Topical treatment for facial burns

  • Review
  • Intervention

Authors


Abstract

Background

Burn injuries are an important health problem. They occur frequently in the head and neck region - the area central to a person's identity, that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of partial-thickness burns to the face.

Objectives

To assess the effects of topical interventions on wound healing in people with facial burns of any depth.

Search methods

We searched the Cochrane Wounds Group Specialised Register (searched 12 November 2012); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); Ovid MEDLINE (1950 to November Week 1 2012); Ovid MEDLINE - In-process & Other Non-Indexed Citations (searched November 12, 2012); Ovid EMBASE (1980 to 2012 Week 45); and EBSCO CINAHL (1982 to 9 November 2012) for relevant trials. We did not apply date or language restrictions.

Selection criteria

Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review.

Data collection and analysis

Two review authors independently assessed and included the references identified by the search strategy. Included trials were assessed using a risk of bias form, and data were extracted using a standardised data extraction sheet. For dichotomous and continuous outcomes, we calculated risk ratios and mean differences, respectively, both with 95% confidence intervals (CI).

Main results

We included five RCTs, comprising a total of 119 participants. Two studies compared two different antimicrobial agents and three compared a biological or bioengineered skin substitute with an antimicrobial agent. All studies had small sample sizes and were at high risk of bias. Heterogeneity of interventions and outcomes prevented pooling of data. In three studies time to complete wound healing was significantly shorter for those using a skin substitute than for those using an antibacterial agent, but the quality of the evidence was low. Pain was significantly reduced with the use of skin substitutes in both studies that reported this outcome in all groups, range mean differences -2.00 (95% CI -3.82 to -0.18) to -4.00 (95% CI -5.05 to -2.95) on a 10-point scale.

Authors' conclusions

There is insufficient high quality research and evidence to enable conclusions to be drawn about the effects of topical interventions on wound healing in people with facial burns.

Résumé scientifique

Traitement topique des brûlures faciales

Contexte

Les brûlures sont un problème de santé important. Elles surviennent fréquemment dans la région de la tête et du cou - la zone au cœur de l'identité d'une personne, et au travers de laquelle s’articulent nos moyens de communication les plus expressifs. Les interventions topiques sont actuellement la pierre angulaire du traitement des brûlures faciales d'épaisseur partielle.

Objectifs

Évaluer les effets des interventions topiques sur la cicatrisation des plaies chez les personnes atteintes de brûlures faciales, quelle qu’en soit l’épaisseur.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre spécialisé du groupe Cochrane sur les plaies et contusions (recherche datant du 12 novembre 2012), le registre Cochrane des essais contrôlés (CENTRAL) (The Cochrane Library 2012, Numéro 10) ; Ovid MEDLINE (de 1950 à la 1ère semaine de novembre 2012) ; Ovid MEDLINE - In-Process & Other Non-Indexed Citations, (recherche datant du 12 novembre 2012) ; Ovid EMBASE (de 1980 à la semaine 45 de 2012) et EBSCO CINAHL (de 1982 au 09 novembre 2012). Nous n’avons appliqué aucune restriction concernant la date ou la langue.

Critères de sélection

Les essais contrôlés randomisés (ECR) ayant évalué les effets d'un traitement topique des brûlures faciales étaient éligibles pour être inclus dans la présente revue.

Recueil et analyse des données

Deux auteurs ont évalué et inclus de manière indépendante les références identifiées par la stratégie de recherche. Les essais inclus ont été évalués à l'aide d'un formulaire de risque de biais, et les données ont été extraites à l'aide d'un formulaire d'extraction des données normalisé. Pour les résultats dichotomiques et continus, nous avons calculé les risques relatifs et les différences moyennes, respectivement, avec dans chaque cas des intervalles de confiance (IC) à 95 %.

Résultats principaux

Nous avons inclus cinq ECR, comprenant un total de 119 participants. Deux études ont comparé deux agents antimicrobiens différents et trois ont comparé un substitut cutané biologique ou issu des techniques de bio-ingénierie avec un agent antimicrobien. Toutes ces études avaient une petite taille de l’échantillon et présentaient un risque élevé de biais. L'hétérogénéité des interventions et des critères de jugement n’a pas permis de regrouper les données. Dans trois études, le délai jusqu’à l’obtention de la cicatrisation complète des plaies s’est avéré significativement plus court chez les sujets qui utilisaient un substitut cutané que chez ceux qui utilisaient un agent antibactérien, mais la qualité des preuves était faible. La douleur a été réduite significativement avec l'utilisation de substituts cutanés dans les deux études ayant évalué ce critère dans tous les groupes, plage des différences moyennes de -2,00 (IC à 95 % de -3,82 à -0,18) à -4,00 (IC à 95 % de -5.05 à -2.95) sur une échelle de 10 points.

Conclusions des auteurs

Il n’existe pas suffisamment de recherches et de preuves de qualité élevée pour pouvoir tirer des conclusions quant aux effets des interventions topiques sur la cicatrisation des plaies chez les personnes atteintes de brûlures faciales.

Resumo

Tratamento tópico de queimaduras faciais

Introdução

Queimaduras são um importante problema de saúde. Elas ocorrem frequentemente na região da cabeça e pescoço - a área central para a identidade da pessoa, e responsável por nosso meio mais expressivo de comunicação. Intervenções tópicas são, atualmente, a pedra-angular do tratamento de queimaduras de espessura parcial na face

Objetivos

Avaliar os efeitos de intervenções tópicas no reparo de feridas em pessoas com queimaduras faciais de qualquer profundidade.

Métodos de busca

Buscamos no Cochrane Wounds Group Specialised Register (pesquisado em 12 de Novembro de 2012); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012 Edição 10); Ovid MEDLINE (1950 a Novembro 2012, Semana 1); Ovid MEDLINE - In-process & Other Non-Indexed Citations (pesquisado em 12 de Novembro de 2012); Ovid EMBASE (1980 a 2012, Semana 45); e EBSCO CINAHL (1982 a 9 de Novembro de 2012) em busca de ensaios clínicos relevantes. Não aplicamos restrição de data ou língua.

Critério de seleção

Ensaios clínicos controlados randomizados (ECR) que avaliaram os efeitos do tratamento tópico para queimaduras faciais foram elegíveis para inclusão nesta revisão.

Coleta dos dados e análises

Dois autores da revisão independentemente avaliaram e incluíram as referências identificadas pela estratégia de busca. Os ensaios clínicos incluídos foram avaliados utilizando um formulário de risco de viés, e os dados foram extraídos utilizando um padrão de extração de dados. Para desfechos dicótomos e contínuos, calculamos o risco relativo e a diferença média, respectivamente, ambos com 95% de intervalo de confiança (IC)

Principais resultados

Incluímos cinco ECRs, contabilizando um total de 119 participantes. Dois estudos compararam dois antimicrobianos diferentes e três compararam um substituto de pele biológico ou artificial com um antimicrobiano. Todos os estudos possuiam amostras pequenas e alto risco de viés. Heterogeneidade das intervenções e desfechos impediram a coleta dos dados. Em três estudos, o tempo para o completo reparo da ferida foi significantemente menor nos grupos que usaram substituto de pele do que nos grupos que usaram agente antimicrobiano, mas a qualidade da evidência foi baixa. A dor foi significantemente reduzida com o uso dos susbstitutos de pele nos dois estudos que relataram sobre esse desfecho, variação de diferença média de -2.00 (IC 95% -3,82 a -0,18) a -4.00 (IC 95% -5,05 a -2,95) em uma escala de 10 pontos.

Conclusão dos autores

Há pesquisas e evidências de alta qualidade insuficientes para se concluir sobre os efeitos de intervenções tópicas no reparo de feridas em pessoas com queimaduras faciais.

Notas de tradução

Notas de tradução CD008058.pub2

Plain language summary

Topical treatment for facial burns

Burn injuries are an important health problem. Burns frequently occur on the head or neck. These areas are central to a person's identity and play a vital role in communication. Other basic abilities such as hearing, smelling and breathing may become affected as a direct result of a facial burn. The authors of this Cochrane review wanted to assess the effects of topical (surface) treatments for wound healing in facial burns. Examples of topical treatments are antimicrobial creams and ointments and biological, or bioengineered (artificial), skin substitutes.

Five small studies were included in the review. Two studies compared two different antimicrobials whilst three compared antimicrobials with skin substitutes. All studies were small and at high risk of bias therefore we cannot be confident in the results and the overall evidence is of low quality. There is insufficient reliable evidence as to whether topical treatments improve outcomes for people with facial burns including improved wound healing, rates of infection, the need for surgery, improved appearance of scars, reduced pain, improved overall patient satisfaction, reduced adverse effects, improved quality of life or reduced the length of the hospital stay. More research is needed.

Résumé simplifié

Traitement topique des brûlures faciales

Les brûlures sont un problème de santé important. Les brûlures se produisent fréquemment sur la tête ou le cou. Ces zones sont le siège de l'expression de l'identité d'une personne et jouent un rôle essentiel dans la communication. D’autres capacités fondamentales telles que l'ouïe, l'odorat et la respiration peuvent être touchées en conséquence directe d'une brûlure faciale. Les auteurs de la présente revue Cochrane ont voulu évaluer les effets des traitements topiques (surface) sur la cicatrisation des plaies dans les brûlures faciales. Les traitements topiques sont, par exemple, les crèmes et les onguents antimicrobiens ainsi que les substituts cutanés biologiques ou issus des techniques de bioingénierie (artificiels).

Cinq petites études ont été incluses dans la revue. Deux études ont comparé deux produits antimicrobiens différents, tandis que trois études ont comparé des produits antimicrobiens à des substituts cutanés. Toutes les études étaient petites et présentaient un risque élevé de biais ; par conséquent, nous ne pouvons pas nous fier à leurs résultats et les éléments de preuve dans l’ensemble sont de faible qualité. Il n'existe pas suffisamment de preuves fiables pour déterminer si les traitements topiques améliorent les résultats chez les personnes atteintes de brûlures faciales, notamment en ce qui concerne l’amélioration de la cicatrisation des plaies, les taux d'infection, la nécessité d’intervenir chirurgicalement, l’amélioration de l'aspect des cicatrices, la réduction de la douleur, l'amélioration de la satisfaction globale des patients, la réduction des effets indésirables, l’amélioration de la qualité de vie ou la réduction de la durée d’hospitalisation. Des recherches supplémentaires sont nécessaires.

Notes de traduction

Traduit par: French Cochrane Centre 5th February, 2013
Traduction financée par: Minist�re du Travail, de l'Emploi et de la Sant� Fran�ais

Resumo para leigos

Tratamento tópico de queimaduras faciais

Lesões por queimaduras são um importante problema de saúde. Queimaduras frequentemente acontecem no pescoço ou na cabeça. Estas são áreas centrais para a identidade da pessoa e tem um papel vital para a comunicação. Outras habilidades básicas como audição, olfato e respiração também podem ser afetados diretamente por queimaduras faciais. Os autores dessa revisão Cochrane quiseram avaliar os efeitos de tratamentos tópicos (superficiais) no reparo de ferimentos causados por queimados faciais. Exemplos de tratamentos tópicos são antimicrobianos cremes e pomadas, e substitutos de pele biológicos ou artificiais.

Cinco pequenos estudos foram incluídos nessa revisão. Dois estudos compararam dois antimicrobianos diferentes, enquanto os outros três compararam antimicrobianos com susbtitutos de pele. Todos os estudos eram pequenos e com alto risco de viés. Por isso, os resultados podem não ser confiáveis e a qualidade global da evidência é baixa. Não há evidência confiável de que tratamentos tópicos para pessoas com queimaduras faciais melhoram os resultados, incluindo melhora no reparo da ferida, taxas de infecção, necessidade de cirurgia, melhora da aparência das cicatrizes, redução da dor, melhora da satisfação global do paciente, redução dos efeitos adversos, melhora da qualidade de vida ou redução do tempo de permanência no hospital. São necessárias mais pesquisas a respeito.

Notas de tradução

Notas de tradução CD008058.pub2

Streszczenie prostym językiem

Leczenie miejscowe oparzeń twarzy

Oparzenia są istotnym problemem zdrowotnym. Najczęściej oparzenia występują w okolicy głowy lub szyi. Te części ciała mają zasadnicze znaczenie dla tożsamości osoby i odgrywają istotną rolę w komunikacji. Inne podstawowe umiejętności, takie jak słyszenie, odczuwanie zapachów i oddychanie mogą zostać bezpośrednio upośledzone w wyniku oparzenia twarzy. Celem autorów niniejszego przeglądu Cochrane była ocena wpływu stosowania miejscowego leczenia (powierzchniowego) na gojenie się ran po oparzeniu twarzy. Do miejscowego leczenia zaliczamy: kremy antybakteryjne i maści oraz substytuty skóry żywe lub uzyskiwane dzięki technologiom bioinżynieryjnym.

