Decreasing Pain and Increasing the Rate of Chronic Wound Closure With the Use of a Noninvasive Bioelectronic Medical Device: A Case Series
Abstract
Introduction. Chronic wounds are a source of significant morbidity. Medical and scientific efforts are ongoing to further therapeutic modalities improving pain scores and augmenting healing while decreasing complications and reducing the social and economic burden of wounds. Electrical current therapy, or electrical stimulation (ES), has been shown to decrease and modulate both acute and chronic pain; however, understanding of the role of ES in wound closure is limited. Objective. This single-center case series reports use of a topical ultrahigh frequency ES (UHF-ES) therapy to decrease wound pain and improve the rate of closure in difficult-to-heal wounds in 9 patients. Materials and Methods. Initially, each patient underwent individualized care of their chronic wounds for a minimum of 8 weeks, after which adjunct UHF-ES therapy was provided 3 times per week for an average of 8 additional weeks. Wound size and pain level were documented for the period before and after UHF-ES. Results. Overall, pain improved across the 9 patients. One patient was insensate, and another experienced an increase in pain during treatment. Of the 8 patients with sensation, 7 (88%) experienced a decrease in wound pain, with an average 3.4-point reduction per 10-point visual analog scale. Average pain level was 4.14 before treatment and 0.71 after. The average wound size was 5.70 cm2 ± 5.23 cm2 approximately 8 weeks before the initiation of treatment, 4.34 cm2 ± 4.51 cm2 at the time of treatment, and 1.2 cm2 ± 1.75 cm2 at the conclusion of treatment. The average percentage of wound closure with individualized wound care alone was 23.77%, which increased to 64.58% with the addition of UHF-ES therapy. The weekly percentage of wound closure was statistically significant (P = .0027) between the 2 treatment methods. Conclusions. While additional research into the use of ES (namely, UHF-ES in wound healing) is warranted, the device reported herein may be an effective, safe, and low-cost adjunct treatment in the care of chronic, difficult-to-heal wounds.
Introduction
The incidence of chronic wounds continues to increase in the United States, and the economic and physical demands of healing on patients are overwhelming. Over 8.2 million Medicare beneficiaries are being treated for at least one type of wound or wound-related infection, and up to 12 million people in the United States have a chronic wound of any type.1,2
Lower extremity ulcers are common, secondary to venous insufficiency and diabetes. Venous leg ulcers affect nearly 2% of the US population, and the prevalence of a foot ulcer in individuals with diabetes is as high as 13%.3,4 Chronic wounds are an additional complication secondary to surgical interventions, and the prevalence of incision dehiscence after spinal surgery has been reported to be as high as 15%.5,6 Furthermore, while an estimated 2 million people in the United States are newly diagnosed with cancer annually, about 50% will undergo radiation therapy, with subsequent therapy-related skin complications reportedly in as many as 95% of these individuals.7–11
The cost of wound care continues to rise. In 2018, Nussbaum et al1 calculated Medicare costs for wound care (all types) to be between $28.1 billion and $96.8 billion in 2015 alone. While hospitalization for the treatment of chronic wounds and associated complications can be costly, the financial burden of hospitalization ($5.0 billion–$24.3 billion) was remarkably less onerous than the cost of outpatient wound care ($9.9 billion–$35.8 billion).1 At least one catalyst in the dramatically rising cost of wound healing is the wound closure product market. Wound care products permeate both outpatient and hospital settings, and market analysis reports expect the financial impact of closure products to exceed $15 billion annually by 2022.12
Reducing cost while discovering wound closure modalities that promote healing and decrease morbidity is a scientific and medical imperative. This case series explores the improvement in pain levels and the rate of healing of chronic wounds before and after the use of ultrahigh frequency electrical stimulation (UHF-ES) as a novel adjunct therapy to normal regimented wound care.
Materials and Methods
A total of 9 patients with chronic wounds undergoing wound care therapy at a single-center, single-physician clinic were started on UHF-ES therapy after not demonstrating wound healing with standard care.13 All other patients who did not demonstrate wound healing with standard care were offered, yet declined, the novel therapy. The 9 patients included in this study were treated with UHF-ES irrespective of the wound care regimen at the time and only as an adjunct to the wound treatment previously performed. After each treatment, the wound was measured and dressed according to each patient’s individualized protocol. Wound pain levels according to a 10-point visual analog scale (VAS), with 10 being worst, were noted before and after each treatment.
The UHF-ES therapy was performed using the TrueRelief device (TrueRelief). The UHF-ES device, which has received clearance from the US Food and Drug Administration, is a pain-modulating device used in the treatment and alleviation of acute and chronic pain. Unlike other ES devices, the study device delivers electrical current at a UHF of 20 000 Hz. Therapy is provided via 2 stainless steel handheld probes that are held in contact with the patient’s body and are directly controlled at the area of treatment by the clinician.
The device settings for each treatment were set to “ultra-high” frequency, carrier “10,” and calibration “5.” After undergoing wound debridement and cleansing, each patient received the electroceutical treatment at anterior-posterior and medial-lateral aspects of the wound for a total of 10 minutes 3 times weekly. For circular wounds, treatment followed the circumference of the wound, with the probes remaining on opposite sides of the wound.
Pain measurements were obtained by requesting a patient’s subjective value relative to VAS. Wound measurements were documented by direct measurement. Finally, patient dermal oxygen perfusion was measured at precise points along the periphery of the wound using a noninvasive near-infrared imaging device (SnapshotNIR; Kent Imaging).
Results
Four weeks into intervention, 1 patient died from complications of a severe comorbidity; however, those data have been included for consideration and calculation as the wound demonstrated an increase in the healing rate per week with the use of the UHF-ES device up until time of death.
