Richard J. Kagan

Clinical Evaluation of an Acellular Allograft Dermal Matrix in Full-Thickness Burns

A multicenter clinical study assessed the ability of an acellular allograft dermal matrix to function as a permanent dermal transplant in full-thickness and deep partial-thickness burns. The study consisted of a pilot phase (24 patients) to identify the optimum protocol and a study phase (43 patients) to evaluate graft performance. Each patient had both a test and a mirror-image or contiguous control site. At the test site, the dermal matrix was grafted to the excised wound base and a split-thickness autograft was simultaneously applied over it. The control site was grafted with a split-thickness autograft alone. Fourteen-day take rates of the dermal matrix were statistically equivalent to the control autografts. Histology of the dermal matrix showed fibroblast infiltration, neovascularization, and neoepithelialization without evidence of rejection. Wound assessment over time showed that thin split-thickness autografts plus allograft dermal matrix were equivalent to thicker split-thickness autografts.

Comparative assessment of cultured skin substitutes and native skin autograft for treatment of full-thickness burns.

ObjectiveComparison of cultured skin substitutes (CSSs) and split-thickness autograft (STAG) was performed to assess whether the requirement for autologous skin grafts may be reduced in the treatment of massive bums. Summary Background DataCultured skiasubstitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been demonstrated to close full-thickness skin wounds in athymic mice and to express normal skin antigens after closure of excised wounds in burn patients. MethodsData were collected from 17 patients between days 2 and 14 to determine incidence of exudate, incidence of regrafting, coloration, keratinization, and percentage of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 = worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10) and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface roughness, skin suppleness, and raised scar. ResultsSites treated with CSSs had increased incidence of exudate (p = 0.06) and decreased percentage of engraftment (p < 0.05) compared with STAG. Outcome parameters during the first year showed no differences in erythema, blistering, or suppleness. Pigmentation was greater, scar was less raised, but regrafting was more frequent in CSS sites than STAG. No differences in qualtative outcomes were found after 1 year, and antibodes to bovine collagen were not detected in patientsera. ConclusionsThese results suggest that outcome of engrafted CSSs is not different from STAG and that increased incidence is related to decreased percentage of initial engraftment. Increased rates of CSSs may lead to improved outcome for closure of burn wounds, allow greater availability of materials for grafting, and reduce requirements for donor skin autogratt.

A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century.

Toxic epidermal necrolysis (TEN) is a potentially fatal disorder that involves large areas of skin desquamation. Patients with TEN are often referred to burn centers for expert wound management and comprehensive care. The purpose of this study was to define the presenting characteristics and treatment of TEN before and after admission to regional burn centers and to evaluate the efficacy of burn center treatment for this disorder. A retrospective multicenter chart review was completed for patients admitted with TEN to 15 burn centers from 1995 to 2000. Charts were reviewed for patient characteristics, non-burn hospital and burn center treatment, and outcome. A total of 199 patients were admitted. Patients had a mean age of 47 years, mean 67.7% total body surface area skin slough, and mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 10. Sixty-four patients died, for a mortality rate of 32%. Mortality increased to 51% for patients transferred to a burn center more than one week after onset of disease. Burn centers and non-burn hospitals differed in their use of enteral nutrition (70 vs 12%, respectively, P < 0.05), prophylactic antibiotics (22 vs 37.9%, P < 0.05), corticosteroid use (22 vs 51%, P < 0.05), and wound management. Age, body surface area involvement, APACHE II score, complications, and parenteral nutrition before transfer correlated with increased mortality. The treatment of TEN differs markedly between burn centers and non-burn centers. Early transport to a burn unit is warranted to improve patient outcome.

The 1999 clinical research award. Cultured skin substitutes combined with Integra Artificial Skin to replace native skin autograft and allograft for the closure of excised full-thickness burns.

