Natural remedies in burn care: a systematic review and network meta-analysis

Muhammad Azri Ismail1, Krisanto Tanjaya1, Gisella Sekar Wruhastanti1, Yudi Siswanto2

Background

Burn injuries are a global public health issue that impact healing time and cause complications. While silver sulfadiazine (SSD) cream is commonly used for treatment, research indicates that SSD can hinder the wound healing process. Natural alternatives like Aloe vera, honey, and amniotic membranes have shown promise in promoting wound healing. This study aimed to evaluate their efficacy by their wound healing time and infection rate.

 

Methods

3 independent reviewers conducted a literature search across 6 databases (Cochrane Central Register of Controlled Trials, PubMed, ScienceDirect, Taylor & Francis, Wiley, and ProQuest). Quality assessment was conducted using the Cochrane Risk of Bias 2 tool, while network meta-analysis was performed using the netmeta package in R. The variable in this study is the average time to burn wound healing and infection occurrence by analyzing MD data or OR of each intervention, with 95% CI to calculate the efficacy.

 

Results

A total of 3,434 patients from 37 studies were included. In the analysis of 26 studies comparing the healing time to SSD, A. vera has the best efficacy (MD: −4.75; 95% CI: −8.67 to −0.86), followed by amniotic membrane (MD: −4.71; 95% CI: −7.45 to −1.97), and honey (MD: −4.25; 95% CI: −6.76 to −1.73). Meanwhile, the occurrence of infection analysis in burn wounds across 24 studies highlighted that honey has the lowest infection rate (OR: 0.09; 95% CI: 0.04 to 0.23) and was the only statistically significant finding when compared to SSD.

 

Conclusions

Aloe vera and amniotic membrane are effective for wound healing, while honey is particularly effective in preventing wound infection in patients with burn injuries.

 

Keywords

Aloe vera, amniotic membrane, burns, honey, silver sulfadiazine

Burn injuries pose a major public health concern, especially in low- and middle-income countries, with higher rates in Africa and Southeast Asia. They are classified as first-, second-, or third-degree.1,2 Abnormal scarring from burns may result from factors such as burn severity, affected surface area, healing time, skin type, burn location, and wound healing process. The primary topical antimicrobial for burn injuries is 1% silver sulfadiazine (SSD) cream, which can cause delayed healing, resistance, renal toxicity, and leukopenia.3 Studies confirm that prolonged SSD cream use on large wounds should be avoided.4

Aloe vera is widely used topically for various skin conditions, as it inhibits thromboxane, reduces inflammation, and promotes healing.5,6 Honey, rich in beneficial compounds, offers antibacterial, anti-inflammatory, immune-boosting, and wound-healing properties, with its composition depending on the nectar source.7,8 These effects result from honey’s acidic pH and high sugar content, which causes osmotic effects, hydrogen peroxide production, and bioactive compounds.9 The human amniotic membrane’s antibacterial properties arise from antimicrobial peptides (AMPs) secreted by its cells.10,11 AMPs like α- and β-defensins exhibit antibacterial, antiviral, and antifungal effects. Antimicrobial agents in amniotic fluid, including transferrin, lysozyme, IgA, globulin β1C/β1A, 7S immunoglobulin, and peptides such as α-defensins and calprotectin, also enhance its antimicrobial properties.12 Side effects of SSD in patients with burns are well-documented, with common issues like leukopenia, itching, rashes, and skin discoloration (1–10% of patients). Severe side effects include anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, kidney failure, and liver toxicity.3,13

In Indonesia, honey is more accessible and affordable than SSD, with local honey priced around 25,000–40,000 IDR per bottle, depending on quality and source. In contrast, SSD requires a prescription or must be bought from pharmacies, making it harder to obtain, especially in rural areas with limited medical supplies. Its high cost as a regulated medication also makes it less affordable.14,15 In Indonesia, A. vera products are widely available online and in retail shops, while SSD, a regulated medication, requires a prescription, limiting its accessibility outside urban centers and specialized healthcare institutions.16 Onion extracts, like Mederma, are more accessible than SSD and commonly used for wound healing and scar reduction, available in traditional and retail stores.17

While SSD is widely available, amniotic membrane is mainly limited to specialized medical settings, with increasing studies on its preparation and use in wound healing. Amniotic membrane use in hospitals and research highlights its specialized medical availability. This study aimed to evaluate the effectiveness of A. vera, honey, and amniotic membrane versus SSD for superficial and partial-thickness burns, focusing on healing time, wound sterility, and infection rates. Secondary outcomes included a network meta-analysis of how these dressings performed compared to SSD. This review may inspire further research, promoting broader use of natural remedies as a wound dressing.

 

 

This systematic review and network meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines with network meta-analysis.18 Disagreements were resolved through discussion.

 

Search strategy and eligibility criteria

Inclusion and exclusion criteria were set before the search to ensure specificity. Inclusion criteria covered human trials, peer-reviewed publications, and comparative studies of burn wound interventions. Exclusion criteria excluded non-human trials, non-burn wound studies, and gray literature. No language restrictions were applied.

The literature search was conducted from February 27 to April 29, 2024, by three reviewers (MAI, KT, and GSW) across six databases: Cochrane Central Register of Controlled Trials, PubMed, ScienceDirect, Taylor & Francis, Wiley, and ProQuest. Key search terms were (“silicone gel” OR “silicone wax” OR “silicone elastomer”) AND (“onion extract” OR “Allium Cepa”) AND (“Burn” OR “Burn management” OR “Burn care” OR “Burn treatment”). A full search strategy report is available. Results were screened for duplicates, followed by title and abstract reviews. Selected studies were then evaluated using inclusion and exclusion criteria before data extraction.

