[The effect of growth hormone on wound healing rate in adult burns]. Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns. Effects of recombinant human growth hormone on donor-site healing in severely burned children. [Effectiveness of recombinant human growth hormone treatment for severe burn injury]. [Effect of recombinant growth hormone on wound healing in severely burned adults. A placebo controlled, randomized double-blind phase II study]. Recombinant human growth hormone treatment in pediatric burn patients and its role during the hepatic acute phase response. Effects of human recombinant growth hormone on donor-site healing in burned adults. Effects of recombinant human growth hormone on the development of burn scarring. Beneficial effects of extended growth hormone treatment after hospital discharge in pediatric burn patients.
To determine the wound healing effect of rHGH in adult burn patients.
                16 patients with burn wounds covering over 60% of total body surface (TBSA) were enrolled in this placebo controlled prospective study. They were comparable in nutrient intake, TBSA, and full thickness burn area. rHGH group patients were given rHGH subcutaneously in the dose of 0.3u.Kg-1 at 8 am each morning for 10 days beginning from POD 1. The control group patients were given normal saline as placebo. All the patients received scar excision within 4 days postburn, and the excision wounds were covered with autologous skin pulp grafting. Serum amino acid profile was analyzed at day 1 and day 20 post burn. Healing time of burn wound area and donor site was recorded. Wound healing rate was assessed at day 30 after day.
                1. The healing time of autologous skin pulp grafting and donor site, and the length of hospital stay were significantly shorter in GH group patients than control group. 2. The amino acid profile showed no difference between two groups at day 1 and was significantly better in GH group at day 20.
                rHGH could enhance the wound healing rate, improve amino acid profile, and reduce the length of hospital stay of severe burn patients. Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated.
                Growth hormone has been shown to reduce wound healing times in burned pediatric patients. Through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. Two forms of growth hormone were used in these studies, Protropin (Genentech, Inc., San Francisco, CA), a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin (Genentech, Inc., San Francisco, CA), which, as yet, is not commercially available. Through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children.
                Forty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhGH within 8 days of injury. Twenty received (0.2 mg/kg/day) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically (0.2 mg/kg/day). Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze (Sherwood Medical, St. Louis, MO). The initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site.
                Donor sites in patients receiving Nutropin (n = 20) or Protropin (n = 18) healed at 6.8 +/- 1.5 and 6.0 +/- 1.5 (mean +/- SD) days, respectively, whereas those receiving placebo (n = 26) had a first donor site healing time of 8.5 +/- 2.3 days. Both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo at p < 0.01. When subgroups were compared, no difference in healing times could be shown with regards to age or time of admission after injury.
                Our results indicate that both forms of rhGH are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. With this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25%. The beneficial effects of growth hormone on wound healing in severely burned children were studied. Forty patients who were 2 to 18 years old, with 40% or more total body surface area (TBSA) and 20% or more TBSA full-thickness flame or scald burns, were randomized in a double-blind study to receive placebo or 0.1 mg/kg/day recombinant human growth hormone (rHGH) until the first donor site healed or to receive 0.2 mg/kg/day rHGH or placebo from admission throughout hospitalization. Patients receiving 0.2 mg/kg/day rHGH demonstrated significantly higher serum IGF-1 levels at 4.8 +/- 1.7 U/mL compared to placebos at 1.6 +/- 0.4 U/mL (p less than 0.05) and a significant decrease in donor-site healing times compared to placebo (p less than 0.05). Length of hospital stay (LOS/%TBSA) was decreased from 0.80 +/- 0.10 days/%TBSA burned in the placebo group to 0.54 +/- 0.04 days/%TBSA burned in the 0.2 mg/kg/day treatment group (p less than 0.05). This translates, for the average 60% TBSA burned patient, to a decrease in LOS from 46 to 32 days. In order to investigate the effectiveness and safety of recombinant human growth hormone(rhGH) treatment for severe burn injury, we designed a randomized prospective study. The patients in rhGH group were given rhGH in a dose of 0.5 IU/(kg.d) subcutaneously between days 3-17 post-burn. Indices about protein metabolism, wound healing, hepatic and renal function and blood were measured regularly. Patients were monitored until their wound healed sufficiently so that they could be discharged for rehabilitation. The results showed: all patients survived; the rhGH group had less weight loss, increased level of serum albumin and shorter healing time of deep partial-thickness burn and donor site. The hospital stay time decreased from the control value of 45 +/- 17 days to 37 +/- 12 days for rhGH treated patients, i.e. a significant improvement. Resistant hyperglycemia was present in 2 patients in the rhGH group and disappeared after transient insulin administration. This study demonstrates that rhGH treatment for severe burn injury has obvious beneficial effects with slight side-effects. Recombinant growth hormone (rGH) has been used successfully in burned children with a shortened donor-site healing time and length of hospital stay as well as a protein-sparing effect. In adult burn patients, no comparable study exists to date.
