Healing Rate of Chronic and Subacute Lower Extremity Ulcers Treated With Contact Ultrasound Followed by Noncontact Ultrasound Therapy: The VIP Ultrasound Protocol

Background. Contact and noncontact ultrasounds are types of low-frequency ultrasonic treatments for wound care. Objective. The purpose of this research was to collect data in order to see if healing rates are accelerated when both forms of ultrasound therapies are utilized. Materials and Methods. The Viana-Pompeo (VIP) Ultrasound Protocol consists of high-intensity, low-frequency, contact ultrasound therapy followed by low-intensity, low-frequency, noncontact ultrasound therapy. A total of 11 subjects with a total of 24 chronic or subacute lower extremity wounds were enrolled in the study. Of the 11 subjects, 6 finished the protocol (12 wounds). All subjects started with contact ultrasound for debridement at a frequency of 25 kHz and at the maximum intensity the subject could tolerate (equipment range, 20%–100% of 1.0 W/cm²). Once the wound was sufficiently clean with ≤ 20% of necrotic tissue or adherent slough, therapy was switched to noncontact, low-frequency ultrasound (NLFU) for cellular stimulation at 40 kHz and intensities of 0.1 W/cm² to 0.5 W/cm². Subjects received ultrasound treatment 3 times weekly for the 12-week study. Progress was analyzed based on reductions in wound area, volume, and slough and increases in granulation and epithelialization. Wounds were divided into 2 groups: group A, wound duration between 4 and 21 weeks; and group B, wound duration ≥ 47 weeks. There were no wounds between 21 and 47 weeks. Results. In group A (4 wounds), all wounds improved in wound area and epithelialization; 75% achieved an improvement of > 99% before or at 12 weeks of treatment. In addition, all wounds saw a wound volume reduction of 93% to 100%. Granulation in group A was 100%, and by visit 10 of 36, all wounds had 0% slough or eschar. In group B (8 wounds), 50% of wounds improved with a wound volume reduction of 50%; all wounds increased in granulation, with 50% achieving 75% to 100% granulation. Sixty-two percent of wounds in group B saw an increase in epithelialization, and 75% of wounds had 85% to 100% reduction in slough and eschar by the last visit (end of week 12). There was a strong positive correlation between wound age and healing time (r = 0.94). Conclusions. Both groups benefited from the VIP Protocol, which promoted wound closure or wound bed preparation for graft. The results seem to favor an earlier start of the protocol for best outcomes and indicate that contact and noncontact ultrasound therapies are not exclusionary but rather complementary.

There are 6.5 million people in the United States affected with chronic wounds, and more than $25 billion is spent annually on wound care treatments.¹ The financial burden is rising each year due to increased health care costs and numbers of at-risk patients with diagnoses such as diabetes and obesity. Research and development of treatments that can accelerate wound healing are of extreme significance.

The phases of wound healing are hemostatic, inflammatory, proliferative, and remodeling. Chronic wounds do not go through these stages in an orderly fashion and may stall during any phase (but especially the inflammatory phase) due to multiple reasons. A compromised vascular system and bacterial colonization are common culprits for delayed wound healing. Low-frequency ultrasound therapies act to remove some of the healing barriers, and by doing so, they stimulate the wound to progress along the phases of healing.

Ultrasound is a wound care modality designed to promote healing at faster rates. The term ultrasound is often associated with imaging tests or rehabilitation of soft tissue injuries, but the equipment used in wound care is different from those in diagnostic as well as therapeutic ultrasounds (ie, used in sports medicine and traditional physical therapy). The frequencies used in wound care are much lower, falling in the kHz range, whereas the frequency in therapeutic and diagnostic ultrasounds is in the MHz range.

There are 2 types of low-frequency ultrasonic treatments available to wound care clinicians: contact ultrasound and noncontact, low-frequency ultrasound (NLFU). It is important to know their similarities and how they differ in their designed role in accelerated wound healing.

