The effects of short bouts of ergometric exercise for severely burned children in intensive care: A randomized controlled trial.

OBJECTIVE: To determine the effects of short bouts of ergometric exercises on the number of days in the burn intensive care unit (ICU), body mass, and functional ambulation. DESIGN: Multi-center, randomized controlled trial. SETTING: Burn intensive care unit. PARTICIPANTS: Children ages 7-17 with severe burns covering over 30% total body surface area (TBSA). INTERVENTION: All patients received standard of care (Control) with the experimental group receiving additional exercise with a cycle ergometer (Exercise). MAIN MEASURES: The number of days in the ICU, total weight, lean body mass (LBM), and functional ambulation were taken shortly after randomization and again within one week of the scheduled hospital discharge. Results of outcomes are expressed as median ± interquartile range (IQR), unless otherwise noted (e.g. demographics). RESULTS: Fifty-four severely burned children (n = 18 Control, n = 36 Exercise) were included. The average ± standard deviation for age was 12 ± 3 years and TBSA was 48 ± 16%. The median ± IQR ICU days for Control was 46 ± 51 days vs 31 ± 29 days for Exercise. The median total weight loss for Control was 2.2 ± 1.2 kg vs 1.8 ± 1.4 kg in Exercise. Control lost 0.75 ± 0.8 kg of LBM vs 0.46 ± 0.43 kg in Exercise. Both groups showed significant improvement in functional ambulation (p < 0.01). However, exercise did not add additional benefits. CONCLUSION: Short bouts of ergometric exercises are feasible for severely burned patients while receiving care in the ICU but did not add additional benefits.

One-Year Comparison of a Community-Based Exercise Program Versus a Day Hospital-Based Exercise Program on Quality of Life and Mental Health in Severely Burned Children.

OBJECTIVE: To compare the effects of long-term psychosocial functioning and mental health of a "day hospital"-based exercise program (DAYEX) versus a community-based exercise program (COMBEX). DESIGN: A prospective design that consisted of 2 groups (DAYEX and COMBEX). SETTING: A children's hospital specialized in burn care. PARTICIPANTS: Patients (N=18; DAYEX [n=9], COMBEX [n=9]) were assessed at intensive care unit discharge and up to 1 year postburn. INTERVENTIONS: The Child Health Questionnaires (CHQ-Child Form [CHQ-CF87] and CHQ-Parent Form [CHQ-PF28]) were used to assess changes in quality of life from discharge to 1 year postburn. MAIN OUTCOME MEASURES: CHQ-PF28 and CHQ-CF87. RESULTS: Demographic characteristics and total body surface area burned were similar in both groups. Length of hospital stay was significant in the COMBEX group. CHQ-CF87 and CHQ-PF28 documented significant improvements in both groups between discharge and 1 year. Significance was evident in Physical Functioning, Bodily Pain, Self-Esteem, Change in Health, and Family Activities. CHQ-CF87 showed improvement in Family Cohesion in COMBEX more than DAYEX. CHQ-PF28 showed improvement in Role/Social Limitations-Emotional, Bodily Pain, and Family Activities in COMBEX more than DAYEX. CONCLUSIONS: The proposed COMBEX program is feasible and beneficial physically, psychosocially, and mentally. The results show some improvements in the COMBEX group in optimizing function and health in severely burned children. The COMBEX group performed at least as well as the DAYEX group. Larger-scale studies are needed to validate current findings.

Effects of Community-Based Exercise in Adults With Severe Burns: A Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy of community-based exercise programs in the rehabilitation of adult patients with burns compared with standard of care (SOC). DESIGN: Randomized controlled trial, with 2:1 randomization. SETTING: Assessments were performed in a hospital setting. The intervention was performed in a community setting. PARTICIPANTS: Adult patients (N=45) with ≥30% total body surface area burns were randomized to participate in a community-based exercise program (n=31) or SOC (n=14). Patient sampling was consecutive and referred. INTERVENTIONS: The community-based exercise program consisted of 12 weeks of exercise with a community-based trainer after hospital discharge. The SOC group did not receive exercise training. MAIN OUTCOME MEASURES: Change in lean body mass index, peak torque, and peak oxygen consumption from discharge to 12 weeks postdischarge, presented as mean ± SE. RESULTS: The community-based exercise program group showed a significant increase in peak oxygen consumption compared with SOC (community-based exercise program: Δ=7.723±1.522mL/kg/min, P=.0006; SOC: Δ=2.200±1.150mL/kg/min, P=.0765; community-based exercise program vs SOC, P=.0236). The community-based exercise program group exhibited a significant within group increase in lean body mass index (Δ=1.107±0.431kg/m2, P=.0003; SOC: Δ=1.323±0.873kg/m2, P=.2808). Both groups showed significant within-group increases in peak torque (community-based exercise program: Δ=35.645±7.566Nm, P=.0003; SOC: Δ=34.717±11.029Nm, P=.0082). No significant differences were noted between the 2 groups for lean body mass index or peak torque. CONCLUSIONS: Patients who participate in a community-based exercise program show significant improvements in cardiopulmonary fitness compared with SOC, supporting the use of a community-based exercise program as an alternative therapy to SOC in adults with severe burns.

