Sepsis Increases Muscle Proteolysis in Severely Burned Adults, but Does not Impact Whole-Body Lipid or Carbohydrate Kinetics.

Sepsis is a common and often fatal consequence of severe burn injury, but its exact effects on whole body and muscle metabolism in the burn patient is unclear. To address this, 13 septic and 11 nonseptic patients (age: 36.9 ±â€Š13.0 years) with burns encompassing >30% of their total body surface area underwent muscle protein kinetic studies under postabsorptive conditions using bolus injections of ring-C6 and N phenylalanine isotopes. In parallel, whole-body lipid and carbohydrate kinetics were assessed using constant infusions of [U-C6]palmitate, [6,6-H2]glucose, and [H5]glycerol, and during a 2-h hyperinsulinemic euglycemic clamp. Muscle mRNA levels of genes implicated in the development of muscle cachexia were assessed by qPCR. Fractional breakdown rates of mixed-muscle proteins were found to be 2.4-fold greater in septic versus nonseptic patients (P < 0.05). No discernable differences in fractional synthetic rate of mixed-muscle proteins or rate of appearance of plasma free fatty acids, glycerol, or glucose could be observed between patient groups, although the latter was significantly associated with burn size (P < 0.05). Hyperinsulinemia stimulated whole-body glucose uptake and suppressed endogenous glucose production and whole-body lipolytic rate to equivalent degrees in both groups. Muscle mRNA levels of genes spanning autophagy, lysosomal, and ubiquitin proteasome-mediated proteolysis were not enhanced in septic versus nonseptic patients. Our results demonstrate that accelerated muscle proteolysis appears to be the principal metabolic consequence of sepsis in severe burn patients and could be a contributing factor to the accelerated loss of muscle mass in these individuals. The exact mechanistic basis for these changes remains unclear.

Effects of a restrictive blood transfusion protocol on acute pediatric burn care: Transfusion threshold in pediatric burns.

BACKGROUND: Blood transfusion is costly and associated with various medical risks. Studies in critically ill adult and pediatric patients suggest that implementation of more restrictive transfusion protocols based on lower threshold hemoglobin concentrations can be medically and economically advantageous. The purpose of this study was to evaluate the implications of a hemoglobin threshold change in pediatric burn patients. METHODS: We implemented a change in hemoglobin threshold from 10 g/dL to 7 g/dL and compared data from patients before and after this protocol change in a retrospective review. Primary endpoints were hemoglobin concentration at baseline, before transfusion, and after transfusion; amount of blood product administered; and mortality. Secondary endpoints were the incidence of sepsis based on the American Burn Association physiological criteria for sepsis and mean number of septic days per patient. All endpoint analyses were adjusted for relevant clinical covariates via generalized additive models or Cox proportional hazard model. Statistical significance was accepted at p less than 0.05. RESULTS: Patient characteristics and baseline hemoglobin concentrations (pre, 13.5 g/dL; post, 13.3 g/dL; p > 0.05) were comparable between groups. The group transfused based on the more restrictive hemoglobin threshold had lower hemoglobin concentrations before and after transfusion throughout acute hospitalization, received lower volumes of blood during operations (pre, 1012 mL; post, 824 mL; p < 0.001) and on days without surgical procedures (pre, 602 mL; post, 353 mL; p < 0.001), and had a lower mortality (pre, 8.0%; post, 3.9%; mortality hazard decline, 0.55 [45%]; p < 0.05). Both groups had a comparable incidence of physiological sepsis, though the more restrictive threshold group had a lower number of sepsis days per patient. CONCLUSION: More restrictive transfusion protocols are safe and efficacious in pediatric burn patients. The associated reduction of transfused blood may lessen medical risks of blood transfusion and lower economic burden. LEVEL OF EVIDENCE: Therapeutic, level IV.

Correlation between invasive and noninvasive blood pressure measurements in severely burned children.

INTRODUCTION: Accurate blood pressure monitoring is essential for burn management, with the intra-arterial line method being the gold standard. Here we evaluated agreement between cuff and intra-arterial line methods. METHODS: Data from burned children admitted from 1997 to 2016 were retrospectively reviewed. Simultaneously collected intra-arterial and cuff measurements were cross-matched and linear regression performed to assess agreement for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). RESULTS: We identified 9969 matches for SBP, DBP, and MAP in 872 patients (579 male) aged 8±5years with burns covering 52±20% of the total body surface area and a hospitalization lasting 33±31 days. Intra-arterial lines had a complication rate of 1%. The mean bias (95% CI) between methods was 1.3 (0.5, 2.1) mm Hg for SBP, -6.4 (-7.0, -5.7) mmHg for DBP, and -5.8 (-6.4, -5.3) mmHg for MAP. The standard deviation of the bias (95% limit of agreement) was 12.1 (-22.5, 25.1) mmHg for SBP, 9.9 (-25.8, 13.0) mmHg for DBP, and 8.7 (-22.8, 11.1) mmHg for MAP. CONCLUSIONS: Cuff measurements vary widely from those of intra-arterial lines, which have a low complication rate. Intra-arterial lines are advisable when tight control of the hemodynamic response is essential.

