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Acs0715 Management Of The Burn Wound
1.
© 2004 WebMD,
Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 1 15 MANAGEMENT OF THE BURN WOUND Matthew B. Klein, M.D., David Heimbach, M.D., F.A.C.S., and Nicole Gibran, M.D., F.A.C.S. Advances in resuscitation and critical care have significantly The fibroblast is the principal cell of the dermis and is respon- improved survival after thermal injury. Ultimately, survival sible for synthesis and degradation of fibrous and elastic dermal remains contingent on effective wound management and com- proteins. The dermis also contains various inflammatory cells plete wound closure. Current approaches to burn management (derived from bone marrow stem cells), mast cells, and cells asso- are based on an understanding of the biology and physiology of ciated with vascular, lymphatic, and nervous tissue. human skin and the pathophysiology of the burn wound. The BMZ is a complex region of extracellular matrix con- necting the basal cells of the epidermis with the papillary dermis. At the light-microscopic level, the dermal-epidermal junction Anatomic and Physiologic Considerations consists of protrusions of dermal connective tissue known as dermal papillae, which interdigitate with epidermal projections BIOLOGY OF SKIN known as rete ridges. The structure of the BMZ is best appreci- Skin consists of two distinct layers, the epidermis and the dermis; ated on electron microscopy, where it appears as a trilaminar these layers are integrated by a structure known as the basement zone consisting of a central electron-dense region (the lamina membrane zone (BMZ) [see Figure 1]. The epidermis is the outer densa) flanked on both sides by regions of lower electron densi- layer and acts as the barrier between body tissues and the environ- ty [see Figure 2]. Within the basal cells of the epidermis are mul- ment. This layer protects against infection, ultraviolet light, and tiple sites of attachment to the basal lamina, which are known as evaporation of fluids and provides thermal regulation. The epider- hemidesmosomes. On the dermal side of the basal lamina are mis is derived from fetal ectoderm and thus, like other ectodermal numerous anchoring fibrils, which reach from the lamina into derivatives, is capable of regeneration. Repair of epidermal wounds the connective tissue of the dermis.1 The BMZ plays a significant is achieved through regeneration of epidermal cells both from the role in burn wound healing: epithelialized wounds undergo blis- perimeter of the wound and from the adnexal structures of the epi- dermis (i.e., hair follicles, sweat glands, and sebaceous glands). Accordingly, pure epidermal injuries heal without scarring.1 The principal cell of the epidermis is the keratinocyte. These cells are arranged into five progressively differentiated layers, or strata: the stratum basale, the stratum spinosum, the stratum granulosum, the stratum lucidum, and the stratum corneum.The outermost of these layers—the relatively impermeable stratum corneum—provides the barrier mechanism that protects the underlying tissues. Besides keratinocytes, the epidermis contains cells from other embryologic layers that carry out specific func- Epidermis tions. Melanocytes, derived from fetal neuroectoderm, produce melanosomes, which become pigmented as a result of the forma- tion of melanin through the action of the enzyme tyrosinase. Papillary Melanin provides the skin with its pigment and absorbs harmful Dermis ultraviolet radiation. Langerhans cells, derived from bone marrow cells, play a critical role in the immune function of the skin.These Dermis cells recognize, phagocytize, process, and present foreign antigens and, through their expression of class II antigens, initiate the rejec- tion process in skin transplantation.1 In contrast to the epidermis, the dermis is a complex network Reticular comprising cellular and acellular components. This layer provides Dermis skin with its durability and elasticity. Structurally, the dermis con- sists of two sublayers, a superficial one (the papillary dermis) and a deeper one (the reticular dermis). Collagen is the major structural Subcutaneous matrix molecule, constituting approximately 70% of the skin’s dry Tissue weight. Elastic fibers account for approximately 2% of the skin’s dry weight and play an important role in maintaining the integrity of the skin after mechanical perturbation.1 Glycosaminoglycans (GAGs), the third major extracellular component of the dermis, Figure 1 Cross-sectional diagram shows the two distinct layers regulate intracellular and intercellular events by binding to, releas- of the skin—the epidermis and the dermis (papillary and reticu- ing, and neutralizing cytokines and growth factors.2,3 lar)—and the underlying subcutaneous fat.
2.
© 2004 WebMD,
Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 2 Table 1 Overview of Burn Wound Management Basal Keratinocyte Burn Wound Type Clinical Features Management Cell Superficial Erythematous, painful Soothing, moisturizing Membrane lotions (i.e., aloe) Silver sulfadiazine; BP230 BP180 α6 β4 Partial-thickness Blistered, pink, moist, greasy gauze once painful epithelial buds are Hemidesmosome present Silver sulfadiazine dress- ings daily; surgical Deep partial-thickness Dry, mottled pink-and- excision and grafting if white, less painful not going to heal within 3 wk Intermediate Lamina Filament Lucida Silver sulfadiazine; early Full-thickness Dry, leathery, black or excision and skin Laminin 5 white, painless Lamina grafting Densa B Type IV Collagen ed.The zone of coagulation is surrounded by the zone of stasis, an Anchoring Sublamina area characterized by vasoconstriction and ischemia. Tissue in this Fibril (Type VII Densa zone is initially viable; however, it may convert to coagulation as a Collagen) consequence of the development of edema, infection, and decreased perfusion.4 With good wound perfusion, tissue in the zone of stasis generally remains viable. Surrounding the zone of sta- Figure 2 The basement membrane zone (BMZ) integrates the sis is the zone of hyperemia, an area characterized by vasodilation epidermis with the underlying dermis. On electron microscopy, resulting from the release of inflammatory mediators from resident the BMZ has three layers: a central electron-dense region known cutaneous cells.Tissue in this zone typically remains viable. as the lamina densa and two regions of lower electron density to either side of this central region. Clinical Evaluation and Initial Care of Burn Wound tering until the anchoring structures of the BMZ mature and After admission to the burn center, the burn wound is cleaned provide protection from shearing. with soap and water, blisters and debris are removed, and the extent and depth of the wound are assessed. Management of tar PATHOPHYSIOLOGY OF THERMAL INJURY burns warrants special mention.When tar that has been heated to Jackson’s classification of burn wounds remains the foundation maintain a liquid form comes into contact with skin, it can trans- of our understanding of the pathophysiology of thermal injury to fer sufficient energy to cause a significant burn injury. As the tar the skin.4 In this classification, there are three zones of tissue injury cools on the skin, it solidifies, thereby becoming difficult to resulting from a burn [see Figure 3].The central, most severely dam- remove. Solvents such as petrolatum, petrolatum-based oint- aged area is called the zone of coagulation because the cells in this ments, lanolin, and Medi-Sol (Orange-Sol, Inc., Gilbert, Arizona) area are coagulated or necrotic.Tissue in this zone must be debrid- are useful for tar removal. For optimal effect, 10 to 15 minutes should be allowed after solvent application before removal of the tar is attempted. Repeat applications may be necessary for com- plete removal. ASSESSMENT OF BURN DEPTH Thermal injury can damage the epidermis alone, the epidermis along with a portion of the dermis, or the entire skin and can even extend into the underlying subcutaneous tissue.The depth of the injury affects the subsequent healing of the wound; thus, assess- ment of burn wound depth is important for selection of wound dressings and, ultimately, for determination of the need for surgery [see Table 1]. Superficial burns involve only the epidermis.They typically are erythematous and painful, much as a sunburn would be. Most such burns heal within 3 to 4 days, without scarring. The usual treatment is a soothing moisturizing lotion (e.g., one containing aloe vera), which both optimizes the rate of reepithelialization and provides comfort to the patient. Partial-thickness burns extend through the epidermis and into Figure 3 A burn wound is characterized by three zones of the papillary dermis. Blistering is their hallmark [see Figure 4]. injury: A represents the zone of coagulation, B the zone of stasis, These burns can be further categorized as superficial or deep. and C the zone of hyperemia. Superficial partial-thickness burns are typically pink, moist, and
3.
