ANTICATABOLIC AND ANABOLIC STRATEGIES AFTER BURNS & TRAUMA

James Knox, MD, Robert Demling, MD, Douglas Wilmore, MD, Pasha Sarraf, BSA, and Alfred Santos, MD

Background: Advances in the management of patients with major thermal injury have resulted in a progressive increase in survival rates. We report preliminary data evaluating the safety and potential efficacy of human growth hormone (HGH) administration in a high-risk population of burned patients.

Methods: From 1989 to 1993, 69 patients sustaining major burns (defined as patient age plus percentage of body surface area with deep second- and third-degree burns > 90) were evaluated. Patients routinely received anti-inflammatory pharmacotherapy including antioxidants, an endotoxin binder, and cyclooxygenase blockade. Half of the 54 patients who survived more than 7 days received HGH to enhance wound healing. Injury severity, morbidity, and mortality for patients receiving HGH was compared to the 27 patients not receiving HGH.

Results: For the entire population (n=69), average age was 56± 23 years, body surface area burned was 58%± 24%, and 30% sustained smoke inhalation. Actual mortality was 41%, significantly less than the more than 70% mortality rate predicted from reported outcome data. Patients receiving HGH were well matched with the group not receiving HGH with respect to extent of injury, burn management, pharmacotherapy, and in-hospital morbidity. Mortality of the patients receiving HGH was 11%, significantly less than the 37% mortality rate of the patients without HGH (r =0.027).

Conclusion: Compared to standard predictors of burn mortality our small patient group appears to have an improved survival rate, suggesting that the use of anti-inflammatory agents appears safe and potentially beneficial. Patients receiving HGH exhibited minimal drug-related complications and mortality rates were improved when this population was compared with both predicted mortality rates and a well-matched control population of concurrently treated patients. Prospective blinded trials are now necessary to confirm these findings in a larger patient group.

Christopher Gatzen, FRCS(E), Marc R. Scheltings, MD, Thomas D. Kimbrough, MD, Danny O. Jacobs, MD, MPH, and Douglas W. Wilmore, MD, FACS

From the Laboratory for Surgical Metabolism and Nutrition, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Background: Catabolic illness is associated with fluid retention and extracellular space expansion. To determine the effect of human growth hormone (GH) on body water compartments, critically ill surgical patients were studied for a 2-week period during which they either continued to receive standard intensive care unit support, or in addition, received GH, 10mg/day.

Methods: Body water compartments were measured at the beginning and end of the period by the indicator dilution technique with sodium bromide and heavy water used as the indicators of extracellular (ECW) and total body water (TBW), respectively; intracellular water (ICW) was calculated by subtraction.

Results: Neither group lost significant amounts of weight or TBW. A marked ECW expansion and disturbance of the ECW/TBW ratio occurred in the patients receiving standard care, which was associated with a dramatic reduction in ICW, a critical component of the body cell mass (BCM). In contrast, GH-treated patients maintained ECW and ICW, indicating a preservation of BCM, and their ECW/TBW ratio normalized.

Conclusion: GH administration prevents ECW retention and stabilizes or normalizes fluid distribution during critical illness. Taken together with its known anabolic effects under these conditions, the maintenance of ICW demonstrates that GH can be used to preserve BCM in complex surgical patients.

From the Shriners Burns Institute and the Departments of Surgery and Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas

OBJECTIVE: Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated.

Summary Background Data: 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 tehse 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.

Methods: 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.

Results: Donor sites in patients receiving Nutropin (n=20) or Protropin (n=18) healed at 6.8± 1.5 and 8.0± 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.

Conclusion: 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%.