Do przeglądu włączono pięć badań klinicznych z małą liczbą uczestników. W dwóch badaniach porównywano dwa różne środki przeciwbakteryjne, natomiast w pozostałych trzech badaniach porównywano środki przeciwbakteryjne z substytutami skóry. Wszystkie badania obejmowały małą liczbę uczestników i były obciążone dużym ryzykiem błędu systematycznego, dlatego nie możemy być jednoznacznie pewni wniosków, także ogólna jakość danych naukowych była niska. Dostępnych jest zbyt mało wiarygodnych danych naukowych, które wykazałyby czy leczenie miejscowe poprawia wyniki u osób z oparzeniami skóry pod względem poprawy gojenia się ran, odsetka zakażeń ran, potrzeby zabiegu chirurgicznego, poprawy wyglądu blizn, zmniejszenia bólu, poprawy ogólnej satysfakcji pacjenta, zmniejszenia działań niepożądanych, poprawy jakości życia lub skrócenia czasu hospitalizacji. Niezbędne są dalsze badania.

Uwagi do tłumaczenia

Tłumaczenie: Magdalena Koperny Redakcja: Joanna Zając

Background

(We have provided a glossary of some of the terms used in this review in Appendix 1.)

Burn injuries are an important health problem, resulting in 45,000 admissions annually in the United States of America (USA), of which more than 25,000 admissions to hospitals with specialised burn centres (American Burn Association 2011). In the United Kingdom, approximately 13,000 people a year are admitted to hospital for treatment of burns (Hettiaratchy 2004a), while in the Netherlands the annual figure is about 1800 people (Ormel 2010), 550 to 600 of whom are treated in one of the three Dutch burn centres. Mortality rates from burn injuries have substantially decreased because of major improvements in burn care made in the 20th century. This has resulted in a shift in attention towards the functional outcome after a burn injury rather than mortality (Van Baar 2006). The head and neck region is estimated to be the site of burn injury in between 27% (Fatusi 2006) and 60% (Chien 2003; Fraulin 1996) of burn cases. The face is central to our identity and also provides our most expressive means of communication. Appearance, communication and other basic senses and abilities such as hearing, smelling and breathing may be affected as a direct result of a facial burn, or its sequelae (Serghiou 2004). Impaired function and distorted appearance may both induce psychological problems, problems with social reintegration and affect quality of life (Van Loey 2003).

Description of the condition

A burn injury to the skin occurs when some, or all, the different layers of skin are destroyed by physical energy delivered via a hot liquid, flame, contact with a hot surface, ultraviolet/infrared radiation, radioactivity, electricity or chemicals (World Health Organization 2011). Severity of burn wounds is characterised by their size and depth as well as their location and associated injuries. The size of a burn is measured by the percentage of Total Body Surface Area affected (% TBSA), which is the percentage of the surface area of the skin burned, while the depth of a burn is determined by the layers of skin destroyed. So far, no consensus has been reached on the exact classifications of burns, especially not in relation to the classification of depth (Klasen 2004). In general, skin burns are classified as either superficial partial-thickness burns, deep partial-thickness burns or full-thickness burns. In superficial partial-thickness burns only the epidermal layer and the superficial part of the dermis is destroyed. Healing generally occurs within two weeks, with very little, or no, scarring, due to the migration of epithelial cells to the surface of the skin. In deep partial-thickness burns, the epidermis and most of the dermis is destroyed, with damage to deeper structures within the skin such as blood vessels, nerves and hair follicles. If re-epithelialisation does not occur within two to three weeks, then hypertrophic scarring may occur (Cubison 2006; Deitch 1983). Finally, full-thickness burns involve all the layers of skin and may involve structures underneath, such as muscle and bone, leaving little chance of healing from the epithelial elements at the bottom of the wound. In the case of a very small burn, healing might occur by contraction and growth of epithelial cell from the wound edges. Full-thickness burns will nearly always result in hypertrophic (raised) scarring. Hypertrophic scarring can be assessed with different tools, but there is still no consensus concerning its definition (Bloemen 2009).

Full-thickness facial burns are rare, since the face's high vascularity rapidly dissipates heat (Choi 2008). Facial burns are often caused by flash burns, which usually cause partial-thickness burns. Nonetheless, full-thickness facial burns do occur, especially in flame and contact burns, and in the event of prolonged exposure to a heating source, for example if the person was unconscious or paralysed at the time of accident. In addition, in some places (e.g. nose and ears) facial skin is very thin, and, therefore, more vulnerable to deep burns. When nose and ears are deeply burned, the anatomical structures can change or disappear.

Immediately after the thermal injury the surfaces of burn wounds are sterile, but they are rapidly colonised by a variety of micro-organisms (Erol 2004; Wysocki 2002). These micro-organisms originate from the patient’s own skin, respiratory and gastro-intestinal flora, and also from contact with contaminated surfaces in the external environment, hands of healthcare workers and even air (Erol 2004; Weber 2004; Wysocki 2002). Burn wounds provide a favourable niche for microbial colonisation and proliferation because of their protein-rich environment and avascular necrotic tissue (Barret 2003; Erol 2004). This avascularity of eschar (necrotic tissue) results in impaired migration of host immune cells and restricts delivery of systemically administered antimicrobial agents to the area. The most common burn wound pathogens are Staphylococcus aureus and Pseudomonas aeruginosa (Nagoba 2010). Microbial colonisation of burn wounds has been associated with delayed wound healing, increased need for surgical interventions and prolonged length of stay at burn centres (Vermeulen 2007).

Once 30% of the total body surface area has been burned there may be systemic (whole body) responses in addition to local responses. This occurs because of the release of inflammatory mediators at the site of injury (Hettiaratchy 2004b). Besides generating excessive oedema in burns, these systemic reactions can further compromise the healing of a burn wound, and so it is important to consider adequate local treatment, as well as systemic management of a burn, as this may influence the final outcome of the injury.

Another possible outcome of a burn injury is hypertrophic scarring, which occurs when the balance between collagen synthesis and breakdown is disrupted (Herndon 2007). The post-burn hypertrophic scar may present itself either as a pink to red in colour and slightly thickened, or as a red to purple inelastic mass of skin tissue. If a hypertrophic scar surrounds openings such as the eyes or mouth, functional impairment of the face can occur. The eyes for instance, may not close, due to the inelasticity and contraction of the hypertrophic skin, and the mouth may not open maximally. Furthermore, these scars can result in discomfort, because of itching, and sometimes cause neuropathic (nerve) pain (Van Loey 2008). The degree of hypertrophic scarring differs among individuals and depends on a variety of factors, one of which is time to wound healing, with hypertrophic scar formation being seen more often when wound healing takes more than 21 days (Cubison 2006). In general, a deeper burn wound results in the formation of more hypertrophic tissue. Other factors that affect hypertrophic scarring are race, age, genetic factors, type of injury, anatomic region and mechanical tension on the wound (Bloemen 2009).

Description of the intervention

The focus of this review is topical treatment for facial burns. Topical treatment comprises any remedy, agent, substance, device or skin substitute that is placed on the face as a therapy for burn wounds. This definition excludes invasive surgical intervention, which is another important treatment in burn care. Excluding this intervention is necessary in order to narrow the scope of this review and increase the comparability of outcomes. Numerous dressings and topical ointments are used to treat facial burns. Hansen 2004 conducted a survey on the standards of topical wound care for facial burns among burn centres in the USA. Most burn centres used topical bacitracin for partial-thickness facial burns and silver sulphadiazine (SSD) or bacitracin for full-thickness facial burns, with variations in treatment modalities. A survey of European burn centres reported that most centres agreed that some kind of antibacterial topical agent should be used, particularly for deep facial burns, but there were large variations in practice (De Haas 2005). Before applying topical or surgical treatment, a burn wound surface might need additional preparation in the form of debridement (removal of dead tissue). The debridement of burns is divided in two main approaches, namely:

  • superficial debridement: cleaning the wound surface using a brush, gauze or chemical, and removing the superficial loose wound surface;

  • surgical debridement: the excision of the burn wound, with removal of all non-vital tissue.

In this review only superficial debridement will be considered.

How the intervention might work

Interventions used in topical treatment of facial burns can be divided into four main categories: wound preparation agents and antiseptics; wound dressings; antimicrobial agents; and other treatments, including alternative remedies. An elaboration of each category is described below.

Wound preparation agents and antiseptics

Antiseptics are topical agents designed to reduce or eliminate micro-organisms in a wound. They can be used to cleanse facial burn surfaces after injury, or to prepare wounds for surgical debridement, or the application of a further topical agent (Ward 1995). Examples of antiseptics include chlorhexidine digluconate and povidone iodine. Other wound-preparation agents include enzymatic debriding agents. These agents prepare the wound by chemical debridement, but their use is controversial for facial burns (Leon-Villapalos 2008).

Wound dressings

Wound dressings, including biological dressings and bioengineered skin substitutes, are used to create an optimal environment for epidermal wound healing. For a long time, a moist environment was regarded as optimal (Winter 1962), however, more recently Jonkman 1989 has suggested that epidermal wound healing is best accelerated in an environment "between moist and dry", i.e. a more jelly-like wound exudate environment. Nowadays, several wound dressings have these moist or gel-forming qualities. Occlusive dressings, such as hydrocolloids and hydrogel dressings, form a moist or jelly-like environment by incorporating wound fluids into the dressing. Semi-occlusive dressings (e.g. polyurethane film, foam or a hydrofibre) permit evaporation of excess water and prevent maceration, while maintaining a moist environment. Silicon-coated nylon dressings function primarily as non-adherent dressing layers, and, therefore, reduce potential damage during dressing changes (Walmsley 2002). Simple wound dressings, such as synthetic non-adherent or paraffin gauze dressings, sometimes incorporate medication such as chlorhexidine.

Biological dressings (e.g. cadaver allografts (skin from corpses) and porcine (pig) skin xenografts) can be used to treat partial-thickness burns. These provide temporary wound coverage until full healing can be achieved, or until autografting (skin graft(s) using the patient's own skin) can take place. Their use is limited due to their lack of availability, acceptability, and the possibility of disease transfer (Pham 2007). Another biological dressing, amnion (derived from the membranous sac that surrounds the developing embryo), has recently been proposed as a wound dressing for burn treatment (Kesting 2008). In addition, bioengineered skin substitutes can be used as "smart dressings" in topical therapy; these not only provide immediate wound cover, but are also available in large quantities, with a negligible possibility of disease transfer. Unfortunately, most skin substitutes are expensive and considerable expertise is required to select the appropriate material for the situation (Pham 2007).

Antimicrobial agents

Topical antimicrobial agents are used with the aim of controlling and limiting infection, and they are central to topical burn therapy. The ideal topical prophylactic antimicrobial agent would have a broad spectrum of activity with a long duration of action, low toxicity and the ability to penetrate eschar (necrotic tissue) without being absorbed by the body (Monafo 1990). Ideal topical antimicrobials do not hamper epithelial outgrowth and deliver a high concentration of active ingredients to devitalised, devascularised and potentially necrotic wounds, helping to provide a favourable wound healing environment. Use of topical antimicrobials may help to minimise wound deepening, and the need for extensive debridement and subsequent grafting. This is fundamentally important for facial wounds, where overzealous debridement may affect function and appearance (Leon-Villapalos 2008).

The antimicrobial agents used in burn care include silver preparations. Silver sulphadiazine (SSD), in particular, is widely used and acts on burn eschar to limit the extent of non-viable tissue in situations where surgery is either not possible, or would not be the immediate first option - as in facial burns (Leon-Villapalos 2008). Cerium nitrate is another antimicrobial agent which penetrates burned tissue and has a broad spectrum of activity against Gram-positive and Gram-negative bacteria, and fungal species, especially in combination with SSD. Cerium nitrate also has a hardening effect on burn eschar, which is thought to prevent bacterial ingress and helps maintain a moist wound. Furthermore, cerium is supposed to bind and denature the lipid-protein complex released from burned skin responsible for the profound immunosuppression associated with major cutaneous burns (Allgöwer 2008; Garner 2005). Despite their popularity and widespread use, silver-based modalities are not without complications, including frequently observed delayed wound healing, which might be due to the retardation of sloughing in partial-thickness burns. In addition, increased hypertrophic scarring has been described with SSD; while skin irritation, black staining of the skin and the possibility of systemic absorption of silver have also been reported (Atiyeh 2007; Pham 2007). Furhermore, a Cochrane systematic review concluded that "there is insufficient evidence to establish whether silver-containing dressings or topical agents promote wound healing or prevent wound infection; some poor quality evidence for SSD suggests the opposite" (Storm-Versloot 2010).

Other antimicrobial agents include natrium fusidate and nitrofuran. It has been reported that some antimicrobial medications might delay proper healing mechanisms of the wound (Le Duc 2007; Teepe 1993), and that improper use can contribute to the emergence of resistant microbes (Nagoba 2010). In this review, simple wound dressings will be included in this antimicrobial category when they contain an antimicrobial medication.

Other treatments, including alternative remedies

Several additional forms of topical therapy are available, including alternative remedies such as honey and Aloe vera. Honey is said to prevent bacterial growth, form a physical barrier, act as an enzymatic debrider and promote epithelialisation and angiogenesis (formation of new blood vessels). Aloe vera could accelerate the wound healing process and rate of re-epithelialisation in partial-thickness burns (Maenthaisong 2007; Somboonwong 2000). Other alternative remedies, such as covering with banana or cabbage leaves, or potato skins, are sometimes used in places where treatment resources are limited. Any other topical treatment for facial burns which does not fall into one of the main groups above will be included in this category of alternative remedies.

