Recombinant Human Growth Hormone Accelerates Wound Healing in Children with Large Cutaneous Burns

113

ObjectiveTo determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn. Summary Background DataThe hypermetabolic response to severe burn is associated with increased energy expenditure, insulin resistance, immunodeficiency, and whole body catabolism that persists for months after injury. Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses. MethodsSeventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone (0.05 mg/kg per day) on muscle accretion and bone growth. Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn. Total body weight, height, dual-energy x-ray absorptiometry, indirect calorimetry, and hormone values were measured at discharge, then at 6 months, 9 months, and 12 months after burn. Results were compared between groups.

Section: Discussionmentioning

confidence: 99%

“…Larger dosages (up to 0.2 mg/kg per day) have shown proportionally greater gains in growth and wound healing, but they have also shown an increased frequency of hyperglycemia. 8,9 Further study is necessary to determine the optimal balance of safety and efficacy.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Posttraumatic Muscle Catabolism and Osteopenia by Long-Term Growth Hormone Therapy

Hart¹,

Herndon²,

Klein³

et al. 2001

113

“…13 With the advent of a recombinant human growth hormone, the study of this anabolic agent has increased in an effort to modulate the postburn hypermetabolic response. Growth hormone treatment has been shown to improve leg protein metabolism, 3 accelerate donor site healing, 14 increase expression of dermal proteins in healing wounds, 15 and decrease hospital stays 16 in severely burned children. Unfortunately, treatment with growth hormone was shown to increase the mortality rate in critically ill nonburned adults.…”

Section: Discussionmentioning

confidence: 99%

Muscle Protein Catabolism After Severe Burn: Effects of IGF-1/IGFBP-3 Treatment

Herndon¹,

Ramzy²,

DebRoy³

et al. 1999

179

ObjectiveTo determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children. Summary Background DataSevere burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study. MethodsTwenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/ day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls. ResultsSeventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization. ConclusionsIGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and increased circulating levels of catabolic hormones such as catecholamines, glucagon, and cortisol.

“…Donor site healing was assessed by the number of days required for removal of a standard donor-site dressing. 7,8 Hospital costs were estimated for individual patients by multiplying hospital days by $2,000 7 and adding the costs of CEA. Sepsis was defined as pathologic bacteremia on blood culture, and pneumonia was defined as lung infiltrate on chest x-ray combined with fever and a pathologic organism isolated on a class III sputum.…”

Section: Methodsmentioning

confidence: 99%

Cost-Efficacy of Cultured Epidermal Autografts in Massive Pediatric Burns

Barret¹,

Wolf²,

Desai³

et al. 2000

ObjectiveTo assess the efficacy of cultured epidermal autografts (CEA) for closure of burn wounds in pediatric burn patients with fullthickness burns of more than 90% total body surface area. Summary Background DataPaucity of donor sites in massive burns makes the use of expanded skin of paramount importance. CEA techniques have been used in burned patients with differing and controversial results. The true impact and the efficacy of such techniques in massive burns remain uncertain. MethodsPatients with full-thickness burns of more than 90% body surface area treated between May 1988 and May 1998 were studied. Patients grafted with CEA were compared with patients grafted with conventional meshed autografts. Rates of death and complications, length of hospital stay (LOS), hospital cost, acute readmissions for reconstruction, and quality of scars were studied as outcome measures. ResultsPatients treated with CEA had a better quality of burn scars but incurred a longer LOS and higher hospital costs. Both groups had comparable readmissions for open wounds, but patients treated with CEA required more reconstructive procedures during the first 2 years after the injury. The incidence of sepsis and pneumonia in both groups was comparable. ConclusionsConventional meshed autografts are superior to CEA for containing hospital cost, diminishing LOS, and decreasing the number of readmissions for reconstruction of contractures. However, the use of CEA provides better scar quality such that perhaps future research should focus on bioengineered dermal templates to promote take and diminish long-term fragility.Severe full-thickness burns covering more than 90% of the total body surface area (TBSA) continue to pose an immense challenge to even the most experienced burn teams. In the past few decades, the burn-related death rate has declined dramatically, and this can be attributed in part to early excision and closure of the burn wound. Currently, even children sustaining full-thickness burns of more than 90% TBSA have a better than 50% rate of survival. 1The approach to skin coverage in the massively burned patient depends on the type and extent of injury. Burns of less than 30% TBSA can be covered with autograft skin at one operation. In full-thickness burns of more than 30% TBSA, however, the autograft donor site is quickly exhausted, so that alternative skin coverage is necessary. This is particularly true in patients with massive burns, in whom a paucity of donor sites makes skin substitutes and the use of expanded skin of paramount importance. For years, these patients have been treated with traditional methods of widely expanded meshed autografts with an overlay of cadaveric allograft. 2,3 More recently, the use of cultured epidermal autografts (CEA) has been advocated for wound closure in massive burn injury. 4 Nevertheless, cost, longterm fragility, and the lack of an optimal dermal equivalent for CEA have restricted its routine use. 5,6 Recurrent open wounds, increased rates of burn scar contractures, and troublesome re...