                The study was performed on 49 adults, aged 18-60, with an Abbreviated Burn Severity Index (ABSI) score of 7-I1 as a randomized, placebo-controlled, double-blind study. The treatment period was 28 days and follow-up period 1 year. rGH was administered subcutaneously at a dose of 0.5 lU/kg per day in 26 patients, 23 patients were in the placebo group. Wound-closure assessment was performed on the day of admission and on each day of dressing change. A wound-closure index (WCI) was calculated.
                Thirty-seven patients, 19 in the rGH group and 18 in the placebo group, survived and were available for primary efficacy analysis. The mean total body surface area (TBSA) burned was 41.5% (rGH) versus 36.7% (placebo); the average ABSI score was 8.27 (rGH) versus 7.9 (placebo). The wound-closure index was not significantly different in patients treated with rGH (1.92) compared with patients treated with placebo (1.72). WCI for partial thickness-loss burn wounds did not significantly differ from rGH (0.9) to placebo (0.69). The donor site healing time in rGH-treated patients (12 days) was not significantly different compared to placebo patients (10.4 days).
                In severely burned adult patients rGH has no positive effect on burn wound or donor-site healing. Recombinant human growth hormone (rHGH) has been shown to increase mortality in adult trauma patients; however, little has been reported on its side effects in children. The acute phase response has been suggested to be a contributing factor to trauma mortality. Therefore, the purpose of this study was to examine the effects of exogenous rHGH on the acute phase response in pediatric bum patients.
                Prospective, randomized, double-blind study.
                Shriners Hospital for Children.
                Thermally injured pediatric patients, ranging in age from 0.1 to 16 yrs.
                Twenty-eight thermally injured children received either 0.2 mg/kg/day of rHGH or saline (placebo) within 3 days of admission and for at least 25 days.
                Measurements were patient demographics, incidence of sepsis, inhalation injury, mortality, serum constitutive proteins, acute phase proteins, proinflammatory cytokines and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3. No differences could be demonstrated in age, gender, burn size, incidence in sepsis (20% vs. 26%), inhalation injury (46% vs. 27%), or mortality (8% vs. 7%) between those receiving rHGH or placebo. Serum IGF-I and IGFBP-3 increased with rHGH treatment, whereas serum IGFBP-1 decreased compared with placebo (p < .05). Burned children treated with rHGH required significantly less albumin substitution to maintain normal levels compared with placebo (p < .05). Those receiving rHGH demonstrated a decrease in serum C-reactive protein and serum amyloid-A and an increase in serum retinol-binding protein compared with placebo (p < .05). rHGH decreased serum tumor necrosis factor-alpha and interleukin (IL)-1beta, whereas no changes were found for serum IL-1alpha, IL-6, and IL-10 compared with placebo (p < .05). Free fatty acids were elevated in burned children who received rHGH (p < .05).
