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1.  Evidence for Clinical Use of Honey in Wound Healing as an Anti-bacterial, Anti-inflammatory Anti-oxidant and Anti-viral Agent: A Review 
To provide an updated review of published literature on the anti-oxidant, anti-bacterial and anti-inflammatory properties of honey.
Evidence Acquisition
CINAHL, BioMed Central, Cochrane Library, Medline and Embase data bases and reference lists were used to find randomized controlled trials and review articles. Randomized controlled trials using honey with a comparator were reviewed, along with published review articles to determine the relative benefits of tropical honey. These methods were undertaken by three reviewers.
Honey has anti-oxidant, anti-bacterial and anti-inflammatory properties. It can be used as a wound dressing to promote rapid and improved healing. These effects are due to honey’s anti-bacterial action, secondary to its high acidity, osmotic effect, anti-oxidant content and hydrogen peroxide content. The use of honey leads to improved wound healing in acute cases, pain relief in burn patients and decreased inflammatory response in such patients. However, it has proven to be ineffective in chronic leg ulcers. Overall, studies have been done in favor of the use of honey in medicine.
Honey has almost equal or slightly superior effects when compared with conventional treatments for acute wounds and superficial partial thickness burns. More randomized controlled trials with significant statistical power comparing different kinds of honey, are required in order to create a strong body of evidence towards definite recommendations for medical use. There is biological plausibility.
PMCID: PMC3941901  PMID: 24624197
Honey; Biological Dressings; Burns; Anti-inflammatory Agents
2.  A comparative study to evaluate the effect of honey dressing and silver sulfadiazene dressing on wound healing in burn patients 
To compare the effect of honey dressing and silver-sulfadiazene (SSD) dressing on wound healing in burn patients. Patients (n=78) of both sexes, with age group between 10 and 50 years and with first and second degree of burn of less than 50% of TBSA (Total body surface area) were included in the study, over a period of 2 years (2006-08). After stabilization, patients were randomly attributed into two groups: ‘honey group’ and ‘SSD group’. Time elapsed since burn was recorded. After washing with normal saline, undiluted pure honey was applied over the wounds of patients in the honey group (n=37) and SSD cream over the wounds of patients in SSD group (n=41), everyday. Wound was dressed with sterile gauze, cotton pads and bandaged. Status of the wound was assessed every third and seventh day and on the day of completion of study. Patients were followed up every fortnight till epithelialization. The bacteriological examination of the wound was done every seventh day. The mean age for case (honey group) and control (SSD group) was 34.5 years and 28.5 years, respectively. Wound swab culture was positive in 29 out of 36 patients who came within 8 hours of burn and in all patients who came after 24 hours. The average duration of healing in patients treated with honey and SSD dressing at any time of admission was 18.16 and 32.68 days, respectively. Wound of all those patients (100%) who reported within 1 hour became sterile with honey dressing in less than 7 days while none with SSD. All of the wounds became sterile in less than 21 days with honey, while tthis was so in only 36.5% with SSD treated wounds. The honey group included 33 patients reported within 24 hour of injury, and 26 out of them had complete outcome at 2 months of follow-up, while numbers for the SSD group were 32 and 12. Complete outcome for any admission point of time after 2 months was noted in 81% and 37% of patients in the honey group and the SSD group. Honey dressing improves wound healing, makes the wound sterile in lesser time, has a better outcome in terms of prevention of hypertrophic scarring and post-burn contractures, and decreases the need of debridement irrespective of time of admission, when compared to SSD dressing.
PMCID: PMC2845359  PMID: 20368852
Honey dressing; silver-sulfadiazine dressing; wound healing in burn
3.  Stress-Mediated Increases in Systemic and Local Epinephrine Impair Skin Wound Healing: Potential New Indication for Beta Blockers 
PLoS Medicine  2009;6(1):e1000012.
Stress, both acute and chronic, can impair cutaneous wound repair, which has previously been mechanistically ascribed to stress-induced elevations of cortisol. Here we aimed to examine an alternate explanation that the stress-induced hormone epinephrine directly impairs keratinocyte motility and wound re-epithelialization. Burn wounds are examined as a prototype of a high-stress, high-epinephrine, wound environment. Because keratinocytes express the β2-adrenergic receptor (β2AR), another study objective was to determine whether β2AR antagonists could block epinephrine effects on healing and improve wound repair.
Methods and Findings
Migratory rates of normal human keratinocytes exposed to physiologically relevant levels of epinephrine were measured. To determine the role of the receptor, keratinocytes derived from animals in which the β2AR had been genetically deleted were similarly examined. The rate of healing of burn wounds generated in excised human skin in high and low epinephrine environments was measured. We utilized an in vivo burn wound model in animals with implanted pumps to deliver β2AR active drugs to study how these alter healing in vivo. Immunocytochemistry and immunoblotting were used to examine the up-regulation of catecholamine synthetic enzymes in burned tissue, and immunoassay for epinephrine determined the levels of this catecholamine in affected tissue and in the circulation. When epinephrine levels in the culture medium are elevated to the range found in burn-stressed animals, the migratory rate of both cultured human and murine keratinocytes is impaired (reduced by 76%, 95% confidence interval [CI] 56%–95% in humans, p < 0.001, and by 36%, 95% CI 24%–49% in mice, p = 0.001), and wound re-epithelialization in explanted burned human skin is delayed (by 23%, 95% CI 10%–36%, p = 0.001), as compared to cells or tissues incubated in medium without added epinephrine. This impairment is reversed by β2AR antagonists, is absent in murine keratinocytes that are genetically depleted of the β2AR, and is reproduced by incubation of keratinocytes with other β2AR-specific agonists. Activation of the β2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein ± standard error of the mean: unburned control, 0.6 ± 0.36; immediately postburn, 9.6 ± 1.58; 2 h postburn, 3.1 ± 1.08; 24 h post-burn, 6.7 ± 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with βAR antagonists results in a significant increase (44%, 95% CI 27%–61%, p < 0.00000001) in the rate of burn wound re-epithelialization.
This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte β2AR and the impairment of cell motility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in response to wounding, epinephrine levels are locally, as well as systemically, elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific β2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach to improving skin wound repair in the stressed individual.
Rivkah Isseroff and colleagues describe how stress-induced elevation of epinephrine levels can impair the healing of burns in mice and suggest that β2 adrenergic receptor antagonists may have a role in improving skin wound repair.
Editors' Summary
Skin—the largest organ in the human body—protects the rest of the body against infection by forming an impervious layer over the whole external body surface. Consequently, if this layer is damaged by rubbing, cutting, or burning, it must be quickly and efficiently repaired. Wound repair (healing) involves several different processes. First, the clotting cascade stops bleeding at the wound site and immune system cells attracted into the site remove any bacteria or debris in the wound. Various factors are released by the immune cells and the other cells in and near the damaged area that encourage the migration of several different sorts of cells into the wound. These cells proliferate and prepare the wound for “re-epithelialization.” In this process, keratinocytes (a type of epithelial cell that makes a tough, insoluble protein called keratin; epithelial cells cover all the surfaces of the body) migrate into the wound site and form a new, intact epithelial layer. If any of these processes fail, the result can be a chronic (long-lasting) nonhealing wound. In particular, if the wound does not re-epithelialize, it remains open and susceptible to infection and loss of body fluids.
Why Was This Study Done?
One factor that impairs the repair of skin wounds is stress. In stressful situations (including situations in which wounds are likely to occur), the human body releases several chemicals that prepare the body for “fight or flight,” including cortisol and epinephrine (also called adrenaline). Most scientists ascribe the effects of stress on wound healing to stress-induced increases in cortisol, but might stress-induced epinephrine also affect wound healing? In this study, the researchers test whether epinephrine impairs keratinocyte migration and re-epithelialization of burn wounds (keratinocytes have a receptor for epinephrine called the β2 adrenergic receptor [β2AR] on their cell surface that allows them to respond to epinephrine). They chose to study burn wounds for two reasons. First, major burns cause a massive release of stress chemicals into the bloodstream that raises blood levels (systemic levels) of cortisol and epinephrine for days or weeks after the initial trauma. Second, despite recent therapeutic advances, many people still die from major burns (4,000 every year in the USA alone) so there is a pressing need for better ways to treat this type of wound.
What Did the Researchers Do and Find?
The researchers investigated the effects of epinephrine on wound healing in three types of experiments. First, they looked at the effect of epinephrine on keratinocytes growing in dishes (in vitro experiments). Levels of epinephrine similar to those in the blood of stressed individuals greatly inhibited the motility and migration of human keratinocytes (isolated from the foreskin of newborn babies) and of mouse keratinocytes. It also inhibited the repair of scratch wounds made in monolayers of keratinocytes growing on dishes. Treatment of the cultures with a β2AR antagonist (a chemical that prevents epinephrine activating the β2AR) reversed the effects of epinephrine. In addition, the migration of mouse keratinocytes that had been genetically altered so that they did not express β2AR was not inhibited by epinephrine. Next, the researchers investigated the healing of burn wounds made in small pieces of human skin growing in dishes (ex vivo experiments). Burn injuries rapidly increased the amount of epinephrine in these tissue explants, they report, and treatment of the explants with a βAR antagonist (an inhibitor of all types of βARs) greatly increased wound re-epithelialization. Finally, the researchers report that the re-epithelialization of burn wounds in living mice was improved when the mice were treated with a β2AR antagonist.
