Low-Frequency Ultrasound Debridement in Patients with Diabetic Foot Ulcers and Osteomyelitis

Abstract: Background. Although debridement plays a significant role in the healing of diabetic foot ulcers, it may delay the healing process by damaging the granulation tissue. In this study, the efficacy of low-frequency ultrasound (LFU) in chronic wound healing in diabetic foot ulcers in patients with osteomyelitis was evaluated. Methods. This randomized clinical trial was conducted on 40 patients with diabetes recruited from the Diabetic Foot Ulcer Clinic of the Endocrinology and Metabolism Research Center of Tehran University of Medical Sciences, Tehran, Iran. All patients with a grade 3 ulcer (Wagner Classification) with 0.6 ≤ ankle brachial index ≤ 1.2, were included. Patients were divided into 2 groups; 1 group received ultrasound-assisted wound therapy (UAW) in conjunction with standard wound care (n = 20) and the control group received only standard wound care. Patients were followed for 6 months. Results. The complete healing rate in the study population was 55.7% (control group = 55%, UAW group = 60%). The mean wound size reduction percentage was significantly higher in the UAW group only in the second month (78% ± 28.7 vs 55.7% ± 31.4, P = 0.01) and third month ( 63.6% ± 24.5 vs 39.3% ± 32.2 , P = 0.02) of follow up, but not at 6 months. Conclusion. In grade 3 diabetic foot ulcers, LFU debridement accompanied by standard wound care can initially accelerate ulcer healing; however, there is no significant difference between the 2 modalities in the healing rate after 6 months.

Introduction

The prevalence of diabetes mellitus is increasing worldwide. About 15% of patients with diabetes will experience a diabetic foot ulcer in their lifetime, and despite all efforts in the management of this problem, diabetic foot ulcers are still considered one of the most costly complications of diabetes.¹ Therapeutic strategies for diabetic foot ulcers include wound care with effective debridement, improvement of the blood supply, off loading, and control of infection and other associated disease.² The gold standard of treatment is sharp debridement, which is the most effective method of removing necrotic tissue. Surgeons in specialized clinics should perform this type of debridement because necrotic tissue and scars are sometimes firmly attached to layers under the tissue, and must be separated selectively and carefully from healthy tissue in the wound bed. The pain associated with this procedure may interfere with debridement and attenuate the outcome. With each debridement, healthy and living tissue can be separated from the ulcer bed, which is a risk factor for slowing the healing process.³ Low-frequency ultrasound (LFU) debridement (20 - 60kHz) is 1 of the novel techniques of wound debridement that is less traumatic and less painful, and can achieve faster healing rates. Low-frequency ultrasound debridement is a noncontact debridement method that is performed at a 5 mm - 15 mm distance from the wound surface. This can accelerate the wound healing process by removing the necrotic tissue, fibrosis, exudate, and bacteria with minimum bleeding and pain.⁴ The beneficial effects of LFU therapy on chronic wound healing with various causes have been demonstrated by several studies.^5,6 This type of treatment has also been approved by the United States Food and Drug Administration (FDA) for the management of diabetic foot ulcers.⁵ Most studies that have evaluated the effects of LFU waves on diabetic foot ulcers were performed on low intensity wounds (Wagner classification grades 1 and 2). In this study, the authors aimed to evaluate the efficacy of LFU waves in chronic wound healing in patients with diabetic foot ulcers and osteomyelitis, a group that typically presents with a higher grade of foot ulcer.

