The use of a bioactive skin substitute decreases length of stay for pediatric burn patients

The use of a bioactive skin substitute decreases length of stay for pediatric burn patients

The Use of a Bioactive Skin Substitute Decreases Length of Stay for Pediatric Burn Patients By Jeffrey R. Lukish, Martin R. Eichelberger, Kurt D. Newm...

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The Use of a Bioactive Skin Substitute Decreases Length of Stay for Pediatric Burn Patients By Jeffrey R. Lukish, Martin R. Eichelberger, Kurt D. Newman, Maryland Pao, Kerilyn Nobuhara, Maryam Keating, Naomi Golonka, Geraldine Pratsch, Vinita Misra, Eric Valladares, Patricia Johnson, James C. Gilbert, David M. Powell, and Gary E. Hartman Washington, DC

Background: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA). This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children. Methods: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n ⫽ 20). These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy. Standard therapy consisted of application of antimicrobial ointments and hydrodebridement. The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS. Data were analyzed using the student’s t test. Results: Data for age, percent TBSA burn and LOS are reported as means ⫾ SEM. The children who received standard therapy were 2.99 ⫾ 0.7 years compared with those receiving TransCyte were 3.1 ⫾ 0.8 years. There was no difference

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ARE OF CHILDREN with burns is among the most resource intensive of all pediatric trauma care.1 Conventional pediatric burn care involves dressing changes twice daily in which the burn is cleansed, a topical antibiotic ointment is applied, and the wound is dressed with sterile gauze, until the wound has healed or needs a skin graft.2 Because of the challenges of pediatric burn wound care including both pain control and the frequent cleansing to avoid infection, most children require hospital care. Herndon et al3 report that one half of From the Department of Pediatric Surgery, Children’s National Medical Center, Washington, DC. Presented at the 2000 Annual Meeting of the Section on Surgery of the American Academy of Pediatrics, Chicago, Illinois, October 28November 1, 2000. Address reprint requests to Martin R. Eichelberger, MD, Professor of Surgery and Pediatrics, George Washington University, Department of Pediatric Surgery, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC 20010. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3608-0003$35.00/0 doi:10.1053/jpsu.2001.25678 1118

between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 ⫾ 1.4% TBSA versus TransCyte, 12.7 ⫾ 1.3% TBSA. There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group. Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%). Children treated with TransCyte had a statistically6 significant decreaed LOS compared with those receiving standard therapy, 5.9 ⫾ 0.9 days versus 13.8 ⫾ 2.2 days, respectively (P ⫽ .002).

Conclusions: This is the first study using TransCyte in children. The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS. This new approach to pediatric burn care is effective and improves the quality of care for children with burns. J Pediatr Surg 36:1118-1121. Copyright © 2001 by W.B. Saunders Company. INDEX WORDS: Pediatric burns, TransCyte, wound care, bioactive skin substitute.

all burned children will require hospitalization for up to 1 month, 25% will require 2 months, and 25% will require 3 months or more.3 The current pressures and trends in health care financing have created a heightened need for effective and cost-efficient treatment of pediatric burns. Early wound closure of partial-thickness burns in children by an occlusive dressing or an adherent skin substitute has been reported in adult patients to increase the rate of healing, while also decreasing pain and improving function.2,4,5 This form of wound care is a practical alternative to standard hospital burn wound care in children. TransCyte (Advanced Tissue Sciences, La Jolla, CA), a bioactive skin substitute, recently has been shown to heal burns in adults more rapidly and with less scarring compared with conventional burn wound care.6,7 The need for local wound care is decreased greatly using these biological materials; therefore, associated pain, time requirements, and costs of patient care are reduced. This study was designed to determine if the use of TransCyte is safe, efficacious, and decreases hospital Journal of Pediatric Surgery, Vol 36, No 8 (August), 2001: pp 1118-1121

BIOACTIVE SKIN SUBSTITUTE FOR BURN MANAGEMENT

Fig 1. Diagram represents application of Transcyte on dermal elements. Superficial layer is nylon mesh, which is bonded to the underlying layer, a polymer membrane containing fibroblasts and a variety of biologically active proteins.

length of stay (LOS) compared with conventional burn management in children. MATERIALS AND METHODS The cases of all children who were admitted to the regional pediatric burn center at Children’s National Medical Center from June 1999 to March 2000, with burns covering more than 7% total body surface area (TBSA) and whose burns did not affect the hands were reviewed. Burn size was estimated using the Lund and Browder forms, with designations for children in 4 age categories.3 Children who had full-thickness burns at presentation and those who had chronic diseases that might affect the healing process, such as white blood cell deficiency, were excluded from the study. All patients underwent burn wound debridement of nonviable tissue at admission using systemic and topical analgesia. No tangential excision was performed. Standard therapy consisted of twice-a-day hydrodebridement with application of silver sulfadiazine to the burn wound followed by a sterile gauze dressing. TransCyte is a bioactive skin substitute consisting of a polymer membrane with newborn human fibroblast cells cultured under aseptic conditions in vitro on a nylon mesh. The nylon mesh is bonded to the polymer membrane, which provides a translucent synthetic epidermis when applied (Fig 1).8 The children who underwent burn wound

