THERAPY IN PRACTICE

Am J Clin Dermatol 2002; 3 (8): 529-534 1175-0561/02/0008-0529/$25.00/0 Adis International Limited. All rights reserved.

Topical Treatment of Pediatric Patients with Burns

A Practical Guide
Tina L. Palmieri and David G. Greenhalgh
Shriners Hospitals for Children Northern California and Department of Surgery, University of California Davis, Sacramento, California, USA

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Evaluation and Treatment of Burn Wounds . . . . . . . . . . . . 1.1 Management of First-Degree Burns . . . . . . . . . . . . . . 1.2 Management of Second-Degree (Partial Thickness) Burns 1.3 Management of Third-Degree (Full Thickness) Burns . . . . 2. Topical Antimicrobial Use After Skin Grafting . . . . . . . . . . . 3. Re-Evaluation of Burn Wounds . . . . . . . . . . . . . . . . . . . 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529 530 530 530 532 533 533 534

Abstract

Over 440 000 children receive medical attention for burn injuries each year in the US. Burn wound infections are a major source of morbidity and mortality in these patients. Infected wounds not only heal more slowly, but also may lead to systemic infections. The factors that contribute to wound complications are both the size and depth of the wound. Burn depth is usually categorized into first-degree (superficial, involving only the epidermis), second-degree (partial thickness, involving both epidermis and dermis), and third-degree (full thickness, through the epidermis, dermis, and into fat). Burns that will not heal within 2 weeks are at least second-degree and should generally be referred to a burn surgeon for possible excision and grafting, due to the increased risk of infection and scarring. The burn wound is dynamic. Proper treatment minimizes the extent of the burn injury, whereas improper treatment (lack of proper wound-care, edema formation, lack of resuscitation) may actually increase the size and/or depth of the wound. Topical antimicrobial agents have been shown to decrease wound-related infections and morbidity in burn wounds when used appropriately. The goal of topical antimicrobial therapy is to control microbial colonization, thus preventing development of invasive infections. A wide variety of agents are available for treatment of burn wounds, including ointments, creams, biological and nonbiological dressings. Topical antimicrobials of choice include bacitracin, neomycin, silver sulfadiazine and mafenide.

Burn injury continues to be a common problem for children. Each year in the US over 440 000 children receive medical attention and 20 000 are admitted to burn units with severe burns.[1] Countless others are evaluated by pediatricians, dermatologists, and emergency room physicians. Burn wound infections continue to be a major source of morbidity and mortality in patients with burns.[2] Loss of the normal skin barrier, as well as disruption of many systemic host defense mechanisms, make burn wounds sus-

ceptible to colonization and infection by multiple endogenous microorganisms. The patient remains vulnerable to invasive infection until the wound has completely epithelialized. Early burn wound closure is important in decreasing the risk of serious burn wound infection. In general, any burn wound that is not healed within 2 weeks has an increased risk of significant scarring, infection, and functional limitation. A burn surgeon should evaluate wounds in this category. Early excision and

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Table I. Guidelines for burn center referral in children Partial thickness burns greater than 10% total body surface area Burns that involve the face, hands feet, genitalia, perineum, and major joints Third-degree burns in any age group Electrical burns including lightning injury Chemical burns Inhalation injury Burn injury in patients with preexisting medical disorders that could complicate management, prolong recovery, or affect mortality Any patients with burns and concomitant trauma (such as fractures, and so on) in which the burn injury poses the greatest risk of morbidity or mortality Burned children in hospitals without qualified personnel or equipment for the care of children Burn injury in patients who will require special social, emotional and/or long-term rehabilitative intervention

1. Evaluation and Treatment of Burn Wounds

1.1 Management of First-Degree Burns

grafting of burn wounds is the standard of care for the treatment of large full thickness burns.[3-6] In addition, second- and thirddegree burns to critical areas, such as the hands, face and feet, should be evaluated promptly by a burn surgeon. The extent of burn injury can be estimated using either the age-specific LundBrowder[7] chart (table I) or by using the patients palm, which represents approximately 1% of their body surface area. The guidelines for burn center referral, established by the American Burn Association, appear in table II.[8] The fundamental initial wound-care for all patients with burn injury is initial cleansing of the wound, removal of nonadherent nonviable tissue, and application of a topical antimicrobial agent. The agent chosen will depend on several factors such as the depth of the wound, the location of the burn, the size of the burn, and the presence or absence of infection. Topical antimicrobial therapy represents an important component of wound-care in patients who are hospitalized, and the choice of topical agent should be made based on a systematic assessment of the burn wound.

