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Cochrane Database of Systematic Reviews Protocol - Intervention

Topical treatment for facial burns

Authors' declarations of interest

Version published: 07 October 2009 Version history

https://doi.org/10.1002/14651858.CD008058

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view the current version 29 July 2020
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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effectiveness of topical interventions on wound healing in people with facial burns of all depths.

Background

Burn injuries are an important health problem, annually resulting in 40,000 admissions in the United States of America (USA), including more than 25,000 admissions to hospitals with specialized burn centres (American Burns Association 2009). In the United Kingdom, approximately 13,000 people are admitted to hospital each year (Hettiaratchy 2004a). In the Netherlands about 1800 patients per year are admitted to a hospital for treatment of burns (Stolte 2008), including 550 to 600 patients in one of the three Dutch Burn Centres.

The head and neck region is the most frequent site where a burn injury occurs. These percentages vary between 27 to 60%, depending on country, the setting and the definition of what constitutes a facial burn (Hop 2008). The face is involved in 40 to 50% of patients admitted to the Dutch Burn Centres. Children represent 25 to 50% of the total burn population and the prevalence of facial burns in children is between 24 and 52% (Hop 2008).

Because of major improvements in burn care in the twentieth century, mortality rates from burn injuries have substantially decreased. This has resulted in a shift in attention from mortality towards morbidity, for example, the functional outcome after a burn injury (Van Baar 2006). The face is central to our identity and is also one of our most expressive means of communication. These and other basic senses or abilities such as hearing, smelling and breathing may become affected as a direct result of a facial burn, or its sequelae (Serghiou 2004). Both impaired function and distorted appearance may induce psychological problems, problems with social reintegration and that affect quality of life (Van Loey 2003).

Description of the condition

A burn injury of the skin occurs when some or all the different layers of the skin are destroyed. In addition to the location of the burn and associated injuries, the severity of the burn wound is characterized by size and depth.

The size of a burn is measured by the Total Body Surface Area percentage (TBSA%), which is the percentage of the skin surface area burned by physical energy such as hot liquid, flame, contact burns or ultraviolet/infrared radiation, radioactivity, electricity or chemicals (Burns facts, World Health Organization 2004).

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 by depth as either superficial or 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 due to the migration of epithelial cells to the surface, with very little or no scarring.

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‐epithelialization does not occur within 2 to 3 weeks then hypertrophic scarring may occur (Deitch 1983; Cubison 2006).

Finally, full‐thickness burns involve all layers of the skin and may involve the structures beneath such as muscle and bone, leaving little chance of healing from the epithelial elements in the bottom of the wound unless the burn is very small, in which case it might heal by contraction and epithelial cell growth from the wound edges. Full‐thickness burns will nearly always result in hypertrophic scarring.

In the face, full‐thickness burns are rare since the high vascularity of the face rapidly dissipates the heat (Choi 2008). Also facial burns are often caused by flash burns, which usually cause partial‐thickness burns. However, full‐thickness burns can be seen, especially in contact burns and in the event of prolonged exposure to the heating source, for example if the patient was sub‐ or unconscious or paralysed at the time of accident. In addition, in some places (e.g. the nose and ears) facial skin is very thin and more vulnerable to deep burns. If nose and ears are deeply burned, the anatomical structures can change or disappear.

Although burn wound surfaces are sterile immediately following thermal injury, they are rapidly colonized by a variety of micro‐organisms (Wysocki 2002; Erol 2004). The burn wound surface is a protein‐rich environment consisting of a vascular necrotic tissue that provides a favourable niche for microbial colonization and proliferation (Barret 2003; Erol 2004). The avascularity of the eschar (necrotic tissue) results in impaired migration of host immune cells and restricts delivery of systemically administered antimicrobial agents to the area.

Micro‐organisms colonizing the burn wounds originate from the patient’s own skin, respiratory and gastro‐intestinal flora, but the bacteria may also be transferred to a patient’s skin surface via contact with contaminated external environmental surfaces, the hands of health care workers and even air (Wysocki 2002; Erol 2004; Weber 2004). The most common burn wound pathogens are S. aureus and P. aeruginosa. Colonization of burn wounds has been associated with delayed wound healing, increased need for surgical interventions and prolonged length of stay at burn centres.

Hypertrophic scarring occurs if the balance between collagen synthesis and breakdown is disrupted (Herndon 2007). The post burn hypertrophic scar might present itself as a pink to red, slightly thickened or as a red to purple inelastic mass of skin tissue. Functional impairment of the face can occur, especially if the hypertrophic scar surrounds openings like the eyes or mouth. The eyes for instance, may not close due to the inelasticity and contraction of the hypertrophic skin and the mouth might not open maximally. Furthermore, scars can result in discomfort because of itching and sometimes cause neuropathic pain after the burn injury (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 if wound healing takes more than 21 days (Cubison 2006). The general rule is that the deeper the burn wound, the more hypertrophy is formed.

