SKIN RESURFACING FOR THE BURNED PATIENT

Transcription

1 NEW DIRECTIONS IN PLASTIC SURGERY, PART II /02 $ SKIN RESURFACING FOR THE BURNED PATIENT Ryan A. Stanton, MD, and David A. Billmire, MD The ultimate goal and eventual reward in treating severely burned patients is the establishment of a protective barrier from the outside world. Skin resurfacing for the burned patient has made large strides since the midtwentieth century. Improvements in resuscitation, management of inhalation injuries, and other advances in critical care are responsible for survival rates in burned patients nearly doubling since the 1950s, increasing by almost 1% each year. Several factors have 49, 57 contributed extensively to the evolution of clinical burn care, including a better understanding of the critical need for adequate fluid resuscitation immediately postburn, prophylaxis against wound sepsis and its complications, the importance of adequate nutritional support, burn pathophysiology and its inflammatory mediators, management of airway and pulmonary complications, and early surgical intervention. As a result, burned patients commonly are surviving with greater than 90% total body surface area (TBSA) burns. As of the year 2000, with the advances in tissue engineering, it was technically feasible to resurface a nearly 100% total body surface burn. Despite the long-term sequelae of burn injuries, many burned patients achieve a satis- factory quality of life and adapt a functional postburn lifestyle. A rough indicator of individual psychologic rehabilitation is reflected by employment status. Patients who return to work after burn injury have less behavioral avoidance, higher self esteem, and greater attention to goals. It has been shown that the most significant predictors of return to work are involvement of the hand, grafting, size of burn, and age. Patients younger than 45 have a higher return to work rate. 74 The care of a severely burned patient requires the infrastructure of a dedicated burn center with interdisciplinary involvement of nursing, counseling, group therapy, and occupational and physical therapy. Interventions designed to aid adjustment, work hardening, and other rehabilitative services and marital and family therapy are also important. All these services are crucial in maximizing a patient s psychologic and functional outcome. MANAGEMENT OF THE ACUTE BURN WOUND The goal for managing an acute burn is coverage. The initial wound should be kept moist and surrounding tissues protected from From the Division of Plastic, Reconstructive, and Hand Surgery, University of Cincinnati College of Medicine (RAS); and Department of Plastic Surgery, The Children s Hospital Medical Center and The Shriners Hospital for Children Cincinnati Burn Unit (DAB), Cincinnati, Ohio CLINICS IN PLASTIC SURGERY VOLUME 29 NUMBER 1 JANUARY

2 30 STANTON & BILLMIRE trauma. From the time the burn wound presents until the time it is resurfaced completely, it is subjected to a variety of modalities, from the initial cleansing techniques to application of topical agents and dressings, escharectomy, and grafting with temporary or permanent coverage by allograft, autograft, or various skin substitutes. A review of the steps from start to finish provides the clinician with an up-to-date, logical management protocol for the burned patient. Cleansing Techniques Most patients with a burn injury undergo some form of hydrotherapy. 60 For obvious full-thickness injury with frank eschar, patients simply are cleansed with a soapy solution upon arrival to the burn unit. The preferred antimicrobial soap at the authors institution is 4% chlorhexidine. The wounds then are cleansed daily and dressed with a topical antimicrobial and gauze. Those patients whose burns have not yet declared themselves as deep-partial thickness or fullthickness injury are treated to some form of nonsubmersion or immersion hydrotherapy. In the nonsubmersion group, they usually are treated daily with a shower or bed bath, depending on their mobility. Showers must be combined with wiping or scrubbing to decrease the bacterial load on the surface of the wound effectively. Immersion with or without agitation is used additionally in some facilities. This immersion is usually in the form of a whirlpool and should be limited to less than 30 minutes with water temperatures of 90 to 100 Fahrenheit (32.3 to 37.8 Celsius). Slightly cooler temperatures are needed for the elderly and the young whose thinner dermis is less tolerant to the warmer temperatures. Although blisters may be thought of as biologic dressings, there is controversy whether blisters should be left intact or debrided. Research has shown that the fluid in blisters can inhibit white cell function and increase the inflammatory response. 55 For that reason, removal of blisters is common in burn wound management, particularly if they are large, thin walled, or across a joint. Another reason to remove blisters is that they can obscure the view of tissue beneath and its ongoing evaluation for healing or infection. Topical Agents Topical agents were developed in the 1960s to help prevent burn wound infection or sepsis. 47 When the eschar is still present, the clinician needs to use topical agents that have penetrating properties. All topical agents should have the quality of being nontoxic locally and systemically. Location, depth of the burn wound, and the type of micro-organisms present will dictate the choice of topical agent. Topical agents currently available include silver sulfadiazine, most commonly used as a topical preparation in the form of a 1% soluble cream. It is effective against grampositive and gram-negative bacteria, including some Pseudomonas. There is some eschar penetration, so it will kill some organisms below the surface. Unfortunately, it has been shown to inhibit fibroblast growth and slow epithelial migration and hence may thwart these processes in superficial partial-thickness burns. Mafenide acetate is available in a cream or 5% solution. The cream is an extremely useful topical agent because of its ability to penetrate eschar with relative ease. The solution is used for wet dressings. Both formulations are effective against essentially all bacteria. It is not effective against yeast, however, and therefore not recommended as prophylaxis or therapy for yeast infections. Because of its ability to inhibit carbonic anhydrase, it can lead to metabolic acidosis, especially in large-percentage TBSA burns in the pediatric population. Silver nitrate is available as a 0.5% solution or a 95% stick. It can be used to treat yeast colonization but does not penetrate eschar. If needed to target yeast infection in the subeschar region, it is recommended to cross-hatch the eschar to allow its penetration into the subeschar plane. Although the ability to penetrate the eschar is a factor, it is of less concern in current therapy, which is based on rapid excision and coverage. Silver nitrate also is harmful to fibro-