First-degree burns involve only the epidermis and are usually red, warm, and painful (figure 1). There is no blistering in the classic first-degree burn. The most common cause of superficial burns is excess exposure to sunlight. Topical antimicrobial therapy is not warranted in this burn because the skin retains its barrier function. Treatment generally involves cleansing of the area and application of a moisturizer. Ointments containing lidocaine (lignocaine) or other topical anesthetics are not indicated, as patients can develop systemic toxicity from excessive absorption of the active ingredients. Analgesia is best obtained with the use of acetaminophen (paracetamol) or nonsteroidal anti-inflammatories. Occasionally, patients will need to be admitted to the hospital for pain control or dehydration due to environmental exposure. Children are especially prone to dehydration in this setting.
1.2 Management of Second-Degree (Partial Thickness) Burns

Partial thickness burns involve both the dermis and the epidermis. The most common cause of second-degree burns in children is contact with hot liquids. Superficial partial thickness burns disrupt the epidermis and the superficial portion of the dermis. They are manifested as painful, red, blistered, and moist areas when blisters are broken (figure 2). Deep partial thickness burns involve deeper layers of the dermis and can present as pale or cherry red wounds that can be either painful or relatively anesthetic (figure 3). These wounds should be cleansed with a mild soap, containing chlorhexidine, and water during the initial management. Using the bath or shower is perfectly acceptable and usually much less cumbersome. If the blister ruptures it should be completely removed, as it becomes a nidus for infection. However, thick intact blisters, especially on the palm or sole, should

Table II. Lund-Bowder chart of body surface area size by age group % Total body surface area head 0-1 year 1-4 years 5-9 years 10-14 years 15 years Adult 19 17 13 11 9 7 neck 2 2 2 2 2 2 anterior trunk 13 13 13 13 13 13 posterior trunk 13 13 13 13 13 13 buttocka 2.5 2.5 2.5 2.5 2.5 2.5 genitalia 1 1 1 1 1 1 upper arma lower arma 4 4 4 4 4 4 3 3 3 3 3 3 handa 2.5 2.5 2.5 2.5 2.5 2.5 thigha 5.5 6.5 8 8.5 9 9.5 lega 5 5 5.5 6 6.5 7 foota 3.5 3.5 3.5 3.5 3.5 3.5

a Represents percentage of body surface area per side, e.g. right upper arm is 4% and left upper arm is 4% of the total body surface area.

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Fig. 1. First-degree (superficial) burn; note the red, but intact, appearance of the skin.

be left alone unless they are markedly raised (>1cm) or encompass a large surface area (i.e. the entire palm or sole of the foot). Thin fragile blisters should be debrided, as they will frequently rupture spontaneously. Topical antimicrobial agents are ineffective when placed on intact blisters and should not be used unless the blister ruptures. In general, wounds should be cleansed at least once, and preferably twice, a day with reapplication of the topical antimicrobial. A wide variety of topical agents can be used in the treatment of second-degree burns after the initial wound debridement. The advantage of topical (as opposed to systemic) antimicrobials is

