|Year : 2019 | Volume
| Issue : 1 | Page : 25-30
Prospective randomized comparison of controlled release ionic silver hydrophilic dressings and medicated honey-impregnated dressings in treating neuropathic diabetic foot ulcer
Mohammed Al Saeed
Department of Surgery, College of Medicine and Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
|Date of Web Publication||16-May-2019|
Dr. Mohammed Al Saeed
Department of Surgery, College of Medicine and Medical Sciences, Taif University, PO Box 888, Taif 21947
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Background and Aim of the Work: Recent studies proved that ionic silver hydrogel is a cost-effective and clinically effective method of the treatment of wounds and in particular diabetic foot ulcer; in addition, the antibacterial and tissue-healing properties of manuka honey (MH) had been proved by various investigators. This study aimed to compare the effectiveness of the use of controlled release ionic silver hydrophilic dressing with that of MH-impregnated dressings in patients with diabetic neuropathic plantar ulcers. Patients and Methods: This was a prospective, double-blind, randomized comparative clinical trial conducted in diabetic foot care unit at the King Abdul Aziz Specialist Hospital in Taif, Saudi Arabia. Seventy-one patients were enrolled from January 2015 to December 2017. Patients with neuropathic plantar ulcers were included in the study with exclusion of ischemic and neuroischemic ulcers. Patients who met the inclusion criteria of this study were subdivided and randomized into two groups: Group I (honey group) and Group I (silver hydrogel group); in both the groups after drainage of any collection and surgical debridement of hyperkeratotic and necrotic tissues and irrigating the ulcers, in Group I, MH-impregnated dressing containing 35 g of Unique Manuka Factor-13 was applied, and in Group II, controlled release ionic silver hydrophilic dressings were used to cover the ulcer. The mean time required for eradicating infection, hospital length of stay (LOS), and the mean time of complete healing of the ulcers were the primary outcomes. Secondary outcome was to correlate the mean time of ulcer healing with duration of diabetes, hemoglobin A1c, and presence of nephropathy or neuropathy. Results: There was no significant difference in the demographic data, size of the ulcers, mean duration of diabetes, and clinical and laboratory data between both the groups (P > 0.05). The mean time to eradicate infection and hospital LOS were reduced in the silver treatment group compared to honey treatment group, but the difference does not reach a statistical significance (P > 0.05); the table shows also that the mean time required for complete ulcer healing was shorter in MH group than the silver hydrophilic dressing group (P > 0.05, insignificant). In both the groups, the duration of healing was significantly correlated with the patient age, pretreatment level of HbA1c, pretreatment duration of the ulcer, and the ulcer size; however, there was no significant correlation with gender and duration of diabetes. Conclusions: The present study verified the effectiveness of MH-impregnated dressings and the controlled release silver hydrophilic dressings in controlling wound infection and promoting the complete healing of neuropathic ulcers.
Keywords: Diabetic foot, manuka honey, neuropathic plantar ulcer, silver hydrogel
|How to cite this article:|
Al Saeed M. Prospective randomized comparison of controlled release ionic silver hydrophilic dressings and medicated honey-impregnated dressings in treating neuropathic diabetic foot ulcer. Saudi J Health Sci 2019;8:25-30
|How to cite this URL:|
Al Saeed M. Prospective randomized comparison of controlled release ionic silver hydrophilic dressings and medicated honey-impregnated dressings in treating neuropathic diabetic foot ulcer. Saudi J Health Sci [serial online] 2019 [cited 2019 Jun 18];8:25-30. Available from: http://www.saudijhealthsci.org/text.asp?2019/8/1/25/257761
| Introduction|| |
The prevalence of diabetes mellitus in the Kingdom of Saudi Arabia is much higher than that recorded in various global reports., The incidence of diabetic foot ulcers (DFUs) in Saudi Arabia particularly in the rural areas is expected to be higher than that recorded globally.,,
The value of medicated honey preparations has been proved by many investigators where they verified that it provides a moist wound environment with enhancement of desloughing and healing of the ulcer in addition to its potent anti-inflammatory, immune-modulatory, and antibacterial properties., Previous studies found that standardized manuka honey (MH)-impregnated dressings have been proved to be an effective treatment for neuropathic DFUs leading to a significant reduction in the time of healing and rapid disinfection of ulcers.,,,, Researchers reported the ability of silver hydrogel preparations to deliver ionic silver with it antimicrobial properties in addition to its moisturizing effect that provides an optimal environment for wound healing. Several studies verified also that silver hydrogel dressings are cost-effective and clinically effective method of the treatment of DFUs and associated with atraumatic and virtually pain-free removal., It was reported that silver hydrogel was superior to povidone-iodine-soaked gauze in facilitating the rapid epithelialization of infected or potentially infected ulcers and resulted in more reduction in the overall bioburden.,,,,,,,, Therefore, this study aimed to compare the effectiveness of the use of ionic silver hydrogel-perforated dressings with that of MH-impregnated dressings in patients with diabetic neuropathic plantar ulcers.