3 SKIN RESURFACING FOR THE BURNED PATIENT 31 blasts and should not be used on a clean, healing partial-thickness wound. Topical antibiotic ointments include bacitracin (Polysporin and Neosporin) and are used primarily for the antimicrobial activity against grampositive organisms. They have not yet been shown to slow re-epithelialization, and they can be used on clean, healing partial-thickness wounds if a topical agent is desired. It is important that they be used sparingly to avoid maceration of the surrounding tissue. As the wound begins to heal, antibiotic ointments are no longer necessary and should be halted to avoid a yeast infection. Other topical agents available include enzymatic debriding agents, arginine-glycineaspartic acid-peptide matrix, and pheny- 39, 44 toin. All have been shown in one study or another to enhance the healing of partialthickness burns and donor sites. The overall use of these agents is probably rather modest. Finally, the evolving understanding of basic wound healing and its growth factor milieu is being manipulated in the burn wound to accelerate healing of the skin graft donor site 27, 61, 62 and interstices of meshed skin grafts. BURN WOUND CLASSIFICATION Superficial Burns (First Degree) 1. Epidermis only 2. Red or pink coloration 3. Dry and peels 4. Occasional tiny blisters 5. Delayed pain 6. Modest edema, most pronounced in eyelids 7. Spontaneously heals in 3 5 days 8. No scar Superficial Partial-Thickness Burns (Second Degree, Superficial) 9. Epidermis and papillary dermis involved 10. Large, intact blisters 11. Weeps exudate 12. Exquisite pain 13. Blanches with brisk capillary refill 14. Variable, moderate edema 15. Spontaneously heals within days (re-epithelializes) 16. Minimal scar (some dyschromia possible) Deep Partial-Thickness Burns (Second Degree, Deep) 17. Epidermis, papillary dermis, and partial reticular dermis 18. Mix of red and waxy white coloration 19. Large amounts of exudate 20. Sluggish capillary refill 21. Dull pain 22. Massive edema, causing problems with range of motion over joints 23. Spontaneously heals within 21 days (reepithelializes) 24. Hypertrophic scarring and scar contractures evolve Full-Thickness Burns (Third Degree) 25. Epidermis and entire dermis involved 26. Mosaic of colors possible including black, tan, red, and white 27. No blanching; reddened areas stay red when pressure is applied because of hemoglobin from trapped ruptured red blood cells 28. Superficial veins may be thrombosed 29. Dry, rigid, leathery tissue consistency 30. Eschar appears depressed with significant edema distally 31. Escharotomy or fasciotomy may be required 32. Not painful or tender 33. Hair is avulsed easily from burned hair follicles 34. No spontaneous healing Subdermal Burns 35. Involve subcutaneous tissue (fat, bone, muscle, tendon), commonly from electrical burns 36. Slow demarcation (up to 5 7 days) with electrical burns 37. Mummified appearance 38. Thrombosed blood vessels possible, superficial and deep 39. Neuromuscular involvement/paralysis possible 40. Insensate 41. No spontaneous healing BURNS REQUIRING RESURFACING Burns traditionally have been classified according to depth of injury and hence, require-

4 32 STANTON & BILLMIRE ment for skin resurfacing. Generally speaking, epidermal and superficial partialthickness burns are those that will re-epithelialize in 10 to 14 days and do not need resurfacing. Deep partial-thickness wounds usually heal with significant scarring and wound contraction. These wounds should be resurfaced for better results. Full-thickness wounds obviously require resurfacing. For most recorded history, burn wounds were attended to in a conservative medical fashion. They were essentially washed gently and then left open or lightly wrapped in dressings. The eschar was left intact and allowed to separate naturally during the next 2 to 3 weeks. This process allowed for the inevitable bacterial colonization of the intact eschar. Partial-thickness burns would heal during this process of natural separation, but full-thickness burns would granulate, providing a substrate for autografting. The advantage that this process had in delaying surgical treatment until natural separation of the eschar was the ability to delineate clearly the areas that would heal spontaneously from those that would require grafting. In severe burn injury, however, this advantage is outweighed by the protracted time of healing and the enormous likelihood that the bacterial colonization of the burn wound will lead to wound infection, sepsis, and death. Further understanding of burn wound pathology was advanced greatly by the work of Jackson, 35 who first described the three concentric zones of thermal injury, that is, zone of coagulation, zone of stasis, and zone of hyperemia. Others extended this work and showed that progressive microvascular compromise occurs in the zone of stasis in unexcised burn wounds for up to 48 hours postburn. Progressive compromise of tissue perfusion, because of edema, release of vasoconstrictive inflammatory mediators, and arteriolar thrombosis, leads to further tissue death in the zone of stasis and effectively widens and deepens the nonviable portion of the burn wound. 8 Once these mechanisms were understood sufficiently, the importance of removal of the burn eschar in a timely fashion was appreciated. Removal of eschar not only eliminates a substrate for bacterial growth but also limits conversion of damaged tissue into devitalized tissue by reducing the production of inflammatory mediators that drive this process. Escharectomy: Standard of Care Concern about removal of unnecessary tissue during primary excision was addressed by Janzekovic, who developed the technique of tangential excision. 36 In this technique, serial layers of deep partial-thickness burns were shaved until pinpoint arteriolar bleeding was seen, indicating the level of viable tissue had been reached. This approach proved to have clear advantages compared with aggressive excisions down to fascia, including more rapid healing, less surgical blood loss, shorter hospital stays, reduced medical costs, less disfigurement, and decreased hypertrophic scarring. By the 1990s staged primary excision of major burn wounds was instituted commonly during the acute phase of resuscitation, coinciding with approximately the third day postburn. Most burn surgeons today would advocate undertaking early escharectomy from 1 to 3 days postburn. 31, 32, 45, 46, 64 It should be noted that the process of incising the burn eschar or escharotomy must be performed emergently in cases of circumferential burn wounds with compartment pressures greater than 30 mm Hg to avoid compartment syndrome. Research (in lab animals) regarding early escharectomy has shown that immediate removal of dead and severely damaged tissue interrupts and attenuates systemic inflammatory response syndrome and normalizes immune function 11, 15, 17, 18, 19, 34 after burn injury. The potential for significant blood loss should always be a serious concern of the burn surgeon. Recommendations to minimize blood loss include doing staged excisions, especially for large-percentage TBSA. 16 A conservative recommendation is to perform less than 25% TBSA escharectomy per session. It is possible to do up to 60% TBSA escharectomies using the following recommendations, however. The subeschar tissue plain should be infiltrated with a 1:1,000,000 epinephrine solution (1 ml of 1:100,000 epinephrine per 1 L of lactated Ringers solution) and 10 minutes,

