Burn wounds are conduits for infections. From the inciting thermal trauma to finalization of therapy, burn patients are exposed to multiple drug-resistant organisms. This chapter presents the definitions and types of infections afflicting burn patients, from cellulitis and wound infections to pneumonias and bloodstream infections. Topical and systemic antimicrobials are covered, as well as specific etiologic bacteria, fungi, and viruses. A care algorithm is elaborated, centered on source control with early surgical excision and skin grafting augmented by culture-directed antimicrobial therapy. Regardless of the etiologic organism, the best intervention for both prophylaxis and treatment of infections in the burn patient is the prompt closure of burn wounds with skin.

The hypermetabolic response to severe burn injury can profoundly delay recovery and rehabilitation after the injury. Increased cardiac work, elevated resting energy expenditure, and loss of lean body mass with subsequent decreased muscle strength result from post-burn hypermetabolism. Additionally, elements of the hypermetabolic response remain elevated above normal for up to 3 years. This chapter reviews the metabolic alterations that occur after severe burn injury as well as various pharmacological therapies that are being used and/or investigated for use to attenuate the hypermetabolic response.

Exercise training for burn patients has become a major part of rehabilitation programs within the last decades. One of the main reasons for prolonged and long-term increased morbidity and mortality in this population is a persistent catabolic state with subsequent loss of lean body mass (LBM). A combination of resistance and aerobic exercises as well as stretching has shown to improve physical function by enhancing cardiopulmonary fitness, LBM, and strength and thus leading to ameliorated long-term outcomes of patients recovering from burns. In this literature review, we show an outline of the implementation of exercise training over the last decades into standardized care for patients with burns.

Abstract Introduction The hypermetabolic response induced by a large burn is associated with increased cardiac work, total body wasting, and impaired physical function, leading to delays in psychosocial recovery and reintegration into society, and persistence of chronic conditions. Modulation of this response could reduce long-term burn morbidity. Catecholamines drive burn-induced hypermetabolism, therefore clinicians have employed the non-selective beta-adrenergic receptor blocker propranolol to reduce cardiac stress and the hypermetabolic response. Here, in a masked, placebo-controlled study, we investigated the safety and efficacy of the administration of propranolol to adult burn patients during the acute hospitalization period. Methods Adults with large burns (n=157, mean 38 ± 15% TBSA) were enrolled at 13 participating centers. Subjects were randomized to receive placebo (n=75) or propranolol (n=82) with data collected for 72 and 79 subjects, respectively. Propranolol administration was initiated with an oral dose of 0.2 mg/kg dose and adjusted to decrease mean heart rate by 20%. The primary endpoint was effect on cardiac rate pressure product (CRPP), while the secondary endpoints included infections and survival. Adverse events were also tracked. Assessments were conducted between the time of consent and discharge, with a long-term follow-up visit occurring approximately 5 months post-burn on average. Results CRPP was significantly reduced with propranolol during the acute hospitalization period (p< 0.0001, Fig 1). The initial dose of propranolol adequately reduced heart rate in most patients. Infections were not different between cohorts. Cardiac complications (atrial arrhythmias, ventricular arrhythmias, cardiac arrest) occurred at similar rates for each group, as did additional complications (abdominal compartment syndrome, deep vein thromboses, pneumothorax, pulmonary embolus). Mortality was similar for both the placebo and propranolol cohorts. Post-discharge heart rates and blood pressures were similar in both groups at approximately 5 months following injury. Conclusions This study demonstrates that the short-term administration of propranolol to adults with large burns decreases CRPP without increasing complications, infections, or mortality. Furthermore, a safe dosing strategy was identified. This strategy may be effective for reducing acute cardiac stress and hypermetabolism. Future studies should focus on the effects of propranolol administration for longer periods, determining the effects on additional endpoints like the hypermetabolic response, pathologic scarring, long-term cardiac dysfunction, whether smaller burns benefit from the administration of propranolol.