What Do These Findings Mean?
These findings reveal a second pathway by which stress can impair wound healing. They show that stress-induced increases in systemic and local epinephrine activate β2ARs on keratinocytes and that this activation inhibits keratinocyte motility and wound re-epithelialization. Although results obtained in animals do not always reflect what happens in people, the finding that the treatment of mice with β2AR antagonists improves the rate of burn wound re-epithelialization, suggests that beta blockers—drugs that inhibit all βARs and that are widely used to treat high blood pressure and to prevent heart disease—or specific β2AR antagonists might provide a new therapeutic approach to the treatment of burns and, perhaps, chronic nonhealing wounds.
Additional Information.
Please access these Web sites via the online version of this summary at
Wikipedia has pages on wound healing, burn injuries, and epinephrine (Note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The MedlinePlus Encyclopedia has a page on burns (in English and Spanish)
MedlinePlus provides links to other information on burns (in English and Spanish)
PMCID: PMC2621262  PMID: 19143471
4.  A Comparative Study of the Wound Healing Properties of Moist Exposed Burn Ointment (MEBO) and Silver Sulphadiazine 
Burns expose the deeper tissues of the skin or body to invasive microbes. Topical preparations for treating burn wounds, to be useful, should ideally have antibiotic power and promote healing. Silver compounds have been the mainstay of topical burn treatment for decades. However, most chemical substances retard wound healing. Several natural agents such as honey and moist exposed burn ointment (MEBO) are believed to protect wounds from infection and promote healing without causing any of the adverse effects of purified chemicals. In this study, we compared the wound healing properties of MEBO, a herbal preparation of Chinese origin, with silver sulphadiazine (SSD), a long-standing conventional burn dressing. Ten adult Sprague Dawley rats were divided into two groups. They were housed in separate cages and received partial-thickness burn wounds on their dorsal skin. They were then treated with MEBO and SSD. The wounds were inspected daily until day 8, when all the animals were sacrificed, perfused with normal saline, and had their wounds excised and prepared for histology. It was found that animals in both groups were well preserved. No clinical infections occurred. Wound healing was at an advanced stage by day 8 in all the animals. Clinical and histological examination showed that the two agents gave the animals comparable protection and healing possibilities. It is concluded that MEBO is a suitable and efficacious alternative to conventional silver-based topical therapies for treating partial-thickness burn wounds.
PMCID: PMC3188221  PMID: 21991159
5.  Antimicrobial Effect of Bee Honey in Comparison to Antibiotics on Organisms Isolated From Infected Burns 
Despite recent advances in antimicrobial chemotherapy and burn wound management, infection continues to be an important problem in burns. Honey is the most famous rediscovered remedy that is used to treat infected wounds and promote healing. The present study aims to evaluate the antimicrobial effect of bee honey on organisms isolated from infected burns in comparison to the antibiotics used in treatment of burn infection, and to evaluate the effects produced when bee honey is added to antibiotic discs. Thirty patients with burn infection were selected for this study. The collected specimens were cultured on blood agar plates. The isolated colonies were identified by different methods. The isolated organisms were inoculated onto Müller-Hinton agar. Each agar plate was divided by a marker pen into two halves - in one half the antibiotic discs were plated while on the opposite side each antibiotic disc, immersed in honey, was plated opposite to the same antibiotic disc. At the centre of the agar, a sterile filter paper disc immersed in honey was applied. The most frequently isolated organism was Pseudomonas aeruginosa, representing 53.3% of the isolates. The mean inhibition zones (in mm) produced by honey (18.2 ± 2.5 mm) when applied to isolated gram-negative bacteria were significantly higher than amoxicillin/clavulinic acid, sulbactam/ampicillin, and ceftriaxone (p1 = 0.005 for each). When honey was added to the antibiotic discs there was highly significant increased sensitivity of isolated gram-negative bacteria compared with each of the antibiotic discs alone and with honey alone. The susceptibility of isolated staphylococci revealed the synergistic effect of added honey to the antibiotic discs tested. The antimicrobial effect of honey (18.7 ± 2.2 mm) was significantly higher than antibiotics - ciprofloxacin, sulbactam/ampicillin, ceftriaxone, and vancomycin (p1 ≤ 0.05 for each). After the addition of honey to the tested antibiotic discs there were highly significant increased inhibition zones of antibiotic mixed with honey compared with antibiotic alone - ciprofloxacin, vancomycin, and methicillin (p3 ≤ 0.001 for each). Also, the increase was significant compared with antibiotics alone - imipenem, amoxicillin/clavulinic acid, and ceftriaxone (p3 ≤ 0.05). In conclusion, honey had more inhibitory effect (85.7%) on isolated gram-negative bacteria (Pseudomonas aeruginosa, Enterobacter spp., Klebsiella) than commonly used antibiotics, while it had an inhibitory effect on all methicillin-resistant Staphylococcus aureus (100%) compared with antibiotics used. A synergistic effect of honey was observed when it was added to antibiotics for gram-negative bacteria and also for coagulase-positive staphylococci.
PMCID: PMC3188067  PMID: 21991075
6.  Honey Dressing Versus Silver Sulfadiazene Dressing for Wound Healing in Burn Patients: A Retrospective Study 
The aim was to evaluate the effect of honey dressing and silver sulfadiazene (SSD) dressing on wound healing in burn patients.
Materials and Methods:
We retrospectively reviewed the records of 108 patients (14–68 years of age), with first and second degree burns of less than 50% of the total body surface area admitted to our institution, over a period of 5 years (2004–2008). Fifty-one patients were treated with honey dressings and 57 with SSD. Time elapsed since burn, site, percentage, degree and depth of burns, results of culture sensitivity at various time intervals, duration of healing, formation of post-treatment hypertrophic scar, and/or contracture were recorded and analyzed.
The average duration of healing was 18.16 and 32.68 days for the honey and SSD group, respectively. Wounds of all patients reporting within 1 h of burns became sterile with the honey dressing in less than 7 days while there was none with SSD. All wounds treated with honey became sterile within 21 days while for SSD-treated wounds, this figure was 36.5%. A complete outcome was seen in 81% of all patients in the “honey group” while in only 37% patients in the “SSD group.”
Honey dressings make the wounds sterile in less time, enhance healing, and have a better outcome in terms of hypertropic scars and postburn contractures, as compared to SSD dressings.
PMCID: PMC3263128  PMID: 22279383
Burns; honey dressing; silver sulfadiazine dressing
7.  Negative Pressure Wound Therapy 
Executive Summary
This review was conducted to assess the effectiveness of negative pressure wound therapy.
Clinical Need: Target Population and Condition
Many wounds are difficult to heal, despite medical and nursing care. They may result from complications of an underlying disease, like diabetes; or from surgery, constant pressure, trauma, or burns. Chronic wounds are more often found in elderly people and in those with immunologic or chronic diseases. Chronic wounds may lead to impaired quality of life and functioning, to amputation, or even to death.
The prevalence of chronic ulcers is difficult to ascertain. It varies by condition and complications due to the condition that caused the ulcer. There are, however, some data on condition-specific prevalence rates; for example, of patients with diabetes, 15% are thought to have foot ulcers at some time during their lives. The approximate community care cost of treating leg ulcers in Canada, without reference to cause, has been estimated at upward of $100 million per year.
Surgically created wounds can also become chronic, especially if they become infected. For example, the reported incidence of sternal wound infections after median sternotomy is 1% to 5%. Abdominal surgery also creates large open wounds. Because it is sometimes necessary to leave these wounds open and allow them to heal on their own (secondary intention), some may become infected and be difficult to heal.
Yet, little is known about the wound healing process, and this makes treating wounds challenging. Many types of interventions are used to treat wounds.
Current best practice for the treatment of ulcers and other chronic wounds includes debridement (the removal of dead or contaminated tissue), which can be surgical, mechanical, or chemical; bacterial balance; and moisture balance. Treating the cause, ensuring good nutrition, and preventing primary infection also help wounds to heal. Saline or wet-to-moist dressings are reported as traditional or conventional therapy in the literature, although they typically are not the first line of treatment in Ontario. Modern moist interactive dressings are foams, calcium alginates, hydrogels, hydrocolloids, and films. Topical antibacterial agents—antiseptics, topical antibiotics, and newer antimicrobial dressings—are used to treat infection.
The Technology Being Reviewed
Negative pressure wound therapy is not a new concept in wound therapy. It is also called subatmospheric pressure therapy, vacuum sealing, vacuum pack therapy, and sealing aspirative therapy.
The aim of the procedure is to use negative pressure to create suction, which drains the wound of exudate (i.e., fluid, cells, and cellular waste that has escaped from blood vessels and seeped into tissue) and influences the shape and growth of the surface tissues in a way that helps healing. During the procedure, a piece of foam is placed over the wound, and a drain tube is placed over the foam. A large piece of transparent tape is placed over the whole area, including the healthy tissue, to secure the foam and drain the wound. The tube is connected to a vacuum source, and fluid is drawn from the wound through the foam into a disposable canister. Thus, the entire wound area is subjected to negative pressure. The device can be programmed to provide varying degrees of pressure either continuously or intermittently. It has an alarm to alert the provider or patient if the pressure seal breaks or the canister is full.