5 SKIN RESURFACING FOR THE BURNED PATIENT 33 preferably 15 to 20 minutes are allowed for the epinephrine to take effect before the escharectomy. When performing excisions on extremities, a pneumatic tourniquet can and should be used. Dilute epinephrine soaked laparotomy pads should be applied to the excised areas immediately after excision. Electrocautery is used to obtain hemostasis of the larger bleeding points as necessary. An efficient team of doctors and nurses helps this process move along smoothly. Contraindications to early escharectomy are few and rare. Congenital or iatrogenic coagulopathies must be addressed before surgery. In multitrauma cases, the patient sometimes requires diagnostic evaluation, stabilization, and treatment of other injuries that are more immediately life threatening than the burn before primary burn excision is considered. Finally, any patient who is in shock on admission is not a candidate for early escharectomy until obviously stabilized. In summary, escharectomy is an early treatment modality of the burned patient that has evolved beyond the initial primary medical management of the burned patient and now can be recognized as one of the most important factors contributing to improved survival after major burn injury. COVERAGE OF THE BURN WOUND After the debridement or tangential excision of the burn wound, the decision needs to be made on how the wound will be covered. For those wounds not requiring grafting, that is, superficial and superficial partialthickness burns, the usual and necessary wound cleansing and debridement of blisters as needed are performed followed by a dressing of the physician s choice. For relatively small burns, a topical antimicrobial impregnated into a nonadherent gauze dressing followed by coarse cotton gauze may be employed. For larger-percentage TBSA, the clinician may elect to do the same or place one of the various biosynthetic dressings, allograft, tissue-engineered skin substitutes, or dermal grafts. Deep partial-thickness and full-thickness burns require a different approach. Blood loss can be rather extensive when excising large burns and harvesting skin graft for their coverage; therefore, staging these two procedures fractionates the blood loss making blood/volume replacement safer. The extent, indeterminate depth, and bleeding from the excision often preclude acute definitive coverage. In these cases, the wound should be dressed in antibiotic gauze type dressing and reinspected in 24 to 48 hours. At this time, the wound will be dry, and the physician can better assess whether the excision was adequate. The coverage can be temporary or permanent, depending on the availability of donor sites. Factors involved in determining coverage go beyond the percent TBSA involved and the availability of donor sites. Burn wounds involving the face and hands take priority. Although autogenous skin grafts are the coverage of choice, large burns require some type of temporary coverage or dressing. Ideally the materials used for temporary coverage have the following qualities and characteristics: they should adhere rapidly to the wound bed; once adherent, limit bacterial colonization and proliferation; control the permeability of water and oxygen; limit fluid/electrolyte/heat loss; and alleviate wound pain. They also should be elastic and durable, sterile, nonantigenic, and readily available for use. Ultimately they should promote re-epithelialization of the wound. Finally, some of the coverage materials have the ability to provide wound healing growth factors to the burned wound bed. Temporary Coverage Materials Temporary coverage materials generally fall into one of two categories: biologic or bioengineered skin substitutes. Of the biologic materials, fresh, irradiated or frozen cadavaric skin (i.e., allograft), amniotic membrane, or porcine xenografts may be used. 41, 67, 70 These biologic dressings generally maintain a clean wound environment until skin grafting can be achieved, or they may be the only dressing placed on a partial-thickness wound until completely re-epithelialized, at which time they slough off. Biologic dressings provide a safe physiologic environment for healing. They reduce heat and fluid

6 34 STANTON & BILLMIRE loss from the wound and markedly reduce pain by protecting dermal nerve endings, thus allowing early mobilization of the patient. The body eventually rejects them as a foreign object, however. Enzymatic degradation and digestion of the biologic dressings ensue relatively soon after their application. Additionally, biologic dressings are susceptible to infection and must be monitored closely for bacterial overgrowth. Fresh allograft is better than frozen. 72 Furthermore, irradiation of allografts serves as a preservative and sterilizing agent, allowing storage at room temperature for up to a year and a significant reduced risk for viral transmission. The graft will take but then is rejected by cell-mediated immunity 10 to 14 days later. Patients with massive burns are essentially immunosuppressed, and the allograft may remain intact for weeks (Fig. 1). 41, 42, 43 In extensive full-thickness burns, the allograft will maintain the wound bed integrity until donor sites have healed and are ready for reharvesting. In partial-thickness burns, the remaining dermal layers of the skin that are protected by this temporary biologic dressing produce permanent epidermal wound coverage in an average of 8 days. At 12 to 14 days postoperatively, the nonadherent portions of the biologic dressings slough off spontaneously or occasionally require serial whirlpool debridements. If significant nonhealing areas are seen after this treatment, elective autografting or other means of permanent coverage can be scheduled. Small open areas that are likely to progress to healing without grafting can continue to be managed usually on an outpatient basis by daily cleansing and application of an antibacterial topical agent. Figure 1. Patient with massive burn (80% total body surface area) status postescharectomy and temporary coverage of lower two thirds of back with fresh allograft. A, Two weeks postoperative showing 90% take and survival of allograft. B, Three weeks postoperative manifesting signs of rejection including cyanosis, loosening, and frank slough. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plate 3, Fig. 5.)