This article presents information on the benefits of exercise in counteracting the detrimental effects of bed rest, and/or severe burns. Exercise is key for maintaining physical function, lean body mass , metabolic recovery, and psychosocial health after major burn injuries. The details of an exercise training program conducted in severely burned persons are presented, as well as information on the importance of proper regulation of body temperature during exercise or physical activity. The sections on exercise and thermoregulation are followed by a section on the role of exercise in scarring and contractures. Finally, gaps in the current knowledge of exercise, thermoregulation, and contractures are presented.

On August 27 and 28, 2018, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn and inhalation injury in Washington, DC. The goal of the meeting was to identify and discuss the existing knowledge, data, and modeling gaps related to understanding cutaneous thermal injury and inhalation injury due to exposure from a fire environment, and in addition, address two more areas proposed by the American Burn Association Research Committee that are critical to burn care but may have current translational research gaps (inflammatory response and hypermetabolic response). Representatives from the Underwriters Laboratories Firefighter Safety Research Institute and the Bureau of Alcohol, Tobacco, Firearms and Explosives Fire Research Laboratory presented the state of the science in their fields, highlighting areas that required further investigation and guidance from the burn community. Four areas were discussed by the full 24 participant group and in smaller groups: Basic and Translational Understanding of Inhalation Injury, Thermal Contact and Resulting Injury, Systemic Inflammatory Response and Resuscitation, and Hypermetabolic Response and Healing. A primary finding was the need for validating historic models to develop a set of reliable data on contact time and temperature and resulting injury. The working groups identified common areas of focus across each subtopic, including gaining an understanding of individual response to injury that would allow for precision medicine approaches. Predisposed phenotype in response to insult, the effects of age and sex, and the role of microbiomes could all be studied by employing multi-omic (systems biology) approaches.

Severe burn injury induces a myriad of deleterious effects to skeletal muscle, resulting in impaired function and delayed recovery. Following burn, catabolic signaling and myofiber atrophy are key fiber-intrinsic determinants of weakness; less well understood are alterations in the interstitial environment surrounding myofibers. Muscle quality, specifically alterations in the extracellular matrix (ECM), modulates force transmission and strength. We sought to determine the impact of severe thermal injury on adaptation to the muscle ECM and quantify muscle fibrotic burden. After a 30% total body surface area dorsal burn, spinotrapezius muscle was harvested from mice at 7 (7d, n = 5), 14 (14d, n = 4), and 21 days (21d, n = 4), and a sham control group was also examined (Sham, n = 4). Expression of transforming growth factor-β (TGFβ), myostatin, and downstream effectors and proteases involved in fibrosis and collagen remodeling were measured by immunoblotting, and immunohistochemical and biochemical analyses assessed fibrogenic cell abundance and collagen deposition. Myostatin signaling increased progressively through 21 days postburn alongside fibrogenic/adipogenic progenitor cell expansion, with abundance peaking at 14 days postburn. Postburn, elevated expression of tissue inhibitor of matrix metalloproteinase 1 supported collagen remodeling resulting in a net accumulation of muscle collagen content. Collagen accumulation peaked at 14 days postburn but remained elevated through 21 days postburn, demonstrating minimal resolution of burn-induced fibrosis. These findings highlight a progressive upregulation of fibrogenic processes following burn injury, eliciting a fibrotic muscle phenotype that hinders regenerative capacity and is not resolved with 21 days of recovery.

Background: One of the most pervasive complications of burn injury is wound progression, characterized by continuous tissue destruction in untreated wounds, which leads to wound infection, inflammation, oxidative stress and excessive scar formation. We determined whether additional tissue destruction could be attenuated with Livionex formulation (LF) lotion, which contains a metal-chelating agent and reduces inflammation in burn wounds. Methods: We subjected male Sprague Dawley rats to a 2% total body surface area (TBSA) burn using a brass comb model and topically applied LF lotion (containing ethylenediaminetetraacetic acid and methyl sulfonyl methane) to the affected area every 8 hours over 3 days. Inflammatory cytokine levels, cell apoptosis and wound healing were compared in LF lotion-treated and untreated rats. Statistical analysis was performed using a one-way analysis of variance in conjunction with Tukey's post-hoc test. Results: Serum inflammatory cytokines were not detectable after 3 days, suggesting that small burn wounds induce only an immediate, localized inflammatory response. Microscopy revealed that LF lotion improved burn site pathology. Deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining showed reduced cell death in the LF-treated samples. LF lotion prevented the spread of tissue damage, as seen by increased amounts of Ki-67-positive nuclei in the adjacent epidermis and hair follicles. Tumor necrosis factor-alpha, interleukin-6 and inducible nitric oxide synthase levels in LF-treated skin sections from burned rats were comparable to the levels observed in unburned control sections, indicating that LF lotion reduces inflammation in and around the burn site. Conclusions: These results establish LF lotion as a therapeutic agent for reducing inflammatory stress, cell death and tissue destruction when applied immediately after a burn injury. Further studies of LF lotion on large TBSA burns will determine its efficacy as an emergency treatment for reducing long-term morbidity and scarring.

