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.

Role of anabolic testosterone agents and structured exercise to promote recovery in ICU survivors.

PURPOSE OF REVIEW: ICU survivors frequently suffer significant, prolonged physical disability. 'ICU Survivorship', or addressing quality-of-life impairments post-ICU care, is a defining challenge, and existing standards of care fail to successfully address these disabilities. We suggest addressing persistent catabolism by treatment with testosterone analogues combined with structured exercise is a promising novel intervention to improve 'ICU Survivorship'. RECENT FINDINGS: One explanation for lack of success in addressing post-ICU physical disability is most ICU patients exhibit severe testosterone deficiencies early in ICU that drives persistent catabolism despite rehabilitation efforts. Oxandrolone is an FDA-approved testosterone analogue for treating muscle weakness in ICU patients. A growing number of trials with this agent combined with structured exercise show clinical benefit, including improved physical function and safety in burns and other catabolic states. However, no trials of oxandrolone/testosterone and exercise in nonburn ICU populations have been conducted. SUMMARY: Critical illness leads to a catabolic state, including severe testosterone deficiency that persists throughout hospital stay, and results in persistent muscle weakness and physical dysfunction. The combination of an anabolic agent with adequate nutrition and structured exercise is likely essential to optimize muscle mass/strength and physical function in ICU survivors. Further research in ICU populations is needed.

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.

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.

Exercise heat acclimation causes post-exercise hypotension and favorable improvements in lipid and immune profiles: A crossover randomized controlled trial.

BACKGROUND: Passive hyperthermic exposure causes an acute hypotensive response following the cessation of heat stress. Chronic heat stress is well documented in animal studies to instigate metabolic and lipid alterations. However, it is unknown if exercise-heat acclimation also causes favorable chronic blood pressure, lipid, and immune responses in humans. PURPOSE: This project tested the hypothesis that 10-day exercise-heat acclimation (HA) would cause greater post-exercise reductions in arterial blood pressure and favorable metabolic, lipid, and immune responses compared to 10-day exercise under neutral conditions (CON). METHODS: Thirteen healthy sedentary participants (8M/5F, 28 ±â€¯6y, 78 ±â€¯17 kg), completed a 10-day (90 min/day exercise bout) clamped hyperthermia HA (increase internal temperature 1.5 °C, in 42 °C, 28% Rh) and control (CON: 23 °C, 42% Rh) protocols in a counterbalanced design with a 2 month washout. Pre- and post-exercise HA/CON blood pressures were taken 1-h post-exercise on exercise days 1 and 10. Metabolic, lipid and immune panels were taken pre-post HA/CON. RESULTS: Exercise under heat stress had greater post-exercise hypotension (systolic; -6 mmHg, diastolic; -8 mmHg; and mean arterial pressure; -7 mmHg) on both days 1 and 10 compared to exercise under neutral conditions (main effect for condition, P ≤ 0.004). Only from pre-to-post HA, total cholesterol (168 ±â€¯19 to 157 ±â€¯15; P < 0.03) and triglycerides (137 ±â€¯45 to 111 ±â€¯30; P < 0.03) were reduced, while absolute lymphocytes (-26%), monocytes (-22%), and basophils (-49%) significantly decreased (each P ≤ 0.04). Relative values of neutrophils increased (18%) and lymphocytes decreased (-20%) only after HA (P ≤ 0.04). CONCLUSION: These data indicate that exercise in the heat (regardless of acclimation status) causes a profound post-exercise hypotensive response, while HA causes favorable lipid, and immune profile changes. Further examination of exercise-heat acclimation on vascular, metabolic, and immune responses will offer insight for benefits in other clinical populations with vascular, metabolic and immune dysfunction.

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.

Reduced Postburn Hypertrophic Scarring and Improved Physical Recovery With Yearlong Administration of Oxandrolone and Propranolol.

