Chronic wounds of the lower extremities are challenging to treat. Recently, honey-based dressings have been shown beneficial effects in diabetic foot ulcers and venous ulcers. Here, we compared Medihoney alginate with a standard alginate dressing in lower extremity chronic wounds.
We performed retrospective chart reviews of 37 patients between January 2019 and January 2021 with chronic lower extremity wounds who were treated with an Algisite M dressing (group A) or a Medihoney alginate dressing (group B). Microorganisms isolated from wound cultures, weekly decrease in wound area over 4 weeks, the number of patients who achieved complete wound closure, and the amount of time required for wound closure were compared between the two groups.
Sixteen patients were assigned to group A and 21 to group B. The isolated microorganisms were confirmed as methicillin-susceptible
Considering the more rapid decrease in wound area in group B, application of a honey-containing alginate dressing to lower extremity chronic wounds, especially those infected with antibiotic-resistant bacteria, was proved to be a good treatment option.
Chronic wounds are defined as wounds that have not healed after 3 months of treatment [
However, the effectiveness of honey-containing alginate dressing materials for the management of chronic wounds of the lower extremities have not been reported. In this study, we compared the wound healing effects of a medical grade honey-containing alginate dressing to a standard alginate dressing.
This study was approved by the Institutional Review Board of Human Research Protection Program (IRB No. VC20RASI0224). All data were analyzed anonymously and according to the principles outlined in the Declaration of Helsinki 1975 (revised in 2008). All patients provided informed consent for the publication of this study.
Retrospective chart review was conducted on patients seen from January 2019 to January 2021 who were treated for chronic wounds on their lower extremities in our department. Most of the patients with chronic wounds on their lower extremities were referred to our department with failed wound closure despite more than 3 months of wound care at other hospitals. Among those patients, those treated with alginate dressing (Algisite M; Smith & Nephew, Hull, UK), or honeycontaining alginate dressing (Medihoney alginate; Derma Sciences Inc., Princeton, NJ, USA) were included in this study. Demographic information collected included age, sex, type of chronic wounds, location of wounds, and number of wounds. Assessment of initial wound condition included size of the wound surface, depth including exposed level, degree of exudate, and character of the exudate. Microorganisms cultured from the wound were recorded. Wounds were usually classified as dry, moist, wet, saturated, or leaking based on the amount of exudate using the World Union of Wound Healing Societies (WUWHS) criteria (2007) [
Based on the type of dressing used, patients were divided into two groups. Patient whose wounds were treated with alginate dressing (Algisite M; Smith & Nephew) were assigned to group A, and those treated with honey-containing alginate were assigned to group B. Dressing material used in group B was Medihoney alginate containing medical grade Manuka honey. In both groups A and B, superabsorbent polymer (DryMax Foam; Absorbent, Kista, Sweden) was applied as the secondary dressing for effective exudate absorption to prevent infection and promote wound healing.
As additional treatment after applying dressing materials, elastic bandage compression was applied to all venous ulcer patients, and 0.12 mg of beraprost sodium (Berasil; Astellas Pharma Inc., São Paulo, Brazil) was applied as daily medication to all diabetes foot ulcer patients according to our routine treatment protocol. There was no difference between the two groups in patient assignment.
Wound beds of most of the chronic wounds were surgically debrided before the dressing was applied. Dressing changes were usually performed 2–3 times a week in the first week, and 1–2 times a week from the second week onwards, but when dressing changes were performed varied depending on the wound condition.
Empirical oral antibiotics therapy was administrated at the first visit in most patients and modified with selective oral antibiotics according to tissue culture results. The duration of antibiotics administration was determined by wound condition.
The number of patients who achieved complete wound closure during 4 weeks of follow-up and the duration until complete wound closure was achieved were assessed in each group. The percentage decrease in wound area every week was calculated by applying the following formula:
Sizes of all wounds were measured using ImageJ software (National Institutes of Health, Bethesda, MD, USA) [
Patient demographics including age, sex, the type of chronic wound, location of wounds, and number of wounds were compared between groups using the Mann-Whitney U test and Fisher extraction.
Initial characteristics of the chronic wounds including initial area, depth, degree of exudate, and isolated microorganism by culturing were analyzed and compared using the Mann-Whitney test and Fisher exact test.
