Noncontact Low-frequency Ultrasound Research Articles

Does noncontact low-frequency ultrasound therapy contribute to wound healing at the molecular level?

Noncontact low-frequency ultrasound (NLFU) is used to treat various types of chronic wounds including venous, diabetic, and pressure ulcers. The objective for this substudy of the IN BALANCE RCT VLU trial was to characterize and compare the NLFU treatment group and patients receiving standard of care (SOC) with respect to the effect of the assigned study treatment on content/quantity of inflammatory cytokines and fibrinogen as well as bacteria. Higher mean wound area reduction was observed in the NLFU treatment group (67.0%) compared to the SOC group (41.6%, p < 0.05). Hypertension, diabetes type II, coronary artery disease, and anemia were identified as the most common comorbidities of the Chronic venous leg ulcer (CVLU) patients included in the study. Pseudomonas, Corynebacterium, and unclassified Enterobacteriaceae were dominant in the highest number of samples. Anaerococcus, Peptoniphilus, and Finegoldia, had the highest median proportion in the samples overall. Peptoniphilus abundance decreased more in the NLFU treatment group relative to SOC; similar trends were observed for Anaerococcus and Finegoldia. Progression of mediators like TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 as well as PF4, TGF-beta, and fibrinogen was monitored and trends for several of the mediators were identified. Fibrinogen amounts were significantly reduced over time in the NLFU treatment group (p < 0.05). IL-8 levels declined in wound fluid from NLFU responders as well as SOC responders. Bacterial load (total bacterial abundance) determined local parameters of ulcer inflammation. If a bioburden of ≥ 10E5 was found compared to < 10E5 , levels of IL-1beta, IL-8, and TNF-alpha were significantly higher. In conclusion, NLFU treatment is an effective adjuvant tool for CVLU therapy. This study demonstrates that it improves wound healing by equally inhibiting abundant levels of pro-inflammatory cytokines as well as by reducing the overall bacterial burden.

Use of Noncontact Low-Frequency Ultrasound in Deep Tissue Pressure Injury: A Retrospective Analysis.

The purpose of this study was to examine the effect of noncontact low-frequency ultrasound (NLFU) on deep tissue pressure injury (DTPI), both hospital-acquired and those present on admission (POA). Retrospective, descriptive study. Medical records from 44 adult patients with a DTPI treated with NLFU were reviewed; 22 had a hospital-acquired DTPI (HADTPI) and 22 had DTPI POA. Their mean age was 71.3 ± 16.3 years (mean ± SD); 52% were male. The study setting was a 318-bed community hospital in the Mid-Atlantic region of the United States. Data were collected from the medical records including demographic and relevant clinical characteristics, DTPI measurements, and DTPI evolution/resolution. Data were summarized and examined using descriptive statistics (eg, frequencies and percentages and means and standard deviations). Differences between groups were examined using paired t tests or the Mann-Whitney U test and the chi-square test as appropriate. In addition, the heel DTPI subgroup (N = 8) was examined separately due to the small sample size. All patients with HADTPI and DTPI POA treated with NLFU exhibited a statistically significant decrease in injury size from initiation to discontinuation of NLFU therapy (24.6 cm vs 14.4 cm, P = .02). No statistically significant difference in wound resolution was found between HADTPI versus DTPI POA (27% vs 18%, P = .47). Mean size of both HADTPI and DTPI POA decreased significantly from 15.9 to 13.4 cm (P = .045) by NLFU therapy. Wounds were classified as resolved at completion of treatment in 23% (10 out of 44) of all treated patients. Of all patients with the potential to be resolved (not discharged early or expired) 63% (10 out of 16) had wounds classified as resolved. Study findings suggest that NLFU is a viable and promising treatment option for both HADTPI and DTPI POA. Future studies are needed to confirm these results and to examine efficacy and feasibility of DTPI across care settings.

Ultrassom terapêutico para cicatrização de feridas: revisão sistemática

Introdução: o uso do ultrassom terapêutico (UST) para cicatrização de feridas ainda é discutido pela comunidade científica. Objetivo: determinar se o UST produz desfechos benéficos na cicatrização de feridas e quais tem sido os parâmetros utilizados para proporcionar melhor dose-resposta. Métodos: Foram pesquisadas as bases de dados PubMEd, SciELO e PEDro. Foram selecionados 19 ensaios clínicos, avaliados pelas escalas PEDro e JADAD. Resultados: dos 19 estudos, 8 relacionaram-se à aplicação do NCLFU (Noncontact Low Frequency Ultrasound) com evidência moderada para sua aplicação, 6 à aplicação do HFU (High Frequency Ultrasound) e 1 à aplicação de LIPUS (Low Intensity Pulsed Ultrasound), ambos com baixa evidência. Quanto a relação dose-resposta, não há concordância entre os estudos desta revisão. Conclusões: existe evidência moderada da NCLFU e limitada da HFU como recurso adjuvante para o tratamento de feridas, não sendo possível responder com clareza a melhor relação dose-resposta.