Negative pressure wound therapy may be used for patients with chronic and acute wounds; subacute wounds (dehisced incisions); chronic, diabetic wounds or pressure ulcers; meshed grafts (before and after); or flaps. It should not be used for patients with fistulae to organs/body cavities, necrotic tissue that has not been debrided, untreated osteomyelitis, wound malignancy, wounds that require hemostasis, or for patients who are taking anticoagulants.
Review Strategy
The inclusion criteria were as follows:
Randomized controlled trial (RCT) with a sample size of 20 or more
Human study
Published in English
Summary of Findings
Seven international health technology assessments on NPWT were identified. Included in this list of health technology assessments is the original health technology review on NPWT by the Medical Advisory Secretariat from 2004. The Medical Advisory Secretariat found that the health technology assessments consistently reported that NPWT may be useful for healing various types of wounds, but that its effectiveness could not be empirically quantified because the studies were poorly done, the patient populations and outcome measures could not be compared, and the sample sizes were small.
Six RCTs were identified that compared NPWT to standard care. Five of the 6 studies were of low or very low quality according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. The low and very low quality RCTs were flawed owing to small sample sizes, inconsistent reporting of results, and patients lost to follow-up. The highest quality study, which forms the basis of this health technology policy assessment, found that:
There was not a statistically significant difference (≥ 20%) between NPWT and standard care in the rate of complete wound closure in patients who had complete wound closure but did not undergo surgical wound closure (P = .15).
The authors of this study did not report the length of time to complete wound closure between NPWT and standard care in patients who had complete wound closure but who did not undergo surgical wound closure
There was no statistically significant difference (≥ 20%) in the rate of secondary amputations between the patients that received NPWT and those that had standard care (P = .06)
There may be an increased risk of wound infection in patients that receive NPWT compared with those that receive standard care.
Based on the evidence to date, the clinical effectiveness of NPWT to heal wounds is unclear. Furthermore, saline dressings are not standard practice in Ontario, thereby rendering the literature base irrelevant in an Ontario context. Nonetheless, despite the lack of methodologically sound studies, NPWT has diffused across Ontario.
Discussions with Ontario clinical experts have highlighted some deficiencies in the current approach to wound management, especially in the community. Because NPWT is readily available, easy to administer, and may save costs, compared with multiple daily conventional dressing changes, it may be used inappropriately. The discussion group highlighted the need to put in place a coordinated, multidisciplinary strategy for wound care in Ontario to ensure the best, continuous care of patients.
PMCID: PMC3379164  PMID: 23074484
8.  Gelam (Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing 
A novel cross-linked honey hydrogel dressing was developed by incorporating Malaysian honey into hydrogel dressing formulation, cross-linked and sterilized using electron beam irradiation (25 kGy). In this study, the physical properties of the prepared honey hydrogel and its wound healing efficacy on deep partial thickness burn wounds in rats were assessed. Skin samples were taken at 7, 14, 21, and 28 days after burn for histopathological and molecular evaluations. Application of honey hydrogel dressings significantly enhanced (P < 0.05) wound closure and accelerated the rate of re-epithelialization as compared to control hydrogel and OpSite film dressing. A significant decrease in inflammatory response was observed in honey hydrogel treated wounds as early as 7 days after burn (P < 0.05). Semiquantitative analysis using RT-PCR revealed that treatment with honey hydrogel significantly (P < 0.05) suppressed the expression of proinflammatory cytokines (IL-1α, IL-1β, and IL-6). The present study substantiates the potential efficacy of honey hydrogel dressings in accelerating burn wound healing.
PMCID: PMC3175734  PMID: 21941590
9.  Antibacterial properties of tualang honey and its effect in burn wound management: a comparative study 
The use of honey as a natural product of Apis spp. for burn treatment has been widely applied for centuries. Tualang honey has been reported to have antibacterial properties against various microorganisms, including those from burn-related diagnoses, and is cheaper and easier to be absorbed by Aquacel dressing. The aim of this study is to evaluate the potential antibacterial properties of tualang honey dressing and to determine its effectiveness as a partial thickness burn wound dressing.
In order to quantitate the bioburden of the swabs, pour plates were performed to obtain the colony count (CFU/ml). Swabs obtained from burn wounds were streaked on blood agar and MacConkey agar for bacterial isolation and identification. Later, antibacterial activity of Aquacel-tualang honey, Aquacel-Manuka honey, Aquacel-Ag and Aquacel- plain dressings against bacteria isolated from patients were tested (in-vitro) to see the effectiveness of those dressings by zone of inhibition assays.
Seven organisms were isolated. Four types of Gram-negative bacteria, namely Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas spp. and Acinetobacter spp., and three Gram-positive bacteria, namely Staphylococcus aureus, coagulase-negative Staphylococcus aureus (CONS) and Streptococcus spp., were isolated. Total bacterial count decreased on day 6 and onwards. In the in-vitro antibacterial study, Aquacel-Ag and Aquacel-Manuka honey dressings gave better zone of inhibition for Gram positive bacteria compared to Aquacel-Tualang honey dressing. However, comparable results were obtained against Gram negative bacteria tested with Aquacel-Manuka honey and Aquacel-Tualang honey dressing.
Tualang honey has a bactericidal as well as bacteriostatic effect. It is useful as a dressing, as it is easier to apply and is less sticky compared to Manuka honey. However, for Gram positive bacteria, tualang honey is not as effective as usual care products such as silver-based dressing or medical grade honey dressing.
PMCID: PMC2908556  PMID: 20576085
10.  Wound contraction effects and antibacterial properties of Tualang honey on full-thickness burn wounds in rats in comparison to hydrofibre 
Full-thickness burn wounds require excision and skin grafting. Multiple surgical procedures are inevitable in managing moderate to severe full-thickness burns. Wound bed preparations prior to surgery are necessary in order to prevent wound infection and promote wound healing. Honey can be used to treat burn wounds. However, not all the honey is the same. This study aims to evaluate the wound contraction and antibacterial properties of locally-produced Tualang honey on managing full-thickness burn wounds in vivo.
Thirty-six female Sprague Dawley rats were randomly divided into three groups. Under anaesthesia, three full-thickness burn wounds were created on the dorsum of the rats. The full-thickness burn wounds were inoculated with a specific organism (104), namely Pseudomonas aeruginosa (n = 12), Klebsiella pneumoniae (n = 12), or Acinetobacter baumannii (n = 12). The three burn wounds were dressed with Tualang honey, hydrofibre and hydrofibre silver respectively. Swab samples were obtained every 3 days (day 3, 6, 9, 12, 15, 18 and 21) for quantitative and semi-quantitative microbiological analyses. Clinical assessments, including observations concerning the appearance and wound size, were measured at the same time.
There was a rapid 32.26% reduction in wound size by day 6 (p = 0.008) in the Tualang honey-treated wounds, and 49.27% by day 15 (p = 0.005). The wounds remained smaller by day 18 (p < 0.032). Tualang honey-treated rats demonstrated a reduction in bacterial growth in Pseudomonas aeruginosa inoculated wounds (p = 0.005). However, hydrofibre silver and hydrofibre-treated wounds are superior to honey-treated wounds with Acinetobacter baumannii (p = 0.035). There was no statistical significant of antibacterial property in Klebsiella pneumonia inoculated wounds.
Tualang honey has better results with regards to its control of Pseudomonas aeruginosa and its wound contraction effects on full-thickness burn wound in vivo.
PMCID: PMC2941475  PMID: 20815896
11.  Comparing oil based ointment versus standard practice for the treatment of moderate burns in Greece: a trial based cost effectiveness evaluation 
The local treatment of burn wounds has long been a subject of debate. The objective of this study was to compare the cost and the effectiveness of Moist Exposed Burn Ointment -MEBO versus a combination of povidone iodine plus bepanthenol cream for partial thickness burns.
The study was carried out in the Burn Center of a state hospital in Athens, Greece. 211 patients needing conservative therapy were prospectively selected according to the depth of the burn wound. The treatment was allocated according to the Stratified Randomization Design. The outcomes measured were mean cost of in-hospital stay, rate of complications, time of 50% wound healing, pain scores, in hospital stay diminution. We have adopted a societal perspective.
In the total groups MEBO presented lower cost, (although not significantly different: p = 0.10) and better effectiveness. The data suggest that MEBO is the dominant therapy for superficial partial burn wound with significantly lower costs and significantly higher effectiveness due to a lesser time of recovery and consequently lower time of hospitalization and follow-up. MEBO presented similar percentages of complications with the comparator, lower pain levels and smaller time of no healthy appearance of the burn limits for superficial partial thickness burns.
The data suggested that topical application of MEBO may be considered for further investigation as a potential first-line treatment modality for superficial partial thickness burns.
Trial registration
The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRCTN74058791.
