Donor-specific tolerance permits burn allografting without increased sepsis

Early excision and allografting of massive burns is beneficial. However, chronic immunosuppression, utilized to prolong allograft survival, increases the potential risk of infection. We have previously shown long-term skin allograft survival in mice with a 30% total body surface area (TBSA) burn by inducing donor-specific tolerance (DST) using only perigrafting administration of antithymocyte globulin (ATG) and donor bone marrow (DBM). Chronic immunosuppression is avoided. This study tests whether induction of DST compromises host resistance to infection. Resistance to a septic challenge created by cecal ligation and puncture (CLP) 10 days after a 30% TBSA burn was investigated in the following groups of mice: [table: see text] Positive blood cultures were documented for 97% of mortalities. Burn excision and grafting significantly (P less than or equal to 0.05) decreased mortality. No increased mortality was seen in allografted mice receiving ATG or ATG and DBM compared to isografted mice receiving no immunosuppression. These studies suggest that skin allografting with DST may permit the benefits of burn excision without the risks of infection seen with chronic immunosuppression.     

Cultured composite autografts as coverage for an extensive body surface area burn: case report and review of the technology

Cultured epithelial autografts (CEA) have been used as an adjunct in the surgical management of extensive thermal burns. Unfortunately, the lack of a dermal matrix makes CEA susceptible to infection, shearing forces and limits their incorporation into the burn wound. A cultured composite autograft (CCA) has been developed in which autologous keratinocytes and fibroblasts are surgically harvested from the burn patient's normal skin. These components are proliferated and then combined to form an epidermal and dermal matrix, grown to confluence then applied.

Standard wound coverage techniques as well as CCA technology were utilized for successful wound closure in a 12 yr-old female with an 81% third degree burn. After fascial excision and allograft coverage, autografts were placed on her posterior burns and then 7500 cm² of CCA was placed onto her anterior thorax, abdomen and lower extremities. Sixty percent of the burn was covered with CCA resulting in a success rate of 40%. No evidence of infection was noted, even in areas where CCA failed, although in those areas random epithelialization appeared to occur which then seemed to facilitate autograft placement. Early debridement and allografting followed by conventional autografts and CCA placement may provide an effective skin coverage strategy in patients with extensive deep burns.     

Utility of acellular allograft dermis in the care of elderly burn patients

BACKGROUND: Because skin thins with advancing age, traditional thickness skin grafts cannot always be obtained in very elderly burn patients without creating a new full-thickness wound at the skin graft donor site. MATERIALS AND METHODS: In an attempt to circumvent this problem, acellular allograft dermis (Alloderm, Life Cell Corp., The Woodlands, TX) and thin autograft (depth 0.005 inches) was used in skin grafting 10 elderly burn patients (age 78 year +/- 2, TBSA burn 17% +/- 2; mean +/- SEM) over a 1-year period. The outcome of patients receiving Alloderm was compared retrospectively to a similar group of 18 elderly patients admitted over the prior year, eight of whom underwent operative wound excision and autografting (depth 0.014 inches) without Alloderm. RESULTS: Length of hospital stay was significantly reduced in patients treated with Alloderm compared to the total group of elderly in whom selective use of operative debridement and skin grafting was used. Functional outcome was improved in those patients who underwent skin grafting regardless of operative technique. Donor site healing time was significantly reduced with Alloderm (12 days +/- 1 versus 18 days +/- 2), while graft take was similar to conventional autografting. Unfortunately, 3-month mortality remained poor regardless of operative skin grafting or technique used. CONCLUSIONS: This initial experience suggests that use of Alloderm may allow more elderly burn patients to undergo operative wound closure, thus improving functional outcome and reducing hospitalization. Unfortunately, long-term survival for very elderly burn patients remains poor.     

The use of non-viable glycerol-preserved cadaver skin combined with widely expanded autografts in the treatment of extensive third-degree burns

Allograft skin lyophilised in 98% glycerol is an effective overlay for widely expanded autografts. The technique was evaluated clinically on a total of 58 sandwich grafting procedures in a group of 39 patients with extensive third-degree burns. Forty-five grafting operations performed within 10 days postburn all resulted in an epithelialisation rate of at least 75% within 5 weeks. Thirty-three of these procedures achieved complete (more than 95%) wound closure. Of 13 operations performed after the 14th postburn day, ten resulted in a wound epithelialisation of at least 75%. Epithelial quality and cosmetic results were good. The mean length of hospitalisation was 56 days. One patient died from unassociated respiratory failure. The absence of allograft viability did not impair its function as an autograft overlay. The apparent attenuation of allograft antigenicity conferred by the action of 98% glycerol may have contributed to the results achieved. The process of cadaver skin preservation in 98% glycerol is simple and inexpensive.     

