Evaluating the effectiveness of ultrasound-assisted wound debridement in managing diabetic foot ulcers: A systematic review and meta-analysis

Abstract

BACKGROUND

Diabetic foot ulcers (DFUs) present a significant clinical challenge due to their high prevalence and profound impact on morbidity. Ultrasound-assisted wound debridement (UAWD) has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.

AIM

To evaluate the efficacy of UAWD in treating DFUs on wound closure rates, treatment duration, and quality of life outcomes.

METHODS

This systematic review and meta-analysis followed PRISMA guidelines, systematically searching PubMed, Embase, Web of Science, and the Cochrane Library with no date restrictions. Randomized controlled trials (RCTs) that evaluated the efficacy of UAWD in DFU treatment were included. Data were independently extracted by two reviewers, with discrepancies resolved through consensus or third-party consultation. The risk of bias was assessed using the Cochrane tool. χ² and I² statistics assessed heterogeneity, informing the use of fixed or random-effects models for meta-analysis, supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.

RESULTS

From 1255 articles, seven RCTs met the inclusion criteria. The studies demonstrated that UAWD significantly reduced DFU healing time (standardized mean difference = -0.78, 95%CI: -0.97 to -0.60, P < 0.001) and increased healing rates (odds ratio = 9.96, 95%CI: 5.99 to 16.56, P < 0.001) compared to standard care. Sensitivity analysis confirmed the stability of these results, and no significant publication bias was detected.

CONCLUSION

UAWD is a promising adjunctive treatment for DFUs, significantly reducing healing times and increasing healing rates. These findings advocate for the integration of UAWD into standard DFU care protocols.

Key Words: Diabetic foot ulcers; Ultrasound-assisted wound debridement; Healing time; Healing rates; Meta-analysis

Core Tip: Ultrasound-assisted wound debridement (UAWD) significantly accelerates the healing process of diabetic foot ulcers (DFUs) compared to standard treatment methods. Our meta-analysis of randomized controlled trials reveals a notable enhancement in DFU healing rates with the application of UAWD. Evidence from the study supports the integration of UAWD into standard DFU care protocols to improve patient outcomes. Sensitivity analysis and rigorous assessment for publication bias confirm the robustness and reliability of our findings regarding the efficacy of UAWD. The adoption of UAWD could represent a pivotal shift in DFU management, offering a more effective solution for a widespread clinical challenge.

INTRODUCTION

The increasing global prevalence of diabetes mellitus, together with a corresponding rise in diabetic foot ulcers (DFUs), highlights an urgent necessity for creative and effective wound management strategies[1]. DFUs are a severe consequence of diabetes and provide considerable dangers to patients, including increased vulnerability to infections, extended hospitalizations, and a greater probability of lower extremity amputations[2,3]. These issues not only diminish the quality of life for affected individuals but also put significant expenses on healthcare systems globally[4]. In this context, ultrasound-assisted wound debridement (UAWD) is an innovative therapeutic approach that has significant potential to transform the traditional treatment for DFUs[5]. Utilizing ultrasonic energy, UAWD precisely removes non-viable tissue, destroys biofilms, and eliminates microbial presence within ulcerative lesions, potentially expediting the healing process[6,7]. The mechanism of UAWD indicates that this technology enables a more precise and delicate debridement process than traditional methods, thus maintaining viable tissues and fostering an optimal environment for wound healing[8].

The theoretical benefits of UAWD surpass simple debridement efficacy. The utilization of ultrasonic waves is believed to promote biological processes essential for wound healing, including increased angiogenesis and accelerated granulation tissue development[9]. Together, these actions may enhance the speed and efficacy of the healing process, potentially alleviating the difficulties related to DFUs[6,10]. Nonetheless, despite the encouraging theoretical foundation and the favorable results documented by preliminary investigations, the scientific community remains prudent. The evidence substantiating the effectiveness of UAWD in managing DFU is now fragmented and is inconsistent[11,12]. Current research contains significant variations in study design, patient demographics, and outcome assessments, complicating the synthesis of definitive evidence about the efficacy of UAWD. This diversity highlights the essential requirement for a more systematic and thorough assessment of UAWD via meticulously designed clinical studies and extensive reviews[13].

This research intends to conduct a systematic review and meta-analysis to assess the efficacy of UAWD in treating DFUs. This research aims to synthesize data from numerous trials to elucidate the therapeutic efficacy of UAWD. The objectives are diverse: To evaluate the influence of UAWD on wound closure rates, to analyze its potential in decreasing treatment duration, and to understand its implications on enhancing the overall quality of life for patients with DFUs.