High-frequency therapeutic ultrasound often produces thermal effects; however, wound-healing benefits are due to the nonthermal effects produced by the low-frequency waves: cavitation and acoustic streaming. Cavitation refers to the formation of oscillating micro gas bubbles in the coupling medium, such as saline or lactated Ringer’s solution. When high enough intensity is present, unstable cavitation occurs. The microbubbles expand, contract, and implode. The energy released when the bubbles collapse contributes to the lysis of fibrin and wound debridement. Acoustic streaming refers to the movement of fluids between cell membranes, bubbles, organelles, tissue fibers, and various cell structures. Research shows that acoustic streaming alters cell membrane permeability and second messenger activity.^2,3 Such changes in the cell membrane result in increased protein synthesis,^4,5 degranulation of mast cells,⁶ and increased production of growth factors.⁷

Contact ultrasound mode offers a way to selectively debride nonviable tissue through cavitation formed at the tip of the sonotrode piece when in contact with the wound tissue and the coupling medium. The forces produced by the cavitation disrupt and fragment the nonviable tissue and bacteria. Debris is washed away from the wound surface with the coupling medium.

Viable tissue and granulation are not damaged in the contact ultrasound process because they are more elastic than nonviable tissue or bacterial cell walls.^8,9 The cell walls of bacteria are brittle; when they vibrate with the ultrasound waves, they fracture and therefore are no longer viable. Contact ultrasound waves are transmitted through the tissues, but a horizontal net effect is achieved as the wound is debrided (eFigure 1). 

In comparison, the NLFU used in the present study delivers ultrasound perpendicularly to the wound bed without touching the tissue through a saline mist. When the ultrasonic energy hits the wound cells, it produces biophysical effects such as stimulation of cellular activity.¹⁰ The mechanical forces that occur at the cellular and molecular levels foster cell division, protein synthesis, activation of inflammatory cells, and activation of fibroblasts through the production of chemical mediators¹⁰; reduction of inflammation^11,12; reduction of bacterial count^13,14; disruption of biofilm¹⁵; vasodilatation¹⁶; angiogenesis^12,17; production of growth factors¹⁸; and collagen deposition.^13,17,19

The progression of accelerated healing should not be limited to just 1 phase of the healing process. The authors believe that more favorable outcomes can be achieved if contact and noncontact ultrasound therapies are utilized to progress a wound more expeditiously through the healing phases. In general, contact ultrasound is used to remove adherent or extensive areas of nonviable tissue, and noncontact ultrasound is used to stimulate healing. While the perpendicular form of noncontact ultrasound is not primarily a debriding agent, it can help soften the nonviable material in preparation for manual sharp excision.

Some patients who received both ultrasound treatments over the course of their physical therapy wound care at the authors’ ambulatory clinic demonstrated visible and rapid progress as determined by clinical assessment. Once their wounds were free of slough and no longer needed aggressive debridement, the proliferation phase was encouraged through deep cellular stimulation via noncontact ultrasound therapy. Such observations led the authors to develop the Viana-Pompeo Ultrasound Protocol (VIP Protocol), where wound patients can benefit from contact ultrasonic debridement and noncontact ultrasonic stimulation through 2 to 3 weekly treatments.

At the time of design for this study on wound healing rates when both forms of therapies were used, no published studies were found. Therefore, the purpose of this study is to evaluate whether healing rates are accelerated when both forms of ultrasound therapies are utilized.

Literature search
A search of the PubMed database from January 2008 to December 2013 was conducted using the key terms “noncontact ultrasound,”  “contact ultrasound,”  “NFLU,” “low-frequency ultrasound,”  and  “ultrasound wound healing.”  The authors found no studies reporting chronic wound healing rates when both modes of ultrasound were used.

Eligibility
Current clinic patients who were being followed by 1 of the wound doctors and who met the inclusion criteria were potential patients for this study. Once a patient was referred to physical therapy for wound care with VIP Protocol or contact ultrasound, potential patients subjects were screened for eligibility.  At the initial assessment, careful chart review and a patient interview were conducted to verify that no history of untreated malignancy was present over the treatment area.

Inclusion and exclusion criteria
Patients had to meet all inclusion criteria: patient with foot or lower extremity wound(s) of any etiology referred to physical therapy for contact ultrasound; wound(s) presented with slough, necrotic tissue, and/or nonviable tissue requiring debridement; wound age > 4 weeks; insurance approval of contact ultrasound and NLFU treatments in the ambulatory setting or of contact ultrasound only if donated noncontact kit was available; patient willing to commit to 3 weekly clinical visits for 12 weeks; patient age ≥ 18 years; and nonpregnant women.

Patients were excluded if they met 1 or more of the following conditions: patient referred to physical therapy for NLFU only; wound(s) not on a lower extremity; clean wound(s) that do not require debridement; wound age < 4 weeks; malignancies on the treatment area; patient also receiving negative pressure wound therapy; lack of insurance approval for both contact ultrasound and NLFU with no available donated noncontact kits; patient age < 18 years; and pregnant women.

