Low-Frequency Contact Ultrasonic Debridement in Diabetic Foot Ulcer

Abstract

Diabetic foot ulcers (DFUs) are important causes of morbidity and mortality in people with diabetes mellitus (DM). Between 19 and 34% of patients with DM will develop a DFU in their lifetime. If not treated correctly, these wounds can result in complications such as infection, amputation, and the death of the patient. A fundamental part of local wound care is debridement, which consists of removing non-viable tissue from the wound bed in order to obtain healthy tissue to promote healing. An alternative to traditional debridement techniques (sharp, enzymatic, autolytic, and biological debridement) is low-frequency ultrasonic debridement (LFUD). The effectiveness of LFUD is based on the non-thermal effects of cavitation and micro-streaming, which generate a series of clinical effects on the wound bed: debridement effect, wound healing stimulant effect, and bactericidal effect. Several recent studies have demonstrated a positive effect of LFUD with higher healing rates, shorter healing times, greater percentages of wound area reduction, and a significant reduction in bacterial load in DFUs. This chapter aims to give an overview of this type of recent mechanical debridement in the treatment of patients with DFUs.

1. Introduction

The International Working Group on the Diabetic Foot (IWGDF) defines diabetic foot ulcers (DFUs) as a break of the skin of the foot that involves a minimum of the epidermis and part of the dermis in a person with current or previously diagnosed diabetes mellitus (DM) and is usually accompanied by peripheral neuropathy and/or peripheral artery disease (PAD) in the lower extremity [1]. DFUs are important causes of morbidity and mortality in people with DM, associated with impaired physical function, reduced quality of life, and increased use of healthcare services [2, 3].

The global prevalence of DFUs is 6.3%, being higher in men (4.5%) than in women (3.5%) and affecting a higher proportion of patients with type 2 DM (6.4%) than patients with type 1 DM (5.5%) [4].

Approximately 19–34% of patients with DM will develop a DFU in their lifetime [5], which can lead to a number of complications such as infection, lower limb amputation, and, in some cases, death of the patient [6].

About 50% of DFUs progress to infection, and 15–20% of moderate-severe diabetic foot infections eventually lead to lower limb amputation [3, 6]. In addition, patients with DFUs have a 5-year mortality rate of 30%, which increases to 70% if they have undergone a major lower limb amputation [7, 8]. Thus, patients with a history of DFUs are 2.5 times more likely to die compared to patients without a history of DFUs [9].

Therefore, knowledge of the pathophysiology of the diabetic foot and early treatment of DFUs and their complications may delay and prevent the development of adverse events [2]. The standard of care (SoC) in patients with DFUs is based on local wound care, use of pressure off-loading devices, infection control, PAD management, metabolic control of diabetes, and treatment of co-morbidities [10].

However, local wound care involves wound bed preparation, based on four components that are summarized in the acronym TIME (non-viable tissue management, inflammation/infection control, moisture imbalance, and epithelial edge advancement) that aim to promote natural wound healing and correct the alterations that lead to impaired healing [11]. The TIME framework describes various wound bed aspects to be systematically addressed to promote wound healing [12].

In cases where the wound evolution is not satisfactory and the wound size is not reduced by 50% after 4 weeks of SoC, advanced therapies are recommended [13], such as negative pressure wound therapy [14], hyperbaric oxygen therapy [15], autologous stem cells [16], as well as low-frequency ultrasonic therapy [17].

2. Debridement

A fundamental part of local wound care is debridement, which aims to remove non-viable or contaminated tissue and foreign material from the wound bed and wound edge in order to obtain healthy, viable tissue, such as granulation tissue, to promote healing [18]. Since non-viable tissue can represent a risk of colonization and infection due to the fact that it promotes biofilm formation, its removal through debridement is essential to encourage the local effectiveness of antibiotic therapy and minimize antibiotic resistance, as well as to allow the clinician to determine the true wound size, facilitate wound drainage, or take a microbiological culture if necessary [8, 19, 20].