In addition to local responses, severe burn injuries can also bring about systemic responses. The release of inflammatory mediators at the site of the injury has a systemic effect once the burn reaches 30% of the total body surface area (Hettiaratchy 2004b). These systemic reactions, besides the generation of excessive edema in burns, can further compromise the healing of the burn wound. It is important to consider adequate local treatment as well as the systemic management of the burn as this may influence the final outcome of the wound injury.

Description of the intervention

The focus of this review is the topical management of facial burns. Topical management is defined as any remedy, agent, substance, device or skin substitute that is placed on the face as a burn wound treatment. Numerous dressings and topical ointments are used to treat facial burns. Hansen conducted a survey on the standards of topical wound care for facial burns among the burn centres in the USA. Most burn centres used topical bacitracin for partial thickness facial burns and silver sulfadiazine or bacitracin for full thickness facial burns, with variations in treatment modalities (Hansen 2004). 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).

Debridement of the wound surface may be done in preparation of applying the topical treatment or during surgical treatment of the wound. There are two main approaches to the debridement of facial burns:

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

  • surgical debridement, which is defined as the excision with removal of all non‐vital tissue of the burn wound.

In this review only superficial debridement will be considered.

How the intervention might work

Topical management of facial burns can be divided into four main categories as follows:

Preparation of the wound bed

Antiseptics are topical agents designed to reduce or eliminate micro‐organisms in the wound. They can be used to cleanse facial burn surfaces after injury or to prevent infection in the preparation of the skin prior to surgical debridement (Ward 1995). Examples of antiseptics are chlorhexidine digluconate and povidone iodine. Other wound preparation agents are enzymatic debriding agents. These agents prepare the wound by chemical debridement. Their use remains controversial in facial burns(Leon‐Villapalos 2008).

Wound dressings

For a long time a moist environment was regarded as optimal for epidermal wound healing (Winter 1962). However, more recently (Jonkman 1989) has suggested that epidermal wound healing is best accelerated in an environment "between moist and dry", a more jellylike 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 jellylike environment by integrating wound fluids into the dressing. Semi‐occlusive dressings, like polyurethane film, foam or a hydrofibre, permit evaporation of excess water vapour so preventing maceration whilst 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 are synthetic non‐adherent or paraffin gauze dressings and sometimes incorporate medication such as chlorhexidine.

Biological dressings (e.g. cadaver allografts and porcine skin xenografts) can be used to treat partial thickness burns. They provide temporary wound coverage until full healing can be achieved or until autografting. The availability and acceptability of allografts and xenografts together with the possibility of disease transfer limits their use (Pham 2007). Amnion, another biological dressing, has recently been proposed as a burn treatment (Kesting 2008).

Additionally bioengineered skin substitutes can be used as a "smart dressing" in topical therapy. Biosynthetic skin substitutes provide immediate wound cover, are available in large quantities and have a negligible risk of cross‐infection. However, most skin substitutes are expensive and considerable expertise is required to decide which material is appropriate for any given situation (Pham 2007).

Antimicrobial agents

Topical antimicrobial agents are used with the aim of controlling and limiting infection and are central to topical burn therapy. The ideal prophylactic topical antimicrobial agent has a broad spectrum with a long duration of action, low toxicity and the ability to penetrate eschar (necrotic tissue) without systemic absorption (Monafo 1990). Ideally, topical antimicrobials should not hamper epithelial outgrowth, when delivering a high concentration of the active ingredients to a devitalized, devascularised and potentially necrotic wound, but help to provide a favourable wound healing environment. Use of topical antimicrobials may help to minimise the conversion into a deeper wound, the need for extensive debridement and subsequent grafting. This is of fundamental importance with a facial wound where overzealous debridement may affect function and appearance (Leon‐Villapalos 2008).

Silver preparations are antimicrobial agents used in burn care. Silver sulphadiazine, in particular, is widely used and is thought to act on burn eschar limiting the extent of the non‐viable tissue when surgery is either not possible or not the immediate first option, as in facial burns (Leon‐Villapalos 2008). Cerium nitrate is another antimicrobial agent which penetrates the burned tissue and has a broad spectrum of activity against both gram‐positive bacteria and gram‐negative bacteria and fungal species, especially if combined with silver sulphadiazine. Other properties are its hardening effect on burn eschar, which is thought to prevent bacterial ingress and helps maintain a moist wound. Furthermore, cerium binds and denatures the lipid protein complex liberated from burned skin that is responsible for the profound immunosuppression associated with major cutaneous burns (Garner 2005; Allgöwer 2008).