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Fig 2. Bar graph represents length of inpatient hospitalization in days (LOS) for children treated with transcyte versus standard therapy groups. Note the statistically significant difference in LOS between the 2 groups (P ⴝ .002).

coverage with TransCyte were treated according to the following protocol. During the first 24 hours the children underwent standard burn wound management. On postburn day 1 they were taken to the operating room and underwent general anesthesia to guarantee a clean environment and to permit precise application of the TransCyte. All children received antibacterial prophylaxis, which was continued for 48 hours postoperatively. The burn wounds underwent blunt debridement with betadine soaked gauze, followed by sterile preparation and drape. Before application of TransCyte, all betadine preparation was cleansed from the burn wound using sterile normal saline. The appropriate amount of TransCyte was thawed at 37°C while still in the sealed containers. After removal from the container, TransCyte was applied to the burn wound and secured into place with suture strips (PROXISTRIP; Ethicon, Johnson & Johnson, Somerville, NJ). The TransCyte burn wound was further immobilized with Exu-Dry dressing (Smith & Nephew, Largo, FL), gauze wrapping, and splints when appropriate. The children underwent burn wound dressing change on postoperative days 2 and 4, then every week until the TransCyte nylon carrier sloughed from the wound. The children were not permitted to wet the TransCyte until the carrier sloughed, this usually occurred between postoperative days 19 to 22. After carrier slough, the remainder of the burn wound care rehabilitation continued according to standard guidelines.3 This protocol was approved by the institutional review board.

Fig 3. (A) Child with a 12% TBSA scald burn. (B) Same child, 1 week status post TransCyte application. (C) Same child, 5 weeks status post-TransCyte application.

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Fig 4. (A) Intraoperative photo of a child with a 35% scald burn after burn wound cleaning, sterile preparation and drape. (B) Same child, 1 week postoperatively with TransCyte adherent to burn wound. (C) Same child, 7 weeks status post-TransCyte application.

The following data were obtained: mechanism of burn injury, age, size of the burn wound, requirement of autograft, and LOS. LOS data were analyzed using the Student’s t test.

RESULTS

The cases of 40 children who met our enrollment criteria were reviewed. Twenty consecutive burns from October 1999 to March 2000 that underwent TransCyte application were compared with 20 consecutive burns from June 1999 to October 1999 that underwent conventional burn wound management. There were no significant differences between the 2 groups with respect to age, percent TBSA, and mechanism of burn. None of the children in the standard therapy group exhibited signs of infection during the dressing changes. Seven children in this group required eventual autograft for wound coverage. One child in the TransCyte group was readmitted after a 5-day hospitalization with TransCyte slough and burn wound cellulitis. This child eventually underwent an autograft. The readmisson days were not included in this child’s LOS analysis (Table 1). The TransCyte group LOS was significantly different from those children who underwent standard treatment: a 50% reduction in length of stay (5.9 ⫾ 0.9 days v 13.8 ⫾ 2.2 days, respectively; P ⫽ .002; Fig 2).

DISCUSSION

The goal of burn therapy in children is to prevent infection, limit pain, decrease metabolic demand, promote healing, and minimize disability. The majority of US burn centers, including Children’s National Medical Center, use silver sulfadiazine ointment to control wound infection. It is the removal of this ointment as well as the adhesion of cotton dressings that are the principal sources of pain during dressing changes. In children, this type of burn care is nursing intensive often requiring intravenous narcotics and sedatives, which usually lead to increased LOS. The use of a biologic wound covering in pediatric burns reduces dressing changes and minimizes all components of standard burn therapy. By protecting the wound and by promoting healing, a biologic dressing may accelerate healing and decrease the development of hypertrophic scar. The use of TransCyte as a biologic wound dressing is effective and increases healing compared with standard burn therapy in adults.6,7 The goal of this study was to evaluate the efficacy of TransCyte and determine if a concomitant decrease in LOS occurs. Children who underwent Transcyte had a statistically significant decrease in LOS when compared with a sim-

Table 1. Standard Burn Therapy Versus Application of Transcyte

Standard therapy Transcyte

Scald Mechanism

Age (yr)

% TBSA Burn

Autograft

LOS*

70% (14 of 20) 90% (18 of 20)

2.99 ⫾ 0.7 3.1 ⫾ 0.8

14.3 ⫾ 1.4 12.7 ⫾ 1.3

35% (7 of 20) 5% (1 of 20)