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.

Contemporary Burn Survival.

BACKGROUND: The standard of burn treatment today reflects major advances. We sought to quantitate the impact of these advances on burn survival via age-stratified mortality ratios compared with other reported mortality analyses in burns. STUDY DESIGN: Age, percent of the total body surface area (TBSA) burned, presence of inhalation injury, length of stay, and survival status were recorded at admission and at discharge for all new burn admissions between 1989 and 2017. The expected mortality probability was calculated using historical multiple regression techniques and compared with observed data. We developed a prediction model for our observed data. RESULTS: Between 1989 and 2017, there were 10,384 consecutive new burn admissions, with 355 mortalities (median age, 13 years; median percent TBSA burn, 11%). We saw a significant decrease in our observed mortality data compared to historical predictions (p < 0.0001), and a 2% reduction per year in mortality during the 3 decades. The prediction model of mortality for the data is as follows: Pr(dying) = ex/(1 + ex) where x = -6.44 - 0.12 age + 0.0042 age2 - 0.0000283 age3 + 0.0499 TBSA + 1.21 Inhalation Injury + 0.015 third degree TBSA. CONCLUSIONS: The reduction in mortality over time may be attributed to successful changes in standard of care protocols in the burn center that improved the outlook for burned individuals, including protocols for management of inhalation injury, nutrition, resuscitation, and early excision and grafting.

Poverty, population density, and the epidemiology of burns in young children from Mexico treated at a U.S. pediatric burn facility.

INTRODUCTION: Children 5 and younger are at risk for sustaining serious burn injuries. The causes of burns vary depending on demographic, cultural and socioeconomic variables. At this pediatric burn center we provided medical care to children from Mexico with severe injuries. The purpose of this study was to understand the impact of demographic distribution and modifiable risk factors of burns in young children to help guide prevention. METHODS: A retrospective chart review was performed with children 5 and younger from Mexico who were injured from 2000-2013. The medical records of 447 acute patients were reviewed. Frequency counts and percentages were used to identify geographic distribution and calculate incidence of burns. Microsoft Powermap software was used to create a geographical map of Mexico based on types of burns. A binomial logistic regression was used to model the incidence of flame burns as opposed to scald burns in each state with relation to population density and poverty percentage. In all statistical tests, alpha=0.05 for a 95% level of confidence. RESULTS: Burns were primarily caused by flame and scald injuries. Admissions from flame injuries were mainly from explosions of propane tanks and gas lines and house fires. Flame injuries were predominantly from the states of Jalisco, Chihuahua, and Distrito Federal. Scalds were attributed to falling in large containers of hot water or food on the ground, and spills of hot liquids. Scald injuries were largely from the states of Oaxaca, Distrito Federal, and Hidalgo. The odds of a patient having flame burns were significantly associated with poverty percentage (p<0.0001) and population density (p=0.0085). Increasing levels of poverty led to decrease in odds of a flame burn, but an increase in the odds of scald burns. Similarly, we found that increasing population density led to a decrease in the odds of a flame burn, but an increase in the odds of a scald burn. CONCLUSIONS: Burns in young children from Mexico who received medical care at this pediatric burn center were attributed to flame and scalds. Potential demographic associations have been identified. Different states in Mexico have diverse cultural and socioeconomic variables that may influence the etiology of burns in young children and this information may help efficiently tailor burn prevention campaigns for burn prevention efforts in each region. APPLICABILITY OF RESEARCH TO PRACTICE: This information will be used to develop and help modify existing prevention campaigns.

Carbon Monoxide and Cyanide Poisoning in the Burned Pregnant Patient: An Indication for Hyperbaric Oxygen Therapy.

