A Systematic Review to Compare the Effect of Low-frequency Ultrasonic Versus Nonsurgical Sharp Debridement on the Healing Rate of Chronic Diabetes-related Foot Ulcers

Management of diabetes-related foot ulcers often involves debridement of devitalized tissue, but evidence regarding the most effective debridement method is limited. Purpose: A systematic review was conducted to determine the effectiveness of nonsurgical sharp debridement (NSSD) versus low-frequency ultrasonic debridement (LFUD) for diabetes-related foot ulceration in adults.Method: Published studies (earliest date available to April 2017) comparing healing outcomes of LFUD- and NSSD-treated foot ulcers in adults were considered. The quality of publications that met inclusion criteria were assessed using the PEDro scale, and a meta-analysis was undertaken to compare percentage healed and percentage of ulcer size reduction. Results: Of the 259 publications identified, 4 met the inclusion criteria but 2 of the 4 did not contain sufficient patient outcomes details for meta-analysis, leaving a sample size of 173 patients. Outcome data for the 2 studies included percentage of ulcers healed between the 2 debridement methods. This difference was not significant (RR = 0.92; 95% CI = 0.76-1.11). The risk of bias for both studies was low. Conclusion: No difference in healing outcomes between NSSD and LFUD debridement of diabetic foot ulcers was found. Well-designed, controlled clinical studies are needed to address the current paucity of studies examining the efficacy and comparative effectiveness of debridement methods.

Globally, diabetes is one of the most common noncommunicable diseases. The number of studies describing the epidemiology of diabetes has increased over the last 20 years, and over the past 15 years the global burden estimates of adults living with diabetes has exceeded predictions. In 2000, the International Diabetes Federation¹ estimated 151 million adults were living with diabetes; by 2010, this number was expected to increase to 285 million and estimated to reach 438 million by 2030.² The most recent report from the International Diabetes Federation³ shows the number of adults likely to have diabetes globally in 2015 was 415 million. 

According to the Australian Institute of Health and Welfare,⁴ people with diabetes may develop complications including peripheral neuropathy, peripheral arterial disease, and foot deformity, which can lead to ulceration, infection, and an increased risk of amputation. One (1) in every 6 people with diabetes in developed countries will have a diabetes-related foot ulcer during their lifetime.³ According to the International Working Group on the Diabetic Foot,⁵ people with diabetes also face a 25 times increased risk of amputation compared to persons without diabetes. Currently, a limb is lost every 20 seconds worldwide as a result of diabetes-related amputation.³  

Optimal management of these ulcers is vital in preventing lower limb amputation. Treatment routinely involves offloading⁶ to redistribute pressure away from the area of ulceration and maintaining a moist wound bed environment⁷ to encourage new tissue growth. Additionally, treatment of diabetes-related foot ulcers often involves routine debridement to remove devitalized tissue from the ulcer base. According to guidelines⁸ and a systematic review,⁹ the process of debridement, regardless of the method applied, is believed to stimulate the inflammatory response and encourage healing. Debridement methods include autolytic debridement using dressings and biological debridement using sterile larvae and chemical enzymes. In addition to these topical agents, mechanical debridement via surgical excision or nonsurgical sharp debridement using either a scalpel or scissors is commonly utilized, according to a Cochrane review⁹ and systematic reviews.^10,11 

Contact and/or noncontact, low-frequency ultrasonic debridement (LFUD) offers an alternative to sharp debridement. LFUD generates sound waves ranging from 20 to 40 kHz (undetectable to human hearing), delivered to the ulcer through a liquid medium such as normal saline. According to systematic reviews,^12-14 ultrasound waves have the mechanical effects of cavitation and microstreaming, leading to an increase in cellular activity which, in turn, promotes healing. Specifically, systematic reviews^13,15 of ulcer healing studies also have determined an increase in protein synthesis and an increase in production of growth factors and endothelial cells occurs, all of which stimulate the ulcer toward healing. In vitro studies^14,16 have found both noncontact and contact LFUD lowers bacterial counts through the mechanical destruction of the bacterial cell wall. An in vitro study¹⁷ has shown direct-contact LFUD has the added benefit of enhanced fibrinolysis due to an increased intensity of ultrasound; this subsequently leads to ulcer angiogenesis without destroying healthy ulcer tissue.¹⁵ 

A Cochrane review⁹ on the debridement of diabetes-related foot ulcers included 6 randomized controlled trials; 5 evaluated the effectiveness of hydrogel as a method of debridement against a range of comparators such as combinations of saline dressings and pressure offloading, hydrogel with an additional bacteriostatic action, larval therapy, and 2 other hydrogel dressings. The sixth trial compared surgical debridement with nonsurgical sharp debridement (NSSD) in addition to relieving the pressure of weight-bearing and providing regular dressing changes. Conclusions from the Cochrane review⁹ suggest that although hydrogels increase diabetes-related foot ulcer healing compared with gauze or standard wound care, it is unclear if this effect is directly due to debridement. Additionally, it was noted that randomized controlled trials on debridement for diabetes-related foot ulcers are small in number and of poor methodological quality. The review concluded that while debridement is regarded as an effective intervention to assist healing, more research is needed to evaluate the effects of a wide range of debridement methods and of debridement per se. No subsequent Cochrane review was conducted since its publication, nor a protocol registered for update. 