13.8 ⫾ 2.2 5.9 ⫾ 0.9*

Note. N ⫽ 20 children in each group. All data reported in terms of means ⫾ SEM. Scald mechanism represents percentage of each group whose injury was secondary to liquid scald. Percent TBSA burn represents total body surface area of burn as calculated with Lund Browder Chart for each group. Autograft represents percentage of each group who underwent split thickness skin grafting. LOS represents length of inpatient hospitalization in days. *P ⫽ .002

BIOACTIVE SKIN SUBSTITUTE FOR BURN MANAGEMENT

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ilar group of children who underwent standard burn wound therapy. The principal limitation of this analysis is the use of historical controls and the lack of treatment randomization. Because LOS in the standard burn therapy group was equivalent to the reported LOS of 801 children with similar burns in the 1990s (13.8 days v 13.1 days, respectively),1 we felt its use as a control group was justified. A randomized study, however, could have removed the potential for treatment bias in this study. Although, there were no unexpected adverse outcomes from the use of Transcyte in our patients, 1 child who underwent Transcyte and was discharged on postoperative day 5, did return on day 8 with burn wound cellulitis. Even if her readmission LOS was included in our analysis (total LOS, 20 days), the LOS difference between the Transcyte and standard therapy groups remained significant (P ⫽ .007, mean LOS, 6.65 ⫾ 1.16 days). She underwent standard therapy and eventually required autograft. As a result of this experience we have found that TransCyte may not adhere well to deeper burns. We still recommend the use of TransCyte on these types of burns for several reasons. First, the fibroblasts on Transcyte deliver a variety of biologically active human proteins (collagens, fibronectin, tenascin, proteoglycans, and glycosaminoglycans)8-10 that stimulate angiogenesis and fibroblast ingrowth. In this milieu, epithelial migration from the remaining epithelial cells of deep partial and

from the peripheral epithelial cells in full-thickness burns may occur. This serves to reduce the area of full-thickness burn and may reduce the need for a subsequent autograft. Those children who received TransCyte were less likely to undergo an autograft than those treated with standard burn therapy (1 v. 7 children, respectively). Second, the use of TransCyte early in the course of a significant burn may serve to seal the wound, minimize insensible loss, and reduce pain. Transcyte benefits children by decreasing LOS and permitting outpatient care. Transcyte appears to decrease pain and the need for an autograft. A rapid return to the child’s home environment may result in fewer nosocomial infections, improved nutritional status, and a favorable psychosocial situation. The economic benefit of the use of TransCyte at our institution certainly is significant. The cost saving observed in this study exceeds previous economic models of TransCyte usage.11 Additionally, since the initiation of our Transcyte protocol, we have found that care of pediatric burns requires less direct nursing care. This factor allows for more efficient and better manpower usage, which leads to improved morale and quality care. Transcyte represents a significant advance in the treatment of pediatric burns (Figs 3 and 4). This bioactive skin substitue is an effective burn treatment that reduces inpatient LOS and appears to improve outcomes for children with burns.

REFERENCES 1. Peclet MH, Newman KD, Eichelberger MD, et al: Patterns of injury in children. J Pediatr Surg 25:85-91, 1990 2. Gotschall CS, Morrison MI, Eichelberger MD: Prospective, randomized study of the efficacy of mepital on children with partial thickness scalds. J Burn Care Rehab 19: 279-83, 1998 3. Herndon DN, Rutan RL, Alison WE, et al: Management of burn injuries, in Eichelberger MR (ed): Pediatric Trauma: Prevention, Acute Care, Rehabilitation. Baltimore, MD, Mosby, 1993, pp 568-590 4. Alverez O, Mertz P, Eaglstein RW: The effect of occlusive dressings on collagen synthesis and epithelialization in superficial wounds. J Surg Res 35:142-148, 1983 5. Hinman C, Maibach H: Effect of exposure and occlusion on experimental human skin wounds. Nature 200: 377-378, 1963 6. Noordenbos J, Dore C, Hansbrough JF: Safety and efficacy of transyte for the treatment of partial thickness burns. J Burn Care Rehab 20:275-281, 1999

7. Demling RH, Desanti L: Management of partial thickness facial burns (comparison of topical antibiotics and bio-engineered skin substitutes). Burns 25:256-261, 1999 8. Hansbrough JF, Mozingo DW, Kealey GP, et al: Clinical trials of a biosynthetic temporary skin replacement, dermagraft-TC, compared with cryopreserved human cadaver skin for temporary coverage of excised burn wounds. J Burn Care Rehab 18:43-51, 1997 9. Hansbrough JF, Morgan J, Greenleaf G, et al: Development of a temporary living skin replacement composed of human neonatel fibroblasts cultured in biobrane synthetic dressing material. Surgery 115: 633-644, 1994 10. Landeen LK, Zeigler EC, Halberstadt C, et al: Characterization of a human dermal replacement. Wounds 4:167-175, 1992 11. Parente ST: Estimating the economic cost offsets of using Dermagraft-TC as an alternative to cadaver Allograft in the treatment of graftable burns. J Burn Care Rehab 18: 18-24, 1997