Carbon monoxide (CO) is a small molecule poison released as a product of incomplete combustion. Carbon monoxide binds hemoglobin, reducing oxygen delivery. This effect is exacerbated in the burned pregnant patient by fetal hemoglobin that binds CO 2.5- to 3-fold stronger than maternal hemoglobin. With no signature clinical symptom, diagnosis depends on patient injury history, elevated carboxyhemoglobin levels, and alterations in mental status. The standard of care for treatment of CO intoxication is 100% normobaric oxygen, which decreases the half-life of CO in the bloodstream from 5 hours to 1 hour. Hyperbaric oxygen (HBO2) is a useful adjunct to rapidly reduce the half-life of CO to 20 minutes and the incidence of delayed neurologic sequelae. Because of the slow disassociation of CO from hemoglobin in the fetus, there is a far stronger indication for HBO2 in the burned pregnant patient than in other burn patient populations.Cyanide intoxication is often a comorbid disease with CO in inhalation injury from an enclosed fire, but may be the predominant toxin. It acts synergistically with CO to effectively lower the lethal doses of both cyanide and CO. Diagnosis is best made in the presence of high lactate levels, carboxyhemoglobin concentrations greater than 10%, injury history of smoke inhalation from an enclosed fire, and alterations in consciousness. While treatment with hydroxocobalamin is the standard of care and has the effect of reducing concomitant CO toxicity, data indicate cyanide may also be displaced by HBO2.Carbon monoxide and cyanide poisoning presents potential complications impacting care. This review addresses the mechanism of action, presentation, diagnosis, and treatment of CO and cyanide poisonings in the burned pregnant patient and the use of HBO2 therapy.

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.

Volume Resuscitation in Patients With High-Voltage Electrical Injuries.

Volume resuscitation of patients with high-voltage electrical injuries (>1000 V) is a more complex challenge than standard burn resuscitation. High voltages penetrate deep tissues. These deep injuries are not accounted for in resuscitation formulae dependent on percentage of cutaneous burn. Myonecrosis occurring from direct electrical injury and secondary compartment syndromes can result in rhabdomyolysis, compromising renal function and urine output. Urine output is the primary end point, with a goal of 1 mL/kg/h for adult patients with high-voltage electrical injuries. As such, secondary resuscitation end points of laboratory values, such as lactate, base deficit, hemoglobin, and creatinine, as well as hemodynamic monitoring, such as mean arterial pressure and thermodilution techniques, can become crucial in guiding optimum administration of resuscitation fluids. Mannitol and bicarbonates are available but have limited support in the literature. High-voltage electrical injury patients often develop acute kidney injury requiring dialysis and have increased risks of chronic kidney disease and mortality. Continuous venovenous hemofiltration is a well-supported adjunct to clear the myoglobin load that hemodialysis cannot from circulation.

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.

Skeletal Muscle Mitochondrial Function is Determined by Burn Severity, Sex, and Sepsis, and is Associated With Glucose Metabolism and Functional Capacity in Burned Children.

BACKGROUND: Restoring normal mitochondrial function represents a new target for strategies aimed at mitigating the stress response to severe burn trauma and hastening recovery. Our objective was to investigate the determinants of skeletal muscle mitochondrial respiratory capacity and function and its association with glucose metabolism and functional capacity in burned children. METHODS: Data from burned children enrolled in the placebo arm of an ongoing prospective clinical trial were analyzed. Mitochondrial respiratory capacity was determined in permeabilized myofibers by high-resolution respirometry on at least one occasion per participant. In subsets of patients, glucose kinetics and cardiorespiratory fitness (VO2peak) were also determined. Mixed multiple regression models were used to identify the determinants of mitochondrial respiratory function and to assess the relationship between mitochondrial respiration and both glucose control and functional capacity (VO2peak). MAIN RESULTS: Increasing full-thickness burn size was associated with greater adjusted coupled (ATP-producing) respiration, adjusted for age, sex, sepsis, and time of testing (P < 0.01; n = 55, obs = 97). Girls had on average 23.3% lower coupled respiration (adjusted mean and 95% confidence of interval [CI], -7.1; -12.6 to -1.7 pmol/s/mg; P < 0.025) and 29.8% lower respiratory control than boys (adjusted mean and 95% CI, -0.66; -1.07 to -0.25; P < 0.01; n = 55, obs = 97). The presence of sepsis was associated with lower respiration coupled to ATP production by an average of 25.5% compared with nonsepsis (adjusted mean and 95% CI, -6.9; -13.0 to -0.7 pmol/s/mg; P < 0.05; n = 55, obs = 97), after adjustment for age, sex, full-thickness burn size, and time of testing. During a hyperinsulinemic euglycemic clamp, hepatic glucose release was associated with greater coupled respiration and respiratory control (P < 0.05; n = 42, obs = 73), independent of age, sepsis, full-thickness burn size, and time postinjury testing. Coupled respiration was positively associated with VO2peak after adjustment for age, full-thickness burn size, and time of exercise testing (P < 0.025; n = 18, obs = 25). CONCLUSIONS: Burn severity, sex, and sepsis influence skeletal muscle mitochondrial function in burned children. Glucose control and functional capacity are associated with altered mitochondrial respiratory function in muscle of burn survivors, highlighting the relationship of altered muscle bioenergetics with the clinical sequelae accompanying severe burn trauma.

