splinting are necessary to prevent recurrence.

Nailbed Reconstruction

Eponychial fold and decreasing range of motion of the distal interphalangeal joint (DIP). To improve

the DIP range of motion and proximal to the DIPJ releasing the skin proximally and distally taking care

not to injure the underlying extensor tendon. A full thickness graft is then placed (Fig. 12-12).

ASSOCIATED COMPLICATIONS OF BURN INJURIES

Muscle Catabolism and Wasting

Burn injury involving large areas of the body is associated with significant pathophysiologic sequelae,

which can persist up to several years after the acute injury. There are significant changes in essential

metabolic processes, which shift physiologic homeostasis to a catabolic state, resulting in loss of lean

body mass. The TBSA affected by the burn injury plays an important role, since reestablishing a

functional skin barrier initially takes priority and requires a protein substrate, which is often provided

by skeletal muscle.105

Muscle catabolism after burn injury is mediated by several factors including increased energy

requirement106 and heightened inflammatory state involving the systemic release of stress hormones,

catecholamines, and glucocorticoids, which mediate the underlying metabolic derangements. Other

factors include prolonged immobilization and the loss of a functional skin barrier, which lead to

disturbed thermoregulation requiring increased energy expenditure to maintain body temperature. The

consequences can have devastating effects on the convalescence of pediatric burn patients, where an

increased catabolic state can lead to delayed linear growth for up to 2 years after the injury.107 The

physiologic response of skeletal muscle to anabolic stimuli is altered in pediatric patients with amino

acid infusion therapy failing to stimulate a net protein deposition in skeletal muscle even 6 to 12

months post injury.108,109

Studies investigating the effect of burn injury on physiologic changes in skeletal muscle have

uncovered a critical role for mitochondrial function showing that processes involving carbohydrate

metabolism, lipid metabolism, and oxidative phosphorylation are significantly altered.110 Righi et al.111

demonstrated that treatment with a mitochondria-targeted antioxidant in a mouse burn model

significantly increases mitochondrial ATP secretion and ameliorates oxidative stress, suggesting that

reactive oxygen species play a significant role in burn pathogenesis. Improvements in skeletal muscle

mitochondrial function have also been attributed to the effect of fenofibrate, a peroxisome proliferatoractivated receptor-α agonist used to treat impaired glucose metabolism commonly observed after burn

injury. In pediatric burn patients, fenofibrate treatment improved glucose levels and insulin

sensitivity.112 Other therapeutic approaches, which have shown significant benefit in clinical trials

include the blockage of beta-adrenergic receptors, resulting in attenuated catecholamine effect and

improved net muscle protein balance.67 Anabolic steroids such as oxandrolone, and physical exercise

have been shown to increase lean body mass in children who suffered from >40% TBSA burn injury.113

When the body is in a prolonged catabolic state due to the increase in caloric requirements, patients

must consume at least 2.5 to 3 g/kg/day of protein.75 Nutritional shakes and high-calorie foods are a

necessity to optimize the conditions for wound healing. It is important to start nutrition as soon as

possible, preferentially using the enteric route. Nasogastric or nasoduodenal/jejunal feeding tubes

should be inserted early in the care of this patient population. Dieticians are crucial members of the

burn care team in creating individualized feeding plans and ensuring that nutrition is at the forefront of

daily care. Albumin and prealbumin levels can be trended over time to ensure that adequate

nourishment is achieved.

Patients should also be referred to physical and occupational therapy. A therapeutic exercise program

should be implemented to maintain normal range of motion, strength, and endurance. In order to

counteract the catabolic effects of burn injuries, a program of active and active-assisted exercise is

necessary. Depending on the severity of the burn and the patient’s willingness to tolerate the associated

pain with exercise, passive range of motion exercises should be prescribed. In the event that full range

of motion is not achievable, a program of stretching can be prescribed in its place. Anesthesia can be

used to assist these exercises when patients cannot tolerate pain.

Range of motion exercises can also minimize skin contractures, as skin is a tissue that requires

sustained mechanical stretch to facilitate lengthening of the underlying collagen and extracellular matrix

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compartments. Initial skin exercises should attempt to elongate the skin with repetitive low loads with

differences in length. Following this initial precondition, a prolonged stretch is applied to maximize skin

laxity. Blanching is a clinical sign that capillary blood flow is impeded and is a good sign that the tissue

has reached its maximum yield point. Strength exercise should follow as soon as the patient can tolerate

it. Strength programs best suited for burn patients should include progressive resistive exercises. Fatigue

and loss of endurance are major issues as a patient recovers. It is important to include endurance

training and monitor cardiopulmonary response. Concurrently, patients should be encouraged to walk as

ambulating patients have fewer lower extremity contractures, endurance problems, and venous

thrombosis.