In summary, debridement is considered an effective intervention to accelerate DFU healing and reduce the risk of serious complications [19].

2.1 Methods of debridement

Among traditional debridement methods, we can find on the one hand mechanical debridement, which includes sharp debridement and wet-to-dry debridement, and on the other hand non-mechanical debridement, which refers to autolytic, enzymatic, osmotic, and biological debridement [12, 19, 20, 21].

• Mechanical debridement

  • Sharp debridement: the European Wound Management Association (EWMA) and IWGDF consider sharp debridement to be the standard debridement method in wound care [18, 22]. Sharp debridement is the quickest and least expensive method of preparing the wound bed; it is a non-selective procedure that can cause damage to healthy tissue [23]. It is carried out using dissecting instruments such as scalpels, scissors, forceps, or curettes to remove devitalized tissue and can be performed in an operating room or in a clinic setting, with the only difference being the use of anesthesia [24].

  • Wet-to-dry debridement: it is generated after applying a gauze saturated in saline to the wound bed. Once dry, the gauze adheres to the wound, and when it is removed, both devitalized tissue and healthy tissue are eliminated in a non-selective manner [22, 23].

• Non-mechanical debridement

  • Autolytic debridement: the aim is to obtain a moist wound environment in order to facilitate the endogenous enzymes produced by the wound itself to digest the non-viable tissue and preserve the healthy tissue [19, 25].

  • Enzymatic debridement: it involves the use of exogenous enzymes such as collagenase, which degrades fibrin and denatures the collagen and elastin that are part of the devitalized tissue while maintaining the integrity of the viable tissue [19, 20].

  • Osmotic debridement: it requires the creation of a moist environment to generate autolytic debridement due to the application of honey to the wound bed [20]. In addition, honey has an antibacterial effect as it reduces the pH of the wound, making it an acidic environment unfriendly to bacteria and other pathogens [26].

  • Biological debridement: it is also known as larval or maggot debridement and is mainly performed by a specimen of the green bottle fly (Lucilia sericata) that is reared under sterile laboratory conditions [27]. It is a selective debridement method in which the larvae destroy dead tissue, leaving healthy tissue intact [28].

Although sharp debridement is considered the gold standard form of debridement, there is no evidence to support the choice of one method of debridement over another [29]. The selection of the optimal method of debridement will depend mainly on the practitioner’s competence and will be based on a variety of factors, such as etiology, location or wound appearance, patient preference, and cost of the procedure [30].

At present, it is calculated that around 50% of patients with diabetes have PAD, and 65% of DFUs are estimated to have an ischemic component; therefore, an effective alternative to traditional debridement techniques is low-frequency contact ultrasonic debridement, which is useful when sharp debridement is contraindicated, such as in patients with a poor vascular status [31, 32].

3. Low-frequency ultrasonic debridement

Ultrasound is defined as acoustic energy transmitted in the form of sound waves at a frequency above the range of human hearing (>20 KHz) [33]. According to the frequency, ultrasounds can be of two types: high-frequency and low-frequency.

High-frequency ultrasound can be used as a diagnostic imaging modality when frequencies are around 5–12 MHz or for therapeutic purposes, taking advantage of its thermal effects in the treatment of different musculoskeletal disorders, when the devices operate in a range of 1–3 MHz. However, low-frequency ultrasound uses frequencies ranging from 20 to 60 KHz to generate non-thermal effects known as cavitation and micro-streaming, which will lead to a variety of clinical effects on the wound bed [34, 35].

3.1 Mechanism of action

The low-frequency ultrasound device consists of a generator, a handpiece known as a sonotrode, and irrigation equipment. In the sonotrode, electrical energy produced from the generator is converted into sound energy, which is transmitted in the form of ultrasound through a fluid medium to the wound surface, where cavitation and micro-streaming effects are produced [36].

