73. Rodeberg DA, Housinger TA, Greenhalgh DG, Maschinot NE, Warden GD. Improved ventilatory function in burn patients using volumetric diffusive respiration. J Am Coll Surg. 1994;179(5): 518-522. 74. Carman B, Cahill T, Warden G, McCall J. A prospective, randomized comparison of the volume diffusive respirator vs conventional ventilation for ventilation of burned children. 2001 aba paper. J Burn Care Rehabil. 2002;23(6):444-448. 75. Cioffi WG, Graves TA, McManus WF, Pruitt BA Jr. Highfrequency percussive ventilation in patients with inhalation injury. J Trauma. 1989;29(3):350-354. 76. Cioffi WG Jr, Rue LW 3rd, Graves TA, McManus WF, Mason AD Jr, Pruitt BA Jr. Prophylactic use of highfrequency percussive ventilation in patients with inhalation injury. Ann Surg. 1991;213(6):575-580; discussion 580-572. 77. Rue LW 3rd, Cioffi WG, Mason AD, McManus WF, Pruitt BA Jr. Improved survival of burned patients with inhalation injury. Arch Surg. 1993;128(7):772-778; discussion 778-780. 78. Kane TD, Greenhalgh DG, Warden GD, Goretsky MJ, Ryckman FC, Warner BW. Pediatric burn patients with respiratory failure: predictors of outcome with the use of extracorporeal life support. J Burn Care Rehabil. 1999;20(2):145-150. 79. Alpard SK, Zwischenberger JB. Extracorporeal membrane oxygenation for severe respiratory failure. Chest Surg Clin N Am. 2002;12(2):355-378, vii. 80. Nehra D, Goldstein AM, Doody DP, Ryan DP, Chang Y, Masiakos PT. Extracorporeal membrane oxygenation for nonneonatal acute respiratory failure: The massachusetts general hospital experience from 1990 to 2008. Arch Surg. 2009;144(5):427-432; discussion 432. 81. Thompson JT, Molnar JA, Hines MH, Chang MC, Pranikoff T. Successful management of adult smoke inhalation with extracorporeal membrane oxygenation. J Burn Care Rehabil. 2005;26(1):62-66. 82. Sheridan RL, Hess D. Inhaled nitric oxide in inhalation injury. J Burn Care Res. 2009;30(1):162-164. 83. Enkhbaatar P, Murakami K, Cox R, et al. Aerosolized tissue plasminogen inhibitor improves pulmonary function in sheep with burn and smoke inhalation. Shock. 2004;22(1):70-75. 84. Fu Z, Yang Z, Liu L, Liu Z, He B, Wu J. [the influence of n-acetyl-lcysteine on pulmonary injury and oxygen stress after smoke inhalation injury]. Zhonghua Shao Shang Za Zhi. 2002;18:152-154. 85. Miller AC, Rivero A, Ziad S, Smith DJ, Elamin EM. Influence of nebulized unfractionated heparin and n-acetylcysteine in acute

Journal of Intensive Care Medicine 26(4)