Ethical statement
The physical therapist (PT) provided prospective study patients with the terms of the study, and if they agreed and signed consent forms, were enrolled. Institutional Review Board study identification was Study ID: Pro00004597. 

Study design
This prospective pilot study was designed to evaluate the clinical effectiveness of a contact and a noncontact ultrasound treatment protocol for chronic or subacute wounds of the lower extremities and of any etiology. The VIP Protocol consists of high-intensity, low-frequency contact ultrasound therapy followed by low-intensity NLFU therapy.

The PT performed the initial assessment and devised an individualized plan of care involving the VIP Protocol. The transition from contact mode to noncontact mode could happen when the wound was sufficiently clean with ≤ 20% of necrotic tissue or adherent slough; ≥ 80% of soft slough could be easily removed from the wound bed with mechanical or selective debridement before or after treatment; or wound bed quality had failed to progress after 3 consecutive contact ultrasound treatments. Only the qualifying wounds present during initial physical therapy assessment were included in the research; new wounds developed during the course of the research were not included.

For the purposes of this study, treatments were to be performed 3 times weekly for 12 weeks. Treatment time was dependent on the wound area with a minimum dose of 20 seconds per cm² as per standard protocol. A minimum of 2 weekly treatments (goal of 3 per week) had to be reached for the 12-week period for a patient’s data to be included in the data analysis.

Patients were allowed to perform home dressing changes as ordered by the physician in addition to the dressing changes performed by the PT or wound clinic nurse on clinic visit days. Patients and/or caregivers were trained in dressing change techniques and understood the procedure prior to performing self-dressing changes.

In addition to either mode of ultrasonic treatment and dressing changes, additional wound debridement could be performed each visit as needed, as determined by the PT or physician. Digital photography and wound measurements were also performed weekly based on wound changes by the PT or physician.

eFigure 2 represents the flow of the study in relation to when the patient was admitted to the wound care service, when the physical therapy wound care started/ended, and when the patient was discharged by the physician. Note that the end of physical therapy wound care could be before, at, or after the end of the study period; also, the beginning of NLFU was dependent on the individual characteristics and wound needs. 

Ultrasound equipment
The Sonoca-180 (Söring Inc, Sunrise, FL) was the contact ultrasound machine used for this study. It has a frequency of 25 kHz and an adjustable intensity from 20% to 100% of 1.0 W/cm². MIST Therapy (Alliqua BioMedical, Inc, Yardley, PA) was used for NLFU, which has a frequency of 40 kHz and intensities of 0.1 to 0.5 W/cm², depending on the distance between the wound surface and the applicator.

Based on available research,¹⁴ the biomechanical effects of NLFU can reach at least 3.5 mm below an open wound surface and at least to 2.5 mm below the closed skin. Clinical effects may even go to the bone, but more research is needed. In comparison, the effects of contact ultrasound are more superficial. The manufacturer indicates the penetration depth of fluid into tissue is seen at 0.9 mm when using the hoof sonotrode at 100% power for 1 minute with a saline flow of 8 mL per minute.

Study endpoints
Length of study was set at 12 weeks from the start of ultrasound therapy. In addition to area reduction, increased granulation, decreased volume, and decreased slough and/or eschar were considered a sign of wound bed progress. Wound closure could happen at any point within the 12 weeks of study.

Patients could be withdrawn from the study without their consent if they missed 3 consecutive visits or a total of 7 visits; failed to comply with the treatment plan of care, such as not dressing the wounds appropriately or not adhering to the required frequency of home dressing changes; were admitted to the hospital; or died. Subjects were also able to self-withdraw at any point. 

Measured variables
Throughout the treatment, the following variables pertaining to the progress of wound healing were observed: area, volume, granulation, slough/eschar, and epithelialization.  A standard disposable paper ruler was used to measure wounds. The PT obtained area and volume measurements in centimeters and performed the visual grading of the granulation, slough, and epithelialization.

Statistics
Comparisons between wound groups were accomplished using a 2-sample t-test. The Pearson product moment correlation was used to compare wound age and healing rate.