Cavitation refers to the formation of oscillating gas microbubbles in a fluid medium; when cavitation occurs, the microbubbles expand, contract, and implode, which in turn generates an interstitial fluid flow induced as a result of the vibration generated, commonly referred to as micro-streaming (Figure 1) [37, 38, 39].

Figure 1.

Mode of operation of low-frequency ultrasound [36].

3.2 Clinical effect of low-frequency ultrasonic debridement

Non-thermal effects (cavitation and micro-streaming) will cause on the wound a debridement effect, a bactericidal effect, and a stimulating effect on wound healing (Table 1):

• Debridement effect: ultrasonic debridement uses acoustic energy to mechanically remove non-viable tissue from the wound bed [41]. When the gas microbubbles generated during cavitation collapse, selective tissue debridement is achieved. Selectivity will depend on the tensile strength and elasticity of the tissue, which will be determined by the amount, type, and organization of the collagen fibers. Therefore, healthy tissue, being more resistant and elastic, remains intact, while devitalized tissue is removed [36, 42, 43].

• Wound healing stimulant effect: the interstitial fluid flow produced by ultrasound stimulates signal transduction pathways involved in wound healing, thereby altering the permeability of the cell membrane and second messenger activity, resulting in increased protein synthesis such as collagen, mast cell degranulation, leukocyte adhesion, and increased growth factor production, which ultimately leads to enhanced immune response through neo-angiogenesis and fibroblast stimulation at the wound site to induce tissue repair [33, 42, 44].

• Bactericidal effect: the destruction of the bacteria and the interruption of the biofilm are produced by the effect that the ultrasonic waves cause, favoring the generation of highly reactive radicals and molecular products such as nitrous oxide or hydrogen peroxide that alter the cell membrane of the bacteria. Subsequently, due to cavitation and microstreaming, a cutting and washing effect is generated in which the bacteria are dislodged and washed away by the saline [36, 45, 46].

Stimulation of angiogenesis-related cytokines: Interlukin-8 (IL-8) Tumor necrosis factor-α (TNF-α) Basic fibroblast growth factor (bFGF) Vascular endothelial growth factor (VEGF) Immune response to induce tissue repair: Leukocyte adhesion Grown factor production Fibroblast proliferation Protein synthesis Collagen deposition Increased fibrinolysis Promotes granulation tissue formation Reduce bacterial bioburden Increased nitrous oxide Increased macrophage responsiveness Prevent biofilm formation Remove non-viable tissue

Table 1.

Clinical effects of low-frequency ultrasonic.

Adaptation of Rastogi et al. [40].

3.3 Modalities of low-frequency ultrasonic debridement

Low-frequency ultrasonic debridement can be conducted with contact or non-contact devices. A non-contact ultrasonic device delivers acoustic energy in the form of ultrasound to the wound bed through a fine mist of sterile saline applied at a distance between 5 and 15 mm from the wound [34, 44].

Both modalities have similar clinical effects on wounds; the only difference between them is how the ultrasound is applied. Although the debridement effect and bactericidal effect are less effective in the non-contact modality due to being farther away from the wound, there is a dissemination of the ultrasonic waves [45, 47].

In the contact ultrasound modality, the handpiece or sonotrode is in direct contact with the wound bed to mechanically remove non-viable tissue. The sonotrode can be of three types, and its choice will depend mainly on the location and depth of the wound. The double ball handpiece is used for cavity wounds, the hoof is used for undulated flat-surfaced wounds with sloped edges, and the spatula is used for large, flat-surfaced wounds (Figure 2) [36, 43].

Figure 2.

Different types of handpieces or sonotrodes [43].

In addition to the type of sonotrode, there are different techniques for performing ultrasound debridement, such as slicing, sliding, sliding with rotation and milling, and the non-contact option of moistening. Undermining is produced using the double-ball sonotrode for cavities. The most damaging techniques are slicing or sliding with rotation and milling, as the sonotrode is used to contact the wound and uses the technique and instrument to mechanically remove devitalized tissue (Figure 3) [48].

Figure 3.