Why it is important to do this review

Treatment of facial burns is more demanding than treatment of burns on other parts of the body, not only because of the location of vital sensory and communication organs but also because the face is highly vascular. This high vascularisation increases the self-healing potential of facial burns and, therefore, justifies a conservative approach to treatment, though this may require intensive daily care. There is uncertainty about which treatment is the most effective for facial burns, and, consequently, there are large variations in practice (De Haas 2005; Leon-Villapalos 2008). Since treatment contributes to outcome - which is especially important for facial burns in terms of both physical and psychological functioning - it is important to consider the most effective treatment.

Existing guidelines to support clinical decision making in burn care are predominantly practice-based or are concerned with the general treatment of burns. For example, an evidence-based guideline was published on treatment of burns and scalds in primary care (New Zealand Guidelines Group 2007). In addition, several systematic reviews have been published in the field of wound care; in 2008 a review on dressings for superficial and partial-thickness burns was published (Wasiak 2008), and in the same year the use of honey as a topical treatment for wounds was systematically reviewed (Jull 2008 ), however neither review specifically considered facial burns. Another systemic review by Vermeulen 2007 reviewed the use of topical silver for treating infected wounds, and Storm-Versloot 2010 recently reviewed the effects of topical silver for prevention of wound infection. In conclusion, current published reviews do not address the effectiveness of topical treatment for facial burns.

Objectives

To evaluate the effects of topical interventions on wound healing in people with facial burns of any depth.

Methods

Criteria for considering studies for this review

Types of studies

We considered all randomised controlled trials (RCTs) that evaluated the effects of topical treatments for facial burns. We decided to consider controlled clinical trials (CCTs) only in the absence of RCTs.

Types of participants

We considered studies that included people of any age with a facial burn wound of any degree in any care setting. Any type of burn injury was eligible (flame, scald, chemical etc).

Types of interventions

Studies were considered for inclusion if topical therapy was applied and compared with any comparator intervention. We defined topical therapy as any remedy, agent, substance, device or skin substitute (biological or bioengineered) that was applied to the surface of the facial wound in the acute phase with the aim of treating the burn. We defined the acute phase as the period of wound healing that occurs up to wound closure (epithelialisation). We divided the topical interventions considered for inclusion into the following four categories:

  • wound preparation agents and antiseptics;

  • wound dressings, e.g. occlusive and semi-occlusive dressings, biological and bioengineered dressings;

  • antimicrobial agents;

  • other treatments, including alternative remedies.

The previously stated definition of topical therapy excluded surgical debridement as an index intervention in this review. Comparator interventions could include any other intervention, no intervention or a placebo intervention.

Types of outcome measures

Study outcomes did not form part of the selection process. We divided outcomes into primary and secondary outcomes; these are listed below.

Primary outcomes
  • Time to complete wound healing.

  • Change in wound surface area over time, or the proportion of the burn wound surface area that had healed within a specified time period.

  • Wound infection (as defined by the trial authors).

We accepted any definition of change in wound surface area over time, or proportion of wound surface area healed in a specified time period. In addition, we accepted any definition of wound infection. All primary outcomes were assessed as short-term endpoints (i.e. three months).

Secondary outcomes
  • Proportion of facial burns requiring (reconstructive) surgery.

  • Scar quality: observed and self-reported (any definition of scar quality was accepted).

  • Pain.

  • Patient satisfaction.

  • Adverse effects: classified as: diagnosed by a clinician, diagnosed by laboratory results or patient-reported symptoms.

  • Quality of life.

  • Length of hospital stay (LOS).

Because we anticipated that primary studies would report and analyse secondary outcomes at different time points, we prespecified time points as either short-term or long-term. The short-term endpoints (i.e. up to three months post burn) included the outcomes: pain, patient satisfaction, adverse effects and length of hospital stay; the long-term endpoints (i.e. after 3 months and up to 12 months post burn) included the outcomes: proportion of facial burns requiring (reconstructive) surgery, scar quality and quality of life.

Search methods for identification of studies

Electronic searches

We searched the following electronic databases for reports of randomized controlled trials:

  • Cochrane Wounds Group Specialized Register (Searched 12 November 2012);

  • the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10);

  • Ovid MEDLINE (1950 to November Week 1 2012);

  • Ovid MEDLINE (In-Process & Other Non-Indexed Citations, searched November 12 2012);

  • Ovid EMBASE (1980 to 2012 Week 45);

  • EBSCO CINAHL (1982 to 9 November 2012).

The search strategies for Ovid MEDLINE, Ovid EMBASE and EBSCO CINAHL can be found in Appendix 2, Appendix 3 and Appendix 4 respectively. The Ovid MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximizing version (2008 revision) (Lefebvre 2011). The EMBASE and CINAHL searches were combined with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2009). No date or language restrictions were applied.

The following CENTRAL search strategy was used:
#1 MeSH descriptor Anti-Bacterial Agents explode all trees
#2 MeSH descriptor Administration, Topical explode all trees
#3 (#1 AND #2)
#4 (topical NEAR/3 antibiotic*):ti,ab,kw
#5 MeSH descriptor Anti-Infective Agents, Local explode all trees
#6 (topical NEAR/3 antiseptic*):ti,ab,kw
#7 MeSH descriptor Anti-Inflammatory Agents explode all trees
#8 MeSH descriptor Glucocorticoids explode all trees
#9 (#7 OR #8)
#10 (#2 AND #9)
#11 (topical NEAR/3 (steroid* or corticosteroid* or glucocorticoid*)):ti,ab,kw
#12 MeSH descriptor Estrogens explode all trees
#13 (#2 AND #12)
#14 (oestrogen or estrogen):ti,ab,kw
#15 MeSH descriptor Enzymes explode all trees
#16 (#2 AND #15)
#17 enzym*:ti,ab,kw
#18 MeSH descriptor Growth Substances explode all trees
#19 (#2 AND #18)
#20 (growth NEXT factor*):ti,ab,kw
#21 MeSH descriptor Collagen explode all trees
#22 collagen*:ti,ab,kw
#23 MeSH descriptor Silver explode all trees
#24 MeSH descriptor Silver Sulfadiazine explode all trees
#25 silver*:ti,ab,kw
#26 cerium nitrate:ti,ab.kw
#27 MeSH descriptor Complementary Therapies explode all trees
#28 MeSH descriptor Honey explode all trees
#29 honey:ti,ab.kw
#30 MeSH descriptor Aloe explode all trees
#31 aloe:ti,ab,kw
#32 MeSH descriptor Ointments explode all trees
#33 (ointment* or lotion* or cream* or gel* or solution*):ti,ab,kw
#34 topical:ti,ab,kw
#35 MeSH descriptor Bandages explode all trees
#36 MeSH descriptor Alginates explode all trees
#37 MeSH descriptor Hydrogel explode all trees
#38 MeSH descriptor Skin, Artificial explode all trees
#39 (dressing* or pad or pads or gauze or tulle or film or bead or foam* or non-adherent or "non adherent" or hydrocolloid* or hydrofibre* or hydrogel* or alginate* or plaster* or compress or absorb* or dextra* or silicon* or amnion*):ti,ab,kw
#40 (#3 OR #4 OR #5 OR #6 OR #10 OR #11 OR #13 OR #14 OR #16 OR #17 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39)
#41 MeSH descriptor Burns explode all trees
#42 (burn or burns or burned or scald*):ti,ab,kw
#43 (thermal NEXT injur*):ti,ab,kw
#44 (#41 OR #42 OR #43)
#45 MeSH descriptor Face explode all trees
#46 MeSH descriptor Facial Injuries explode all trees
#47 MeSH descriptor Ear explode all trees
#48 (face or facial or mouth* or nose* or "ear" or "ears"):ti,ab,kw
#49 (#45 OR #46 OR #47 OR #48)
#50 (#40 AND #44 AND #49)

In addition, we searched the International Clinical Trials Registry Platform Search Portal (www.who.int/trialsearch) (Searched 19 November 2012).

Searching other resources

We checked reference lists within all studies and major review articles retrieved in an effort to identify any additional relevant studies. We sent emails to all authors of included studies requesting information on unpublished data and ongoing studies.

Data collection and analysis

Selection of studies

Without restrictions on language of publication or publication status, two review authors (CH and JH) independently assessed the titles and abstracts of studies identified from the search in terms of their relevance and design. We obtained full versions of articles if they matched the inclusion criteria from this initial assessment. The review authors independently assessed full text articles and determined a final selection of trials eligible for this review. Another review author (MvB) evaluated any discrepancies and advised in case of disagreement.

Data extraction and management

Two review authors (CH and JH), working independently, extracted and summarised details of trials using a data extraction sheet. They extracted data on the following items:

  • Characteristics of the trial: method of randomisation, setting, location of care, country, source of funding.

  • Participants: number, age, gender, type of burn, percentage Total Body Surface Area (TBSA) burned, burn depth, concurrent illnesses.

  • Intervention topical agents: type of dressing, dose used, frequency of dressing changes, time elapsed before treatment, concurrent interventions.

  • Comparator intervention: see above.

  • Outcomes: types of outcomes measured, timing of outcomes.

  • Results.

The authors resolved any discrepancies by discussion with a third review author (MvB), and contacted the trial authors when information was missing from published reports or clarification was needed. Data from trials published in duplicate were included only once, but were maximally data extracted.

Assessment of risk of bias in included studies

Two review authors (CH and JH) made systematic and independent assessments of the risk of bias of each trial, using the Cochrane Risk of Bias criteria (Higgins 2011). The criteria relate to the following issues:

  • sequence generation;

  • allocation concealment;

  • blinding of participants, care providers and outcome assessors;

  • incomplete outcome data: assessment of drop-out rate and intention-to-treat analysis;

  • selective outcome reporting;

  • other sources of bias: baseline similarity, co-interventions, compliance, similar timing of outcome assessment.

Risk of bias increases with each criterion that is judged to be negative. A detailed description of criteria for a judgement of 'low risk of bias', 'high risk of bias' or 'unclear risk of bias' is available (see Appendix 5). Any discrepancies in judgement between the two review authors was resolved by discussion with a third review author (MvB). Final assessment of risk of bias was presented in a risk of bias summary figure, which presents all of the judgements in a cross-tabulation of study by entry. This display of internal validity indicates the weight the reader may give to the results of each study.

Measures of treatment effect

Data analysis was performed according to the guidelines of the Cochrane Collaboration (Deeks 2011). One review author (CH) entered quantitative data into RevMan, this was checked by another review author (JH), and analysed using the Cochrane Collaboration's associated software (RevMan). For each outcome, summary estimates of treatment effect (with 95% confidence intervals (CI)) were calculated for every comparison. Dichotomous outcomes were presented as risk ratios (RR) (also called relative risks) (see Handbook 9.2.2, Deeks 2011) with 95% CI, and continuous outcomes were presented as mean differences (MD) with 95% CI. We intended to use standardised mean differences (SMD) on occasions when studies assessed the same outcome (e.g. quality of life) but measured the outcome in different ways. Time to wound healing would be analysed as a survival (time-to-event) outcome if possible, using an appropriate analytical method (i.e. hazard ratio, Cochrane Reviewers handbook 9.2.6 Deeks 2011).

Unit of analysis issues

We addressed the level at which randomisation occurred in our analysis. In general, the unit of randomisation and measurement was expected to be the patient. Any deviations were described and addressed in the analysis.

Dealing with missing data

We contacted the original investigators to request missing data whenever possible.

Assessment of heterogeneity

We planned to explore both clinical and statistical heterogeneity. Clinical heterogeneity was assessed using information on type of dressing, dose used and frequency of dressing changes. We planned to test statistical heterogeneity using the chi squared test and estimate the amount of heterogeneity using I2 (with 95% CI) (Higgins 2003; Deeks 2011), which examines the percentage of total variation across studies due to heterogeneity rather than to chance.

Assessment of reporting biases

We planned to measure publication bias by the Begg funnel plot (Begg 1994) and the Egger test (Egger 1997), if the included studies were homogeneous and sufficient in number.

Data synthesis

We planned to perform a meta-analysis for each primary outcome if clinical and statistical homogeneity indicated this would be appropriate (Higgins 2003), and calculate summary estimates of treatment effect for every comparison. We planned to conduct a narrative overview, structured by the type of comparison, when statistical meta-analyses was inappropriate.

Subgroup analysis and investigation of heterogeneity

We planned to investigate heterogeneity through subgroup and sensitivity analysis (Deeks 2011), when there was a sufficient number of studies in the meta-analysis (i.e. more than 10). We planned to conduct subgroup analysis for:

  • Partial-thickness burns compared with full-thickness burns, as the effects of topical interventions were expected to differ between patient groups with different burn depths.

  • Adequate concealment of allocation (low risk of bias versus unclear, or high risk of bias).

Sensitivity analysis

If there were a sufficient number of studies in the meta-analysis, we planned to perform a sensitivity analysis showing how conclusions might be affected if studies at high risk of bias were excluded from the analyses. We planned to explore the effect of excluding studies with unclear and inadequate sequence generation and unclear and inadequate allocation concealment within the sensitivity analysis.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification; Characteristics of ongoing studies.