Composite skin graft: frozen dermal allografts support the engraftment and expansion of autologous epidermis

Rapid closure of burn wounds significantly reduces the complications associated with thermal injury. Successful wound coverage, however, is often limited by the lack of suitable autografts. To circumvent this limitation a composite graft was developed which combines the utility and availability of allogeneic skin with the permanence of an autograft. Composite grafts were first employed in a rat wound model and subsequently to treat six patients with thermal injuries. In experiments with rats, full-thickness excised (1") wounds were prepared on thoracic walls, covered with previously frozen allograft skin, dressed, and secured. Five days later, the dead epidermis was removed and trypsin-disaggregated syngeneic epidermal cells applied to the exposed dermal surface. Successful engraftment with complete epidermal coverage could be observed within 7 to 10 days. In eight patients, split-thickness skin bank allografts were placed on full-thickness burn wounds. Four days later the dead epidermis was removed and vacuum blister-prepared sheets of autologous epidermis grafted to the exposed dermal surface. In all eight patients successful engraftment ensued. Increased pigmentation at the site of each original epidermal graft confirmed the stability of underlying allograft dermis. Epidermal expansion ranged from 1:20 to 1:100. All patients were followed from 10 to 12 months with no demonstrated graft loss or significant wound contracture. Composite skin grafts which combine allogeneic dermis and an expanded autologous epidermis can effect rapid wound closure and will remain stable without evidence of rejection or graft breakdown for at least 12 months.     

Management of full-thickness burns of the scalp and skull

Full-thickness burn injury of the scalp, with or without necrosis of underlying bone, is a complex therapeutic problem. Inability to diagnose depth of injury, controversy regarding wound closure, and a high incidence of acute morbidity are all associated with it. We reviewed the records of 17 patients who had suffered such injury. Wound closure was accomplished by split-thickness autograft alone in three patients, by bone dermabrasion and split-thickness autograft in six, by bone excision and split-thickness autograft in five, and by immediate local rotation flap in three. Systemic and/or local septic complications developed in 50% of all patients who underwent bony debridement. When feasible, early excision followed by immediate flap coverage is the procedure of choice. It avoids the multiple operative procedures required by the more conservative approach to wound closure, thereby shortening the period of primary hospitalization and virtually eliminating the risk of sepsis.     

The application of glycerol-preserved skin allograft in the treatment of burn injuries: An analysis based on indications

Introduction

Glycerol-preserved skin allograft (GPA) plays a crucial role in the management of burns. Its indications include wound-bed preparation, definitive dressing and sandwich grafting technique.

Objective

We analysed the experience of using GPA and its efficacy in burn treatment in our burn centre.

Methods

All burns managed with GPA in our burn centre from October 2001 to May 2008 were analysed.

Results

Mean total body surface area (TBSA) of 43 consecutive cases was 28.7%. GPA adhered to the wound for an average of 8.4 days before rejection. The length of hospital stay of the survivors was 42.5 days. The autograft take after wound-bed preparation with GPA was 88.4%. For sandwich grafting technique, the autograft take was 74.4%. When GPA was applied for partial-thickness burn as definitive dressing, all patients achieved complete healing within an average of 19 days without further surgical intervention. Despite colonisation of burn wounds after application of skin allograft, the outcomes of autograft take and wound healing were not significantly different.

Conclusion

The selective and strategic use of the GPA in major burn patients ensures optimal benefits in the management of burns. It is versatile in various categories of burn wounds with minimal morbidity.     