© 2004 WebMD,
Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 3 Figure 4 Shown at left is a shallow scald burn with the pink, moist appearance typical of a superficial par- tial-thickness burn wound. Such injuries typically heal without the need for excision and grafting. A superfi- cial partial-thickness burn (right, a), which involves only the papillary dermis, is visually distinct from a deep partial-thickness burn (right, b), which is mottled in appearance, extends into the reticular dermis, and is more likely to require excision and grafting. painful. They usually heal within 2 to 3 weeks, without scarring or escharotomies are necessary. In general, escharotomies are functional impairment. Deep partial-thickness wounds extend into required only for circumferential full-thickness extremity burns in the reticular layer of the dermis.They are typically a mottled pink- which distal perfusion has been compromised or for chest burns and-white, dry, and variably painful. In some cases, they may be in which eschar poses an external mechanical barrier to respira- difficult to distinguish from full-thickness burns. Deep partial- tion. Escharotomies can be performed at the bedside with either a thickness burn wounds, if they do not become infected, typically scalpel or an electrocautery. They should extend through the heal in 3 to 8 weeks, with severe scarring, contraction, and loss of eschar only, not through the muscle fascia. Adequate release is sig- function.Therefore, if a partial-thickness burn has not healed by 3 naled by separation of the eschar, improved distal perfusion, and, weeks, surgical excision and skin grafting may be required. sometimes, a popping sound. Because an escharotomy is a super- Full-thickness burn wounds extend through the entire dermis ficial incision through dead tissue, only minimal doses of anal- and into the subcutaneous tissue. These burns are typically white gesics and anxiolytics are required. or black, dry, and painless [see Figure 5]. Some full-thickness burns DAILY BURN WOUND CARE appear red, but they can be distinguished from superficial burns because they are not moist and do not blanch with pressure. The use of hydrotherapy tanks, previously a standard compo- Because all skin appendages are burned away, full-thickness burns nent of burn unit wound care, has fallen from favor somewhat can heal only by contraction or migration of keratinocytes from because of the risks of cross-contamination between one burn the periphery of the wound. Accordingly, all full-thickness burns, wound area and another. It is preferable to place the patient on a unless they are quite small (e.g., the size of a quarter or smaller), must be treated with excision and grafting. As a rule, both superficial and full-thickness burns are easily rec- ognized, and treatment decisions are relatively straightforward. It is frequently difficult, however, to determine the ultimate fate of intermediate partial-thickness burns soon after injury. For this rea- son, these wounds are often referred to as indeterminate-thickness wounds. Over the course of the first several postburn days, it usu- ally becomes easier to determine which indeterminate-thickness wounds are likely to heal in a timely manner, without the need for grafting. Various techniques for accurately and readily assessing burn depth have been described, including the use of vital dyes, laser flowmetry, thermography, and magnetic resonance imaging, but none of these has ever been shown to yield a more precise deter- mination of burn depth than clinical evaluation by an experienced burn care provider.5 DETERMINATION OF NEED FOR ESCHAROTOMY Burn wound eschar consists of dead skin, has the consistency of Figure 5 Shown is a full-thickness flame burn with a character- leather, and may restrict limb perfusion by creating a nonelastic istic brown, leathery appearance. Such wounds require excision exoskeleton. A key issue in assessing burn wounds is whether and subsequent skin grafting.
4.