See: Characteristics of included studies; Characteristics of excluded studies.

Results of the search

The search identified, after initial de-duplication, 416 articles. Two review authors (CH and JH) independently assessed the titles and abstracts of these articles and judged 20 citations to be potentially eligible for the review. Two citations appeared to be duplicates, decreasing the number of unique articles to 18. Full texts of the eligible articles were obtained and assessed by the same two review authors. They completed data extraction forms and the risk of bias table, and screened the references in the articles for additional eligible studies. No additional studies were identified with this "snowballing" method. The full text of two articles (Li 2005; Liang 2007) was published only in Chinese and were assessed by Chinese speakers who decided that they were not RCTs. An additional search in the International Clinical Trials Registry Platform Search Portal (www.who.int/trialsearch) resulted in one additional, potentially eligible trial (Lehna 2012).

Included studies

Assessment of the 18 potentially eligible articles (20 citations) resulted in the inclusion of five studies (six citations) (Ang 2000; Demling 1999; Demling 2002; Desai 1991; Horch 2005). The characteristics of these studies are described in the Characteristics of included studies and are summarised below. Four studies (Hindy 2009; Jiaao 2011; Mabrouk 2012; Oen 2012) have been added to the Characteristics of studies awaiting classification and will be assessed in the next update of this review. The details of the trial retrieved from the International Clinical Trials Registry Platform Search Portal (Lehna 2012) has been added to the Characteristics of ongoing studies while we keep in contact with the trialists regarding the progress of the trial.

Health care settings

All five RCTs took place in burn centres; three in the USA (Desai 1991; Demling 1999; Demling 2002); one in Singapore (Ang 2000) and one in Germany (Horch 2005).

Participants

A total of 119 participants (55 intervention, 64 control) were recruited to the five included studies (range of sample size 10 to 39), although it is possible that this number might be lower due to a possible overlap of participants between two studies (Demling 1999; Demling 2002), which potentially would decrease the total to 98. Age and percentage TBSA burned of the included participants are summarised below. The mean age and standard deviation (SD) or standard error (SE) were reported in three studies (Demling 1999; Demling 2002; Desai 1991), and one study reported median age only (34.3 years), and range (24 to 67 years) of the whole study population (Horch 2005). In Desai 1991, the mean age was 11.4 years (SE 1.2 years) in the intervention group and 9.5 years (SE 1.6 years) in the control group. In Demling 1999 and Demling 2002, the mean age varied from 29 years (SD 7 years) to 44 years (SD 10 years). Percentage TBSA burned was reported in four studies (Ang 2000; Demling 1999; Demling 2002; Desai 1991) and varied from 1.56% (SE 0.18) in the control group in Ang 2000, to 50% (SE 6) in the control group in Desai 1991. Horch 2005 did not provide information about the percentage TBSA burned.

Interventions

One study compared two different antimicrobial agents: Moist Exposed Burn Ointment (MEBO) and silver sulphadiazine (SSD) (Ang 2000). Another study compared routine care plus an antimicrobial agent (i.e. 1% gentamicin cream) administered via iontophoresis (use of an electric current to move a drug through the skin to a deep site) with routine care alone (Desai 1991). The routine care comprised of the application of mafenide acetate (another antimicrobial substance) every six hours.

The remaining three studies compared skin substitutes with antimicrobial agents. In Demling 1999 and Demling 2002, the intervention group received bio-engineered skin substitutes (TransCyte®) and the control group received standard care with topical antibiotics. TransCyte® is a bilayered, biologically-active, temporary skin substitute with an outer flexible knitted-nylon layer permeable to water vapour but impermeable to bacteria that decreases environmental insults. The inner layer is impregnated with human fibronectin and collagen Type I. In Demling 1999, the standard care consisted of application of bacitracin two to three times a day in mid-dermal burns, while this procedure was preceded by the application of SSD in the first one to two days in deeper burns. Demling 2002 did not provide additional information about the topical antibiotic used in standard care. In Horch 2005, the biological skin substitute used was an allograft (glycerolised cadaver skin), and the topical antimicrobial ointment was SSD. In both groups the application of treatment followed superficial debridement. No studies investigated wound preparation agents and antiseptics or other treatment, including alternative remedies.

Outcomes

Four studies included time to complete wound healing as an outcome of interest, but differed in their definition of this outcome, measuring it as number of days to complete wound healing (Ang 2000), number of days to complete re-epithelialisation (Horch 2005), time in days to more than 90% re-epithelialisation (Demling 1999), and time in days to more than 95% re-epithelialisation (Demling 2002). In addition, Ang 2000 reported the number of participants healed at 10 days. Wound infection was a pre-specified outcome in three studies (Demling 1999; Demling 2002; Desai 1991), and another study reported this outcome although it had not be pre-specified in the methods section (Horch 2005). Demling 2002 determined wound infection with quantitative swab cultures, using a cut-off value of 105 organisms/g. Demling 1999 and Desai 1991 determined wound infection with qualitative outcome measures, which included increased exudate and surrounding cellulitis (Demling 1999), and the appearance of chondritis (Desai 1991). The Horch 2005 trial did not describe how infection was measured.

Secondary outcomes reported in the five studies included the need for (reconstructive) surgery, hypertrophic scarring, pain, length of hospital stay and adverse effects. Ang 2000 and Desai 1991 examined the need for (reconstructive) surgery with a follow-up of six months post-burn. Hypertrophic scarring was an outcome in one study (Horch 2005), but a measurement instrument was not described. Pain was reported as an outcome of interest only in the Demling studies (Demling 1999; Demling 2002). Both studies used a 10-point scale to assess pain (0 for no pain and 10 for worst pain). Two studies reported the length of hospital stay (Demling 1999; Desai 1991), and additional adverse effects were reported in Horch 2005 and Desai 1991.

Sponsorship

One study explicitly stated that none of the authors had commercial associations or financial interests that might pose a conflict of interest (Ang 2000), while Horch 2005 and Desai 1991 provided no information about sponsorship. In Demling 1999 and Demling 2002 the intervention was an explicitly mentioned brand, but it was not stated whether this application was sponsored or purchased.

Excluded studies

Nine studies (10 citations) were excluded because they were not RCTs (Branski 2008; Covey 1987; Hartmann 2007; Lansdown 2004; Li 2005; Liang 2007; Papp 1990), or because the focus of the study was not on facial burns (Ang 2001; Rege 1999).

Risk of bias in included studies

Two review authors (CH and JH) independently assessed risk of bias in the five included studies and initially disagreed on 14 judgements. Thirteen disagreements were resolved by discussion, and one disagreement was presented to a third review author (MvB) for final judgement. This one disagreement was related to the avoidance or similarity of co-interventions in Demling 1999. Most of the other disagreements were related to blinding of the outcome assessor, which sometimes differed between short-term and long-term follow-up. Details of the risk of bias judgements for the five studies are presented in separate risk of bias tables (part of Characteristics of included studies), a summary figure (Figure 1), and are described below.

Figure 1.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

For risk of bias assessment the term "allocation" included sequence generation and allocation concealment, which both had to be considered.

Sequence generation

Of the five included studies, only Ang 2000 described the method of sequence generation adequately. Ang 2000 described the method as: "Randomly alternating permuted sub-blocks of size 4 and 6, with equal numbers per treatment within each sub-block, were used to obtain an overall block size of 10". The other four studies stated only that participants were randomised, but did not describe the method of sequence generation (Demling 1999; Demling 2002; Desai 1991; Horch 2005).

Allocation concealment

Of the five included studies, only Ang 2000 described the method of allocation concealment employed adequately, stating that allocation was determined by means of telephone calls to a research unit during office hours or by sealed envelopes after office hours. The other four studies did not describe the method of allocation concealment (Demling 1999; Demling 2002; Desai 1991; Horch 2005).

Blinding

Review authors had to judge the blinding of participants, care providers and outcome assessors. None of the five studies reported blinding of participants or care providers, and so, because the nature of treatments made it impossible to blind them, the reviewers made a judgement of "no" rather than one of "unclear". Blinding of outcome assessors was reported in one study (Ang 2000); two studies clearly did not undertake blinded outcome assessment (Demling 1999; Demling 2002), and in two studies it was unclear whether the outcome assessor was blinded (Desai 1991; Horch 2005).

Incomplete outcome data

The item "incomplete outcome data" consisted of two topics: drop-out rate and intention-to-treat analysis (ITT). The drop-out rate was described and acceptable (i.e.did not exceed 20% for short-term follow-up and 30% for long-term follow-up and does not lead to substantial bias) in three studies (Ang 2000; Demling 2002; Horch 2005), while two studies did not report it or make it evident in the outcome assessment (Demling 1999; Desai 1991). ITT-analysis was performed in one study (Demling 2002); another study did not report ITT-analysis specifically, but it appeared likely when the study was assessed (Horch 2005). One study stated that ITT-analysis was performed, but assessment of the study showed clearly that it had not (Ang 2000). The final two studies were unclear on this point (Demling 1999; Desai 1991).

Selective reporting

Four studies were classified as free of suggestion of selective outcome reporting (Ang 2000; Demling 1999; Demling 2002; Horch 2005), but one was not (Desai 1991). In Demling 1999, the pre-specified outcome of length of hospital stay was not reported for major burns, because other non-facial burns interfered with this outcome and prolonged hospital stay. Desai 1991 listed wound healing as an outcome of interest but did not report it in the results section.

Other potential sources of bias

Review authors considered four other potential sources of bias (i.e. baseline characteristics, co-interventions, compliance and timing of outcome assessment). The baseline characteristics between intervention and control group were similar in three studies (Demling 1999; Demling 2002; Horch 2005). In Ang 2000, the description of baseline characteristics was limited to only one important prognostic indicator (i.e. % TBSA burned), which was insufficient to make a judgement of low risk of bias for baseline similarity. In Desai 1991 the percentage TBSA burned in both groups was not similar and no information was provided about etiology. Co-interventions were avoided, or similar, in one study (Demling 1999); cleaning procedures were different in one study (Ang 2000); no information was provided about co-interventions in two studies (Desai 1991; Horch 2005); and one study stated "subsequent care in the intervention group when needed", but did not report whether this care was applied (Demling 2002). Compliance with the intervention was acceptable in all five studies (Ang 2000; Demling 1999; Demling 2002; Desai 1991; Horch 2005). The timing of the outcome assessment was similar in all groups in all five studies (Ang 2000; Demling 1999; Demling 2002; Desai 1991; Horch 2005).

Effects of interventions

Heterogeneity of studies with regard to interventions and outcomes prevented assessment of reporting biases and limited data synthesis to a narrative overview, structured by the type of comparison. Because meta-analysis was inappropriate, no subgroup and sensitivity analyses were performed. The effects of interventions are presented in Table 1 and summarised below.

Table 1. Results from included trials
Study IDMain baseline characteristicsNumber of participants and drop-out ratePrimary outcomesSecondary outcomes
Ang 2000

Number of participants:

I: 17; C: 22.

% TBSA burned (Mean; SE; Range):

I: 2.16; 0.38; 0.13-6.0:
C: 1.56; 0.18; 0.5-3.5.

Initial number of participants: 115.

After randomisation: I: 57; C: 58.

Drop-outs:I: 3; C: 0.

Participants with facial burns: I: 17; C:22.

Particpants in short term analysis:

I: 17; C: 22.

Participants in long term analysis:

I:17; C: 20.

Number of days taken for face-wound to heal:

I: 2-35 days (range); C: not reported.

Proportion completely healed in 10 days:

I: 14/17; C: 17/22.

Need for reconstructive surgery 6 months PB:

I: 0/17; C: 0/20.

Demling 1999

Number of participants:

Minor burns: I: 5; C: 5.
Major burns: I: 5; C: 6.

Mean age (SD years):

Minor burns: I: 31(8); C: 29(7).
Major burns: I: 44(10); C: 40(8).

Etiology: Flame.

% TBSA burned (Mean (SD)):

Minor burns: I: 10(3); C: 7(2).
Major burns: I: 32(9); C: 30(8).

% TBSA burned Full-thickness (Mean (SD)):

Minor burns: I: 0; C:0.
Major burns: I: 10(3); C: 8(2).

Initial number of participants: 21.

Number of participants with minor burns: 10.

Number of participants with major burns: 11.

After randomisation:

Minor burns: I: 5; C: 5.
Major burns: I: 5; C: 6.

Participants in short term analysis:

Minor burns: I: 5; C: 5.
Major burns: I: 5; C: 6.

Mean number of days to > 90% re-epithelialisation (SD):

Minor burns:
I: 8(1); C: 12(3); significantly different P < 0.05.

Major burns:
I: 8(2); C: 14(4); significantly different P < 0.05.

Signs of local wound infection:

Minor burns: I: 0; C: 0.
Major burns: I: 0; C: 0.

Pain during facial care (Mean (SD)):

Minor burns: I: 2(1); C: 5(1).
Major burns: I: 2(1); C: 5(1).