Methods

This randomized clinical trial compared the effects of LFU waves on the diabetic foot ulcer healing process in patients who received the combination of LFU waves plus standard wound care therapy in comparison with patients who received only standard wound care treatment. The research was performed at the Diabetic Foot Ulcer Clinic affiliated with the Endocrine and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences, Tehran, Iran, from March 2009 to May 2010. The inclusion criteria was defined as patients with diabetes (type 1 and type 2) who had chronic diabetic foot ulcers of grade 3 (Wagner classification) covered with firm or loose necrotic tissue for more than 1 month. Patients with an ankle brachial index (ABI) < 0.6 or > 1.2 were excluded from the study. All patients signed an informed consent form and the study protocol was approved by the Endocrinology and Metabolism Research Center ethics committee. The patients (n = 40) were randomly divided into 2 groups based on a simple randomization method. One group received the combination therapy of LFU waves plus standard wound care (UAW group), and the other group received only standard wound care treatment (control group). Demographic and clinical information including foot ulcer risk factors, associated diseases, neuropathy, vascular assessment of lower extremities, drug history, laboratory tests, physical examination, and wound assessment from each visit were collected following enrollment in the study. The vascular assessment of patients was performed by physical examination (ie, pulse palpation, limb temperature and color, shiny skin, and hair loss). Ankle Brachial Index of lower extremities was measured by Atys device (Atys Médical, Soucieu en Jarrest, France) and the degree of neuropathy and muscle stretch reflexes were assessed by Michigan Neuropathy Screening Instrument. Wound assessment was done by means of physical examination. Plain x-ray plans of the foot with ulcer and bone scan were requested for all patients to prove the presence of osteomyelitis. Laboratory tests to check the blood glucose, lipid profile, hemoglobin, and liver and kidney function were requested for all patients. Wound assessment. Patients were visited once a week during the study period. Wound was evaluated at each visit, and photos of the wounds, which were measured with a flexible ruler laid alongside the pressure ulcers, were taken with a digital camera. Patient compliance regarding off loading, medications, and daily dressing changes was assessed. Total contact casting, half shoe, felted foam, and pads were used more as off-loading methods, and all patients received antibiotics. Wounds were assessed based on wound grading by Wagner classification; location; size; depth; type of lesion (ie, ischemic, neuropathic, neuroischemic); granulation tissue, scar or fibrosis, with its percentage of the wound surface; infection progression or decline (as determined by evaluation of exudate, necrotic tissue, erythema, edema, and fever); and callus formation (yes/no). Patients were followed for 6 months from the first debridement or until complete wound healing (ie, wound closure with complete epithelialization without purulent discharge) was observed. The LFU used in this study was the Sonoca 180 (Söring GmbH, Quickborn, Germany) that generated the ultrasound waves with 24 kHz frequency and was equipped with 3 probes with different head types appropriate to the wound depth, ranging from superficial wounds to deep wounds. Each probe was attached to a set of irrigation solution (saline 0.9%) that transformed the electric energy into mechanical vibrations, which in turn produced the tiny particles of water from irrigation fluid. In this way, wound irrigation and gentle loosening of necrotic tissue caused by mechanical vibration were achieved simultaneously. For each square centimeter of wound, 1 minute of ultrasound with 80%-100% power was employed twice (Figure 1). All necrotic tissue and callus were surgically removed, layer by layer, until normal, healthy tissue appeared. When necessary, the procedure was repeated at each visit. After each surgical wound debridement, the ulcer was completely washed with saline 0.9% and immediately covered by a layer of wet gauze. The dressing was completed by putting a few pieces of dry sterile gauzes on the ulcer.

Data analysis

All data analysis was performed by SPSS software (version 18). The rate of wound healing, considering time, was assessed using repeated measurement method, chi squared, and t test. A P ≤ 0.05 was considered statistically significant.