Major full thickness skin burn injuries in premature neonate twins

Burns in neonates have been reported following the use of pulse oximeters, various electrodes, chemical disinfecting agents and phototherapy blankets. Burn injuries in premature neonates are very rare and there have been no reports on major full skin thickness injuries. This case reports on preterm neonate male twins delivered at a Community Hospital. After the delivery they were placed on water warmers for 15-20 min and then transported into incubators. Burn injuries were noticed 1h after the delivery. Infant One, weight 1500 g, had an injury of 20% TBSA on his dorsum, waist and buttocks. The other infant, weight 1835 g, had an injury of 14% TBSA on the same areas. The infants were transported to the University Hospital. At the seventh day after the injury they recovered from respiratory distress and surgical procedures started. The eschar was excised deep to fascia and wounds were grafted with 0.1mm thickness skin grafts harvested from the thigh and cut into islets. Autografts were protected by overlay with fresh allograft harvested from the twins' father. Surgery procedures were performed in two steps, each second day, not exceeding 10% of total body area during excision. Donor sites healed at the eighth day after the surgery. Burn wounds healed gradually by way of spontaneous replacement of allograft and wound closure by spontaneous epithelization from the autograft islets. Eighteen days after the surgery all the grafted wounds were found epithelized. We conclude that in premature neonates relatively low temperatures may cause deep burn injuries. We recommend the delivery of preterm childbirths at well equipped facilities with staff qualified in nursing of premature neonates.     

Clinical practice of glycerol preserved allograft skin coverage

This retrospective study examines the use and advantages/disadvantages of glycerol preserved human allograft skin in our burn care facility between February 1997 and December 1999. Three hundred and twenty patients were included into the study, 85 of whom were treated with human cadaver skin. The usage of allograft slightly increased the number of operative procedures per percent of the total body surface area burn. There were no adverse effects noted from the use of allograft. The group of patients with allograft use had a significantly larger burn size, ABSI score and length of ICU stay. Demographically the groups were comparable. The considerably easier handling and storage of glycerol preserved allograft skin make it preferable to cryopreserved allograft skin in all indications where it is used as a temporary wound closure. We recommend the usage of cryopreserved skin in cases where the integration of a dermal component as a permanent part of wound closure is desired.     

Tangential excision of eschar for deep burns of the hand: analysis of 156 patients collected over 10 years

Deep burns affecting the dorsum of the hand have been treated by tangential excision of the eschar in 156 patients involving 208 hands. From our 10-year experience we have concluded that: If the patient's general condition permits it all hands with deep partial and full thickness skin loss burns are suitable for early tangential excision of the eschar. The best time for the operation is within the first week after injury. If the burn is of limited extent and the requirement for autograft skin is small the operation may be carried out under nerve block anaesthesia. When the burn is more extensive (i.e. involving both hands) intravenous ketamine anaesthesia is recommended. During tangential excision sequential layers of tissue must be removed until the base of the burn appears porcelain white in colour, has a lustrous appearance with many small bleeding points and is firm in consistency. If there are deep burns of the finger webs they are incised or excised and then grafted. Postoperatively an absence of fever, pain or exudation from the wound indicates that inspection of the wound can be delayed for about 2 weeks. By this time the wound is usually healed and functional rehabilitation and physiotherapy can commence.     

微粒皮移植治疗大面积深度烧伤后关节瘢痕挛缩的初步体会

目的 探讨大面积深度烧伤病人自体微粒皮与大张异体皮移植术治疗关节部位瘢痕挛缩的方法.方法 选择大面积深度烧伤后期瘢痕严重增生挛缩造成关节畸形而自体皮匮乏的病人11例,共31个关节,在全麻下切除部分瘢痕,彻底松解,矫正关节畸形,用微粒皮加异体皮覆盖创面,术后进行植皮区压迫和早期功能锻炼.随访12个月以上.通过术前、术后的皮肤外观、关节功能、组织学观察等进行效果评价.结果 微粒皮移植者皮肤外观及关节功能明显改善;组织学可见表皮较厚,部分可见表皮脚,真皮层较薄,胶原纤维排列较有规律.结论 微粒皮加大张异体皮移植术可用于治疗大面积深度烧伤病人关节部位瘢痕挛缩.     

