Shriners Hospitals for Children - Galveston

About: Shriners Hospitals for Children - Galveston is a healthcare organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Burn injury & Lean body mass. The organization has 249 authors who have published 420 publications receiving 15311 citations.

Five-year outcomes after oxandrolone administration in severely burned children: A randomized clinical trial of safety and efficacy

Abstract: Background Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy. Study Design Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored. Results Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration. Conclusions Administration of oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.

Insulin resistance postburn: underlying mechanisms and current therapeutic strategies.

Abstract: The profound hypermetabolic response to burn injury is associated with insulin resistance and hyperglycemia, significantly contributing to the incidence of morbidity and mortality in this patient population. These responses are present in all trauma, surgical, or critically ill patients, but the severity, length, and magnitude is unique for burn patients. Although advances in therapeutic strategies to attenuate the postburn hypermetabolic response have significantly improved the clinical outcome of these patients during the past years, therapeutic approaches to overcome stress-induced hyperglycemia have remained challenging. Intensive insulin therapy has been shown to significantly reduce morbidity and mortality in critically ill patients. High incidence of hypoglycemic events and difficult blood glucose titrations have led to investigation of alternative strategies, including the use of metformin, a biguanide, or fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist. Nevertheless, weaknesses and potential side affects of these drugs reinforces the need for better understanding of the molecular mechanisms underlying insulin resistance postburn that may lead to novel therapeutic strategies further improving the prognosis of these patients. This review aims to discuss the mechanisms underlying insulin resistance induced hyperglycemia postburn and outlines current therapeutic strategies that are being used to modulate hyperglycemia after thermal trauma.

Metabolic and Hormonal Changes of Severely Burned Children Receiving Long-Term Oxandrolone Treatment

Abstract: Severe burns represent a major physical and psychologic event in a child's life. Progress in the treatment of burns, such as fluid resuscitation, early burn wound excision, new antibiotics, and nutritional support has reduced burn mortality.1 A major determination of morbidity in burn patients is the extent and duration of the hypermetabolic and catabolic response to injury. These responses are characterized by tachycardia, increased resting energy expenditure, peripheral insulin resistance, fat and protein catabolism, and muscle and bone wasting, which last for 1 to 2 years after burn and lead to growth retardation.1,2 These posttraumatic responses delay recovery, rehabilitation, and social and psychologic integration back into society.3–6 Various therapeutic approaches have been introduced to ameliorate these adverse effects.7,8 We and others have hypothesized that the use of anabolic agents may attenuate the posttraumatic response and improve long-term outcomes.1,8 Oxandrolone, a synthetic analog of testosterone with minimal virilizing activity and liver toxicity, attenuates muscle wasting after severe trauma, malnutrition, or acquired immunodeficiency virus.9,10 In severely burned children treated during acute hospitalization, oxandrolone significantly improved net protein synthesis, lean body mass, bone mineral content, synthesis of the hepatic constitutive proteins such as albumin and prealbumin, and attenuated the acute phase reactive protein levels.11–13 The aim of this study was to determine whether oxandrolone, administered for 1 year after injury to severely burned children, would attenuate catabolism and growth arrest and whether these positive attributes would persist after the drug is discontinued.

Modulation of the Hypermetabolic Response to Trauma: Temperature, Nutrition, and Drugs

Abstract: Severe burn injury is associated with a profound hypermetabolic, hypercatabolic response proportional to the original size of the injury, which persists for 1 to 2 years postburn.1,2 The response is characterized by supraphysiologic metabolic rates, hyperdynamic circulation, constitutive protein fat and bone catabolism, blunted growth, insulin resistance, and increased risk for infection1–5 (Figs. 1 to ​to33). Figure 1 Physiologic and metabolic changes post severe burn injury. Demonstrates changes in resting energy expenditure, stress hormones (epinephrine), cardiac function (cardiac output), gender hormones (testosterone), cytokines (interleukin-6) and changes in body ... Figure 3 Effects of metabolic dysfunction postburn. Cuthbertson6 originally described a stress response to fractures characterized by an “ebb” phase, with a decrease in tissue perfusion and a decrease in metabolism. This is followed by a “flow” phase—starting 3 to 5 days postinjury—which is characterized by an increase in metabolic rate and hyperdynamic circulation. If left untreated, physiologic exhaustion and death can result.7–10 Severe burns exhibit the most dramatic hypermetabolic stress response of any injury. This article reports our single institution’s experience during the past decade, in >1,000 patients with burns of >40% of their total body surface area (TBSA), delineating the magnitude of the metabolic and catabolic responses to major burn injury. Serially performed randomized prospective clinical studies using common methods are described, demonstrating the efficacy of interventions to mitigate the hypermetabolic response: the effects of early excision and grafting, environmental thermoregulation, early continuous enteral feeding with a high-carbohydrate, high-protein diet, use of anabolic agents (growth hormone, insulin-like growth factor-1 [IGF-1], with insulin-like growth factor binding protein-3 [IGFBP-3], insulin, oxandrolone), the anticatabolic agent (propranolol), and use of therapeutic exercise are compared. This article describes the destructive aspects of the hypermetabolic response and strategies implemented during the last decade to modulate this response, which have improved burn care, survival, and quality of life in burn patients. It is hoped that these strategies might also be applicable to the larger populations of patients who have undergone other forms of injury, including large elective operations.