The aim of this systematic review was to compare available evidence on the effectiveness of bedside NSSD via scalpel without using anesthesia versus contact or noncontact LFUD in terms of percentage of ulcers healed for diabetes-related foot ulceration.

Methodology. The clinical question for this systematic review was generated using the Population Intervention Comparison Outcome¹⁸ (PICO) model for clinical questioning. The question was: In adult patients with chronic diabetes-related foot ulcers, what effect does LFUD have on ulcer healing rates compared to NSSD?

This question was separated into terms to search electronic databases including Ovid, MEDLINE, EMBASE, the Cumulative Index of Nursing and Allied Health Literature Plus, and the Cochrane Database of Systematic Reviews from the earliest date publications were available in each index until April 2017. Table 1 shows the search terms used. Searches were restricted to human studies and English-language articles. 

Two (2) authors independently reviewed the title and abstract of all retrieved studies against the eligibility criteria (see Table 2), which specified chronic diabetes-related foot ulcers (>4 weeks’ duration) in adults >18 years of age. Publications were excluded if 1) the methods of debridement did not involve comparing LFUD to NSSD, 2) wounds demonstrated an etiology other than a diabetes-related foot ulceration, or 3) the study involved acute ulcers, ulcers that did not undergo debridement, and diagnostic or dental ultrasound. 

When the 2 authors disagreed regarding study inclusion, a third author helped resolve the issue through discussion. The full text of articles was obtained when the abstract seemed uncertain. Forward and backward searching strategies also utilized the reference lists and Google Scholar citations of articles included within the full text review. 

Data extraction. General demographics such as gender, country, age, diabetes type, and method of wound debridement of each participant group were extracted from each included study and tabulated and summarized in Table 3. The primary outcome of interest was healing rates of diabetes-related foot ulcers. The secondary outcome of interest was the percentage of ulcers healed. 

All articles included within the review underwent methodological assessment for risk of bias using the quality indicators as outlined by Physiotherapy Evidence Database (PEDro).¹⁹ This scale has 11 indicators to identify any risk of bias. Each indicator was given a score of - if not included, ? if not mentioned, or + if included. According to the PEDro guidelines, criteria 2 to 11 are used for scoring purposes, so a score out of 10 is calculated. 

Two (2) authors completed this assessment independently and resolved any disagreements. Articles also were classified into levels of evidence using criteria set out by the Oxford Centre for Evidence-based Medicine.²⁰ This provides advice on the most appropriate research to guide treatment. Systematic reviews of randomized controlled trials are the highest level of evidence (Level 1), followed by randomized controlled trials (Level 2), nonrandomized controlled cohort/follow-up studies (Level 3), cohort studies and/or case studies (Level 4), and mechanism-based reasoning (Level 5). 

Data collection. Primary outcome of percentage of ulcers healed were extracted into an Excel worksheet (Microsoft Excel, version 16.15, Redmond, WA). 

Data analysis. Analysis was performed using Stata 13 software (College Station, TX). Random effect meta-analysis was performed where data were available for similar outcomes evaluated in more than 1 study. Authors were contacted to request additional data for studies not reporting sufficient outcome data for inclusion in the meta-analysis; however, no responses were received, thus eliminating 2 of the 4 studies from analysis. 

Of the 259 total publications identified using the review search terms after duplicates were removed, 204 titles were determined to be potentially relevant and their abstracts were reviewed. One hundred, ninety-three (193) articles were excluded after reading the abstracts, leaving 11 articles for full text screening. Only 4 articles met the criteria for inclusion in the review. The PRISMA statement lists the reasons for exclusion (see Figure 1). 

Description of studies. Table 3 provides a summary of the 4 articles included: 3 describe clinical trials involving randomization and 1 used historical data from the same clinic as the control with LFUD as the intervention group. Three (3) of the studies used the MIST® noncontact LFUD (Celularity, Inc, Warren, NJ) with varying debridement times and treatment provided either once or 3 times per week. The fourth study used Sonoca 180® noncontact LFUD (Söring GmbH, Quickborn, Germany) performed once per week with debridement duration calculated based on ulcer total area. The control treatments varied between studies, but all studies included NSSD where required and moist wound dressings. Offloading strategies and other treatment modalities varied between the studies, reflecting the complexity and variability of ulcer management and confounding the validity of pooling these studies. The pooled population included 227 patients ranging in age from 40 to 72 years. The included articles described are for the primary outcome (percentage of ulcers healed). 