Pain between facial care (Mean (SD)):

Minor burns: I: 1(0.5); C: 3(2).
Major burns: I: 2(1); C: 4(2).

Mean length of stay (SD):

Minor burns: I: 1(0.5); C: 3(1).
Major burns: Not reported.

Demling 2002

Number of participants:I: 16; C: 18.

Mean age (SD):I: 39(9); C: 40(8).

Etiology:

Flame: I: 11; C: 12.
Scald: I: 5; C: 6.

% TBSA burned (Mean (SD)): I: 24(8); C: 21(9).

% TBSA burned Full-thickness (Mean (SD)):
I: 12(7); C: 10(6).

Initial number of participants: 34.

After randomisation:

I: 16; C: 18.

Participants in short term analysis:

I: 16; C: 18.

Mean number of days to > 95% re-epithelialisation (SD):

I: 9(4); C: 15(4); significantly different P < 0.05.

Signs of infection diagnosed with swab cultures exceeding 105 organisms/gram:

I: 0; C: 0.

Pain during facial care (Mean (SD)): I: 3(1); C: 7(2).

Pain between facial care (Mean (SD)): I: 2(1); C: 4(2).

Desai 1991

Number of participants: I: 7; C: 8.

Mean age (SE):I: 11.4 (1.2); C: 9.5(1.6).

% TBSA burned (Mean (SE)): I: 35(7); C: 50(6).

% TBSA burned Full-thickness (Mean (SE)):I: 20(9); C: 32(7).

Initial number of participants: 15.

After randomisation: I: 7; C: 8.

Participants in short term analysis: I: 7; C: 8.

Cases of wound infection diagnosed with the occurrence of chondritis: I: 3; C: 4.

Mean number (SE) of surgical procedures required: I: 1.2(0.1) C: 1.0(0); significantly different P < 0.05.

Adverse effect of treatment: occurrence of gentamicin-resistant micro-organisms I: 29%; C: 0%.

Mean length of stay (SE): I: 26(1); C: 38(3).

Horch 2005

Number of participants: I: 5; C: 5.

Median age (range): I + C: 34.3(24-67).

Initial number of participants: 10.

After randomisation: I: 5; C: 5.

Participants in short term analysis:

I: 5; C: 5.

Median number of days to complete re-epithelialisation:
I:10.5; C: 12.4; significantly different P < 0.05.

Signs of underlying infection: I: 0; C: not reported

Hypertrophic scar formation: I: 0; C: 2.

Adverse effect of treatment: localized partial integration of the biological dressing I: 1; C: 0.

Abbreviations: I = intervention group; C = control group; TBSA = Total Body Surface Area; SE = Standard Error; PB = post-burn; SD = Standard Deviation; P = P value.

Comparison: antimicrobial agents compared with other antimicrobial agents

Two studies compared antimicrobial agents with another antimicrobial agent in 54 people (Ang 2000; Desai 1991).

Primary outcomes
Time to complete wound healing

One study reported time to complete wound healing (Ang 2000). A study by Ang 2000 compared Moist Exposed Burn Ointment (MEBO) with silver sulphadiazine (SSD) in 39 people with partial thickness facial burns. Although time to complete wound healing was an outcome of interest in this study, the authors reported only the range of this outcome for the intervention group (2-35 days) and stated that MEBO resulted in healing rates similar to those seen with SSD dressings. After adjusting for initial percentage Body Surface Area (BSA) burned of the face wound, the hazard ratio for healing was 0.84 (95% CI 0.38 to 1.85) (no statistically significant difference).

Proportion completely healed in specified time period

Ang 2000 also reported the proportion of participants who were completely healed at 10 days (14 out of 17 participants in the MEBO group and 17 out of 22 participants in the SSD group); risk ratio (RR) 1.07 (95% CI 0.78 to 1.46; Analysis 1.1) (no statistically significant difference).

Wound infection

Desai 1991 compared routine care (application of mafenide acetate cream dressings every six hours) plus an antimicrobial agent (gentamicin) administered via iontophoresis with routine care alone in 15 participants with ear burns. Three participants in the intervention group and four participants in the control group developed infection and chondritis (inflammation of cartilage), RR 0.86 (95% CI 0.29 to 2.58; Analysis 2.1) (no statistically significant difference).

Secondary outcomes
Need for further surgery

The need for further surgery was reported by Ang 2000. At six months post-burn no participant in either the MEBO group (n = 17) or the SSD group (n = 20) received surgery. Desai 1991 reported that the mean number of surgical procedures in the intervention group was 1.2 (SE 0.1) and 1.0 (SE 0) in the control group. This difference was statistically significant (P < 0.05) in favour of the control group.

Adverse effects of treatment

The adverse effects of treatment were reported in one study (Desai 1991). Desai 1991 documented the appearance of gentamicin-resistant organisms in 29% of the participants in the group receiving gentamicin via iontophoresis, and in 0% of the participants in the control group, resulting in a RR of 5.63 (95% CI 0.31 to 100.52; Analysis 2.2) (no statistically significant difference).

Length of stay (LOS)

In Desai 1991, the mean LOS was significantly shorter in the intervention group, 26 days (SD 2.6 days), compared with 38 days (SD 8.5 days) in the control group (mean difference -12.00, 95% CI -18.20 to -5.80; Analysis 2.3), but there was no significant difference in LOS after adjusting for burn size.

Scar quality, pain, patient satisfaction and quality of life were not reported in these trials.

Comparison: wound dressings (skin substitutes) compared with antimicrobials

Three studies compared a skin substitute (a bio-engineered skin substitute (Demling 1999; Demling 2002) or allograft (Horch 2005)) with an antimicrobial (either bacitracin (Demling 1999) or SSD (Horch 2005) or an unspecified antibacterial ointment (Demling 2002)) in 65 people.

Primary outcomes
Time to complete wound healing

Three studies reported time to complete wound healing (Demling 1999; Demling 2002; Horch 2005) but as they did not use the appropriate statistical method for their analyses these data were not plotted graphically. Time to healing is a form of time to event data, more correctly analysed using survival methods which can account for censoring (i.e., just for the time that people were observed so it takes account of when they dropped out), it is inappropriate to report and analyse time to wound healing as if it were a continuous variable unless everyone healed and there was no loss to follow up. Demling 1999 divided 21 participants into two groups for minor and major burns. Wounds in the minor burns skin substitute group had a mean healing time of eight days (SD 1 day), which was significantly less than the mean healing time of 12 days (SD 3 days) in the bacitracin group (P value < 0.05). Similar results were reported for major burns where the skin substitute group had a mean healing time of eight days (SD 2 days), which was significantly less than the mean healing time of 14 days (SD 4 days) in the bacitracin group (P < 0.05). In Demling 2002, wounds in the skin substitute group had a mean healing time of nine days (SD 4 days; n = 16), which was significantly less than the mean healing time of 15 days (SD 4 days; n = 18) in the antibacterial ointment group (P < 0.05). Horch 2005 reported the median time to re-epithelialisation, which was significantly less in the allograft group (10.5 days; n = 5) compared to the SSD group (12.4 days; n = 5) (P < 0.05).

Wound infection

Three studies reported wound infection as an outcome. In Demling 1999 and Demling 2002 none of the participants in the intervention or the control groups showed signs of infection. In Horch 2005 none of the participants in the intervention group showed local infections, while there was no information about wound infection in the control group.

Secondary outcomes
Scar quality

Scar quality was a reported outcome in Horch 2005. Scar quality was defined as the incidence of hypertrophic scar formation six months post-burn. At that point none of the participants in the intervention group (n = 5) and two participants in the control group (n = 5) had hypertrophic scar formation, resulting in a non-significant risk ratio (RR) of 0.20 (95% CI 0.01 to 3.35; Analysis 4.1). Horch 2005 did not report a measurement tool or provide a definition used to classify scars as hypertrophic.

Pain

Pain was an outcome of interest in both studies by Demling (Demling 1999; Demling 2002), which used a 10-point scale to measure it (0 for no pain and 10 for worst pain). Pain measurements were made during, and between, facial care. Demling 1999 divided the participants into two groups for minor and major burns. In the minor burn group, the mean pain score during facial care in the intervention group was 2 (SD 1) and 5 (SD 1) in the control group (mean difference -3.00, 95% CI -4.24 to -1.76; Analysis 3.1); while the mean pain between facial care in the intervention group was 1 (SD 0.5) and 3 (SD 2) in the control group (mean difference -2.00, 95% CI -3.81 to -0.19; Analysis 3.2). In the major burns group, the mean pain during facial care in the intervention group was 2 (SD 1) and 5 (SD 1) in the control group (mean difference -3.00, 95% CI -4.19 to -1.81; Analysis 3.3); while the mean pain between facial care in the intervention group was 2 (SD 1) and 4 (SD 2) in the control group (mean difference -2.00, 95% CI -3.82 to -0.18; Analysis 3.4). All the above mean differences were statistically significant (P < 0.05).

In Demling 2002, the mean pain during facial care in the intervention group was 3 (SD 1) and 7 (SD 2) in the control group (mean difference -4.00, 95% CI -5.05 to -2.95; Analysis 3.5); while the mean pain between facial care in the intervention group was 2 (SD 1) and 4 (SD 2) in the control group (mean difference -2.00, 95% CI -3.05 to -0.95; Analysis 3.6). Both mean differences were statistically significant (P < 0.05).

Adverse effects of treatment

Adverse effects of treatment was reported in one study (Horch 2005). In Horch 2005, one participant in the intervention group suffered a localised integration of the biological dressing, which was removed by two repeated dermabrasion manoeuvres. After these manoeuvres, no more visible allograft remnants remained.

Length of stay (LOS)

Length of stay (LOS) was reported by Demling 1999, for the minor burns group only where the mean LOS was significantly less in the intervention group at 1 day (SD 0.5 days), compared with 3 days (SD 1 day) for the control group (mean difference -2.00, 95% CI -2.98 to -1.02; Analysis 3.7).

Need for (reconstructive) surgery, patient satisfaction and quality of life were not reported in these trials.

Discussion

Summary of main results

We included five randomised controlled trials in this review that evaluated the effect of a variety of topical interventions for facial burns. Three studies compared skin substitutes with different antimicrobial agents whilst two studies compared two different antimicrobial agents. None of the studies investigated wound preparation agents, antiseptics or other treatments, including alternative remedies. The variety of topical interventions evaluated and differences in outcome measures between studies made pooling of data inappropriate, therefore, the results have been presented in a narrative overview by comparison. This summary of main results is divided in two primary outcomes (i.e. wound healing and wound infection) and all secondary outcomes have been combined.

Wound healing

Wound healing was variously measured and reported as: time to complete wound healing, average proportion of wound completely healed within a specified time period, change in wounds and percentage of wound healed during follow up. Time to complete wound healing was reported in four studies, but only Ang 2000 used survival methods (the appropriate approach to statistical analysis of time to event data). This study compared two antimicrobial agents (MEBO and silver sulphadiazine) in 39 participants and found a similar risk of healing with both interventions (hazard ratio 0.84, 95% CI 0.38 to 1.85) (Ang 2000). The other three studies compared a wound dressing (i.e. skin substitute (Transcyte® and allograft)) with an antimicrobial agent. The difference in mean time to complete wound healing in days was significantly reduced with the skin substitutes in two of the studies (Demling 1999; Demling 2002). The third study reported a statistically significant reduction in median days to complete wound healing, which also favoured the skin substitutes (i.e. intervention group 10.5 days, control group 12.4 days) (Horch 2005). Thus, the results of all three studies of skin substitutes compared with antimicrobial agents favoured the skin substitutes. A cautious conclusion might be that the time to complete wound healing is shorter with the application of skin substitutes compared with topical antimicrobials. A reason for our caution is that none of the three studies used the appropriate statistical method - survival analysis - for these analyses (Demling 1999; Demling 2002; Horch 2005) and if not all participants were completely healed or if there were withdrawals during the study this estimate will be biased. The proportion of the wound that was completely healed in a specified time period was reported in Ang 2000, where the results did not show a statistically significant difference. Consequently we can only confidently conclude that there is no high quality evidence of a difference in facial burn wound healing between the antimicrobials studied and either alternative antimicrobials or skin substitutes.

Wound infection

Four studies addressed wound infection as a negative outcome. Demling 1999 and Demling 2002 reported no occurrence of wound infection in any group; Horch 2005 reported no occurrence of wound infection in the intervention group, but did not provide information about the control group; Desai 1991 reported three cases of chondritis in the intervention group and four cases in the control group. These data were insufficient to support any definite conclusions.

Secondary outcomes

Except for patient satisfaction and quality of life, all other secondary outcomes (need for (reconstructive) surgery, scar quality, pain, adverse effects of treatment and length of stay) were addressed by at least one study. One study addressed the number of surgical procedures required (Desai 1991), which significantly favoured the control group. One study addressed the need for reconstructive surgery (Ang 2000); none of the participants needed any in the follow-up period. The follow-up period in this study was six months post-burn, which might be too short for a full assessment of the need for reconstructive surgery. Reconstructive surgery can be divided into urgent, essential and desirable procedures. The urgent and essential procedures might be performed within a six-month follow-up period, but the desirable procedure is usually postponed until scars have fully matured. This maturation can take a year or longer (Barret 2004). Therefore, differences in the need for reconstructive surgery between intervention and control group might appear in a later phase.