| Patients and Methods|| |
This prospective, double-blind, randomized comparative clinical trial was conducted in diabetic foot care unit at the King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia. The study was approved by the ethical committee of the hospital. Seventy-one adult patients of both sexes with a diagnosis of neuropathic DFUs with a Wagner classification of Stage II, III, or IV were enrolled from January 2015 to December 2017. Written informed consent was obtained from all participants.
All patients were fully assessed clinically and by laboratory with imaging tools, and the following patients were excluded: patients below 18 years, patients with ischemic or neuroischemic ulcers, patients with osteomyelitis, patients suffering from liver or kidney failure, and those receiving chemotherapy, radiotherapy, or immunosuppressant drugs or participating in another clinical trial.
Eligible patients were randomized into two groups with similar distributions of sex, age, and Wagner stage: honey treatment group which included 36 patients (MH or Group I) and silver hydrogel group which included 35 patients (Group II). After drainage of any collection and surgical debridement of hyperkeratotic and necrotic tissues, ulcers were washed with povidone-iodine or if the patient developed an allergy to iodine with Edinburgh University Solution of Lime (EUSOL) and irrigated with normal saline.
In Group I, MH-impregnated dressing (TheraHoney™ Sheet, Medline Industries, Northfield, Illinois, USA) was applied, and in Group II, controlled release silver hydrophilic dressing (Silvasorb™ Perforated Sheet Dressings, Medline Industries, Northfield, Illinois, USA) was used to cover the ulcer. In both the groups, an occlusive secondary adsorbent dressing was applied and changed daily in MH group, and in hydrophilic silver group, it can be left for 7 days because of its property of controlled ionic silver release. However, more frequent change of the dressings in both the groups was performed if it was markedly soaked.
Concomitant management included regular clinical and laboratory assessment with management of any detected abnormality, and patients were advised to stop smoking in addition to control of diet, hypertension, hyperlipidemia, and blood glucose level to maintain hemoglobin A1c (HbA1c) around 7%. Suitable systemic antibiotics were given on the basis of weekly culture till infection was eradicated.
Patients were treated in the diabetic care unit in the hospital until the infection was eradicated and healthy granulations were formed followed by completion of the treatment in an outpatient clinic.
Acetate plates (planimetry), weekly ulcer swab, and digital photography were used to the changes in the ulcers.
The primary outcomes were time to eradicate infection, length of hospital stay, and mean time required for complete healing of the ulcer. The changes in the ulcers were recorded every week after the onset of the treatment.
The secondary outcome was to find a correlation between the mean time of ulcer healing and gender, age, duration of diabetes, pretreatment ulcer size, and the pretreatment level of HbA1c.