Due to a limited number of patients the PT can see daily, not every patient could be seen 3 times per week and automatically had to fall on the 2 visits per week schedule (therefore not included in the research). Once the slots available for 3 weekly visits were filled at any given time, patients could not be enrolled in the research (those patients were not tracked). A total of 11 patients with 24 wounds were enrolled in the study. Of the 11 patients, 6 finished the protocol (12 wounds), 2 were withdrawn due to missing 3 consecutive visits, 2 decided to discontinue participation, and 1 was admitted to the hospital (required revascularization surgery).

The 12 remaining wounds in the study were divided into groups according to wound age. The wounds with a duration between 4 and 21 weeks were placed in group A, and wounds ≥ 47 weeks were placed in group B. There were no wounds with a duration between 21 and 47 weeks. Group A had 4 wounds (4 patients) and a standard deviation (SD) of 7.334 ± 12.035. Group B had 8 wounds (2 patients) and a SD of 361.1±219.62.  A 2-sample t-test revealed a significant difference between the 2 groups for wound age, with d = −207.588 and P = .1722 for the null hypothesis d = 0.

Of the 6 patients who finished the study, 66.7% were white and 33.3% were black; 66.7% were male and 33.3% were female; 33.3% were between 56 and 60 years, 33.3% were between 61 and 65 years, 16.7% were between 71 and 75 years, and 16.7% were between 76 and 80 years. A variety of diagnoses were observed in the sample. eTable 1A and 1B shows the distribution of the observed diagnoses and their related wounds.

eFigures 3, 4, 5, 6, 7, 8, 9, and 10 show the progress of the wounds over the course of the treatment visits. Patients were in the study for a period of up to 12 weeks, with a maximum number of 36 visits. Some patients healed prior to the end of the study period (patients 1, 6); consequently, measurements for area, volume, and epithelialization were not included after healing was achieved. Granulation was plotted in the chart up to the point it reached 100% and remained at that level.

It is important to point out that some patients had missed visits. Those missed visits were counted within the allowed 36 visit slots, and so, patients may have reached visit 36 but had only 31 treatment sessions. The visit slots, and not the treatment sessions, are depicted in the charts as the x-axis (eFigures 3, 4, 5, 6, 7, 8, 9, and 10).

Group A: wound age of 4–21 weeks
The scatter charts for group A (eFigures 3, 4, 5, and 6) mostly show a rapidly ascending curve, indicating a rapid healing progress. Half of the wounds in this group needed 3 contact ultrasound sessions prior to switching to NLFU (patients 1, 2), and the other half only needed 2 contact ultrasound visits (patients 4, 6). There were a total of 10 contact treatment visits. Group A tolerated a contact ultrasound intensity of 100% for 90% of the time.

The number of treatments varied between 18 and 33 sessions. The 2 patients (2 wounds) that healed before 12 weeks only missed 1 visit each (patients 1, 6); the other 2 patients (2 wounds) had missed 3 visits each (patients 2, 4).

Patient 4 had an area improvement of 99.57% by the end of the 12 weeks and was considered a clinical success. The wound was almost completely closed at visit 36 and was reported closed within 12.3 weeks from initiation of therapy.

Patient 2 did not heal within 12 weeks but showed significant progress compared with the first day. The wound originally probed to the bone and was located on the patient’s only weight-bearing surface for transfers. This patient did continue NLFU after the 12 study weeks, and the wound was healed 24.6 weeks after the start of the VIP Protocol. 

Patient 1 achieved 100% granulation shortly after 2 weeks from the start of the VIP Protocol. The other wounds in this group (patients 2, 4, 6) achieved 100% granulation at about 7.6 weeks.

Note that the wound area (eFigure 3) and the epithelialization charts (eFigure 6) have different curves.  This is not unexpected since epithelialization is not the only contributing factor to wound closure. Wound contracture and edema reduction also contribute to the decrease of the wound area. eFigures 11, 12, 13, and 14 show progress of patients 1, 2, 4, and 6.

Group B: wound age ≥ 47 weeks
For group B, eFigures 7, 8, 9, and 10 show a less predictable pattern of progress. Patient 5 had 3 wounds and received 5 treatments of contact ultrasound, and patient 7 had 5 wounds and received 3 treatments prior to switching to NLFU for a total of 30 contact ultrasound treatments. An intensity of 100% was tolerated 50% of the time, an intensity of 40% was tolerated 3.33% of the time, and an intensity of 20% was tolerated 46.67% of the time.

