Medical Policy

This document addresses the use of low-frequency, non-contact, non-thermal ultrasound therapy for wound management.

Note: Please see the following related document for additional information:

• DME.00009 Vacuum Assisted Wound Therapy in the Outpatient Setting

Investigational and Not Medically Necessary:

Use of low-frequency, non-contact, non-thermal, ultrasound therapy is considered investigational and not medically necessary for all applications.

The use of low-frequency, non-contact, non-thermal ultrasound has been proposed as supplement to wound therapy. The premise is to promote wound healing through cleansing and debridement of the wound bed. To date, there is limited clinical trial evidence regarding use of low-frequency, non-contact, non-thermal, ultrasound therapy. One such article describes a sham-controlled, randomized, double-blinded, multicenter study of 55 individuals, conducted in hospital-based and private wound care clinics. The therapy was either active 40 KHz ultrasound delivered by a saline mist or a sham device which delivered a saline mist without the use of ultrasound. At 12 weeks of care, results showed that the group who had received the ultrasound therapy had an increase in the healing rate for recalcitrant diabetic foot ulcers, compared to control (40.7% vs. 14.3%). However, it was noted that 5 of the 23 treatment centers had not been doing the treatment protocol correctly, and for this reason, these individuals were not considered evaluable. The results of this study suggest the need for further research, including assessment of the impact of quantitative biopsy results at enrollment, debridement depth and impact on healing, as well as the potential antimicrobial action of this ultrasound device (Ennis, 2005).

In a prospective, randomized controlled trial, Kavros and colleagues (2007a) assigned 35 individuals with non-healing leg and foot ulcers, due to chronic critical limb ischemia, to standard wound care, and another 35 to standard care plus low-frequency, non-contact, non-thermal ultrasound therapy. After 12 weeks, 63% of individuals in the active treatment group achieved at least 50% wound healing, as compared with 29% in the standard care group. In addition, individuals in either group with transcutaneous oxygen pressure less than 20 mm Hg were much less likely to achieve significant healing.

Kavros and colleagues (2007b) also described an open-label, nonrandomized, baseline-controlled, single-center clinical case series conducted at the Gonda Vascular Wound Healing Center at the Mayo Clinic. A total of 51 individuals presenting to this wound center with chronic non-healing wounds of the lower leg or foot of 3 to 18 months duration, were included in the study. Individuals’ comorbidities or prior failure in ulcer therapy did not exclude them from this feasibility study, including the confirmed presence of osteomyelitis. A large proportion of the study participants had a component of limb ischemia and diabetes mellitus (n=38). Sixty-five percent (65%) of the study subjects had transcutaneous oximetry levels less than 30 mm Hg, and 22% had levels less than 20 mm Hg. Fourteen individuals had positive deep culture findings with Staphylococcus aureus and Pseudomonas aeruginosa being the most common pathogens identified. All individuals first received the standard of care protocol followed by the ultrasound therapy when the investigator determined that the wounds were no longer progressing. Study results demonstrated a significant improvement in the rate of healing during the ultrasound therapy time period, compared with the time period when conventional standard wound care alone was administered, with reduction in wound volume of 37.3% in the standard care group and 94.9% in the noncontact low frequency ultrasound group. The authors acknowledge that some degree of bias was possible, due to the baseline-controlled study design, and that further clinical and basic science study of this technology is warranted.

Another author commented about the challenges of conducting randomized controlled trials of wound healing noting that:

In general, designing clinical studies for wound healing is difficult, and surrogate endpoints might enable trials to be constructed with valid outcomes measures, other than total closure. Many randomized controlled clinical wound care studies have failed to deliver the outcomes anticipated by pre-clinical work, an observation that warrants further study on the need for better methods of quantifying the debridement process, in order to accurately compare study results (Margolis 2004).

In a 2014 study by Beheshti and colleagues, 90 participants with venous leg ulcers were randomized to receive standard treatment (consisting of compression therapy) and high frequency ultrasound, standard treatment and MIST^® ultrasound therapy, or standard treatment alone. Study endpoints included the mean time duration of wound healing, edema, pain, size of ulcers and recurrence rate of the ulcers. In the two ultrasound groups, therapy was administered 3 times per week until the wound healed. Monthly visits following therapy were completed with ulcer size, pain and edema recorded. Mean time duration of complete wound healing was 8.13 months in the standard treatment group, 6.10 months in the high frequency ultrasound group, and 5.70 months in the MIST ultrasound group. Edema was mild to severe in all groups at the first visit following treatment. After 4 months, the edema was less in both ultrasound groups when compared to the standard treatment group; however the difference of edema between the two ultrasound groups was not significant. Pain degree was also found to be decreased in the ultrasound groups compared to the standard treatment group, but again no significant differences were found between the two ultrasound groups. Six months following treatment, the venous leg ulcers recurred in 4 participants in the standard treatment group, and 2 participants in each of the ultrasound groups. Although the authors noted improvement in edema, a decrease in pain and less recurrence in the ultrasound groups when compared to compression therapy, there were no significant differences between the high frequency ultrasound and the MIST ultrasound groups. Further studies with larger participant numbers and longer follow-up are needed.

