- Email: [email protected]
Survey: use of skin substitute materials in UK burn treatment centres
Burns 28 (2002) 295–297
Editorial
Survey: use of skin substitute materials in UK burn treatment centres
1. Introduction Skin substitutes, or alternative wound-closure materials, are a major topic of concern for the surgeon and staff involved in the management and closure of burn wounds. This Journal has recently carried several articles on the use and development of these materials. The majority of these are scientific studies, laboratory based studies, theoretical considerations, or review and commentary articles [1–9]. However, what is clear is that there is at present no collected published body of data concerning the efficacy of, or even clinical experience with, these materials in the UK. This situation has probably arisen from the way in which skin substitutes have entered into clinical use. In general the introduction of these materials into the clinical environment has been sporadic, and dependent upon local knowledge, inclination and initiative. Few extended studies have been reported. Perhaps, at this stage, this is not surprising. Outcome measures are poorly, if at all, formulated. The materials may be used for a different range of purposes, according to the licence issued by the regulatory body of each country in which they are used. It is possible that evidence on clinical outcome will be collected but not reach the light of day, as Journals will be reluctant to publish individual case descriptions, which would, in any event, almost certainly be very much selected for “success”, whatsoever that might be. There is at present very little evidence to persuade, or dissuade, the surgeon in relation to the use of such materials. There are other considerations, chief among them being that the skin substitute itself is the tip of a new surgical iceberg. It does not simply substitute for the skin used to cover or close a wound, but use generally involves a new management philosophy with extra resource implications beyond that of the cost of the substitute material itself. Within the UK burn care community there exists a body of clinical experience with skin substitute materials. Some of this may be aired in public through Meeting presentations, some will be shared informally to a varying degree amongst colleagues. Some areas of this practical experience, and the opinions that result from them, will be widely shared and accepted, other areas perhaps will be more controversial. A collected, structured, expression of this experience would be of value in terms of informing the wider burn care community about the usefulness of these materials in practice. 0305-4179/02/$22.00 © 2002 Published by Elsevier Science Ltd. and ISBI. PII: S 0 3 0 5 - 4 1 7 9 ( 0 2 ) 0 0 0 6 2 - 1
As a first step in this direction, this article reports the information gathered from a survey involving Burn Units in the UK. The survey requested information about experience of, and attitudes toward, skin substitutes. Twenty-six major UK burn treatment centres were sent a questionnaire by post. For the purposes of the questionnaire, skin substitutes for treatment of burn injury were defined as three groups of materials: (1) non-cellular matrix e.g. Integra® , (2) matrix+ cultured cells, such as TransCyte, (3) epidermal cell cultures in various forms (CEA). Questionnaires were sent to the Director of each Unit. Twenty-four Units returned replies. 2. Questionnaire responses Replies showed that 12 Units have used skin substitute materials and that 10 of these intended to continue in their use. The other two reported that use of such materials had been discontinued because of small numbers of patients, resource costs, and lack of evidence base to support wider use. Integra® , TransCyte and cultured keratinocytes were the most frequently mentioned, with Integra® having been used at all 12 centres. TransCyte, occasionally in association with Biobrane membrane, had been used at six centres. Cultured epithelial cells were currently in use at six centres although others reported its use in the past. Of the 12 centres, three reported treating 50 or more patients with alternative wound closure materials, two centres had treated 30 or more, two had treated 20 or more and the remainder between 2 and 20 patients. Eleven of the 12 centres returned answers to questions relating to circumstances considered to be of importance in the decision to use these substitutes. These are shown in Table 1. These reasons are interesting and perhaps unexpected. Of particular interest is the low level of indication for use restricted to the major life-threatening burns only. This probably reflects the small number of life-threatening burn injuries admitted to most individual Units. Salisbury, for example, sees only around 20 patients with burns of greater than 20% TBSA in an annual admission of around 270 patients. In general, burn treatment is directed primarily toward wound management, repair, and closure than to the necessity of saving life. This is reinforced by the concern over donor site availability.