                Data indicate that rHGH does not increase mortality. rHGH decreased acute phase proteins, tumor necrosis factor-alpha, and IL-1beta, which is associated with increases in constitutive hepatic proteins and IGF-I. Patients suffering severe burns have an accelerated catabolism with a highly negative nitrogen balance that may worsen their prognosis. Somatropin treatment has been shown to improve this balance in different hypercatabolic situations. Moreover, in children with extensive burns it also reduces the healing time of the skin graft donor site and shortens the hospital stay. In the existing literature there are no controlled prospective clinical trials in adult patients that confirm these data. Our aim was to demonstrate the efficacy of recombinant growth hormone (somatropin) in reducing the healing time of the skin graft donor sites and the length of stay in the burn unit in adult patients with severe burns. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 adult patients with severe burns (more than 40% of the total body surface burned or more than 15% full-thickness burns). Patients received placebo (n = 11) or somatropin (n = 13) at a dosage of 0.15 mg/kg/day divided into two equal doses (every 12 hours) via intramuscular injection. Treatment was initiated the day the first autograft was performed and terminated the day the patient was discharged from the burn unit. The mean number (+/- SD) of skin grafts per patient was similar between the two groups (4.2 +/- 1.8 vs 3.4 +/- 1.8 in the placebo and somatropin groups, respectively). No reduction in the healing time of the skin graft donor site was observed in the somatropin group compared to the placebo group. Likewise, the time admitted to the burn unit was not significantly different, either in the absolute number of days (36.2 +/- 19.7 vs 30.1 +/- 16.8 days in the placebo and somatropin groups, respectively) or in relation to the percentage of the total body surface burned or the body surface with full-thickness burns. Growth hormone and insulin-like growth factor I (IGF-I) levels were three and five times higher, respectively, in the somatropin group than in the placebo group. Ten of the patients treated with somatropin experienced hyperglycemia, and seven of them required insulin treatment. No other adverse side effect was observed. One patient in the placebo group died as a result of sepsis and multiple organ failure. Somatropin, with the treatment regimen and dosage used in these studies, did not reduce the healing time of the skin graft donor sites or the length of hospitalization in the burn unit in adult patients with severe burns. Anabolic agents, such as recombinant human growth hormone (rhGH), have been used effectively to ameliorate the catabolic response to burn injury and to improve wound-healing. However, in experimental animal models, growth hormone has also been associated with increased renal scarring. The effect of rhGH on the development of human scarring is unknown. Therefore, the purpose of this study was to assess the effect of rhGH on the scarring of human skin after burn injury. A series of 94 patients was studied in a prospective randomized double-blind clinical trial. Patients receiving 0.2 mg/kg/day subcutaneous rhGH during their acute hospital stays presented with the same quality and intensity of scarring as patients receiving a placebo. Similar reconstructive needs also resulted. The treatment of severely burned children with recombinant human growth hormone during the acute-phase hospital course did not increase scarring of the burn wound. To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued.
                We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment.
                Forty-four pediatric patients with over 40% total body surface area burns were studied for 24 months after burn. Patients were randomized to receive either rhGH (0.05 mg/kg body weight) or placebo. Height, weight, body composition, serum hormones, resting energy expenditure, cardiac function, muscle strength, and number of reconstructive procedures performed were measured during rhGH treatment and for 12 months after treatment was discontinued. Statistical analysis used Tukey's multiple comparison test. Significance was accepted at P < 0.05.
                Height, weight, lean body mass, bone mineral content, cardiac function, and muscle strength significantly improved during rhGH treatment compared with placebo (P < 0.05). This treatment significantly increased GH, IGF-I, and IGFBP-3, whereas serum cortisol decreased (P < 0.05). The number of operative reconstructive procedures was significantly lower with rhGH (P < 0.05). Improvements in height, bone mineral content, and IGF-1 concentrations persisted after rhGH treatment (P < 0.05). No side effects with rhGH were observed.
                Administration of rhGH for 1 year after burn was safe and improved recovery. These salutary effects continued after rhGH treatment was discontinued.
There is some evidence that using rhGH in people with large burns (more than 40% of the total body surface area) could result in more rapid healing of the burn wound and donor sites in adults and children, and in reduced length of hospital stay, without increased mortality or scarring, but with an increased risk of hyperglycaemia. This evidence is based on studies with small sample sizes and risk of bias and requires confirmation in higher quality, adequately powered trials.