© 2004 WebMD,
Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 4 Topical Burn Wound Treatment GENERAL PRINCIPLES Because thermal injury disrupts the protective barrier function of the skin, dressings are needed to protect the body against envi- ronmental flora. Burn dressings also protect against evaporative heat loss.The ideal burn dressing would be inexpensive and com- fortable and would not require frequent changing. Daily dressing changes allow the burn care provider not only to apply clean dress- ings but also to clean the wounds and debride fragments of sepa- rated eschar and devitalized tissue. Numerous topical agents and dressings are available for use in burn patients; we limit our discussion to the ones that are most commonly employed and have proved most effective. Selection of an appropriate dressing for a given wound is governed by the spe- cific goals of management.With purely superficial wounds, the goal is to create a moist environment that will optimize reepithelializa- tion. Typically, this is achieved by applying ointments or lotions. With partial-thickness and full-thickness wounds, however, it is necessary to include agents that protect against microbial coloniza- tion (see below). Once a partial-thickness burn demonstrates evi- dence of epithelialization, dressings should be changed to a regi- men that facilitates healing (e.g., greasy gauze with ointment). ANTIMICROBIAL AGENTS It must be emphasized that systemic antibiotic prophylaxis plays no role in the management of acute burn wounds and provides no protection against microbial colonization of burn eschar6; in fact, use of prophylactic antibiotics in burn patients increases the risk that opportunistic infections will develop. Because eschar has no microcirculation, it is impossible for systemically administered Figure 6 Shower tables are generally preferred to Hubbard tanks for burn wound care. A clean plastic drape can be used to antibiotics to reach the eschar surface, where colonization occurs. cover the shower table during patient care. Therefore, topical preparations, which are capable of supplying high concentrations of antimicrobial agents at the wound surface, must be used. In the early postburn period, the dominant coloniz- shower table, which is inclined so that water runs off the wounds ing organisms are staphylococci and streptococci—typical skin and into a drain [see Figure 6]. Smaller wounds can often be man- flora. Over time, however, the burn wound becomes colonized with aged with bedside wound care after a shower. Washing with tap gram-negative organisms.5 Thus, topical antimicrobial agents used water and regular soap suffices for daily burn wound cleansing. It in early burn care should have broad-spectrum coverage to mini- is important to be cognizant of the need to provide adequate seda- mize colonization of the wound, but they need not be able to pen- tion and analgesia while performing daily wound care—a particu- etrate the burn eschar deeply. larly challenging task with infants and elderly patients. Of the antimicrobial agents used in this setting [see Table 2], sil- Table 2 Topical Antimicrobial Agents Used in Burn Care Agent Antimicrobial Coverage Advantages Disadvantages/Precautions Bacitracin Gram-positive bacterial Soothes and moisturizes; good for facial Not appropriate for deeper wounds care and epithelializing wounds Broad-spectrum antibacterial; Penetrates eschar well; available as solu- Painful on application; causes metabolic Mafenide acidosis (via carbonic anhydrase anticlostridial tion or cream inhibition) Mupirocin Anti-MRSA Effective against MRSA Narrow (poor gram-negative) antimicro- bial coverage Provides fungal prophylaxis with swish- Nystatin Antifungal (Candida) May interfere with activity of mafenide and-swallow solution Penetrates eschar poorly; causes Effective for both prophylaxis and treat- Silver nitrate Broad-spectrum antibacterial hyponatremia; stains linen and dress- ment of wound infection ings; induces methemoglobinemia Broad-spectrum antibacterial; Soothes on application and causes no Penetrates eschar poorly; causes Silver sulfadiazine antipseudomonal pain leukopenia
5.
© 2004 WebMD,
Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 5 ver sulfadiazine is the one most commonly employed for partial- grafts. With burn wounds, the Acticoat dressing is typically thickness and full-thickness burns. Silver sulfadiazine is soothing on changed every 3 days.The reduced frequency of dressing changes application and is active against a broad spectrum of microorgan- simplifies burn care somewhat but can hinder evaluation of evolv- isms. Because it does not penetrate eschar, very little is systemical- ing partial-thickness burns. With donor sites, Acticoat can be left ly absorbed; therefore, it is ineffective against already established in place until the underlying partial-thickness wound heals. burn wound infections.Wounds treated with silver sulfadiazine may Typically, an adhesive tape such as Hypafix (Smith & Nephew) is form a tenacious yellow-gray pseudoeschar, which can be mistak- used to secure the dressing to the donor site for 7 days. Once the en for true eschar.This pseudoeschar develops when silver sulfadi- tape has been removed, the Acticoat usually is sufficiently adher- azine combines with the wound exudates; it can be gently debrid- ent to allow patients to shower daily and towel-dry the dressing ed during daily wound care. It has been suggested that silver sulfa- until it eventually peels off the healed wound.The development of diazine may be responsible for the leukopenia that sometimes Acticoat has led to the introduction of several other silver-based develops during the first week after a major burn. This attribution dressings. may not be entirely accurate, however, given that this leukopenia Bacitracin, neomycin, and polymyxin B have all been used for may also develop in patients treated with silver nitrate. It is possible coverage of superficial wounds in conjunction with Xeroform or that the leukopenia results not from either agent but from the mar- petrolatum gauze to accelerate epithelialization and minimize col- gination of neutrophils secondary to the pathophysiology of the onization. These ointments also are commonly administered sev- burn injury itself. In any case, the leukopenia is typically self-limit- eral times daily in the care of superficial face burns. Mupirocin has ed and necessitates no change in therapy. Patients with a history of proved effective in treating methicillin-resistant Staphylococcus sulfa allergy typically do not have adverse reactions to silver sulfa- aureus (MRSA) colonization; however, because of the potential for diazine; however, if there is concern about a possible reaction, a test the development of bacterial resistance, it should be employed patch can be applied to a small area of the wound. If the patient is only in MRSA-positive wounds. allergic, silver sulfadiazine will cause pain on application or, in some case, a rash. Mafenide acetate is also commonly used in the management of Surgical Burn Wound Management burn wounds. It provides excellent coverage against gram-negative As noted [see Clinical Evaluation and Initial Care of Burn organisms, but it is not as active against staphylococci and has no Wound, Assessment of Burn Depth, above], superficial burns and antifungal activity. Unlike silver sulfadiazine, mafenide penetrates superficial partial-thickness burns typically heal without any need eschar very well, and this ability makes it effective in treating as for surgical excision and grafting. Dressing changes and daily well as preventing burn wound infections. Mafenide does, howev- wound care can remove necrotic debris and provide an environ- er, have some drawbacks. Because it is a potent carbonic anhy- ment conducive to healing in a timely fashion (2 to 3 weeks), with drase