296
Editorial / Burns 28 (2002) 295–297
Table 1 Factors of importance in decision to use skin substitute materials (11 centres) Depth of burn Availability of donor site Likelihood of infection Site of burn Experience of surgeon with substitute Likely ‘take’ rate Predicted aesthetic outcome Likelihood of wound contracture Age of patient Use with major life threatening burns only Relative cost Time consuming dressings or time on ICU
10 8 8 7 6 6 5 4 4 3 2 0
The table shows that surgeons perceive that use of skin substitutes is a quality issue to enhance wound management, with concern over cost and time utilization in patient management being low on the list. There is some ambivalence shown over perceived effect on aesthetic outcome with outcome being cited by less than half the responding Units. The materials have evidently not (yet) come into widespread and frequent use. Of the 24 responding centres, 12 do not, at the present time, use skin substitutes. Two are intending to start with their use; one Unit cited past purchasing problems, the other had recently appointed a new Director. Reasons for non-use of substitute materials are shown in Table 2. In Units which do not use substitute materials, their use appears to be envisaged mainly for larger burns—lack of suitable patients is a reflection primarily of the relatively low number of extensive burns seen in the UK today. Use of cadaver skin in wound management is well established in the UK, well organised, and perceived to be relatively cheap compared with the cost and extra resource implications of a skin substitute such as Integra® . Some surgeons are understandably reluctant to undertake such a new treatment in the face of such a small evidence base for its beneficial use. Again the concerns are patient and quality centred with ‘cost effectiveness’ being low down on the list of reasons included in the category of non-use. Relative experience of surgeons as a factor in the use of skin substitutes featured Table 2 Reasons for not using skin substitute materials (10 Units) No patients admitted considered as suitable to benefit Prefer to use cadaver skin in FT closure Lack of experience of surgeon with alternative materials Not considered cost effective Not considered beneficial Time consuming dressings/ICU Too much disruption of normal protocol More likelihood of infection/loss of graft More likelihood of wound-contracture
5 5 5 2 1 1 1 0 0
strongly in both the centres using skin substitutes and those not using skin substitutes. Both groups of centres, users and non-users, indicate clearly the strongly clinical base on which use or non-use is decided. This is perfectly correct; there are, as yet, no compelling objective reasons why substitutes should, or should not, be used. Initial steps in the introduction of such materials into clinical practice so that evaluations of their efficacy can be made, must operate on the grounds of perceived benefit (or non-benefit) by individual clinical decision makers. There were very few reports of published work on the subject from UK Units. Only one publication in a peer-reviewed journal was identified by a responding Unit [10] —most that had reported results in public had done so through presentations at Meetings. 3. Individual materials The second part of the questionnaire requested brief details of experience with particular skin substitutes. As would be expected the majority of comments were received on Integra® . A range of use was reported to include burns in the acute stage and also use in reconstructive procedures. 3.1. Integra® Use of Integra® was reported by all 12 centres who had used substitute materials, although two had now discontinued its use. Six Units identified management of infection as a problem. Another problem, perhaps linked with infection was management of the wound in flexor areas. Some patients, as would be expected, had died. In general there was a cautious response in regard to the use of Integra® in the acute stage after injury, but two Units reported positively on its use for full thickness burns. As an example the experience of our burns Unit at Salisbury can be cited. This centre has treated three patients with burns in excess of 40% BSA with Integra® . Infection has not been a significant problem. All survived. At the time of writing the third patient is back on the burns Unit from the ICU. One patient has been lost to follow-up on transfer to his home area of the UK, and one has had significant problems with contractures. All three patients illustrated well the fact that the Integra® itself is only the tip of the iceberg. Extended time in ICU was necessary and there was large expenditure on infection control, especially in terms of topical agents. Large amounts of burn-nursing time were spent on the ICU. It seems that across the UK the Jury is still out on the use of Integra® in the acute stages. There is uncertainty over patient selection and problems with management of the patients. There are, however, good experiences and in general a commitment to continue investigating the material as a wound treatment agent. Interestingly, reconstructive surgery or contracture release appeared also be a major use for this material with positive