Surgical anatomy of ovine facial and hypoglossal nerves for facial nerve reconstruction and regeneration research: An experimental study in sheep.

BACKGROUND: The lack of a clinically relevant animal model for facial nerve research is a challenge. The goal of this study was to investigate the anatomy of the ovine facial and hypoglossal nerves to establish a clinically relevant facial nerve research model. MATERIALS AND METHODS: Six cadaver female Merino sheep (33.5 ± 3 kg, approximately 3 years old) and three anesthetized female Merino sheep (30 ± 3 kg, approximately 3 years old) were used. In cadaver sheep, a right side preauricular to submandibular incision was made. Dimensions of the face, neck, and length of facial nerve were measured. In anesthetized sheep, each facial nerve branch and hypoglossal nerve in the right side was stimulated. The number of myelinated fibers was analyzed histologically. RESULTS: The facial nerve exited the stylomastoid foramen and divided into upper and lower branches. The lower branch then subdivided into buccal and marginal mandibular branches. The hypoglossal nerve was observed behind the digastric posterior belly. Stimulation revealed the temporal, zygomatic, buccal, marginal mandibular, and cervical branch innervated the forehead, orbicularis, upper lip and nasal, lower lip, and platysma, respectively. The number of myelinated fibers of the main trunk, upper, buccal, lower branch, and hypoglossal nerve was 11 350 ± 1851, 4766 ± 1000, 5107 ± 218, 3159 ± 450, and 7604 ± 636, respectively. The length of the main trunk was 9.2 ± 1.5 mm, and distance of the marginal mandibular branch to the facial artery was 94 ± 6.8 mm. CONCLUSIONS: Due to the similarity in nerve anatomy and innervation, the ovine model can be used as a clinically relevant and suitable model for facial nerve research.

Effect of N-(2-aminoethyl) ethanolamine on hypertrophic scarring changes in vitro: Finding novel anti-fibrotic therapies.

Hypertrophic scars (HS) limit movement, decrease quality of life, and remain a major impediment to rehabilitation from burns. However, no effective pharmacologic therapies for HS exist. Here we tested the in vitro anti-fibrotic effects of the novel chemical N-(2-aminoethyl) ethanolamine (AEEA) at non-toxic concentrations. Scanning electron microscopy showed that AEEA markedly altered the structure of the extracellular matrix (ECM) produced by primary dermal fibroblasts isolated from a HS of a burn patient (HTS). Compression atomic force microscopy revealed that AEEA stiffened the 3D nanostructure of ECM formed by HTS fibroblasts. Western blot analysis in three separate types of primary human dermal fibroblasts (including HTS) showed that AEEA exposure increased the extractability of type I collagen in a dose- and time-dependent fashion, while not increasing collagen synthesis. A comparison of the electrophoretic behavior of the same set of samples under native and denaturing conditions suggested that AEEA alters the 3D structure of type I collagen. The antagonization effect of AEEA to TGF-ß1 on ECM formation was also observed. Furthermore, analyses of the anti-fibrotic effects of analogs of AEEA (with modified pharmacophores) suggest the existence of a chemical structure-activity relationship. Thus, AEEA and its analogs may inhibit HS development; further study and optimization of analogs may be a promising strategy for the discovery for effective HS therapies.

Postacute Care Setting Is Associated With Employment After Burn Injury.