inhibitor, regular use and the consequent ongoing systemic minimal scarring. For deep partial-thickness and full-thickness absorption can lead to metabolic acidosis. In addition, because it burns, however, operative debridement with subsequent skin graft is so well absorbed, twice-daily administration is necessary. Finally, coverage is necessary. Timely removal of eschar is critical for suc- topical application of mafenide, particularly to partial-thickness cessful management. Surgical excision removes necrotic tissue burns, is painful, which limits its utility in the routine management that serves as a nidus for microbial proliferation and the develop- of burn wounds. Mafenide is frequently used on the ears and the ment of burn wound sepsis.8 nose because of its ability to penetrate eschar and protect against EARLY EXCISION AND GRAFTING suppurative chondritis; however, silver sulfadiazine appears to be equally effective in this setting.7 Mafenide is available both as a Surgical excision of burn wounds is a concept whose impor- cream and as a solution. The solution is useful as a topical agent tance was not fully appreciated until the 1970s. Previously, the for skin grafts when the wound bed is considered likely to benefit usual practice was to leave eschar intact over the wound surface, from postoperative antimicrobial treatment. the idea being that proteolytic enzymes produced by migrating Silver nitrate provides broad-spectrum antimicrobial coverage, neutrophils and bacteria within the contaminated eschar would including good activity against staphylococci and gram-negative cause a natural separation of the eschar from the wound bed organisms (e.g., Pseudomonas). It is relatively painless on adminis- (sloughing) and that the resulting granulating wound would serve tration and must be reapplied every 4 hours to keep the dressings as the bed for grafting.9 The rationale for delaying surgical man- moist. It does not readily penetrate eschar. Silver nitrate is used in agement was it would presumably allow the burn care provider the form of a 0.5% solution, which is bacteriostatic but is not toxic time to determine which wounds would heal spontaneously and to epithelial cells.The hypotonic formulation (it is reconstituted in which would have to be covered with skin grafts. It has since water) can cause osmolar dilution, resulting in hyponatremia and become clear, however, that in cases of extensive burn injury, hypochloremia.Therefore, careful electrolyte monitoring and dili- delayed management results in more extensive bacterial coloniza- gent replacement are necessary. In rare cases, use of silver nitrate tion, as well as an increased likelihood of burn wound sepsis, mul- solution can also lead to methemoglobinemia; if this condition is tiple organ failure, and, ultimately, death.9 detected, administration of silver nitrate should be discontinued. Early excision and skin grafting of small burn wounds were first A principal disadvantage of silver nitrate solution is that it stains described by Lusgarten in 1891. After the Cocoanut Grove fire in everything it touches black. 1942, Cope suggested that patients treated with early excision and Acticoat (Smith & Nephew, London, England), a relatively new grafting had better overall outcomes.10 In 1960, Jackson and asso- antimicrobial dressing, consists of a polyethylene mesh impreg- ciates reported discouraging results with early burn wound exci- nated with elemental silver. Silver has unique antimicrobial prop- sion,11 and it was not until 10 years later, when Janzekovic report- erties and works by disrupting bacterial cellular respiration. ed good results with surgical burn wound excision,12 that enthusi- Acticoat has been successfully used for coverage of partial-thick- asm for early excision was rekindled. As clinical experience with ness burns, as well as for coverage of donor sites and meshed skin early excision was accumulated, the benefits became clear.
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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 6 Since Janzekovic’s report, studies have repeatedly shown that early wound excision and closure improve survival, reduce the infection rate, and shorten hospital stay.13-24 Other studies have demonstrated that early removal of dead and severely damaged tissue interrupts and attenuates the systemic inflammatory response syndrome (SIRS).8,25 Early excision of deep burn wounds also appears to decrease hypertrophic scarring. Similarly, early excision and grafting have been shown to be beneficial for burns of indeterminate depth as well. In one study of patients with burns covering less than 20% of their total body surface area (TBSA), early excision and grafting reduced length of stay, cost of care, and time away from work in comparison with nonoperative treatment.17 Wound Excision Early staged excision, beginning as early as postburn day 3 if feasible, is now conventional treatment for major burns. Operations are spaced 2 to 3 days apart until all eschar is removed and full wound coverage is achieved. Debrided wounds can be temporarily covered with biologic dressings or cadaveric allograft Figure 7 Fascial excision involves excision of the burned skin and until autogenous donor sites are available. the underlying subcutaneous tissue down to the level of the muscle Generally, the decision whether to perform operative wound fascia. It is typically performed with the electrocautery. As shown excision is guided by whether spontaneous wound healing is like- (arrows), the edges should be tacked down to minimize the ledge at ly to occur in a timely fashion (i.e., within 2 to 3 weeks after the the edge where normal tissue adjoins the exposed fascia. burn). Burn wounds over joint surfaces, however, should undergo excision and grafting sooner so as to minimize healing by wound contraction, which can ultimately lead to disabling contractures. In patients with extensive burns, hemodynamic and pulmonary status must be considered in deciding on the timing of operation. Any critically ill burn patient will have some degree of respiratory dysfunction, but the patient should at least be capable of being safely transported from the ICU to the operating room and back. The risk of hypothermia and the need for blood transfusion must be anticipated before operation and clearly communicated to the anesthesiologist. There are two main technical approaches to surgical excision of the burn wound: fascial excision and tangential excision. Fascial excision, as the name suggests, involves excising the burned tissue and the underlying subcutaneous tissue down to the muscle fascia [see Figure 7]. A major advantage of fascial excision is that it yields an easily defined plane that is well vascularized and therefore can readily accept a graft. In addition, bleeding is generally easier to control at the fascial level of dissection because the vessels are eas- ier to identify and coagulate. Furthermore, the entire excision can Figure 8 Tangential excision of the burn wound is carried out with a Watson knife (as shown here) or a Weck/Goulian blade. be performed with the electrocautery, and blood loss is thereby Eschar is tangentially excised until healthy, bleeding tissue that minimized. The principal drawback of this approach is that the is suitable for skin grafting is reached. excision inevitably includes some healthy, viable subcutaneous tis- sue. Another disadvantage is that the removal of subcutaneous tis- sue may create an unaesthetic contour deformity. Regardless of which excision technique is used, tourniquets can Tangential excision, as the name suggests, involves sequentially be placed on extremities to minimize blood loss, and the extremi- excising the layers of eschar in a tangential fashion until a layer of ties can be suspended from OR ceiling hooks [see Figure 9] to pro- viable