Prompt and permanent closure of excised full-thickness burns remains a critical factor in a patients recovery from massive burn injuries. Hypothetically, Integra Artificial Skin (Integra) may replace the need for allografts for immediate wound coverage, and cultured skin substitutes (CSS) that contain stratified epithelium may replace the need for autografts for definitive wound closure. To test this hypothesis, 3 patients with full-thickness burns of greater than 60% of their total body surface areas had their eschar excised within 14 days of admission. Integra was applied, and a skin biopsy was collected from each patient for the preparation of CSS. At 3 weeks or more after the application of the Integra and the collection of skin biopsies, the outer silastic cover of the Integra was removed and CSS were grafted. The CSS were irrigated with nutrients and antimicrobials for 6 days and then dressed with antimicrobial ointment and cotton gauze. Treated wounds were traced on days 14 and 28 after the grafting of CSS for determination of engraftment and wound closure, respectively. Cost analysis was not performed. Engraftment on postoperative day (POD) 14 was 98%+/-1% (mean +/- standard error of the mean), the ratio of closed:donor areas on POD 28 was 52.3+/-5.2, and no treated sites required regrafting. The histology of the closed wounds showed stable epithelium that covered a layer of newly formed fibrovascular tissue above the reticulated structure of the degrading Integra. The clinical outcomes of the closed wounds after POD 28 demonstrated smooth, pliable, and hypopigmented skin. Two patients who had received CSS grafts over Integra on their backs were positioned supine on air beds from POD 8 or POD 9 with minimal graft loss because of mechanical loading. One patient with a full-thickness burn of 88% of the total body surface area was covered definitively at 55 days postburn. These results demonstrate that the combination of CSS and Integra can accomplish functionally stable and cosmetically acceptable wound closure in patients with extensive full-thickness burns. This combination of alternatives to the conventional grafting of split-thickness skin permits the substitution of cadaveric allograft with Integra and the substitution of donor autograft with CSS. This approach to the closure of excised full-thickness burns is expected to reduce greatly the time to definitive closure of burn wounds and to reduce the morbidity associated with the harvesting of donor sites for split-thickness skin autografts.

Cultured Skin Substitutes Reduce Donor Skin Harvesting for Closure of Excised, Full-Thickness Burns

ObjectiveComparison of cultured skin substitutes (CSS) and split-thickness skin autograft (AG) was performed to assess whether donor-site harvesting can be reduced quantitatively and whether functional and cosmetic outcome is similar qualitatively in the treatment of patients with massive cutaneous burns. Summary Background DataCultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been shown to close full-thickness skin wounds in preclinical and clinical studies with acceptable functional and cosmetic results. MethodsQualitative outcome was compared between CSS and AG in 45 patients on an ordinal scale (0, worst; 10, best) with primary analyses at postoperative day 28 and after about 1 year for erythema, pigmentation, pliability, raised scar, epithelial blistering, and surface texture. In the latest 12 of the 45 patients, tracings were performed of donor skin biopsies and wounds treated with CSS at postoperative days 14 and 28 to calculate percentage engraftment, the ratio of closed wound:donor skin areas, and the percentage of total body surface area closed with CSS. ResultsMeasures of qualitative outcome of CSS or AG were not different statistically at 1 year after grafting. Engraftment at postoperative day 14 exceeded 75% in the 12 patients evaluated. The ratio of closed wound:donor skin areas for CSS at postoperative day 28 was significantly greater than for conventional 4:1 meshed autografts. The percentage of total body surface area closed with CSS at postoperative day 28 was significantly less than with AG. ConclusionsThe requirement for harvesting of donor skin for CSS was less than for conventional skin autografts. These results suggest that acute-phase recovery of patients with extensive burns is facilitated and that complications are reduced by the use of CSS together with conventional skin grafting.

Skin anatomy and antigen expression after burn wound closure with composite grafts of cultured skin cells and biopolymers.

Closure of large skin wounds (i.e., burns, congenital giant nevus, reconstruction of traumatic injury) with split-thickness skin grafts requires extensive harvesting of autologous skin. Composite grafts consisting of collagen-glycosaminoglycan (GAG) substrates populated with cultured dermal fibroblasts and epidermal keratinocytes were tested in a pilot study on full-thickness burn wounds of three patients as an alternative to split-thickness skin. Light microscopy and transmission electron microscopy showed regeneration of epidermal and dermal tissue by 2 weeks, with degradation of the collagen-GAG implant associated with low numbers of leukocytes, and deposition of new collagen by fibroblasts. Complete basement membrane, including anchoring fibrils and anchoring plaques, is formed by 2 weeks, is mature by 3 months, and accounts for the absence of blistering of healed epidermis. All skin antigens tested (involucrin, filaggrin, laminin, collagens IV and VII, fibronectin, and chondroitin-sulfate) were expressed by 16 days after grafting. This cultured skin analogue provides an experimental alternative to split-thickness skin graft that develops histiotypic markers of skin anatomy and antigen expression after wound closure.

Effects of oxandrolone on outcome measures in the severely burned: a multicenter prospective randomized double-blind trial.

Severe burns induce pathophysiologic problems, among them catabolism of lean mass, leading to protracted hospitalization and prolonged recovery. Oxandrolone is an anabolic agent shown to decrease lean mass catabolism and improve wound healing in the severely burned patients. We enrolled 81 adult subjects with burns 20% to 60% TBSA in a multicenter trial testing the effects of oxandrolone on length of hospital stay. Subjects were randomized between oxandrolone 10 mg every 12 hours or placebo. The study was stopped halfway through projected enrollment because of a significant difference between groups found on planned interim analysis. We found that length of stay was shorter in the oxandrolone group (31.6 ± 3.1 days) than placebo (43.3 ± 5.3 days; P < .05). This difference strengthened when deaths were excluded and hospital stay was indexed to burn size (1.24 ± 0.15 days/% TBSA burned vs 0.87 ± 0.05 days/% TBSA burned, P < .05). We conclude that treatment using oxandrolone should be considered for use in the severely burned while hepatic transaminases are monitored.