lung injury after smoke inhalation injury. J Burn Care Res. 2009;30(2):249-256. Adhikari N, Burns KE, Meade MO. Pharmacologic treatments for acute respiratory distress syndrome and acute lung injury: systematic review and meta-analysis. Treat Respir Med. 2004; 3(5):307-328. Palmieri TL. Use of beta-agonists in inhalation injury. J Burn Care Res. 2009;30(1):156-159. Bernard GR, Luce JM, Sprung CL, et al. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med. 1987;317(25):1565-1570. Greenhalgh DG. Steroids in the treatment of smoke inhalation injury. J Burn Care Res. 2009;30(1):165-169. Agarwal R, Nath A, Aggarwal AN, Gupta D. Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis. Respirology. 2007;12(4):585-590. Murphy KD, Thomas S, Mlcak RP, Chinkes DL, Klein GL, Herndon DN. Effects of long-term oxandrolone administration in severely burned children. Surgery. 2004;136(2):219-224. Herndon DN, Tompkins RG. Support of the metabolic response to burn injury. Lancet. 2004;363(9424):1895-1902. Chan MM, Chan GM. Nutritional therapy for burns in children and adults. Nutrition. 2009;25(3):261-269. Carvajal HF. A physiologic approach to fluid therapy in severely burned children. Surg Gynecol Obstet. 1980;150(3):379-384. Curreri PW. Nutritional support of burn patients. World J Surg. 1978;2:215-222. Herndon DN, Curreri PW. Metabolic response to thermal injury and its nutritional support. Cutis. 1978;22(4):501-506, 514. Hildreth MA, Herndon DN, Desai MH, Duke MA. Reassessing caloric requirements in pediatric burn patients. J Burn Care Rehabil. 1988;9(6):616-618. Ireton-Jones C, Jones JD. Improved equations for predicting energy expenditure in patients: the ireton-jones equations. Nutr Clin Pract. 2002;17(1):29-31. Mayes T, Gottschlich MM, Khoury J, Warden GD. Evaluation of predicted and measured energy requirements in burned children. J Am Diet Assoc. 1996;96(1):24-29. Schulman CI, Ivascu FA. Nutritional and metabolic consequences in the pediatric burn patient. J Craniofac Surg. 2008; 19(4):891-894. Liusuwan Manotok RA, Palmieri TL, Greenhalgh DG. The respiratory quotient has little value in evaluating the state of feeding in burn patients. J Burn Care Res. 2008;29(4): 655-659. Joffe A, Anton N, Lequier L, et al. Nutritional support for critically ill children. Cochrane Database Syst Rev. 2009;(2): CD005144. Gottschlich MM, Jenkins ME, Mayes T, Khoury J, Kagan RJ, Warden GD. The 2002 clinical research award. An evaluation of the safety of early vs delayed enteral support and effects on clinical, nutritional, and endocrine outcomes after severe burns. J Burn Care Rehabil. 2002;23(6):401-415. Rettmer RL, Williamson JC, Labbe RF, Heimbach DM. Laboratory monitoring of nutritional status in burn patients. Clin Chem. 1992;38(3):334-337.

86.

87. 88.

89. 90.

91.

92. 93. 94. 95. 96. 97.

98.

99.

100.

101.

102.

103.

104.

