Improved large burn therapy with reduced mortality following an associated septic challenge by early excision and skin allografting using donor-specific tolerance.

These studies demonstrate clearly that the creation of donor-specific tolerance in animals permits the long-term survival of incompatible skin grafts placed following a burn with early eschar excision. Furthermore, the studies demonstrate graphically that such replacement can be done without any increase in the septic mortality in these animals and strongly suggest that such a treatment would be potentially efficacious as a therapy for large body burns that could not be successfully covered with autografts. When animals were observed either in the potentially septic milieu of a large 30% body burn or in a situation of a deliberate attempt to create a septic state using the septic challenge of CLP, the placement of a full-thickness skin graft that survived was clearly beneficial to the animal in reducing mortality. In addition, the donor-specific tolerance technique described permits long-term survival of these skin grafts, which in some of the earlier laboratory studies were able to survive permanently and might well achieve permanent survival in a clinical situation. However, a prolonged graft survival of 90 to 100 days, considering the ability to develop new split thickness skin grafts providing dermal cover at 20- to 25-day intervals, would provide opportunity for a least four "croppings" of the skins. Thus, for example, a small area of remaining autograft skin of 20% in an 80% burn patient could potentially be cropped four times to achieve close to 80% coverage. Coverage would be easier and more successful in the more common burns of less than 70% of TBSA. It is of interest to us that there is virtually no well-developed literature on the use of donor-specific tolerance to aid skin graft survival. There would seem to be a reasonable rationale for considering such therapy since septic problems should not be significantly increased during induction of skin graft tolerance. Once the skin grafting has produced a significant increase in functionally covered skin, the risk of sepsis should decrease markedly. Because sepsis is currently the major factor in 75% of burn deaths, donor-specific tolerance for skins grafts appears to be eminently reasonable for future consideration. Expanded animal studies are probably necessary before clinical trials are undertaken, although skin grafting with immunosuppression has already been tried in patients.