Prospective Randomized Controlled Trial Comparing the Effects of Noncontact Low-Frequency Ultrasound with Standard Care in Healing Split-Thickness Donor Sites

Skin graft donor sites are notoriously painful, with potential complications of fluid loss, delayed healing, infection, and hypertrophic scarring, particularly in patients with burns or traumatic injury. In this population, rapid epithelialization is critical to reducing morbidity and cost. This prospective, randomized controlled trial compared the effects of 40-kHz noncontact low-frequency ultrasound (NLFU) in addition to standard care (SC) with SC alone in subjects with split-thickness donor sites of 20 to 200 cm(2). Standard care consisted of cleansing and moist wound dressings. Outcomes measured were time to healing, defined as absence of drainage and full epithelialization; pain and itching scores; and recidivism rates. Of 33 patients enrolled; 27 were randomized and received a minimum of 4 study treatments. Median age was 49 years, 69% were male, and 84% were burn patients. Comorbidities included hypertension (31%), coronary artery disease (22%), pulmonary disease (38%), anemia (31%), and diabetes (16%). Median donor site area was 136.0 cm(2). Noncontact low-frequency ultrasound and SC compared with SC demonstrated a mean time to heal of 12.1 days vs 21.3 days (p = 0.04). All NLFU+SC subjects had epithelialized by 4 weeks compared with only 71% in SC. Recidivism rates were 8% for NLFU+SC compared with 45% for SC. Pain scores were reduced and significant differences in itching were observed. Noncontact low-frequency ultrasound and SC compared with SC alone in the treatment of split-thickness donor sites demonstrated significant accelerated healing and reduced pain and itching. Noncontact low-frequency ultrasound subjects experienced a better quality of healing with less incidence of infection and recidivism.

Effect of Noncontact Low-Frequency Ultrasound on Wound Healing

Effect of Noncontact Low-Frequency Ultrasound on Wound Healing

Effect of Noncontact Low-Frequency Ultrasound on Wound Healing

Purpose: Recent research suggests the use of noncontact low-frequency ultrasound (US) as an adjunct to standard wound care to facilitate the healing process. The purpose of this systematic review was to examine the effect of noncontact low-frequency US on the healing of chronic wounds. Methods: CINHAL and PubMed were used to identify studies published from 2000 to 2011 written in English with the key words ultrasound and debridement, chronic wounds, ultrasonic-assisted wound treatment, and MIST Therapy®, resulting in the retrieval of 51 potential articles. Ten studies met the inclusion criteria and were included in the review. Two reviewers independently rated study quality and extracted data concerning study methods, quality, and outcomes. Results: Nine of the studies reviewed demonstrated improved wound healing when noncontact low-frequency US was used either as the sole treatment or as an adjunct to standard wound care, whereas the findings of one study were inconclusive. Discussion/Conclusions: The literature reviewed supports the use of noncontact low-frequency US as an adjunct in the treatment of chronic wounds. The studies reviewed suggest that noncontact low-frequency US aids in the reduction of wound volume and that healing occurs at a faster rate than with standard wound care alone. Evidence is limited by the existence of only two studies with control groups. Future research should use comparison groups and focus on dosing parameters, outcomes on the basis of the wound type, and other meaningful patient outcomes such as wound pain or cost of treatment.

Combined Negative Pressure Wound Therapy and Ultrasonic MIST Therapy for Open Surgical Wounds

Surgical wounds are at increased risk of infection when left open to heal through secondary intention; they increase length of hospital stay, hospital costs, readmission rates, and patient morbidity. New technologies and methods of treating acute and chronic wounds are emerging. Two recent developments for the treatment of open wounds are noncontact low-frequency ultrasound (NCLFU) treatment and negative pressure wound therapy (NPWT). This case series reports findings from 4 hospitalized patients with complex conditions who underwent colorectal surgery resulting in open abdominal wounds. The wounds were treated with NCLFU in combination with NPWT. Data were collected via retrospective review of medical records. After concurrent treatment with NPWT (range, 13-18 days) and NCLFU (range, 5-9 treatments), wound areas in these 4 cases were reduced by 4.5% to 37% and wound volume decreased by 17% to 62%. Granulation tissue increased in the open tissue areas in all patients. In addition, 3 of the cases received a mesh graft. Combination treatment with NPWT and NCLFU therapy with or without sharp debridement enhanced wound healing in the open abdominal wounds of these 4 patients.