BACKGROUND: Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for 1 year restores growth in children with large burns. Here, we investigated whether the combined administration of OxProp for 1 year would reduce scarring and improve quality of life compared with control. STUDY DESIGN: Children with large burns (n = 480) were enrolled into this institutional review board-approved study; patients were randomized to control (n = 226) or administration of OxProp (n = 126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained. RESULTS: Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (P < 0.05) occurred in OxProp-treated scars. With OxProp, scar severity was attenuated and pliability increased (both P < 0.05). Analyses of patient-reported outcomes showed improved general and emotional health within the OxProp-treated group (P < 0.05). CONCLUSIONS: Here, we have shown improvements in objective and subjective measures of scarring and an increase in overall patient-reported physical function. The combined administration of OxProp for up to a year after burn injury should be considered for the reduction of postburn scarring and improvement of long-term psychosocial outcomes in children with massive burns.

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.

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.

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.

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.

Body Composition Changes in Severely Burned Children During ICU Hospitalization.

OBJECTIVES: Prolonged hospitalization due to burn injury results in physical inactivity and muscle weakness. However, how these changes are distributed among body parts is unknown. The aim of this study was to evaluate the degree of body composition changes in different anatomical regions during ICU hospitalization. DESIGN: Retrospective chart review. SETTING: Children's burn hospital. PATIENTS: Twenty-four severely burned children admitted to our institution between 2000 and 2015. INTERVENTIONS: All patients underwent a dual-energy x-ray absorptiometry within 2 weeks after injury and 2 weeks before discharge to determine body composition changes. No subject underwent anabolic intervention. We analyzed changes of bone mineral content, bone mineral density, total fat mass, total mass, and total lean mass of the entire body and specifically analyzed the changes between the upper and lower limbs. MEASUREMENTS AND MAIN RESULTS: In the 24 patients, age was 10 ± 5 years, total body surface area burned was 59% ± 17%, time between dual-energy x-ray absorptiometries was 34 ± 21 days, and length of stay was 39 ± 24 days. We found a significant (p < 0.001) average loss of 3% of lean mass in the whole body; this loss was significantly greater (p < 0.001) in the upper extremities (17%) than in the lower extremities (7%). We also observed a remodeling of the fat compartments, with a significant whole-body increase in fat mass (p < 0.001) that was greater in the truncal region (p < 0.0001) and in the lower limbs (p < 0.05). CONCLUSIONS: ICU hospitalization is associated with greater lean mass loss in the upper limbs of burned children. Mobilization programs should include early mobilization of upper limbs to restore upper extremity function.

Correlation Between PaO2/FIO2 and Peripheral Capillary Oxygenation/FIO2 in Burned Children With Smoke Inhalation Injury.

OBJECTIVES: Determine whether the peripheral capillary oxygenation/FIO2 ratio correlates with the PaO2/FIO2 ratio in burned children with smoke inhalation injury, with the goal of understanding if the peripheral capillary oxygenation/FIO2 ratio can serve as a surrogate for the PaO2/FIO2 ratio for the diagnosis of acute respiratory distress syndrome. DESIGN: Retrospective chart review. SETTING: Shriners Hospitals for Children-Galveston. PATIENTS: All burned children with smoke inhalation injury who were admitted from 1996 to 2014 and had simultaneously obtained peripheral capillary oxygenation, FIO2 and PaO2 measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-three patients (63% male, 8 ± 5 yr, 53% ± 24% total body surface area burns) were analyzed. Peripheral capillary oxygenation/FIO2 ratios were divided into four subgroups based on peripheral capillary oxygenation values (≤ 100%, ≤ 98%, ≤ 95%, and ≤ 92%). Significance was accepted at r greater than 0.81. The r (number of matches) was 0.66 (23,072) for less than or equal to 100%, 0.87 (18,932) for less than or equal to 98%, 0.89 (7,056) for less than or equal to 95%, and 0.93 (4,229) for less than or equal to 92%. In the subgroup of patients who developed acute respiratory distress syndrome, r was 0.65 (8,357) for less than or equal to 100%, 0.89 (7,578) for less than or equal to 98%, 0.89 (4,115) for less than or equal to 95%, and 0.91 (2,288) less than or equal to 92%. CONCLUSIONS: PaO2/FIO2 and peripheral capillary oxygenation/FIO2 strongly correlate in burned children with smoke inhalation injury, with a peripheral capillary oxygenation of less than 92% providing the strongest correlation. Thus, peripheral capillary oxygenation/FIO2 ratio may be able to serve as surrogate for PaO2/FIO2, especially when titrating FIO2 to achieve a peripheral capillary oxygenation of 90-95% (i.e., in the acute respiratory distress syndrome range).

