•Immediately postburn, there is a decrease in metabolism and tissue perfusion, an “ebb” phase, which is quickly followed by a period of increased metabolic rates and hyperdynamic circulation, a “flow” phase.

•The “flow” phase is characterized by profoundly accelerated glycolysis, lipolysis, proteolysis, insulin resistance, liver dysfunction, and decreases of lean body mass and total body mass [5].

•The primary mediators of this response after severe burn injury are catecholamines, corticosteroids, and inflammatory cytokines which are elevated for up to 12 months postburn [6].

•Net loss of protein leads to loss of lean body mass, and severe muscle wasting leads to decreased strength and failure to fully rehabilitate. This loss of protein is directly related to increases in metabolic rate and may persist up to 9 months after critical burn injury [6]. In young burned children, protein loss leads to significant growth retardation for longer than 1 year post-injury.

•Investigation has shown that the glycolytic-gluconeogenic cycling may experience an increase of 250 % during the postburn hypermetabolic response together with an increase of 450 % in triglyceride-fatty acid cycling. Collectively, these changes lead to greater glycogenolysis, gluconeogenesis, and increased circulation of glucogenic precursors, which translates into hyperglycemia and impaired responsiveness to insulin, which is in term related to post-receptor insulin resistance.

•Both serum glucose and insulin increase postburn and remain significantly increased throughout the entire acute hospital stay. These increased amounts of available glucose although required as a source of energy to decrease severe protein catabolism after severe burn injury, if left untreated, have led to poor outcomes in studies performed in critically ill patients [7].

•It was originally thought that these metabolic alterations resolve shortly after burn-wound closure or the acute hospitalization. However, current work demonstrated a long-lasting state of this hypermetabolic response persisting for up to 3 years after burn trauma [8–13].

10.3Scarring

•Incidence rates of hypertrophic scarring vary from 40 to 70 % following surgery to up to 91 % following burn injury, depending on the depth of the wound [14, 15].

•Excessive scars represent aberrations in the fundamental processes of wound healing, where there is an obvious imbalance between the anabolic and catabolic phases [16].

•Evidence to date strongly implies a prolonged inflammatory period, the consequence of which may contribute to increased fibroblast activity with greater and more sustained ECM deposition [16].

•Burn scars after deep dermal injury are cosmetically disfiguring and force the scarred person to deal with an alteration in body appearance [17]. Multiple studies on excessive scar formation have been conducted for decades and

have led to a plethora of therapeutic strategies in order to prevent or attenuate excessive scar formation postburn [18].

10.4Therapy

Pressure therapy has been the preferred conservative management for both the prophylaxis and treatment of hypertrophic scars and keloids since the 1970s and is still frequently used for the prophylaxis of hypertrophic burn scar formation [18]:

•Decreased collagen synthesis by limiting the supply of blood, oxygen, and nutrients to the scar tissue [19–21] and increased apoptosis [22] are being discussed as underlying mechanism of action.

•Continuous pressure of 15–40 mmHg for at least 23 h/day for more than 6 months while the scar is still active is currently recommended [20, 23].

•Compression therapy is limited by the ability to adequately fit the garment to the wounded area, and patient discomfort frequently reduces compliance.

Silicone gel sheeting has been a well-established management of scars since its

introduction in the early 1980s, and its therapeutic effects on predominantly hypertrophic scars have been well documented in the literature [24, 25]:

•Normalization of occlusion and transepidermal water loss (TEWL) are likely the mechanisms of the therapeutic action of silicone gel sheeting rather than an inherent anti-scarring property of silicone [26].

•Silicone sheets are recommended to be worn for 12 or more hours a day for at least 2 months beginning 2 weeks after wound healing.

•Silicone gel is favored for areas of consistent movement where sheeting will not conform and should be applied twice daily [27].

Intralesional steroid injections have gained popularity as one of the most com-

mon approaches to attenuate hypertrophic scar and keloid formation since the mid1960s [28]:

•Effects of corticosteroids result primarily from its suppressive effects on the inflammatory process in the wound [26] and secondarily, from reduced collagen and glycosaminoglycan synthesis, inhibition of fibroblast growth [29], and enhanced collagen and fibroblast degeneration [30].

•Three to four injections of triamcinolone acetonide (TAC, 10–40 mg/ml) are generally sufficient, although occasionally injections continue for 6 months or more [28].

•Response rates are highly variable, with figures ranging from 50 to 100 % and a recurrence rate of 9–50 % [31].

•When used alone, intralesional corticosteroid injections have the most effect on younger keloids and can provide symptomatic relief.

•For older hypertrophic scars and keloids, combination with cryotherapy (contact or spray cryotherapy with liquid nitrogen) may show more effective results [32, 33] and represents the most widely used modality in our daily practice. Indeed, combination of cryotherapy with intralesional TAC injections seems to yield marked improvement of hypertrophic scars and keloids [34–36].