High Frequency and Noncontact Low Frequency Ultrasound Therapy for Venous Leg Ulcer Treatment: a Randomized Controlled Study

Background: Ultrasound therapy can be utilized to manage chronic wounds including venous leg ulcers (VLUs). Objectives: A randomized controlled clinical study was conducted to compare the effectiveness of standard treatment and standard treatment plus either high frequency ultrasound (HFU) or noncontact low-frequency ultrasound (NCLFU) on VLU outcomes. Patients and Methods: Ninety outpatients (47 men, 43 women; average age, 38.3 [SD, 11.5] years) were randomly assigned into either of the standard care (n = 30), HFU (n = 30) or NCLFU groups (n = 30). Standard care included multilayered compression bandaging (40 mm Hg of pressure at the ankle graduated to 17 mm Hg to 20 mm Hg below the knee) nonadherent dressing and regular debridement. Standard care dressing changes and ultrasound therapy were provided three times per week for 3 months or until healing. HFU delivers high intensity (0.5 1 W/cm2) high frequency (1 3 MHz) ultrasound for 5 to 10 minutes and NCLFU delivers low-intensity (0.1 0.8 W/cm2) low frequency (40 kHz) ultrasound for 4-10 minutes. Patients were followed until healing. Wound size wound pain and lower leg edema was assessed at baseline and after 2 and 4 months. Data were analyzed using Student's t test ANOVA, chi square or Fisher s exact test. P value of less than 0.05 was considered significant. Results: Initial wound measurements were 9.60 cm2 (SD 5.54) 9.86 cm2 (SD 3.95) and 10.01 cm2 (SD 4.58) for the standard treatment HFU and NCLFU groups respectively. After 4 months measurements were reduced to 4.28 cm2 (SD 2.80) 3.23 cm2 (SD 2.39) and 2.72 cm2 (SD 2.16) for the standard treatment HFU and NCLFU groups respectively which was statistically significant (P = 0.04). All wounds were healed after an average of 8.50 (SD 2.17) 6.86 (SD 2.04) and 6.65 (SD 1.59) months in the standard treatment, HFU and NCLFU groups respectively (P = 0.001). Differences in the amount of edema and pain rating scores were also significant at the 4th month follow up visit (P = 0.05). Conclusions: Outcomes of both methods of ultrasound therapy were better than standard care alone, and some differences between the two ultrasound therapy groups were observed, but they were not statistically significant.

Noncontact, low‐frequency ultrasound as an effective therapy against Pseudomonas aeruginosa–infected biofilm wounds

Bacterial biofilms, a critical chronic wound mediator, remain difficult to treat. Energy-based devices may potentially improve healing, but with no evidence of efficacy against biofilms. This study evaluates noncontact, low-frequency ultrasound (NLFU) in the treatment of biofilm-infected wounds. Six-millimeter dermal punch wounds in rabbit ears were inoculated with 10(7) colony-forming units of Pseudomonas aeruginosa or left as sterile controls. A biofilm was established in vivo using our published model. NLFU treatment was carried out every other day or every day, with contralateral ear wounds acting as internal, untreated controls. Wounds were harvested for several quantitative endpoints and scanning electron microscopy to evaluate the biofilm structure. The P. aeruginosa biofilm consistently impaired wound epithelialization and granulation. NLFU, both every other day and every day, improved healing and reduced bacterial counts relative to untreated controls (p < 0.05). Scanning electron microscopy confirmed a qualitative decrease in bacteria after both treatments. NLFU also reduced inflammatory cytokine expression (p < 0.05). Our study suggests that NLFU is an effective therapy against P. aeruginosa wound biofilm. This represents the first in vivo evidence of energy-based modalities' impact on wound biofilm, setting the foundation for future mechanistic studies. Continued wound care technology research is essential to improving our understanding, and treatment, of biofilm-infected chronic wounds.