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.

The P50 Research Center in Perioperative Sciences: How the investment by the National Institute of General Medical Sciences in team science has reduced postburn mortality.

Since the inception of the P50 Research Center in Injury and Peri-operative Sciences (RCIPS) funding mechanism, the National Institute of General Medical Sciences has supported a team approach to science. Many advances in critical care, particularly burns, have been driven by RCIPS teams. In fact, burns that were fatal in the early 1970s, prior to the inception of the P50 RCIPS program, are now routinely survived as a result of the P50-funded research. The advances in clinical care that led to the reduction in postburn death were made by optimizing resuscitation, incorporating early excision and grafting, bolstering acute care including support for inhalation injury, modulating the hypermetabolic response, augmenting the immune response, incorporating aerobic exercise, and developing antiscarring strategies. The work of the Burn RCIPS programs advanced our understanding of the pathophysiologic response to burn injury. As a result, the effects of a large burn on all organ systems have been studied, leading to the discovery of persistent dysfunction, elucidation of the underlying molecular mechanisms, and identification of potential therapeutic targets. Survival and subsequent patient satisfaction with quality of life have increased. In this review article, we describe the contributions of the Galveston P50 RCIPS that have changed postburn care and have considerably reduced postburn mortality.

The renaissance man of burn surgery: Basil A. Pruitt, Jr.

Dr. Basil A. Pruitt Jr., a consummate clinical and translational surgeon-scientist, has spent over half a century at the forefront of an advancing standard of burn care. Commanding the US Army Institute for Surgical Research in San Antonio, he trained generations of leading burn clinicians and allied scientists. At his direction, there were forged discoveries in resuscitation from shock, treatment of inhalation injury, control of burn-related infections, prevention of iatrogenic complications, and understanding the sympathetic, endocrine, and immune responses to burn injury. Most consequentially, this team was among the first to recognize and define alterations in the basal metabolic rate and thermoregulation consequent to burn injury. These investigations prompted groundbreaking insights into the coordinated nervous, autonomic, endocrine, immune, and metabolic outflows that a severely burned patient uses to remain alive and restore homeostasis. Marking his scientific consequence, many of his reports continue to bear fruit when viewed through a contemporary lens. This article summarizes some of the major findings of his career thus far and is intended to complement a Festschrift recently held in his honor.

Functional Exercise Capacity in Children With Electrical Burns.

Electrical burns are a severe form of thermal injury extending deep into tissue. Here, we investigated the effect of electrical burns on metabolic rate, body composition, and aerobic capacity. We prospectively studied a cohort of 24 severely burned children. Twelve patients had a combination of electrical and flame burns and 12 matched controls had only flame burns. Endpoints were cardiopulmonary fitness (maximal oxygen consumption [VO2]), muscle strength (peak torque per body weight), body mass index, lean body mass index, and days of myoglobinemia (≥500 mg/dl). Demographics of both the groups were comparable. The electrical burn group had more days of myoglobinemia during acute hospitalization than the flame burn group (3.6 ± 1.8 days vs 0.3 ± 0.5 days, P < .0001). Maximal VO2 was significantly lower in the electrical burn group than in the flame burn group at intensive care unit discharge (27 ± 6 ml/kg/min vs 34 ± 5 ml/kg/min, P < .0014). Electrical burns are associated with myoglobinemia and decreased cardiopulmonary fitness.

Human and Mouse Brown Adipose Tissue Mitochondria Have Comparable UCP1 Function.

Brown adipose tissue (BAT) plays an important role in mammalian thermoregulation. The component of BAT mitochondria that permits this function is the inner membrane carrier protein uncoupling protein 1 (UCP1). To the best of our knowledge, no studies have directly quantified UCP1 function in human BAT. Further, whether human and rodent BAT have comparable thermogenic function remains unknown. We employed high-resolution respirometry to determine the respiratory capacity, coupling control, and, most importantly, UCP1 function of human supraclavicular BAT and rodent interscapular BAT. Human BAT was sensitive to the purine nucleotide GDP, providing the first direct evidence that human BAT mitochondria have thermogenically functional UCP1. Further, our data demonstrate that human and rodent BAT have similar UCP1 function per mitochondrion. These data indicate that human and rodent BAT are qualitatively similar in terms of UCP1 function.

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.