Editorial / Burns 28 (2002) 295–297
comments from two of the Units concerned. Even here there were problems identified with infection and managing the interface between the Integra® and the normal skin. This area of use, which we believe is not included in the American Regulatory Approval, perhaps requires more detailed investigation before a general picture can be drawn. 3.2. TransCyte This material was reported as having been used by six Units, generally to allow early excision of deep burn eschar and protection of the wound bed. Four Units made very positive comments about its benefit, with one enthusiastic endorsement as a perceived promoter of healing. 3.3. Cultured epithelial cells/CEA Cultured epithelial cells, or composites of cells seeded onto other materials, were reported as in present use at six centres. One centre had used CEA in many patients over 3 years, and reported that such materials were used in preference to cadaver skin in order to avoid disease transmission. One other Unit reported worthwhile use by seeding onto meshed skin, or on donor sites and that techniques of seeding onto Integra® were being investigated. Little information was given from the other four Units reporting use of CEA. One Unit which had never used cultured cells reported an interest in applying suspensions of cells to promote healing in mesh grafts and donor sites. No information on the use of other skin substitute materials was given in the returned questionnaires.
4. Summary and conclusions The adoption of the use of skin substitute material is evidently not yet widespread amongst UK burn treatment centres. Most Units which had started to use substitutes had done so on the initiative of the Director of the unit, a reason which was equally strongly represented among those not using these materials. In the five centres which are major users of these materials, the view appears to be that they can be of great benefit, and that the use of substitutes in these centres will continue to increase. Those Units treating few patients, may have only recently started to use substitutes, but most show a degree of caution over how they perceive the benefits of use and also a lack of conviction that skin substitutes will be a marked improvement over ‘traditional’ methods of wound repair and closure.
297
The survey did not seek beyond some of the more factual aspects of skin substitute use, but the picture implies that there may be some way to go before the general adoption of skin substitutes is seen in the UK to be a significant development in the treatment of burned patients. Progress will depend upon the development of an evidence base to provide a more rational basis for proceeding. Perhaps National Burn Care Associations have a role to play in the process of building such bases The pages of this journal are open to well-structured studies that will help to build the body of evidence that will assist in the rational evaluation of the utility (or otherwise) of these materials. Acknowledgements The authors acknowledge the co-operation of clinical staff at the Units in completing and returning the questionnaires. References [1] Shakespeare P. Skin substitutes: benefits and costs. Burns 2001;27(5): 7–8. [2] Kearney JN. Clinical evaluation of skin substitutes. Burns 2001;27(5): 545–51. [3] Balasubramani M, Kumar TR, Babu M. Skin substitutes: a review. Burns 2001;27(5):534–44. [4] Boyce ST. Design principles for composition and performance of cultured skin substitutes. Burns 2001;27(5):523–33. [5] Shakespeare P. Burn wound healing and skin substitutes. Burns 2001;27(5):517–22. [6] Sheridan RL, Morgan JR, Cusick JL, Petras LM, Lydon MM, Tompkins RG. Initial experience with a composite autologous skin substitute. Burns 2001;27(5):421–4. [7] Lindberg K, Badylak SF. Porcine small intestinal submucosa (SIS): a bioscaffold supporting in vitro primary human epidermal cell differentiation and synthesis of basement membrane proteins. Burns 2001;27(3):254–66. [8] Sheridan RL, Moreno C. Skin substitutes in burns. Burns 2001; 27(1):92. [9] King P. Artificial skin reduces nutritional requirements in a severely burned child. Burns 2000;26(5):501–3. [10] 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.