•We recommend cryotherapy directly before the administration of intralesional TAC injections since success rates appear to be increased based on the larger amount of TAC that can be injected due to edema formation caused by cryotherapy.

Superficial x-rays, electron beam, and lowor high-dose-rate brachytherapy have

been used in scar reduction protocols primarily as an adjunct to surgical removal of keloids with good results [37]:

•Radiation is thought to mediate its effects on keloids through inhibition of neovascular buds and proliferating fibroblasts, resulting in a decreased amount of collagen produced [26].

•Electron beam irradiation is usually started 24–48 h after keloid excision, and the total dose is limited to 40 Gy over several administrations in order to prevent side effects such as hypoand hyperpigmentation, erythema, telangiectasia, and atrophy [38].

•Since radiation represents a potential risk in terms of carcinogenesis, particularly in areas such as the breast or thyroid, its use should be handled with caution [39, 40]. In 1999, Fitzpatrick [41] was the first to report on using 5-fluorouracil (5-FU) to

effectively reduce scar in his 9-year experience, administering more than 5,000 injections to more than 1,000 patients. Ever since, the use of intralesional 5-FU in combination or as a sole agent for treatment of keloids has been shown to be effective:

•5-FU is normally injected weekly at concentrations of 50 mg/ml, continuing for up to 16 weeks.

•Therapy in pregnant women or patients with bone marrow suppression should be avoided.

•Novel approaches include the combination of intralesional application of TAC and 5-FU (mostly mixtures of 75 % 5-FU and 25 % TAC (40 mg/ml) in weekly intervals for 8 weeks) demonstrating superior results to intralesional steroid therapy alone [42–44].

Surgical approaches include various biological and synthetic substrates to

replace the injured skin:

•Integra® was found to improve aesthetic outcome postburn in the management of severe full-thickness burns of ³50 % TBSA in a pediatric patient population compared to standard autograft-allograft technique [45]. It was also found to inhibit scar formation and wound contraction [46].

•Several strategies have been investigated with the purpose of promoting wound healing by the use of gene transfer, including stimulation of the granulation process, the vascularization, the reepithelialization, or the scar quality [47, 48]. However, more studies are needed to define growth factor levels in different phases of wound healing and to elucidate the precise timing of gene expression or downregulation required to better augment wound healing and control of scar formation [49].

10.5Psychological Aspects

With improvements in mortality, outcomes are increasingly focused on measures of function and community integration [50]. Authors are now reporting new methods to evaluate outcomes through Burn-Specific Health Scales [51] and measures of adjustment:

•Authors found that severely burned adult patients adjust relatively well, although some develop clinically significant psychological disturbances such

as somatization and phobic anxiety [52]. Depression and post-traumatic stress disorder (PTSD), which are prevalent in 13–23 % and 13–45 % of cases, respectively, have been the most common areas of research in burn patients [17].

•Risk factors related to depression represent pre-burn depression and female gender in combination with facial disfigurement [17].

•Social problems include difficulties in sexual life and social interactions. The quality of life initially seems to be lower in severely burn patients when compared with the general population [17].

•Children with severe burns were found to have similar somatization problems as well as sleep disturbances but in general, were well adjusted [52].

•These data intimate that major burns can lead to significant disturbances in psychiatric health and outcomes, but in general, these can be overcome.

10.6Return to Work

The ultimate goal of rehabilitation after burn injury is reintegration into society, which includes employment [53]. A study in 363 burned adults who were employed at the time of injury demonstrated a mean time off work of 17 weeks. Only 37 % returned to the same job, with the same employer, without accommodations in a detailed subgroup analysis [54]. Based on current data, predictors of return to work include the following characteristics:

•TBSA and burn site

•Medical factors such as length of hospitalization and psychiatric history

•Demographic factors including age, race, marital status, and employment status at the time of injury [55–58]

10.7Long-Term Development of Other Diseases

Burn injury is associated with long-term consequences despite adequate and rapid therapy immediately postburn. Recent data delineated the complexity of the pathophysiologic response postburn and identified derangements that are greater and more protracted than previously thought [6]:

•These data indicate the local and systemic effects of a burn are not limited to the 95 % healed stage [52]. Burn injury continues to plague and impair patients over a prolonged time.

•Given the great adverse events associated with the hypermetabolic and hyperinflammatory responses, prolonged treatment needs for severely burned patients are currently identified.

•Several studies aim to determine whether long-term effects can be alleviated [11, 59–62]. Administration of anabolic agents such as oxandrolone, growth hormone, or propranolol may improve long-term outcomes. Also, exercise can tremendously improve strength and rehabilitation of severely burned patients [63].