An adverse effect of treatment that consisted of a localised integration of the biological dressing (removed by two dermabrasion manoeuvres) was reported in Horch 2005. Another adverse effect of treatment was reported in Desai 1991 where gentamicin-resistant micro-organisms appeared in the intervention group. The only study that assessed scar quality did not find a significant treatment effect (Horch 2005). Both studies that assessed pain found significantly better results for the groups receiving skin substitutes (Demling 1999; Demling 2002). The results showed a greater mean difference in pain levels during facial care sessions, which scored 3 to 4 points on the pain scale compared to pain experienced between facial care sessions, which scored 2 points. This finding might not be surprising because the intervention group had hardly any wound dressing sessions: after the application of a skin substitute, facial care was usually restricted to the first day, although the control group received facial care two or three times a day. The two studies that addressed length of stay did report a statistically significant difference (Demling 1999; Desai 1991), but only in the minor burns sub-group (n = 10) (Demling 1999), or before adjusting for burn size (Desai 1991). After adjusting for burn size in Desai 1991 no difference could be determined between the intervention and control groups for length of hospital stay. All secondary outcomes should be interpreted with caution due to wide 95% confidence intervals and lack of sufficient data.

Overall completeness and applicability of evidence

The objective of this review was to assess the effectiveness of topical interventions on wound healing in people with facial burns of any depth. All topical interventions were eligible for inclusion, but only seven different interventions were identified. Furthermore, four of the included studies investigated only partial-thickness burns, and one did not specify the depth(s) of the facial burns of its participants (Desai 1991). None of the included studies addressed the outcomes of patient satisfaction or quality of life. Therefore, overall completeness has clearly not been achieved. The included studies were heterogeneous, so we could not assess publication bias with a Begg funnel plot or an Egger test. In addition, applicability of evidence might be restricted to specialised burn centres in developed countries, because of the relatively high costs of skin substitutes.

Quality of the evidence

The evidence combined in this review was of insufficient quality to allow definite conclusions to be drawn. In particular, the methodological quality of the included studies was relatively low: all five studies had small sample sizes, ranging from 10 to 39, which increase the spread of confidence intervals and decrease validity of results. While pooling data from small trials could increase statistical power and give a more precise overall estimate of effect size, the studies in this review did not compare similar interventions and had different outcome measures, which prevented pooling. Most of the included studies had other shortcomings regarding sequence generation, allocation concealment, blinding and intention-to-treat (ITT) analysis. Only one study described sequence generation and allocation concealment adequately (Ang 2000); the other four studies only stated that participants were randomised. Blinding of participants and care providers is not easy in studies that compare topical interventions, but outcome assessors could have been blinded. Despite this possibility, only one study reported blinding of outcome assessors for all outcomes (Ang 2000). Intention-to-treat analysis was reported and confirmed in only one study (Demling 2002). Another study did not report ITT-analysis, but it appeared likely when the study was assessed (Horch 2005). The other three studies did not perform ITT-analysis (Ang 2000), or did not report this clearly (Demling 1999; Desai 1991), possibly introducing bias. As a result of all these deficiencies, evidence from the included studies should be interpreted with caution.

Potential biases in the review process

Potential bias in the review process might have arisen as a result of the minimal response to our queries from authors of the eligible studies. The review authors tried to contact study authors by email in an attempt to retrieve all possible data to assess the studies thoroughly. Despite issuing a reminder, we received only one reply from Branski 2008 with answers to our questions. As a result of those answers, we excluded this study as sequence generation and allocation concealment were inadequate and therefore judged not to be a randomised controlled trial. Four other studies scored unclear on these items, but as additional information was not provided, they were included. Another potential bias might have occurred due to a possible patient overlap between Demling 1999 and Demling 2002. Both studies were performed in the same hospital, and did not provide inclusion periods. Therefore, we were unable to confirm whether there was a patient overlap, or determine how one might alter our conclusions.

Agreements and disagreements with other studies or reviews

In general, the results of this review are in accordance with the results of the included studies, but some conclusions in the studies are slightly premature. None of the studies provided firm evidence, so conclusions should be cautious. This review agrees with the statement in Horch 2005 that "it would be worthwhile to perform more clinical studies with a larger number of patients to further evaluate the effect and function of allogenic skin for facial burns", and shows this statement is applicable for skin substitutes in general. Furthermore, the small number of included studies in this review is in accordance with a Cochrane review on a similar topic with a broader search (Wasiak 2008). In that review, burns of all types - except hand burns - were eligible, resulting in 26 included studies. In this review only facial burns were eligible, resulting in five included studies. Another review investigated the methodological quality of randomised controlled trials in burn care (Danilla 2009). Danilla 2009 included 257 eligible studies (from OVID Medline 1950 to January 2008) and concluded that "the reporting standards of RCTs are highly variable and less than optimal in most cases". Furthermore, their results showed an increase in RCTs over time without a significant improvement in methodological quality. These findings are in line with our results, as four out of the five included RCTs were performed in the last decade, but included no studies of high methodological quality. In summary, the number of studies in burn care is growing, but the body of evidence is still hampered due to an insufficient number of studies that follow appropriate evidence-based standards.

Authors' conclusions

Implications for practice

There is insufficient high quality research and evidence to enable conclusions to be drawn about the effects of topical interventions on wound healing in people with facial burns.

Implications for research

In order to improve the quality of the evidence, future studies should be designed in conjunction with a trials expert and a statistician and include a sample size calculation. An appropriate sequence generation and allocation concealment should be used in order to reduce risk of bias, and blinding should be attempted. Although it is difficult to blind participants and care providers, it is possible to blind outcome assessors. A sample size calculation should be used in order to increase statistical power and give a more precise overall estimate of effect size. Furthermore, future trialists might add patient satisfaction and quality of life to their outcomes of interest, as these outcomes are especially important for patients. In addition, future trialists might give some extra thought to the outcome wound healing, as this outcome can be reported in numerous ways and it is not always analysed correctly (i.e. survival analyses). Ideally, all trialists should use the same measurement for wound healing, and as a result, allow comparisons to be made. We suggest a clinical important measurement, for instance time to 95% wound healing, that could be considered as the percentage of wound healing necessary for discharge to outpatient management. This subjective wound assessment, performed by an experienced observer, is found to be a reliable (Bloemen 2011) and valid tool (Bloemen 2012). Topical interventions are numerous, so future research should focus on those interventions most likely to benefit patients.

Acknowledgements

The review authors would like to thank Johannes van der Wouden for his advice on methodology and the people who refereed the protocol and/or review: Wounds Group Editors Andrew Jull, Liz McInnes, Dirk Ubbink, Methodologist: Lois Orton, Statistician: Gill Worthy and Peer referees: Heather Cleland, Mary Mondozzi and Jane Nadel for their comments. Furthermore, we would like to thank Mingming Zhang for assessing two Chinese articles and Elizabeth Royle for copy editing the review.

Data and analyses

Download statistical data

Comparison 1. MEBO vs silver sulphadiazine (SSD)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Proportion completely healed in 10 days1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 MEBO vs silver sulphadiazine (SSD), Outcome 1 Proportion completely healed in 10 days.

Comparison 2. Gentamicin iontophoresis vs routine care
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Chondritis1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
2 Gentamicin-resistant micro-organisms1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
3 Length of hospital stay in days1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 2.1.

Comparison 2 Gentamicin iontophoresis vs routine care, Outcome 1 Chondritis.

Analysis 2.2.

Comparison 2 Gentamicin iontophoresis vs routine care, Outcome 2 Gentamicin-resistant micro-organisms.

Analysis 2.3.

Comparison 2 Gentamicin iontophoresis vs routine care, Outcome 3 Length of hospital stay in days.

Comparison 3. Bioengineered skin substitute vs topical antibiotic
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Pain in minor burns during facial care1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2 Pain in minor burns between facial care1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3 Pain in major burns during facial care1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4 Pain in major burns between facial care1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5 Pain during facial care1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
6 Pain between facial care1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
7 Length of hospital stay in days1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 3.1.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 1 Pain in minor burns during facial care.

Analysis 3.2.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 2 Pain in minor burns between facial care.

Analysis 3.3.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 3 Pain in major burns during facial care.

Analysis 3.4.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 4 Pain in major burns between facial care.

Analysis 3.5.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 5 Pain during facial care.

Analysis 3.6.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 6 Pain between facial care.

Analysis 3.7.

Comparison 3 Bioengineered skin substitute vs topical antibiotic, Outcome 7 Length of hospital stay in days.

Comparison 4. Biological skin substitute vs SSD
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Hypertrophic scar formation1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 4.1.

Comparison 4 Biological skin substitute vs SSD, Outcome 1 Hypertrophic scar formation.

Appendices

Appendix 1. Glossary

Allografting: transplantation of tissue/organs between individuals of the same species.
Amnion: the innermost membranous sac that surrounds and protects the developing embryo, bathed in amniotic fluid.
Angiogenesis: the development of new blood vessels.
Autografting: transplantation of an individual’s own tissue from one site to another site.
Avascular: not associated with, or supplied by, blood vessels.
Bioengineered skin substitute: an artificially-manufactured replacement for skin.
Biological dressings: human or animal tissue used as temporary wound coverings.
CCT: Controlled Clinical Trial.
Debridement: usually surgical removal of lacerated, devitalised, or contaminated tissue.
Dermis: the deep inner layer of the skin, beneath the epidermis, containing connective tissue, blood vessels and fat.
Epidermal: related to the outer epithelial layer of the skin.
Eschar: a scab or dry crust that results from trauma, such as a thermal or chemical burn, infection, or excoriating skin disease.
Flash burn: a lesion caused by exposure to an extremely intense source of radiant energy or heat.
Gastro-intestinal flora: micro-organisms living in both stomach and intestine.
Hypertrophic scar: an elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of scar tissue and regresses spontaneously.
Immunosuppression: deliberate prevention or diminution of the host’s immune response.
Iontophoresis: the introduction of an ionised substance (as a drug) through intact skin by the application of a direct electric current.
MD: Mean Difference.
Necrosis: the pathological process that occurs in cells dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative enzymes, leading to mitochondrial swelling, nuclear flocculation and cell lysis (breakdown). Distinguished from apoptosis (programmed cell death), which is a normal, regulated cellular process.
Occlusive dressing: material, usually gauze or absorbent cotton, used to cover and protect wounds, to seal them from contact with air or bacteria.
Ointment: semisolid preparation used topically for protective emollient effects, or as a vehicle for local administration of medications.
PB: post-burn.
Prophylactic: guarding from, or preventing, the spread or occurrence of disease or infection.
RCT: Randomised Controlled Trial.
Re-epithelialisation: healing by the growth of epithelium over a denuded surface.
Scald: burn caused by a hot liquid, or a hot, moist vapour.
SD: Standard Deviation.
SE: Standard Error.
SMD: Standardised Mean Difference.
Sloughing: process of separating necrotic tissue from viable portions of the body.
SSD: silver sulphadiazine.
Systemic response: reaction related  to the whole body rather than to a localized area or regional part of the body.
TBSA: Total Body Surface Area.
Vascular: relating to the vessels in the body, which circulate fluid, such as blood.
Wound exudate: the material composed of serum, fibrin, and white blood cells that escapes from blood vessels into a superficial lesion.
Xenografting: transplantation of tissue/organs between animals of different species.