bleeding tissue capable of supporting a skin graft is encoun- vide access to their entire circumference. tered [see Figure 8].26,27 The goal is to remove only the nonviable A water jet–powered instrument (VersaJet Hydrosurgery tissue, particularly in the case of deep dermal wounds. Typically, System; HydroCision, Andover, Massachusetts) is available that tangential excision is performed with a handheld knife (a Watson can be used for tangential burn wound excision.This device offers knife or a Weck/Goulian blade). A back-and-forth carving motion an easy and relatively precise way of excising eschar and is partic- is used, and very little force is applied.The guard on the knife can ularly useful for excising nonviable tissue from the concave sur- be used to control the depth of excision.The appearance of diffuse faces of the hands and feet, as well as the eyelids and ears. punctate bleeding signals that viable tissue has been reached. The To minimize hematoma formation and graft loss, it is critical main disadvantages of tangential excision are that (1) it may be that adequate hemostasis be achieved before the placement of skin difficult to control the diffuse bleeding from the wound bed, and grafts, cadaveric grafts, or skin substitutes. Telfa pads (Kendall, (2) it may be difficult to assess the suitability of the underlying fat Mansfield, Massachusetts) soaked in an epinephrine solution for accepting a graft. (1:10,000) are a mainstay of hemostasis, combined with topical
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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 7 dermis harvested with the graft. The thinner the skin graft, the greater the degree of contraction that occurs at the recipient site after engraftment. Although thicker grafts have the advantage of contracting less, they leave a greater dermal deficit at the donor site, which can lengthen the time needed for healing and increase the risk of hypertrophic scarring at that site. Full-thickness skin grafts can be harvested either through use of a dermatome or through direct excision of skin from the flank, the groin crease, the hypothenar eminence, or the forearm and can be used for coverage of small defects of the hand or the face. Standard (intermediate) split-thickness grafts are typically harvested at a thickness of 0.010 to 0.012 in.Thin (0.006 in.) split-thickness skin grafts are generally used in conjunction with skin substitutes, whereas thick (0.018–0.025 in.) split-thickness grafts are typically used in grafting of the hand and the face.The thickness of the graft depends both on the dermatome setting and on the pressure the harvester applies to the dermatome during harvesting.30 Donor site selection for split-thickness skin grafts is based on the distribution of the burn. The anterolateral thigh, when avail- able, is the donor site of choice for most adult patients: it can be harvested in the supine position, it can easily be left open to the air so the donor-site dressing can dry, and it can be covered by shorts if desired.When larger grafts are needed or the thighs are burned, Figure 9 Extremities can be suspended from OR ceiling hooks the back, the buttocks, and the abdomen can serve as donor sites. to facilitate exposure for burn excision and grafting. Subcutaneous infiltration of a physiologic salt solution yields a smooth, firm surface that facilitates the harvesting of these areas. If this is done, the anesthesiologist should be informed that addi- pressure and cauterization when necessary. A fibrinogen thrombin tional fluid is being administered. In children, the buttocks and the delivery system (Tisseel Fibrin Sealant; Baxter, Deerfield, Illinois) scalp are commonly employed as donor sites. Once healed, these is commercially available that improves the ability to control sites are usually inconspicuous: the buttock donor site can be har- bleeding after excision. vested in such a way that it can be covered by a bikini, and the scalp donor site is typically covered by regrown hair. It is impor- Skin Grafting tant to reassure the patient’s parents that if the graft is harvested The best replacement for lost skin is clearly skin itself.The first appropriately, the donor site will not exhibit alopecia and the known report of skin grafting comes from the Sushruta Samhita, recipient site will not grow hair. Generally, however, these sites are an ancient Indian surgical treatise that may date back as far as the sufficient only for the grafting of small wounds. seventh century B.C.This text describes the use of both skin flaps Skin grafts can be applied as sheet (or unmeshed) grafts, or they and grafts for the repair of mutilations of the nose, the ears, and can be meshed at ratios ranging from 1:1 to 4:1 [see 3:7 Surface the lips. The Indian method of grafting was first introduced to Reconstruction Procedures]. Meshing allows the egress of serum and Western medicine by English surgeons, who observed it during blood from wounds, thereby minimizing the risk that hematomas the late 18th century.28 or seromas will form that could compromise graft survival. In It was not until 1804 that successful transplantation of free skin addition, meshed grafts can be expanded or stretched to cover grafts was reported by Baronio of Milan, who successfully grafted larger surface areas. When grafts are meshed at ratios of 3:1 or large pieces of autogenous skin onto different sites on sheep.28 In higher, allograft skin or another biologic dressing can be applied 1869, F. J. C. Guyon and Jacques Reverdin, in a report to the over them to prevent the interstices from becoming desiccated Societe Imperiale de Chirurgie, described the use of a small epi- before they close.20 Because of the lack of dermis in the interstices, dermal graft, which became known as the pinch graft. This tech- widely expanded mesh always scars, takes a long time to close, and nique did not, however, gain wide recognition until 1870, when results in permanent unattractive mesh marks. In our center, wide- successful experiments in skin grafting for the treatment of burn ly spread mesh is never used unless it is grafted onto a dermal tem- patients were performed by George David Pollock.29 In 1872, plate to minimize scarring (see below). Ollier described the use of both full-thickness and split-thickness Sheet grafts should be used on the face, the neck, the hands [see skin grafts and realized the possibility of covering large areas with Figure 10], and, whenever possible, on the forearms and the legs. In such grafts if a satisfactory method of cutting them could be these exposed areas, the superior cosmetic and functional results devised.28 obtainable with sheet grafts make such grafts preferable. Because Currently, a 95% success rate is the standard of care for skin sheet grafts have no interstices, they must be closely monitored and grafting. To achieve this level of success requires adequate wound periodically rolled with a cotton-tipped applicator to drain any fluid bed preparation (see above), careful selection of suitable donor collection. Any serous or bloody blebs that form beneath the graft sites, and appropriate postoperative care. should be incised with a No. 11 scalpel and drained expeditiously. Skin grafts are broadly classified as either full-thickness or split- A common practice known as pie-crusting, which involves making thickness grafts, depending on whether they contain the full thick- incisions in a sheet graft at the time of surgery, actually does not ness of the dermis or a partial thickness [see 3:7 Surface yield much improvement in graft survival, because blebs often form Reconstruction Procedures]. Split-thickness grafts are further catego- in areas without incisions. Use of fibrin sealant at the time of graft- rized as thin, intermediate, or thick, depending on the amount of ing may lower the incidence of blebs.