In a 2019 retrospective review by Messa and colleagues, the authors reported on 51 participants with 82 non-healing lower extremity wounds who received low-frequency, high-intensity, ultrasonic debridement. Primary outcomes included wound healing assessed by the percentage of wound reduction up to 180 days post ultrasound treatment, readmission rates and reoperation rates. Overall, 60% of the wounds improved following ultrasound treatment and 40% were non-improved. There were 24 participants (47%) who were readmitted and 23 participants (45%) underwent a reoperation. This study has several limitations which include the single-institution retrospective design and small sample size. The lack of a comparison group may not allow for generalizable results. Additional studies are necessary with randomized controlled trials to further assess wound outcomes and comparison to other treatment modalities.

In a 2019 randomized, double-blind, sham control, single-center study by Rastogi and colleagues, the authors reported on the efficacy of noncontact, low-frequency airborne ultrasound therapy in participants with neuropathic, clinically infected or noninfectioned diabetic foot ulcers. There were 60 participants enrolled in the study with 58 participants completing the study. The included participants had a foot ulcer of at least 2 cm² in size. The therapy duration was for 28 days; daily for an initial 6 days followed by twice a week for the next 3 weeks. Both study participants and investigators were blinded to the treatment as the ultrasound devices were coded by the manufacturers. The primary outcome measure was the percentage of participants with greater than 50% decrease in the ulcer area. Secondary outcomes were the percentage of participants with complete wound healing and percentage decrease in wound area at the end of the study. In the ultrasound therapy group, there was a greater than 50% reduction in wound area observed in 33 of 34 participants (97.1%). There were 8 participants (23.5%) who had a complete wound closure. The duration of the wound was 15.8 ± 11.2 weeks. One participant had less than 50% wound healing. In the sham group, there was a greater than 50% reduction in wound area observed in 19 of 26 participants (73.1%). There were 3 participants (11.5%) who had a complete wound closure. The duration of the wound was 12.1 ± 10.9 weeks. Seven (7) participants had less than 50% wound healing. There was a progressive reduction in wound size in both groups when compared to baseline. Limitations of this study include small sample size, short follow-up period and single-center study design. The authors note that additional randomized, sham-control studies with larger participant populations and longer follow-up times are needed to corroborate the results of this study.

In a 2017 systematic review by Chang and colleagues, the authors reported on 25 studies which examined efficacy of low-frequency ultrasound for wound debridement. While the authors noted that the use of low-frequency ultrasound as an adjunctive therapy in the treatment of chronic wounds is supported, the majority of the evidence is limited by study designs. In the articles reviewed, the authors noted eight different types of ultrasound debridement tools which led to uncertainty regarding the effectiveness and mechanism of action of each tool and the lack of well-designed clinical trials.

The MIST Therapy System (Celleration, Inc. Eden Prairie, MN) is an ultrasound wound cleaning system that received 510(k) marketing clearance from the United States Food and Drug Administration (FDA) in June 2004 and a second FDA clearance in May 2005. The FDA classified this device as a Class II device that is considered to be substantially equivalent to other devices of this generic type, that is, low-energy, ultrasound wound cleanser devices. However, this FDA approval is subject to special controls (contained within the Class II Special Controls Guidance Document issued Nov. 7, 2005). According to the FDA, “The special controls document aids in mitigating the risk by establishing performance characteristics, safety testing, and appropriate labeling.” The MIST Therapy System is FDA cleared for prescription use only, at this time, and is indicated to promote wound healing through wound cleansing and maintenance debridement through the removal of yellow slough, fibrin, tissue exudates and bacteria. Potential risks to health that may be associated with this device were identified by the FDA as: delayed wound healing, thermal damage, inflammation/foreign body response, infection and electrical shock (FDA, 2005). Since the marketing clearance of the MIST Therapy System, other similar devices have also received FDA 510(k) clearance and list the MIST Therapy System as the predicate device.

