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Usage of autograft and allograft skin in treatment of burns in children
Burns 27 (2001) 599– 602 www.elsevier.com/locate/burns
Usage of autograft and allograft skin in treatment of burns in children S. Qaryoute a,*, I. Mirdad b, A. Abu Hamail a a
Plastic Surgery Unit, King Fahd Military Medical Complex, Dhahran, Saudi Arabia b Al Hada Military Hospital, Taif, Saudi Arabia Accepted 8 December 2000
Abstract Large burns still present problems regarding the availability of enough autologous skin cover. The two Units have no experience in using cultured keratinocytes as a substitute for split skin grafts, as these are not available in the Kingdom of Saudi Arabia and are therefore not practical. At the same time, we have been obliged to abandon the use of human allograft skin from cadavers and other patients, because it is not acceptable in our culture. Our favoured method for resurfacing large burn areas in children is to use widely meshed autologous skin, overlaid with meshed allograft from a parent (to minimise the risk of HIV transmission). We report our experience using this technique in five children. The fate of the intermingled grafts has been followed clinically, and in some cases histologically. There has been long-term persistence of the parental skin without rejection and although allograft dermis appears to contribute to the final cover, the cellular elements of the parental skin apparently do not survive. © 2001 Elsevier Science Ltd and ISBI. All rights reserved. Keywords: Allograft; Autograft; Intermingled
1. Introduction At present, most full thickness burn wounds are best closed as quickly as possible with split thickness autograft. However, split thickness autograft is an imperfect replacement for full thickness skin, may be limited in quantity and is associated with donor site limitation and morbidity. A useful permanent skin substitute remains the holy grail of burn research. The ideal skin substitute does not exist at the present time [1]. Allograft has been used as temporary cover whilst awaiting healing of autograft donor areas between multiple cropping, or as a biological dressing. Rejection is unavoidable if allograft is left more than 2 weeks [2]. Further attention has been given to the potential use of allograft as a longer-term substitute for the patient’s skin. It has been used in the treatment of a variety of wounds to reduce the incidence of infection and wound
pain and presumably even to accelerate re-epithelisation of the underlying injured epithelium. Methods have been applied to prevent or delay rejection of allograft, either by modifying the immune response of the recipient, or by reducing the antigenicity of the allograft. In the absence of deliberate immunosuppression, allograft occasionally appears to persist indefinitely. This might be due to close HL-A matching; or to depression of the patient’s immune response to the graft; or the allograft may simply be replaced by gradual substitution with autologous epithelium. Use of parental allograft may allow prolongation of graft survival time and hence facilitate wound cover by allowing the use of widely expanded autograft and improving the quality of final repair. This study presents the results of five cases of burned children where parental allograft was used in the course of treatment.
2. Patients and methods * Corresponding author: KFMMC, Bld 53, Apt 202, PO Box 946, Dhahran 31932, Saudi Arabia; fax: 966 3 840 5540.. E-mail address: [email protected] (S. Qaryoute).
The cases in whom this method was employed are described in Table 1. The five children were aged from
0305-4179/01/$20.00 © 2001 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 0 ) 0 0 1 5 2 - 2
S. Qaryoute et al. / Burns 27 (2001) 599–602
600
5 to 13 years on admission, and had generally sustained mixed-depth burns with a large deep component. The extent of the burn injury ranged from 50– 65% body surface area, but was typically 55%. All the cases underwent surgery after 12– 40 days of treatment with dressings; three cases had been referred from other hospitals after many days of hospitalisation. The allograft skin obtained from the donor was sufficient to cover all the wound, except in the fifth patient where it was planned to cover only 50% of the wound, due to his cardiac status (cardiomyopathy). The skin was donated by the mother in all cases. The mothers were more motivated to donate skin to their children. Allograft was freshly donated during the same operating session as the burn excision, and meshed at 1.5:1– 3:1 expansion ratio. The donor site of the mother was mainly one or both thighs (Fig. 1); it was covered by sofra tulle and gauze dressing and within 10– 12 days had healed completely. Small quantities of thin autograft split skin were meshed 3:1 – 6:1 and spread on the excised burn wound. This means that only 17% of the wound was covered with
autograft (meshed 6:1) while in joint areas nearly 33% of the wound was covered (meshed 3:1). This overcame the limitation of the donor sites in such cases. All areas of the burn wound were covered partially by the allograft, then meshed allograft 1.5:1 or 3:1 was laid over the widely expanded autograft to produce a sandwich graft (Fig. 2). Both layers were fixed to the edge of the wound separately or together using skin staples. The skin grafts were then covered in the conventional way, using sofra tulle then cotton wool soaked with betadine, with the application of certain degree of pressure. The outcome of the grafting was assessed using normal clinical criteria at subsequent dressing changes (Fig. 3). In two patients (2 and 3) we had the opportunity to take a small punch biopsy from areas of the intermingled grafts on two occasions (second and fourth week) from their application. Unfortunately, we do not have the facilities to do y-chromosome identification, which would have enabled us to differentiate male and female cells in the biopsy, and helped us to assess unequivocally the fate of the allograft cells.
