Robert E. Barrow

Effects of Recombinant Human Growth Hormone on Donor-site Healing in Severely Burned Children

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.

A comparison of conservative versus early excision. Therapies in severely burned patients.

Early excision and grafting of small burn wounds is a generally accepted treatment. Early excision of burn injuries greater than 30% total body surface area (TBSA) in adults, however, has not been universally accepted. In this study, 85 patients whose ages ranged from 17 to 55 years with greater than 30% total body surface area (TBSA) burns were randomly assigned to either early excision or topical antimicrobial therapy and skin grafting after spontaneous eschar separation. Mortality from burns without inhalation injury was significantly decreased by early excision from 45% to 9% in patients who were 17 to 30 years of age (p less than 0.025). No differences in mortality could be demonstrated between therapies in adult patients older than 30 years of age or with a concomitant inhalation injury. Children (n = 259) with similar large burns treated by early excision showed a significant increase in mortality with increasing burn size and with concomitant inhalation injury (p less than 0.05). The mean length of hospital stay of survivors was less than one day per per cent of TBSA burn in both children and adults.

Increased mortality with intravenous supplemental feeding in severely burned patients

Patients with large cutaneous burns are characterized by an elevated metabolic rate and lose up to 25% of their body weight within 3 weeks. A previous study suggested that intravenous supplementation to attain nutritional requirements was of no benefit in patients with cutaneous burns covering greater than 50% of their total body surface area. In this study 39 patients with burns greater than 50% of their total body surface area were randomly assigned to receive intravenous supplementation of enteral calories (n = 16) or enteral calories alone (n = 23). Intravenous supplementation decreased the amount of enteral calories that patients with burns could tolerate. The mortality rate was significantly higher (p less than 0.05) in the intravenously supplemented group at 63% as compared with 26% in the group receiving enteral calories alone. Both groups showed significant decrease in natural killer cell activity when compared with controls at both 0 to 7 and 7 to 14 days after injury. T cell helper/suppressor ratios were depressed in both groups when compared with controls; however, the intravenously supplemented group was significantly depressed at 7 to 14 days after burn. Both groups demonstrated hepatomegaly, moderate fatty infiltration, and cholestasis. It is suggested that intravenous supplementation should be carefully evaluated and used only in patients with total enteral failure.

Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns.

ObjectiveTwo forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated. Summary Background DataGrowth 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, GA), 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. MethodsForty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-bind, 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. ResultsDonor 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.

Effects of insulin on wound healing.

BACKGROUND Insulin plus glucose, given for 7 days to hypermetabolic burn patients, has been shown to stimulate limb protein anabolism. We hypothesized that insulin plus glucose given to burn patients would also stimulate wound healing. METHODS Six patients with burns >40% total body surface area were randomized to receive insulin or placebo in a crossover study during the healing of their first and second donor sites. Insulin treatment was titrated at 25 to 49 U/h to achieve a plasma insulin level of 400 to 900 microU/mL for 7 days. Patients receiving insulin received dextrose 50 at 20 to 50 mL/h, titrated to maintain euglycemia. Donor-site biopsies were taken at 7 days and evaluated by three observers blinded to the treatment. RESULTS The mean (+/-SD) donor-site healing time was reduced from 6.5 +/- 1.0 days with placebo to 4.7 +/- 1.2 days during insulin infusion (p < 0.05). Laminin showed intense staining along the basal lamina and blood vessels. Collagen type IV staining also increased after insulin therapy compared with placebo. CONCLUSION Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation.

Early burn wound excision significantly reduces blood loss.

The hypothesis that near-total early excision of large burns in children can be performed safely with a reduction in blood loss was tested. Of 1662 acutely burned patients admitted to this institution between 1982 and 1989, 594 underwent near-total excision of cutaneous flame or scald burn injuries in a single procedure. Operations took less than 3 hours and there were no operative deaths. Blood losses in burns of more than 30% total body surface area (TBSA) were significantly less at 0.40 +/- 0.06 mL/cm2 and 0.49 +/- 0.49 mL/cm2 excised when surgery was performed within the first 24 hours or after the 16th day after burn, respectively, when compared to 0.75 +/- 0.02 mL/cm2 for those excised between 2 and 16 days after burn (p less than 0.05). Blood loss for burns of less than 30% TBSA was of 1.19 +/- 0.13 mL/cm2. Early excision did not increase mortality rate when compared to later excision times. We suggest that near-total excision of large burns within the first 24 hours reduces blood requirements and morbidity without adversely altering hemodynamic stability or increasing mortality risks.

Effect of propranolol administration on hemodynamic and metabolic responses of burned pediatric patients.

