The MIST therapy system is a low-frequency, noncontact ultrasound device. The generator converts voltage to high-frequency electrical energy. The electrical energy is transmitted to a piezoelectric transducer (lead zirconate titanate PZT), where it is changed to mechanical energy. The transducer operates at 40 KHz with a distal displacement of 60 to 70 microns. The mechanical energy is transferred to a transducer horn (titanium alloy) that vibrates longitudinally, creating an acoustic pressure output. When the leading edge of the applicator tip touches tissue (10 mm), the maximum transducer intensity at a distal displacement of 65 microns is 1.25 W/cm2. Sterile saline in a disposable reservoir is used to create the vaporized mist, which acts as a conduit, or coupler, for delivery of the ultrasound energy to the wound bed without the need for direct patient contact.
The atomized saline is directed at the wound bed, with the device held perpendicular to the wound. It is passed horizontally and vertically multiple times during a 4-minute period. The device has a fixed frequency; therefore, the intensity at the wound is a function of the distance from the radiating surface of the transducer to the wound surface. The leading edge of the disposable applicator is held at a distance of 5 to 15 mm from the wound bed during treatment. It is also 10 mm from the transducer’s radiating surface, allowing the actual treatment range to be 15 to 25 mm from the transducer’s radiating surface. Therefore, at a distal displacement of 65 microns, the treatment intensity within the therapeutic range is 0.1 to 0.5 W/cm2.
MIST treatment
After removal of the dressing and irrigation of the wound with saline, the MIST device was opened and a new sterile saline bottle was attached to the transducer. The treatment was conducted holding the device perpendicular to the wound bed and moving the device in an up and down pattern across the wound bed, as described above. After treatment, the wound was covered with an appropriate dressing that provided a moist environment, and the patient was given discharge instructions.
RESULTS
Twenty-three patients with 29 wounds were enrolled in the study. The overall group demographics are presented in Table 2. To compare this therapy with the authors’ previously published clinical outcomes, the clinic database was filtered to search the most recent 3 years for wounds with a duration between 1 and 30 months, which was the range obtained in the present 29-wound study. In addition, the database was filtered to include only the wound etiologies that were represented in the present trial. There were almost twice as many men as women in this study, although that was not statistically significant. The average age of the patients was 61 years, and they suffered from numerous chronic comorbid conditions. Patient demographics were comparable between patients included in the present study and the historic control group.
Wounds with a variety of clinical etiologies were included in this study. The wounds were recalcitrant, with a mean duration of 9.86 months. Venous and ischemic ulcers in this trial had a statistically significant longer wound duration on enrollment compared with historic controls. Diabetic ulcers were significantly larger in the historic control group. The most common wound etiology, diabetic foot ulcers, comprised 41% of the total wounds treated in the present study. Although diabetic wound etiology was the most predominant in this study, in the authors’ published experience, there has been no statistically significant difference in healing rates from wounds of various etiologies.41 Wound size ranged from 0.3 to 45 cm2 at enrollment, with a mean of 5.5 +/- 1 cm2.
The clinician performed sharp/surgical debridement when indicated at each visit. Venous and ischemic ulcers were less likely than wounds with other etiologies (P < .05) to be debrided during this trial.
The mean value for the baseline periwound TcPO2 measurement was 30, which is considered a borderline low value for healing42 (Table 4). The mean regional perfusion index was also low at 0.56; it is generally accepted that a perfusion index of 0.7 is required for normal healing.42
Three patients, each with 1 wound, were lost to follow-up because they transferred to a different care setting during the course of the study. One patient was transferred due to insurance purposes and the other 2 were hospitalized at outside facilities. Another patient with 2 wounds died from a hemorrhagic stroke unrelated to the study device, leaving 2 wounds unhealed. Another patient experienced acute thrombosis of a peripheral leg bypass graft. Subsequently, this patient suffered a myocardial infarction and lost the leg to amputation, leaving 2 wounds unhealed. Two additional wounds were unhealed at the conclusion of the trial, for a total of 9 wounds that did not achieve closure. The data are reported on all 29 wounds, however, in an intent-to-treat approach. In addition, all area and volume reduction values are included for patients lost to follow-up as part of the Kaplan-Meier analysis. Those lost to follow-up, death, or amputation are included in the MIST-only group if they only received MIST therapy during the study. The final outcomes are described as those healed by MIST alone and those healed by MIST assisted by a secondary procedure.