Results are expressed as mean ± standard deviation. Analyses were performed using SPSS version 22 (SPSS Inc., Chicago, IL, USA). The significance between two means was tested by Student's t-test. Chi-square test and Fisher's exact tests were used to differentiate between two groups. Pearson and Spearman's correlation tests were used to correlate between each parameter and different variants in the same group to find significant differences. Nonparametric tests were used if the distribution did not satisfy the parametric assumptions. P < 0.05 was considered significant.
| Results|| |
A total of 71 patients participated in the study. The protocol was strictly followed throughout the study. Thirty-six patients were randomized to MH treatment (Group II) and 35 patients to silver hydrophilic dressing group (Group II). [Table 1] shows no significant difference in the demographics, ulcer size, duration of diabetes, and clinical and laboratory data between both the groups (P > 0.05). The distribution of patients according to the Wagner grade of the foot ulcer is shown also in [Table 1]. [Table 2] shows that the mean time to eradicate infection and hospital length of stay (LOS) were reduced in the silver treatment group compared to honey treatment group, but the difference does not reach a statistical significance (P > 0.05); the table shows also that the mean time required for complete ulcer healing was shorter in MH group than the silver hydrophilic dressing group (P > 0.05, insignificant). Comparing the mean duration of healing in both the groups below and above the median values of the age, level of HbA1c, pretreatment ulcer duration, and the ulcer size, significant correlations were found. The duration of healing was not significantly correlated with gender or duration of diabetes [Table 3]. There were no deaths in either group during the follow-up period. [Figure 1] shows the progress of healing of neuropathic ulcer after application of hydrophilic silver dressings. [Figure 2] shows the progress of healing of neuropathic ulcer after application of MH dressings.
|Table 2: The mean duration of healing, time to eradicate infection, and length of stay|
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|Table 3: Correlating mean time of ulcer healing in both the groups with gender, age, pretreatment hemoglobin A1C level, the size of the ulcer, and duration of diabetes|
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|Figure 1: Progress of healing of neuropathic ulcer after application of hydrophilic silver dressings|
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|Figure 2: Progress of healing of neuropathic ulcer after application of manuka honey dressings|
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| Discussion|| |
The lifetime risk development of foot ulcer in a diabetic patient is about 20%, and due to several factors, the healing of these ulcers represents a challenge for the surgeon. Proper treatment of DFU must include; glycemic control, debridement of necrotic and hyperker
atotic lesions, and control of infection by drainage of any collection with the use of local or systemic antibacterial agents.,
Successful treatment also requires suitable dressing, off-loading, and improving the tissue perfusion by correction of any arterial insufficiency.,,, The previous guidelines were in accordance with the protocol of treatment of the patients in the current study; however, ischemic and neuroischemic ulcers were excluded from the trial. The ideal dressing of DFU is not existent as it must provide moist environment, decrease the bioburden and impermeable to microorganisms, allow gaseous exchange, promote healing, help in removal of sloughs, and excess exudate with its toxic components and, finally, should be easily removed and cost-effective. Medicated honey as MH has an antibacterial and anti-inflammatory effect in addition to its hygroscopic effect that produces moist environment and helps desloughing.,,,,, The antibacterial and the anti-inflammatory effects of silver were verified by many investigators; however, the moisturizing property can be produced by certain hydrophilic silver-containing dressings. In the current study, the mean duration of healing of neuropathic DFU was slightly shorter in the group of patients treated by MH-impregnated dressing than the hydrophilic silver group of patients; however, the difference was statistically insignificant. To the best of my knowledge, no study compared ionic silver hydrophilic dressings with MH as the treatment of DFU; however, Tsang et al. recorded in their pilot study that nanocrystalline silver alginate was potentially superior to MH and conventional dressing in terms of ulcer size reduction rate. Al Saeed recorded, in his study on neuroischemic DFU, a complete healing of 61.3% and 87.5% of patients after 6 weeks and 6 months, respectively, of treatment with MH-impregnated dressings. The results obtained by the trial of Imran et al. using honey in DFU were in adherence with that of the current study Nametka et al. found that silver hydrophilic dressing benefits management of recurrent nonhealing wounds. Dong et al. in their study reported the value of ionic silver as a dressing in the treatment of DFU recording a shorter mean duration of healing than that recorded in the present study even though they verified that oil silver gauze had a better outcome for DFU healing. The difference in the results between the previous studies and the current study may be explained by the difference between the various silver preparations, in addition to the difference in the studied specimens.