Meta-analysis/pooling of data. Data extracted included patient demographics, study design and criteria, measurement tool, clinical outcome, and follow-up period. Results from the 2 studies included in the meta-analysis found 30% of the patients in the NSSD groups healed, and 33% in the LFUD groups healed. A meta-analysis was performed on only 2 of the 4 articles; 2 articles had insufficient outcome data, although the current authors attempted to secure the missing data from the original researcher^21,22 in a format that would allow for meta-analysis. Therefore, meta-analysis was performed with 2 articles^23,24 and a total sample size of 173; the analysis did not identify any relationships that suggested a greater effectiveness of either LFUD or NSSD in total healing diabetes-related foot ulcers (RR = 0.92; 95% CI = 0.76-1.11) (see Figure 2). 

Quality of evidence. Scores of the 4 articles indicated a risk of bias according to the PEDro scale (see Table 4). Three (3) of the studies were randomized controlled trials and the fourth used historical data from the same clinic as the control. Not all criteria on the PEDro scale could be satisfied in these studies (eg, the blinding of participants  and clinicians). In 2 of the publications, certain information was not documented and therefore led to a query if the criterion of participant allocation concealment and participants, therapists, and assessors blinding were met. In all 3 randomized controlled trials, participants were randomized to treatment groups and received the allocated treatment or control; these studies also noted between-group statistical comparisons reported for the primary outcome. The 2 studies included in the meta-analysis had a low risk of bias (PEDro score 9/20). 

This review identified that available evidence is insufficient to determine whether LFUD or NSSD provides better outcomes in the treatment of diabetes-related foot ulcers. A total of 110 participants that were provided LFUD was compared to 117 participants treated with NSSD within the same studies. Devices that deliver LFUD are available with varying applications (contact vs. noncontact) that influence the ultrasound intensity delivered to the ulcer. Much variation also was evident in the examined studies in the application time for LFUD as well as the frequency of debridement with treatments, ranging from 3 times per week to once per week. Interim therapy also was a confounding factor. 

It is important to establish whether LFUD is more effective than NSSD to justify its use in clinical practice. Without high-quality evidence supporting the use of LFUD in the treatment of diabetes-related foot ulcers, clinicians using this technology must rely on expert opinion and guidance from the manufacturer. In the current authors’ experience, the different application methods and settings are recommended based on limited research available; clinicians are faced with the potential to be under- or overutilizing this therapy. 

This review demonstrated a relative paucity of evidence supporting the use of LFUD as an alternative to NSSD. Use of NSSD for the management of diabetes-related foot ulcers is recommended in several guidelines,^5,8 which is why it was considered in this study an appropriate standard for comparison in this review. 

It is a limitation of the scope of this review that the effectiveness of NSSD alone was not considered. In addition, the variety of outcome measures among the 4 studies included in this review (percentage of ulcers healed, reduction in ulcer size/volume) made comparisons across the studies difficult. Ideally, a uniform set of outcomes and time points of collection would be reported in the literature to enable pooling across studies. Also, no studies that investigated the use of contact LFUD were found; therefore, the effects of contact versus noncontact LFUD cannot be reported. This was variable outside the study question should other authors wish to undertake further research in this area. Finally, the control groups for all 4 studies were significantly varied. In 3 of the 4 studies, offloading with footwear, orthotics, or padding was not standardized, including the 2 studies in the meta-analysis. Mechanical offloading is known to be vital in managing diabetes-related foot ulcers and plays a large role in healing outcomes,³⁰ but in this research the variety of offloading approaches was a confounding factor. Finally, other important outcomes such as pain, cost, and provider variables were not considered. 

A diabetes-related foot ulcer is a common complication of diabetes that is often a primary cause of hospital admission. LFUD and NSSD are used to manage diabetic foot ulcers, whereby clinicians observe an immediate reduction in nonviable tissue which is believed to facilitate healing. The results of this study showed no difference in healing rates between LFUD and NSSD. More rigorous randomized controlled trials with long follow-up periods and an adequate sample size are needed to identify whether debridement aids the healing of diabetes-related foot ulcers and if so, which is the optimum method when used as an adjunct with best practice ulcer management.

Ms. Michailidis is supported through an Australian Government Research Training Program Scholarship. Dr. Williams is supported through a National Health and Medical Research Early Career Health Professional Fellowship.

Ms. Michailidis is a podiatrist, Monash Health, Podiatry Department, Monash Medical Centre, Clayton, VIC, Australia; and a post-graduate student, Monash University, School of Primary and Allied Health Care, Physiotherapy Department, Frankston, VIC, Australia. Dr. Bergin is a podiatrist, Monash Health, Podiatry Department, Monash Medical Centre. Professor Haines is the Head of School, Monash University, School of Primary and Allied Health Care, Physiotherapy Department. Dr. Williams is an academic, Monash University, School of Primary and Allied Health Care, Physiotherapy Department; and in Allied Health Research, Peninsula Health, Allied Health, Frankston, VIC, Australia.

Please address correspondence to: Lucia Michailidis, B Pod, Monash Health, Podiatry Department, Monash Medical Centre, 246 Clayton Road, Clayton, VIC, 3168, Australia; email: lmichailidis@phcn.vic.gov.au