7 SKIN RESURFACING FOR THE BURNED PATIENT 35 Biobrane (Woodruff Labs, Santa Ana, CA) is a biosynthetic wound dressing constructed of a silicone film with a nylon fabric partially embedded in the film. The fabric presents to the wound bed a complex, three-dimensional structure of trifilamentous threads to which collagen has been bound chemically. Within 24 hours, blood and sera clot in the nylon matrix, thereby firmly adhering the dressing to the wound until epithelialization occurs. While this is going on, the material is adherent enough such that the patient can move freely. Because it is a semipermeable membrane, it establishes a homeostatic environment, decreasing fluid loss and pain, and does not have to be changed because it falls off the wound bed as epithelialization occurs and is trimmed as needed. 21 When it is placed on a full-thickness burn, it should be changed at any sign of bacterial colonization and infection or separation. Table 1 gives a fairly thorough explanation of the composition and use of many various biologic tissue engineered materials available. Basically, these are made up of cellular or acellular materials and their combinations. In essence, they provide an epidermal substitute or a dermal substitute. The agents that are dermal substitutes also provide a substrate for eventual overgrafting with thin autogenous split thickness skin grafts (i.e., permanent coverage). This approach allows earlier reharvest of donor sites. Of course, depending on these components, most, if not all, can be used as temporary coverage, and about half of them can be used for permanent closure of deep partial- and full-thickness burns. Epidermal Substitutes Epicel (Genzyme, Cambridge, MA) is produced from culturing autologous human epidermal keratinocytes from a patient biopsy and during a 3- or more week period can be grown up to 100-fold. The advantage of this product is that it is entirely autogenous and therefore nonimmunogenic. It tends to be a rather fragile permanent resurfacing material, however. Dermal Substitutes TransCyte (Smith and Nephew, Largo, FL) is produced by culturing neonatal human dermal fibroblasts on to a biosynthetic material consisting of an ultrathin, semipermeable membrane of silicone bonded to a scaffold of nylon mesh and bovine collagen. The nylon mesh forms a three-dimensional scaffold for growth of dermal tissue and the membrane forms synthetic (nonimmunogenic) epidermis. As the fibroblasts proliferate in the nylon mesh, they secrete structural proteins and growth factors, thereby generating a three- Table 1. TISSUE-ENGINEERED MATERIALS Material Structure Coverage Oasis (Cook, Spencer, IN) Lyophilized, acellular porcine small Temporary for partial-thickness intestinal submucosa burns and skin donor sites TransCyte (Smith and Nephew, Silicone and bovine collagen polymer Temporary for partial-thickness and Largo, FL) membrane containing cultured full-thickness burns neonatal human fibroblasts Alloderm (LifeCell, Woodland, TX) Freeze-dried (lyophilized) acellular Permanent for partial-/fullcadaveric dermis, which is thickness burns (when combined nonantigenic with epidermal graft) Integra Artificial Skin (Integra Life Acellular three-dimensional porous Permanent for deep partial- Sciences, Plainsboro, NJ) matrix of cross-linked bovine thickness and full-thickness burns collagen and chondroitin-6-sulfate (when combined with cultured with Silastic outer covering autologous keratinocytes or autologous thin epidermal grafts) Epicel (Genzyme, Cambridge, MA) Cultured human epidermal Permanent for full-thickness burns keratinocytes from patient biopsy Apligraf (Organogenesis, Canton, Bovine collagen matrix containing Temporary or permanent for small MA) neonatal human epidermal full-thickness burns keratinocytes and dermal fibroblasts

8 36 STANTON & BILLMIRE dimensional human dermal matrix. This product is strictly for temporary coverage. Integra Artificial Skin (Integra Life Sciences, Plainsboro, NJ) is a bioengineered dermal substitute (Fig. 2). It consists of a bilayer membrane system for skin replacement. The dermal replacement layer is made up of a porous matrix of fibers of cross-linked bovine tendon collagen in a glycosaminoglycan (chondroitin-6-sulfate) and is manufactured with a controlled porosity and defined degradation rate. The epidermal substitute layer is made of synthetic polysiloxane polymer (silicone) and functions to control moisture loss from the wound. The collagen dermal replacement layer serves as a matrix for the infiltration of fibroblasts, macrophages, lymphocytes, and capillaries from the wound bed. As healing progresses, an endogenous collagen matrix is deposited by fibroblasts and simultaneously the dermal layer of Integra Artificial Skin is degraded. By about 2 to 3 weeks of time, adequate vascularization of the dermal layer has occurred and donor autograft tissue is available for reharvesting (Fig. 3). The temporary silicone layer is removed, and a thin, meshed, nonexpanded layer of epidermal autograft can be placed over the neodermis. Cells from the epidermal autograft grow and form a confluent stratum corneum, thereby closing the wound and reconstituting a functional dermis and epidermis. Advantages of this product are that it simultaneously provides temporary wound coverage, improves the success of epidermal cell grafting (i.e., permanent coverage), and allows use of thinner autografts, which speeds donor site healing. Alloderm (Lifecell, Woodland, TX) is made of a lyophilized acellular cadaveric dermis, with all the immunogenic cells removed by special processing. Eliminating the immune cells, which cause rejection of cadaver skin as a foreign object, essentially tricks the body into believing its own dermis has been applied. Again, like some of the other products, an extremely thin autogenous skin graft or cultured keratocytes can be used over the Alloderm to provide permanent coverage. 73 Oasis (Cook, Spencer, IN) is a biomaterial derived from porcine small intestinal submucosa and is recommended as a temporary coverage for partial-thickness burns. It has been shown to provide excellent protective properties and to have an ability to act as a natural template for wound repair. 53 Oasis is extracted from the porcine intestine using a process that retains the natural composition of matrix molecules such as collagen (Types I, II, and V), and growth factors (TGF- FGF- 2, VEGF). Glycosaminoglycans (hyaluronic acid, chondroitin sulfate A and B, heparin, Figure 2. Integra Artificial Skin (Integra Life Sciences, Plainsboro, NJ) applied to entire anterior trunk of patient in Figure 1. The widely meshed stretch netting used to help hold the Integra in place allows for good visibility and monitoring for signs of infection, fluid collection, and incision and drainage of these, if necessary. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plate 3, Fig. 6.)