Patient 5 had 31 treatment days and 5 missed visits. Of the 3 wounds patient 5 had, wound 2 showed progress in area, volume, and granulation but no improvement in epithelialization. Halfway through the protocol, it achieved 80% improvement in granulation before declining. However, it still had a better wound bed quality than that seen at the initial visit. 

Patient 7 had 33 treatments days and 3 missed visits. Of the 5 wounds patient 7 had, wound 2 had very consistent improvement across all variables. Wound 4 also showed good signs of healing throughout, despite small progresses in epithelialization and wound area. Wound 3 increased in size, likely due to a number of factors such as venous insufficiency and tight burned skin, which was unable to accommodate skin expansion from the edema as time progressed during the 12 weeks, but wound volume started an upward trend around visit 26. Granulation improved significantly early on and reached 85% at the end of 12 weeks.

All wounds in group B showed improvement in granulation, which is an important step in wound bed preparation. It is evident that these wounds had an improvement in wound bed quality; however, they did not necessarily have a major reduction in area. Nonetheless, they still benefited from the protocol.

Wound area
All wounds in group A were smaller at the end of the 12-week study.  A decrease in wound area > 99% was seen in 75% of wounds (patients 1, 4, 6), and a decrease of 65.82% was seen in the remaining 25% (patient 2) (eFigure 18). In group B, there was a wound area reduction in 50% of the wounds: 12.5% with a reduction of 82.86% (patient 7/wound 2), 12.5% with 40.7% reduction (patient 7/wound 4), and 25% with a reduction between 15.24% and 17.15% (patient 5/wound 2; patient 7/wound 1). The other 50% of wounds saw no improvement or increase in wound area (patient 5/wounds 1, 3; patient 7/wounds 3, 5) (eFigure 19).

The time it took for the wounds to achieve closure was another point analyzed in this study. In group A, 75% of wounds achieved > 99% closure before or at 12 weeks (patients 1, 4, 6). It was noted that 50% achieved 100% closure between 6 and 9 weeks, and 25% achieved 99.57% closure at exactly 12 weeks (complete closure at 12.3 weeks). Median time to closure was 10.45 weeks with a standard error of 4.117. The remaining 25% achieved closure at 24.6 weeks (eFigure 20). 

In group B, none of the wounds closed in 12 weeks. A total of 62.5% of wounds closed after 12 weeks, but 50% underwent surgical debridement and placement of a skin graft in group B (all wounds from patient 5 and patient 7/wound 1; patient 5 stopped protocol at visit 36 and received graft application, and patient 7/wound 1 healed at 45.7 weeks from start of treatment). The remaining 12.5% of the wounds achieved closure in 51.7 weeks (patient 7/wound 3).

The time frame for closure (eFigure 21) was unable to be determined for 37.5% of wounds (patient 7/wounds 2,4,5) because the patient moved to a different city after 51.5 weeks of treatment. Before he moved, the patient received a skin substitute graft twice on wound 5; that wound did not close prior to moving. 

There was no significant difference between groups A and B for initial wound area (P = .57; 95% confidence interval [CI], 5.97–10.35), but wound area reduction within 12 weeks was found to be significantly different between these 2 groups (P = .0324; 95% CI, 33.13–341.82). 

Wound volume
All wounds in group A had an improvement in wound volume > 93% during the 12 weeks of VIP Protocol (eFigure 22). Of these, 50% achieved 100% reduction and closure (patients 1, 6) and 25% achieved a wound volume decrease of 99.95% (patient 4). The remaining 25% experienced a wound volume reduction of 93.16% (patient 2). 

In group B, 50% of wounds had a decrease and 50% had an increase. For the wounds that saw a decrease in volume, 25% had a decrease between 91.53% and 95.71% and the other 25% had between 33.33% and 43.49% reduction (eFigure 23).  

By the time of the last treatment visit, both groups showed a 66.67% wound volume improvement. The remaining 33.33% of wounds showed an increase in wound volume. Wound volume reduction within 12 weeks was found to be significantly different in groups A and B (P = .0228; 95% CI, 17.35–328.04). 

Wound granulation
All wounds in group A achieved 100% granulation before treatment week 12, with a mean of 18.25 treatment sessions (minimum, 8; maximum, 24) (eFigure 24). All wounds in group B improved in granulation by week 12: 12.5% improved 100%, 37.5% improved between 75% to 98%, 25% between 30% to 38%, and 25% between 5% to 10% (eFigure 25). One wound in group B improved 100% by treatment session 25. The wounds that improved 85% to 98% reached this level of granulation in an average of 32.5 visits, and 1 wound reached 75% in 19 sessions. Wound volume reduction within 12 weeks was found to be significantly different between groups A and B (P = .0228; 95% CI, 0.42–89.33). 