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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 8 Figure 10 Sheet grafts are the gold standard for skin grafting of the face, the neck, and, whenever possible, the forearms and the legs. This 1-month follow-up demonstrates the aesthetic superiority of sheet grafts. Graft and Donor Site Dressings ally best managed by draining them with a clean pin, reapplying Once the graft is secured in place, a dressing may be applied to the epithelial layer to the wound surface, and covering the site with protect it from shearing, as well as to accelerate closure of meshed adhesive bandages.The bandages can be soaked off in the shower graft interstices. Numerous options for graft dressings exist, to ensure that the adhesive causes no additional injury. including wet dressings and greasy gauze.The use of a nonadher- Inclusion cysts may develop in healed grafts that were placed ent dressing such as Conformant 2 (Smith & Nephew) along with over excised wound beds that still contained a thin layer of dermis an outer antimicrobial wet dressing allows the overlying dressings with adnexal structures. The secretions from the adnexal struc- to be periodically removed without dislodging the graft from the tures collect beneath the skin graft to form the cysts. Inclusion wound bed. Bolsters consisting of cotton and greasy gauze are cysts are treated by unroofing the affected area with a needle. employed to help grafts conform to concave wound surfaces, and A condition known as sponge deformity (so called because the splinting of extremities may be necessary for safe graft immobi- skin looks like a bridge of coral sponge [see Figure 11]) may occur lization, especially over joints. The Vacuum Assisted Closure sys- if a skin graft is placed over a wound that heals underneath the tem (Kinetic Concepts Inc., San Antonio,Texas) is another option graft in multiple small areas, with or without sloughing of the over- for promoting graft healing. Alternatively, an Unna boot can be lying graft.32 Where the graft does not slough, a bridge forms.This placed on both the upper and the lower extremity to immobilize unsightly deformity can be treated by incising the bridges over the the graft and provide vascular support, allowing mobilization of healed tissue with sharp scissors. the extremity in the immediate postoperative period.31 Healed donor sites, skin grafts, and ungrafted burns can also Sheet grafts can be either left open to the air to allow continu- break down as a result of infection—a process referred to as melt- ous monitoring and rolling (depending on the patient) or wrapped ing. Such melting can occur quite rapidly: a graft or healed wound with dry dressings, which can be removed if necessary to allow that demonstrates complete take one day may exhibit significant interval inspection and deblebbing. breakdown the next day.Wound cultures should be obtained from There are also various options for donor-site dressings. The these areas, and the open sites should be treated with topical antibi- ideal donor-site dressing would not only minimize pain and infec- otic ointment and, if the problem worsens, systemic antibiotics. tion but also be cost-effective. Greasy gauze and Acticoat are often Malignant degeneration can occur in healed burn wounds employed for this purpose. Typically, these dressings are left in decades after the initial injury.These tumors—known as Marjolin place until the donor site reepithelializes, at which time the dress- ulcers—are usually squamous cell carcinomas and are more ing is easily separated from the healed wound. Op-Site, a trans- aggressive than typical skin cancers.33 Marjolin ulcers have a high parent polyvinyl adherent film, is also commonly used. With Op- metastatic potential and are associated with a high mortality. New Site, the underlying wound is easily examined without removal of or chronic ulcers in burn wounds should raise the suspicion of the dressing; however, intermittent drainage of the wound fluid malignancy and be considered an indication for biopsy. that accumulates is necessary. Op-Site does not work well over joint surfaces and concave or convex areas (e.g., the back). Silver BIOLOGIC DRESSINGS AND SKIN SUBSTITUTES sulfadiazine in a diaper is an excellent covering for buttock donor As noted [see Early Excision and Grafting, above], conventional sites in children; dressing changes can be done with each diaper burn wound management dictates early, aggressive excision of change. burn wound eschar to minimize the chances of sepsis or progres- sion of burn wound depth.15,17,34-36 In some cases, the body sur- Postoperative Wound Care face area to be excised is larger than can be covered by autografts Even with complete graft take and timely donor-site reepithe- from the available donor sites.The solution is to strategically select lialization, several wound management issues may still arise in the areas for autograft coverage and then temporarily cover the early postoperative period. Physical therapy and scar management remaining open areas with biologic dressings. Donor sites typical- are discussed in more detail elsewhere [see 7:17 Rehabilitation of the ly reepithelialize within about 2 weeks, after which time they can Burn Patient]. Blisters are common on newly healed donor sites be reharvested, allowing temporary dressings to be serially and ungrafted wounds. The new epithelial layer of these wounds removed and covered with new autograft.37 lacks the connections to the underlying wound bed normally pro- Biologic dressings perform several important functions. By vided by the BMZ, which protect the epidermis from shearing. adhering to the wound bed, they provide a physical covering that During the months it takes for these structures to reconstitute, controls water vapor transmission, thus minimizing loss of water, their absence frequently leads to blistering.These blisters are usu- electrolytes, and proteins and preventing desiccation and macera-
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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 9 tion of wounded tissue (which can lead to extension of the depth definitive closure of large burn wounds.11 In 1985, Heck and asso- of injury). In addition, biologic dressings help prevent microbial ciates constructed the first deliberate combination of allogeneic invasion from the environment.38 dermis with autologous epidermis.36 This basic idea was subse- quently expanded on by Cuono and colleagues, who used cryo- Allograft and Xenograft Skin preserved allogeneic dermis as a bed for autologous keratinocyte Although the technique of skin grafting is thousands of years cultures.45,46 These investigators demonstrated long-term survival old, skin grafting between individuals was not reported until the and documented the reconstitution of a normal-appearing BMZ late 19th century. In 1869, Reverdin published a report on the with anchoring fibrils. transplantation of small epidermal grafts from his own arm onto a Use of allograft skin as a temporary cover or as the permanent patient’s burn wound.28 In 1881, Girdner described transplanta- dermal replacement in the composite technique does have several tion of skin grafts from a cadaver to a burn patient and reported a drawbacks, including the limited availability of suitable skin, the 75% immediate take rate. It was widely noted that these grafts ini- variable quality of the skin obtained, the substantial cost of allograft tially performed well but survived for only 6 to 8 weeks.28 The procurement and preservation, and the significant potential for dis- mechanisms underlying the rejection of these grafts were eventu- ease transmission.47 In addition, the cryopreservation process sig- ally elucidated by the efforts of Sir Peter Medawar, who received nificantly compromises the viability, and therefore the efficacy, of the Nobel Prize in 1960 for his seminal work on defining the basis the allograft.38 of allograft rejection and tolerance induction. Xenografts from a number of species have also been used as The use of allograft was popularized by James Barrett Brown in biologic dressings. Porcine xenograft has been used in the man- the 1940s and 1950s,39 and with the subsequent development of agement of exfoliative skin disorders (e.g., toxic epidermal necrol- skin banking, allograft became the standard temporary graft for ysis) as well as for temporary wound coverage after excision and excised burn wounds when sufficient autograft is unavailable or before definitive autografting.48 autografting is not indicated.40 Since the 1980s, research efforts have focused on the develop- Ultimately, allograft skin is always rejected unless the donor and ment of skin replacements that could serve as either a temporary the recipient are immunologically