Downloaded from jic.sagepub.com at CAPES on August 7, 2011

Kasten et al
105. 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(4):673-677; discussion 677-678. 106. Wolfe RR, Miller HI, Spitzer JJ. Glucose and lactate kinetics in burn shock. Am J Physiol. 1977;232(4):E415-418. 107. Jeschke MG, Boehning DF, Finnerty CC, Herndon DN. Effect of insulin on the inflammatory and acute phase response after burn injury. Crit Care Med. 2007;35(9 suppl):S519-523. 108. Holm C, Horbrand F, Mayr M, von Donnersmarck GH, Muhlbauer W. Acute hyperglycaemia following thermal injury: friend or foe? Resuscitation. 2004;60(1):71-77. 109. Ellger B, Westphal M, Stubbe HD, Van den Heuvel I, Van Aken H, Van den Berghe G. [Glycemic control in sepsis and septic shock: friend or foe?]. Anaesthesist. 2008;57(1):43-48. 110. Norbury WB, Jeschke MG, Herndon DN. Metabolism modulators in sepsis: propranolol. Crit Care Med. 2007;35(9 suppl): S616-620. 111. Arbabi S, Ahrns KS, Wahl WL, et al. Beta-blocker use is associated with improved outcomes in adult burn patients. J Trauma. 2004;56(2):265-269; discussion 269-271. 112. Mohammadi AA, Bakhshaeekia A, Alibeigi P, et al. Efficacy of propranolol in wound healing for hospitalized burn patients. J Burn Care Res. 2009;30(6):1013-1017. 113. Baron PW, Barrow RE, Pierre EJ, Herndon DN. Prolonged use of propranolol safely decreases cardiac work in burned children. J Burn Care Rehabil. 1997;18(3):223-227. 114. Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR. Reversal of catabolism by beta-blockade after severe burns. N Engl J Med. 2001;345(17):1223-1229. 115. Jeschke MG, Norbury WB, Finnerty CC, Branski LK, Herndon DN. Propranolol does not increase inflammation, sepsis, or infectious episodes in severely burned children. J Trauma. 2007;62(3):676-681. 116. Peng X, Yan H, You Z, Wang P, Wang S. Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns. 2004;30(2):135-139. 117. Alexander JW. Nutritional pharmacology in surgical patients. Am J Surg. 2002;183:349-352. 118. Gottschlich MM, Jenkins M, Warden GD, et al. Differential effects of three enteral dietary regimens on selected outcome variables in burn patients. JPEN J Parenter Enteral Nutr. 1990;14(3):225-236. 119. Saffle JR, Wiebke G, Jennings K, Morris SE, Barton RG. Randomized trial of immune-enhancing enteral nutrition in burn patients. J Trauma. 1997;42(5):793-800; discussion 800-792. 120. Aida T, Murata J, Asano G, Kanda Y, Yoshino Y. Effects of polyprenoic acid on thermal injury. Br J Exp Pathol. 1987; 68(3):351-358. 121. Voruganti VS, Klein GL, Lu HX, Thomas S, Freeland-Graves JH, Herndon DN. Impaired zinc and copper status in children with burn injuries: Need to reassess nutritional requirements. Burns. 2005;31(6):711-716. 122. Jeschke MG, Finnerty CC, Suman OE, Kulp G, Mlcak RP, Herndon DN. The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute

235
phase postburn. Ann Surg. 2007;246(3):351-360; discussion 360-352. Miller JT, Btaiche IF. Oxandrolone treatment in adults with severe thermal injury. Pharmacotherapy. 2009;29(2):213-226. Wolf SE, Edelman LS, Kemalyan N, et al. Effects of oxandrolone on outcome measures in the severely burned: a multicenter prospective randomized double-blind trial. J Burn Care Res. 2006;27(2):131-139; discussion 140-131. Caldwell FT Jr, Bowser BH, Crabtree JH. The effect of occlusive dressings on the energy metabolism of severely burned children. Ann Surg. 1981;193(5):579-591. Thomson PD, Moore NP, Rice TL, Prasad JK. Leukopenia in acute thermal injury: evidence against topical silver sulfadiazine as the causative agent. J Burn Care Rehabil. 1989;10(5):418-420. Wasiak J, Cleland H. Burns (minor thermal). Clin Evid. 2005; (14):2388-2396. Wasiak J, Cleland H, Campbell F. Dressings for superficial and partial thickness burns. Cochrane Database Syst Rev. 2008;(4): CD002106. Demling RH, DeSanti L. Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes). Burns. 1999;25(3):256-261. Supp DM and Boyce ST. Engineered Skin Substitutes: Practices and Pitfalls. Clin Dermatol. 2005;23:403-412. Hart DW, Wolf SE, Chinkes DL, et al. Effects of early excision and aggressive enteral feeding on hypermetabolism, catabolism, and sepsis after severe burn. J Trauma. 2003;54(4):755-761; discussion 761-754. Barret JP, Herndon DN. Modulation of inflammatory and catabolic responses in severely burned children by early burn wound excision in the first 24 hours. Arch Surg. 2003; 138(2):127-132. Barret JP, Herndon DN. Effects of burn wound excision on bacterial colonization and invasion. Plast Reconstr Surg. 2003;111: 2):744-750; discussion 751-742. Xiao-Wu W, Herndon DN, Spies M, Sanford AP, Wolf SE. Effects of delayed wound excision and grafting in severely burned children. Arch Surg. 2002;137(9):1049-1054. Monafo WW. Initial management of burns. N Engl J Med. 1996; 335:1581-1586. Muangman P, Sullivan SR, Honari S, Engrav LH, Heimbach DM, Gibran NS. The optimal time for early excision in major burn injury. J Med Assoc Thai. 2006;89(1):29-36. Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai MH, Abston S. A comparison of conservative versus early excision. Therapies in severely burned patients. Ann Surg. 1989;209:(5): 547-552; discussion 552-543. Wang Y, Tang HT, Xia ZF, et al. Factors affecting survival in adult patients with massive burns. Burns. 2010;36(1):57-64. Nguyen LN, Nguyen TG. Characteristics and outcomes of multiple organ dysfunction syndrome among severe-burn patients. Burns. 2009;35(7):937-941. Murray CK, Hoffmaster RM, Schmit DR, et al. Evaluation of white blood cell count, neutrophil percentage, and elevated temperature as predictors of bloodstream infection in burn patients. Arch Surg. 2007;142(7):639-642.