Hypermetabolism, increased heart rate, and lipolysis are responses to high catecholamine levels associated with burn injury. This study tests the hypothesis that adrcncrgic beta blockade in burns could reduce myocardial work, lipolysis, and negative nitrogen balance without adversely affecting cardiac or metabolic function. Eighteen patients with burns of 70 ± 3% total burn surface area (TBSA) (Mean ± SEM), were studied after a 5-day infusion of 2 nig/Kg of intravenous (I.V.) propranolol infusion every 24 hours without their cardiac output or resting energy expenditure being adversely reduced. Heart rate, left ventricular work, and rate pressure product were significantly reduced by 20, 22, and 36%, respectively (P < 0.05). Plasma glucose, free fatty acids, triglycerides, and insulin levels remained unchanged. The rate of urea production, however, was significantly increased by 54 ± 12% in fasted patients, and to a much lesser 12 ± 2% in fed patients. The marked decrease in myocardial work afforded by propranolol administration may be of clinical benefit in the treatment of large burns. Variations in drug dosage and feeding regimens will, however, need to be perfected to limit catabolic effects.

Characterization of growth hormone enhanced donor site healing in patients with large cutaneous burns

BackgroundHuman growth hormone is an anabolic agent that attenuates injury-induced catabolism and stimulates protein synthesis. Recombinant human growth hormone (rhGH) administered therapeutically to patients with massive burns has been shown to increase the rate of skin graft donor site healing. It has been postulated that growth hormone affects wound healing and tissue repair by stimulating the production of insulin-like growth factor-1 (IGF-1) by the liver to increase circulating IGF-1 concentrations. The mechanism by which it improves wound healing, however, remains in question. The authors hypothesize that rhGH up-regulates IGF-1 receptors and IGF-1 levels both systemically and locally in the wound site to stimulate cell mitosis and increase synthesis of laminin, collagen types IV and VII, and cytokeratin. This hypothesis was tested in nine patients with burns covering >40% of total body surface area. ObjectiveThe authors assessed the efficacy of rhGH in promoting several major building materials in the donor site of patients with massive burns. MethodsTen massively burned patients with full-thickness burns covering more than 40% of total body surface area were participants in a placebo-controlled prospective study to determine the efficacy of 0.2 mg/kg/day rhGH on donor site wound healing and to identify some of the major components involved in wound healing and its integrity. ResultsDonor sites in burn patients receiving rhGH showed an increased coverage by the basal lamina of 26% for placebo to 68% coverage of the dermal-epidermal junction. Insulin-like growth factor-1 receptors and laminin, types IV and VII collagen, and cytokeratin-14 all increased significantly. Healing times of the donor sites were significantly decreased compared with patients receiving placebo. ConclusionResults indicate that growth hormone or its secondary mediators may directly stimulate the cells of the epidermis and dermis during wound healing to produce the structural proteins and other components needed to rebuild the junctional structures.

Electrical injuries: A 30-year review

INTRODUCTION Electrical injuries currently remain a world-wide problem. This study determines whether electrical injuries at our institution have changed in the past 30 years, and identifies electrical burn complications and any high-risk groups. METHODS From 1967 to 1997, 185 children admitted to our institute were identified with electrical burns. Fifty-five percent of these electrical burns occurred from 1987 to 1997. RESULTS During the last 10 years of this study, 43% of the electrical injuries (n = 44) were from low voltage (120-240 V) and 57% (n = 58) from high voltage (>1,000 V). In 17 children, serious low-voltage burns were identified as oral commissure burns. These were treated conservatively with one to two reconstructive procedures within 2 years. High-voltage injuries were mainly identified in male children (age 11 to 18 years). Thirty-three percent of high-voltage burns required amputation, 29% had deep muscle involvement, and 24% required either escharotomy or fasciotomy. No mortalities were reported. CONCLUSION Although the incidence of low-voltage burns is currently on a steady decline, high-voltage injuries remain a problem, particularly in adolescent males.

Growth hormone treatment in pediatric burns: a safe therapeutic approach.

OBJECTIVE To determine the safety and efficacy of recombinant human growth hormone (rhGH) in the treatment of children who are severely burned. SUMMARY BACKGROUND DATA During the last decade, we have used recombinant human growth hormone (rhGH; 0.2 mg/kg/day s.q.) to successfully treat 130 children with more than 40% total body surface area (TBSA) burns to enhance wound healing and decrease protein loss. A significant increase in the mortality of adult patients in the intensive care unit who were given rhGH has recently been reported in two large European trials which questions the therapeutic safety of rhGH. METHODS The records of 263 children who were burned were reviewed. Patients receiving either rhGH at 0.2 mg/kg/day subcutaneously as part of a randomized clinical trial (n = 48) or therapeutically (n = 82) were compared with randomized placebo-administered controls (n = 54), contiguous matched controls (n = 48), and matched patients admitted after August 1997, after which no patients were treated with rhGH (n = 31). Morbidity and mortality, which might be altered by rhGH therapy, were considered with specific attention to organ function or failure, infection, hemodynamics, and calcium, phosphorous, and albumin balance. RESULTS A 2% mortality was observed in both rhGH and saline placebo groups in the controlled studies, with no differences in septic complications, organ dysfunction, or heart rate pressure product identified. In addition, no difference in mortality could be shown for those given rhGH therapeutically versus their controls. No patient deaths were attributed to rhGH in autopsies reviewed by observers blinded to treatment. Hyperglycemic episodes and exogenous insulin requirements were higher among rhGH recipients, whereas exogenous albumin requirements and the development of hypocalcemia was reduced. CONCLUSIONS Data indicate that rhGH used in the treatment of children who were severely burned is safe and efficacious.