Contact ultrasonic debridement techniques [48].

Another factor to consider is the ultrasonic device settings: ultrasound intensity (amplitude) and saline flow rate (irrigation), which are manually set by the clinician according to wound features and patient tolerance. Improper setting of the ultrasonic device could have a detrimental effect on the wound bed [48, 49].

Personal protective equipment consisting of a disposable long-sleeved gown, a surgical mask, a face shield with a plastic visor, and sterile gloves is indispensable during ultrasonic debridement to protect the patient and clinician from contamination that may occur due to the dispersion of solution and microbes (aerosolization) from the wound bed into the clinical environment [50].

In order for ultrasonic wound debridement to be effective, a certain degree of training and clinical experience is required [34].

3.4 Clinical effectiveness in DFUs

Low-frequency ultrasonic debridement is a novel technique that has shown great potential for wound bed preparation, with sufficient evidence to indicate that it is a safe and effective method [37, 40].

Several investigations have studied the clinical effect of ultrasonic debridement on DFUs compared to sharp debridement, placebo, or other debridement methods. Ennis et al. [17] in their randomized, double-blinded, controlled, multicenter study compared ultrasonic debridement with placebo (sham device), observing a higher healing rate (40.7% vs. 14.3%, p = 0.03) and shorter healing time of DFUs in the ultrasonic debridement group (9.12 ± 0.58 vs. 11.74 ± 0.22 weeks, p < 0.01).

In a clinical trial comparing the effect of ultrasonic debridement applied three times or once a week versus SoC, a reduction in pro-inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α, and GM-CSF), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and macrophages was found, indicating an improvement in tissue regeneration that translates into a percentage of DFUs area reduction of 86% versus 39% (p < 0.05) when ultrasonic debridement was applied three times a week [51].

Bactericidal and clinical effects of ultrasonic debridement on neuroischaemic DFUs were assessed over 6 weeks in a single-center, non-comparative study, where it was observed that ultrasonic debridement disrupts biofilms and reduces bacterial load independent of bacterial species. Bacterial load reduction was associated with an improvement in the condition of the wound bed with a higher percentage of granulation tissue and a significant reduction in wound size (4.45 cm² at week 0 and 2.75 cm² at week 6, p = 0.04) [52].

An open-label, randomized, controlled, and parallel clinical trial comparing ultrasonic debridement versus surgical debridement in patients with DFUs demonstrated a significant improvement in cellular proliferation, with an increase in endothelial cells (neo-angiogenesis) and an enhancement in collagen deposition and fibroblast proliferation. Furthermore, this study showed a reduced bacterial load and shorter healing time in patients in the ultrasonic debridement group (9.7 ± 3.8 vs. 14.8 ± 12.3 weeks, p = 0.04), but healing rates of DFUs were similar between both groups [53].

Recent systematic reviews and meta-analyses have shown a positive effect of low-frequency ultrasonic debridement with higher healing rates, shorter healing times, greater percentages of wound area reduction, and a significant reduction in bacterial load in DFUs [54, 55, 56]. However, IWGDF guidelines recommend not using any form of ultrasonic debridement over standard of care (sharp debridement) due to the studies performed having a high risk of bias, low certainty of evidence of benefit, and lack of cost-effectiveness data [57].

4. Conclusion

Although the quality of the evidence is generally low due to the high risk of bias and the absence of blinding in the studies, low-frequency ultrasonic has been demonstrated to have a debridement effect, wound healing stimulant effect, and bactericidal effect on wound beds. These effects are reflected in higher healing rates, a greater percentage of wound area reduction, shorter healing times, and a significant reduction in bacterial load, but greater quality evidence is needed to confirm these findings. Likewise, low-frequency ultrasonic debridement could be an effective alternative when traditional debridement methods are not available or are contraindicated for use on patients with DFUs.

Conflict of interest

The authors declare no conflict of interest.

Funding

This research did not receive any specific grants from public, commercial, or not-for-profit funding agencies.