 

Data extraction and outcome of interest

Three reviewers (MAI, KT, and GSW) extracted data using a spreadsheet (Microsoft Excel V.16; Microsoft, USA). Discussions were held with the supervisor (YS) regarding unclear data. Extracted information included author, study design, location, injury severity, treatment, and comparative data.

The primary outcomes extracted were average healing time and the percentage of wounds achieving sterility. These metrics, commonly used as primary outcomes in randomized controlled trials, assessed the efficacy of A. vera, honey, and amniotic membrane compared to SSD.

 

Assessment of quality and inconsistency

The three reviewers verified all included studies and assessed potential bias using the Cochrane Risk of Bias 2 tool.19 The tool evaluates five domains: outcome measurement, treatment variations, missing data, randomization method, and reported result selection.

The domains were rated as low, moderate, or high risk of bias to assess study quality. Local and global consistencies were evaluated using a loop-specific approach, with local inconsistency assessed through indirect and direct evidence methods.20 Inconsistencies were shown using a net heat plot, where red elements indicate evidence inconsistencies and blue elements indicate consistency.

 

Data analysis

Quantitative analysis was performed using the Netmeta package in R version 3.0.0 (R software, USA).21 Dichotomous outcomes were estimated using odds ratios (ORs) with 95% confidence intervals (CIs), while mean differences (MDs) were used for continuous data. Statistical heterogeneity in pairwise and network meta-analysis comparisons was expressed using I2 and t2. Cochran’s Q statistics assessed heterogeneity across studies and indirect comparisons. Higgins’ I2 calculation classified the score as insubstantial (0–25%), low (25–50%), moderate (50–75%), or high (75–100%).22

Treatments were ranked using the surface under the cumulative ranking curve and P-score. Results are shown in forest plots for all studies and for high- and middle-low-income studies. Connections between analyzed triages are displayed in a network graph using R.

 

 

Study selection and characteristics

The search of six databases yielded 286 papers from the last 10 years (Figure 1). After a full-text review, 231 studies were excluded due to comorbidities or unrelated interventions. After data extraction, 37 studies were deemed suitable for quantitative analysis.10,23–58 The characteristics and summary of these 37 studies are shown in the table (Table 1).

 

 

 

 

 

Average time to burn wound healing

The 26 studies compared the healing time between SSD and other interventions, including honey, A. vera, and amniotic membrane. Details on all observed interventions are shown in Figure 2a. A. vera showed the best efficacy (MD: −4.75; 95% CI: −8.67 to −0.86), followed by amniotic membrane (MD: −4.71; 95% CI: −7.45 to −1.97), and honey (MD: −4.25; 95% CI: −6.76 to −1.73) (Figure 3a).

 

 

 

Infection occurrence

Twenty-four studies compared infection rates between SSD and other interventions, mainly focusing on honey, amniotic membrane, or A. vera (Figure 2b). Honey showed the lowest infection rate (OR: 0.09; 95% CI: 0.04 to 0.23) and was the only intervention with a statistically significant difference (Figure 3b).

 

 

 

Studies inconsistencies and quality appraisal

Inconsistencies across studies were shown using a net heat plot (Figure 4), indicating low inconsistencies in direct and indirect interventions of the available treatments acquired from the quantitative analysis.

 

 

 

 

This meta-analysis included 37 studies on healing time, 24 on infection rates, and 3,434 patients with burns to compare natural remedies with SSD. A. vera can accelerate healing compared to other remedies, including SSD. It is cost-effective, widely available, and generally safe.59 The exact mechanism of A. vera in wound repair is not fully understood. Still, studies suggest its gel contains polysaccharides, amino acids, tannins, and enzymes, which can stimulate cell proliferation in vitro.60 A. vera stimulates fibroblast and keratinocyte proliferation and migration while positively regulating growth factors and cytokines.61 Some studies suggest topical A. vera may cause redness, burning, stinging, and rarely generalized dermatitis in sensitive patients, particularly due to anthraquinones like aloin and barbaloin. It is recommended to apply A. vera to a small area first to test for allergic reactions.⁶²

Honey reduces infection rates and accelerates healing compared to SSD. Honey is a traditional treatment in the Indian subcontinent. Its viscosity, osmolarity, acidic pH, and nutrients inhibit bacterial growth and promote healing.62,63 Honey is effective against antibiotic-resistant bacteria and more affordable.⁶⁴ Precautions are needed when using honey to avoid allergic reactions, contaminated honey infections, or inadequately cleaned wounds.³⁴

Due to their fragile nature, amniotic membranes have drawbacks, such as burn wound dressings. They may lack mechanical support for large or deep wounds, and improper application can lead to detachment or complications requiring further intervention. Natural shedding of the membrane can cause odor, requiring frequent dressing changes and discomfort. amniotic membrane’s efficacy varies by patient response and wound characteristics, meaning benefits may differ.65

This meta-analysis highlights the benefits of A. vera and honey for treating burns, considering potential side effects. These alternatives are accessible and cost-effective, particularly in low-income countries, but further research on side effects is needed. A limitation of this study is its reliance on published studies, which may underrepresent those with negative or inconclusive results that are less likely to appear in peer-reviewed journals. Excluding patients with comorbidities limits the study’s real-world applicability, where patients with burns often have other health conditions. Additionally, the analysis focused mainly on efficacy, such as healing time and infection rates, without addressing the safety or side effects of the interventions, which are crucial for clinical decision-making.

In conclusion, A. vera accelerates healing, while honey is superior to SSD in preventing infections. However, these results come from a study with a small sample and high heterogeneity. We encourage further research on natural remedies for burn treatment, following the Consolidated Standards of Reporting Trials to improve trial quality.

 

 

 

 

 

 

 

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