Background: Researchers have explored the use of adipose-derived stem cells (ASCs) as a cellbased therapy to cover wounds in burn patients; however, underlying mechanistic aspects are not completely understood. We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways. Methods: To test the hypothesis, we used an ovine burn model. A 5 cm(2) full thickness burn wound was induced on each side of the dorsum. After 24 hours, the burned skin was excised and a 2 cm(2) patch of autologous donor skin was grafted. The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment (phosphate-buffered saline [PBS]). Effects of ASCs culture media was also compared to those of PBS. Wound healing was assessed at one and two weeks following the application of ASCs. Allogeneic ASCs were isolated, cultured and characterized from non-injured healthy sheep. The identity of the ASCs was confirmed by flow cytometry analysis, differentiation into multiple lineages and gene expression via real-time polymerase chain reaction. Wound blood flow, epithelialization, graft size and take and the expression of vascular endothelial growth factor (VEGF) were determined via enzyme-linked immunosorbent assay and Western blot. Results: Treatment with ASCs accelerated the patch graft growth compared to the control (p < 0.05). Topical application of ASCs significantly increased wound blood flow (p < 0.05). Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control (p < 0.05). Conclusions: ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.

Survival after burn injury has steadily improved in recent decades. The models for assessing the severity of burn injury and predicting burn-associated mortality have been used for over 20 years. The predictive accuracy of these models should be reconsidered now.In this retrospective study on all burn patients (n = 9625) admitted to the Burn Department, Southwest Hospital between 2008 and 2017, we compared the predictive performance of the four burn-severity models (Abbreviated Burn Severity Index, Ryan score, revised Baux score and Belgian Outcome of Burn Injury) by area under the receiver operating curve (AUC) and Hosmer–Lemeshow test. We developed a new model with the data from 2008 to 2012 (5006 patients) by logistic regression, data from 2013 to 2017 (4619 patients) were used for validation.The overall mortality rate of the burn patients was 1.14%. The four previously validated burn models showed good discrimination power of death risk (AUC > 0.890) but poor fitness to the observed mortality rate (p < 0.001). Risk factors associated with mortality included sex, age, total burn area, full thickness burn area, and inhalation injury. The new logistic model was devised with high sensitivity and specificity (0.913 and 0.806, respectively) and an AUC of 0.940. The new model also had good fitness to the observed mortality of burn patients (p = 0.588).The four widely used burn models have poor accuracy in predicting burn-associated mortality, and an accurate new model was developed based on simple and objective clinical characteristics of burn patients at admission.

OBJECTIVES:The objective of the study was to determine whether postburn reduction of bone formation occurred earlier than 2-3 weeks after burn injury and whether that reduction was inversely related to marrow adiposity.METHODS:Using a rat model of burn injury with sacrifice at 3 days postburn, we measured serum osteocalcin, a biomarker of bone formation, as well as a regulator of glucose metabolism, and counted tibial marrow adipocytes.RESULTS:Serum osteocalcin was reduced as early as 3 days postburn, coinciding with a trend toward decline in marrow adipocyte number rather than demonstrating an inverse relationship with adipocyte count.CONCLUSIONS:Factors that may be responsible for the dissociation include lack of circulating sclerostin, previously reported, increased energy demands following burn injury, increased sympathetic tone and perhaps oxidative stress. The relationship between bone formation and marrow adiposity is complex and subject to a variety of influences.