PMCID: PMC3298496  PMID: 22132709
12.  Therapy of acute wounds with water-filtered infrared-A (wIRA) 
Water-filtered infrared-A (wIRA) as a special form of heat radiation with a high tissue penetration and with a low thermal load to the skin surface acts both by thermal and thermic as well as by non-thermal and non-thermic effects. wIRA produces a therapeutically usable field of heat in the tissue and increases tissue temperature, tissue oxygen partial pressure, and tissue perfusion. These three factors are decisive for a sufficient tissue supply with energy and oxygen and consequently as well for wound healing and infection defense.
wIRA can considerably alleviate the pain (with remarkably less need for analgesics) and diminish an elevated wound exudation and inflammation and can show positive immunomodulatory effects. wIRA can advance wound healing or improve an impaired wound healing both in acute and in chronic wounds including infected wounds. Even the normal wound healing process can be improved.
A prospective, randomized, controlled, double-blind study with 111 patients after major abdominal surgery at the University Hospital Heidelberg, Germany, showed with 20 minutes irradiation twice a day (starting on the second postoperative day) in the group with wIRA and visible light VIS (wIRA(+VIS), approximately 75% wIRA, 25% VIS) compared to a control group with only VIS a significant and relevant pain reduction combined with a markedly decreased required dose of analgesics: during 230 single irradiations with wIRA(+VIS) the pain decreased without any exception (median of decrease of pain on postoperative days 2-6 was 13.4 on a 100 mm visual analog scale VAS 0-100), while pain remained unchanged in the control group (p<0.001). The required dose of analgesics was 57-70% lower in the subgroups with wIRA(+VIS) compared to the control subgroups with only VIS (median 598 versus 1398 ml ropivacaine, p<0.001, for peridural catheter analgesia; 31 versus 102 mg piritramide, p=0.001, for patient-controlled analgesia; 3.4 versus 10.2 g metamizole, p=0.005, for intravenous and oral analgesia). During irradiation with wIRA(+VIS) the subcutaneous oxygen partial pressure rose markedly by approximately 30% and the subcutaneous temperature by approximately 2.7°C (both in a tissue depth of 2 cm), whereas both remained unchanged in the control group: after irradiation the median of the subcutaneous oxygen partial pressure was 41.6 (with wIRA) versus 30.2 mm Hg in the control group (p<0.001), the median of the subcutaneous temperature was 38.9 versus 36.4°C (p<0.001). The overall evaluation of the effect of irradiation, including wound healing, pain and cosmesis, assessed on a VAS (0-100 with 50 as indifferent point of no effect) by the surgeon (median 79.0 versus 46.8, p<0.001) or the patient (79.0 versus 50.2, p<0.001) was markedly better in the group with wIRA compared to the control group. This was also true for single aspects: Wound healing assessed on a VAS by the surgeon (median 88.6 versus 78.5, p<0.001) or the patient (median 85.8 versus 81.0, p=0.040, trend) and cosmetic result assessed on a VAS by the surgeon (median 84.5 versus 76.5, p<0.001) or the patient (median 86.7 versus 73.6, p=0.001). In addition there was a trend in favor of the wIRA group to a lower rate of total wound infections (3 of 46, approximately 7%, versus 7 of 48, approximately 15%, p=0.208) including late infections after discharge, caused by the different rate of late infections after discharge: 0 of 46 in the wIRA group and 4 of 48 in the control group. And there was a trend towards a shorter postoperative hospital stay: 9 days in the wIRA group versus 11 days in the control group (p=0.037). The principal finding of this study was that postoperative irradiation with wIRA can improve even a normal wound healing process.
A prospective, randomized, controlled, double-blind study with 45 severely burned children at the Children’s Hospital Park Schönfeld, Kassel, Germany, showed with 30 minutes irradiation once a day (starting on the first day, day of burn as day 1) in the group with wIRA and visible light VIS (wIRA(+VIS), approximately 75% wIRA, 25% VIS) compared to a control group with only VIS a markedly faster reduction of wound size. On the fifth day (after 4 days with irradiation) decision was taken, whether surgical debridement of necrotic tissue was necessary because of deeper (second degree, type b) burns (11 of 21 in the group with wIRA, 14 of 24 in the control group) or non-surgical treatment was possible (second degree, type a, burns). The patients treated conservatively were kept within the study and irradiated till complete reepithelialization. The patients in the group with wIRA showed a markedly faster reduction of wound area: a median reduction of wound size of 50% was reached already after 7 days compared to 9 days in the control group, a median reduction of wound size of 90% was already achieved after 9 days compared to 13 days in the control group. In addition the group with wIRA showed superior results till 3 months after the burn in terms of the overall surgical assessment of the wound, cosmesis, and assessment of effects of irradiation compared to the control group.
In a prospective, randomized, controlled study with 12 volunteers at the University Medical Center Charité, Berlin, Germany, within each volunteer 4 experimental superficial wounds (5 mm diameter) as an acute wound model were generated by suction cup technique, removing the roof of the blister with a scalpel and a sterile forceps (day 1). 4 different treatments were used and investigated during 10 days: no therapy, only wIRA(+VIS) (approximately 75% wIRA, 25% VIS; 30 minutes irradiation once a day), only dexpanthenol (= D-panthenol) cream once a day, wIRA(+VIS) and dexpanthenol cream once a day. Healing of the small experimental wounds was from a clinical point of view excellent with all 4 treatments. Therefore there were only small differences between the treatments with slight advantages of the combination wIRA(+VIS) and dexpanthenol cream and of dexpanthenol cream alone concerning relative change of wound size and assessment of feeling of the wound area. However laser scanning microscopy with a scoring system revealed differences between the 4 treatments concerning the formation of the stratum corneum (from first layer of corneocytes to full formation) especially on the days 5-7: fastest formation of the stratum corneum was seen in wounds treated with wIRA(+VIS) and dexpanthenol cream, second was wIRA(+VIS) alone, third dexpanthenol cream alone and last were untreated wounds. Bacterial counts of the wounds (taken every 2 days) showed, that wIRA(+VIS) and the combination of wIRA(+VIS) with dexpanthenol cream were able to inhibit the colonisation with physiological skin flora up to day 5 when compared with the two other groups (untreated group and group with dexpanthenol cream alone). At any investigated time, the amount of colonisation under therapy with wIRA(+VIS) alone was lower (interpreted as more suppressed) compared with the group with wIRA(+VIS) and dexpanthenol cream.
During rehabilitation after hip and knee endoprosthetic operations the resorption of wound seromas and wound hematomas was both clinically and sonographically faster and pain was reduced by irradiation with wIRA(+VIS).
wIRA can be used successfully for persistent postoperative pain e.g. after thoracotomy.
As perspectives for wIRA it seems clinically prudent to use wIRA both pre- and postoperatively, e.g. in abdominal and thoracic operations. wIRA can be used preoperatively (e.g. during 1-2 weeks) to precondition donor and recipient sites of skin flaps, transplants or partial-thickness skin grafts, and postoperatively to improve wound healing and to decrease pain, inflammation and infections at all mentioned sites. wIRA can be used to support routine pre- or intraoperative antibiotic administration or it might even be discussed to replace this under certain conditions by wIRA.
PMCID: PMC2831241  PMID: 20204084
water-filtered infrared-A (wIRA); wound healing; acute wounds; prospective, randomized, controlled, double-blind studies; reduction of pain; problem wounds; wound infections; infection defense; wound exudation; inflammation; thermal and non-thermal effects; thermic and non-thermic effects; energy supply; oxygen supply; tissue oxygen partial pressure; tissue temperature; tissue blood flow; visual analog scales (VAS); quality of life
13.  Evaluations of bacterial contaminated full thickness burn wound healing in Sprague Dawley rats Treated with Tualang honey 
The effect of Tualang honey on wound healing in bacterial contaminated full-thickness burn wounds was evaluated in 36 male Sprague Dawley rats.
Materials and Methods:
The rats were randomly divided into three groups (n = 12/group). Three full-thickness burn wounds were created on each rat. Each group of rats was inoculated with a different organism in the burn wounds: Group A was inoculated with Pseudomonas aeruginosa, Group B was inoculated with Klebsiella pneumoniae and Group C was inoculated with Acinetobacter baumannii. One wound on each rat was dressed with either Tualang honey, Chitosan gel or Hydrofibre silver. Each wound size was measured on day 3, 6, 9, 12, 15, 18 and 21 of the study.
The mean wound size of the Tualang honey-treated wounds was not statistically different than that of the Chitosan gel or Hydrofibre silver-treated wounds when the wounds were compared throughout the entire experiment (P > 0.05). However, comparing the mean wound size on day 21 alone revealed that the Tualang honey-treated wounds were smaller in comparison to that of the Chitosan gel and Hydrofibre silver-treated groups.
This study shows that topical application of Tualang honey on burn wounds contaminated with P. aeruginosa and A. baumannii gave the fastest rate of healing compared with other treatments.
PMCID: PMC3111101  PMID: 21713196
Burn wound; honey; Pseudomonas aeruginosa; Acinetobacter baumannii; wound healing
14.  Topical Silver for Infected Wounds 
Journal of Athletic Training  2009;44(5):531-533.
Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007(1);CD005486.
Clinical Question:
What is the clinical evidence base for silver dressings in the management of contaminated and infected acute and chronic wounds?