123. 124.

125.

126.

127. 128.

129.

130. 131.

132.

133.

134.

135. 136.

137.

138. 139.

140.

Downloaded from jic.sagepub.com at CAPES on August 7, 2011

236
141. Barati M, Alinejad F, Bahar MA, et al. Comparison of wbc, esr, crp and pct serum levels in septic and non-septic burn cases. Burns. 2008;34(6):770-774. 142. Bargues L, Chancerelle Y, Catineau J, Jault P, Carsin H. Evaluation of serum procalcitonin concentration in the icu following severe burn. Burns. 2007;33(7):860-864. 143. Neely AN, Fowler LA, Kagan RJ, Warden GD. Procalcitonin in pediatric burn patients: an early indicator of sepsis? J Burn Care Rehabil. 2004;25(1):76-80. 144. Venet F, Tissot S, Debard AL, et al. Decreased monocyte human leukocyte antigen-dr expression after severe burn injury: correlation with severity and secondary septic shock. Crit Care Med. 2007;35(8):1910-1917. 145. Carr JA, Phillips BD, Bowling WM. The utility of bronchoscopy after inhalation injury complicated by pneumonia in burn patients: results from the national burn repository. J Burn Care Res. 2009;30(6):967-974. 146. Wahl WL, Taddonio MA, Arbabi S, Hemmila MR. Duration of antibiotic therapy for ventilator-associated pneumonia in burn patients. J Burn Care Res. 2009;30(5):801-806. 147. Mosier MJ, Pham TN. American burn association practice guidelines for prevention, diagnosis, and treatment of

Journal of Intensive Care Medicine 26(4)

ventilator-associated pneumonia (vap) in burn patients. J Burn Care Res. 2009;30(6):910-928. Wibbenmeyer L, Danks R, Faucher L, et al. Prospective analysis of nosocomial infection rates, antibiotic use, and patterns of resistance in a burn population. J Burn Care Res. 2006;27(2): 152-160. Newton T, Still JM, Law E. A comparison of the effect of early insertion of standard latex and silver-impregnated latex foley catheters on urinary tract infections in burn patients. Infect Control Hosp Epidemiol. 2002;23(4):217-218. Davenport K, Keeley FX. Evidence for the use of silveralloy-coated urethral catheters. J Hosp Infect. 2005;60(4): 298-303. Schuerer DJ, Zack JE, Thomas J, et al. Effect of chlorhexidine/ silver sulfadiazine-impregnated central venous catheters in an intensive care unit with a low blood stream infection rate after implementation of an educational program: a before-after trial. Surg Infect (Larchmt). 2007;8(4):445-454. Rickard CM, Lipman J, Courtney M, Siversen R, Daley P. Routine changing of intravenous administration sets does not reduce colonization or infection in central venous catheters. Infect Control Hosp Epidemiol. 2004;25(8):650-655.

148.

149.

150.

151.

152.

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