The decrease in wound area every week was compared between groups using repeated-measures analysis of variance. The number of patients who achieved complete wound closure within 4 weeks was compared between groups using Fisher exact test, and the duration of complete wound closure was compared between groups using the Mann-Whitney U test. All statistical analyses were executed in GraphPad Prism version 9.0.1 (GraphPad Software Inc., San Diego, CA, USA). To reduce the conditional probability of assignment to a specific treatment group by effects of covariates, the propensity scores were estimated using logistic regression and matched by nearest neighbor matching method [
From January 2019 to January 2021, a total of 82 patients presented to our department with chronic wounds of the lower extremities. Sixteen of these patients were treated with Algisite M and DryMax Foam dressing (6 males, 10 females) and assigned to group A, and 21 patients were treated with Medihoney alginate and DryMax Foam dressing (11 males, 10 females) and assigned to group B.
Mean patient age was similar between groups (61.13±12.62 years in group A and 58.95±13.51 years in group B) (P>0.05). Diabetic wounds were the most common, occurring in 24 patients (64.86%), followed by venous stasis ulcers in eight patients (21.62%) and pressure sores in five patients (13.51%) (
Mean area of the initial wound was 12.71 cm2 (±3.12) in group A and 13.89 cm2 (±3.25) in group B, which was not a significant difference. Initial depth of the wound was most commonly dermal to subcutaneous in nine patients (56.25%) in group A and 13 patients (61.90%) in group B. Most wounds were classified as being “saturated” in both groups based on the amount of exudate, followed by “leaking.” Methicillin-susceptible
Wound area decreased from 12.71±3.97 to 2.34±1.30 cm2 in group A, and from 14.07±3.14 to 1.71±1.21 cm2 in group B by 4 weeks. On a weekly basis, wound area decreased from 12.71±3.97 to 8.10±2.00 cm2 (36.13%±6.87%) by the 1st week, 5.80±2.53 cm2 (55.19%±8.94%) by the 2nd week, 3.99±1.88 cm2 (69.28%±10.26%) by the 3rd week, and 2.34±1.30 cm2 (82.26%±8.87%) by the 4th week in group A. In group B, wound area decreased from 14.07±3.14 to 7.33±2.13 cm2 (47.54%± 9.72%) by the 1st week, 4.69±1.89 cm2 (67.40%±9.66%) by the 2nd week, 2.89±1.59 cm2 (80.39%±8.04%) by the 3rd week, and 1.71±1.21 cm2 (88.34%±7.78%) by the 4th week. The decrease in wound area was greater in group B than in group A. Wound healing was accelerated in group B compared to group A especially during the first week based on the decrease in wound area (P<0.05) (
After the propensity score matching by nearest neighbor matching method, 13 pairs of patients from each group were re-evaluated resulting that reduction of wound area was greater in group B than in group A (P=0.021) (
Seven of 16 patients achieved complete wound closure in group A (43.75%) and 15 of 21 patients achieved complete wound closure in group B (71.43%) by 4 weeks. Mean duration of wound closure was 36.31±11.12 days in group A and 34.62±14.31 days in group B (P>0.05) (
Alginate dressing materials are widely used to treat wounds, especially contaminated wounds with a large amount of exudate, as they can reduce microbial burden, absorb exudate, and have excellent biocompatibility [
As mentioned above, medical grade honey dressings have been reported to be effective at treating chronic wounds of the lower extremities such as venous stasis ulcers and DFUs [
Medical grade honey has topical antimicrobial activity and can remove and inhibit the formation of biofilms, which is significant in the treatment of chronic wounds. Most honey-containing wound dressing materials contain medical grade Manuka honey with a pH of around 3.2–4.5. The low pH of medical grade honey provides an environment that inhibits the growth of bacteria. Moreover, honey has bactericidal effects against bacteria that easily colonize skin and wounds, such as
Medical grade honey can induce the removal of necrotic and contaminated tissue from wounds. The high concentration of sugars and high viscosity of honey form strong osmotic gradients that absorb fluid from the wound surface and surrounding subdermal tissue. The high osmotic pressure of Manuka honey, corresponding to 105 atm of pressure, cause it to act as a hypertonic solution with excellent exudate absorption activity. This not only contributes to auto-debridement of the necrotic tissue, but also protects the wound surface from the external environment and bacteria due to formation of a hydration barrier until wound closure is established [
We recommend the use of a secondary dressing material with strong absorption capacity to prevent secondary infection from the wet wound surface due to the large amount of exudate present during the early phases of wound care. In this study, we used DryMax Foam as the secondary dressing material. DryMax is a superabsorbent dressing with a cellulose core and superabsorbent polymers contained within a polypropylene cover [