that they are effective in decreasing the incidence of invasive wound infections. Intravenous antibacterial therapy should be reserved for evidence of an overt wound infection, not in the initial management of the burn injury. Inappropriate use of intravenous antibacterials in the initial management of burn wounds will not be effective and risks selecting for more virulent pathogens later. Thus, topical therapy remains the mainstay of initial burn treatment. Topical antimicrobials do not eradicate skin flora; even noninfected burn wounds will frequently have evidence of bacteria on wound culture. The most frequently used topical antimicrobials in partial thickness burns in children are ointments (bacitracin and neosporin). In general, ointments should be applied thick enough to cover the wound and to keep the wound moist. They should then be covered with a nonadherent dressing, such as Adaptic1 or bismuth impregnated gauze (such as Xeroform) and bulky gauze dressings. Ointments are generally tolerated better than cream by children because they are soothing, easy to apply and clean, and are more occlusive and lubricating than many other preparations. Due to their shorter half-life, dressings containing ointments should be cleansed and changed approximately every 12 hours. Perhaps the most frequently used ointment in second-degree burns in children is bacitracin, which is a polypeptide antibacterial available in a petroleum base. It is effective against Grampositive cocci and bacilli and acts by inhibiting bacterial cell-wall synthesis.[9] Development of resistance to bacitracin is low, and bacitracin promotes wound-healing indirectly by controlling the level of colonization on a wound surface. It may also stimulate polymorphonuclear leukocyte (PMN) function.[10] Systemic hypersensitivity and systemic toxicity are extremely rare. Bacitracin is also commonly used on facial burns in both adults and children. Approximately 43% of burn care facilities use bacitracin in their wound management.[11] Bacitracin, when used on healed burn wounds, tends to promote colonization with yeast, and healed wounds will tend to develop a rash if bacitracin is continued.[11] Thus, it should be discontinued promptly when wounds have epithelialized. Another popular topical antibacterial used in children is neomycin, which is effective against Gram-negative organisms such as Escherichia coli and Enterobacter, as well as Gram-positive organisms. It inhibits bacterial replication by binding to the ribosomal subunit. Bacterial resistance and cutaneous hypersensitivity are more common than with bacitracin, and ototoxicity and nephrotoxicity have occurred after application to large surface
1 Use of tradenames is for product identification purposes only and does not imply endorsement.
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Fig. 2. Superficial second-degree burn. Moist, weeping skin beneath the blister is predominant and these wounds are extremely painful.

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Fig. 3. Deep second-degree burn with somewhat drier skin beneath the blister with a paler appearance, but intact hair follicles at the base.

areas.[11] It is usually mixed with bacitracin or polymixin to decrease the incidence of adverse effects. Silver sulfadiazine may also be used in the treatment of second-degree burns. The advantage of bacitracin and neosporin over silver sulfadiazine is the ease of application and removal of the topical antimicrobial. Silver sulfadiazine leaves a whitish residue, which can be difficult to remove during cleansing. Silver sulfadiazine has also been reported to delay wound-healing in an experimental model.[12] In general, superficial second-degree burns will heal within 2 weeks and will not require grafting. Deep second-degree burns often need grafting if they cover large surface areas or are in key locations, such as the hands, feet and face, and have not healed within 2 weeks.
1.3 Management of Third-Degree (Full Thickness) Burns

Full thickness burn wounds involve destruction of the entire dermis and epidermis. The wounds are characteristically dry and leathery with a tan color (figure 4). The wounds are insensate at the central portion of the wound due to destruction of the sensory nerves to the skin in the area of the burn. The most common etiology of third-degree burns in children is flame injury, although many scald burns will be third-degree as well. Of note, the periphery of the wound, which is usually not as deeply burned, is often quite painful. The majority of full thickness burn wounds will not heal within 14 days. As such, children with full thickness burn wounds should be promptly referred to a burn center for timely excision and grafting of the wound. The topical antimicrobials of choice in the treatment of full thickness burns are creams, including silver sulfadiazine and mafenide. Creams are oil-in-water emulsions that contain more water than oil. Creams are easy to apply, generally soothing, and useful in wounds of various depths, they are ideal for children. After the initial burn wound is cleansed, the creams are applied thick enough so that the underlying wound cannot be visualized and then covered with gauze dressings. The dressings should be
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removed, the wound lightly debrided, and cream reapplied every 12 to 24 hours due to the short half-life of the drug. Creams are subject to drying, and the wound debridement associated with dressing changes is often not tolerated well by children. Nonetheless, creams are the most frequently used topical for full thickness burns. Silver sulfadiazine 1% cream is perhaps the most popular topical agent in use for massive burn wounds in children. It is a topical compound of silver nitrate and sodium sulfadiazine prepared in a 1% water miscible cream. As such, it should not be used in patients with a documented sulfur allergy. Silver sulfadiazine is bactericidal against a wide variety of bacteria ranging from Gram-negative (E. coli, Enterobacter, Pseudomonas), as well as Gram-positive bacteria (Staphylococcus aureus) and some yeasts.[13] Although silver sulfadiazine decreases bacterial colonization, it has been demonstrated to impede wound-healing due to its toxicity to keratinocytes and fibroblasts.[14] Adverse effects include leukopenia and rare cutaneous hypersensitivity reactions. The clinical significance of the leukopenia that sometimes accompanies silver sulfadiazine use is not clear. Care should be taken in the use of this agent on the face, due to potential ocular injury. Due to the risk of kernicterus from the sulfonamide component of the cream, it is not recommended for premature infants, infants less than 2 months of age, or during pregnancy. The cream itself is easy to apply and soothing to patients. Its wide spectrum of activity makes it an attractive agent in the treatment of full thickness burns. Mafenide acetate 0.5% cream is a methylated sulfonamide with bacteriostatic action against most Gram-negative and Grampositive pathogens, but not against yeast. Like silver sulfadiazine, it inhibits keratinocytes and fibroblasts and thus may delay wound-healing, and it also impairs PMN and lymphocyte activ-

Fig. 4. Third-degree burn characterized by leathery appearance and insensate at center.