9 SKIN RESURFACING FOR THE BURNED PATIENT 37 Figure 3. Histology (scale bar: 320 m between inset notches) approximately 1 month after application of Integra Artificial Skin to excised full-thickness burn bed. The fibrovascular tissue ingrowth will support the application of an overlay epidermal autograft/substitute. (From Boyce ST, Kagan RJ, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for the closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission). and heparan sulfate), proteoglycans, and glycoproteins (fibronectin) signal host cells to repopulate the Oasis scaffold with host tissues. To date there have been no reports of serious allergic responses to this material. Dermal-Epidermal Substitutes Apligraf (Organogenesis, Canton, MA) is a viable, bilayered skin construct; the epidermal layer is formed by human keratinocytes and has a well-differentiated stratum corneum; the dermal layer is composed of human fibroblasts in a bovine Type I collagen lattice. Although matrix proteins and cytokines found in human skin are present, Apligraf, like most other skin substitutes, does not contain Langerhans cells, melanocytes, macrophages, lymphocytes, blood vessels, or hair follicles. The source of skin cells for Apligraf comes from human neonatal male foreskin tissue. The mechanism of permanent resurfacing is thought to occur by way of actual take of Apligraf with subsequent remodeling of the tissue to blend with the patient s own. As noted in Table 1 and discussed later, autologous cultured keratinocytes over a dermal substitute constitutes a skin substitute. All these engineered materials are contraindicated for use on clinically infected wounds. Also, patients with known allergies to any of the xenogenic components should not be treated with any of those materials. The astute burn clinician should always be familiar with the individual bioengineered materials he or she may be using and the information in the product insert regarding product description, indications, contraindications, warnings, and directions for use, including preoperative, intraoperative, and postoperative management. In summary, indications for using the various products available include superficial and partial-thickness burns expected to heal spontaneously, large wounds with permanent coverage unavailable, the burned patients or burn wound beds too unstable to endure autografting, and as overlay grafts to cover widely meshed skin autografts as a method to enhance epithelialization of the graft 48, 63 interstices. Permanent Coverage Deep partial-thickness and full-thickness wounds require permanent coverage. Although full-thickness wounds usually can be

10 38 STANTON & BILLMIRE determined early, deep partial-thickness wounds may take 10 to 14 days to declare themselves. Nonhealing by this point in time signifies injury to the level of the reticular dermis. Spontaneous healing at this level will produce significant hypertrophic scarring. Split-Thickness Autografting Autografts remain the preferred material for definitive wound closure after primary excision of deep partial-thickness and fullthickness burns. Of course, availability of donor sites is the rate-limiting step. Several important surgical decisions must be made about the graft and donor site. The thickness of the graft, whether it is expanded, and the degree to which it is expanded affect the final result. Generally, the thinner the graft, the higher rate of take, but the more the wound undergoes secondary contracture and hypertrophic scarring. Meshed grafts have a better take rate and achieve closure effectively. A meshed skin graft can be expanded to provide more coverage in burn wounds with less available unburned skin. The interstices allow for drainage and thus diminish the risk for seroma, hematoma, and infection. The higher the ratio skin grafts are meshed or expanded, however, the higher the rate of secondary contracture and cobblestoning appearance results. 20 These two undesirable qualities present functional and aesthetic problems. As alluded to earlier, the burn surgeon may choose to use a meshed skin graft as an overlay graft with one of the previously mentioned tissue-engineered materials. 48 This technique may result in a smoother, more pliable end result. As would be expected, meshed skin grafts should not be used on aesthetically sensitive areas such as the face, neck, and hands. In fact, in this day and age with the realization of the undesirable effects of meshed skin grafts and the availability of skin substitutes, about the only absolute indication for the use of a meshed skin graft is on an elderly patient with a large burn. The increased metabolic demands of a large donor site and lack of concern about aesthetic outcome may make mesh grafting a better option. When sufficient donor sites are available, sheet skin grafting should be the burn clinician s first, second, and third choice for autografting. These grafts are by far more aesthetically acceptable than meshed skin grafts. Because they have more dermis, they are also more pliable, durable, and have significantly less secondary contracture. Even in instances of large-percentage TBSA, the ability to reharvest donor sites makes the use of sheet grafting a viable and preferred option. Indeed, sheet skin grafts are technically more difficult to use. They take more time because they must be handled gingerly and the wound bed must be hemostatically prepared to prevent postoperative subgraft hematoma and seroma formation. In large burns, harvesting autologous skin can be a problem because donor site availability sometimes is limited. Essentially, donor sites should be used from anywhere there is unburned skin (except the face). General recommendations for donor graft thickness according to age can be found in Table 2. Two areas that frequently are overlooked and are excellent sites for donor skin are the back and scalp. 14, 26, 40 The back frequently is unburned and provides an area of skin with the thickest dermis on the body and thus makes early reharvesting possible (Fig. 4). The scalp, too, frequently is unburned, and because of its vascularity, it re-epithelializes quickly and can be reharvested at intervals of as early as 7 to 10 days. Table 2. SAFE THICKNESSES FOR HARVESTING SKIN GRAFTS RELATIVE TO AGE AND DONOR SITE Thickness (inches) Age Infant Thigh, buttocks, scalp Trunk 3 12 years Thigh, buttocks, trunk, scalp Teenager/adult Thigh, buttocks, scalp, trunk Elderly Thigh, buttocks Scalp, trunk