Table 1 Description of the patients, their burns and initial surgery. Patient c
Age (years)
Sex
%BSA
Aetiology
First Surgery
1
5
M
65
4 weeks post accident
2
7
M
60
Fire burn Gas explosion Scald
3 4 5
8 7 13
M F M
50 65 60
Fire burn Fire burn Barbecue fire
Fig. 1.
6 weeks post accident Referred from another hospital Excision & grafting at 19 days post accident Desloughed & grafting at 12 days post accident Desloughed & grafting at 30 days post accident
S. Qaryoute et al. / Burns 27 (2001) 599–602
601
Fig. 2.
3. Results The results of using intermingled autograft and parental allograft skin cover in these five patients are summarised in Table 2. In every patient there was successful take of both elements of the graft, in all the areas. As a result of localised wound infection, we experienced partial loss of the intermingled grafts, but there were no signs of rejection of large-scale areas. One patient (case 5) with 60% body surface area burns died on the 20th day post-surgery with intact grafts. We aimed through this technique to achieve complete cover in one stage, but in cases 1 and 2 further autografting was needed, and in case 3 small areas of autograft ‘‘ patching’’ were required. In case 4, complete take of the graft was observed without further surgery. Clinical evaluation of all the cases and the results of biopsies taken from two cases (2 and 3) revealed no signs of acute rejection of the allograft.
4. Discussion The essence of plastic surgery lies in the placement and replacement of skin. From the earliest skin grafts to the present day, plastic surgeons have trod a steady path towards the evaluation of techniques to provide a healed wound. Various attempts have been made, none of which have produced a perfect solution but each of which is another step along the path. Further research
Fig. 3.
S. Qaryoute et al. / Burns 27 (2001) 599–602
602 Table 2 The outcome of intermingled grafting. Pt c Outcome
Further surgery required
Biopsy
1 2
Partial loss Partial loss
3
Partial loss
4 5
Complete take Complete take
Further Autograft None Further Autograft 3 weeks – no rejection Adjacent area 3 weeks – no patched rejection None None None Died 4 weeks later
is necessary so that a skin substitute will truly be a skin replacement. Recent advances in keratinocyte cultivation has made it possible to generate enough epidermis to cover the entire body within 3 weeks. Its ‘‘take’’ is significantly lower than that of split thickened skin graft [3]. This type of treatment needs special facilities and is not practical in our part of the world, and it is still a limited solution to the problem of skin replacement and repair. Split thickness cadaver allografts have been used as biological dressings in the treatment of burn wounds, to reduce incidence of infection and wound pain and presumably even to accelerate re-epithelisation of the underlying injured epithelium [4–6]. The use of cadaver allograft is not acceptable in our society, neither for the donor nor the recipient. Allograft usage was introduced to protect the limited amounts of autograft that are available. Initially, slits were created in the allograft, then changed to windows after 48 hours if the allograft survived. Autograft was inlaid into each window, then the wound was bandaged [7]. This method conserves the autograft and saves the lives of patients with very extensive deep burns. Generally, the autografts can expand 6– 10 times their original size after intermingled transplantation with allografts [7]. Use of allograft to overlay the widely meshed autograft skin contributed significantly to the healing of the wound [8]. There were no signs of rejection, although immune suppression agents were not used. The allograft layer left evidence of long-term contribution to the final quality of the healed wounds, the mesh patterns of both the autograft and the allograft being clearly discernible. The idea of taking skin from parents is always suggested by the parents themselves, and it is well-accepted and encouraged in this country. Burn surgeons have to take the opportunity to make use of this proven method. In this paper, we analyse five cases where we applied this technique, which was successful in each case. It is suitable for use in children with extensive burns with limited donor site. No clear distinction was made
between the fate of autograft and allograft until the work of Medawar, which defined immunologic rejection and initiated modern immunology. However, earlier workers realised that although allograft would heal onto the open wound it would only survive 3–10 weeks [9]. It must be remembered that the major difficulty in usage of allograft is the possibility of transmitting viruses in the graft (i.e. HIV and hepatitis), but these can be excluded by specific pre-operative tests. Due to previous difficulties in using alternative methods, we have adopted the method of using meshed allograft skin as an overlay to cover widely meshed autograft in patients when the donor site is limited, e.g. in children with extensive burns, when the parents (especially the mother) are willing to donate, and after exclusion of virus infection. We conclude that techniques using intermingled autograft and parental allograft provide a safe and satisfactory means to produce cover in large burns in children with extensive burns, without exposure to HIV or hepatitis and without using immunosuppression. It is applicable to our society, in the absence of alternatives, as it is acceptable to the relatives. We have adopted this technique in the Military Burn Units in both Dhahran and Taif in Saudia Arabia.