MATERIALS AND METHODS

Search strategy

The systematic review adhered to the guidelines set forth by the PRISMA[14]. To achieve a broad and inclusive literature search, ed PubMed, Embase, Web of Science, and the Cochrane Library was searched on September 19, 2023, with no publication date limits to maximize the scope of relevant findings. The targeted search strategy employed the following keywords and MeSH terms to ensure a comprehensive collection of pertinent studies: Keywords: "ultrasonic debridement", "ultrasound debridement", "diabetic foot", "diabetic wound", "DFU", "debridement" and "sonic debridement"; MeSH Terms: "diabetic foot", "debridement" and "ultrasonics". Search Combinations: ("ultrasonic debridement" OR "ultrasound debridement" OR "sonic debridement" OR "low-frequency ultrasound" OR "ultrasound therapy") AND ("diabetic foot" OR "diabetic wound" OR "diabetic foot ulcer" OR "DFU" OR "foot ulcer" OR "diabetic ulcer") AND ("treatment" OR "management" OR "therapy" OR "healing" OR "wound care"). Additionally, a manual examination of reference lists from identified articles was performed to capture any studies not detected through database searches, thereby enhancing the robustness and comprehensiveness of the meta-analysis.

Inclusion criteria and exclusion criteria

Inclusion criteria: (1) Study design: Only randomized controlled trials (RCTs) that assessed the efficacy of UAWD in the treatment of DFUs were included; (2) Participants: Studies involving patients diagnosed with DFUs, regardless of age, sex, or diabetes type, were considered; (3) Intervention: The primary intervention of interest was UAWD. Studies were included if they provided clear descriptions of the UAWD technique, including frequency and duration of treatment; (4) Comparators: Studies that compared UAWD with standard wound care practices, other debridement methods, or no treatment were included; and (5) Outcomes: Eligible studies reported on clinically relevant outcomes, such as wound healing rate, time to healing, reduction in wound size, infection rates, and limb salvage rates.

Exclusion criteria: Non-empirical studies: Reviews, editorials, opinion pieces, and case reports were excluded to focus on empirical evidence.

Data extraction

In the meta-analysis, literature scans and data extractions were executed, independently undertaken by two reviewers to guarantee accuracy and objectivity. Each paper was meticulously analyzed, and pertinent data were diligently retrieved and subsequently cross-verified among the assessors to ensure consistency and reliability. When inconsistencies occurred, the reviewers conducted thorough conversations to resolve differences, and if required, a third-party reviewer was consulted to achieve consensus. The extracted data included essential information for the research, such as the authors' names, the publication year of each study, and the total number of cases assessed. Certain types of diabetes were specified according to the Wagner Grading System, the period of wound existence prior to intervention, the nature of interventions implemented, and the outcome measures evaluated in each trial. In instances where relevant data were not explicitly presented in the published articles, the original researchers were contacted via email to solicit the missing information.

Quality assessment

The methodological rigor of the chosen papers was assessed utilizing the risk of bias evaluation instrument from the Cochrane Collaboration[15]. This assessment was performed autonomously by two reviewers, who examined various essential elements of each study, including the generation of random sequences, allocation concealment, blinding of participants and personnel, management of incomplete outcome data, selective outcome reporting, and the detection of any additional sources of bias. The risk linked to each of these domains was classified as low, ambiguous, or high. When the two reviewers held divergent perspectives, they conducted a comprehensive conversation to achieve consensus, and if required, a third reviewer was consulted to arbitrate and resolve the disagreement.

Statistical analyses

The heterogeneity among the included studies was initially assessed by employing χ² statistics and quantifying the variance using the I² statistic. A low level of heterogeneity was indicated by an I² value below 50% combined with a P value ≥ 0.10, under which circumstances, a fixed-effect model was applied to calculate the combined effect size. Conversely, when I² reached 50% or higher, or the P value was < 0.10, this was considered evidence of significant heterogeneity and used a random-effects model to derive the pooled effect size. To ensure the reliability of our findings, sensitivity analysis was conducted by systematically excluding each study in turn and recalculating the overall effect size to identify any single study's undue influence on the meta-analysis results. This step was crucial for assessing the robustness of the results and identifying potential sources of heterogeneity. Further, the possibility of publication bias was evaluated by examining the symmetry of the funnel plot; an asymmetrical distribution suggested potential bias. Egger's linear regression test provided a more quantitative approach to detecting publication bias, with a P value less than 0.05 indicating statistical significance. All statistical analyses were performed using Stata version 17 (StataCorp, College Station, TX, United States), adhering to a two-sided significance threshold, where a P value less than 0.05 was considered indicative of statistical significance.