11 SKIN RESURFACING FOR THE BURNED PATIENT 39 Some unique features about harvesting skin grafts from the scalp should be kept in mind. Because of the increased vascularity of the scalp, these tend to be bloody donor sites. Because skin is being harvested from an area with a dense population of hair follicles, there is a small but significant risk for hair transfer 9, 37, 38, 69, 75 and donor site alopecia. Repeated harvests from the same scalp donor site are more likely to produce hair transfer and donor site alopecia. Actual thickness of the graft has less propensity to produce these complications than repetitive harvesting. When using the scalp as donor skin, the skin from the first pass should be used to resurface the face and neck regions and subsequent passes used for less conspicuous areas (Fig. 5). Thinner grafts should be harvested for each subsequent pass to help prevent hair transfer. 38 In those instances with hair transplant from scalp donor sites to head and neck burns or even from other donor sites to the face and palms, laser hair epilation is being trialed. As would be expected, more darkly pigmented hairs are eliminated more effectively. Important techniques to keep in mind when harvesting skin from the scalp: the hair should be shaved; the subcutaneous plane should be tumesced with 2:1,000,000 epinephrine solution; the curvature of the skull makes actual harvesting more technically demanding so the burn surgeon should enlist an extra set of hands to help immobilize the patient s head; mineral oil then is applied and the desired thickness skin graft harvested; immediately thereafter, 1:100,000 epinephrine solution soaked laparotomy pads are applied and left on until the final donor site dressing can be placed. This technique also works well when harvesting skin grafts from other parts of the body. Dressing of the donor sites comes down to a matter of preference and experience with one modality or another. Any of the topical antimicrobials and nonadherent dressings may be used and changed on a daily or twice daily basis. Some studies have recommended one form or another of occlusive dressings. The occlusive dressings are low maintenance, changed as infrequently as every 5 to 7 days. They are thought to be less painful because they provide coverage for the nerve endings, and they possibly result in earlier re-epithelialization of the donor sites. Another longterm dressing that can be used is Xeroform. 28 This dressing can be placed at the end of the procedure and left on until re-epithelialization occurs. It naturally sloughs just trimming the edges as they lift up from the healing wound bed. Alginates are also a convenient donor site dressing material that consists of a calcium-sodium alginate composition derived from seaweed. Released calcium ions help with hemostasis. This type of dressing can be left on for as long as 4 to 5 days. At day 5 or 6 it can be soaked off and the wound dressed with a nonadherent gauze. Full-Thickness Autografts Although full-thickness grafts are usually not a concern in the case of large-percentage TBSA, they are mentioned here for completeness and select use for burns to functionally and aesthetically sensitive areas such as the hands and eyelids. 52, 59 As the name implies, the entire thickness of skin is removed from the donor site (usually the groin, supraclavicular area, preauricular or postauricular area) and transplanted to the recipient site. These grafts have more primary contraction but less secondary contraction compared with splitthickness skin grafts and are more durable because the entire thickness of the dermis is included. Primary closure is used for the donor site. If the site is too large for primary closure, a split-thickness graft from another area may be used. Skin Graft Fixation and Dressing Skin grafts can fail for five reasons: 1) subgraft hematoma or seroma; 2) mobility and shearing of the graft on the recipient bed; 3) inadequate debridement of the burn wound; 4) presence of infection; and 5) poor vascularity of the bed. With these considerations in mind, fixation techniques, including suture, permanent versus absorbable staples, Opsite spray, cyanoacrylates, and fibrin glue are 24, 51, 65, 71 used. For full-thickness skin grafts over relatively small areas with convolutions and difficult topography, using some form of

12 40 STANTON & BILLMIRE Figure 4. Resurfacing of full-thickness burns to the entire left hand using thick (0.015 in) split-thickness sheet autografts harvested from the patient s back. A, Full-thickness burn to the volar surface. B, Fullthickness burn to the dorsum. The flexion contracture of the fingers (and wrist) and the necessary escharotomy are apparent. This burn was complex subdermal involving some of the extensor mechanisms. C, One month postoperative resurfacing with K-wires in digits 1, 3, 4, and 5 to hold interphalangeal joints in extension as extensor mechanisms granulate in and grafts mature. Illustration continued on opposite page

13 SKIN RESURFACING FOR THE BURNED PATIENT 41 Figure 4 (Continued). D, Four months postoperative, volar surface. E, Eight months postoperative, dorsal surface. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plates 3 and 4, Fig. 7.)

14 42 STANTON & BILLMIRE Figure 5. Resurfacing of full-thickness burns to the entire left face using splitthickness sheet autografts harvested from the patient s scalp. A, Full-thickness burn to face, shown from left lateral view. B, Post Operative Day 2 (POD), totally resurfaced face with completely adherent grafts. Facial aesthetic units were resurfaced individually with sheets of autograft. a bolster dressing works well. Two methods that are convenient and efficient include Reston foam (3M, Forest City, IA) or moistened burn cotton secured into place with staples or tie over silk suture. The bolster usually can be left in place for approximately 7 days before removal. A nonadherent topical antimicrobial dressing should cover split-thickness skin grafts. In instances with increased risk for infection, the authors recommend placing fine mesh gauze immediately over the skin graft followed by moistened coarse burn gauze and red rubber irrigation catheters. The catheters can be irrigated with antimicrobial solutions such as mafenide acetate (Sulfamylon) or GU irrigant (neomycin/polymyxin). The irrigations continue until the first dressing change, at which time the skin grafts and wounds are evaluated for potential colonization or infection. The decision can be made at that time to continue irrigations or to switch to a twicea-day dressing change with a topical antimicrobial, nonadherent gauze dressing. Problem areas can be addressed by stapling stretchfabric over the dressing. For split-thickness