Acknowledgements The authors would like to thank Mrs Susan Brown and Mrs Maria Rodrigues for their excellent secretarial assistance with this article.
References [1] Sheriden RL, Tompkins RG. Skin substitute in burns. Burns 1999;25:97. [2] Jackson DM. A clinical study of the use of homografts for burns. Br J Plast Surg 1954;7:26. [3] Donati L, Magliacani G, Bormioli M, et al. Clinical experiences with keratinocyte grafts. Burns 1922;18:519 – 25 supplement I. [4] Brown JB, Fryer MP, Randall P, et al. Postmortem homograft as ‘‘biological dressings’’ for extensive burns and denuded areas. Ann Surg 1953;138:618. [5] Zaroff LI, Mills W, Duckett J, et al. Multiple uses of viable cutaneous homografts in the burned patient. JA Surg 1966;59:368. [6] Graham WP. Allografting split thickness skin donor sites. Surg 1969;66:460. [7] Burn Unit, RUI Jin Hospital, Shanghai 2nd Medical College, editors. Management of third degree eschar. In: Burn Treatment. Shanghai: Shanghai People’s Publisher, 1975. [8] Phipps AR, Clarke JA. The use of intermingled autograft and parental allograft skin in the treatment of major burns in children. Br J Plast Surg 1991;44:608. [9] Gallico GG, O’Connor NE. Cultured epithelium as a skin substitute. Clin Plast Surg April 1985;12:150 c 2.
Usage of autograft and allograft skin in treatment of burns in children S. Qaryoute a,*, I. Mirdad b, A. Abu Hamail a a
Plastic Surgery Unit, King Fahd Military Medical Complex, Dhahran, Saudi Arabia b Al Hada Military Hospital, Taif, Saudi Arabia Accepted 8 December 2000
Abstract Large burns still present problems regarding the availability of enough autologous skin cover. The two Units have no experience in using cultured keratinocytes as a substitute for split skin grafts, as these are not available in the Kingdom of Saudi Arabia and are therefore not practical. At the same time, we have been obliged to abandon the use of human allograft skin from cadavers and other patients, because it is not acceptable in our culture. Our favoured method for resurfacing large burn areas in children is to use widely meshed autologous skin, overlaid with meshed allograft from a parent (to minimise the risk of HIV transmission). We report our experience using this technique in five children. The fate of the intermingled grafts has been followed clinically, and in some cases histologically. There has been long-term persistence of the parental skin without rejection and although allograft dermis appears to contribute to the final cover, the cellular elements of the parental skin apparently do not survive. © 2001 Elsevier Science Ltd and ISBI. All rights reserved. Keywords: Allograft; Autograft; Intermingled
1. Introduction At present, most full thickness burn wounds are best closed as quickly as possible with split thickness autograft. However, split thickness autograft is an imperfect replacement for full thickness skin, may be limited in quantity and is associated with donor site limitation and morbidity. A useful permanent skin substitute remains the holy grail of burn research. The ideal skin substitute does not exist at the present time [1]. Allograft has been used as temporary cover whilst awaiting healing of autograft donor areas between multiple cropping, or as a biological dressing. Rejection is unavoidable if allograft is left more than 2 weeks [2]. Further attention has been given to the potential use of allograft as a longer-term substitute for the patient’s skin. It has been used in the treatment of a variety of wounds to reduce the incidence of infection and wound
pain and presumably even to accelerate re-epithelisation of the underlying injured epithelium. Methods have been applied to prevent or delay rejection of allograft, either by modifying the immune response of the recipient, or by reducing the antigenicity of the allograft. In the absence of deliberate immunosuppression, allograft occasionally appears to persist indefinitely. This might be due to close HL-A matching; or to depression of the patient’s immune response to the graft; or the allograft may simply be replaced by gradual substitution with autologous epithelium. Use of parental allograft may allow prolongation of graft survival time and hence facilitate wound cover by allowing the use of widely expanded autograft and improving the quality of final repair. This study presents the results of five cases of burned children where parental allograft was used in the course of treatment.