Appendix 2. Ovid MEDLINE search strategy

1 exp Burns/
2 (burn or burns or burned or scald$).ti,ab.
3 thermal injur$.ti,ab.
4 1 or 2 or 3
5 exp Face/
6 exp Facial Injuries/
7 exp Ear/
8 (face or facial or nose$1 or mouth$1 or ear$1).ti,ab.
9 or/5-8
10 4 and 9
11 exp Anti-Bacterial Agents/
12 exp Administration, Topical/
13 11 and 12
14 (topical adj3 antibiotic$).ti,ab.
15 (topical adj3 antimicrobial$).ti,ab.
16 exp Anti-Infective Agents, Local/
17 (antiseptic$ or eusol or furagin or sodium hypochlorite or furaltadon).ti,ab.
18 exp Anti-Inflammatory Agents/
19 exp Glucocorticoids/
20 18 or 19
21 12 and 20
22 (topical adj3 (steroid$ or corticosteroid$ or glucocorticoid$)).ti,ab.
23 exp Estrogens/
24 12 and 23
25 (oestrogen$ or estrogen$).ti,ab.
26 exp Enzymes/
27 12 and 26
28 enzym$.ti,ab.
29 exp Growth Substances/
30 12 and 29
31 growth factor$.ti,ab.
32 exp Collagen/
33 collagen$.ti,ab.
34 exp Silver/
35 exp Silver Sulfadiazine/
36 silver$.ti,ab. (14809)
37 cerium nitrate.ti,ab. (42)
38 exp Complementary Therapies/
39 exp Honey/
40 honey$.ti,ab.
41 exp Aloe/
42 aloe.ti,ab.
43 exp Ointments/
44 (ointment$ or lotion$ or cream$ or gel$ or solution$).ti,ab.
45 topical.ti,ab.
46 exp Bandages/
47 exp Alginates/
48 exp Hydrogel/
49 exp Skin, Artificial/
50 exp Hemostatics/
51 (dressing$ or pad or pads or gauze or tulle or film or bead or foam$ or non-adherent or non adherent or hydrocolloid$ or hydrofibre$ or hydrogel$ or alginate$ or plaster$ or compress or absorb$ or dextra$ or silicon$ or amnion$).ti,ab.
52 or/13-17,21-22,24-25,27-28,30-51
53 10 and 52

Appendix 3. Ovid EMBASE search strategy

1 exp Burns/
2 (burn or burns or burned or scald$).ti,ab.
3 thermal injur$.ti,ab.
4 1 or 2 or 3
5 exp Face/
6 exp Facial Injuries/
7 exp Ear/
8 (face or facial or nose$1 or mouth$1 or ear$1).ti,ab.
9 or/5-8
10 4 and 9
11 exp Anti-Bacterial Agents/
12 exp Administration, Topical/
13 11 and 12
14 (topical adj3 antibiotic$).ti,ab.
15 (topical adj3 antimicrobial$).ti,ab.
16 exp Anti-Infective Agents, Local/
17 (antiseptic$ or eusol or furagin or sodium hypochlorite or furaltadon).ti,ab.
18 exp Anti-Inflammatory Agents/
19 exp Glucocorticoids/
20 18 or 19
21 12 and 20
22 (topical adj3 (steroid$ or corticosteroid$ or glucocorticoid$)).ti,ab.
23 exp Estrogens/
24 12 and 23
25 (oestrogen$ or estrogen$).ti,ab.
26 exp Enzymes/
27 12 and 26
28 enzym$.ti,ab.
29 exp Growth Substances/
30 12 and 29
31 growth factor$.ti,ab.
32 exp Collagen/
33 collagen$.ti,ab.
34 exp Silver/
35 exp Silver Sulfadiazine/
36 silver$.ti,ab.
37 cerium nitrate.ti,ab.
38 exp Complementary Therapies/
39 exp Honey/
40 honey$.ti,ab.
41 exp Aloe/
42 aloe.ti,ab.
43 exp Ointments/
44 (ointment$ or lotion$ or cream$ or gel$ or solution$).ti,ab.
45 topical.ti,ab.
46 exp Bandages/
47 exp Alginates/
48 exp Hydrogel/
49 exp Skin, Artificial/
50 exp Hemostatics/
51 (dressing$ or pad or pads or gauze or tulle or film or bead or foam$ or non-adherent or non adherent or hydrocolloid$ or hydrofibre$ or hydrogel$ or alginate$ or plaster$ or compress or absorb$ or dextra$ or silicon$ or amnion$).ti,ab.
52 or/13-17,21-22,24-25,27-28,30-51
53 10 and 52

Appendix 4. EBSCO CINAHL search strategy

S48 S4 and S8 and S47
S47 S11 or S12 or S13 or S14 or S15 or S16 or S17 or S18 or S20 or S21 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31 or S32 or S33 or S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46
S46 AB dressing* or pad or pads or gauze or tulle or film or bead or foam* or non-adherent or non adherent or hydrocolloid* or hydrofibre* or hydrogel* or alginate* or plaster* or compress or absorb* or dextra* or silicon* or amnion*
S45 TI dressing* or pad or pads or gauze or tulle or film or bead or foam* or non-adherent or non adherent or hydrocolloid* or hydrofibre* or hydrogel* or alginate* or plaster* or compress or absorb* or dextra* or silicon* or amnion*
S44 (MH "Skin, Artificial")
S43 (MH "Alginates")
S42 (MH "Bandages and Dressings+")
S41 TI topical or AB topical
S40 TI ( ointment* or lotion* or cream* or gel* or solution*) or AB ( ointment* or lotion* or cream* or gel* or solution*)
S39 (MH "Creams")
S38 (MH "Ointments")
S37 TI aloe or AB aloe
S36 (MH "Aloe")
S35 TI honey or AB honey
S34 (MH "Honey")
S33 TI cerium nitrate or AB cerium nitrate
S32 TI silver or AB silver
S31 (MH "Silver Sulfadiazine")
S30 (MH "Ionic Silver Dressings")
S29 (MH "Silver")
S28 TI collagen* or AB collagen*
S27 (MH "Collagen")
S26 TI growth factor* or AB growth factor*
S25 (MH "Growth Substances+")
S24 TI enzyme* or AB enzyme*
S23 S10 and S22
S22 (MH "Enzymes+")
S21 TI ( oestrogen* or estrogen* ) or AB ( oestrogen* or estrogen* )
S20 (S10 and S19)
S19 (MH "Estrogens+")
S18 TI ( topical N3 steroid* or topical N3 corticosteroid* or topical N3 glucocorticoid* ) or AB ( topical N3 steroid* or topical N3 corticosteroid* or topical N3 glucocorticoid* )
S17 (MH "Glucocorticoids, Topical+")
S16 (MH "Antiinflammatory Agents, Topical+")
S15 TI ( antiseptic* or eusol or furagin or sodium hypochlorite or furaltadon ) or AB ( antiseptic* or eusol or furagin or sodium hypochlorite or furaltadon )
S14 (MH "Antiinfective Agents, Local+")
S13 TI topical N3 antimicrobial* or AB topical N3 antimicrobial*
S12 TI topical N3 antibiotic* or AB topical N3 antibiotic*
S11 S9 and S10
S10 (MH "Administration, Topical+")
S9 (MH "Antibiotics+")
S8 S5 or S6 or S7
S7 TI ( face or facial ) or AB ( face or facial )
S6 (MH "Facial Injuries+")
S5 (MH "Face+")
S4 S1 or S2 or S3
S3 TI thermal* injur* or AB thermal* injur*
S2 TI ( burn or burns or burned or scald* ) or AB ( burn or burns or burned or scald* )
S1 (MH "Burns+")

Appendix 5. Assessing risk of bias

1.  Was the allocation sequence randomly generated?

Low risk of bias

The investigators describe a random component in the sequence generation process such as: referring to a random number table; using a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.

High risk of bias

The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some systematic, non-random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.

Unclear

Insufficient information about the sequence generation process to permit judgement of low or high risk of bias.

2.  Was the treatment allocation adequately concealed?

Low risk of bias

Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation); sequentially-numbered drug containers of identical appearance; sequentially-numbered, opaque, sealed envelopes.

High risk of bias

Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation based on: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear

Insufficient information to permit judgement of low or high risk of bias. This is usually the case if the method of concealment is not described or not described in sufficient detail to allow a definite judgement, for example if the use of assignment envelopes is described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.

3.  Blinding - was knowledge of the allocated interventions adequately prevented during the study?

Low risk of bias

Any one of the following.

  • No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by lack of blinding.

  • Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

  • Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of others unlikely to introduce bias.

High risk of bias

Any one of the following.

  • No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.

  • Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.

  • Either participants or some key study personnel were not blinded, and the non-blinding of others likely to introduce bias.

Unclear

Any one of the following.

  • Insufficient information to permit judgement of low or high risk of bias.

  • The study did not address this outcome.

4. Were incomplete outcome data adequately addressed?

Low risk of bias

Any one of the following.

  • No missing outcome data.

  • Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias).

  • Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.

  • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate.

  • For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size.

  • Missing data have been imputed using appropriate methods.

High risk of bias

Any one of the following.

  • Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups.

  • For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate.

  • For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size.

  • ‘As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.

  • Potentially inappropriate application of simple imputation.

Unclear

Any one of the following.

  • Insufficient reporting of attrition/exclusions to permit judgement of low or high risk of bias (e.g. number randomised not stated, no reasons for missing data provided).

  • The study did not address this outcome.

5. Are reports of the study free of suggestion of selective outcome reporting?

Low risk of bias

Any of the following.

  • The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way.

  • The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon)

High risk of bias

Any one of the following.

  • Not all of the study’s pre-specified primary outcomes have been reported.

  • One or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified.

  • One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect).

  • One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis.

  • The study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear

Insufficient information to permit judgement of low or high risk of bias. It is likely that the majority of studies will fall into this category.

6. Other sources of potential bias

Low risk of bias

The study appears to be free of other sources of bias.

High risk of bias

There is at least one important risk of bias. For example, the study:

  • had a potential source of bias related to the specific study design used; or

  • has been claimed to have been fraudulent; or

  • had some other problem.

Unclear

There may be a risk of bias, but there is either:

  • insufficient information to assess whether an important risk of bias exists; or

  • insufficient rationale or evidence that an identified problem will introduce bias.

 

Contributions of authors

Cornelis J. Hoogewerf coordinated the review, extracted and interpreted data, checked the quality of data extraction, undertook quality assessment, performed and checked quality of statistical analysis, completed the first draft of the review, edited the review, made an intellectual contribution, approved final review prior to submission, and wrote to authors/experts/companies.
Magriet E. Van Baar conceived, designed and coordinated the review, checked quality of data extraction, undertook quality assessment, interpreted data, checked quality of statistical analysis, completed first draft of the review, edited the review, made an intellectual contribution,  approved final review prior to submission, advised, secured funding, performed previous work that was the foundation for the current review, and is guarantor for the review.
Jenda M. Hop extracted data, checked quality of data extraction, undertook quality assessment, interpreted data, completed first draft of the review, performed part of the writing or editing, made an intellectual contribution, approved final review prior to submission and advised on the review.
Irma MMH Oen conceived and designed the review, interpreted data, completed the first draft of the review, performed part of the writing or editing, made an intellectual contribution, approved final review prior to submission, advised on the review and performed previous work that was the foundation of the current review.
Ester Middelkoop conceived and designed the review, interpreted data, completed first draft of the review, edited the review, made an intellectual contribution, approved final review prior to submission, advised on the review, secured funding and performed previous work that was the foundation of the current review.
Marianne K. Nieuwenhuis conceived and designed the review, interpreted data, checked quality of statistical analysis, completed first draft, performed part of the writing or editing, made an intellectual contribution, approved final review prior to submission, advised, and performed previous work that was the foundation of the review.

Contributions of editorial base:

Nicky Cullum: edited the protocol; advised on methodology, interpretation and protocol content, approved the final protocol and review prior to submission.
Sally Bell-Syer: coordinated the editorial process, advised on methodology, interpretation and content, edited the protocol and review.
Ruth Foxlee: designed the search strategy, ran the searches and edited the search methods section.

Declarations of interest

Magriet van Baar, Irma Oen, Esther Middelkoop and Marianne Nieuwenhuis were involved in a trial (Oen 2012) which has been added to the Characteristics of studies awaiting classification and may be eligible for inclusion in future updates of this review.
No other conflicts of interest are declared.

Sources of support

Internal sources

  • The Association of Dutch Burn Centres, Netherlands.

External sources

  • NIHR/Department of Health (England), (Cochrane Wounds Group), UK.

Differences between protocol and review

There are four significant differences between protocol and review. Firstly, two authors were added to the review (CH and JH). Secondly, the electronic search strategy was revised. We expanded the search string and added an extra database (i.e. Ovid MEDLINE - In-Process). Another database changed platform from Ovid CINAHL to EBSCO CINAHL. Thirdly, we changed one question on our data extraction sheet. The question concerning sponsorship was changed from, "Was the trial sponsored by a manufacturer who potentially had an interest in the results?" to, "Was the trial guarded from sponsoring by a manufacturer who potentially had an interest in the results?". In the former question, an affirmative answer (yes) would have a negative meaning (sponsorship). This flaw was detected in a pilot study performed by two review authors (CH and JH), and the question was changed in the latter in order to give an affirmative answer a positive meaning (guarded from sponsorship). Finally, we could not perform all analyses described in the protocol. It was not possible to analyse time to wound healing as survival outcome due to insufficient data. Furthermore, none of the studies assessed the same outcome with the same definition (e.g. 90% or 95% re-epithelialisation for complete wound healing), so no standardised mean differences were used. For the same reason, no meta-analyses or associated analyses were performed.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ang 2000

MethodsRCT.
Participants39 participants (17 intervention, 22 control) with partial-thickness burns up to 40% BSA burned and suffering facial burns.
Exclusion criteria: > 40% BSA burned, extremes of age (< 6 years and > 80 years), chemical and electrical burns, no facial burns.
InterventionsTreatment intervention: Moist Exposed Burn Ointment (MEBO), 1 mm thick layer applied 6 times/day.
Control intervention: SSD applied 2 times/day.
OutcomesNumber of days for the face wound to heal.
Number of participants completely healed in 10 days.
Number of participants requiring reconstructive surgery within 6 months post-burn.
Notes

Participants were a subgroup of a larger study conducted by Ang et al (Ang 2001). That study included not only facial burns but also burns to other locations. 3 participants were excluded from this study: 1 withdrew, 1 was an illegal worker and 1 had a TBSA burned of 68% - not clear whether these participants had facial burns. Also, in this study, 2 participants in the control group died at 36 and 49 days post-burn. These two participants were included in Ang 2000, therefore, the number of participants in the long-term analyses was 20 instead of 22. The short-term analysis was not affected.