Despite their popularity and wide use, silver‐based modalities are not without complications. Delayed wound healing is often observed. This might be due to the retardation of the sloughing of dead tissue in partial thickness burns. In addition increased hypertrophic scarring has been described using silver sulphadiazine and skin irritation, black staining of the skin, and the possibility of systemic absorption of silver have been reported (Pham 2007; Atiyeh 2007).

Other antimicrobial agents include natrium fusidate and nitrofuran. If simple wound dressings are medicated with an antimicrobial medication (e.g. containing povidone iodine, fucidin or chlorhexidine), they will be included in this category. It has been reported that some antimicrobial medications might slow down the proper healing mechanisms of the wound (Teepe 1993; Le Duc 2007).

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, to form a physical barrier, to act as an enzymatic debrider and promote epithelialization and angiogenesis. Aloe vera could accelerate the wound healing process and rate of re‐epithelization in partial‐thickness burns(Somboonwong 2000; Maenthaisong 2007). Other alternative remedies such as covering with (banana) leaves, cabbage 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

The face is highly vascularised and hosts vital areas that make the treatment of facial burns more complicated than treating burns on other parts of the body. Moreover, there is uncertainty about which is the most effective treatment for facial burns and there are large variations in practice (de Haas 2005; Leon‐Villapalos 2008). As treatment contributes to outcome, and in facial burns outcome is specifically important, both in terms of physical as psychological functioning, it is important to consider the most effective treatment.

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, concerning the treatment of burns and scalds in primary care (New Zealand Guidelines Group 2007). Several systematic reviews have been published in the field of wound care. Wasiak 2008 published a review on dressings for superficial and partial thickness burns, and in the same year Jull 2008 systematically reviewed honey as a topical treatment for wounds. However, both reviews did not specifically consider facial burns. Another systemic review by Vermeulen 2008 reviewed the use of topical silver for treating infected wounds and a review is in preparation considering topical treatments for prevention wound infection (Ubbink 2007). In conclusion, published reviews do not address the effectiveness of topical treatment for facial burns.

Objectives

To assess the effectiveness of topical interventions on wound healing in people with facial burns of all depths.

Methods

Criteria for considering studies for this review

Types of studies

We will consider all randomized controlled trials (RCTs), evaluating the effects of topical agents in people with facial burns. Controlled clinical trials (CCTs) will be considered only in the absence of RCTs.

Types of participants

Studies including people of any age with a facial burn wound of any degree in any care setting. Any type of burn injury will be eligible (flame, scald, chemical etc).

Types of interventions

Studies will be considered for inclusion if topical therapy is applied and compared with any comparator intervention. Topical management is defined as any remedy, agent, substance, device or skin substitute that is applied to the surface of the wound in the acute phase with the aim of treating the facial burn. The acute phase is defined as the phase of wound healing that occurs up to wound closure.

Four categories of topical interventions will be considered:

  • Wound preparation agents and antiseptics.

  • Wound dressings, e.g. occlusive and semi‐occlusive dressings, biological dressings and bioengineered dressings.

  • Antimicrobial agents.

  • Other treatments, including alternative remedies.

Surgical debridement is not a topical therapy and therefore will not be included as an index intervention in this review.

Comparator interventions can include any other intervention, no intervention or a placebo intervention. Any type of comparator intervention will be considered.

Types of outcome measures

Study outcome will not form part of the selection process.

Primary outcomes

The positive primary outcomes:

  • Time to complete wound healing or the proportion of the burn wound completely healed (epithelialized) in a specific time period.

  • Change in wound surface area over time or the proportion of burn wounds partly healed in a specific time period.

The negative primary outcome:

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

We will accept any definition of change in wound surface area over time/ proportion of wounds partly healed in a specific time period. In addition, we will accept any definition of wound infection. Both primary outcomes will be assessed as short term end point (three months).

Secondary outcomes

  • Proportion of facial burns requiring surgery.

  • Scar quality: observed and self‐reported (any definition of scar quality will be accepted).

  • Pain.

  • Patient satisfaction.

  • Adverse effects. Adverse effects will be classified as a) diagnosed by clinician, b) diagnosed by laboratory results or c) patient‐reported symptoms.

  • Quality of life.

  • Length of hospital stay (LOS).