OBJECTIVE: To examine differences in long-term employment outcomes in the postacute care setting. DESIGN: Retrospective review of the prospectively collected Burn Model System National Database. SETTING AND PARTICIPANTS: A total of 695 adult survivors of burn injury enrolled between May 1994 and June 2016 who required postacute care at a Burn Model System center following acute care discharge were included. Participants were divided into 2 groups based on acute care discharge disposition. Those who received postacute care at an inpatient rehabilitation facility (IRF) following acute care were included in the IRF group (N=447), and those who were treated at a skilled nursing facility, long-term care hospital, or other extended-care facility following acute care were included in the Other Rehab group (N=248). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment status at 12 months postinjury. Propensity score matching and logistic regression were utilized to determine the effect of postacute care setting on employment status. RESULTS: Individuals in the IRF group had larger burns and were more likely to have an inhalation injury and to undergo amputation. At 12 months postinjury, the IRF group had over 9 times increased odds of being employed compared to the Other Rehab group, using propensity score matching (P=.046). CONCLUSIONS: While admitting patients with more severe injuries, IRFs provided a long-term benefit for survivors of burn injury in terms of regaining employment. Given the current lack of evidence-based guidelines on postacute care decisions, the results of this study shed light on the potential benefits of the intensive services provided at IRFs in this population.

Short-term metformin and exercise training effects on strength, aerobic capacity, glycemic control, and mitochondrial function in children with burn injury.

Severely burned children experience a chronic state of sympathetic nervous system activation that is associated with hypermetabolic/cardiac stress and muscle wasting. Metformin, a diabetes medication, helps control hyperglycemia in obese diabetic populations, and exercise has been shown to improve exercise strength and aerobic exercise capacity after severe burns. However, whether exercise improves glycemic control in burned children and whether combining exercise and metformin improves outcomes to a greater degree than exercise alone are unknown. We tested the hypothesis that a 6-wk exercise program combined with short-term metformin administration (E + M) improves aerobic and strength exercise capacity to a greater degree than exercise and placebo (E), while improving glucose tolerance and muscle metabolic function. We found that, before exercise training, the metformin group compared with the placebo group had attenuated mitochondrial respiration (pmol·s-1·mg-1) for each state: state 2 (-22.5 ± 3), state 3 (-42.4 ± 13), and oxphos (-58.9 ± 19) ( P ≤ 0.02, M vs. E + M group for each state). However, in the E + M group, exercise increased mitochondrial respiration in each state ( P ≤ 0.05), with respiration being comparable to that in the E group (each P > 0.05). In both groups, exercise induced comparable improvements in strength (change from preexercise, Δ1.6 ± 0.6 N-M·kgLBM) and V̇o2peak (Δ9 ± 7 mlO2·kgLBM) as well as fasting glucose (Δ19.3 ± 13 mg·dl) and glucose AUC (Δ3402 ± 3674 mg·dl-1·min-1), as measured by a 75-g OGTT (all P ≤ 0.03). Exercise reduced resting energy expenditure in E + M (Δ539 ± 480 kcal/24 h, P < 0.01) but not E subjects ( P = 0.68). Both groups exhibited reduced resting heart rate (Δ30 ± 23 beats/min, P ≤ 0.02). These data indicate that short-term metformin combined with exercise provides no further improvement beyond that of exercise alone for strength, exercise capacity, and glycemic control.

Cardiorespiratory Capacity and Strength Remain Attenuated in Children with Severe Burn Injuries at Over 3 Years Postburn.

OBJECTIVES: To compare physical capacity and body composition between children with burn injuries at approximately 4 years postburn and healthy, fit children. STUDY DESIGN: In this retrospective, case-control study, we analyzed the strength, aerobic capacity, and body composition of children with severe burn injuries (n = 40) at discharge, after completion of a 6- to 12-week rehabilitative exercise training program, and at 3-4 years postburn. Values were expressed as a relative percentage of those in age- and sex-matched children for comparison (n = 40 for discharge and postexercise; n = 40 for 3.5 years postburn). RESULTS: At discharge, lean body mass was 89% of that in children without burn injuries, and exercise rehabilitation restored this to 94% (P < .01). At 3.5 years postburn, lean body mass (94%), bone mineral content (89%), and bone mineral density (93%; each P ≤ .02) remained reduced, whereas total body fat was increased (148%, P = .01). Cardiorespiratory fitness remained lower in children with burn injuries both after exercise training (75%; P < .0001) and 3.5 years later (87%; P < .001). Peak torque (60%; P < .0001) and average power output (58%; P < .0001) were lower after discharge. Although exercise training improved these, they failed to reach levels achieved in healthy children without burns (83-84%; P < .0001) but were maintained at 85% and 82%, respectively, 3.5 years later (P < .0001). CONCLUSIONS: Although the benefits of rehabilitative exercise training on strength and cardiorespiratory capacity are maintained at almost 4 years postburn, they are not restored fully to the levels of healthy children. Although the underlying mechanism of this phenomenon remains elusive, these findings suggest that future development of continuous exercise rehabilitation interventions after discharge may further narrow the gap in relation to healthy adolescents.