Sponsorship: Quote: "None of the investigators had any financial interest in or received any benefits or privileges from the company manufacturing MEBO".

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "patients were randomly assigned either to the conventional (C) group or MEBO group either by telephone calls to the NMRC Clinical Trials and Epidemiology Research Unit, Singapore during office hours, or by sealed envelopes after office hours. Randomly alternating permuted sub-blocks of size 4 and 6, with equal numbers per treatment within each sub-block, were used to obtain an overall block size of 10".
Allocation concealment (selection bias)Low risk

Quote: "patients were randomly assigned either to the conventional (C) group or MEBO group either by telephone calls to the NMRC Clinical Trials and Epidemiology Research Unit, Singapore during office hours, or by sealed envelopes after office hours. Randomly alternating permuted sub-blocks of size 4 and 6, with equal numbers per treatment within each sub-block, were used to obtain an overall block size of 10".

Comment: Probably done, although not stated explicitly that envelopes were opaque.

Blinding (performance bias and detection bias)
All outcomes - patients
High riskNot possible, frequency and appearance of treatments were different.
Blinding (performance bias and detection bias)
All outcomes - care provider
High riskNot possible, frequency and appearance of treatments were different.
Blinding (performance bias and detection bias)
All outcomes - outcome assessor
Low riskThis article used a subgroup. In Ang 2001 the whole population was used and "a burn surgeon not involved in management of cases" assessed the outcomes. Therefore, the judgement is one of low risk of bias.
Incomplete outcome data (attrition bias)
All outcomes - drop-out rate?
Low risk3 drop-outs in the intervention group that were eligible for inclusion (n = 57), but unclear if the drop-outs had facial burns.
Incomplete outcome data (attrition bias)
All outcomes - ITT analysis?
High riskDrop-outs were not analysed.
Selective reporting (reporting bias)Low risk

Outcomes listed in methods were described in results.

Comment: Not seen protocols.

Similarity of baseline characteristics?Unclear riskOnly one characteristic was described (mean % TBSA burned).
Co-interventions avoided or similar?High risk

Co-interventions varied, with different cleaning methods for the different treatments in Ang 2001.

Comment: Since the participants in Ang 2000 were a subgroup from the participants in Ang 2001, it is likely that the co-interventions were different.

Compliance acceptable?Low riskNot mentioned explicit, but likely.
Timing outcome assessments similar?Low riskAfter 5 days, then every 3 days until discharge for both groups.

Demling 1999

MethodsRCT.
Participants21 participants (10 intervention, 11 control) > 18 years with partial-thickness (mid-dermal) burns of at least 50% of the facial surface.
Exclusion criteria: < 18 years, < 50% of facial surface burned, no partial-thickness burns.
InterventionsTreatment intervention: biological skin substitute coated with fibronectin (TransCyte).
Control intervention: topical antibiotics (bacitracin).
OutcomesTime to complete wound healing (> 90% re-epithelialisation).
Wound infection.
Pain (0-10 scale, 0 lowest and 10 highest).
Length of hospital stay.
NotesSponsorship: Authors used TransCyte, unclear if this was sponsored or purchased.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomisation stated, but nothing mentioned about sequence generation.
Allocation concealment (selection bias)Unclear riskRandomisation stated, but nothing mentioned about allocation concealment.
Blinding (performance bias and detection bias)
All outcomes - patients
High riskNot possible due to different appearances of treatments.
Blinding (performance bias and detection bias)
All outcomes - care provider
High riskNot possible due to different appearances of treatments.
Blinding (performance bias and detection bias)
All outcomes - outcome assessor
High riskBurn nurse was not blinded to the intervention.
Incomplete outcome data (attrition bias)
All outcomes - drop-out rate?
Unclear riskNot reported.
Incomplete outcome data (attrition bias)
All outcomes - ITT analysis?
Unclear riskNot reported.
Selective reporting (reporting bias)Low riskOne prespecified outcome, length of hospital stay, was not reported for the major burns group. In this group, the outcome was insignificant due to interference from other burns that lengthened the hospital stay.
Similarity of baseline characteristics?Low riskSubgroups were similar, described in Tables 1 & 2.
Co-interventions avoided or similar?Low riskSome participants in the control group were treated with 2 antimicrobials, some participants only with bacitracin. These are still topical interventions.
Compliance acceptable?Low riskNot mentioned explicitly, but likely.
Timing outcome assessments similar?Low riskDaily assessment.

Demling 2002

MethodsRCT.
Participants34 participants (16 intervention, 18 control) with major burns including partial-thickness facial burns at least mid-dermal in depth.
Exclusion criteria: superficial partial-thickness burns.
InterventionsTreatment intervention: bioactive skin substitute (a bilayered, biologically active, temporary skin substitute (TransCyte)).
Control intervention: antibacterial ointment, no further details available.
OutcomesTime to complete wound healing (> 95% re-epithelialisation).
Wound infection.
Pain (0-10 scale, 0 lowest and 10 highest).
NotesSponsorship: Used: TransCyte®, Smith & Nephew, Inc., Largo, Florida.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomisation stated, but nothing mentioned about sequence generation.
Allocation concealment (selection bias)Unclear riskRandomisation stated, but nothing mentioned about allocation concealment.
Blinding (performance bias and detection bias)
All outcomes - patients
High riskNot possible due to different appearances of treatments.
Blinding (performance bias and detection bias)
All outcomes - care provider
High riskNot possible due to different appearances of treatments.
Blinding (performance bias and detection bias)
All outcomes - outcome assessor
High riskBurn nurse was not blinded to the intervention.
Incomplete outcome data (attrition bias)
All outcomes - drop-out rate?
Low riskNo drop-outs.
Incomplete outcome data (attrition bias)
All outcomes - ITT analysis?
Low riskNot reported, but likely.
Selective reporting (reporting bias)Low riskOutcomes in methods section were described in results section.
Similarity of baseline characteristics?Low riskSubgroups were similar, described in Table 1.
Co-interventions avoided or similar?Unclear risk"Subsequent care in intervention group when needed", not reported how often.
Compliance acceptable?Low riskNot mentioned explicitly, but likely.
Timing outcome assessments similar?Low riskDaily assessment.

Desai 1991

MethodsRCT.
Participants15 participants (7 intervention, 8 control) with ear burns admitted within 72 hours of burn injury.
Exclusion: no informed consent, < 5 years old, not responding to tactile stimulation, not able to communicate discomfort verbally.
InterventionsTreatment intervention: gentamicin iontophoresis + routine care (mafenide acetate).
Control intervention: routine care only (6-hourly application of mafenide acetate).
OutcomesWound infection.
Need for (reconstructive) surgery.
Adverse effects of treatment.
Length of hospital stay.
NotesSponsorship: Not stated. Although sponsorship seems unlikely, still unclear.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "Subjects were randomly assigned."

Comment: No method of sequence generation described.

Allocation concealment (selection bias)Unclear risk

Quote: "Subjects were randomly assigned."

Comment: No method of allocation concealment described.

Blinding (performance bias and detection bias)
All outcomes - patients
High riskNature of intervention made blinding impossible.
Blinding (performance bias and detection bias)
All outcomes - care provider
High riskNature of intervention made blinding impossible.
Blinding (performance bias and detection bias)
All outcomes - outcome assessor
Unclear riskNot stated who assessed the outcomes.
Incomplete outcome data (attrition bias)
All outcomes - drop-out rate?
Unclear riskNo drop-out rate described.
Incomplete outcome data (attrition bias)
All outcomes - ITT analysis?
Unclear riskNot stated, unable to confirm.
Selective reporting (reporting bias)High riskWound healing listed as outcome, but no results presented.
Similarity of baseline characteristics?High riskOnly age, % full thickness burns and time since burn. Not similar with regard to % TBSA burned. Etiology was not mentioned.
Co-interventions avoided or similar?Unclear riskNot stated.
Compliance acceptable?Low riskNot mentioned explicitly, but likely.
Timing outcome assessments similar?Low riskDaily evaluation of infection. Timing of other outcomes was until closure of ear burns.

Horch 2005

  1. a

    Abbreviations

    < = less than
    > = more than
    BSA = body surface area
    NMRC = National Medical Research Council
    RCT = randomised controlled trial
    SSD = silver sulphadiazine
    TBSA = total body surface area

MethodsRCT.
Participants10 severely burned participants (5 intervention, 5 control) with superficial and deep partial-thickness facial burns.
Exclusion criteria: superficial partial-thickness burns or third-degree facial burns.
InterventionsTreatment intervention: glycerolised allograft cadaver (corpse) skin.
Control intervention: open treatment with SSD ointment.
OutcomesTime to complete wound healing.
Wound infection.
Scar quality.
Adverse effects.
NotesSponsorship: Not reported.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "were randomized into groups"

Comment: No method of sequence generation described.

Allocation concealment (selection bias)Unclear risk

Quote: "were randomized into groups"

Comment: No method of allocation concealment described.

Blinding (performance bias and detection bias)
All outcomes - patients
High riskNot possible due to different appearances of treatments.
Blinding (performance bias and detection bias)
All outcomes - care provider
High riskNot possible due to different appearances of treatments.
Blinding (performance bias and detection bias)
All outcomes - outcome assessor
Unclear riskNot evident who assessed the outcome.
Incomplete outcome data (attrition bias)
All outcomes - drop-out rate?
Low riskNo drop-outs.
Incomplete outcome data (attrition bias)
All outcomes - ITT analysis?
Low riskNot reported, but likely.
Selective reporting (reporting bias)Low riskOutcomes listed in methods section were described in results section.
Similarity of baseline characteristics?Low riskStated similar, but not possible to check.
Co-interventions avoided or similar?Unclear riskNot reported.
Compliance acceptable?Low riskNot mentioned explicitly, but likely.
Timing outcome assessments similar?Low riskIncidence of hypertrophic scar formation at 6 months post-burn.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    Abbreviations

    CCT = controlled clinical trial
    RCT = randomised controlled trial

Ang 2001Facial burns not distinguishable from other burns. The participants with facial burns were described in a previous study (Ang 2000), which was included in this review.
Branski 2008Not a randomised controlled trial. After personal communication, this study was judged to be a CCT because allocation was not concealed as every other patient eligible for this trail received amnion.
Covey 1987In the absence of the abstract, this study was included on the basis of the title only. After judging full text it was decided that this was not an RCT.
Hartmann 2007Not an RCT.
Lansdown 2004Not an RCT.
Li 2005Not an RCT.
Liang 2007Not an RCT.
Papp 1990Not an RCT.
Rege 1999No facial burns.

Characteristics of studies awaiting assessment [ordered by study ID]

Hindy 2009

MethodsRCT.
Participants60 participants with superficial dermal burns to the face.
Interventions

Group 1: Sodium carboxymethyl-cellulose silver (Aquacel Ag®).

Group 2: Moist Exposed Burn Ointment (MEBO®).

Group 3: Saline soaked dressing.

Outcomes

Time necessary for healing.

Pain.

Quality of healing.

Patient satisfaction.

NotesStudy was identified in latest search update. Full text is not yet assessed.

Jiaao 2011

MethodsRCT.
Participants30 children.
Interventions

Treatment intervention: rhGM-CSF hydrogel.

Control intervention: placebo hydrogel.

Outcomes

Percentage of wound healing.

Time to complete wound healing.

Adverse effects.

NotesStudy was identified in latest search update. Full text is not yet assessed.

Mabrouk 2012

MethodsRCT.
Participants40 participants with partial-thickness facial burns.
Interventions

Intervention 1: occlusive dressing (Aquacel Ag®).

Intervantion 2: Moist Exposed Burn Ointment (MEBO®).

Outcomes

Lenght of hospital stay.

Rate of infection.

Time to total healing.

Frequency of dressing changes.

Pain.

Cost benefit.

Patient discomfort.

Incidence of hypertrophic scarring.

NotesStudy was identified in latest search update. Full text is not yet assessed.

Oen 2012

Methods"A Randomized Multicentre Clinical Trial".
Participants180 participants of 18 years of age or older, competent or temporarily incompetent, admitted to one of the 3 dedicated Dutch Burn Centres with burn injuries involving the face.
Exclusion criteria: not seen within 24 hours post-burn, mental or cognitive deficits that may interfere with providing informed consent, poor proficiency in Dutch, chemical burns.
InterventionsIntervention 1: cerium nitrate SSD (flammacerium).
Intervention 2: silver sulphadiazine (SSD) (flammazine).
OutcomesNumber of participants requiring surgical excision of their facial burns.
Quality of life and self esteem.
Quality of scar.
Scar elasticity, vascularisation and pigmentation.
Hypertrophic surface area.
NotesStudy was identified in latest search update. Full text is not yet assessed.

Characteristics of ongoing studies [ordered by study ID]

Lehna 2012

Trial name or titleComparison of wound bed establishment in facial burns.
MethodsRCT.
Participants30 participants of 18 years of age or older, admitted to the burn unit with a minimum of 1% partial-thickness burns each side of the face.
InterventionsCollagenase versus Bacitracin.
OutcomesDifference in wound bed establishment; pain; anxiety; itch levels; wound healing.
Starting dateApril 2012.
Contact informationc0lehn01@louisville.edu
Notes 

Ancillary