Early Tangential Excision and Immediate Mesh Autografting of Deep Dermal Hand Burns

Thermal injuries to the hand constitute not only one of the most common burns, but one of the most difficult for the burn surgeon to treat. Early wound closure is mandatory if maximum functional return is to be attained and scarring minimized. Over the last three and one-half years, 60 patients with deep dermal dorsal hand and finger burns were treated by tangential excision and immediate mesh autografting. All patients were admitted to the hospital within 24 hours of injury and excision was performed between the third to the tenth post burn day. Operative technique consisted of sequential eschar excision using the Humby knife or Goulian-Weck dermatome until viable dermis was visible. Mesh autograft, ratio 1 to 1(1/2) without expansion, was applied. There was 100% graft take in all but four hands. Hand function with full range of motion returned by the tenth postoperative day. Complications were minor. Patient follow-up ranged from six months to three and one-half years. No patient has required subsequent surgery for scar revision or contracture release. Range of motion in all patients has been excellent and all patients have continued to maintain normal hand function. The cosmetic appearance has been good except for the early "mesh" appearance of the graft which has become less apparent with time. In summary, early tangential excision and immediate mesh autografting of deep dermal dorsal hand burns has fulfilled the following burn principles-preservation of tissue, prevention of wound infection, maintenance of function and early wound closure.     

Candida infection in massively burned patients

Immunosuppressed burned patients receiving antibiotics for suppression of bacterial infection are ideal hosts for opportunistic fungi. Massive excision of burns with autograft and homograft coverage has radically changed the course of disease. Three hundred ninety-three patients were admitted to the Shriners Burns Institute, of whom 125 patients had fungus cultured during their hospitalization and 42 patients subsequently developed involvement of three or more organs. Twenty-one of the 42 patients developed Candida septicemia requiring amphotericin B or flucytosine therapy. The mean third-degree burn in patients with Candida septicemia was 65% total body surface area compared to three-organ involvement/no clinical sepsis at 38% mean third-degree burn. Patients developing candidemia did so during the first week postburn and 7 days after excision therapy. It is hypothesized that massive burns with immunosuppression are further suppressed by repeated surgical intervention, anesthesia, and perioperative use of broad-spectrum antibiotics, further predisposing these patients to early development of Candida septicemia. With early recognition of burn wound invasion by routine biopsies, wound swabs, and early amphotericin therapy, the mortality has been reduced to 14% compared to 60-90% reported in other series.     

Burn wound coverage and burn wound closure

Early excision and grafting changed dramatically topical wound treatment, but are restricted by difficulty in diagnosing burn depth, by limited donor sites and by technical skills to excise special areas (perineum, face). In addition to the extent of burn and the age of the patient the depth is determinant of mortality, morbidity and of patient's quality of life. It results from the time-temperature relation and is further influenced by local and systemic causes of conversion: dehydration, edema, infection and shock hypoxia, metabolic derangements, peripheral vessels diseases may contribute do deepening of burn wound. Superficial burn on day one appears deep dermal by day three, where spontaneous epithelization lasts much longer than 21 days and results in hypertrophic scarring. To prevent this sequelae deep dermal burn may be treated like full-thickness injury with excision and autografting. Another way is removal of dead layers of corium and using biological or synthetic cover. We have found a more effective way to reach wound closure (not only cover) in the method of "upside-down" application of recombined human/pig skin (RHPS), composed of allogeneic human keratinocytes cultured on cell-free pig dermis. The allogeneic epidermal cells temporarily "take", "close" the excised wound and simultaneously encourage epithelization from adnexa remnants in the wound bed. Thus definitive closure is achieved.     

Specific unresponsiveness to skin allografts in burns

We have examined the potential to provide long-term or even permanent wound coverage in a mouse model of a 30% total body surface area burn using skin allografts. Treatment of the recipient mouse with rabbit anti-mouse thymocyte serum (ATS) followed by donor bone marrow infusion induces a state of specific unresponsiveness to the skin allograft without the need for chronic immunosuppression. Specifically, a B6AF1 mouse receives a burn on Day -2 relative to grafting, ATS on Day -1, and Day +2, a skin allograft from a C3H/He mouse on Day 0, and infusion of C3H/He donor bone marrow on Day +6. We studied three groups of burned mice: Group I, allograft control (n = 5); Group II, allograft plus ATS (n = 12); and Group III, allograft plus ATS and bone marrow infusion (n = 15). Mean graft survival was compared using a one-way analysis of variance and a Student-Newman-Keuls post hoc test. There was no statistical difference in animal mortality among any of the three groups, and there was no evidence of infectious morbidity. Mean skin allograft survival was as follows: Group I, 9 days; Group II, 29 days; and Group III, 66 days (P less than 0.05 vs Group I and II). Nine animals in Group III had intact hair bearing grafts at 90 days when the study was terminated. This study suggests the potential use of induced specific unresponsiveness to skin allografts for wound coverage in thermal injury without use of chronic immunosuppression. In our animal study this was accomplished without increased mortality or apparent infectious morbidity.     