15 SKIN RESURFACING FOR THE BURNED PATIENT 43 Figure 5 (Continued). C, Three months postoperative showing tailor-made continuous pressure face mask (and soft cervical collar for neck pressure/extension) being worn through the hypertrophic contractile phase of graft maturation. D, Fully matured resurfaced face with good symmetry, smoothness, pliability, and preserved facial animation. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plate 4, Fig. 8.) sheet grafts on postoperative day 1 (POD 2 for split-thickness meshed grafts), the spandex can be incised down the middle and the rest of the burn dressing removed and the skin graft inspected for any problems. Any hematomas or seromas can be lanced and evacuated or rolled out. The irrigation catheter dressing is replaced until the second dressing change on day 5. Skin grafts on the face and neck area usually are left open with a topical antimicrobial ointment applied to keep them moistened and minimally colonized. For the first 4 hours after grafting, these grafts should be rolled every 15 minutes with a cotton swab to prevent any subgraft hematoma or seroma. Again, any fluid collections that get loculated should be lanced and drained. Perseverence with this routine for the first 4 hours pays off, and the clinician can cut back to rolling the grafts every 1 to 2 hours because they become more and more adherent during the first 24 hours. Assuming a stable airway, patients with skin grafts to the anterior neck should be placed on a hyperextension mattress. For sheet skin grafts over the trunk region, the irrigation catheter bulky burn gauze dressing with spandex fabric covering works well, and grafts can be inspected at 24 (or 48) hours, and, if all is well, again at 5 days postoperatively. For grafts over the extremities, irrigation catheter and bulky burn gauze dressings work and can be held snugly into place with elastic wrap bandages. Grafts are inspected on postoperative day 1 or 2 for adherence and subgraft fluid collections, which are evacuated as needed. For those grafts proximal to the knees and elbows, a second dressing change is performed on day 5, and the patient is allowed to get out of bed at this time. For grafts distal to the knees and elbows, a second dressing change is awaited until day 7, and, if all looks well, the patients are allowed to get out of bed. For skin grafts over joints, splinting is an excellent method of immobilization to avoid shear forces. Hexcelite (X-lite, Runlite SA, Copenhagen, Denmark) is a light-weight, low-profile, userfriendly splinting material used for intraoperative application. 25 Specific recommendations for positions include the following: axilla 90 horizontal with bedside troughs or an airplane splint; elbow: fully extended; wrist: slightly extended (10 ); metacarpal phalangeal joints of the fingers: flexed 60 to 70 ; interphalangeal joints: fully extended (Kwires may be necessary if the extensor mecha-

16 44 STANTON & BILLMIRE nism is involved); thumb: 40 to 50 of abduction with the interphalangeal joint in extension. Once again, the first dressing change is on postoperative day 1 (or 2), when skin grafts are evaluated and manipulated as needed. The patient is left at bed rest for a total of 5 days, at which time a second dressing change is performed and the patient then allowed out of bed. The timing of the first dressing change is controversial. Hematomas and seromas will not likely affect engraftment if drained within the first 48 hours. Even dislodged or misplaced skin grafts can be repositioned successfully in the first 2 days after placement. If early graft infection is recognized at the first dressing change, a more effective antimicrobial agent such as mafenide acetate (Sulfamylon) can be instituted. The above recommendations for sheet autografting vary from institution to institution. Suffice it to say that for large burns with limited donor sites, there is only one chance at engraftment, and, therefore, the earlier a problem is recognized, the earlier it can be dealt with and the better the chance of graft survival and good outcome. Mesh grafts, on the other hand, are a little more forgiving and, with the exception of a high suspicion for infection, rarely need a dressing change and evaluation until postoperative day 2. For completeness, Unna boot type management has been advocated by some for skin grafts to areas such as the scalp, 10, 13, 58, 68 hand, and upper and lower extremities. SKIN SUBSTITUTES FOR PERMANENT COVERAGE Tissue engineering has been used in burn management since the early 1980s. 22 The primary indication for using cultured skin is in the management of extensive deep partialthickness and full-thickness burns. These grafts provide permanent skin coverage in circumstances in which adequate donor sites for conventional skin grafting are not available. 6 The economics of cultured skin in burn wound management have not been elucidated fully; however, it seems as though those burns with 50% or greater TBSA burn in which the burn wounds cannot be excised and grafted within a 3- to 4-week period (with conventional autografting) may be treated more efficiently with cultured skin substitutes. 7 The two general categories of skin substitutes available are monolayer cultured kerotinocytes or bilayered composite dermal-epidermal skin substitutes (see Table 1). Cultured keratinocytes were the first option available. These are produced by harvesting a small biopsy of split-thickness skin from the patient (less than 1% TBSA) then transferring it to the laboratory for culturing of keratinocytes. It is currently possible to expand these small skin biopsies to greater than 100- fold in approximately 3 to 4 weeks, at which time a significant-sized burn wound can be covered. These keratinocytes then can be engrafted onto a stable burn wound bed. At initial placement, these grafts must be cared for delicately and diligently with an individualized protocol of nutrient and antimicrobial irrigations and dressing changes. 4, 5 Obviously, lacking a dermis, these grafts provide only epithelial coverage and, unfortunately, are fragile, subject to infection, and have a variable take rate. Long-term results have been somewhat disappointing, with significant graft contraction, hypertrophic scarring, and hypopigmentation. The resulting epidermis remains fragile and frequently blisters. 54, 56 This occurrence seems to be caused by the slow development of anchoring complexes. For these reasons, burn clinicians and researchers now concentrate their efforts on the application and development of bilayered composite cultured skin substitutes, which provide not only autologous epidermis but also dermis made from fibroblasts, collagen, 1, 33 and glycosaminoglycans. Bilayered dermal-epidermal substitutes come in various forms, from simply placing a thin (less than or equal to.008 ) autograft over a chosen dermal substitute (i.e., Integra or Alloderm) to a combination of cultured autologous keratinocytes over a dermal substitute versus cultured kerotinocytes and fibroblasts placed over a dermal substitute (e.g., cultured skin substitute combined with Integra. S. Boyce, Shriners Hospital for Children Cincinnati Burn Unit, Cincinnati, OH). 28, 30, 76 The acute burn wound is managed in the typical fashion initially, and temporary coverage is accomplished by placement of a