Buprenorphine-Sustained Release Alters Hemodynamic Parameters in a Rat Burn Model.

BACKGROUND: It has been previously shown that anesthesia and analgesia can affect outcomes in the rat burn model and that buprenorphine alleviated pain without drastically altering the outcomes of interest. Recently, the use of a sustained release (SR) formulation of buprenorphine has been promoted over conventional buprenorphine. In this study, we assessed whether buprenorphine-SR altered hemodynamic parameters in our rat model of severe burn injury. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomized to receive either conventional buprenorphine (0.05 mg/kg) or buprenorphine-SR (1 mg/kg). Buprenorphine-SR was administered 24 h before the experiment. Buprenorphine was administered on the day of experiment. These groups were further randomized to control or scald burn (60% of total body surface area). Systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) were measured using a noninvasive blood pressure system before receiving analgesia and after 72 h. RESULTS: As expected, HR was significantly higher after burn injury regardless of analgesic (P <0.0001). Both SBP and DBP were significantly decreased in burned animals receiving conventional buprenorphine (P < 0.0001), but neither was altered in the buprenorphine-SR-treated burned animals. However, SBP, DBP, and HR were significantly increased after 72 h in control animals receiving buprenorphine-SR (P < 0.0001). CONCLUSIONS: These data indicate that buprenorphine-SR alters the hemodynamic response to injury and may not be an appropriate choice for a model of severe burn injury. If this analgesic is used, investigators must cautiously form conclusions, especially in experimental conditions that would be expected to alter cardiac hemodynamics.

Reasons for Distress Among Burn Survivors at 6, 12, and 24 Months Postdischarge: A Burn Injury Model System Investigation.

OBJECTIVE: To identify important sources of distress among burn survivors at discharge and 6, 12, and 24 months postinjury, and to examine if the distress related to these sources changed over time. DESIGN: Exploratory. SETTING: Outpatient burn clinics in 4 sites across the country. PARTICIPANTS: Participants who met preestablished criteria for having a major burn injury (N=1009) were enrolled in this multisite study. INTERVENTIONS: Participants were given a previously developed list of 12 sources of distress among burn survivors and asked to rate on a 10-point Likert-type scale (0=no distress to 10=high distress) how much distress each of the 12 issues was causing them at the time of each follow-up. MAIN OUTCOMES MEASURES: The Medical Outcomes Study 12-Item Short-Form Health Survey was administered at each time point as a measure of health-related quality of life. The Satisfaction With Appearance Scale was used to understand the relation between sources of distress and body image. Finally, whether a person returned to work was used to determine the effect of sources of distress on returning to employment. RESULTS: It was encouraging that no symptoms were worsening at 2 years. However, financial concerns and long recovery time are 2 of the highest means at all time points. Pain and sleep disturbance had the biggest effect on ability to return to work. CONCLUSIONS: These findings can be used to inform burn-specific interventions and to give survivors an understanding of the temporal trajectory for various causes of distress. In particular, it appears that interventions targeted at sleep disturbance and high pain levels can potentially effect distress over financial concerns by allowing a person to return to work more quickly.

Fifty Years of Burn Care at Shriners Hospitals for Children, Galveston.

More than 50 years ago, Shriners Hospitals for Children expanded their philanthropy to include care for burned children. In so doing, the effects of their work weightily expanded from rehabilitation and quality of life outcomes to include survival proper. As the first facility dedicated to the care of burned children, originally designated the Shriners Burn Institute, the Galveston hospital remains the cornerstone of this endeavor. Shriners maintains charitable pediatric hospitals, provide care irrespective of the patient's or the family's ability to pay, and promote research. The sole criterion for admission at Shriners Hospitals for Children is the determination by a surgeon at a Shriners hospital that "the child's trouble may be corrected or improved." This philanthropic effort to provide medical care for children is one expression of the human commonality recognized by Shriners. In this article, we provide some background information on how this hospital came into existence as well as a global summary of its interventions toward greater survival and more complete rehabilitation of burned children. Based on the findings presented herein, we assert that there is less suffering and less loss of life due to childhood burns today than in previous years. We attribute much of this improvement to the simple voluntary collective decision by Shriners to provide alms for burned children.