Data Sources:
Investigations were identified by Cochrane Wounds Group Specialized Register (2006), CENTRAL (2006), MEDLINE (2002–2006), EMBASE (2002–2006), CINAHL (2002–2006), and digital dissertations (2006) searches. Product manufacturers were contacted to identify additional eligible studies. The search terms included wound infection, surgical wound infection, ulcer, wound healing, and silver.
Study Selection:
Each study fulfilled the following criteria: (1) The study was a randomized controlled trial of human participants that compared dressings containing silver with any dressings without silver, dressings with other antiseptics, or dressings with different dosages of silver. (2) The participants were aged 18 years and older with contaminated and infected open wounds of any cause. (3) The study had to evaluate the effectiveness of the dressings using an objective measure of healing. No language or publication status restrictions were imposed, and participants could be recruited in any care setting. Studies were excluded if the wounds were ostomies (surgically formed passages).
Data Extraction:
Study quality assessment was conducted independently by 3 authors using the Dutch Institute for Health Care Improvement and Dutch Cochrane Centre protocols. Characteristics of the study, participants, interventions, and outcome measures were extracted by one author and verified by a second using a standard form. The principal outcome measure was healing (time to complete healing, rate of change in wound area and volume, number and proportion of wounds healed within trial period). Secondary measures were adverse events (eg, pain, maceration, erythema), dressing leakage, and wound odor. Based on the unique comparisons in the studies, a meta-analysis was not conducted. As a result, summary estimates of treatment effect were calculated for each outcome comparison. RevMan software (version 4.2; Cochrane Centre, Oxford, United Kingdom) was used for statistical analysis.
Main Results:
Specific search criteria identified 31 studies for review, of which 3 met the inclusion and exclusion criteria. Lack of randomization and absence of wound infections excluded the majority of studies from the review. In the 3 studies selected, silver-containing dressings were compared with nonsilver dressings and dressings with other antimicrobials. One group used a silver-containing foam dressing and a nonsilver foam dressing; another group used a silver-containing alginate and a nonsilver alginate; and a third group used a silver-containing foam and various dressings (nonsilver foams, alginates, hydrocolloids, and gauze and other antimicrobial dressings). Sample sizes ranged between 99 and 619 participants. Most of the wounds in the included studies were pressure, diabetic, and venous leg ulcers. Wound infection was subjectively defined by 1 group as the presence of 2 or more signs and symptoms (eg, continuous pain, erythema, heat, or moderate to high levels of exudate) and by the other 2 groups as signs of critical colonization (eg, delayed healing, increased pain and exudate levels, discoloration, and odor). The primary measure in the included studies was healing outcome. The 3 groups used various assessments of healing, including relative and absolute reduction in wound area and number of wounds healed during the trial period. The trial period in each study was 4 weeks. In the 3 trials, the authors randomized the participants to the treatment groups.
Examining healing, one group (129 participants) compared Contreet silver foam (Coloplast A/S, Humlebaek, Denmark) with Allevyn foam (Smith & Nephew, St-Laurent, Quebec, Canada). The authors reported no differences for rates of complete healing (risk difference [RD]  =  0.00, 95% confidence interval [CI]  =  −0.09, 0.09) and median wound area reduction (weighted mean difference [WMD]  =  −0.30 cm2, 95% CI  =  −2.92, 2.35). However, Contreet was favored over Allevyn (P  =  .034) for median relative reduction in wound area (WMD  =  −15.70 cm2, 95% CI  =  −29.5, −1.90). One group (99 participants) compared Silvercel silver alginate (Johnson & Johnson Wound Management, Somerville, NJ) with Algosteril alginate (Johnson & Johnson Wound Management). The authors found no differences in rates of complete healing (RD  =  0.00, 95% CI  =  −0.06, 0.05), mean absolute (WMD  =  4.50 cm2, 95% CI  =  −0.93, 9.93) and relative wound area reduction (WMD  =  −0.30 cm2, 95% CI  =  −17.08, 16.48), or healing rate per day (week 1 to 4) (WMD  =  0.16 cm2, 95% CI  =  −0.03, 0.35). One group (619 participants) compared Contreet with various dressings (nonsilver foams, alginates, hydrocolloids, and gauze and other antimicrobial dressings). For median relative wound area reduction, the authors noted a superiority of Contreet over the various dressings (P  =  .0019).
Examining secondary outcomes, 2 groups used subjective analysis to compare adverse reactions among the dressings. One group reported no difference between Contreet (in satellite ulcers, deterioration of periwound tissue) and Allevyn (in satellite ulcers, maceration, eczema) (RD  =  0.02, 95% CI  =  −0.07, 0.12), and one group found no difference between Silvercel (in pain during dressing change, eczema, periwound erythema, maceration) and Algosteril (in pain during dressing change, eczema, erythema) (RD  =  −0.01, 95% CI  =  −0.12, 0.11). Two groups subjectively assessed leakage among silver and nonsilver dressings. The data from one group demonstrated superiority of Contreet over Allevyn (P  =  .002; RD  =  −0.30, 95% CI  =  −0.47, −0.13), and one group found Contreet better than various dressings (eg, nonsilver foams, alginates, hydrocolloids, and gauze, and other antimicrobial dressings) (P  =  .0005; RD  =  −0.11, 95% CI  =  −0.18, −0.05). Using a subjective 4-point scale, one group compared silver and nonsilver dressings and reported a difference favoring Contreet over Allevyn in terms of wound odor (P  =  .030; RD  =  −0.19, 95% CI  =  −0.36, −0.03).
Overall, this review provides no clear evidence to support the use of silver-containing foam and alginate dressings in the management of infected chronic wounds for up to 4 weeks. However, the use of silver foam dressings resulted in a greater reduction in wound size and more effective control of leakage and odor than did use of nonsilver dressings. Randomized controlled trials using standardized outcome measures and longer follow-up periods are needed to determine the most appropriate dressing for contaminated and infected acute and chronic wounds.
PMCID: PMC2742464  PMID: 19771293
antiseptics; moist dressings; critical colonization; contamination
15.  Glycerin-Based Hydrogel for Infection Control 
Advances in Wound Care  2012;1(1):48-51.
Infection is a major problem in the health and wellbeing of patients in hospitals, nursing homes, and other medical facilities as well as the homecare patients and the general public. According to Scientia Advisors, wound care costs the healthcare system over $7 billion in 2009. After adding the cost associated with potential complications such as infections, extended physician care, and lengthy hospital stays, the annual wound care expenditures well exceeded over $20 billion.1 There are 20 million reported cases of diabetes per year and more every day. Because of the fact that leg ulcers are the number one health problem of men coupled with the rise in drug resistance of infections, the importance of providing the professional and the public with relatively simple and affordable wound care is of extreme importance. Often the wounds can become chronic wounds, which then result in long-term nursing expense in time and supplies or, worse yet, can result in expensive amputations ranging from $5000 to $40,000 per patient.
There are many dressing options now available for treating wounds with components such as glycerin, honey, salt, and many other natural products, with some dressings being more appropriate than others. In 1988, a patented glycerin-based dressing was introduced to the market, called Elasto-Gel™.2
New Technology
Elasto-Gel™ is a glycerin-based gel sheet (65%) combined with a hydrophilic polymer that causes the sheet to absorb the exudate from the wound and simultaneously release the glycerin from the gel, which adds many benefits to the wound for excellent healing outcomes. The gel sheet is 1/8th of an inch thick with a four-way stretch backing. It has the ability to absorb 3–4 times its own weight of fluids. The dressing will not dry out or allow the exudate to dry out, thus keeping the dressing from becoming bonded to the wound or the surrounding tissue. It does not have adhesive properties and, therefore, will not cause damage to the wound bed or periwound area upon dressing removal. Because of the thickness, the product provides excellent cushion and padding support. It has been also proven to be bacteriostatic/fungistatic. (Bacteriostatic is the ability to restrain the development or reproduction of bacteria.3)
Product Technology
Glycerin is a huamectant by definition and has been recognized by the U.S. Food and Drug Administration (FDA). Humectants attract, bind, and hold moisture to the site of application. The actual concentration of glycerin in a wound dressing is indicative of the ability to absorb excess moisture. Exudate management is an important function of topical treatment. The ability to absorb drainage and prevent pooling of exudate in the wound or on the surrounding skin are attributes specific to high glycerin content. Perhaps, the most significant advantage of the glycerin-based hydrogel sheet is its impact on wound bioburden and pathogenic organisms.4 Glycerin is a simple three-carbon tri-alcohol and is a natural humectant. It is used as a carrier in many medicines and as plasticizer in gelatin gel capsules. Glycerin is a component of cosmetics, conditioners, soaps, foods, and other common products. It is a component of mono-, di-, and triglycerides naturally occurring in the body. These glycerides and glycerin are constantly reacted with each other by the natural enzymes and reversed with the natural metabolic processes already present in the body. Any glycerin that may be absorbed into the body fluid is rapidly diluted in these fluids and is no longer toxic but is metabolized as another component of the food chain. It is well known that glycerin in high concentration will exhibit dehydrating effect on many systems including living cells by the commonly known process of osmosis. (Osmosis: the flow or diffusion that takes place through a semipermable membrane, as of living cell, typically separating a solvent such as water, thus bringing about equilibrium conditions.5) It has been shown that glycerin at high concentration will be cytotoxic to all cells that have been tested if they are exposed long enough. These properties of glycerin have been recognized by the European Skin Bank, where they use 85% glycerin solutions to store cadaver skin at ∼42F, and can be used for potential wound coverings. The cadaver skin that has been prepared by this method has been available since 1994.6 The concern for safety resulted in a three-day international synmposium7 with emphasis on glycerin-preserved cadaver skin providing healthy environment for the preserved skin to be successfully accepted without rejection, having no complications of infection and providing excellent healing outcomes and minimal scaring. Additional research by Dr. David P. Mackie of the Red Cross Hospital, The Netherlands, reported that using 85% glycerin solutions had slow bactericidal effects and also showed virocidal activity on several types of viruses.8 Dr. Hoekstra has observed that within 2 hours after application of Elasto-Gel™, the inflammatory reaction is reduced.9 Vandeputte, Belgium, showed that wounds covered with Elasto-Gel™ had fewer myofibroblasts than those covered with hydrocolloid.10 It has been proposed that myofibroblasts in high concentrations contribute to the formation of hypertrophic and keloid scars. As noted earlier, there is less scar formation when glycerin-based gel sheets are used. The data sited here have shown that glycerin and glycerin-based products are effective antimicrobial agents with less side effects. Many verbal reports along with personal communications have indicated that applying glycerin-based gel sheets to stalled wounds, some 15–20-year-old chronic wounds, resulted in healing in 1–20 weeks (data/case studies on file).