RESULTS

Search results and study selection

In the initial phase of our meta-analysis, we conducted a comprehensive search that yielded 1255 articles. Through a systematic process to eliminate duplicates and a rigorous review of titles and abstracts against our predefined criteria, we narrowed the field to 36 articles for full-text examination. The detailed assessment led to the exclusion of 29 articles for various reasons, including reviews, redundancies, data insufficiency, and the absence of control groups. Consequently, 7 studies met all our inclusion criteria and were selected for the final analysis, providing a focused and high-quality evidence base for our research[10,16-21] (Figure 1).

Figure 1 Study inclusion flowchart.

Study characteristics

The meta-analysis included a diverse range of studies spanning from 2009 to 2019, examining the efficacy of UAWD in the management of DFUs. While the diabetes type was often not mentioned in these studies, the patient populations typically involved those with a range of Wagner Grade ulcer classifications, predominantly between 0-3. The duration of ulcers before intervention commonly extended to 2 weeks or more, with one study specifying a minimum of 4 weeks. Control interventions across the studies consistently involved standard treatments combined with conventional debridement techniques. These standard treatments comprised a comprehensive approach to diabetes management, including glycemic control, anti-infection measures, circulation improvement, lipid reduction, and intensified control of blood glucose and lipids. The intervention measures varied slightly but generally centered around the application of ultrasound-assisted debridement, either with standard treatment protocols or as a standalone treatment. The application frequency of UAWD ranged from daily to every other day, with one study specifying a 30-60 second duration per treatment session. Notably, one study differentiated by employing low-frequency ultrasound debridement, indicating a variation in the ultrasound debridement methodologies being investigated (Table 1).

Table 1 Characteristics of studies included in the study.

Ref.	Year	Diabetes type	Wagner grade	Ulcer duration	Control intervention	Intervention measures
Xu et al[17]	2019	NA	0-3	≥ 2 weeks	Standard treatment + conventional debridement	Standard treatment + ultrasound debridement (daily)
Lin et al[16]	2017	NA	Not mentioned	Not mentioned	Standard treatment + conventional debridement	Standard treatment + ultrasound debridement (daily)
Xu et al[19]	2016	Type 1/2	2 or 3	≥ 2 weeks	Standard treatment + conventional debridement	Standard treatment + ultrasound debridement
Lu et al[20]	2014	NA	0-3	≥ 2 weeks	Standard treatment + conventional debridement	Standard treatment + ultrasound debridement (daily/every other day)
Amini et al[10]	2013	Type 1/2	0-3	≥ 4 weeks	Standard treatment	Standard treatment + low-frequency ultrasound debridement
Cao et al[21]	2010	Type 1/2	0-3	≥ 2 weeks	Standard treatment + conventional debridement	Standard treatment + ultrasound debridement (daily, 30-60 seconds)
Ye et al[18]	2009	Type 2	Not mentioned	Not mentioned	Surgical debridement	Ultrasound debridement (daily/every other day)

Standard treatment encompasses glycemic control, anti-infection measures, circulation improvement, lipid reduction, and intensified control of blood glucose and lipids. NA: Not available.

Results of quality assessment

The comprehensive quality evaluation of studies in our meta-analysis indicates a generally strong methodological framework, as evidenced by the risk of bias chart. A considerable percentage of the studies analyzed demonstrated little risk of bias in essential domains, including random sequence generation and allocation concealment, which are crucial for mitigating selection bias. This indicates that the randomization process and the concealment of allocation sequences were typically executed with considerable rigor. Concerning performance bias, the majority of research indicated little risk, signifying that blinding of participants and personnel was successfully executed. The evaluation of detection bias indicated that the blinding of outcome assessments was largely effectively executed throughout the investigations. The chart indicated a relatively low risk of attrition bias, as seen by incomplete outcome data, suggesting thorough reporting and management of outcome data. The likelihood of selective reporting was inconsistent, suggesting the possibility of reporting bias in certain research, necessitating careful examination when interpreting findings (Figure 2).

Figure 2 Risk of bias in studies as assessed by Cochrane Criteria, with high risk marked in red and low risk in green.