Epithelialization
All wounds in group A had improved epithelialization; 75% reached near 100% reepithialization by week 12. Of those, 50% reached complete closure and the remaining 25% reached 99% epithelialization. The remaining wound reached 35% epithelialization by week 12 (eFigure 26). The majority of wounds in group B (62.5%) had improved epithelialization: 12.5% had 80% improvement, 12.5% had 38% improvement, and 37.5% had 3% to 12% improvement; the remaining 37.5% of wounds had 0% epithelialization (eFigure 27). Wound epithelialization within 12 weeks was found to be significantly different between groups A and B (P = .0159; 95% CI, 25.60–106.15). 

Slough and eschar
All wounds in group A had a decrease in posttreatment slough and/or eschar on visit 2. By visit 10, 100% of the wounds had 0% slough/eschar posttreatment (eFigure 28). In group B, all wounds had a decrease in slough/eschar on visit 2. On visit 10 and on the last VIP ultrasonic treatment visit (visit 36), 50% of the wounds had 0% slough/eschar and 25% of the wounds had decreased levels. On the last visit, 25% had an increase since visit 10 (eFigure 29). There was no significant difference between groups A and B for slough/eschar present on the last day of treatment (P = .12; 95% CI, -63.89–18.89). 

Correlation between wound age and healing time
A Pearson product-moment correlation revealed a strong positive correlation (r = 0.94) between wound age at the beginning of the VIP Protocol and healing time (eFigure 30). The data of the wounds with known healing dates (those that achieved closure without the use of grafts) from groups A and B were compared. For this small sample, healing time was roughly equal to the wound age at the start of the protocol. In this correlation, time was measured in weeks. A total of 5 patients were included in this calculation. 

One way to analyze the ultrasound modes is to look at healing rates.  A pilot study²⁰ on chronic leg ulcers treated with the same contact ultrasound equipment used in the present study and compression bandages showed 39% of patients achieved complete healing in the follow-up period of 12 to 24 weeks (mean, 16 weeks). It also showed 55% of patients had no changes in wound area during the treatment period.  All patients who healed showed improvement within the first 5 sonication treatment sessions.

Some differences between noncontact mode and standard of care (SC) regarding healing rates have been published.
According to a meta-analysis by Driver et al,²¹ wounds treated with NLFU had an average of 85% wound area reduction in 7 weeks, 80% wound volume reduction in 12 weeks, and 79% wound pain reduction. The average time to complete healing was 8.2 weeks. Linear regression calculations estimated that 33% of wounds would be healed by 6 weeks and 42% by 12 weeks. When compared with SC not including ultrasounds, Driver et al²¹ showed that controls utilizing SC only had a 62% wound area reduction, 37% to 77% wound volume reduction, and a healing rate of 24.2% in 12 weeks. These outcomes were less favorable than the ones seen in the NLFU group.

When selecting the ultrasonic mode that best suits specific healing objectives, clinicians should consider which tissue layers are being stimulated during treatment. The depth of  the applied ultrasonic penetration should ideally match the targeted tissue. If the primary goal is debridement and pain is not a major concern, then contact ultrasound should be the mode of choice. The net effect of the contact ultrasound is more parallel with the wound surface, allowing debridement to happen. In addition, enough energy should be going across the wound bed in order for debridement to take place. It is possible that some of the ultrasonic energy is still transferred down to the tissue in contact mode, but to the best of the authors’ knowledge a detailed study on this topic has not been published yet. If pain is an issue or if the wound bed is sufficiently free of nonviable material, then the noncontact mode should be selected. In this case, the main goal would be wound bed stimulation, including the wound borders. Noncontact, low-frequency ultrasound is said to reach depths of 3.5 mm to 2.5 mm over the open wound as well as intact skin,¹⁴ respectively.

There are challenges with making determinations on the depth of penetration that must be taken into account. The depths noted by Serena et al¹⁴ may underestimate the actual reach of the ultrasound wave. The size of the red dye particle used to establish the penetration of the ultrasound wave may have limited how deep it could go in the tissue; the ultrasound wave may have gone even deeper than the depth where the red particle stopped. More studies on the depth of penetration of contact, low-frequency ultrasound and NLFU would be beneficial.