Molan and Eddy and Gideonsen explained in their studies that MH accelerates ulcer healing through its antimicrobial effect which decreases the bioburden, hygroscopic effect which facilitates wound debridement, and slough separation that prepares the site for the healing process in addition to the activation of monocytes and other cells to produce cytokines stimulating the growth of granulation tissue and epithelialization. Imran et al. clarified in their study that MH promotes ulcer healing through the increase in the nitric oxides in the wound with its anti-inflammatory mediator effect, its ability to induce cell proliferation, and immune response. Other studies verified that honey reduces edema and exudates, promotes angiogenesis and induces wound contraction, and stimulates collagen synthesis.,,
Gunasekaran et al. reported in their review that the mechanism by which topical silver preparations in DFU is not exactly known; however, the hastened healing process, especially in silver nanoparticles preparations, is not only related to its antibacterial effect but also directly acts on suppressing the process of inflammation. Similar observations were obtained by Tian et al. in their animal model study where they found that silver nanoparticles exert positive effects on healing process through their antimicrobial properties, reduction in wound inflammation, and modulation of fibrogenic cytokines, and they emphasized that rapid healing and improved cosmetic appearance were dose dependent.
The mean time to eradicate infection (which reflects the LOS) in our study varies from few days to about 6 weeks in both groups of patients, a result which is similar to that recorded by Kamaratos et al. Tsang et al. found in their study that patients treated by silver dressings showed the greatest decreasing trend in the number of species of microorganisms though silver group did not show a significant decrease in bacteriology as compared with the MH group, and they concluded that the results of their study and the other studies showed that the patients treated with MH dressing or silver dressing had an observable lower number in bacteria but did not reach the statistical significance. The findings in the current trial were in agreement and support the results of the previous studies. In accordance with the previous findings, Hammouri reported in his study that the use of Jordanian natural honey-soaked dressings in the treatment of neuropathic DFU lowered time to eradicate infection and length of hospital stay by 34% and 43%, respectively. Supporting findings were also obtained by other studies.
Researchers found that the antibacterial effect of MH is multifactorial, where hyperosmolarity dehydrates bacteria and its acidic nature inhibits the growth of most microorganisms, such as Salmonella More Details species, Streptococcus pyogenes, Escherichia More Details coli, Pseudomonas aeruginosa, and noncoagulase producer Staphylococcus aureus.,, Honey inhibits catalases that metabolize hydrogen peroxide with its known antibacterial effect. Phytochemical factors in particular methylglyoxal and methyl syringate glycoside (leptosin) are found in MH in higher concentration than other honeys have broad-spectrum antimicrobial effect which is closely related to the level of antibacterial activity.,
Silver preparations, especially nanocrystalline and controlled release hydrophilic silver which require less frequent change, have a broad spectrum of antimicrobial activity, low development of resistance, and a low risk of systemic toxicity and adverse reactions. The mechanisms of nanosilver and silver ions were similar but that the former has a smaller particle which allows more solubility and in turn appears to be significantly more efficient than silver ions. The antimicrobial effect of silver is related to its effect on bacterial cell wall and membrane permeability and interaction with thiol group-containing enzymes, such as NADH-dehydrogenase II in the respiratory system which will lead to the formation of hydroxyl radicals and to an attack on the cell itself and DNA damage., In addition, silver can enhance apoptosis inside the bacteria leading to their death.
Christman et al. and Margolis et al. found that the factors which may contribute to neuropathic ulcer healing were pretreatment glycemic control, ulcer surface area, and pretreatment ulcer duration, with no relationship with age and sex., The results in the current study were in adherence to the that of the previous trials; however, the only difference was in the age which showed a significant correlation with duration of healing in the currently treated patients.
Edmonds et al. confirmed in their study on patients with neuroischemic DFU that the dressing and the duration of ulcer before treatment were the most significant variables and better outcomes were reached in wounds with duration of <6 months recommending treating wounds as soon as possible. The current study confirmed the significant correlation between durations of healing; however, there was no significant difference in the outcome using silver hydrophilic dressings and MH dressings.
| Conclusions|| |
The present study verified the effectiveness of MH-impregnated dressings and the controlled release silver hydrophilic dressings in controlling wound infection and promoting the complete healing of neuropathic ulcers.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]