identical. The rejection process or a permanent substitute for human skin. Conceptually, any skin usually begins within 10 days in an immunologically competent replacement must recapitulate the native skin biology—that is, it host, but allografts can be tolerated for up to 1 month in a host must include an epidermal component, a dermal component, and who is severely immunocompromised (e.g., as a result of extensive a BMZ equivalent linking the two. burn injury).9,41 The use of immunosuppressive agents such as cyclosporine has led to the achievement of prolonged allograft tol- Cultured Epidermal Autografts erance,14,42-44 but it also exposes the burn patient to the risks inher- Replacement of the epidermis alone was successfully accom- ent in prolonged systemic immunosuppression. plished in the 1970s with the development of cultured epidermal In addition to providing temporary wound closure, allograft has autografts (CEAs). In 1975, Rheinwald and Green reported the been used as an overlay for meshed autograft with the aim of accelerating epithelialization of the interstices. Allograft has also successful isolation and culture of epidermal keratinocytes,49 and been used to cover donor sites after autograft harvesting and to several years later, O’Connor and coworkers reported the first cover wounds after excision as a means of assessing the suitability clinical use of CEAs to cover burn wounds.9 In 1984, Gallico and of a bed for autograft placement.15 associates described the use of CEAs to resurface the burn Recognition of the weaker immunogenicity of the dermal layer wounds of two children who had sustained injuries over 95% of of cadaver allograft stimulated various attempts to employ allo- their TBSA.29 CEAs are grown in the laboratory from a biopsy of graft for permanent dermal replacement. Jackson was the first to the patient’s own skin. A current example is Epicel (Genzyme report the use of alternating strips of autograft and allograft for Biosurgery, Cambridge, Massachusetts), which is approved by the Food and Drug Administration for use in the United States. CEAs are most commonly applied to the granulation tissue of chronic wound beds. As more clinical experience with CEAs was amassed, the drawbacks of using epidermal components alone to replace full-thickness skin loss became evident.50-54 The lack of a dermal component made the CEAs extremely fragile and led to high rates of sloughing and infection. Even when CEA engraft- ment occurred, the BMZ structures critical to graft durability were poorly reconstructed.54 Compton and coworkers compared the outcome of wounds covered with CEAs alone with the outcome of wounds covered first with allograft dermis and then with CEAs. They found that in wounds containing the allograft dermal com- ponent, there was greater initial take, better long-term durability, and accelerated formation of important BMZ structures.55 It is now well recognized that CEAs are capable of replacing the epi- dermis but are not effective when used alone to resurface deep partial-thickness and full-thickness wounds. In vitro development of an epidermal replacement was made Figure 11 Sponge deformity can occur if a skin graft is placed possible by the simpler biology of the epidermis. Development of over a wound that heals beneath without sloughing of the overly- a dermal replacement has proved a more formidable challenge. ing graft. Arrows depict the bridge of skin graft (a) that forms Dermis consists mainly of extracellular matrix, and its complex over healed skin (b). structure is not amenable to growth in culture.
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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 10 a b Figure 12 A bilaminar skin substitute is placed on the excised burn wound (a) and secured with staples. The skin substitute typically vascularizes in 2 weeks, at which point the Silastic outer layer is removed (b) and the neodermis can be autografted. Skin Substitutes thicker the autograft, the lower the take rates.44,63 Alloderm has The drawbacks of allograft and xenograft skin have further also been used for abdominal wall reconstruction and for soft tis- underscored the need for an off-the-shelf dermal replacement. A sue augmentation in the face.64 pioneering approach to the development of a skin replacement A product known as TransCyte (Smith & Nephew)—formerly containing both an epidermal and a dermal component was Dermagraft-TC—is approved by the FDA as a temporary (as described by Yannis and Burke in the early 1980s.56-59 Recognizing opposed to permanent) cover for full-thickness wounds after exci- the importance of the dermis in skin replacement, they developed sion.TransCyte is produced by seeding neonatal fibroblasts isolat- a bilayer construct that is now commercially available under the ed from foreskin onto Biobrane, a synthetic dressing consisting of name Integra (Integra LifeSciences Corporation, Plainsboro, New Silastic attached to a nylon mesh, which is coated with porcine Jersey). The epidermal component of this construct consists of a peptides prepared from type I collagen. The Silastic layer of layer of Silastic film, which acts as a protective barrier against infec- Biobrane serves as a temporary impermeable barrier, whereas the tion and evaporation from the wound bed; the dermal layer consists fibroblast-impregnated nylon mesh serves as a dermal compo- of a porous matrix of fibers composed of cross-linked bovine colla- nent.65 TransCyte is placed on an excised wound bed; when clini- gen and a single type of GAG (chondroitin-6-sulfate). Integra can cally indicated, it is removed and replaced with split-thickness be placed on a completely excised, noninfected wound bed. Initial autograft. TransCyte has been found to be statistically equivalent studies indicated that a neodermis forms, created by the ingrowth to cryopreserved human allograft skin with respect to adherence of fibroblasts and endothelial cells into the dermal matrix template to the wound bed, fluid accumulation, and ease of removal.66 It provided by the Integra. Once this neodermis forms and the der- has also been used as a dressing for partial-thickness wounds, mal scaffold is well incorporated into the wound (typically, after 14 including donor sites.67,68 days), the Silastic component is removed. A thin (0.006 in.) split- Dermagraft (Smith & Nephew), in contrast, is employed as a thickness autograft is then placed on the neodermis [see Figure permanent dermal replacement. Dermagraft consists of human 12].56,60 Integra not only is a useful adjunct in the management of neonatal fibroblasts seeded onto an absorbable polyglactin mesh large burn wounds but also can play an important role in the man- scaffold, which is intended to mimic the native dermal architec- agement of hand and facial burns requiring excision and grafting.61 ture.35,69 It is approved by the FDA for treatment of venous stasis It must be emphasized, however, that for Integra to vascularize ulcers, but it was developed for coverage of excised burn wounds completely, it must be applied to a viable, noninfected wound bed. in conjunction with a split-thickness autograft. In addition, meticulous surgical technique and appropriate postop- Although a permanent off-the-shelf skin replacement has yet to erative care are critical for a successful outcome.62 be developed, the available products have already significantly Another product marketed for dermal replacement is Alloderm influenced the management of burn wounds. In addition, the (LifeCell, Branchburg, New Jersey), which is an acellular dermal shortcomings of each product and strategy have improved our matrix produced from human cadaveric skin. The cadaveric skin understanding of skin biology and physiology and confirmed the is first stored in normal saline for 15 hours to remove the epider- importance of both the epidermis and the dermis in the structure mal component. The cadaveric dermis is then incubated in sodi- and function of skin. One group has combined keratinocytes genet- um dodecyl sulfate to extract any remaining cellular components. ically modified to overproduce vascular endothelial growth factor The decellularized substrate is freeze-dried and reconstituted by with a fibroblast-collagen-GAG biopolymer matrix to accelerate soaking it in crystalloid solution before use.44 Alloderm can be the vascularization of these constructs and improve the overall heal- used for immediate wound coverage in combination with a thin ing of wounds covered with them.70 This approach addresses the split-thickness autograft. Data from multicenter trials indicate that shortcomings of using CEAs alone and the absence of an epider- Alloderm works best with thin (0.006–0.008 in.) autografts: the mal component in the currently available dermal substitutes.