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ity. Mafenide acetate penetrates eschar much more effectively than other topical agents. As such, it is often used in invasive wound infections and in sites with limited blood supply, such as the ears to prevent chondritis.[13] Disadvantages of mafenide acetate include a cutaneous rash, metabolic acidosis due to carbonic anhydrase inhibition, and pain on application.[11,15] The use of this cream is generally restricted to small full thickness wounds. It is applied approximately every 12 hours due to its short halflife.

3. Re-Evaluation of Burn Wounds The depth of a burn wound can be difficult to determine upon initial evaluation due to a variety of factors, including inadequate debridement, injury extension, pain issues, and development of the burn wound itself over the first 24 to 48 hours. It is exceedingly rare for a burn wound to become infected during this time frame. Re-evaluation of the child with a second-degree burn wound on a daily basis, especially wounds with decreased sensation or blistering, will help to delineate the extent of the burn and facilitate early identification of wound infection. Wound culture results, both quantitative and qualitative, should be clinically correlated. The distinction between wound colonization, which nearly always occurs, and wound infection, which is relatively uncommon, is primarily clinical. Early signs of infection include increased redness, warmth, pain, and swelling of the wound. Early burn wound infections tend to result from Gram-positive organisms, such as Staphylococcus and Streptococcus, which are normal cutaneous flora. Red streaking, extending from the

2. Topical Antimicrobial Use After Skin Grafting Topical antimicrobials are also frequently used after skin grafting to decrease the incidence of graft infection and to keep the wound bed moist, although the use of petroleum products (such as Xeroform) or irrigation with non-antimicrobial agents may be carried out if the grafted bed is clean. The majority of these agents are liquids, as occlusive creams and ointments will impede graft-healing. In general, topical irrigation of graft sites is continued every 2 to 3 hours until the transplanted skin has engrafted, usually in 5 to 7 days. A 5% solution of mafenide acetate, as opposed to the topical cream, is frequently used for postoperative graft site irrigation. It is effective against the same microorganisms as the cream, and, like the cream, can also induce a metabolic acidosis due to carbonic anhydrase inhibition. Patients with large open areas need to be monitored closely for the development of metabolic acidosis. Nystatin is frequently added to the mafenide acetate solution to decrease the incidence of fungal colonization of the graft site. Another popular topical solution for grafts (and patients with sulfa allergies) is 0.5% silver nitrate solution. Silver nitrate is effective against S. aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and some yeasts, but has limited activity against other Gram-negative species. Silver nitrate solution is hypotonic, which causes it to precipitate chloride and leach large quantities of sodium, potassium, and other solutes into the dressings. Electrolytes thus need to be monitored closely when using silver nitrate solution. Another major disadvantage of silver nitrate solution is that it oxidizes on contact with air, permanently staining everything it contacts brown-black. Methemoglobinemia can also occur, but fortunately this complication is extremely rare.[14] Despite these drawbacks, silver nitrate solution can be a valuable topical agent when used in the proper setting. An irrigant containing a mixture of neomycin and polysporin (genitourinary irrigant) is occasionally used for irrigation of grafted burn wounds. It is easy to apply, inexpensive, and readily available. However, this solution has poor Pseudomonas coverage and is of limited use in large burns.
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Fig. 5. (a) Wound colonized by Gram-negative organisms; a greenish exudate is common in colonized burn wounds and does not necessarily connote infection. (b) Wound with invasive Pseudomonas infection; note the purplish hue, edema, and lack of exudate.