Efficacy of UAWD in DFU healing time

In this meta-analysis, the impact of UAWD on the healing time of DFUs was evaluated across seven studies. Significant heterogeneity was detected among the studies (I² = 45.6%, P = 0.088), which necessitated the use of a random-effects model for analysis. The results indicated that UAWD significantly reduced the healing time for DFUs. The combined effect size demonstrated a standardized mean difference of -0.78 with a 95%CI ranging from -0.97 to -0.60, and the results were statistically significant (P < 0.001, Figure 3). The analysis revealed that the healing times for ulcers in the intervention groups where UAWD was utilized were significantly shorter than those in the control groups, which received conventional treatment. These findings suggest that UAWD is an effective modality for reducing the healing time in patients suffering from DFUs, highlighting its potential as a valuable addition to standard wound care protocols.

Figure 3 Forest plots showing the impact of ultrasound-assisted wound debridement on healing times in diabetic foot ulcers.

Efficacy of UAWD in DFU healing rates

The present meta-analysis assessed the healing rates of DFUs after treatment with UAWD, synthesizing data from seven studies. A fixed-effects model was employed due to the absence of substantial heterogeneity among the included studies (I² = 34.3%, P = 0.166), suggesting consistent results across the research. The meta-analytical findings revealed a notably higher healing rate in the UAWD treatment groups compared to the control groups receiving standard care. The odds ratio (OR) for healing in the UAWD group was 9.96, with a 95%CI strongly favoring the treatment effect, ranging from 5.99 to 16.56, and the statistical significance was marked (P < 0.001, Figure 4). These results demonstrate that the application of UAWD significantly enhances the likelihood of ulcer healing in patients with DFUs.

Figure 4 Forest plots demonstrating the effectiveness of ultrasound-assisted wound debridement on healing rates of diabetic foot ulcers.

Sensitivity analysis: Assessing the robustness of meta-analysis findings

To evaluate the strength of the cumulative evidence in our meta-analysis, particularly given the evident heterogeneity among the included studies, we conducted a thorough sensitivity analysis. This analysis aimed to assess the impact of each individual study on the overall effect size and to verify the robustness of our findings. Utilizing a leave-one-out methodology, we recalibrated the overall effect estimates by sequentially excluding each trial. This methodological approach is essential for recognizing the potential disproportionate influence of any individual study on the meta-analysis. The results of this sensitivity analysis repeatedly indicated that the exclusion of any single study did not substantially affect the pooled impact estimates, hence affirming the robustness and dependability of our findings. The uniformity of the effect sizes, even after the sequential elimination of individual studies, significantly bolsters the trust in our meta-analytical findings. The synthesized data accurately represent the impact of the intervention being examined. This sensitivity study reinforces the outcomes of the meta-analysis, establishing a robust basis for the research implications (Figure 5).

Figure 5 Results of sensitivity analysis assessing the stability of findings on healing times with ultrasound-assisted wound debridement in diabetic foot ulcers.

Publication bias assessment

To evaluate the presence of publication bias within our meta-analysis, we utilized funnel plot analysis as a graphical tool, plotting the included studies to visually assess asymmetry. The constructed funnel plots displayed symmetry, suggesting no apparent publication bias (Figure 6). This visual inspection was corroborated by Egger's linear regression test, a more quantitative method, which showed no significant evidence of publication bias across various variables examined in the meta-analysis (all P values > 0.05). The absence of publication bias as indicated by both the funnel plots and Egger's test enhances the credibility of our meta-analysis findings. Together, these results collectively substantiate the meta-analysis's robustness, ensuring that the conclusions are reflective of unbiased research data.

Figure 6 Funnel plot analysis to evaluate publication bias across included studies.

DISCUSSION

The management of DFUs is a critical issue in diabetes care because of its widespread occurrence and significant effects on morbidity, quality of life, and healthcare costs[22]. As diabetes mellitus increasingly impacts the global population, the prevalence of DFUs correspondingly rises, highlighting an urgent need for improved treatment strategies[23,24]. Current standard care protocols, including glycemic control and conventional wound debridement, have provided substantial benefit, yet they leave a significant need for interventions that can further enhance healing outcomes. UAWD has emerged as a promising technique that could potentially revolutionize the approach to DFU management. The utilization of ultrasonic energy aims to selectively debride necrotic tissue and disrupt biofilms, which are frequently resistant to conventional treatments. By facilitating a more conducive wound healing environment, UAWD is posited to not only expedite healing but also to improve the quality of healing, reducing the risk of infection and subsequent amputations. The findings of this meta-analysis provide substantial evidence that UAWD is an effective intervention for reducing the healing time and increasing the healing rates of DFUs[25,26]. The significant reduction in healing time and the improvement in healing rates observed in patients receiving UAWD compared to those receiving standard care may be attributed to several underlying mechanisms.