Indications for Use
Elasto-Gel™ has been approved for all types of wounds, that is, pressure ulcers, acute and chronic wounds, diabetic wounds, traumatic wounds, dermatology wounds, cancer tumors, and first- and second-degree burns, to name a few. Because of the product's features and benefits, it may be used on a variety of wounds. Because of its padding properties, it may be also used as a preventative product over bony prominence areas so that wounds do not occur. The glycerin properties act as a skin substitute and may also be used for scar reduction.
Elasto-Gel™ is not approved for third-degree burns as no dressing has been approved by the FDA for this type of wound.
PMCID: PMC3839013  PMID: 24527279
16.  Comparison between topical honey and mafenide acetate in treatment of burn wounds 
Histological and clinical studies of wound healing were performed in comparable cases of fresh partial-thickness burns treated with honey dressing or mafenide acetate in two groups of 50 randomly allocated patients. Of the patients with honey-treated wounds, 84% showed satisfactory epithelialization by day 7 and 100% by day 21. In wounds treated with mafenide acetate, epithelialization occurred by day 7 in 72% of cases and in 84% by day 21. Histological evidence of reparative activity was observed in 80% of wounds treated with honey dressing by day 7 with minimal inflammation. Fifty-two per cent of the mafenide acetate treated wounds showed reparative activity with inflammatory changes by day 7. Reparative activity reached 100% by day 21 with the honey dressing and 84% with mafenide acetate. Thus, in honey-dressed wounds, early subsidence of acute inflammatory changes, better control of infection, and quicker wound healing were observed, while in mafenide acetate treated wounds a sustained inflammatory reaction was noted even on epithelialization.
PMCID: PMC3293229  PMID: 22396671
burn wounds; mafenide acetate; Honey
17.  Comparison of three different dressings for partial thickness burns in children: study protocol for a randomised controlled trial 
Trials  2013;14:403.
In the paediatric population, pain and distress associated with burn injuries during wound care procedures remain a constant challenge. Although silver dressings are the gold standard for burn care in Australasia, very few high-level trials have been conducted that compare silver dressings to determine which will provide the best level of care clinically. Therefore, for paediatric patients in particular, identifying silver dressings that are associated with lower levels of pain and rapid wound re-epithelialisation is imperative. This study will determine whether there is a difference in time to re-epithelialisation and pain and distress experienced during wound care procedures among Acticoat™, Acticoat™ combined with Mepitel™ and Mepilex Ag™ dressings for acute, paediatric partial thickness burns.
Children aged 0 to 15 years with an acute partial thickness (superficial partial to deep partial thickness inclusive) burn injury and a burn total body surface area of ≤10% will be eligible for the trial. Patients will be randomised to one of the three dressing groups: (1) Acticoat™ or (2) Acticoat™ combined with Mepitel™ or (3) Mepilex Ag™. A minimum of 28 participants will be recruited for each treatment group. Primary measures of pain, distress and healing will be repeated at each dressing change until complete wound re-epithelialisation occurs or skin grafting is required. Additional data collected will include infection status at each dressing change, physical function, scar outcome and scar management requirements, cost effectiveness of each dressing and staff perspectives of the dressings.
The results of this study will determine the effects of three commonly used silver and silicone burn dressing combinations on the rate of wound re-epithelialisation and pain experienced during dressing procedures in acute, paediatric partial thickness burn injuries.
Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12613000105741
PMCID: PMC4222277  PMID: 24274190
Child; Burn injuries; Partial thickness; Silver dressings; Healing; Pain; Distress; Randomised clinical trial
18.  Review of the Medicinal Effects of Tualang Honey and a Comparison with Manuka Honey 
Tualang honey (TH) is a Malaysian multifloral jungle honey. In recent years, there has been a marked increase in the number of studies published in medical databases regarding its potential health benefits. The honey is produced by the rock bee (Apis dorsata), which builds hives on branches of tall Tualang trees located mainly in the north-western region of Peninsular Malaysia. This review collates the results of the various studies of TH that range from research on tissue culture to randomised control clinical trials. Findings thus far show that, TH has antimicrobial, anti-inflammatory, antioxidant, antimutagenic, antitumor, and antidiabetic properties, in addition to wound-healing attributes. Some of its properties are similar to the well-researched Manuka honey (New Zealand and/or Australian monofloral honey). Distinct differences include higher phenolics, flavonoids, and 5-(hydroxymethyl) furfural (HMF). Compared with Manuka honey, TH is also more effective against some gram-negative bacterial strains in burn wounds.
PMCID: PMC3743976  PMID: 23966819
ailments; antitumor; properties of Tualang honey; Tualang honey; wound healing
19.  Management of Superficial to Partial-Thickness Wounds 
Journal of Athletic Training  2007;42(3):422-424.
Reference/Citation: Wiechula R. The use of moist wound-healing dressings in the management of split-thickness skin graft donor sites: a systematic review. Int J Nurs Pract. 2003; 9:S9–S17.
Clinical Question: Do rates of healing, infection, and pain differ depending on whether nonmoist or moist dressings are used to manage superficial to partial-thickness wounds?
Data Sources: Investigations were identified by CINAHL, MEDLINE, Pre-MEDLINE, Cochrane Library, Current Contents, Health STAR, EMBASE, Expanded Academic Index, and Dissertation Abstracts International searches. The search terms included skin, graft, and donor. Additional searches were performed with reference lists and bibliographies of retrieved studies.
Study Selection: To be included in the review, each study had to fulfill the following criteria: it had to be an intraindividual or prospective randomized controlled trial of human subjects; it had to include patients with postharvest split-thickness skin graft donor sites; it had to evaluate the effectiveness of primary and secondary wound dressings; and it had to have outcome measures that included healing (objective), infection (subjective), and pain (objective).
Data Extraction: Data extraction and study quality assessment procedures were developed specifically for this review based on Cochrane Collaboration, Centre for Reviews and Dissemination, and Joanna Briggs Institute protocols and were performed independently by the author. Details of the procedures were not fully explained. The principal outcome measures were healing (proportion of sites healed within the study period or time to complete healing), rate of infection, and pain scores. The studies were grouped according to broad dressing type (nonmoist and moist) and specific types of moist dressings (hydrocolloids and polyurethane semipermeable transparent films). When comparable, study results were pooled and analyzed with a fixed-effects model. Data within broader dressing categories (nonmoist and moist) were analyzed with a random-effects model. χ 2 analysis was used to determine heterogeneity among the studies. RevMan software (version 4.04; Cochrane Centre, Oxford, UK) was used for statistical analysis.
Main Results: The searches identified 111 studies and 1 integrative review, of which 58 studies met the inclusion and exclusion criteria. Inconsistency and variation in outcome measures and incomplete reporting of results prevented analysis of many studies. Wound healing was measured by days to complete healing (when dressings could be removed without trauma and pain) and wounds healed by day X (removal of dressings at regular intervals). Wound infection was subjectively measured based on clinical signs of infection (edema, heat, pain, or smell). Visual analog scales were used to measure pain levels.