Peter Shakespeare∗ , Valerie Shakespeare The Laing Laboratory for Burn Injury Investigation Salisbury District Hospital, Salisbury SP2 8BJ, UK ∗ Corresponding
author. Tel.: +44-1722-328-722 fax: +44-1722-328-722 E-mail address: [email protected] (P. Shakespeare)
Editorial
Survey: use of skin substitute materials in UK burn treatment centres
1. Introduction Skin substitutes, or alternative wound-closure materials, are a major topic of concern for the surgeon and staff involved in the management and closure of burn wounds. This Journal has recently carried several articles on the use and development of these materials. The majority of these are scientific studies, laboratory based studies, theoretical considerations, or review and commentary articles [1–9]. However, what is clear is that there is at present no collected published body of data concerning the efficacy of, or even clinical experience with, these materials in the UK. This situation has probably arisen from the way in which skin substitutes have entered into clinical use. In general the introduction of these materials into the clinical environment has been sporadic, and dependent upon local knowledge, inclination and initiative. Few extended studies have been reported. Perhaps, at this stage, this is not surprising. Outcome measures are poorly, if at all, formulated. The materials may be used for a different range of purposes, according to the licence issued by the regulatory body of each country in which they are used. It is possible that evidence on clinical outcome will be collected but not reach the light of day, as Journals will be reluctant to publish individual case descriptions, which would, in any event, almost certainly be very much selected for “success”, whatsoever that might be. There is at present very little evidence to persuade, or dissuade, the surgeon in relation to the use of such materials. There are other considerations, chief among them being that the skin substitute itself is the tip of a new surgical iceberg. It does not simply substitute for the skin used to cover or close a wound, but use generally involves a new management philosophy with extra resource implications beyond that of the cost of the substitute material itself. Within the UK burn care community there exists a body of clinical experience with skin substitute materials. Some of this may be aired in public through Meeting presentations, some will be shared informally to a varying degree amongst colleagues. Some areas of this practical experience, and the opinions that result from them, will be widely shared and accepted, other areas perhaps will be more controversial. A collected, structured, expression of this experience would be of value in terms of informing the wider burn care community about the usefulness of these materials in practice. 0305-4179/02/$22.00 © 2002 Published by Elsevier Science Ltd. and ISBI. PII: S 0 3 0 5 - 4 1 7 9 ( 0 2 ) 0 0 0 6 2 - 1
As a first step in this direction, this article reports the information gathered from a survey involving Burn Units in the UK. The survey requested information about experience of, and attitudes toward, skin substitutes. Twenty-six major UK burn treatment centres were sent a questionnaire by post. For the purposes of the questionnaire, skin substitutes for treatment of burn injury were defined as three groups of materials: (1) non-cellular matrix e.g. Integra® , (2) matrix+ cultured cells, such as TransCyte, (3) epidermal cell cultures in various forms (CEA). Questionnaires were sent to the Director of each Unit. Twenty-four Units returned replies. 2. Questionnaire responses Replies showed that 12 Units have used skin substitute materials and that 10 of these intended to continue in their use. The other two reported that use of such materials had been discontinued because of small numbers of patients, resource costs, and lack of evidence base to support wider use. Integra® , TransCyte and cultured keratinocytes were the most frequently mentioned, with Integra® having been used at all 12 centres. TransCyte, occasionally in association with Biobrane membrane, had been used at six centres. Cultured epithelial cells were currently in use at six centres although others reported its use in the past. Of the 12 centres, three reported treating 50 or more patients with alternative wound closure materials, two centres had treated 30 or more, two had treated 20 or more and the remainder between 2 and 20 patients. Eleven of the 12 centres returned answers to questions relating to circumstances considered to be of importance in the decision to use these substitutes. These are shown in Table 1. These reasons are interesting and perhaps unexpected. Of particular interest is the low level of indication for use restricted to the major life-threatening burns only. This probably reflects the small number of life-threatening burn injuries admitted to most individual Units. Salisbury, for example, sees only around 20 patients with burns of greater than 20% TBSA in an annual admission of around 270 patients. In general, burn treatment is directed primarily toward wound management, repair, and closure than to the necessity of saving life. This is reinforced by the concern over donor site availability.