11.
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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 11 References 1. Cuono CB: Skin replacements in severe burn 24. Yamamoto H, Siltharm S, deSerres S, et al: 45. Cuono CB, Langdon R, Birchall N, et al: injury: biologic requirements and therapeutic Immediate burn wound excision restores anti- Composite autologous-allogeneic skin replace- approaches. Prespect Plast Surg 2:123, 1988 body synthesis to bacterial antigen. J Surg Res ment: development and clinical application. 2. Antonelli A, D’Amore PA: Density-dependent 63:157, 1996 Plast Reconstr Surg 80:626, 1987 expression of hyaluronic acid binding to vascular 25. Demling R, LaLonde C: Early burn excision 46. Cuono CB, Langdon R, McGuire J: Use of cul- cells in vitro. Microvasc Res 41:239, 1991 attenuates the postburn lung and systemic tured epidermal autografts and dermal allografts 3. Faham S, Hileman RE, Fromm JR, et al: response to endotoxin. Surgery 108:28, 1990 as skin replacement after burn injury. Lancet Heparin structure and interactions with basic 26. Monafo W: Tangential excision. Clin Plast Surg 1:1123, 1986 fibroblast growth factor. Science 271:1116, 1996 1:591, 1974 47. Monafo WW, Tandon SN, Bradley RE, et al: 4. Jackson D: The diagnosis of the depth of burn- 27. Monafo W, Auelenbacher C, Papplardo C: Early Bacterial contamination of skin used as a biolog- ing. Br J Surg 40:588, 1953 tangential excision of the eschars of major burns. ic dressing: a potential hazard. JAMA 235:1248, Arch Surg 104:503, 1972 1976 5. Heimbach D, Mann R, Engrav L: Evaluation of the burn wound management decisions. Total 28. Bollinger RR, Delford LS: Transplantation. 48. Heimbach DM, Engrav LH, Marvin J, et al: Burn Care, 2nd ed. WB Saunders Co, New York, Textbook of Surgery, 14th ed. Sabiston DC, Ed. Toxic epidermal necrolysis: a step forward in 2002 WB Saunders Co, Philadelphia, 1991 treatment. JAMA 257:2171, 1987 6. 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Drost A, Burleson D, Cioffi W, et al: Plasma cytokines following thermal injury and their rela- 31. Nakamura DY, Gibran NS, Mann R, et al: The 51. McAree KG, Klein RL, Boeckman CR: The use tionship with patient mortality, burn size, and Unna’s sleeve: an effective postoperative dressing of cultured epithelial autografts in the wound time postburn. J Trauma 35:335, 1993 for pediatric arm burns. J Burn Care Rehabil care of severely burned patients. J Pediatr Surg 19:349, 1998 28:166, 1993 9. O’Connor BE, Mulliken JB, Banks-Schlagel S, et al: Grafting of burns with cultured epithelium 32. Engrav LH, Gottlieb JR,Walkingshaw MD, et al: 52. Rue LW, Cioffi WG, McManus WF, et al:Wound prepared from autologous epidermal grafts. The “sponge deformity” after tangential excision closure and outcome in extensively burned Lancet 1:75, 1981 and grafting of burns. Plast Reconstr Surg patients treated with cultured autologous ker- 83:468, 1989 atinocytes. J Trauma 34:662, 1993 10. 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Inc. All rights reserved. ACS Surgery: Principles and Practice 7 TRAUMA AND THERMAL INJURY 15 MANAGEMENT OF THE BURN WOUNS — 12 ment composed of human fibroblast cultured in compared with cryopreserved human cadaver skin 70. Supp DM, Boyce ST: Overexpression of vascu- Biobrane, a synthetic dressing material. Surgery for temporary coverage of excised burn wounds. J lar endothelial growth factor accelerates early 115:633, 1995 Burn Care Rehabil 18:43, 1997 vascularization and improves healing of geneti- 66. Purdue GF, Hunt JL, Still JM, et al: A multicen- 68. Hansbrough J: Dermagraft-TC for partial thick- cally modified cultured skin substitutes. J Burn ter trial of a biosynthetic skin replacement, ness burns: a clinical evaluation. J Burn Care Care Rehabil 23:10, 2002 Dermagraft-TC, compared with cryopreserved Rehabil 18:24S, 1997 human cadaver skin for temporary coverage. J 69. Hansbrough JF, Dore C, Hansbrough W: Burn Care Rehabil 18:52, 1997 Acknowledgments Clinical trials of a living dermal tissue replace- 67. Hansbrough JF, Mozingo DW, Kealey P, et al: ment placed beneath meshed, split-thickness Clinical trials of a bio-synthetic temporary skin skin grafts on excised burn wounds. J Burn Care Figure 1 Tom Moore. replacement, Dermagraft-Transitional Covering, Rehabil 13:519, 1992 Figure 2 Seward Hung.