The MIST Therapy System: This device consists of an equipment component (an ultrasonic generator and transducer) and a disposable component (sterile applicator). The sterile disposable applicator is attached to the generator’s transducer and has been designed to accept a pre-packaged sterile bottle of saline. Generally, treatment consists of three sessions per week, during which time the nurse or therapist holds the device near the wound while ultrasonic energy generated by the device atomizes the saline and delivers a continuous mist to the treatment site. The disposable applicator contains an on/off valve that controls the flow of sterile saline to the ultrasound transducer surface. This device is designed to deliver low levels of ultrasound energy to the wound bed by means of the generated mist without direct contact of the device with the wound, thereby avoiding possible contamination.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
For the following procedure code for all indications or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Peer Reviewed Publications:

1. Beheshti A, Shafigh Y, Parsa H, Zangivand AA. Comparison of high-frequency and MIST ultrasound therapy for the healing of venous leg ulcers. Adv Clin Exp Med. 2014; 23(6):969-975.
2. Bell AL, Cavorsi J. Noncontact ultrasound therapy for adjunctive treatment of nonhealing wounds: retrospective analysis. Phys Ther. 2008; 88(12):1517-1524.
3. Chang YR, Perry J, Cross K. Low-frequency ultrasound debridement in chronic wound healing: a systematic review of current evidence. Plast Surg (Oakv). 2017; 25(1):21-26.
4. Ennis WJ, Foremann P, Mozen N, et al. Ultrasound therapy for recalcitrant diabetic foot ulcers: results of a randomized double-blind controlled multicenter study. Ostomy Wound Manage. 2005; 51(8):24-39.
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):437-446.
6. Gehling ML, Samies JH. The effect of noncontact, low-intensity, low-frequency therapeutic ultrasound on lower-extremity chronic wound pain: a retrospective chart review. Ostomy Wound Manage. 2007; 53(3):44-50.
7. Hinchliffe RJ, Valk GD, Apelqvist J, et al. A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2008; 24 Suppl 1:S119-S144.
8. Kavros SJ, Liedl DA, Boon AJ, et al. Expedited wound healing with noncontact, low-frequency ultrasound therapy in chronic wounds: a retrospective analysis. Adv Skin Wound Care. 2008; 21(9):416-423.
9. Kavros SJ, Miller JL, Hanna SW. Treatment of ischemic wounds with non-contact, low-frequency ultrasound: the Mayo Clinic experience, 2004-2006. Adv Skin Wound Care. 2007a; 20(4):221-226.
10. 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. 2007b; 97(2):95-101.
11. Keltie K, Reay CA, Bousfield DR, et al. Characterization of the ultrasound beam produced by the MIST therapy, wound healing system. Ultrasound Med Biol. 2013; 39(7):1233-1240.
12. Margolis D. The swings and roundabouts of randomized controlled studies in wound healing. Int J Low Extrem Wounds. 2004; 3(1):4-6.
13. Messa CA, Chatman BC, Rhemtulla IA, et al. Ultrasonic debridement management of lower extremity wounds: retrospective analysis of clinical outcomes and cost. J Wound Care. 2019; 28(Sup5):S30-S40.
14. Ramundo J, Gray M. Is ultrasonic mist therapy effective for debriding chronic wounds? J Wound Ostomy Continence Nurs. 2008; 35(6):579-583.
15. Rastogi A, Bhansali A, Ramachandran S. Efficacy and safety of low-frequency, noncontact airborne ultrasound therapy (Glybetac) for neuropathic diabetic foot ulcers: a randomized, double-blind, sham-control study. Int J Low Extrem Wounds. 2019; 18(1):81-88.
16. Samies J, Gehling M. Acoustic pressure wound therapy for management of mixed partial- and full-thickness burns in a rural wound center. Ostomy Wound Manage. 2008; 54(3):56-59.
17. Serena T. Wound closure and gradual involution of an infantile hemangioma using a noncontact, low-frequency ultrasound therapy. Ostomy Wound Manage. 2008; 54(2):68-71.

Government Agency, Medical Society, and Other Authoritative Publications:

1. U.S. Food and Drug Administration 510(k) Premarket Notification Database. Celleration MIST Therapy System Summary of Safety and Effectiveness. No. K032378. Rockville, MD: FDA. June 25, 2004. No. K050129. May 2005. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf5/K050129.pdf. Accessed on July 6, 2020.

Misonix SonicOne^® Plus
MIST Therapy System
Qoustic Wound Therapy System^™
Ultrasound, low-frequency wound therapy
Wound management, ultrasound MIST therapy

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.