A pilot study evaluating non‐contact low‐frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers

Non-contact low-frequency ultrasound (NCLF-US) devices have been increasingly used for the treatment of chronic non-healing wounds. The appropriate dose for NCLF-US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non-healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non-healing DFUs for 5 weeks receiving standard of care and/or NCLF-US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF-US thrice per week (Group 1), NCLF-US once per week (Group 2) and the control (Group 3) that received no NCLF-US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of 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 in response to NCLF-US consistent with wound reduction, when compared with control group subjects. This proof-of-concept pilot study demonstrates that NCLF-US is effective in treating neuropathic diabetic foot ulcers through, at least in part, inhibiting pro-inflammatory cytokines in chronic wound and improving tissue regeneration. Therapeutic application of NFLU, thrice (3) per week, renders the best wound area reduction.

Adjunctive Use of Noncontact Low-Frequency Ultrasound for Treatment of Suspected Deep Tissue Injury

We lack a clear understanding of the mechanisms of damage associated with suspected deep tissue injuries (SDTI) and sufficient evidence to determine the efficacy of various preventive interventions. The purpose of this article is to evaluate noncontact low-frequency ultrasound (NLFU) as one component of a preventive program designed for preventing SDTI from progressing to higher-stage pressure ulcers. In March 2009, we added NLFU treatments daily for 5 days, then every other day until healed, to our prevention protocol in order to prevent progression of SDTI to a higher-stage pressure ulcer. We report the course and outcomes of 6 SDTIs that were treated adjunctively with NLFU. Treatment was limited to patients with an SDTI identified within 3 to 4 days of onset. Following the addition of NLFU to the SDTI plan of care, these 6 cases of SDTI did not progress to advanced-stage pressure ulcers. These initial findings suggest that the addition of NLFU to SDTI identified within 3 to 4 days of onset may be effective for preventing progression to higher-stage pressure ulcers.

Noncontact low‐frequency ultrasound therapy in the treatment of chronic wounds: A meta‐analysis

Our objective was to summarize and quantify the effects of a noncontact low-frequency ultrasound (NLFU) therapy on healing of chronic wounds. We performed a meta-analysis of eight published studies reporting effects of NLFU on wound size and healing rate of chronic wounds in 444 NLFU-treated patients. A search of the PubMed database was conducted in January 2010 and updated in October 2010. We used random-effects linear regression models to estimate the proportional reductions in wound area and volume and the proportion of wounds healed from baseline to last follow-up. In four studies (N=188) reporting change in wound area from baseline, NLFU was associated with 85.2% area reduction (95% CI 64.7%-97.6%) over a mean 7 weeks. In four studies (N=278) reporting reduction in wound volume, NLFU was associated with 79.7% volume reduction (95% CI 46.1%-98.8%) over a mean 12 weeks. In seven studies (N=429) reporting proportion of wounds healing by study end (mean time to healing 8.2 weeks; median 6.8 weeks), meta-analyzed healing rates over time suggest 32.7% of wounds healed on average by 6 weeks (95% CI 23.3%-42.1%) and 41.7% by 12 weeks. NLFU for treatment of chronic wounds was associated with consistent and substantial wound size reductions, as well as favorable rates of healing.

Use of Noncontact Low-Frequency Ultrasound in the Treatment of Chronic Foot and Leg Ulcerations

A feasibility study was conducted to characterize the effects of noncontact low-frequency ultrasound therapy for chronic, recalcitrant lower-leg and foot ulcerations. The study was an open-label, nonrandomized, baseline-controlled clinical case series. Patients were initially treated with the Mayo Clinic standard of care before the addition of or the switch to noncontact low-frequency ultrasound therapy. We analyzed the medical records of 51 patients (median +/- SD age, 72 +/- 15 years) with one or more of the following conditions: diabetes mellitus, neuropathy, limb ischemia, chronic renal insufficiency, venous disease, and inflammatory connective tissue disease. All of the patients had lower-extremity ulcers, 20% had a history of amputation, and 65% had diabetes. Of all the wounds, 63% had a multifactorial etiology, and 65% had associated transcutaneous oximetry levels below 30 mm Hg. The mean +/- SD treatment time of wounds during the baseline standard of care control period versus the noncontact low-frequency ultrasound therapy period was 9.8 +/- 5.5 weeks versus 5.5 +/- 2.8 weeks (P < .0001). Initial and end measurements were recorded, and percent volume reduction of the wound was calculated. The mean +/- SD percent volume reduction in the baseline standard of care control period versus the noncontact low-frequency ultrasound therapy period was 37.3% +/- 18.6% versus 94.9% +/- 9.8% (P < .0001). Using noncontact low-frequency ultrasound improved the rate of healing and closure in recalcitrant lower-extremity ulcerations.