296
Editorial / Burns 28 (2002) 295–297
Table 1 Factors of importance in decision to use skin substitute materials (11 centres) Depth of burn Availability of donor site Likelihood of infection Site of burn Experience of surgeon with substitute Likely ‘take’ rate Predicted aesthetic outcome Likelihood of wound contracture Age of patient Use with major life threatening burns only Relative cost Time consuming dressings or time on ICU
10 8 8 7 6 6 5 4 4 3 2 0
The table shows that surgeons perceive that use of skin substitutes is a quality issue to enhance wound management, with concern over cost and time utilization in patient management being low on the list. There is some ambivalence shown over perceived effect on aesthetic outcome with outcome being cited by less than half the responding Units. The materials have evidently not (yet) come into widespread and frequent use. Of the 24 responding centres, 12 do not, at the present time, use skin substitutes. Two are intending to start with their use; one Unit cited past purchasing problems, the other had recently appointed a new Director. Reasons for non-use of substitute materials are shown in Table 2. In Units which do not use substitute materials, their use appears to be envisaged mainly for larger burns—lack of suitable patients is a reflection primarily of the relatively low number of extensive burns seen in the UK today. Use of cadaver skin in wound management is well established in the UK, well organised, and perceived to be relatively cheap compared with the cost and extra resource implications of a skin substitute such as Integra® . Some surgeons are understandably reluctant to undertake such a new treatment in the face of such a small evidence base for its beneficial use. Again the concerns are patient and quality centred with ‘cost effectiveness’ being low down on the list of reasons included in the category of non-use. Relative experience of surgeons as a factor in the use of skin substitutes featured Table 2 Reasons for not using skin substitute materials (10 Units) No patients admitted considered as suitable to benefit Prefer to use cadaver skin in FT closure Lack of experience of surgeon with alternative materials Not considered cost effective Not considered beneficial Time consuming dressings/ICU Too much disruption of normal protocol More likelihood of infection/loss of graft More likelihood of wound-contracture
5 5 5 2 1 1 1 0 0
strongly in both the centres using skin substitutes and those not using skin substitutes. Both groups of centres, users and non-users, indicate clearly the strongly clinical base on which use or non-use is decided. This is perfectly correct; there are, as yet, no compelling objective reasons why substitutes should, or should not, be used. Initial steps in the introduction of such materials into clinical practice so that evaluations of their efficacy can be made, must operate on the grounds of perceived benefit (or non-benefit) by individual clinical decision makers. There were very few reports of published work on the subject from UK Units. Only one publication in a peer-reviewed journal was identified by a responding Unit [10] —most that had reported results in public had done so through presentations at Meetings. 3. Individual materials The second part of the questionnaire requested brief details of experience with particular skin substitutes. As would be expected the majority of comments were received on Integra® . A range of use was reported to include burns in the acute stage and also use in reconstructive procedures. 3.1. Integra® Use of Integra® was reported by all 12 centres who had used substitute materials, although two had now discontinued its use. Six Units identified management of infection as a problem. Another problem, perhaps linked with infection was management of the wound in flexor areas. Some patients, as would be expected, had died. In general there was a cautious response in regard to the use of Integra® in the acute stage after injury, but two Units reported positively on its use for full thickness burns. As an example the experience of our burns Unit at Salisbury can be cited. This centre has treated three patients with burns in excess of 40% BSA with Integra® . Infection has not been a significant problem. All survived. At the time of writing the third patient is back on the burns Unit from the ICU. One patient has been lost to follow-up on transfer to his home area of the UK, and one has had significant problems with contractures. All three patients illustrated well the fact that the Integra® itself is only the tip of the iceberg. Extended time in ICU was necessary and there was large expenditure on infection control, especially in terms of topical agents. Large amounts of burn-nursing time were spent on the ICU. It seems that across the UK the Jury is still out on the use of Integra® in the acute stages. There is uncertainty over patient selection and problems with management of the patients. There are, however, good experiences and in general a commitment to continue investigating the material as a wound treatment agent. Interestingly, reconstructive surgery or contracture release appeared also be a major use for this material with positive