Further differences between the 2 forms of ultrasound therapy can be noted when taking into account their bactericidal effects. A poster by Schulze et al⁸ indicated that bactericidal effects in the contact mode are dependent on the intensity output selected and the germ count present. Bacteria studied were Staphylococcus pyogenes, S aureus, Escherichia coli, and Pseudomonas aeruginosa. After 60 seconds of treatment at an intensity of 20%, bacteria samples with low germ count (10–10² colony-forming unit [CFU]) were killed, whereas samples with high germ count (10³–10⁴ CFU) survived.  After 60 seconds of treatment at an intensity of 100%, bacteria in all samples were killed. Another poster by Schulze et al²² shows a decrease in germ count on diabetic foot ulcers. In this study, small biopsy samples were taken prior to sonication and a second sample was taken the day after treatment. The study, however, does not state which intensities were used and when and how often the biopsies were performed during the course of treatment as well as offers little detail on their results and types of bacteria studied. A recent study on biofilm²³ showed a significant reduction in the number of viable bacteria on wounds when sonication was applied prior to the administration of an antiseptic solution.

A study on NLFU and bacteria count¹⁴ revealed that after 6 treatments over a 2-week period, highly colonized stage III pressure ulcers (> 10⁵ CFU) had a decrease in bacteria count. S aureus decreased by 93.9%, Acinetobacter baumannii by 99.6%, and E coli by 100%.¹⁴

Very often in the authors’ ambulatory practice, patients are unable to tolerate contact ultrasound intensities of 100%. In acute care, patients with intravenous pain medication may tolerate higher intensities than their ambulatory counterparts. Ambulatory patients are usually on oral pain medication (as needed) or use a topical ointment such as lidocaine gel of various strengths. When pain is a significant factor, NLFU therapy could potentially be a better selection.

When analyzing the effectiveness of the 2 modes of ultrasound on the macroscopic removal of nonviable tissue, debridement results are seen more immediately when using contact ultrasound. Its effects are concentrated in the more superficial tissue layers, and removal of nonviable tissue is achieved more rapidly; however, there are several types of nonviable tissue. More fibrous nonviable tissue may require further debridement and may not be effectively removed via contact ultrasound. Other types of nonviable tissues are more easily removed in 1 or more sonication sessions. In the authors’ experience, soft slough often becomes loose after a NLFU therapy session and may be easily removed through mechanical or sharp debridement. However, more adherent slough or eschar on average remains on the wound bed after a NLFU treatment and no macroscopic changes are seen.

Since ultrasound therapy directly affects cell division and activation of fibroblasts,¹⁰ a study by Ågren et al²⁴ cannot be ignored; their results showed that the mitogenic response of chronic wound fibroblasts is wound-age dependent. In their study,²⁴ wounds were divided into 2 groups: chronic and acute. Chronic wounds had a wound age ranging from 6 months to 20 years, and the acute group had a wound age of 4 to 45 days. The authors herein found it helpful to consider wound age for this study as well.

Continuing on the relationship between wound age and healing, Gibbons et al²⁵ reported that older and larger venous leg ulcers were significantly less likely to heal on a SC treatment alone. The study also observed that area reduction in ulcers > 6 months was lower in both the NLFU plus SC group and the SC group. However, the NLFU-only group responded favorably regardless of the initial wound size or duration.

The results of the present pilot study suggest the VIP Protocol is an effective treatment for subacute and chronic leg ulcers < 20 weeks old. Wound age at the start of therapy seems to be an important variable for the analysis of the wound healing rate using ultrasonic therapy, as suggested by the strong positive correlation (r = 0.94). This evidence supports the idea that the start of the VIP Protocol should not be delayed for very long.

There is a difference between the results of the VIP Protocol and the results reported by the studies mentioned in eTable 2.^20,21,26 It is important to note that those studies did not report results separately for the different wound durations. In the present study, patients with wounds < 20 weeks have a superior healing rate and a better volume reduction than the wounds in the meta-analysis²¹ undergoing SC or NLFU only. Enough of a percentage of the wounds ≥ 47 weeks still improved with the ultrasound therapy, but the primary benefit in group B was wound bed preparation for graft. 