Results

Demographic and clinical characteristics of patients are expressed in Table 1. Mean age of patients was 55.2 ± 9.4 years and the mean of diabetes duration was 14.8 ± 7.3 years. Ninety-five percent of patients in the study had type 2 diabetes. The HbA1c was similar in the UAW group and the control group, with mean levels of 8.9 ± 2.3. No significant difference was presented between the 2 groups regarding the percent of patients with hypertension, dyslipidemia, and eye or kidney diseases, while the percent of patients with a history of heart disease and myocardial infarction was significantly different in the 2 groups (P = 0.04). Features of diabetic foot ulcer risk factors are presented in Table 2. Assessment of neuropathy, using the Michigan Neuropathy Screening Instrument, revealed that 10% of patients were normal (score from 0-6), 40% had mild neuropathy (score from 7-12), and the remaining patients had moderate neuropathy (score from 13-29). In vascular evaluation, all the patients had minimal pulse intensity (pulse of 1 +) in lower extremities. About half of the patients had signs of ischemia in the lower extremities, indicating peripheral vascular disease. The mean time of wound duration, number of debridements, complete healing duration, and initial size of wound before first debridement in the UAW group and in the control group were 3.9 ± 4.2 months, 8.5 ± 3.4 times, 2.5 ± 2.4 months, 6.8 ± 3.5cm², and 9.9 ± 7.6cm², respectively, with no significant difference between the 2 groups in these variables. No significant difference in ulcer size reduction after 6 months was observed between the 2 groups (87.9% ± 33.8% in UAW, and 82.4% ± 33% in control group); however, at the end of the second and third months the rate of wound size reduction was significantly higher in the UAW group (Table 3). Repeated measurement method also did not reveal any significant difference in wound size reduction percentage and healing rate between the 2 groups after 6 months (Figure 2).

Discussion

This clinical trial was done to evaluate the efficiency of noncontact LFU waves to treat chronic diabetic foot ulcers in patients with osteomyelitis. The characteristics of this modality include debridement; local stimulation for autolysis of necrotic tissue with little bleeding and pain, and no damage to healthy tissue around the wound; reduction of the level of bacterial colonies; and acceleration of granulation tissue formation. Previous studies have suggested that LFU waves have an effective role in the treatment of chronic wounds. For example, Kavros and colleagues⁷ observed that the rate and speed of complete healing in a group receiving UAW treatment in combination with standard wound care was significantly higher than the control group that received only standard wound care. In that study, the subjects had ulcers with various causes, though the severity of wounds was not evaluated. In a randomized, double-blinded controlled study using a sham device (ie, a device with similar structure to an ultrasound machine but without low-frequency ultrasound waves), 55 patients with diabetic foot ulcers were followed for 12 weeks. The complete healing rate was significantly higher in the UAW group than the sham group (40.7% vs 14.3%) and there was no difference in terms of numbers and types of complications during treatment between the groups. The authors concluded that LFU waves can accelerate the healing rate of chronic and recalcitrant diabetic foot ulcers.⁶ In a comparative study, Ennis et al⁵ observed that UAW treatment in patients with various lower extremity wounds caused a 30% decrease in wound healing time, which confirms the role of UAW in reducing health care costs compared to current standard chronic wound care. In a nonrandomized research study performed by the Mayo Clinic (Rochester, MN),⁸ a 44% reduction in mean wound healing time in the UAW group compared to the standard wound care group was observed. The rate of wound volume reduction was significantly higher in the UAW group (94.9% ± 9.8 vs 37.3% ± 18.6). In another randomized and controlled research study done by the Mayo Clinic on lower extremity wounds with severe chronic ischemia,⁹ it was found that LFU waves lead to a more than 50% decrease in wound size, even in chronic severe ischemic wounds. In the authors’ study, a significant difference in wound healing time and size reduction, after 6 months, when 2 groups were compared, was not observed. The probable causes include high wound severity, low sample numbers, and low numbers of weekly visits in both groups due to lack of convenient access to the clinic for patients. In a majority of the studies, the number of visits in UAW treatment protocol were 3 times a week,^6,7,9 which was 3 times higher than in the current study. Low-frequency ultrasound waves act through 2 mechanisms: microcavitation and acoustic streaming. Microcavitation leads to cell changes and destruction of tissue adjacent to the ultrasound wave, and will also cause a rapid lysis of the necrotic tissue and fibrosis from the ulcer. Acoustic streaming increases cell permeability and activates the intracellular secondary messenger system, which in turn causes an increase in synthesis and production molecules such as collagen, growth factors, and nitrite oxide synthase. These molecules all take part in accelerating the wound healing process.^3,5-7 Considering the advantages of LFU waves in the treatment of chronic wounds, which include being easy to use for the clinician, painless, less stressful, and better accepted by patients; as well as having a lower cost and reduced rate of amputation, this modality is of great interest for treatment of diabetic ulcers. Further studies with a focus on wounds with high severity are recommended to evaluate the effectiveness of these ultrasound waves on the healing process of chronic wounds.