2. Patients and methods * Corresponding author: KFMMC, Bld 53, Apt 202, PO Box 946, Dhahran 31932, Saudi Arabia; fax: 966 3 840 5540.. E-mail address: [email protected] (S. Qaryoute).
The cases in whom this method was employed are described in Table 1. The five children were aged from
0305-4179/01/$20.00 © 2001 Elsevier Science Ltd and ISBI. All rights reserved. PII: S 0 3 0 5 - 4 1 7 9 ( 0 0 ) 0 0 1 5 2 - 2
S. Qaryoute et al. / Burns 27 (2001) 599–602
600
5 to 13 years on admission, and had generally sustained mixed-depth burns with a large deep component. The extent of the burn injury ranged from 50– 65% body surface area, but was typically 55%. All the cases underwent surgery after 12– 40 days of treatment with dressings; three cases had been referred from other hospitals after many days of hospitalisation. The allograft skin obtained from the donor was sufficient to cover all the wound, except in the fifth patient where it was planned to cover only 50% of the wound, due to his cardiac status (cardiomyopathy). The skin was donated by the mother in all cases. The mothers were more motivated to donate skin to their children. Allograft was freshly donated during the same operating session as the burn excision, and meshed at 1.5:1– 3:1 expansion ratio. The donor site of the mother was mainly one or both thighs (Fig. 1); it was covered by sofra tulle and gauze dressing and within 10– 12 days had healed completely. Small quantities of thin autograft split skin were meshed 3:1 – 6:1 and spread on the excised burn wound. This means that only 17% of the wound was covered with
autograft (meshed 6:1) while in joint areas nearly 33% of the wound was covered (meshed 3:1). This overcame the limitation of the donor sites in such cases. All areas of the burn wound were covered partially by the allograft, then meshed allograft 1.5:1 or 3:1 was laid over the widely expanded autograft to produce a sandwich graft (Fig. 2). Both layers were fixed to the edge of the wound separately or together using skin staples. The skin grafts were then covered in the conventional way, using sofra tulle then cotton wool soaked with betadine, with the application of certain degree of pressure. The outcome of the grafting was assessed using normal clinical criteria at subsequent dressing changes (Fig. 3). In two patients (2 and 3) we had the opportunity to take a small punch biopsy from areas of the intermingled grafts on two occasions (second and fourth week) from their application. Unfortunately, we do not have the facilities to do y-chromosome identification, which would have enabled us to differentiate male and female cells in the biopsy, and helped us to assess unequivocally the fate of the allograft cells.
Table 1 Description of the patients, their burns and initial surgery. Patient c
Age (years)
Sex
%BSA
Aetiology
First Surgery
1
5
M
65
4 weeks post accident
2
7
M
60
Fire burn Gas explosion Scald
3 4 5
8 7 13
M F M
50 65 60
Fire burn Fire burn Barbecue fire
Fig. 1.
6 weeks post accident Referred from another hospital Excision & grafting at 19 days post accident Desloughed & grafting at 12 days post accident Desloughed & grafting at 30 days post accident
S. Qaryoute et al. / Burns 27 (2001) 599–602
601
Fig. 2.
3. Results The results of using intermingled autograft and parental allograft skin cover in these five patients are summarised in Table 2. In every patient there was successful take of both elements of the graft, in all the areas. As a result of localised wound infection, we experienced partial loss of the intermingled grafts, but there were no signs of rejection of large-scale areas. One patient (case 5) with 60% body surface area burns died on the 20th day post-surgery with intact grafts. We aimed through this technique to achieve complete cover in one stage, but in cases 1 and 2 further autografting was needed, and in case 3 small areas of autograft ‘‘ patching’’ were required. In case 4, complete take of the graft was observed without further surgery. Clinical evaluation of all the cases and the results of biopsies taken from two cases (2 and 3) revealed no signs of acute rejection of the allograft.
4. Discussion The essence of plastic surgery lies in the placement and replacement of skin. From the earliest skin grafts to the present day, plastic surgeons have trod a steady path towards the evaluation of techniques to provide a healed wound. Various attempts have been made, none of which have produced a perfect solution but each of which is another step along the path. Further research
Fig. 3.