Lastly, medical grade honey has the ability to promote tissue repair following the release of acute inflammatory cytokines, fibroblasts, and revascularization. The mechanism of tissue repair is linked to the low pH and high glucose content of honey, which stimulate macrophages to secrete inflammatory cytokines, monocytes to secrete inflammatory mediators such as tissue necrosis factor, interleukin 6, and interleukin 1, and promotes fibroblast proliferation, contributing to tissue proliferation and remodeling [
Surgical reconstruction is usually the first choice for wound care of wounds with bone exposure, therefore we did not include these types of wounds in our study. However, if the wound base cannot be transformed sufficiently for surgical reconstruction using a local flap or skin graft, wound closure can fail, followed by infection and recurrence of chronic wounds. Moreover, if vascular conditions are unfavorable for free tissue transfer with insufficient surrounding tissue, surgical reconstruction as an option for treating lower extremity wounds is limited. Application of a honey-containing alginate dressing to this type of wound might allow development of a sufficiently healthy wound base for a secondary skin graft, and make surgery a feasible option with a reduction in the surgical failure rate. However, further studies are needed to test these hypotheses.
The limitation of this study is the study was designed as retrospective chart review and selection bias inevitably occurs. Therefore, the possibility that the various covariates suggested in this study influenced the treatment effects could not be completely excluded. However, it was suggested that difference between the two groups by covariate was not statistically significant by Mann-Whitney U test and Fisher extraction. Moreover, to minimize the selection bias, the patients were reevaluated by propensity score matching resulting statistically significant results. After propensity score matching, the statistical power decreases from<0.001 to 0.021, which is thought to be due to the effects of small number of patients, which is also a limitation of this study.
In conclusion, we found that treatment of chronic wounds of the lower extremities with honey-containing alginate dressing decreased wound area more rapidly than an alginate-only dressing as well as the duration until wound closure. Based on our results, application of a honey-containing alginate dressing for treating lower extremity chronic wounds, especially those infected with antibiotic-resistant bacteria, is a good treatment option.
After propensity score matching by nearest neighbor matching method, 13 pairs of patients from each group were matched.
Supplemental data can be found at:
After propensity score matching, decreased wound area were re-evaluated resulting that reduction of wound area was greater in group B than in group A (P=0.201).
Supplemental data can be found at:
No potential conflict of interest relevant to this article was reported.
Decrease in wound area over 4 weeks. (A) Wound area decreased from 12.71±3.97 to 2.34±1.30 cm2 in group A and from 14.07±3.14 to 1.71±1.21 cm2 in group B by 4 weeks (P<0.001). (B) Decrease in percentage wound area was 82.26%±8.87% in group A and 88.34%±7.78% in group B by 4 weeks (P<0.05). The decrease in wound area was faster in group B than group A especially during the first week after treatment. Significant differences were evaluated by repeated-measures analysis of variance. Group A, Algisite M dressing group; group B, Medihoney alginate dressing group.
The application of Medihoney alginate on chronic lower extremity wounds. A 71-year-old female patient with diabetes had calf injury due to trauma. (A) Clinical photo showing a skin defect of about 5.14 cm2 on the anterior portion of the calf. (B) Honey-containing alginate dressing was used to treat the wound. (C) The clinical photo taken about 1 week later shows that the size of the wound had decreased to about 1.32 cm2. (D) Picture obtained 3 weeks after treatment showing complete wound closure.
The application of Medihoney alginate on venous ulcers. A 68-year-old male patient with a history of venous stasis ulcers developed a chronic ulcer in his calf after cellulitis. (A) Clinical photo shows a skin defect on the medial portion of the calf of about 11.25 cm2. (B) Honey-containing alginate dressing was used to treat the wound. (C) The clinical photo taken approximately 2 weeks after treatment showed that the wound had decreased in size to about 6.57 cm2. (D) After 4 weeks of wound care, the wound had healed completely.