Among the broad categories of nonmoist (sterile gauze, fine mesh gauze, Xerofoam [Tyco Healthcare Group LP, Mansfield, MA]) and moist (DuoDERM hydrocolloid [ConvaTec, Princeton, NJ], Tegaderm transparent film [3M Health Care, St Paul, MN], Opsite transparent film [Smith & Nephew, London, UK]) dressings, the outcomes of healing, infection, and pain were analyzed. In 6 studies, the findings significantly favored moist dressings, compared with nonmoist dressings, for days to complete healing (weighted mean difference [WMD] = −3.97, 95% confidence interval [CI] = −5.91, −2.02). In 9 studies, wounds healed by day X (day 7, 8, 9, 10, or 12) were analyzed. The results were varied and inconclusive because of a small number of trials and subjects. Among 10 studies, no significant difference was noted in infection rates between nonmoist and moist dressings (odds ratio [OR] = 0.41, 95% CI = 0.14, 1.18). Three studies using visual analog scales for the outcome of pain were converted into a uniform scale of 1 to 10 (10 representing most painful). The findings significantly favored moist dressings over nonmoist dressings (WMD = −1.75, 95% CI = −2.94, −0.56).
Among nonmoist and specific types of moist dressings, a subset analysis was performed to examine the outcomes of healing, infection, and pain. For days to complete healing, 2 investigations significantly favored hydrocolloid dressings over nonmoist dressings (WMD = −2.19, 95% CI = −2.89, −1.49). Additionally, in 2 studies, hydrocolloid dressings were significantly favored over other moist dressings (semiocclusive hydrocolloid and transparent film) for days to complete healing (WMD = −1.45, 95% CI = −2.17, −0.74). In 3 studies, the data significantly favored polyurethane semipermeable transparent film dressings over nonmoist dressings for days to complete healing (WMD = −2.82, 95% CI = −3.58, −2.07). For infection rates, 4 studies significantly favored hydrocolloid dressings over nonmoist dressings (OR = 0.21, 95% CI = 0.07, 0.65). In 4 other studies, polyurethane semipermeable transparent film dressings were significantly favored over nonmoist dressings with regard to infection rates (OR = 0.28, 95% CI = 0.09, 0.91). For the outcome of pain, varied outcome measures and insufficient data prevented analysis among specific types of moist dressings.
Conclusions: Moist dressings decreased the days to complete healing and pain scores when compared with nonmoist dressings. Among the broad categories of nonmoist and moist dressings, no differences were found in infection rates. The data on specific types of moist dressings revealed that days to complete healing were decreased with hydrocolloid dressings compared with nonmoist and other moist dressings. Hydrocolloid dressings also decreased infection rates compared with nonmoist dressings. Polyurethane semipermeable transparent film dressings also decreased days to complete healing and infection rates compared with nonmoist dressings. Overall, the data indicated that hydrocolloid dressings are more effective than nonmoist dressings in terms of rates of healing, infection, and pain in the management of superficial to partial-thickness wounds. The variations in outcome measures among the included studies should be considered in interpreting these findings.
PMCID: PMC1978464  PMID: 18059999
moist dressings; abrasions
20.  Honey: A Potential Therapeutic Agent for Managing Diabetic Wounds 
Diabetic wounds are unlike typical wounds in that they are slower to heal, making treatment with conventional topical medications an uphill process. Among several different alternative therapies, honey is an effective choice because it provides comparatively rapid wound healing. Although honey has been used as an alternative medicine for wound healing since ancient times, the application of honey to diabetic wounds has only recently been revived. Because honey has some unique natural features as a wound healer, it works even more effectively on diabetic wounds than on normal wounds. In addition, honey is known as an “all in one” remedy for diabetic wound healing because it can combat many microorganisms that are involved in the wound process and because it possesses antioxidant activity and controls inflammation. In this review, the potential role of honey's antibacterial activity on diabetic wound-related microorganisms and honey's clinical effectiveness in treating diabetic wounds based on the most recent studies is described. Additionally, ways in which honey can be used as a safer, faster, and effective healing agent for diabetic wounds in comparison with other synthetic medications in terms of microbial resistance and treatment costs are also described to support its traditional claims.
PMCID: PMC4216698  PMID: 25386217
21.  Modalities for the Assessment of Burn Wound Depth 
Objective: Burn wound depth is a significant determinant of patient treatment and morbidity. While superficial partial-thickness burns generally heal by re-epithelialization with minimal scarring, deeper wounds can form hypertrophic or contracted scars, often requiring surgical excision and grafting to prevent a suboptimal result. In addition, without timely intervention, more superficial burn wounds can convert to deeper wounds. As such, the rapid and accurate assessment of burn wound depth is a priority in treating burn-injured patients. The object of this article is to review current research on modalities useful in the assessment of burn wound depth with emphasis on the relative costs and benefits of each technique. Methods: PubMed and Cochrane computerized databases were used for data retrieval, using the search terms “burns,” “burn wounds,” “burn depth,” “burn depth measurement,” and “burn depth progression.” In addition, bibliographic references from prior reviews of burn depth were reviewed. All peer-reviewed, English-language articles relevant to the topic of burn depth measurement were reviewed, including those focusing on animal and human populations. Where appropriate, conclusions drawn from review articles and expert analyses were included. Results: Although bedside evaluation remains the most common modality of diagnosing the depth of burn wounds, recent technological advances have broadened the scope of depth assessment modalities available to clinicians. Other depth assessment techniques include biopsy and histology, and perfusion measurements techniques such as thermography, vital dyes, indocyanine green video angiography, and laser Doppler techniques. Conclusion: Of the depth assessment modalities currently used in clinical practice, LDI and ICG video angiography offer the best data-supported estimates of accuracy. Until the future of new modalities unfolds, a combination of clinical evaluation and another modality—thermography, biopsy, or, ideally, ICG video angiography or LDI—is advised to best assess the depth of acute burn wounds.
PMCID: PMC1687143  PMID: 16921415
22.  Hyperbaric Oxygen Therapy for Non-Healing Ulcers in Diabetes Mellitus 
Executive Summary
To examine the effectiveness and cost-effectiveness of hyperbaric oxygen therapy (HBOT) to treat people with diabetes mellitus (DM) and non-healing ulcers. This policy appraisal systematically reviews the published literature in the above patient population, and applies the results and conclusions of the review to current health care practices in Ontario, Canada.
Although HBOT is an insured service in Ontario, the costs for the technical provision of this technology are not covered publicly outside the hospital setting. Moreover, access to this treatment is limited, because many hospitals do not offer it, or are not expanding capacity to meet the demand.
Clinical Need
Diabetes mellitus is a chronic disease characterized by an increase in blood sugar that can lead to many severe conditions such as vision, cardiac, and vascular disorders. The prevalence of DM is difficult to estimate, because some people who have the condition are undiagnosed or may not be captured through data that reflect access to the health care system. The Canadian Diabetic Association estimates there are about 2 million people in Canada with diabetes (almost 7% of the population). According to recent data, the prevalence of DM increased from 4.72% of the population aged 20 years and over in 1995, to 6.19% of the population aged 20 years and over in 1999, or about 680,900 people in 1999. Prevalence estimates expanded to 700,000 in 2003.
About 10% to 15% of people with DM develop a foot wound in their lifetimes because of underlying peripheral neuropathy and peripheral vascular disease. This equals between 70,000 and 105,000 people in Ontario, based on the DM prevalence estimate of 700,000 people. Without early treatment, a foot ulcer may fester until it becomes infected and chronic. Chronic wounds are difficult to heal, despite medical and nursing care, and may lead to impaired quality of life and functioning, amputation, or even death.
The Technology
Hyperbaric oxygen therapy has been in use for about 40 years. It is thought to aid wound healing by supplying oxygen to the wound. According to the Hyperbaric Oxygen Therapy Association, HBOT acts as a bactericidal, stops toxin production, and promotes tissue growth to heal difficult wounds.
During the procedure, a patient is placed in a compression chamber with increased pressure between 2.0 and 2.5 atmospheres absolute for 60 to 120 minutes, once or twice daily. In the chamber, the patient inhales 100% oxygen. Treatment usually runs for 15 to 20 sessions.
Noted complications are rare but may include claustrophobia; ear, sinus, or lung damage due to pressure; temporary worsening of short sightedness; and oxygen poisoning. Careful monitoring during the treatment sessions and follow-up by a trained health care provider is recommended.
Review Strategy
The aims of this health technology policy appraisal were to assess the effectiveness, safety, and cost-effectiveness of HBOT, either alone, or as an adjunct, compared with the standard treatments for non-healing foot or leg ulcers in patients with DM. The following questions were asked:
Alone or as an adjunct therapy, is HBOT more effective than other therapies for non-healing foot or leg ulcers in patients with DM?
If HBOT is effective, what is the incremental benefit over and above currently used strategies?
When is the best time in a wound treatment strategy to use HBOT?
What is the best treatment algorithm with HBOT?
The Medical Advisory Secretariat searched for health technology assessments in the published and grey literature. The search yielded 4 reports, which were published from 2000 to 2005. The most recent from the Cochrane Collaboration had a literature review and analysis of randomized control trials to 2003.
As an update to this review, as per the standard Medical Advisory Secretariat systematic review strategy, the abstracts of peer-reviewed publications were identified using Ovid MEDLINE, EMBASE, MEDLINE in-process and not-yet-indexed citations, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, and INAHTA using key words and searching from January 1, 2003 to 2004.
The criteria for inclusion were as follows:
Patients with diabetes
Live human study
English-language study
HBOT as adjunctive therapy or alone
Randomized control trial
The number of excluded studies included the following:
2 animal studies
13 focus on condition other than DM
8 review/protocol for HBOT use
3 HBOT not focus of report
2 health technology assessments (2)
1 non-RCT
Outcomes of interest were wound healing and prevention of amputation.