The present meta-analysis evaluates the efficacy of UAWD in the management of DFUs, considering its potential as an adjunct to standard wound care. The focus on RCTs aims to provide evidence on critical outcomes, namely healing time and healing rate, which are important for DFU treatment. Unlike previous reviews that included a variety of study designs, this analysis sought to reduce bias by concentrating exclusively on RCTs. Clinically, UAWD was found to significantly reduce healing time and increase healing rates compared to conventional care, enhancing treatment efficiency, reducing healthcare costs, and mitigating the risk of complications like amputation. These findings highlight the inspiration for expanding the use of UAWD beyond traditional methods, particularly in challenging clinical scenarios with high risks of complications. Furthermore, our results guide clinical practice by supporting the integration of UAWD into DFU care protocols, offering a non-invasive, efficient, and replicable treatment option that improves patient outcomes and quality of life across various healthcare settings.

UAWD is recognized for its ability to accelerate the wound healing process via its mechanical and biological mechanisms[27]. The ultrasonic energy mechanically disturbs the wound surface, facilitating the clearance of necrotic tissue and bacterial biofilms that may obstruct natural healing processes[28]. The debridement results in a cleaner wound bed, which is crucial for subsequent healing stages. Furthermore, ultrasonic waves can induce microstreaming and cavitation at the cellular level, potentially enhancing cell membrane permeability and facilitating the migration and proliferation of cells pertinent to wound healing[29]. UAWD can stimulate angiogenesis, the process of new blood vessel creation. Augmented angiogenesis is essential in chronic wounds such as DFUs, as it enhances blood circulation and oxygenation, hence expediting tissue repair and regeneration[30-32]. Furthermore, the mechanical effect of UAWD has been postulated to release growth factors from the extracellular matrix, which further stimulates cellular activities crucial for healing. The heterogeneity observed among the studies (I² = 45.6%) could be reflective of different UAWD protocols, patient populations, or wound characteristics. Despite this, the robustness of the results was confirmed through sensitivity analysis, indicating that the overall conclusions of the meta-analysis are not overly reliant on any individual study.

Moreover, the ultrasonic activity may modify the inflammatory response, mitigating excessive inflammation that typically hinders healing in diabetes wounds. The decrease in inflammatory cytokines and the elevation of anti-inflammatory mediators may foster a more favorable environment for recovery. The standard mean difference of -0.78 and the OR of 9.96 in favor of the UAWD treatment group demonstrate not only the clinical relevance of these findings but also the potential for UAWD to significantly enhance the standard of care for patients with DFUs[33,34]. This effect size is indicative of a substantial clinical benefit, which is further reinforced by the sensitivity analysis, underscoring the dependability of the meta-analysis results. Moreover, the fixed-effects model used in assessing the healing rates points to a consistency in the effects of UAWD across studies, suggesting a reliable and reproducible benefit in the treatment of DFUs. The lack of significant publication bias as revealed by funnel plots and Egger's test adds to the credibility of these findings[35]. However, it is essential to recognize that while UAWD shows promise, it is not without its limitations and may not be universally applicable to all patient populations. Factors such as ulcer etiology, patient compliance, and underlying comorbidities may affect the effectiveness of UAWD.

The research presented has several limitations. Heterogeneity in UAWD protocols and patient characteristics among studies may have influenced outcomes. Small sample sizes and varying follow-up durations limit statistical power and generalizability. Lack of uniformity in secondary outcome reporting, such as quality of life and cost-effectiveness, affects broader implications. Methodological limitations include potential publication bias due to only published RCTs being included, inconsistent risk of bias (e.g., allocation concealment and blinding), incomplete datasets, and variability in wound classification and outcome definitions. Despite its limitations, this meta-analysis provides valuable insights into the clinical utility of UAWD in DFU management. The findings suggest that UAWD may enhance wound healing and reduce the risk of complications, indicating its potential integration into standardized care protocols. Future research should focus on addressing the limitations, such as conducting larger-scale RCTs with consistent protocols, extended follow-up, and standardized outcome definitions, including quality of life and cost-effectiveness. Additionally, evaluating UAWD's impact in diverse clinical settings and patient subgroups, particularly in high-risk populations, could further clarify its role and optimize treatment strategies.

CONCLUSION

In conclusion, for patients with DFUs, the addition of UAWD to conventional treatment regimens can significantly reduce healing times and enhance healing rates. This evidence underscores the potential of UAWD as a valuable adjunctive therapy in the comprehensive management of DFUs. Future studies should address current methodological limitations to further validate UAWD's efficacy and define its optimal application across diverse patient populations and healthcare settings.

ACKNOWLEDGEMENTS

We thank all study participants for their collective efforts in completing this paper.