Heterotopic Ossification

Heterotopic ossification (HO) is the pathologic formation of bone in extraskeletal regions of soft tissue

including muscle, joint spaces, and often encasing major nerves (Fig. 12-13). This complication of burn

injury causes significant pain, joint restriction, and contractures.113 The incidence of HO is proportional

to the severity of the injury with an increased incidence in severely burned patients. HO may affect all

areas of the body but is most frequently encountered in the elbow joint (Fig. 12-13).114,115 While the

etiology of HO remains elusive, common risk factors that have been identified include upper extremity

burns, large TBSA burns, young age, prolonged immobilization116 and a delay in time to wound

closure.117

Early detection and diagnosis of heterotopic bone formation is critical in the clinical management of

this complication, which oftentimes involves surgical resection. The success rates of surgical

intervention are not well established and are associated with a high recurrence rate. Perioperative

radiotherapy has been suggested as an adjunct to surgical resection and has been shown to reduce the

recurrence rate to some extent.118 While the pathophysiologic processes underlying the development of

heterotopic bone formation are poorly understood, several studies have implicated increased

inflammatory signaling and the involvement of progenitor cells as crucial contributing elements.

Pharmacologic interventions have been shown to have some efficacy in limiting the severity of HO.

Bisphosphonates and non-steroidal anti inflammatory have been used for prophylaxis and treatment of

HO with some success.119,120 However, there is no consensus on which drug should be prescribed and

when treatment should begin. It has been proposed that bisphosphonates should be prescribed as soon

as elevated alkaline phosphatase is noted or imaging studies establish the presence of HO. NSAIDs limit

the severity of HO when delivered as a preventative therapy. The primary pathway thought to play a

role is the bone morphogenetic protein (BMP) receptor 1 pathway; specifically the ALK2 kinase domain

which stimulates canonical smad signaling. Though diagnosis is often not made until after 3 to 4 weeks

after the burn injury, pathologic changes occur much sooner and thus treatments should target this early

osteogenic signaling if prophylaxis is to be achieved. The effect of early active and passive range of

motion on HO is unknown. Though the elbow is the most common site, the reason for this high

incidence is unknown.

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Figure 12-13. Heterotopic ossification.

Marjolin’s Ulcer

Similar to chronic wounds from other etiologies, chronic untreated burn scars can lead to malignant

degeneration. Squamous cell carcinoma is the most common type of malignancy observed. Malignancies

are rare in an era of early excision and grafting. Malignancy requires wide excision with at least a 2 cm

margin as well as sentinel lymph node biopsy. If the sentinel node is positive, a compete lymph node

excision should be performed.

Clinical Research

Clinical research determines the safety and efficacy of medications, devices, diagnostic tools, and

treatment regimens and has provided new insights to effectively care for burn patients. Within the last

decade, critical care, wound care treatment, and burn reconstruction research have advanced in both

diagnosis and identification of efficacious therapies to improve the overall recovery process for burn

victims.

Critical care research has focused on the delivery of adequate care during the initial phase following

the traumatic burn injury. Immediately following the trauma, burn patients experience severe shock due

to concomitant inflammation leading to severe edema. While rigorous fluid resuscitation has been

shown to increase overall survival for patients with high TBSA involvement, novel resuscitation

methods have recently been investigated. In a prospective randomized study, clinicians investigated the

use of colloids within the first 24 hours of resuscitation.121 Patients with a TBSA burn injury greater

than 15% were either provided with crystalloid resuscitation or a mixture of crystalloid and

hydroxyethyl starch. Patients given colloids required less fluid, experienced less edema, and had a lower

C-reactive protein indicative of less inflammation. Additional studies have investigated the use of

therapeutic plasma exchange for refractory burn resuscitation and discovered that patients had reduced

lactate levels, increased mean arterial pressure, and improved urine output after treatment.122 Our

recommendation and common practice use crystalloid rather than colloid as outcomes in burn patients

have not been conclusively shown to be improved. These studies highlight the complexity of burn shock

resuscitation and the need for ongoing research in the field.