National Burn Repository 2005: a ten-year review.

In the early 1990s, the American Burn Association (ABA) started its first burn registry development initiatives. The impetus for the registry development software originated from several directions, including the following: (1) the recognition that national registries were widespread and of proven benefit; (2) growing demands from accrediting institutions, payers, and patient advocacy groups for objective and verifiable data regarding patient costs, treatments, and outcomes; and (3) the shift toward “evidence-based” medicine and the ongoing analysis of treatment effectiveness. The ABA has issued three calls for burn registry data for its National Burn Repository (NBR): 1994, 2002, and 2005. In 1994, 28 burn centers contributed data for more than 6,400 patients treated from 1991 to 1993. The ABA announced its second call for data in 2001 and distributed the published results of more than 54,000 acute burn admissions treated from 1974 to 2002 at the Association’s 2002 Annual Meeting. The third ABA call for data was issued in the Fall of 2005. The results are detailed in this report, which provides a summary of more than a quarter million acute burn admissions from 1995 to 2005, representing 70 hospitals from 30 states plus the District of Columbia. Statistics are presented in chart and table format to illustrate such key factors as patient age, burn size group, types of injuries, mortality rates, and average hospital charges by etiology and length of hospital stay. The data presented herein should help stimulate quality improvement programs in burn care, as burn centers compare their performance with the national data and as research is expanded using the NBR. The NBR will be published annually and, with continued refinements to the registry software, should become of increasing importance to clinicians, payers, researchers, and the public.

The 2002 Clinical Research Award. An evaluation of the safety of early vs delayed enteral support and effects on clinical, nutritional, and endocrine outcomes after severe burns.

Early enteral support is believed to improve gastrointestinal, immunological, nutritional, and metabolic responses to critical injury; however, this premise is in need of further substantiation by definitive data. The purpose of this prospective study was to examine the effectiveness and safety of early enteral feeding in pediatric patients who had burns in excess of 25% total body surface area. Seventy-seven patients with a mean percent total body surface area burn of 52.5 +/- 2.3 (range 26-91), percent full thickness injury of 44.7 +/- 2.8 (range 0-90), and age ranging from 3.1 to 18.4 (mean 9.3 +/- 0.5) were randomized to two groups: early (feeding within 24 hours of injury) vs control (feeding delayed at least 48 hours postburn). Nutrient intake was measured daily, indirect calorimetry was performed biweekly, and blood and urine samples were obtained for the assay of cortisol, glucagon, insulin, gastrin, epinephrine, norepinephrine, dopamine, triiodothyronine, tetraiodothyronine, albumin, transferrin, prealbumin, retinol-binding protein, glucose, nitrogen balance, and 3-methylhistidine throughout the study period. Three protocol violations occurred, and two patients were transferred to another hospital; these patients were excluded from the study. No patient in either group experienced tube feeding aspiration. No differences were evident in infection, diarrhea, hospital length of stay, or mortality outcomes. A higher incidence of reportable adverse events coincided with early feeding (22 vs 8%), but this was not statistically significant. The delayed feeding group demonstrated a significant caloric deficit during postburn week (PBW) 1 (P <.0001) and PBW2 (P =.0022). Serum insulin (P =.0004) and triiodothyronine (P =.0162) were higher in the early fed group during PBW1. A decrease in 3-methylhistidine output (suggesting a decrease in protein breakdown) was also evident during PBW1 (P =.0138). No other significant trends in study outcome variables were noted. In conclusion, provision of enteral nutrients shortly after burn injury reduces caloric deficits and may stimulate insulin secretion and protein retention during the early phase postburn. These data, however, do not necessarily reaffirm the safety of early enteral feeding, nor do they associate earlier feeding with a direct improvement in endocrine status or a reduction in morbidity, mortality, hypermetabolism, or hospital stay. Future studies are needed to establish precise feeding implementation times that maximize clinical benefit while minimizing morbidity in the critically injured burn patient.

National burn repository 2006: A ten-year review

This article presents findings from the National Burn Repository (NBR) 2006 Annual Report. Data reported herein cover a 10-year period from January 1, 1996, through June 30, 2006. This year’s report includes the first comparative presentations of data over time to show what appear to be trends in the dataset. The purpose of this report is to share information about the current state of care for burned patients in the United States. Some of the implications include epidemiology, burn-prevention efforts, research, education, acute care and quality improvement in burn programs, resource allocation, and reimbursement issues.