Effect of Exercise Training on the Frequency of Contracture-Release Surgeries in Burned Children.

BACKGROUND: Intensive physical exercise (IPE) increases strength, lean body mass, aerobic capacity, and range of motion in children with extensive burns. However, whether IPE decreases the frequency of burn scar contracture-releasing procedures in children with extensive burns is unknown. MATERIALS AND METHODS: Prospectively collected surgical records of 184 children who had undergone axilla, elbow, and/or wrist contracture-releasing procedures were reviewed. All children were 7 years or older and had sustained burns of at least 40% of the total body surface area. Eighty-two children completed an IPE program, and 102 children did not. For both groups, the axilla, elbow, and wrist were examined for tightness and restricted movement. Children with contractural difficulty were prescribed a releasing procedure. Logistic regression was used to model the relationship between multiple release surgeries and group. RESULTS: Patients in both groups had comparable injury severity. A total of 120 releases were carried out in the 82 IPE patients. In contrast, 211 releases were needed in the 102 non-IPE patients. An approximately 60% decrease in the frequency of rerelease operations was noted in IPE patients (12.5% for the IPE group and 31.8% for non-IPE group; P < 0.05). CONCLUSIONS: When used as an adjunct therapy in postburn rehabilitation, IPE may be useful for reducing the need for contracture release. The mechanisms underlying the beneficial effects of exercise remain undefined and should be investigated.

Satellite cell activation and apoptosis in skeletal muscle from severely burned children.

KEY POINTS: Severe burns result in profound skeletal muscle atrophy that hampers recovery. The activity of skeletal muscle stem cells, satellite cells, acutely following a severe burn is unknown and may contribute to the recovery of lean muscle. Severe burn injury induces skeletal muscle regeneration and myonuclear apoptosis. Satellite cells undergo concurrent apoptosis and activation acutely following a burn, with a net reduction in satellite cell content compared to healthy controls. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors. ABSTRACT: Severe burns result in profound skeletal muscle atrophy; persistent muscle loss 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 propose that an impaired muscle satellite cell response is key in the aetiology of burn-induced cachexia. Muscle biopsies from the m. vastus lateralis were obtained from 12 male pediatric burn patients (>30% total body surface area burn) and 12 young, healthy male subjects. Satellite cell content, activation and apoptosis were determined via immunohistochemistry, as were muscle fibre regeneration and myonuclear apoptosis. Embryonic myosin heavy chain expression and central nucleation, indices of skeletal muscle regeneration, were elevated in burn patients (P < 0.05). Myonuclear apoptosis, quantified by TUNEL positive myonuclei and cleaved caspase-3 positive myonuclei, was also elevated in burn patients (P < 0.05). Satellite cell content was reduced in burn patients, with approximately 20% of satellite cells positive for TUNEL staining, indicating DNA damage associated with apoptosis (P < 0.05). Additionally, a significant percentage of satellite cells in burn patients expressed Ki67, a marker for cellular proliferation (P < 0.05). Satellite cell activation was also observed in burn patients with increased expression of MyoD compared to healthy controls (P < 0.05). Robust skeletal muscle atrophy occurs after burn injury, even in muscles located distally to the site of injury. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors.

Reversal of Growth Arrest With the Combined Administration of Oxandrolone and Propranolol in Severely Burned Children.

BACKGROUND: The hypercatabolic response in severely burned pediatric patients is associated with increased production of catecholamines and corticosteroids, decreased formation of testosterone, and reduced strength alongside growth arrest for up to 2 years after injury. We have previously shown that, in the pediatric burned population, the administration of the testosterone analog oxandrolone improves lean body mass accretion and bone mineral content and that the administration of the ß1-, ß2-adrenoceptor antagonist propranolol decreases cardiac work and resting energy expenditure while increasing peripheral lean mass. Here, we determined whether the combined administration of oxandrolone and propranolol has added benefit. METHODS: In this prospective, randomized study of 612 burned children [52% ±â€Š1% of total body surface area burned, ages 0.5-14 years (boys); ages 0.5-12 years (girls)], we compared controls to the individual administration of these drugs, and the combined administration of oxandrolone and propranolol at the same doses, for 1 year after burn. Data were recorded at discharge, 6 months, and 1 and 2 years after injury. RESULTS: Combined use of oxandrolone and propranolol shortened the period of growth arrest by 84 days (P = 0.0125 vs control) and increased growth rate by 1.7 cm/yr (P = 0.0024 vs control). CONCLUSIONS: Combined administration of oxandrolone and propranolol attenuates burn-induced growth arrest in pediatric burn patients. The present study is registered at clinicaltrials.gov: NCT00675714 and NCT00239668.

Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine With Burn and Smoke Inhalation Injury.

OBJECTIVES: To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action-bronchodilation (ß2-adrenergic receptor agonism) and attenuation of airway hyperemia (α1-adrenergic receptor agonism) with minimal systemic effects. DESIGN: Randomized, controlled, prospective, and large animal translational studies. SETTING: University large animal ICU. SUBJECTS: Twelve chronically instrumented sheep. INTERVENTIONS: The animals were exposed to 40% total body surface area third degree skin flame burn and 48 breaths of cooled cotton smoke inhalation under deep anesthesia and analgesia. The animals were then placed on a mechanical ventilator, fluid resuscitated, and monitored for 48 hours in a conscious state. After the injury, sheep were randomized into two groups: 1) epinephrine, nebulized with 4 mg of epinephrine every 4 hours starting 1 hour post injury, n = 6; or 2) saline, nebulized with saline in the same manner, n = 6. MEASUREMENTS AND MAIN RESULTS: Treatment with epinephrine had a significant reduction of the pulmonary transvascular fluid flux to water (p < 0.001) and protein (p < 0.05) when compared with saline treatment from 12 to 48 hours and 36 to 48 hours, respectively. Treatment with epinephrine also reduced the systemic accumulation of body fluids (p < 0.001) with a mean of 1,410 ± 560 mL at 48 hours compared with 3,284 ± 422 mL of the saline group. Hemoglobin levels were comparable between the groups. Changes in respiratory system dynamic compliance, mean airway pressure, PaO2/FiO2 ratio, and oxygenation index were also attenuated with epinephrine treatment. No considerable systemic effects were observed with epinephrine treatment. CONCLUSIONS: Nebulized epinephrine should be considered for use in future clinical studies of patients with burns and smoke inhalation injury.

Effects of Slackline Training on Postural Control, Jump Performance, and Myoelectrical Activity in Female Basketball Players.

The main goal of the study was to assess the effects of slackline training on the postural control system and jump performance of athletes. Twenty-five female basketball players were randomized into 2 groups: control (N = 12) and experimental (N = 13). The latter experienced a 6-week supervised slackline training (3 sessions per week, 5-9 minutes per session). Participants underwent center of pressure (CoP) testing through three 10-second tasks (bipedal, left leg, and right leg support) over firm and compliant surfaces with eyes open. Several CoP parameters were assessed: length, area, length/area, speed, Ymean, Xmean, deltaY, deltaX, RMS (root-mean-squared amplitude of the CoP), RMSY, and RMSX. Surface electromyography recordings were obtained too. Participants were also tested on jump performance, provided perceived exertion (6-20 Borg scale) and local muscle perceived exertion. Center of pressure parameters significantly differed before and after training only in the experimental group and only on the compliant surface (left leg: length, area, speed, deltaY, and deltaX; right leg: length, speed, Ymean, deltaY, and RMSY). Surface electromyography recordings were comparable before and after training in both groups. Performance on a countermovement jump test significantly improved only in the experimental group (effect side was 3.21 and 1.36 [flight time and jump height, respectively], which is described as a large effect). Mechanical power of the legs, as measured through the 30-second maximal performance jump test, did not improve in either group. The slackline training was rated as "somewhat hard" with the quadriceps, soleus, and gastrocnemius being rated as the most engaged muscles. Data indicate that slacklining requires activation of the main lower limb muscles. On conclusion, slacklining may be a valid cross-training tool for female basketball players.

The role of exercise in the rehabilitation of patients with severe burns.

Severe burn trauma results in persistent skeletal muscle catabolism and prolonged immobilization. We hypothesize that structured rehabilitative exercise is a safe and efficacious strategy to restore lean body mass and physical function in burn victims. Here, we review the evidence for the utility of rehabilitative exercise training in restoring physiological function in burn survivors.