Considering the closure rates of all group A wounds, regardless of when it happened, the average time to achieve closure was 12.875 weeks. The actual data shows that 75% of wounds achieved closure before or at 12.3 weeks (minimum, 6 weeks; maximum, 12.3 weeks).

Group A had clearer and faster progress to healing when compared with group B. Progress is also visible in group B, especially on granulation (eFigures 9, 25), but the progress of that group was more erratic or lacking a steep trend line.

Wound area can be affected by a number of factors such as edema and wound contraction, not just by how much epithelialization is present. In this study, the goal was not to measure all of these factors separately; instead, the authors chose to measure only the changes in wound area and epithelialization. 

Wound volume reflects the filling of the wound bed with granulation, thus improving wound bed quality. Like wound area, it is also affected by the presence of edema and wound contraction. It is important to note that debridement of nonviable material performed during physical therapy did not directly affect the wound volume to the level that would be detectable by a standard paper ruler. Only nonviable material was targeted.

Removal of eschar and slough can be achieved through manual selective sharp debridement. However, when it is done through contact ultrasound, there is a bactericidal component that is not present with other forms of manual debridement. Once the presence of the nonviable material is minimized, it is important to start the NLFU in order to continue with the bactericidal effects and promote stimulation of the wound tissue.

Similar to a study by Sheehan et al²⁷ on the predictive value of nonhealing at 30 days for diabetic foot wounds, the present study shows that wounds persisting for several months become very difficult to heal. Time to initiate therapy has also been a reason for discussion about other advanced therapies such as hyperbaric oxygen.²⁸

More research may in time allow clinicians to choose wounds that initially should have treatments such as the VIP Protocol. For now, starting this protocol on stalled wounds of 30 days’ duration seems to be a reasonable allocation of resources. Such wounds should also have all aspects of the treatment plan evaluated, whether it is offloading or vascular supply for patients with diabetes, compression therapy for venous ulcers, or nutritional issues. In addition, modalities such as those in the VIP Protocol should be considered to prevent the development of the chronic wound environment in which wounds become more difficult to heal.

There are limitations in this study that should be acknowledged. The sample size was small; even though group B had 8 wounds, it only had 2 patients. Also, this was a pilot study and not a randomized controlled trial. It was designed to closely match the reality of the authors’ wound clinic and how this clinical multidisciplinary team is involved in the care of the patient. 

Wound diagnosis and treatment modalities may not be the only elements affecting the healing rate of subacute and chronic lower extremity wounds. Clinicians should consider the age of the wound when devising a plan of care. Based on this study, wounds that started the VIP Protocol at an earlier wound age (group A) had significantly better results, with 75% achieving wound closure by treatment week 12. These wounds also had a faster healing rate than that reported by Driver et al,²¹ both in the SC and in the NLFU categories.

Wounds with a more advanced age (group B) benefited from the VIP Protocol, improving wound bed quality, but the percentage of wound closure as a result of the protocol was not as high as in group A. This fact may indicate that a more realistic objective for such wounds is wound bed preparation for graft rather than further prolonging the time these wounds remain open.

The authors’ clinical experience can attest to the healing benefits of NLFU and to the effectiveness of the contact ultrasound as a debridement tool. Both machines are valuable tools that can be used to accelerate healing. Nonetheless, the authors believe both ultrasonic treatments complement each other greatly. Ideally, they should be used sequentially but possibly in an alternating fashion, depending on the wound needs. The differences between contact and noncontact ultrasound therapies must be taken into consideration when creating a plan of care that targets wound healing in a comprehensive manner.

The main goal of ultrasound therapy, for either contact or noncontact modes, is expediting wound healing. The VIP Protocol aims to move wounds through the various phases of healing as quickly as possible by starting with the efficient removal of nonviable material and progressing to deeper wound bed stimulation.

The authors would like to thank Patricia Rivera, PT, DPT; Stephanie Bird, PT, DPT, CLT-LANA, CCI; and Elizabeth Moran, MD, for their involvement with this project.

Affiliations: Texas Health Presbyterian Hospital Dallas, Dallas, TX

Correspondence: Lisley Viana, PT, MS Texas Health Presbyterian Hospital Dallas Wound Care Clinic 8198 Walnut Hill Lane Jackson Building, Clinic 1-A Dallas, TX 75231 LisleyViana@texashealth.org

Disclosure: The authors disclose no financial or other conflicts of interest. This study is registered with ClinicalTrials.gov: ID NCT02045303.