New biological temporary skin cover Xe-Derma® in the treatment of superficial scald burns in children

Results No significant difference in the epithelization time, percentage of conversion from superficial to deep dermal burns and percentage of infectious complication was detected between the two groups. However, patients in the Xe-Derma ® group were burned on a more extensive burn surface area ( p ≤ 0.028). Xe-Derma ® showed adherence to the wound and therefore there has been no need to be changed The number of reapplications and therefore also the number of square centimetres needed for successful healing of 1% BSA were statistically higher in the Askina THINSite ® group ( p < 0.01) due to increased secretion and accumulation of fluid underneath this hydrocoloid cover. The minimal frequency of changes of this biological cover material brings a significant benefit to pediatric patients. Conclusion Acellular pig dermis Xe-Derma ® represents a reliable biological cover material. It is an advantageous alternative to synthetic temporary skin covers in the treatment of superficial scald burns in children. Keywords Biological cover Xenograft Hydrogel Wound healing Scald burns 1 Introduction Partial thickness scald burn wounds represent the most frequent injury in childhood. However, only for the first and third degree burns there exists a clear treatment protocol. The choice of dressing for the second degree burns still remains controversial [1] . Superficial and deep dermal burns have to be differentiated. There are several local and systemic causes of conversion from superficial to deep dermal burn such as impaired blood flow (hypovolemia, collateral or general edema), infection, surface desiccation, surface exudate buildup, mechanical or chemical trauma, septicemia, excess catabolism, comorbidity (diabetes mellitus) [2] . The therapeutic strategy plays a crucial role in wound healing. The main requirements in burn wound management are: readily available dressing or method of cover with easy application that would provide good pain relief, protect the wound from infection, promote healing, prevent heat and fluid loss, be elastic and non-antigenic, and adhere well to the wound while waiting for spontaneous epithelization of dermal burns [1] . Biological covers fulfill most of these functions, but are not always available. In this study we analyzed the effect of dry biological temporary skin cover material Xe-Derma ® (developed in collaboration of the Prague Burn Center, Academy of Sciences of the Czech Republic and Bio-Skin company) in comparison with synthetic hydrogel wound dressing Askina THINSite ® in superficial scald burns in children. 2 Materials and methods Our clinical trial was a prospective study of Xe-Derma ® and Askina THINSite ® use in children suffering from sustained scald burns since October 2007 to September July 2009 and treated in the Prague Burn Centre. 2.1 Eligibility The following inclusion criteria were used: age range was from 5 months to 7 years, etiology of the burn was scald (hot liquid), depth of the injury was superficial, and extent of the burn wound was from 1% to 35% BSA ( Table 1 ). 2.2 Study sample Eighty-six patients fulfilled the inclusion criteria. The group of children treated with Xe-Derma ® (Xe-Derma group) included 43 patients (15 girls, 28 boys). The group of children treated with Askina THINSite ® (Askina group) was of the same composition (43 patients, 15 girls and 28 boys) ( Table 1 ). 2.3 Dressing materials Xe-Derma ® is a dry, sterile, commercially available biological temporary cover material derived from acellular pig dermis. It was developed from xenografts. The final product consists of collagen fibers and fragments of elastic fibers. Hydrated Xe-Derma ® has bio-mechanical properties similar to normal human skin, and therefore it can be used as a temporary replacement for the patient's own skin. Since 2007, we have successfully used Xe-Derma ® in the treatment of superficial and deep dermal burns, donor sites and chronic wounds. Moreover, this cover can protect the burn wound after surgical debridement and maintain the wound clean until autografts are available. We have also applied this acellular porcine dermis as a biological cover to widely meshed skin autografts. Askina THINSite ® is a hydrocellular wound dressing based on a patented dry hydrogel formula providing optimal fluid management, where the dry hydrogel is able to transfer fluid away from the wound, capture it, and eliminate the excess moisture. Askina THINSite ® consists of two layers: hydrogel layer with high absorption capacity and semi-permeable outer layer. Indications of Askina THINSite ® are partial thickness wounds and chronic ulcers. 2.4 Treatment protocol The burn areas were cleaned and all blisters were removed. Swabs were taken for microbiological examination. Xe-Derma ® was hydrated for 2–5 min in sterile water and applied to the burn wound. The dressing was covered with one layer of paraffin meshed gauze and with plain gauze wetted with 3% boracic acid solution. Dry gauze and bandage were used as superficial dressing . No topical or prophylactic antibiotics were used. The first dressing change was performed on the second or third day after admission. When Xe-Derma ® had adhered to the wound, we carefully changed the outer dressing only. Xe-Derma ® was left on the burn surface. The outer dressing was changed every 2 or 3 days, until Xe-Derma ® started to peel off and more than 95% of burn wound were re-epithelized. In case of non-adherence of Xe-Derma ® to the wound surface, microbiological examination was repeated. In case of conversion to deep dermal burns or infection occurrence, Xe-Derma ® was changed for antibacterial cream (Flammazine ® ). Askina THINSite ® was applied to the burn surface after removing blisters and covered with dry plain gauze. When Askina THINSite ® had adhered to the wound, we changed only dry gauze and Askina THINSite ® was left on the surface. In case of secretion from the wound, Askina THINSite ® was removed and reapplied. When the wound was converted to a deep dermal burn, Askina THINSite ® was changed for antibacterial cream (Flammazine ® ). 2.5 Data collection Comparison was made between synthetic temporary wound cover dressing material represented by product Askina THINSite ® and biological temporary skin cover material represented by acellular pig skin dermis Xe-Derma ® . Our data collection comprised: the percentage of body surface area (BSA) covered with synthetic or biological material, the number of conversions from superficial to deep dermal burn, the percentage of covered area converted to deep dermal burn, infectious complications, and epithelization time. Full epithelization time was defined as 95% full epithelization as assessed by a senior burn surgeon after common evaluation with other members of the burn team. We have compared the number of cover material reapplications in both groups and square centimetres of dressing material necessary for successful healing of 1% BSA (in this age group, we determined 1% BSA as 57 cm 2 on average). 2.6 Statistical analysis In our study we used Statistica 8 software from Statsoft. Continuous data were tested for normality of distribution using Shapiro–Wilk test. Most data were not distributed normally ( p < 0.05), and therefore are given as median (lower upper quartile, e.g. 25(15,39), and statistical significance was assessed by non-parametric Mann–Whitney test. Categorical data were evaluated by Fisher's exact test. Additionally, we performed power analysis. Due to the small number of patients enrolled into the study (43 and 43 patients), discrimination can be done only between the groups of 31% and more. p value of ≤0.05 was considered statistically significant. 3 Results Age, burn extent, covered area : Age, burn extent and size of area covered with Xe-Derma ® or Askina THINSite ® are presented in Table 1 . In both groups, age and gender distribution was similar. BSA burned was significantly larger in the Xe-Derma group. Epithelization time ( Table 2 ) in both groups, Xe-Derma and Askina, was not significantly different. However, patients in the Xe-Derma group were burned on a statistically more extensive burn surface area ( p ≤ 0.028). Description of healing : In the group treated with Xe-Derma ® the secretion was unmeasurable, the dressing adhered firmly to the wound and had not to be changed in the course of the treatment ( Table 2 ). It peeled off between postoperative days 6 and 15, revealing neoepithelium with soft and pliable healed skin. In converted areas, Flammazine ® or autografting was used for further treatment. In the group treated with Askina THINSite ® , in 60% of cases (26 out of 43) the cover adhered and was not changed until healing ( Table 2 ). In 40% of cases (17 out of 43) the wound secretion was significant and the wound secretion exceeded the absorption capacity of Askina, the cover floated on the wound bed and had to be changed even several times (two times in 10 cases, three times in 6 cases, four times in 1 case). Askina THINSite ® also peeled off between postoperative days 6 and 15, revealing healed skin underneath. In converted areas, Flammazine ® or autografting was used for further treatment. Complete conversion (conversion of 100% of covered area) from superficial dermal to deep dermal burn wound: In the Xe-Derma group the burn converted completely in one child (infected wound, scalded area 1% TBSA). In the Askina group the burn wound converted completely in four children. This difference was not statistically significant ( Table 2 ). Partial conversion (conversion of less than 100% of covered area): In the Xe-Derma group a part of area covered with Xe-Derma ® converted in 16 patients; in the Askina group partial conversion happened in 18 cases. The difference in the number and extent of converted areas was not statistically significant ( Table 2 ). Infection: During the course of the treatment, infection was proved in six cases of the Xe-Derma group and in 10 cases of the Askina group. The difference was not statistically significant ( Table 2 ). In the Xe-Derma group the most important detected pathogen was Staphylococcus aureus in two cases, Streptococcus agalactiae in one case and Acinetobacter baumannii in one case. In the Askina group, Staphylococcus aureus was found in five cases, Stenotrophomonas mantofila in one case, Enterococcus fecalis in one case, Klebsiella oxytoca in two cases and Proteus mirabilis in one case. Number of reapplications and extent (cm 2 ) of the cover material ( Table 2 ): Significantly remarkable was the difference between the number of dressing changes. Askina THINSite ® had to be changed repeatedly in 17 cases, while Xe-Derma ® had not to be changed at all. The reason for Askina THINSite ® changes was lower adherence due to accumulation of fluids beneath the cover. Significantly higher in the Askina group was also the extent (cm 2 ) of cover material used to reach complete healing of 1% of burn surface. 4 Discussion The temporary skin substitutes can be classified according to their biological activity. Temporary skin substitutes are biological, full synthetic or composite synthetic-biological [3] . In our study we compared two temporary skin cover materials widely used at the Prague Burn Centre in the treatment of scald burns in pediatric population: synthetic hydrocolloid temporary dressing, Askina THINSite ® , and biological temporary skin cover, acellular pig dermis Xe-Derma ® . There is a long tradition (since 1973) in using xenografts for the burn treatment at the Prague Burn Centre. Fresh xenografts were used as a standard dressing for superficial burns and as a temporary cover preparing wound bed for definitive closure after necrectomy [4,5] . Xenografts represent adequate substitutes for skin autografts for the following reasons: similar histological structure compared with human skin, low content of proteolytic enzymes, no capillary ingrowth, and no vessel-to-vessel connections. There is neither immunologic response nor toxicity [6] . There is a distinctive epithelization effect [7–9] and very important effects of pig skin are reduction of heat, liquids, protein and electrolyte losses [8–10] . Many studies have reported pain-relieving effects of pig skin in the patients [10,11] . Xe-Derma ® is produced from xenografts in such a way that the epidermis and all the other cells are enzymatically removed from the porcine skin and the residual matrix is dried and sterilized with radiation—there is therefore no risk of zoonosis transition [6] . We have been using Xe-Derma ® in the burn treatment at the Prague Burn Centre since 2007 [12] . Its dry form makes it available at any time with easy handling and storage. Xe-Derma ® becomes transparent when applied to the wound. Our clinical experience has shown that Xe-Derma ® provides an efficacious adherent biological matrix that reduces pain when applied and stimulates reepithelization. Hydrogels play an important role in moisture control in healing of burn and non-burn wounds. Hydrogel has very high liquid absorption capacity. This important feature provides special advantages to hydrogels when compared with the other dressings: fluid absorption, hydration of the wound bed, cooling of the wound surface, and pain control [13,14] . Askina THINSite ® is a thin, sterile, multilayered, semi-permeable dressing which consists of the following parts: adhesive layer (bonds to the intact skin), hydrogel layer with high absorption capacity and semi-permeable outer layer (vapor permeable and water and bacteria impermeable). Askina ThinSite ® has often been preferred in our clinical use because of safe manipulation and appropriate immediate adhesion to the wound. It has been successfully used at the Prague Bur Centre in more than 100 patients per year. That is why it was chosen as representative of hydrocolloid dressings. There are numerous individual factors influencing both the general condition of the patient and the wound healing. That is why comparing groups of patients in clinical trials is very treacherous in the burn medicine. In our prospective study both compared groups corresponded in the number of patients, age, mechanism of injury, burn depth and localization. In the Xe-Derma group children were burned on a significantly more extensive burn area. In spite of that, no statistical difference was observed in the healing time and percentage of conversion from superficial to deep dermal burn. This indicates higher healing effect of Xe-Derma. In all cases (except conversion) Xe-Derma ® adhered firmly to the wound, the secretion under it was unmeasurable. We suppose that such adhesion was caused by means of firm fibrin collagen junction between the bed and 3D matrix of acellular pig dermis. As Xe-Derma ® had adhered, it was not necessary to change it until it started to peel off spontaneously, which occurred in a 10-day period after application on average. Peeling off was the sign of full epithelization. Xe-Derma ® did not adhere to the wound in areas where conversion took place. In such cases there was accumulation of fluid. Conversion may have been caused by two phenomena: collateral edema surrounding the wound or infection either exogenous, set in by treating staff, or endogenous, originating in the skin adnexa. In patients with proved infection Xe-Derma ® was changed for another product with an antibacterial component (most frequently Flammazine ® ). In contrast to Xe-Derma, which necessitated no change, it was often necessary to change Askina THINSite ® cover repeatedly. The number of reapplications and therefore also the number of square centimeters of Askina THINSite ® required for full healing of 1% burn wound were significantly higher than for Xe-Derma ® . This statistically significant difference can be explained by wound secretion and accumulation of fluids exceeding the absorption capacity of the hydrogel part of Askina THINSite ® cover. This observation is important, as any change of dressing is stressful for children even with analgesic therapy which is indispensable. The necessary reapplication of Askina THINSite ® increases also exposure to infection. The percentage of infectious complications in the Askina group was higher but was not proved to have statistically significant difference by power analysis (difference ≥ 31%). Further statistical identification of this parameter requires multiplication of both groups of patients. From the clinical point of view, an important disadvantage of Askina THINSite ® cover is lacking transparency. Xe-Derma ® is fully transparent and accumulation of fluid under the cover can be easily detected. It is well known that any cover (synthetic or biological) of exposed nerve endings decreases burning pain [8,15] . Our clinical experience has shown that Xe-Derma ® provides an efficacious adherent biological matrix that reduces pain which has been proved by patients reaction. However, in small children the pain is combined with fear. Pain evaluation in toddlers can never be exact, as the response to any discomfort depends upon the level of the family background and upon the individual child. In the study by Hossein et al. [11] superficial dermal scalds were successfully treated with temporary biological cover—lyophilized xenograft Xenoderm. In our clinical practice, we consider as a disadvantage of Xenoderm the protracted (30–60 min) preparation of the product prior to application to the wound. Xe-Derma ® can be wetted only 2–3 min before application. Another disadvantage of Xenoderm is worse transparency, making monitoring of the wound inadequate. In our clinical practice we have also documented that Xenoderm started to dissolve after a couple of days, which may be caused by differing biotechnology of Xenoderm production. The comparative study by Cassidy published in Burns 2005 [16] compared occlusive hydrocolloid cover Duoderm with biosynthetic cover Biobrane in the treatment of superficial burns in children. No significant differences were found in the period of healing and pain. In our next studies we would like to compare biological cover Xe-Derma ® with biosynthetic cover materials. Our second goal is to prove the possibility to culture allogeneic or autologous keratinocytes on Xe-Derma ® for “sandwich” grafting in critical burns [17,18] . 5 Conclusion Our comparative study demonstrated that acellular pig skin dermis Xe-Derma ® provides an effective treatment for second degree scald burns in children. Because of its skin-like consistency and structure it encourages wound healing. Advantageous properties of Xe-Derma ® are excellent adhesiveness, transparency, non-toxicity, elasticity and easy availability, offering multiple clinical use. In comparison with a temporary synthetic cover in pediatric scald burn population, we did not find significant differences in the healing time, percentage of conversion from superficial to deep dermal burn, and percentage of infectious complications. Nevertheless, the group of Xe-Derma ® included children with statistically higher percentage of the burn surface area. The number of reapplications and square centimeters needed for successful healing of 1% BSA was statistically higher in the group of Askina ThinSite ® . Further research in this field is warranted. Conflict of interest All authors of this manuscript hold no financial or personal relationships with other people or organizations that could inappropriately influence their work, all within 3 years of beginning the work submitted. Acknowledgement This work was supported by grant No. NS10507-3 from the Grant Agency of the Ministry of Health of the Czech Republic. References [1] B.S. Atiyeh S.N. Hayek S. William Gunn New technologies for burn wound closure and healing. Review of the literature Burns 31 2005 944 956 [2] Demling RH, DeSanti L. Adapted from www.burnsurgery.com , Surgical Excision & Grafting Management, SECTION VII. [3] I. Jones L. Currie R. Martin Aguide to biological skin substitutes Br J Plast Surg 55 2002 185 193 [4] R. 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