17 SKIN RESURFACING FOR THE BURNED PATIENT 45 bioengineered material containing a dermal substitute. Autologous keratinocytes plus or minus fibroblasts are cultured up to the desired volume (the timing of this coincides with fibrovascular ingrowth into the artificial dermal substitute). At this time, the patient is taken back to the operating room for engraftment. Postoperatively, these are cared for in a similar fashion as noted above for engraftment of monolayered cultured keratinocytes. With successful engraftment, these patients are allowed to get out of bed by postoperative day 7, the grafted areas can be put through a range of motion, and topical antimicrobials can be discontinued and moisturizing lotion commenced (Fig. 6). Figure 6. Postoperative view of bilayered dermal-epidermal (staged Integra-Cultured Skin Substitute [CSS]) substitute resurfacing the entire back of patient in Figure 3. Tape measures in centimeters. A, POD 7, essentially 100% take, grafted wounds dry, keratinized, and clinically covered. B, POD 28; healed skin becoming smoother with a more confluent surface architecture and is tolerating physical therapy and pressure garments. (From Boyce ST, Kagan RT, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission.)

18 46 STANTON & BILLMIRE The microscopic anatomy of bilayered dermal-epidermal substitutes resembles splitthickness skin; it is made up of well-stratified epidermal substitute and a dermal substitute, and its total thickness is usually less than.5 mm (Fig. 7). Anatomic deficiencies of cultured skin include lack of vascularized plexus, glands, follicles, and nerve and immune cells. 3 During the ensuing first several months, the artificial dermal substitute material gradually is replaced by ongoing fibrovascular ingrowth and creation of a neodermis (Fig. 8). 7 Because of the presence of a neodermis, pliability and durability of this healed skin is excellent, and there are virtually no problems with blistering or hypertrophic scarring, even between edges of adjacent grafts. 2, 7, 76 The skin has pronounced hypopigmentation with an occasional few discrete foci of pigmentation (Fig. 9), however. It is actually now possible to impregnate the skin substitutes with cultured melanocytes and minimize or hopefully eliminate the problems of hypopigmentation. 66 POSTOPERATIVE CARE: LONG TERM Once successful engraftment has been achieved and grafts are stable (usually 5 to 7 days after surgery), long-term planning and care must be instituted. The potential problems of healing skin grafts must be anticipated and measures instituted, if possible, before their occurrence. Because skin grafts, especially for the first several months, lack glandular tissue, they have a tendency to dry out and therefore must be moisturized with a thick moisturizing cream at least 3 times a day. A set of goals for rehabilitative therapy should be used for every patient. GOALS OF THERAPY 1. Prevent, minimize, or correct deformity 2. Protect weak muscles from overstretching 3. Maintain range of motion 4. Provide positional function 5. Protect any exposed joints or tendons 6. Provide immobilization across joints after grafting 7. Minimize scarring with pressure garments or masks 8. Develop functional skills to facilitate independence in activities of daily living and community/occupational reentry In general, active and passive range-of-motion exercises are used to retain motion. Figure 7. Histology of CSS as engineered 1 month past harvesting skin biopsy from patient in Figure 6 (scale bar: 320 m between inset notches). CSS have well stratified epidermal substitute biologically attached to dermal substitute. (From Boyce ST, Kagan RJ, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft or allograft for the closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999, with permission.)

19 SKIN RESURFACING FOR THE BURNED PATIENT 47 Figure 8. Histology of wounds from patient in Figure 6; wounds are grafted with CSS over Integra Artificial Skin. A, POD 21, at which time stable epidermis attached to connective tissue and reticulations of Integra remain in wound (scale bar: 320 m between inset notches). B, POD 63, at which time epidermis and dermis are stable and small fragments of Integra remain in connective tissue (scale bar: 256 m between inset notches). (From Boyce ST, Kagan RT, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission.)

20 48 STANTON & BILLMIRE Figure 9. Postoperative view of patient in Figure 6 at 5 months demonstrating aesthetics of CSS/Integra resurfaced back. Surface architecture is smooth and soft, seams are fine and nearly imperceptible, overall pliability is excellent but pigmentation is mostly absent. (From Boyce ST, Kagan RT, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission.) Splinting is used to retain positioning when the patient is not moving. The guidelines for positioning are similar to those for immediate postoperative care. Because of the propensity for intense wound contractures, early and aggressive use of these modalities is essential to maintain function. When grafts are secure and stable (usually by 2 to 3 weeks), most patients are measured for pressure garments, which apply 25 mm Hg of pressure. 12 In general, scarring is most intense at about 3 to 6 months and takes 12 to 15 months to mature; however, hypertrophic scars can take much longer. The pathophysiology of hypertrophic scars is incompletely understood. It has been associated with elevated levels of transforming growth factor in the scar. 23 Hypertrophic scarring is more common and intense in children, darker-skinned races, and in areas of stretch and motion. It is thought that the mechanism of action of pressure garments and masks is caused by a combination of pressure-induced collagen remodeling and hypoxia-induced tissue atrophy. Silicone sheeting has been another commonly used modality to improve the appearance, soften, and reduce redness and itching of hypertrophic scars. Frequently, these two modalities are used in combination. Corticosteroid local injections also have been found to improve the appearance of hypertrophic scars and reduce itching. Injections usually are adminis-