S. Qaryoute et al. / Burns 27 (2001) 599–602
602 Table 2 The outcome of intermingled grafting. Pt c Outcome
Further surgery required
Biopsy
1 2
Partial loss Partial loss
3
Partial loss
4 5
Complete take Complete take
Further Autograft None Further Autograft 3 weeks – no rejection Adjacent area 3 weeks – no patched rejection None None None Died 4 weeks later
is necessary so that a skin substitute will truly be a skin replacement. Recent advances in keratinocyte cultivation has made it possible to generate enough epidermis to cover the entire body within 3 weeks. Its ‘‘take’’ is significantly lower than that of split thickened skin graft [3]. This type of treatment needs special facilities and is not practical in our part of the world, and it is still a limited solution to the problem of skin replacement and repair. Split thickness cadaver allografts have been used as biological dressings in the treatment of burn wounds, to reduce incidence of infection and wound pain and presumably even to accelerate re-epithelisation of the underlying injured epithelium [4–6]. The use of cadaver allograft is not acceptable in our society, neither for the donor nor the recipient. Allograft usage was introduced to protect the limited amounts of autograft that are available. Initially, slits were created in the allograft, then changed to windows after 48 hours if the allograft survived. Autograft was inlaid into each window, then the wound was bandaged [7]. This method conserves the autograft and saves the lives of patients with very extensive deep burns. Generally, the autografts can expand 6– 10 times their original size after intermingled transplantation with allografts [7]. Use of allograft to overlay the widely meshed autograft skin contributed significantly to the healing of the wound [8]. There were no signs of rejection, although immune suppression agents were not used. The allograft layer left evidence of long-term contribution to the final quality of the healed wounds, the mesh patterns of both the autograft and the allograft being clearly discernible. The idea of taking skin from parents is always suggested by the parents themselves, and it is well-accepted and encouraged in this country. Burn surgeons have to take the opportunity to make use of this proven method. In this paper, we analyse five cases where we applied this technique, which was successful in each case. It is suitable for use in children with extensive burns with limited donor site. No clear distinction was made
between the fate of autograft and allograft until the work of Medawar, which defined immunologic rejection and initiated modern immunology. However, earlier workers realised that although allograft would heal onto the open wound it would only survive 3–10 weeks [9]. It must be remembered that the major difficulty in usage of allograft is the possibility of transmitting viruses in the graft (i.e. HIV and hepatitis), but these can be excluded by specific pre-operative tests. Due to previous difficulties in using alternative methods, we have adopted the method of using meshed allograft skin as an overlay to cover widely meshed autograft in patients when the donor site is limited, e.g. in children with extensive burns, when the parents (especially the mother) are willing to donate, and after exclusion of virus infection. We conclude that techniques using intermingled autograft and parental allograft provide a safe and satisfactory means to produce cover in large burns in children with extensive burns, without exposure to HIV or hepatitis and without using immunosuppression. It is applicable to our society, in the absence of alternatives, as it is acceptable to the relatives. We have adopted this technique in the Military Burn Units in both Dhahran and Taif in Saudia Arabia.
Acknowledgements The authors would like to thank Mrs Susan Brown and Mrs Maria Rodrigues for their excellent secretarial assistance with this article.
References [1] Sheriden RL, Tompkins RG. Skin substitute in burns. Burns 1999;25:97. [2] Jackson DM. A clinical study of the use of homografts for burns. Br J Plast Surg 1954;7:26. [3] Donati L, Magliacani G, Bormioli M, et al. Clinical experiences with keratinocyte grafts. Burns 1922;18:519 – 25 supplement I. [4] Brown JB, Fryer MP, Randall P, et al. Postmortem homograft as ‘‘biological dressings’’ for extensive burns and denuded areas. Ann Surg 1953;138:618. [5] Zaroff LI, Mills W, Duckett J, et al. Multiple uses of viable cutaneous homografts in the burned patient. JA Surg 1966;59:368. [6] Graham WP. Allografting split thickness skin donor sites. Surg 1969;66:460. [7] Burn Unit, RUI Jin Hospital, Shanghai 2nd Medical College, editors. Management of third degree eschar. In: Burn Treatment. Shanghai: Shanghai People’s Publisher, 1975. [8] Phipps AR, Clarke JA. The use of intermingled autograft and parental allograft skin in the treatment of major burns in children. Br J Plast Surg 1991;44:608. [9] Gallico GG, O’Connor NE. Cultured epithelium as a skin substitute. Clin Plast Surg April 1985;12:150 c 2.