Topical Antimicrobials in Burn Care: Part 1-Topical Antiseptics.

Burn wounds disrupt the body's primary defense against invasion and colonization by microorganisms. Topical antimicrobials are one component in burn wound care. These agents suppress microbial growth to advantage skin cells and wound healing. Topical antimicrobials can be divided into 2 superclasses: antiseptics and antibiotics. We review the 4 main classes of topical antiseptics (emulsifiers, acids, oxidizers, and heavy metals) and antiseptic-impregnated dressings in current clinical use and address the mechanisms, as well as the advantages and disadvantages of each antiseptic for burn wound management.

Inhalation Injury in the Burned Patient.

Inhalation injury causes a heterogeneous cascade of insults that increase morbidity and mortality among the burn population. Despite major advancements in burn care for the past several decades, there remains a significant burden of disease attributable to inhalation injury. For this reason, effort has been devoted to finding new therapeutic approaches to improve outcomes for patients who sustain inhalation injuries.The three major injury classes are the following: supraglottic, subglottic, and systemic. Treatment options for these three subtypes differ based on the pathophysiologic changes that each one elicits.Currently, no consensus exists for diagnosis or grading of the injury, and there are large variations in treatment worldwide, ranging from observation and conservative management to advanced therapies with nebulization of different pharmacologic agents.The main pathophysiologic change after a subglottic inhalation injury is an increase in the bronchial blood flow. An induced mucosal hyperemia leads to edema, increases mucus secretion and plasma transudation into the airways, disables the mucociliary escalator, and inactivates hypoxic vasocontriction. Collectively, these insults potentiate airway obstruction with casts formed from epithelial debris, fibrin clots, and inspissated mucus, resulting in impaired ventilation. Prompt bronchoscopic diagnosis and multimodal treatment improve outcomes. Despite the lack of globally accepted standard treatments, data exist to support the use of bronchoscopy and suctioning to remove debris, nebulized heparin for fibrin casts, nebulized N-acetylcysteine for mucus casts, and bronchodilators.Systemic effects of inhalation injury occur both indirectly from hypoxia or hypercapnia resulting from loss of pulmonary function and systemic effects of proinflammatory cytokines, as well as directly from metabolic poisons such as carbon monoxide and cyanide. Both present with nonspecific clinical symptoms including cardiovascular collapse. Carbon monoxide intoxication should be treated with oxygen and cyanide with hydroxocobalamin.Inhalation injury remains a great challenge for clinicians and an area of opportunity for scientists. Management of this concomitant injury lags behind other aspects of burn care. More clinical research is required to improve the outcome of inhalation injury.The goal of this review is to comprehensively summarize the diagnoses, treatment options, and current research.

Inducible satellite cell depletion attenuates skeletal muscle regrowth following a scald-burn injury.

KEY POINTS: Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors. ABSTRACT: Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7CreER -DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2'-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P < 0.05). Burn injury induced robust atrophy in muscles located both proximal and distal to the injury site (∼30% decrease in fibre cross-sectional area, P < 0.05). Additionally, burn injury induced skeletal muscle regeneration, satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P < 0.05). These findings support an integral role for satellite cells in the aetiology of lean tissue recovery following a severe burn injury.

Predicting Heterotopic Ossification Early After Burn Injuries: A Risk Scoring System.

OBJECTIVE: The purpose of this study is to develop a scoring system that stratifies burn patients at the time of hospital admission according to risk of developing heterotopic ossification (HO). SUMMARY OF BACKGROUND DATA: HO in burns is an uncommon but severely debilitating problem with a poorly understood mechanism and no fully effective prophylactic measures. METHODS: Data were obtained from the Burn Model System National Database from 1994 to 2010 (n = 3693). The primary outcome is diagnosis of HO at hospital discharge. Logistic regression analysis was used to determine significant demographic and medical predictors of HO. A risk scoring system was created in which point values were assigned to predictive factors and final risk score is correlated with the percent risk of developing HO. The model was internally and externally validated. RESULTS: The mean age of the subjects is 42.5 ±â€Š16.0 years, the mean total body surface area (TBSA) burned is 18.5 ±â€Š16.4%, and the population is 74.9% male. TBSA and the need for grafting of the arm, head/neck, and trunk were significant predictors of HO development (P < 0.01). A 13-point risk scoring system was developed using these significant predictors. The model c-statistic is 0.92. The risk scoring system demonstrated evidence of internal and external validity. An online calculator was developed to facilitate translation of knowledge to practice and research. CONCLUSIONS: This HO risk scoring system identifies high-risk burn patients suitable for diagnostic testing and interventional HO prophylaxis trials.