Editorial / Burns 28 (2002) 295–297
comments from two of the Units concerned. Even here there were problems identified with infection and managing the interface between the Integra® and the normal skin. This area of use, which we believe is not included in the American Regulatory Approval, perhaps requires more detailed investigation before a general picture can be drawn. 3.2. TransCyte This material was reported as having been used by six Units, generally to allow early excision of deep burn eschar and protection of the wound bed. Four Units made very positive comments about its benefit, with one enthusiastic endorsement as a perceived promoter of healing. 3.3. Cultured epithelial cells/CEA Cultured epithelial cells, or composites of cells seeded onto other materials, were reported as in present use at six centres. One centre had used CEA in many patients over 3 years, and reported that such materials were used in preference to cadaver skin in order to avoid disease transmission. One other Unit reported worthwhile use by seeding onto meshed skin, or on donor sites and that techniques of seeding onto Integra® were being investigated. Little information was given from the other four Units reporting use of CEA. One Unit which had never used cultured cells reported an interest in applying suspensions of cells to promote healing in mesh grafts and donor sites. No information on the use of other skin substitute materials was given in the returned questionnaires.
4. Summary and conclusions The adoption of the use of skin substitute material is evidently not yet widespread amongst UK burn treatment centres. Most Units which had started to use substitutes had done so on the initiative of the Director of the unit, a reason which was equally strongly represented among those not using these materials. In the five centres which are major users of these materials, the view appears to be that they can be of great benefit, and that the use of substitutes in these centres will continue to increase. Those Units treating few patients, may have only recently started to use substitutes, but most show a degree of caution over how they perceive the benefits of use and also a lack of conviction that skin substitutes will be a marked improvement over ‘traditional’ methods of wound repair and closure.
297
The survey did not seek beyond some of the more factual aspects of skin substitute use, but the picture implies that there may be some way to go before the general adoption of skin substitutes is seen in the UK to be a significant development in the treatment of burned patients. Progress will depend upon the development of an evidence base to provide a more rational basis for proceeding. Perhaps National Burn Care Associations have a role to play in the process of building such bases The pages of this journal are open to well-structured studies that will help to build the body of evidence that will assist in the rational evaluation of the utility (or otherwise) of these materials. Acknowledgements The authors acknowledge the co-operation of clinical staff at the Units in completing and returning the questionnaires. References [1] Shakespeare P. Skin substitutes: benefits and costs. Burns 2001;27(5): 7–8. [2] Kearney JN. Clinical evaluation of skin substitutes. Burns 2001;27(5): 545–51. [3] Balasubramani M, Kumar TR, Babu M. Skin substitutes: a review. Burns 2001;27(5):534–44. [4] Boyce ST. Design principles for composition and performance of cultured skin substitutes. Burns 2001;27(5):523–33. [5] Shakespeare P. Burn wound healing and skin substitutes. Burns 2001;27(5):517–22. [6] Sheridan RL, Morgan JR, Cusick JL, Petras LM, Lydon MM, Tompkins RG. Initial experience with a composite autologous skin substitute. Burns 2001;27(5):421–4. [7] Lindberg K, Badylak SF. Porcine small intestinal submucosa (SIS): a bioscaffold supporting in vitro primary human epidermal cell differentiation and synthesis of basement membrane proteins. Burns 2001;27(3):254–66. [8] Sheridan RL, Moreno C. Skin substitutes in burns. Burns 2001; 27(1):92. [9] King P. Artificial skin reduces nutritional requirements in a severely burned child. Burns 2000;26(5):501–3. [10] 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.
Peter Shakespeare∗ , Valerie Shakespeare The Laing Laboratory for Burn Injury Investigation Salisbury District Hospital, Salisbury SP2 8BJ, UK ∗ Corresponding
author. Tel.: +44-1722-328-722 fax: +44-1722-328-722 E-mail address: [email protected] (P. Shakespeare)