Innovative Wundtherapie und Hautersatz bei Verbrennungen

The success of modern burn therapy is based mainly on special burn intensive care, topical treatment, early eschar excision, and wound closure by immediate skin grafting or skin substitutes. This paper describes the current state of wound care and skin substitutes in burn therapy.     

Artificial skin, split-thickness autograft and cultured autologous keratinocytes combined to treat a severe burn injury of 93% of TBSA

Despite refinements in burn shock resuscitation, improvements in surgical techniques, advances in intensive care medicine and the presence of very expert surgeons, the treatement of patients with severe burns exceeding 60% TBSA remains a big challenge. A major problem in the treatment of severe burn injuries is the lack of autologous skin. In selected cases cultured epidermal autograft (CEA) may be used. However, they are available only 2-3 weeks after biopsy, thus requiring a temporary wound closure after necrosectomy. A new option is Integra(TM), an artificial skin consisting of a bilayer membrane system. The three-dimensional porous matrix from bovine tendon collagen and a glycosaminoglycan layer is covered by a silicon sheet. The latter prevents fluid loss from the wounds and serves as a barrier against germ invasion. After adequate vascularisation of the dermal template, the silicon layer is removed and replaced by a thin autograft. We present a 26-year old male who sustained a 93% TBSA burn injury (60% full-thickness burn, 33% partial-thickness burn). He was treated with artificial skin, split-thickness autograft and CEA in combination. The clinical history and the follow-up of approx. 1 year are presented and the results discussed. We consider the survival of this patient being a result of the therapeutic progress of the recent decades.     

Therapeutic efficacy of Biobrane in partial- and full-thickness thermal injury

Cadaver allograft skin, porcine xenograft skin, and amniotic membranes have been proved to be adequate temporary thermal wound coverings in four clinical situations: coverage of shallow wounds while awaiting epithelialization (SW), coverage of deep wounds after eschar excision (DEW), coverage of widely meshed autograft while awaiting closure of interstices (AC), and coverage of massive donor sites (DS). This study was undertaken to evaluate the therapeutic efficacy of a new biosynthetic bilaminate dressing, Biobrane. Two hundred one applications of Biobrane were studied in 82 SW, 46 DEW, 19 AC, 54 DS. A total of 124 applications were left in place until healing occurred, with a mean healing time of 12.8 days. Sixty of SW, 10/46 DEW, 10/19 AC, and 44/54 DS remained intact until complete healing. Only four DEW, two SW, and 0 AC applications had to be removed because of suppuration. Twenty five of the applications (SW and DEW) with the Biobrane glove had rare complications.     

Microskin autografting in the treatment of burns over 70% of total body surface area: 14 years of clinical experience

Despite the fact that early excision and grafting have significantly improved burn outcomes, the management of severely burned patients whose burn size exceeds 70% total body surface area (TBSA) still represents a big challenge for burn surgeons all over the world. During the period of 1997-2010 at our centre, aggressive excision and microskin autografting were performed in 63 severely burned patients. Their burn sizes ranged from 70% to 98% TBSA with a mean of 84.9%. The average full-thickness burn was 66.3% (range, 29-94%). Thirty patients had concomitant inhalation injury. Two to 7 days after burn, these patients underwent aggressive excisions ranging from 25% to 60% TBSA and transplantation of microskin autograft overlaid with allograft. The ratios of donor-site to recipient-site surface area were between 1:6 and 1:18. Signs of epithelialization were shown within 35-55 days. The wound healing rate was 74.9% (176/235), with 51.1% of cases (120/235) healing completely and 23.8% (56/235) improving. Microskin autografting yielded an overall survival rate of 63.5%; only 23 patients died. Our clinical experience in using the microskin autografting for burn coverage suggests that the technique is very effective in covering extensive burns, and that it is particularly useful when graft donor sites are very limited due to its high utilization rate of donor site. The factors affecting the outcome of microskin autografting are discussed herein.     

Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions

This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries.