- Email: [email protected]
glycosaminoglycate skin substitute—six years of experiences with artificial skin in 15 German burn centers
Burns 30 (2004) 471–475
Update on the use of collagen/glycosaminoglycate skin substitute—six years of experiences with artificial skin in 15 German burn centers夽 A. Heitland, A. Piatkowski∗ , E.M. Noah, N. Pallua Department of Plastic and Reconstructive Surgery, Burns Unit, RWTH, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany Accepted 1 June 2004
Abstract The clinical use of an artificial skin substitute (Integra® ) has been celebrated enthusiastically as an improvement in burn therapy over a period of more than 10 years. Many case-reports have shown the positive effects of the treatment with Integra® as a skin substitute. In this study we examine the alterations of Integra® -usage in Germany. Fifteen German burn centres have been interviewed respectively over a time period of 6 years with interviews in the years 1999, 2001, and 2003. The goal of this study is to focus on the problems associated with the use of artificial skin and to create a manual for Integra® -therapy including indication, pre-, intra-, and postoperative treatment. Since the first Integra® Users seminar in Germany in 1999 repeated interviews have been conducted with fifteen German burn centres. The collected results of the last 6 years were evaluated. These results show a change in the indication for the therapy with artificial skin towards extensive full thickness burned patients and as extended indication especially for posttraumatic reconstruction. This article gives our guidelines for the usage and handling of Integra® and shows that Integra is an important reconstructive dermal substitute for the severely burned or posttraumatic patient if handled by a skilled surgeon in a correct way. © 2004 Elsevier Ltd and ISBI. All rights reserved. Keywords: Integra; Artificial skin; Soft tissue reconstruction; Retrospective study
1. Introduction Artificial skin (Integra® ) consists of an upper silicone sheet and a lower layer of porous cross-linked bovine collagen and chondroitin-6-sulfate as a template for dermal regeneration. It is a cell free solution for temporary wound closure and produces a well vascularized dermis analogue [1]. Because of the upper silicone sheet it provides a nonpermeable wound closure and therefore a reduction of fluid loss in burned patients. The lower layer, as a dermal substitute, provides a matrix for cell invasion, i.e. fibroblasts or macrophages [2]. The pore size of the cross-linked collagen matrix was therefore adjusted to 70–200 m. After a time period of 14–21 days, a well vascularized neodermis is found beneath the silicone dressing which allows a secondary closure with a thin epidermal autograft as neodermis. Treatment with Integra® was described for the first time in 1981 by Burke and Yannas in the USA [3]. Many differ夽
A. Heitland and A. Piatkowski contributed equally to this paper. Corresponding author. Tel.: +49-241-80-89351; fax: +49-241-80-82448. E-mail address: [email protected] (A. Piatkowski). ∗
0305-4179/$30.00 © 2004 Elsevier Ltd and ISBI. All rights reserved. doi:10.1016/j.burns.2004.01.010
ent case-reports have followed with promising and enthusiastic results, i.e. for reconstruction of huge surface area burns, neck contracture therapy, etc. [4–8]. Introduced as a trigger for fast wound closure in the severely burned patient further extended indications have been described over the last 10 years, i.e. for extremity reconstruction, forehead reconstruction, or reconstruction in combination with cultured keratinocytes [9–12]. Since the approval by the FDA in 1996 followed by the approval of the European Union in 1998 fewer cases have been reported from Europe than from the USA. Nevertheless, all these reports have demonstrated excellent long-term results [13]. The keypoint of the clinical result is the correct application of Integra and the treatment of the wound and wound dressings. This corresponds to a high failure rate at the first cases of Integra® use with a steep and sometimes frustrating learning curve [1]. The correct indication, application, and postoperative treatment of the dermal substitute demand a longtime experience. We are summarizing an overview of the use of Integra in 15 different German burn centers by a descriptive analysis of our questionnaire. In order to give a guideline for Integra® -usage we are concerning the indications, pre-, peri-, and postoperative treatment and the cost effectiveness.
472
A. Heitland et al. / Burns 30 (2004) 471–475
Unfortunately, over the last decades the German system has become more and more restrictive concerning the cost of medical treatment. Such economic pressure requires that therapy with Integra® is used within clearly understood and rational indications and guidelines.
2. Materials Over a period of 6 years, 15 German burn centres with 77 acute burn intensive care beds (including 4 children beds) have been asked, using a standardized questionaire, about their experiences with Integra® . The questionnaire was divided into four topics. The first topic examines the indication for Integra® as well as the influence of the initial trauma, ABSI score, and posttraumatic timing on the use of artificial skin. The second bundle of questions concentrated on the pre-, intra-, and postoperative treatment with Integra® , especially focussing on microbiological testing, the amount of excision of necrotic tissue required, and the application on different wound beds. The postoperative treatment was assessed concerning the wound dressing, the antimicrobiological therapy used, and the microbiological situation in the wound. The interview also contained questions about the method of skin transplantation, i.e. MEEK or Mesh-transplants, and especially the combination of Integra as dermal substitute with autologous keratinocyte cultures as cellular grafts. The long-term treatment was investigated in the third bundle of questions which concerned the use of cremes, compression therapy, and long time histology investigation. The forth topic contained questions about the cost and effectiveness of Integra® during the operation of the DRG (diagnosis related groups) system.
3. Methods The interviews were conducted over two time periods of 24 months in September 1999, 2001, and 2003. The questionnaires were evaluated and summarized descriptively.
4. Results 4.1. Indications The indication for the use of Integra® has changed over the last 6 years. In 1999, Integra® was used for a variety of injuries such as small full thickness burns, unstable scars after burn trauma, or full thickness burns over 50% of total body surface area (TBSA). Over the years, the indications have switched to full thickness burns of over 50–60% TBSA. This narrows the indication of Integra® to a small number of patients in whom
wound closure with split skin grafts cannot be achieved in the early phase of burn care. Recently, a new indication has been described by a small group of burn centres, an increased use in degloving injuries. Promising results have been demonstrated in the cases reported. A smaller change is noted for the contraindications. The key point has been and still whether there is an infection of the wound surface. In early times, it was considered a contraindication to use Integra® after a posttrauma interval longer than 5 days, but this strict indication changed over time. In 1999, only three burn centres described a posttrauma period of more than 5 days as a contraindication, in 2001 only two and in 2003 no single burn center restricted the use of Integra® to this narrow time frame. 4.2. Pre-, peri-, and postoperative treatment The use of preoperative microbiological testing has been constantly described by the majority of the interviewed clinics. In 1999, postoperative microbiological testing was performed by almost all hospitals every second day. Over the years, this practice has changed to a postoperative wound evaluation based on clinical findings. Further, there was a change in the application of Integra® in relation to the cleaned wound bed. In 1999, almost all burn centres recorded the strict and limited use of Integra® following epifascial excision. In 2001 and 2003, half of the burn centres saw the indication for Integra® after both epifascial and tangential excision. Application onto adipose tissue was considered in all clinics as undesirable as well as the use of Integra® following cadaveric allograft application. The wounds were closed by skin staplers with the exception of only one hospital which used sutures as well as staplers. There was no change in the aspect over time. Almost all interviewed hospitals immobilized, the Integra® reconstructed extremities. In 1999, the first wound dressing change of the multilayered wound dressing in all participants was conducted in eight clinics on the first postoperative day (POD). Only one clinic reported a first dressing change after 1 week. These standards changed as well. In 2003, the majority changed the wound dressing on the third POD with only one clinic still performing wound dressing changes at the first POD followed by a daily wound dressing change. We also observed a change in the use of different antimicrobial agents. Argentum nitricum (silver nitrate) (n = 7) was most frequently used in 1999, followed by Lavasept® (polyhexamethylbiguanide, n = 6) and mafenide acetate ( n = 3). The frequency of use for silver nitrate fell over time (2001, n = 5; 2003, n = 3), whereas Lavasept® stayed stable. Over the last years, an increase in the use of Octenisept® is observed (Fig. 1). There was no clear therapy recommendation from any of the burn centres to cope with the difficult case of partial Integra® -loss. Half of the burn centers decided on a reuse of
A. Heitland et al. / Burns 30 (2004) 471–475 Use of Antimicrobial Agents
Percentage of use
60,00%
Percent
50,00% 40,00% 30,00% 20,00% 10,00% 0,00% 1999
Lavasept
2001
AgNi
2003
Mafenid
93,33% 71,43%
1999
2001
2003
4.4. Cost-effectiveness
80,00% 70,00% 60,00% 50,00% 40,00% 30,00% 20,00% 10,00% 0,00% 2001
78,13%
Fig. 3. Chronological use of Integra® in the asked burn centres.
Proceeding in the case of total loss
Reapplication
100,00% 90,00% 80,00% 70,00% 60,00% 50,00% 40,00% 30,00% 20,00% 10,00% 0,00%
Octenisept
Fig. 1. Overview of the applied disinfectants.
1999
473
2003
A decrease in the clinical use of Integra® was noted. In 2001, three of the fifteen burn centres did not use Integra® any more due to uncertain outcome and high costs. This tendency continued in 2003 as four burn centres had not used Integra® in the last 2 years. This means there is a more than 20% decrease in the use of Integra® in German burn centres (Fig. 3).
Therapy change
5. Discussion Fig. 2. Management of complete Integra® loss.
Integra® whereas the other half favored a standard conventional therapy. Interestingly, most of the burn centers favored adding Integra® in the case of a total loss (Fig. 2). Unfortunately, only one clinic interviewed documented the degree of vascularisation using histological methods. All other clinics assessed vascularisation clinically using the color scale depicted in Table 1. All burn centers used the Mesh technique for wound coverage without a change in postoperative treatment. 4.3. Long-term treatment The postoperative long-term treatment basically consists of the same treatment used following skin grafts. The well known postoperative care of daily creme, compression therapy, silicone pads over hypertrophic scars and avoiding sun exposure is the standard recommendation of all burn centers asked. Unfortunately, there are no long-term histological results available on the structure of the neodermis. Table 1 Clinical Integra® evaluation concerning color changes Color
Meaning
Red White Yellow Orange Grey, green, brown Pink, vanilla, peach
Haematin, postoperatively First phase Cell infiltration Neovascularisation Infection Neodermis
The ongoing reduction of artificial skin substitute use reflects two major problems associated with Integra® . These problems are the complicated and very intensive care of the patients treated and the high cost. Many positive reports have been published over recent years concerning the application of Integra® . The long-term outcomes described are positive, in terms of the good structure of the skin and a lower tendency to form hypertrophic scars [14,15]. The treatment phase between application and the skin transplantation 3 weeks later is very problematic. The upper silicone layer protects the excised surface against fluid loss but it also acts as a nonpermeable occlusive wound dressing that cannot be changed easily. A precise inspection of the applied Integra® sheet has to be undertaken every day to ensure a good outcome. This has to be accompanied by repeated microbiological testing and the use of potent antimicrobiological agents such as Lavasept® or silver nitrate. A very promising idea is the use of the silver releasing dressing Actisorb® on the wound edges. Undoubtedly, the most important factor in promoting a positive outcome is a well trained surgeon with experience of Integra® use. The use of Integra® is not easy and the surgeon’s learning curve is steep at the beginning [12,16]. Failures in therapy are therefore most common in the early cases. The high costs of this treatment reveal a problematic financial situation because clinical budgets in Germany are now being reduced. Except for two clinics, all burn centres had to finance Integra® by a so-called “mixed calculation” for their burn patients. This explains the reduced use of this
474
A. Heitland et al. / Burns 30 (2004) 471–475
therapy option. The G-DRG (German Diagnosis Related Groups)-system uses a “mixed calculation”, concluding that expensive treatments that may not be completely funded can only be offered if other DRG-therapies had created a positive financial effect. Therefore unfortunately, the clinical use of Integra® in the burn centres asked has decreased to a narrow field of indications. In our opinion, this financial limitation of Integra® reduces its benefit for many patients. A very promising combination of Integra® is its use in combination with cultivated autologous keratinocytes. Case-reports from the interviewed burn centres as well as cases described in literature present a very good outcome with consistent quality reconstructed skin [11,17]. Especially for severely burned children, this procedure seems to be a promising and important solution. Comparing Integra® to different skin substitutes on the market Integra® is still not as expensive as other products, such as Alloderm® , Dermagraft® , Apligraf® . Only cadaveric allograft represents a cheaper alternative of temporary wound coverage, but without the benefits of a neodermis formation like in the above mentioned products [1]. In summary, we recommend the following guidelines for Integra® .
6. Summarized therapy scheme 1. The main indications are extensive full thickness burns on the trunk and extremities as well as early posttraumatic reconstruction. 2. Preoperative microbiological testing is suggested. 3. Optimal timing for Integra® application is within the first posttraumatic week. 4. A radical debridement must precede the Integra® application. 5. Immobilization is strongly suggested for reconstruction of the extremities with Integra® . 6. A daily wound dressing change should be conducted by an experienced surgeon with special attention paid to the Integra color scheme. 7. Clinical evaluation of vascularisation should replace histological probes. 8. In the case of partial or complete Integra® loss, a reapplication is favored. 9. Skin coverage is achieved by an ultra thin meshed skin transplantation. 10. Postoperative treatment follows the rules for skin transplantation.
7. Conclusion The indications for Integra® are narrowing in the burn sector but are switching simultaneously to the posttraumatic reconstruction sector for example degloving injuries. The use of Integra® demands an experienced surgeon and it has to
be used with great attention to detail and clinical condition of the patient. We are recommending our summarized therapy scheme as mentioned above. Special medical budgets should be negotiated for the use of Integra® with the hospital administration or the health insurance companies in order to provide patients with the optimal care and the newest therapeutical options.
Acknowledgements We wish to thank the participating burn centres in alphabetic order for their repeated work over the years 1999, 2001, and 2003. Klinik für Plastische Chirurgie und Schwerbranntverletzte, Handchirurgiezentrum BG Kliniken Bergmannsheil, Bochum; Klinik für Unfall-, Hand-, und Wiederherstellungschirurgie, Städtische Kliniken Nord Dortmund; BG Unfallklinik Duisburg Abt. für Handchirurgie, Plastische Chirurgie und Branntverletzte; Klinik für Plastische und Handchirurgie/Branntverletztenzentrum BG Kliniken Bregmannstrost Halle/Saale; Klinik und Poliklinik für Kinderchirurgie Halle an der Saale; BG Unfallkrankenhaus Hamburg Abt. für Handchirurgie, Plastische und Mikrochirurgie-Zentrum für Schwerbrandverletzte; Klinik für Plastische Chirurgie, Handchirurgie, Schwerverbranntenzentrum Klinikum Köln Merheim; Städtisches Klinikum Sankt Georg Zentrum für Traumatologie mit Brandverletztenzentrum Leipzig; Plastische Chirurgie, Handchirurgie, Intensiveinheit für Schwerbrandverletzte an der MUL Lübeck; Abt. für Plastische Chirurgie, Handchirurgie, Zentrum für Schwerstbrandverletzte Krankenhaus Bogenhausen München; Abt. für Plastische Chirurgie Fachklinik Hornheide Münster; Klinik für Plastische, Wiederherstellende und Handchirurgie Zentrum für Schwerbrandverletzte Klinikum Süd Nürnberg; Klinik für Unfallchirurgie Marienhospital Stuttgart.
References [1] Jones I, Currie L, Martin R. A guide to biological skin substitutes. Br J Plast Surg 2002;55:185–93. [2] Stern R, McPherson M, Longaker MT. Histologic study of artificial skin used in the treatment of full-thickness thermal injury. J Burn Care Rehabil 1990;11:7–13. [3] Burke JF, Yannas IV, Quinby Jr WC, Bondoc CC, Jung WK. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann Surg 1981;194:413–28. [4] Lorenz C, Petracic A, Hohl HP, Wessel L, Waag KL. Early wound closure and early reconstruction. Experience with a dermal substitute in a child with 60% surface area burn. Burns 1997;23:505–8. [5] Besner GE, Klamar JE. Integra artificial skin as a useful adjunct in the treatment of purpura fulminans. J Burn Care Rehabil 1998;19:324–9. [6] Winfrey ME, Cochran M, Hegarty MT. A new technology in burn therapy: INTEGRA artificial skin. Dimens Crit Care Nurs 1999;18:14–20. [7] Hunt JA, Moisidis E, Haertsch P. Initial experience of Integra in the treatment of post-burn anterior cervical neck contracture. Br J Plast Surg 2000;53:652–8.
A. Heitland et al. / Burns 30 (2004) 471–475 [8] King P. Artificial skin reduces nutritional requirements in a severely burned child. Burns 2000;26:501–3. [9] Wang JC, To EW. Application of dermal substitute (Integra) to donor site defect of forehead flap. Br J Plast Surg 2000;53:70–2. [10] Chou TD, Chen SL, Lee TW, Chen SG, Cheng TY, Lee CH, et al. Reconstruction of burn scar of the upper extremities with artificial skin. Plast Reconstr Surg 2001;108:378–84 (discussion 85). [11] Loss M, Wedler V, Kunzi W, Meuli-Simmen C, Meyer VE. Artificial skin, split-thickness autograft and cultured autologous keratinocytes combined to treat a severe burn injury of 93% of TBSA. Burns 2000;26:644–52. [12] Fitton AR, Drew P, Dickson WA. The use of a bilaminate artificial skin substitute (Integra) in acute resurfacing of burns: an early experience. Br J Plast Surg 2001;54:208–12. [13] Berger A, Tanzella U, Machens HG, Liebau J. Administration of Integra on primary burn wounds and unstable secondary scars. Chirurg 2000;71:558–63.
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[14] Ryan CM, Schoenfeld DA, Malloy M, Schulz 3rd JT, Sheridan RL, Tompkins RG. Use of Integra artificial skin is associated with decreased length of stay for severely injured adult burn survivors. J Burn Care Rehabil 2002;23:311–7. [15] Palao R, Gomez P, Huguet P. Burned breast reconstructive surgery with Integra dermal regeneration template. Br J Plast Surg 2003;56:252–9. [16] Heimbach DM, Warden GD, Luterman A, Jordan MH, Ozobia N, Ryan CM, et al. Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment. J Burn Care Rehabil 2003;24:42–8. [17] Boyce ST, Kagan RJ, Meyer NA, Yakuboff KP, Warden GD. The 1999 clinical research award. Cultured skin substitutes combined with Integra artificial skin to replace native skin autograft and allograft for the closure of excised full-thickness burns. J Burn Care Rehabil 1999;20:453–61.
Update on the use of collagen/glycosaminoglycate skin substitute—six years of experiences with artificial skin in 15 German burn centers夽 A. Heitland, A. Piatkowski∗ , E.M. Noah, N. Pallua Department of Plastic and Reconstructive Surgery, Burns Unit, RWTH, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany Accepted 1 June 2004
Abstract The clinical use of an artificial skin substitute (Integra® ) has been celebrated enthusiastically as an improvement in burn therapy over a period of more than 10 years. Many case-reports have shown the positive effects of the treatment with Integra® as a skin substitute. In this study we examine the alterations of Integra® -usage in Germany. Fifteen German burn centres have been interviewed respectively over a time period of 6 years with interviews in the years 1999, 2001, and 2003. The goal of this study is to focus on the problems associated with the use of artificial skin and to create a manual for Integra® -therapy including indication, pre-, intra-, and postoperative treatment. Since the first Integra® Users seminar in Germany in 1999 repeated interviews have been conducted with fifteen German burn centres. The collected results of the last 6 years were evaluated. These results show a change in the indication for the therapy with artificial skin towards extensive full thickness burned patients and as extended indication especially for posttraumatic reconstruction. This article gives our guidelines for the usage and handling of Integra® and shows that Integra is an important reconstructive dermal substitute for the severely burned or posttraumatic patient if handled by a skilled surgeon in a correct way. © 2004 Elsevier Ltd and ISBI. All rights reserved. Keywords: Integra; Artificial skin; Soft tissue reconstruction; Retrospective study
1. Introduction Artificial skin (Integra® ) consists of an upper silicone sheet and a lower layer of porous cross-linked bovine collagen and chondroitin-6-sulfate as a template for dermal regeneration. It is a cell free solution for temporary wound closure and produces a well vascularized dermis analogue [1]. Because of the upper silicone sheet it provides a nonpermeable wound closure and therefore a reduction of fluid loss in burned patients. The lower layer, as a dermal substitute, provides a matrix for cell invasion, i.e. fibroblasts or macrophages [2]. The pore size of the cross-linked collagen matrix was therefore adjusted to 70–200 m. After a time period of 14–21 days, a well vascularized neodermis is found beneath the silicone dressing which allows a secondary closure with a thin epidermal autograft as neodermis. Treatment with Integra® was described for the first time in 1981 by Burke and Yannas in the USA [3]. Many differ夽
A. Heitland and A. Piatkowski contributed equally to this paper. Corresponding author. Tel.: +49-241-80-89351; fax: +49-241-80-82448. E-mail address: [email protected] (A. Piatkowski). ∗
0305-4179/$30.00 © 2004 Elsevier Ltd and ISBI. All rights reserved. doi:10.1016/j.burns.2004.01.010
ent case-reports have followed with promising and enthusiastic results, i.e. for reconstruction of huge surface area burns, neck contracture therapy, etc. [4–8]. Introduced as a trigger for fast wound closure in the severely burned patient further extended indications have been described over the last 10 years, i.e. for extremity reconstruction, forehead reconstruction, or reconstruction in combination with cultured keratinocytes [9–12]. Since the approval by the FDA in 1996 followed by the approval of the European Union in 1998 fewer cases have been reported from Europe than from the USA. Nevertheless, all these reports have demonstrated excellent long-term results [13]. The keypoint of the clinical result is the correct application of Integra and the treatment of the wound and wound dressings. This corresponds to a high failure rate at the first cases of Integra® use with a steep and sometimes frustrating learning curve [1]. The correct indication, application, and postoperative treatment of the dermal substitute demand a longtime experience. We are summarizing an overview of the use of Integra in 15 different German burn centers by a descriptive analysis of our questionnaire. In order to give a guideline for Integra® -usage we are concerning the indications, pre-, peri-, and postoperative treatment and the cost effectiveness.
472
A. Heitland et al. / Burns 30 (2004) 471–475
Unfortunately, over the last decades the German system has become more and more restrictive concerning the cost of medical treatment. Such economic pressure requires that therapy with Integra® is used within clearly understood and rational indications and guidelines.
2. Materials Over a period of 6 years, 15 German burn centres with 77 acute burn intensive care beds (including 4 children beds) have been asked, using a standardized questionaire, about their experiences with Integra® . The questionnaire was divided into four topics. The first topic examines the indication for Integra® as well as the influence of the initial trauma, ABSI score, and posttraumatic timing on the use of artificial skin. The second bundle of questions concentrated on the pre-, intra-, and postoperative treatment with Integra® , especially focussing on microbiological testing, the amount of excision of necrotic tissue required, and the application on different wound beds. The postoperative treatment was assessed concerning the wound dressing, the antimicrobiological therapy used, and the microbiological situation in the wound. The interview also contained questions about the method of skin transplantation, i.e. MEEK or Mesh-transplants, and especially the combination of Integra as dermal substitute with autologous keratinocyte cultures as cellular grafts. The long-term treatment was investigated in the third bundle of questions which concerned the use of cremes, compression therapy, and long time histology investigation. The forth topic contained questions about the cost and effectiveness of Integra® during the operation of the DRG (diagnosis related groups) system.
3. Methods The interviews were conducted over two time periods of 24 months in September 1999, 2001, and 2003. The questionnaires were evaluated and summarized descriptively.
4. Results 4.1. Indications The indication for the use of Integra® has changed over the last 6 years. In 1999, Integra® was used for a variety of injuries such as small full thickness burns, unstable scars after burn trauma, or full thickness burns over 50% of total body surface area (TBSA). Over the years, the indications have switched to full thickness burns of over 50–60% TBSA. This narrows the indication of Integra® to a small number of patients in whom
wound closure with split skin grafts cannot be achieved in the early phase of burn care. Recently, a new indication has been described by a small group of burn centres, an increased use in degloving injuries. Promising results have been demonstrated in the cases reported. A smaller change is noted for the contraindications. The key point has been and still whether there is an infection of the wound surface. In early times, it was considered a contraindication to use Integra® after a posttrauma interval longer than 5 days, but this strict indication changed over time. In 1999, only three burn centres described a posttrauma period of more than 5 days as a contraindication, in 2001 only two and in 2003 no single burn center restricted the use of Integra® to this narrow time frame. 4.2. Pre-, peri-, and postoperative treatment The use of preoperative microbiological testing has been constantly described by the majority of the interviewed clinics. In 1999, postoperative microbiological testing was performed by almost all hospitals every second day. Over the years, this practice has changed to a postoperative wound evaluation based on clinical findings. Further, there was a change in the application of Integra® in relation to the cleaned wound bed. In 1999, almost all burn centres recorded the strict and limited use of Integra® following epifascial excision. In 2001 and 2003, half of the burn centres saw the indication for Integra® after both epifascial and tangential excision. Application onto adipose tissue was considered in all clinics as undesirable as well as the use of Integra® following cadaveric allograft application. The wounds were closed by skin staplers with the exception of only one hospital which used sutures as well as staplers. There was no change in the aspect over time. Almost all interviewed hospitals immobilized, the Integra® reconstructed extremities. In 1999, the first wound dressing change of the multilayered wound dressing in all participants was conducted in eight clinics on the first postoperative day (POD). Only one clinic reported a first dressing change after 1 week. These standards changed as well. In 2003, the majority changed the wound dressing on the third POD with only one clinic still performing wound dressing changes at the first POD followed by a daily wound dressing change. We also observed a change in the use of different antimicrobial agents. Argentum nitricum (silver nitrate) (n = 7) was most frequently used in 1999, followed by Lavasept® (polyhexamethylbiguanide, n = 6) and mafenide acetate ( n = 3). The frequency of use for silver nitrate fell over time (2001, n = 5; 2003, n = 3), whereas Lavasept® stayed stable. Over the last years, an increase in the use of Octenisept® is observed (Fig. 1). There was no clear therapy recommendation from any of the burn centres to cope with the difficult case of partial Integra® -loss. Half of the burn centers decided on a reuse of
A. Heitland et al. / Burns 30 (2004) 471–475 Use of Antimicrobial Agents
Percentage of use
60,00%
Percent
50,00% 40,00% 30,00% 20,00% 10,00% 0,00% 1999
Lavasept
2001
AgNi
2003
Mafenid
93,33% 71,43%
1999
2001
2003
4.4. Cost-effectiveness
80,00% 70,00% 60,00% 50,00% 40,00% 30,00% 20,00% 10,00% 0,00% 2001
78,13%
Fig. 3. Chronological use of Integra® in the asked burn centres.
Proceeding in the case of total loss
Reapplication
100,00% 90,00% 80,00% 70,00% 60,00% 50,00% 40,00% 30,00% 20,00% 10,00% 0,00%
Octenisept
Fig. 1. Overview of the applied disinfectants.
1999
473
2003
A decrease in the clinical use of Integra® was noted. In 2001, three of the fifteen burn centres did not use Integra® any more due to uncertain outcome and high costs. This tendency continued in 2003 as four burn centres had not used Integra® in the last 2 years. This means there is a more than 20% decrease in the use of Integra® in German burn centres (Fig. 3).
Therapy change
5. Discussion Fig. 2. Management of complete Integra® loss.
Integra® whereas the other half favored a standard conventional therapy. Interestingly, most of the burn centers favored adding Integra® in the case of a total loss (Fig. 2). Unfortunately, only one clinic interviewed documented the degree of vascularisation using histological methods. All other clinics assessed vascularisation clinically using the color scale depicted in Table 1. All burn centers used the Mesh technique for wound coverage without a change in postoperative treatment. 4.3. Long-term treatment The postoperative long-term treatment basically consists of the same treatment used following skin grafts. The well known postoperative care of daily creme, compression therapy, silicone pads over hypertrophic scars and avoiding sun exposure is the standard recommendation of all burn centers asked. Unfortunately, there are no long-term histological results available on the structure of the neodermis. Table 1 Clinical Integra® evaluation concerning color changes Color
Meaning
Red White Yellow Orange Grey, green, brown Pink, vanilla, peach
Haematin, postoperatively First phase Cell infiltration Neovascularisation Infection Neodermis
The ongoing reduction of artificial skin substitute use reflects two major problems associated with Integra® . These problems are the complicated and very intensive care of the patients treated and the high cost. Many positive reports have been published over recent years concerning the application of Integra® . The long-term outcomes described are positive, in terms of the good structure of the skin and a lower tendency to form hypertrophic scars [14,15]. The treatment phase between application and the skin transplantation 3 weeks later is very problematic. The upper silicone layer protects the excised surface against fluid loss but it also acts as a nonpermeable occlusive wound dressing that cannot be changed easily. A precise inspection of the applied Integra® sheet has to be undertaken every day to ensure a good outcome. This has to be accompanied by repeated microbiological testing and the use of potent antimicrobiological agents such as Lavasept® or silver nitrate. A very promising idea is the use of the silver releasing dressing Actisorb® on the wound edges. Undoubtedly, the most important factor in promoting a positive outcome is a well trained surgeon with experience of Integra® use. The use of Integra® is not easy and the surgeon’s learning curve is steep at the beginning [12,16]. Failures in therapy are therefore most common in the early cases. The high costs of this treatment reveal a problematic financial situation because clinical budgets in Germany are now being reduced. Except for two clinics, all burn centres had to finance Integra® by a so-called “mixed calculation” for their burn patients. This explains the reduced use of this
474
A. Heitland et al. / Burns 30 (2004) 471–475
therapy option. The G-DRG (German Diagnosis Related Groups)-system uses a “mixed calculation”, concluding that expensive treatments that may not be completely funded can only be offered if other DRG-therapies had created a positive financial effect. Therefore unfortunately, the clinical use of Integra® in the burn centres asked has decreased to a narrow field of indications. In our opinion, this financial limitation of Integra® reduces its benefit for many patients. A very promising combination of Integra® is its use in combination with cultivated autologous keratinocytes. Case-reports from the interviewed burn centres as well as cases described in literature present a very good outcome with consistent quality reconstructed skin [11,17]. Especially for severely burned children, this procedure seems to be a promising and important solution. Comparing Integra® to different skin substitutes on the market Integra® is still not as expensive as other products, such as Alloderm® , Dermagraft® , Apligraf® . Only cadaveric allograft represents a cheaper alternative of temporary wound coverage, but without the benefits of a neodermis formation like in the above mentioned products [1]. In summary, we recommend the following guidelines for Integra® .
6. Summarized therapy scheme 1. The main indications are extensive full thickness burns on the trunk and extremities as well as early posttraumatic reconstruction. 2. Preoperative microbiological testing is suggested. 3. Optimal timing for Integra® application is within the first posttraumatic week. 4. A radical debridement must precede the Integra® application. 5. Immobilization is strongly suggested for reconstruction of the extremities with Integra® . 6. A daily wound dressing change should be conducted by an experienced surgeon with special attention paid to the Integra color scheme. 7. Clinical evaluation of vascularisation should replace histological probes. 8. In the case of partial or complete Integra® loss, a reapplication is favored. 9. Skin coverage is achieved by an ultra thin meshed skin transplantation. 10. Postoperative treatment follows the rules for skin transplantation.
7. Conclusion The indications for Integra® are narrowing in the burn sector but are switching simultaneously to the posttraumatic reconstruction sector for example degloving injuries. The use of Integra® demands an experienced surgeon and it has to
be used with great attention to detail and clinical condition of the patient. We are recommending our summarized therapy scheme as mentioned above. Special medical budgets should be negotiated for the use of Integra® with the hospital administration or the health insurance companies in order to provide patients with the optimal care and the newest therapeutical options.
Acknowledgements We wish to thank the participating burn centres in alphabetic order for their repeated work over the years 1999, 2001, and 2003. Klinik für Plastische Chirurgie und Schwerbranntverletzte, Handchirurgiezentrum BG Kliniken Bergmannsheil, Bochum; Klinik für Unfall-, Hand-, und Wiederherstellungschirurgie, Städtische Kliniken Nord Dortmund; BG Unfallklinik Duisburg Abt. für Handchirurgie, Plastische Chirurgie und Branntverletzte; Klinik für Plastische und Handchirurgie/Branntverletztenzentrum BG Kliniken Bregmannstrost Halle/Saale; Klinik und Poliklinik für Kinderchirurgie Halle an der Saale; BG Unfallkrankenhaus Hamburg Abt. für Handchirurgie, Plastische und Mikrochirurgie-Zentrum für Schwerbrandverletzte; Klinik für Plastische Chirurgie, Handchirurgie, Schwerverbranntenzentrum Klinikum Köln Merheim; Städtisches Klinikum Sankt Georg Zentrum für Traumatologie mit Brandverletztenzentrum Leipzig; Plastische Chirurgie, Handchirurgie, Intensiveinheit für Schwerbrandverletzte an der MUL Lübeck; Abt. für Plastische Chirurgie, Handchirurgie, Zentrum für Schwerstbrandverletzte Krankenhaus Bogenhausen München; Abt. für Plastische Chirurgie Fachklinik Hornheide Münster; Klinik für Plastische, Wiederherstellende und Handchirurgie Zentrum für Schwerbrandverletzte Klinikum Süd Nürnberg; Klinik für Unfallchirurgie Marienhospital Stuttgart.
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