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wound, is indicative of a streptococcal infection and mandates immediate therapy with intravenous antibacterials effective against Gram-positive organisms, in addition to topical agents. Gram-negative wound infections tend to predominate after 7 to 10 days of topical therapy in larger full thickness burns. Gram-negative infections are heralded by increased greenish exudate from the wound, high fevers, and pain in the burned areas. Many burn wounds which are colonized, rather than infected, by Gram-negative organisms, will also have a green exudate, as depicted in figure 5. Clinical correlation is required prior to the institution of systemic antibacterials. Topical therapy with silver sulfadiazine or mafenide acetate would be appropriate, in conjunction with systemic antibacterials effective against Gramnegative organisms, in wounds infected by Gram-negative organisms. One of the most aggressive Gram-negative wound infections is invasive Pseudomonas, which is characterized by sudden onset of high fevers, hypotension, wound tenderness, and a classical purplish appearance, as depicted in figure 5. Topical antimicrobials alone are not adequate therapy for this serious burn wound infection. Treatment involves administration of systemic antibacterials, injection of antibacterials into the wound (wound clysis), and wound debridement. Invasive Pseudomonas infection is a surgical emergency and needs to be seen immediately by a surgeon. 4. Conclusion A wide variety of topical agents are available for the treatment of burn wounds. The appropriate choice of topical antimicrobial agent is determined by evaluating of the size, depth, and location of the wound. Wound-cleansing and debridement should precede placement of topical antimicrobial agents, as this alone decreases the incidence of burn wound infection. The most commonly used topical agent for second-degree burns in children is bacitracin due to its easy application and low incidence of adverse effects. Silver sulfadiazine is generally used in deeper burns. Full thickness wounds often require excision and grafting and should be referred to a burn specialist if the wound will not heal within 14 days. Close monitoring of pediatric patients with burns is imperative. Burn wound sepsis can occur rapidly and

result in significant morbidity and mortality if not recognized and treated in a timely fashion. Acknowledgments
The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

References
1. 2. 3. 4. 5. 6. 7. 8. Center for Disease Control. 1990 Mortality Data. Atlanta (GA): Center for Disease Control, 1990 Yurt RW, McManus AT, Mason AD, et al. Increased susceptibility to infection related to extent of burn injury. Arch Surg 1984; 119: 183-8 Hunt JL, Sato RM. Early excision of full thickness hand and digit burns; factors affecting morbidity. J Trauma 1982; 22: 414-9 Wolf SE, Rose JK, Desai MH, et al. Mortality determinants in massive pediatric burns. Ann Surg 1997; 225: 554-69 Herndon DN, Barrow RE, Rutan RL, et al. A comparison of conservative versus early excision therapies in severely burned patients. Ann Surg 1989; 209: 547-52 Sheridan RT, editor. Advanced burn life support provider manual. Chicago (IL): American Burn Association, 2001: 13-23 Lund C, Browder NC. The estimation of areas of burns. Surg Gynecol Obstet 1944; 79: 352-8 Jacobs MR, Zanowiak P. Topical anti-infective products. In: Feldman EG, editor. Handbook of nonprescriptive drugs. 9th ed. Washington, DC: American Pharmaceutical Association, 1990: 779-81 Taddonio TE, Thomson PD, Smith Jr DJ, et al. A survey of wound monitoring and topical antimicrobial therapy practices in the treatment of burn injury. J Burn Care Rehabil 1990; 11: 423-7 Sheth KV, Abdulatiff M, Al-Sedairy S. Effects of bacitracin on the human neutrophil oxidative respiratory burst and chemotaxis. Int J Immunopathol Pharmacol 1993; 6 (1): 43-9 Monafo WW, West MA. Current treatment recommendations for topical burn therapy. Drugs 1990; 40: 364-73 Kaiser W, Von der Lieth H, Potel J, et al. Local application of silver sulfadiazine, cefsulodin and povidone iodine on burns in animals: an experimental study. Infection 1984; 12 (1): 31-5 Lineaweaver W, McMorris S, Soucy D, et al. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg 1985; 75: 394-6 Ward RS, Saffle JR. Topical agents in burn and wound care. Phys Ther 1995; 75: 526-38 Lee JJ, Marvin JA, Heimbach DM, et al. Use of 5% sulfamylon (mafenide) solution after excision and grafting of burns. J Burn Care Rehabil 1988; 9 (6): 602-5

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13. 14. 15.

Correspondence and offprints: Dr Tina L. Palmieri, Shriners Hospitals for Children Northern California, 2425 Stockton Blvd, Suite 718, Sacramento, CA 95817, USA. E-mail: tina.palmieri@ucdmc.ucdavis.edu

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