Conclusion

In the treatment of chronic grade 3 (Wagner Classification) diabetic foot ulcers, LFU debridement accompanied by standard wound care, in comparison with the sole use of standard wound care, can initially accelerate ulcer healing, especially in the second and third months. However, there is no significant difference between the 2 modalities in terms of the healing rate after 6 months.

Acknowledgment

The authors would like to thank the Endocrinology and Metabolism Research Center for financial support, and for providing the necessary staff for this study. They would also like to thank the Kavoush Pasand Novin Company (Tehran, Iran) for providing a Sonoca 180 device free of charge, as well as the necessary training to work with the device.

References

1. Boulton AJ, Meneses P, Ennis WJ. Diabetic foot ulcers: A framework for prevention and care. Wound Repair Regen. 1999;7(1):7-16. 2. Frykberg RG, Armstrong DG, Giurini J, et al. Diabetic foot disorders: A clinical practice guideline for the American College of Foot and Ankle Surgeons and the American College of Foot and Ankle Orthopedics and Medicine. J Foot Ankle Surg. 2000;39(5 Suppl):S1-60. 3. Stanisic MM, Provo BJ, Larson DL, Kloth LC. Wound debridement with 25 kHz ultrasound. Adv Skin Wound Care. 2005;18(9):484-490. 4. Breuing KH, Bayer L, Neuwalder J, Orgill DP. Early experience using low-frequency ultrasound in chronic wounds. Ann Plast Surg. 2005;55(2):183-187. 5. Ennis WJ, Valdes W, Gainer M, Meneses P. Evaluation of clinical effectiveness of MIST ultrasound therapy for the healing of chronic wounds. Adv Skin Wound Care. 2006;19(8):437-46. 6. Ennis WJ, Foremann P, Mozen N, Massey J, Conner-Kerr T, Meneses P. Ultrasound therapy for recalcitrant diabetic foot ulcers: results of a randomized, double-blind, controlled, multicenter study. Ostomy Wound Manage. 2005;51(8):24-39. 7. Kavros SJ, Liedl DA, Boon AJ, Boon AJ, Miller JL, Hobbs JA, Andrews KL. Expedited wound healing with noncontact, low-frequency ultrasound therapy in chronic wounds: a retrospective analysis. Adv Skin Wound Care. 2008;21(9):416-23. 8. Kavros SJ, Schenck EC. Use of noncontact low-frequency ultrasound in the treatment of chronic foot and leg ulcerations: a 51-patient analysis. J Am Podiatr Med Assoc. 2007;97(2):95-101. 9. Kavros SJ, Miller JL, Hanna SW. Treatment of ischemic wounds with noncontact, low-frequency ultrasound: The Mayo clinic experience, 2004-2006. Adv Skin Wound Care. 2007;20:221-226. Sareh Amini, MD; Zohreh Annabestani, MD; Mohsen Rezaie Hammami, MD; Zahra Shaiganmehr, BS; Bagher Larijani, MD; Shahrzad Mohseni, MD; Maryam Aboee Rad, BS; and Mohammad Reza Mohajeri-Tehrani, MD are from Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Abolfazl ShojaeeFard, MD is from General and Vascular Surgery Ward, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Hamid Reza Afshani, MD is from Iran Endocrine Society, Tehran, Iran. Address correspondence to: Mohammad Reza Mohajeri-Tehrani 5th Floor-Shariati Hospital North Kargar Ave Endocrinology and Metabolism Research Center Tehran, Iran mrmohajeri@tums.ac.ir Disclosure: The authors disclose no financial interest in the products used in this study. An ultrasound device was provided free-of-charge by the Kavoush Pasand Novin Company (Tehran, Iran) for the purposes of the study.