Patient demographics
Variable | Total (n=37) | Algisite M dressing group (n=16) | Medihoney alginate dressing group (n=21) | P-value |
---|---|---|---|---|
Age (yr) | 59.89±13.18 | 61.13±12.62 | 58.95±13.51 | 0.631 |
Sex | 0.509 | |||
Male | 17 (45.94) | 6 (37.50) | 11 (52.38) | |
Female | 20 (54.05) | 10 (62.50) | 10 (47.62) | |
Cause of chronic wounds | 0.165 | |||
Diabetes foot ulcer | 24 (64.86) | 8 (50.00) | 16 (76.19) | |
Venous ulcer | 8 (21.62) | 4 (25.00) | 4 (19.05) | |
Pressure sore | 5 (13.51) | 4 (25.00) | 1 (4.76) | |
Location of wounds | 0.544 | |||
Pretibial area | 9 (24.32) | 5 (31.25) | 4 (19.04) | |
Calf area | 3 (8.11) | 2 (12.50) | 1 (4.76) | |
Ankle area | 4 (10.81) | 2 (12.50) | 2 (9.52) | |
Foot | 21 (56.75) | 7 (43.75) | 14 (66.67) | |
No. of wounds | 0.145 | |||
1 | 22 (59.46) | 9 (56.25) | 13 (61.90) | |
2 | 11 (29.73) | 5 (31.25) | 6 (28.57) | |
More than 3 (multiple) | 4 (10.81) | 2 (12.50) | 2 (9.52) |
Values are presented as mean±SD or number (%).
Statistically significant, P<0.05.
Initial wound status
Variable | Algisite M dressing group (n=16) | Medihoney alginate dressing group (n=21) | P-value |
---|---|---|---|
Initial wound size (cm2) | 12.71±3.12 | 13.89±3.25 | 0.251 |
Depth of initial wounds | 0.749 | ||
Dermal to subcutaneous exposure level | 9 (56.25) | 13 (61.90) | |
Muscle exposure level | 7 (43.75) | 8 (38.10) | |
Exudate | |||
Type | >0.999 | ||
Watery | 10 (62.50) | 12 (57.14) | |
Thick | 6 (37.50) | 9 (42.28) | |
Level | 0.899 | ||
Dry | 2 (12.50) | 1 (4.76) | |
Moist | 2 (12.50) | 4 (19.05) | |
Saturated | 8 (50.00) | 10 (47.62) | |
Leaking | 4 (25.00) | 6 (28.57) | |
Bacteria isolated by culturing | 0.998 | ||
MSSA | 6 (37.50) | 7 (33.33) | |
MRSA | 3 (18.75) | 5 (23.80) | |
|
3 (18.75) | 4 (19.04) | |
|
1 (6.25) | 2 (9.52) | |
Multiple mixed organism | 3 (18.75) | 3 (14.28) |
Values are presented as mean±SD or number (%).
MSSA, methicillin-susceptible
Statistically significant, P<0.05.
Decrease in wound area over 4 weeks
Variable | Algisite M dressing group (n=16) | Medihoney alginate dressing group (n=21) | P-value | P-value (PSM) |
---|---|---|---|---|
Decreased in wound area | <0.001b) | 0.021a) | ||
Initial area (cm2) | 12.71±3.97 | 14.07±3.14 | ||
1st week | 8.10±2.00 | 7.33±2.13 | ||
2nd week | 5.80±2.53 | 4.69±1.89 | ||
3rd week | 3.99±1.88 | 2.89±1.59 | ||
4th week | 2.34±1.30 | 1.71±1.21 | ||
Decrease in wound area (%) | 0.023a) | |||
Initial to 1st week | 36.13±6.87 | 47.54±9.72 | ||
Initial to 2nd week | 55.19±8.94 | 67.40±9.66 | ||
Initial to 3rd week | 69.28±10.26 | 80.39±8.04 | ||
Initial to 4th week | 82.26±8.87 | 88.34±7.78 | ||
Patients with complete wound closure by 4 weeks | 7 (43.75) | 15 (71.43) | 0.107 | |
Duration to wound closure (day) | 36.31±11.12 | 34.62±14.31 | 0.705 |
Values are presented as mean±SD or number (%).
PSM, propensity score matching.
Statistically significant, a)P<0.05, b)P<0.001.