The timing of secondary outcome assessment will be limited to one time point. Pain, other adverse effects, patient satisfaction and quality of life will be a short term end‐point (three months). The proportion of facial burns requiring surgery and scar quality, adverse effects, quality of life will be a long‐term end point (e.g. 12 months post burn).

Search methods for identification of studies

Electronic searches

The following electronic databases will be searched for reports of randomized controlled trials:

  • Cochrane Wounds Group Specialized Register (most recent);

  • The Cochrane Central Register of Controlled Trials (CENTRAL) ‐ The Cochrane Library (latest Issue);

  • Ovid MEDLINE ‐ 1950 to date;

  • Ovid EMBASE ‐ 1980 to date;

  • Ovid CINAHL ‐ 1982 to date.

The MEDLINE search will be combined with the Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity‐ and precision‐maximizing version (2008 revision); Ovid format. This filter is published in the Cochrane Handbook for Systematic Reviews of Interventions (Lefebvre 2008). We will combine the EMBASE and CINAHL searches with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN 2009). We will not apply date or language restrictions.

The following CENTRAL search strategy will be used:
#1 MeSH descriptor Burns explode all trees
#2 (burn or burns or burned or scald*):ti,ab,kw
#3 (thermal NEXT injur*):ti,ab,kw
#4 (#1 OR #2 OR #3)
#5 MeSH descriptor Face explode all trees
#6 (face or facial):ti,ab,kw
#7 (#5 OR #6)
#8 (#4 AND #7)
#9 MeSH descriptor Anti‐Bacterial Agents explode all trees
#10 MeSH descriptor Administration, Topical explode all trees
#11 (#9 AND #10)
#12 (topical NEAR/3 antibiotic*):ti,ab,kw
#13 MeSH descriptor Anti‐Infective Agents, Local explode all trees
#14 (topical NEAR/3 antiseptic*):ti,ab,kw
#15 MeSH descriptor Anti‐Inflammatory Agents explode all trees
#16 MeSH descriptor Glucocorticoids explode all trees
#17 (#15 OR #16)
#18 (#10 AND #17)
#19 (topical NEAR/3 (steroid* or corticosteroid* or
glucocorticoid*)):ti,ab,kw
#20 MeSH descriptor Estrogens explode all trees
#21 (#10 AND #20)
#22 (topical NEAR/3 (oestrogen or estrogen)):ti,ab,kw
#23 MeSH descriptor Enzymes explode all trees
#24 (#10 AND #23)
#25 (topical NEAR/3 enzym*):ti,ab,kw
#26 MeSH descriptor Growth Substances explode all trees
#27 (#10 AND #26)
#28 (topical NEAR/3 (growth NEXT factor*)):ti,ab,kw
#29 MeSH descriptor Collagen explode all trees
#30 (#10 AND #29)
#31 (topical NEAR/3 collagen*):ti,ab,kw
#32 (topical NEAR/3 silver*):ti,ab,kw
#33 MeSH descriptor Ointments explode all trees
#34 (ointment* or lotion* or cream*):ti,ab,kw
#35 (topical NEAR/3 (agent* or preparation* or therap* or
treatment*)):ti,ab,kw
#36 (#11 OR #12 OR #13 OR #14 OR #18 OR ( #19 AND #21 ) OR #22 OR
#24 OR #25 OR #27 OR #28 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35)
#37 MeSH descriptor Surgery explode all trees
#38 MeSH descriptor Surgical Procedures, Operative explode all trees
#39 surg*:ti,ab,kw
#40 (#37 OR #38 OR #39)
#41 (#36 OR #40)
#42 (#8 AND #41)

In addition we will search the International Clinical Trials Registry Platform Search Portal (www.who.int/trialsearch).

Searching other resources

We will check citation lists within all studies retrieved and major review articles in an effort to identify any additional relevant studies.

Data collection and analysis

Selection of studies

Two review authors will independently assess the titles and abstracts of studies identified from the search in terms of their relevance and design. Full versions of articles will be obtained if they match the inclusion criteria from this initial assessment. These review authors will also carry out the final selection of trials to be included. Another review author will evaluate any discrepancies and will advise in case of disagreement.

There will be no restrictions on the inclusion of reports based on language of publication or publication status.

Data extraction and management

Two review authors, working independently, will extract and summarize details of trials using a data extraction sheet. We will resolve any discrepancies by discussion with a third review author. We will contact the trial authors to obtain missing information if data are missing from reports, or clarification is needed. Data from trials published in duplicate will be included only once.

We will extract the following data:

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

  • Participants: number, age, gender, type of burn and percentage total body surface area (TBSA) and 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.