Studies have investigated the role of regulating glucose levels in burn patients during the critical

phase. Stress hyperglycemia after severe burn injury has long been established as a physiologic response

to trauma. Recent studies have demonstrated the need for early glycemic control, as burn patients who

did not have optimal glucose levels experienced increased mortality. Intensive insulin therapy in

critically ill burn patients limited the number of infections and sepsis and improved overall organ

function.123 In general moderate glycemic control as demonstrated by the NICE-SUGAR trial appears

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efficacious.124 Delivery of insulin also decreased inflammatory responses, as noted by decrease levels of

systemic IL-6 and C-reactive protein, and also improved body density, body fat, and lean body mass.

Insulin therapy also reduced resting energy expenditure in the first week following the burn injury,

improved mitochondrial function, and hepatic glucose metabolism.125 Furthermore, the glucose

variability experienced by a burn patient during the critical period is also associated with increased

mortality rates, suggesting that consistent and tight glucose control may provide a significant survival

benefit.126 Taken together, these studies build an argument that in burn patients, glucose control with

insulin therapy may reduce inflammation, improve energy utilization, and improve overall prognosis.

Another important area of research is the development of new technology to aid in wound assessment

and treatment. Punch biopsy, laser Doppler imaging, and near-infrared spectroscopy have been

employed to diagnosis the burn depth and severity of the primary wound site. Additional studies

advocate for the use of confocal laser scanning microscopy (CLSM) due to its greater contrast and

sensitivity. This technology images wounds in vivo without any physical dissection using a laser source.

CLSM was able to determine wound depth by assessing the number of perfused dermal papillae and was

able to accurately classify burns based on the amount of perfusion.127 Recent development of

extracorporeal shock wave treatment (ESWT) has shown promise as it promotes angiogenesis, increases

perfusion, and accelerates wound healing. In a pilot study, patients treated with ESWT demonstrated

increase blood flow to the burn wound within 3 weeks.128 This therapy shows great promise, as it is a

noninvasive measure to improve wound healing.

Advances in burn reconstruction have also been noted in the last decade. While TEs have been a

mainstay of burn reconstruction, several studies have surveyed the use of endoscopic-assisted placement

of expanders and the use of osmotic TEs.129,130 Both endoscope-assisted placement of expanders and

osmotic TEs offer advantages over the traditional methods, as they are more cosmetically acceptable

and require fewer injections, respectively. As TE technology continues to improve with new expansion

techniques and devices, discovering the best technique and devices will be an important component of

burn reconstruction. Cultured epithelial autografts, as discussed in previous sections, have gained

interest as an alternative for cutaneous coverage for patients with large burn wounds and small

potential donor sites. With final engraftment percentages as high as 73% and 90% patient survival rate,

it is an attractive alterative for patients with severe and extensive burns.

BASIC SCIENCE AND TRANSLATIONAL SCIENCE RESEARCH

Basic science and translational science research in burn injuries have significantly advanced in the last

50 years and have focused on both understanding and treating the primary wound site as well as

complications that arise from these traumatic burn injuries.

Wound healing can be described in three different stages: inflammation, proliferation, and remodeling

phase. Hypertrophic scarring is an aberrant form of the normal wound healing process that does not

extend beyond the original wound margins. Hypertrophic scar formation involves the constitutively

active proliferative phase of wound healing, resulting in high vascularity and dense extracellular matrix

deposition.131 Histologic studies suggest that a robust inflammatory response, involving mast cells,

macrophages, fibrocytes, and lymphocytes, may underlie the excessive fibrosis seen in hypertrophic scar

formation.132 The secretion of TGF-beta1, platelet-derived growth factors (PDGFs), and epidermal

growth factor contributes to the inflammatory response and results in excessive inflammatory cell

stimulation, fibroblast proliferation, adhesion, neovascularization, matrix production, and ultimately

contraction.133 As such, translational science research from the bench to the bedside focuses on new

therapies targeted at quenching the inflammatory response, limiting fibrosis, and inhibiting

angiogenesis by targeting the mediators of this scaring process.134,135 Additional basic science research

aimed at understanding the wound healing process and translational science research investigating new

treatment options will continue to advance our understanding and treatment of burn-related injuries.

Additional studies into the precise cause of secondary complications such has HO has gained

significant interest due to the increase in presence of HO in veterans who have sustained combat

injuries. While the precise pathophysiology behind HO is still unclear, it is thought to be related to local

and systemic factors, causing osteoblastic differentiation of local cells. Previous studies have attempted

to elucidate the local and systemic wound inflammatory response leading to HO, through the

identification of cytokine and chemokines secreted from the wound.136 Serum analysis demonstrated a

profound systemic inflammatory response in burn patients, as burn patients maintained increased levels

of IL-6 and macrophage chemoattractant protein (MCP)-1 over time. Both IL-6 and MCP-1 are

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