Table 5 describes the final outcomes for the 29 wounds subdivided into their various etiologies. An overall healing rate of 69% was achieved during a maximum treatment time of 27 weeks (2 wounds) and a mean treatment time of 13 weeks in this study, despite the loss of 7 wounds from patients lost to follow-up, death, or amputation. Removing these cases results in a 91% healing rate, although this would not represent the intent-to-treat analysis, which is accepted as standard for reporting scientific reports.
A subgroup analysis of outcomes stratified to either those treated with MIST therapy alone or with MIST therapy followed by another treatment protocol yields noteworthy results (Table 6). Wound volume reduction was achieved to a statistically significant greater degree in wounds treated by MIST therapy alone than wounds treated with MIST therapy assisted by a secondary procedure (P = .04). Volume reduction appears to be an indicator of therapeutic benefit from MIST therapy. Wounds that achieved total closure using only MIST therapy were older in duration and smaller in size than those that healed in the MIST-assisted group, although there was no statistical significance noted.
Wounds achieving closure by MIST therapy alone were healed in a mean of 8 weeks compared with 18.71 weeks (Kaplan-Meier method) for those patients healed with MIST therapy followed by an additional modality (P = .0005; Table 7). Again, it was expected that wounds that required additional therapy post-MIST treatments would take longer to heal, but the relatively short treatment time to healing was surprising in the MIST-only group.
Many modalities are available for managing wounds, and the wound care clinician often selects a therapy based on anecdotal experience. The authors have utilized physical therapy-based wound modalities throughout the past 10 years for patients with wounds that fail to improve during an initial 2 to 4 weeks of SOC. The database used in this study was prospectively collected and includes all patients seen more than once. Patients in the present study had an average wound duration of 9.86 months prior to presenting to the wound care clinic. Patients were further stratified by using a 2-week washout period to ensure that only wounds that did not respond to treatment were included in the study.
Patient demographics, wound size, and duration were matched without any statistically significant differences. The overall percentage of wounds healed in the present study was 69%, compared with 72% of wounds in the historic control group, which was not statistically significant (P > .05). The historic control group was treated with electrical stimulation, megahertz-based ultrasound, or a combination of the 2 if patients failed to improve with 2 to 4 weeks of SOC; this occurred in 12% of the cases. Further analysis of the treatments performed in the historic control group revealed that another 20% of patients were admitted to the hospital, and 17% of those underwent surgical debridement and/or closure of the wound, compared with 3.3% and 0%, respectively, of the patients in the present study (P = .04). The statistically significant trend toward increased surgical intervention in the historic control group resulted in shorter median healing times. There are striking differences in the healing rates of the MIST-only group compared with the MIST-assisted group. MIST-only therapy resulted in healing with a Kaplan-Meier mean of 8 weeks, which is highly significant compared with MIST-assisted healing (P = .024). For practicing clinicians with a myriad of treatment options available, having a quantitative parameter such as this that could be used to determine treatment duration and, ultimately, its success would be helpful.
Laser Doppler imaging was performed at each visit during the study. The laser system is able to generate a digital image of the wound that can then be used for planimetric analysis in addition to measuring microcirculatory flow. A sterile string is applied to the perimeter of the wound, which marks the outline of the wound and allows for easy recognition on the digital image. Wound area can then be planimetrically calculated by adding the sum of pixels within the outlined region. Wound volumes in this study were calculated using standard length, width, and depth measurements. Figure 1 shows the volume reduction over the first 10 weeks of the trial. There is an immediate separation between MIST-only and MIST-assisted cases within the first 4 weeks. The MIST-only cases achieve a 20% volume reduction compared with essentially no change in the MIST-assisted cases. The area reduction is also predictive, with a 40% reduction in area compared with a 15% reduction in area noted in the MIST-assisted group