The metabolic stress response to burn trauma: current understanding and therapies.

Major burns provoke a profound stress response, which is unrivalled in terms of its magnitude and duration. Evidence suggests that the pathophysiological stress response to severe burn trauma persists for several years after injury. Thus, there is a pressing need for novel strategies that mitigate this response and restore normal metabolic function in patients with burns. This is the first in a Series of three papers about the care of people with burns. In this paper, we review the current knowledge of the stress response to burn trauma, with a focus on hypermetabolism, muscle wasting, and stress-induced diabetes. We highlight recent developments and important knowledge gaps that need to be pursued to develop novel therapeutic strategies to improve outcomes in burn survivors.

Hypertrophic scarring: the greatest unmet challenge after burn injury.

Improvements in acute burn care have enabled patients to survive massive burns that would have once been fatal. Now up to 70% of patients develop hypertrophic scars after burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. Approaches to optimise healing potential of burn wounds use targeted wound care and surgery to minimise the development of hypertrophic scarring. Such approaches often fail, and modulation of the established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventive and therapeutic strategies.

Pathophysiology, research challenges, and clinical management of smoke inhalation injury.

Smoke inhalation injury is a serious medical problem that increases morbidity and mortality after severe burns. However, relatively little attention has been paid to this devastating condition, and the bulk of research is limited to preclinical basic science studies. Moreover, no worldwide consensus criteria exist for its diagnosis, severity grading, and prognosis. Therapeutic approaches are highly variable depending on the country and burn centre or hospital. In this Series paper, we discuss understanding of the pathophysiology of smoke inhalation injury, the best evidence-based treatments, and challenges and future directions in diagnostics and management.

ß-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

OBJECTIVE: We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. METHODS: In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3 years, 147±20 cm, 45±23 kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3 years, 152±15 cm, 52±13 kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. RESULTS: Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, P<.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBFmax ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC50 , P>.05) under either condition. CONCLUSION: Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children.

Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in adult and pediatric burn patients.

BACKGROUND: Burn patients are prone to infections which often necessitate broad antibiotic coverage. Vancomycin is a common antibiotic after burn injury and is administered alone (V), or in combination with imipenem-cilastin (V/IC) or piperacillin-tazobactam (V/PT). Sparse reports indicate that the combination V/PT is associated with increased renal dysfunction. The purpose of this study was to evaluate the short-term impact of the three antibiotic administration types on renal dysfunction. METHODS: All pediatric and adult patients admitted to our centers between 2004 and 2016 with a burn injury were included in this retrospective review if they met the criteria of exposition to either V, V/IC, or V/PT for at least 48 h, had normal baseline creatinine, and no pre-existing renal dysfunction. Creatinine was monitored for 7 days after initial exposure; the absolute and relative increase was calculated, and patient renal outcomes were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria depending on creatinine increases and estimated creatinine clearance. Secondary endpoints (demographic and clinical data, incidences of septicemia, and renal replacement therapy) were analyzed. Antibiotic doses were modeled in logistic and linear multivariable regression models to predict categorical KDIGO events and relative creatinine increase. RESULTS: Out of 1449 patients who were screened, 718 met the inclusion criteria, 246 were adults, and 472 were children. Between the study cohorts V, V/IC, and V/PT, patient characteristics at admission were comparable. V/PT administration was associated with a statistically higher serum creatinine, and lower creatinine clearance compared to patients receiving V alone or V/IC in adults and children after burn injury. The incidence of KDIGO stages 1, 2, and 3 was higher after V/PT treatment. In children, the incidence of KDIGO stage 3 following administration of V/PT was greater than after V/IC. In adults, the incidence of renal replacement therapy was higher after V/PT compared with V or V/IC. Multivariate modeling demonstrated that V/PT is an independent predictor of renal dysfunction. CONCLUSION: Co-administration of vancomycin and piperacillin-tazobactam is associated with increased renal dysfunction in pediatric and adult burn patients when compared to vancomycin alone or vancomycin plus imipenem-cilastin. The mechanism of this increased nephrotoxicity remains elusive and warrants further scientific evaluation.