Assessment of risk of bias in included studies

Two review authors will make systematic and independent assessments of the risk of bias of each trial, using the Wounds Group adaptation of the Cochrane Risk of Bias criteria (Higgins 2008a). We will resolve any discrepancies by discussion with a third review author.

The criteria are related to the following issues:

  • Sequence generation;

  • Allocation concealment;

  • Blinding of participants, personal and outcome assessors;

  • Incomplete outcome data: assessment 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, trial sponsorship.

A detailed description of criteria for a judgment of 'yes' is available (see Appendix 1). We will present assessment of risk of bias using a 'risk of bias summary figure', which presents all of the judgments in a cross‐tabulation of study by entry. This display of internal validity indicates the weight the reader may give the results of each study.

Measures of treatment effect

Data analysis will be performed according to the guidelines of the Cochrane Collaboration (Deeks 2008). One review author will enter quantitative data into RevMan, it will be checked by another review author, and analysed using the Cochrane Collaboration's associated software (RevMan).

For each outcome, summary estimates of treatment effect (with 95% confidence intervals) will be calculated for every comparison.

Time to wound healing will be analysed as survival (time to event) outcomes if possible, using an appropriate analytical method (i.e. hazard ratio, Cochrane Reviewers handbook 9.2.6 Deeks 2008). Dichotomous outcomes will be presented as risk ratios (also called relative risks) (see Handbook 9.2.2, Deeks 2008.) with 95% CI.

When appropriate, mean differences or standardized mean differences will be presented for continuous outcomes. Standardized mean differences will be used when studies assess the same outcome (for instance quality of life) but measure it in a variety of ways.

Unit of analysis issues

We will address in our analysis the level at which randomization occurred. In general, the unit of randomization and measurement is the patient. Devations will be described and addressed in the analysis.

Dealing with missing data

In the case of missing data, we will contact the original investigators to request missing data whenever possible. If necessary, we will perform data imputation according to the principles from the Handbook (Higgins 2008b). We will explicitly describe our assumptions in case of imputing missing data. In addition, we will perform sensitivity analyses to assess how sensitive results are to changes in the assumptions that are made. Also, we will address the potential impact of missing data on the findings of the review in the Discussion section.

Assessment of heterogeneity

We will explore both clinical and statistical heterogeneity. Clinical heterogeneity will be assessed, using information on type of dressing, dose used and frequency of dressing changes. We will test statistical heterogeneity using the chi squared test and estimate the amount of heterogeneity using I2(with 95% confidence interval (Higgins 2003; Deeks 2008). This examines the percentage of total variation across studies due to heterogeneity rather than to chance.

Assessment of reporting biases

We will present the overall risk of bias in a risk of bias summary per primary or secondary outcome (Higgins 2008a). Publication bias will be measured by the Begg funnel plot (Begg 1994) and the Egger test (Egger 1997). We will analyse study reports on reported biases, using the results of the standardized list, (i.e. Wounds Group adaptation of the Cochrane Risk of Bias criteria, Appendix 1).

Data synthesis

We will perform a meta‐analysis for each primary outcome, if clinical and statistical homogeneity indicate this would be appropriate (Higgins 2003), and calculate summary estimates of treatment effect for every comparison. We will focus on direct comparisons between topical interventions.

No totals will be calculated if trial heterogeneity is considerable (I2greater than 75%). If pooling is appropriate (I2 less than 75%) we will use both a fixed effect and a random effects model. The fixed‐effect model ignores heterogeneity, and gives an estimate of the intervention effect, assuming a single intervention effect. A random effects model incorporates heterogeneity amongst studies (Ioannidis 2007; Deeks 2008).

The primary analyses will be restricted to studies at low risk of bias (Higgins 2008a). We define studies with low risk of bias as RCTs which fulfilled the two criteria of adequate sequence generation, adequate allocation concealment and blinded outcome assessment.

Where statistical meta‐analysis is inappropriate we will undertake a narrative overview. This narrative overview will be structured by the type of experimental interventions.

Subgroup analysis and investigation of heterogeneity

Where there is a sufficient number of studies in the meta‐analysis (N>10), we will investigate heterogeneity through subgroup and sensitivity analysis (Deeks 2008). We will conduct subgroup analyses for:

  • Partial thickness burns versus full thickness burns. The effectiveness of topical interventions is expected to differ between patients groups with different burn depth.

  • Adequate concealment of allocation (yes versus unclear/no).

Sensitivity analysis

Where there is a sufficient number of studies in the meta‐analysis (N>10), we will perform a sensitivity analysis showing how conclusions might be affected if studies at high risk of bias were included in analyses. We will add studies with unclear sequence generation and unclear allocation concealment.