The search yielded 29 articles published between 2003 and 2004. All 29 of these were excluded, as shown beside the exclusion criteria above. Therefore, this health technology policy assessment focused exclusively on the most recently published health technology assessments and systematic reviews.
Summary of Findings
Four health technology assessments and reviews were found. Cochrane Collaboration researchers published the most recent review in 2005. They included only randomized controlled trials and conducted a meta-analysis to examine wound healing and amputation outcomes. They found that, based on findings from 118 patients in 3 studies, HBOT may help to prevent major amputation (relative risk, 0.31; 95% confidence interval [CI], 0.13–0.71) with a number needed to treat (NNT) of 4 (95% CI, 3–11). They noted, however, that the point estimates derived from trials were not well reported, and had varying populations with respect to wound severity, HBOT regimens, and outcome measures. These noted limitations rendered the comparison of results from the trials difficult. Further, they suggested that the evidence was not strong enough to suggest a benefit for wound healing in general or for prevention of minor amputations.
The Medical Advisory Secretariat also evaluated the studies that the Cochrane Collaboration used in their analysis, and agreed with their evaluation that the quality of the evidence was low for major and minor amputations, but low to moderate for wound healing, suggesting that the results from new and well-conducted studies would likely change the estimates calculated by Cochrane and others.
In 2003, the Ontario Health Technology Advisory Committee recommended a more coordinated strategy for wound care in Ontario to the Ministry of Health and Long-term Care. This strategy has begun at the community care and long-term care institution levels, but is pending in other areas of the health care system.
There are about 700,000 people in Ontario with diabetes; of these, 10% to 15% may have a foot ulcer sometime in their lifetimes. Foot ulcers are treatable, however, when they are identified, diagnosed and treated early according to best practice guidelines. Routine follow-up for people with diabetes who may be at risk for neuropathy and/or peripheral vascular disease may prevent subsequent foot ulcers. There are 4 chambers that provide HBOT in Ontario. Fewer than 20 people with DM received HBOT in 2003.
The quality of the evidence assessing the effectiveness of HBOT as an adjunct to standard therapy for people with non-healing diabetic foot ulcers is low, and the results are inconsistent. The results of a recent meta-analysis that found benefit of HBOT to prevent amputation are therefore uncertain. Future well-conducted studies may change the currently published estimates of effectiveness for wound healing and prevention of amputation using HBOT in the treatment of non-healing diabetic foot ulcers.
Although HBOT is an insured service in Ontario, a well conducted, randomized controlled trial that has wound healing and amputation as the primary end-points is needed before this technology is used widely among patients with foot wounds due to diabetes.
PMCID: PMC3382405  PMID: 23074462
23.  Wound-Healing and Potential Anti-Keloidal Properties of the Latex of Calotropis Procera (Aiton) Asclepiadaceae in Rabbits 
Calotropis Procera (CP) has been used in the management of toothache, fresh skin burns, gum bleeding as well as others to make it qualify as a medicinal plant. This study was designed to assess its wound-healing property in rabbits and its potentials for anti keloidal activity.Fresh latex of Calotropis were obtained and evaluated phytochemically. Fifteen male rabbits were used and four excisional wounds were created on each rabbit. The rabbits were divided into five groups of three each. Group 1 was the negative control and received no treatment. The wounds of group 2 animals were treated with 2mL of Calotropis latex; group 3 with 2mL honey; and group 4 with a mixture of 1ml honey and 1 mL of the latex. The animals in group 5 were given 2mg triamcinolone intramuscularly. All the groups had their wounds treated daily for 21 days. The wounds' diameters were measured on the day of wound creation, thereafter on days 7, 14 and 21 post wound creation. Biopsies of the wounds were taken on days 3 and 21 and viewed histologically. Phytochemical study of the latex revealed the presence of glycosides, tannins and alkaloids. The wounds were found to be significantly (p<0.05) reduced in groups treated with 50% latex in honey and triamcinolone, respectively, on day 7 post wound creation while there was a significant (p<0.05) reduction in wound surface area in all treated groups on days 14 and 21 post wound creation. Histological findings in untreated group showed thick bundle of collagen fibres some of which had broad based configurations, reminiscent of keloid. The group treated with 2mL of Calotropis latex revealed the presence of florid granulation tissues on day 3 while there was a marked reduction in quantity and size of collagen fibres on day 21 post wound creation which was comparable with what was seen for the triamcinolone-treated group.The general effect of Calotropis latex on wound-healing was noted. Likewise it's similarity to that of triamcinolone, an anti-keloidal agent; this makes it a probable candidate for future anti-keloidal study using a suitable model.
PMCID: PMC3777603  PMID: 24146491
Calotropis procera; latex; wound-healing; potential anti-keloidal property
24.  Polypragmasia in the therapy of infected wounds – conclusions drawn from the perspectives of low temperature plasma technology for plasma wound therapy 
As long as a wound is infected, the healing process cannot begin. The indication for wound antiseptic is dependent on the interaction between the wound, the causative micro-organisms, and the host immune system. An uncritical colonisation is a condition whereby micro-organisms on a wound will proliferate, yet the immune system will not react excessively. Wound antiseptic is most often not necessary unless for epidemiologic reasons like colonisation with multi-resistant organisms. In most instances of a microbial contamination of the wound and colonisation, thorough cleaning will be sufficient.
Bacterial counts above 105 to 106 cfu per gram tissue (critical colonisation) might decrease wound healing due to release of toxins, particularly in chronic wounds. Traumatic and heavily contaminated wounds therefore will require anti-infective measures, in particular wound antiseptic. In such situations, even a single application of an antiseptic compound will significantly reduce the number of pathogens, and hence, the risk of infection. If a wound infection is clinically manifest, local antiseptics and systemic antibiotics are therapeutically indicated.
The prophylactic and therapeutic techniques for treatment of acute and chronic wounds (chemical antiseptics using xenobiotics or antibiotics, biological antiseptic applying maggots, medical honey or chitosan, physical antiseptic using water-filtered infrared A, UV, or electric current) mostly have been empirically developed without establishing a fundamental working hypothesis for their effectiveness.
The most important aspect in controlling a wound infection and achieving healing of a wound is meticulous debridement of necrotic material. This is achieved by surgical, enzymatic or biological means e.g. using maggots. However, none of these methods (with some exception for maggots) is totally gentle to vital tissue and particularly chemical methods possess cytotoxicity effects.
Derived from the general principles of antiseptic wound treatment, the following working hypothesis is postulated: the most ideal constellation for treatment of wounds is the superficial destruction of microbial layers without deep tissue alteration, like it is caused by antiseptics, in order not to endanger the regenerative granulation tissue. At the same time, it is desirable to support and increase cell proliferation and granulation capacities. These two aspects might be achieved by using low temperature plasma technology.
PMCID: PMC2831521  PMID: 20204115
25.  Collagen Dressing Versus Conventional Dressings in Burn and Chronic Wounds: A Retrospective Study 
Biological dressings like collagen are impermeable to bacteria, and create the most physiological interface between the wound surface and the environment. Collagen dressings have other advantages over conventional dressings in terms of ease of application and being natural, non-immunogenic, non-pyrogenic, hypo-allergenic, and pain-free. This study aims to compare the efficacy of collagen dressing in treating burn and chronic wounds with that of conventional dressing materials.
Materials and Methods:
The records of 120 patients with chronic wounds of varied aetiologies and with mean age 43.7 years were collected and analyzed. The patients had been treated either with collagen or other conventional dressing materials including silver sulfadiazine, nadifloxacin, povidone iodine, or honey (traditional dressing material). Patients with co-morbidities that could grossly affect the wound healing like uncontrolled diabetes mellitus, chronic liver or renal disease, or major nutritional deprivation were not included. For the purpose of comparison the patients were divided into two groups; ‘Collagen group’ and ‘Conventional group’, each having 60 patients. For assessment the wound characteristics (size, edge, floor, slough, granulation tissue, and wound swab or pus culture sensitivity results) were recorded. With start of treatment, appearance of granulation tissue, completeness of healing, need for skin grafting, and patients’ satisfaction was noted for each patient in both groups.
With two weeks of treatment, 60% of the ‘collagen group’ wounds and only 42% of the ‘conventional group’ wounds were sterile (P=0.03). Healthy granulation tissue appeared earlier over collagen-dressed wounds than over conventionally treated wounds (P=0.03). After eight weeks, 52 (87%) of ‘collagen group’ wounds and 48 (80%) of ‘conventional group’ wounds were >75% healed (P=0.21). Eight patients in the ‘collagen group’ and 12 in the ‘conventional group’ needed partial split-skin grafting (P=0.04). Collagen-treated patients enjoyed early and more subjective mobility.
No significant better results in terms of completeness of healing of burn and chronic wounds between collagen dressing and conventional dressing were found. Collagen dressing, however, may avoid the need of skin grafting, and provides additional advantage of patients’ compliance and comfort.
PMCID: PMC3081477  PMID: 21572675
Burns; chronic wounds; collagen dressing

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