Patient information gathered during data collection included patient age and sex as well as etiology, location, and duration of wound (Table 1). Additional wound data included the total weeks of active treatment with the UHF-ES device, change in pain levels as assessed using the VAS scale, percentage of tissue oxygenation change from the start of treatment, the wound size calculated at 8 weeks prior to the initiation of therapy, and final wound dimensions upon termination of treatment with the UHF-ES device (Table 2).
Wound change calculations were performed, including closure in measured surface area in centimeters squared during the 8 weeks prior to initiation of UHF-ES treatment as well as closure demonstrated during treatment (Table 3). The rates of closure were normalized by converting the change in dimensions and each phase to percentages of total wound closure based on the measurement at the beginning and end of each phase. Additionally, because the number of weeks of treatment per patient varied, a final calculation correcting for this difference as rate of closure per week of treatment was performed.
The average treatment time was 7.9 weeks. One patient was insensate and another patient experienced an increase in pain during treatment. Of the 8 patients with sensation, 7 (88%) experienced a decrease in wound pain. During treatment, those 8 patients experienced an average reduction in pain of 3.4 points based on the VAS; the mean level of pain was 4.14 before treatment and 0.71 after. The rates of closure per week before and after treatment were evaluated for statistical significance using two-tailed paired t test in Excel (2007; Microsoft) and were found to be statistically significant (P = .0027). Calculation of the percentage of change as a sum of each patient change with treatment versus without treatment was also statistically significant (P = .001) (Table 4, Table 5). However, the data presented within these parameters were not corrected for change per week; thus, this determination of significance was not used. Calculation of the significance of change in level of pain on VAS was not performed, nor was calculation of the significance of tissue oxygenation saturation performed.
All 9 cases in this report are presented and expanded below.
Case 1
A 70-year-old male with a medical history of stage 3 chronic kidney disease, hypertension, rheumatoid arthritis, and lower extremity edema with venous stasis dermatitis was undergoing treatment for a painful right ankle venous ulceration that had been present since early 2017. Lower extremity vascular studies indicated venous disease without arterial compromise. Wound care treatment included debridement, multilayer compression dressings, and application of biologic skin graft substitutes. The patient subsequently underwent 9 weeks of adjunct UHF-ES treatment to the point of wound closure and reported a decrease in VAS pain score from 3 to 0. The wound had 6.64% closure per week prior to using UHF-ES and 11.11% closure per week with the addition of UHF-ES. The patient experienced complete wound healing (Figure 1).
Case 2
An 84-year-old male with a history of chronic lymphoid leukemia, severe aortic stenosis, pulmonary hypertension, and peripheral arterial disease (PAD) had been undergoing treatment since September 2019 for a right lower extremity wound sustained in 2016 due to local trauma. The patient was followed by a vascular specialist and underwent endovascular intervention for perfusion optimization prior to this period of observation. Wound care treatment included antimicrobial topical ointments, antimicrobial dressings, moisture control dressings, and wound debridement. The patient died due to complications of the comorbid conditions during the study period. Before death, the patient underwent a total of 4 weeks of UHF-ES treatment, during which time he reported a decrease in VAS pain score from a range of 5 to 7 to a range of 2 to 3. The wound had 3.75% closure per week prior to using UHF-ES and 9.29% closure per week with the addition of UHF-ES (Figure 2).
Case 3
A 68-year-old male with a medical history of PAD, hypertension, and idiopathic lower extremity neuropathy presented in June 2019 for treatment of a neuropathic right medial heel wound of 5 months' duration. Arterial duplex and tissue perfusion studies demonstrated adequate perfusion for healing. Wound care treatment consisted of antimicrobial alginate dressings, weekly wound debridement, and biologic topical agents. The patient then underwent 9 weeks of adjunct UHF-ES. Pain-related information was not gathered because the wound was insensate. The wound experienced 0% closure per week prior to using UHF-ES and 8.73% closure per week with the addition of UHF-ES. Complete wound healing was achieved (Figure 3).
Case 4
A 53-year-old female with a medical history of kyphosis and scoliosis had been undergoing wound treatment since June 2017 for a large surgical site wound after complications of spinal surgery closure. The patient underwent continuous wound care, including multiple surgical revisions, attempted closure using a split-thickness skin graft (STSG), serial debridement, and intermittent negative pressure wound therapy several months at a time. Local wound care was performed for 8 weeks prior to using UFH-ES with biologic wound healing topicals and dressing changes done 3 times per week. She then underwent 6 weeks of adjunct UHF-ES. At 6 weeks, the patient willfully withdrew from the adjunct treatment owing to new-onset, intolerable, radiculopathy type pain clinically attributed to the use of UHF-ES. The wound had 1.13% closure per week prior to using UHF-ES and 12.95% closure per week with the addition of UHF-ES (Figure 4).
Case 5
A 58-year-old male with a medical history of hypercholesterolemia, smoking 10 packs of cigarettes per year, thyroid disorder, and third-degree burns of the entire left lower extremity from childhood presented in November 2019 for evaluation of a recurrent wound to the left thigh that had most recently been present for 2 months. The patient’s comorbid conditions were controlled with medications, and palpable pedal and common femoral pulses with brisk capillary fill time (CFT) were noted. The patient was treated with continuous wound care from presentation, including sharp excisional debridement, nonadherent dressings, and silicone bandaging. Then the patient underwent adjunct UHF-ES therapy for 11 weeks. The VAS pain score decreased from 6 to 2. The wound had 4.52% closure per week prior to using UHF-ES and 10.43% closure per week with the addition of UHF-ES (Figure 5).
Case 6
A 70-year-old male with a medical history of controlled type 2 diabetes, coronary artery disease, hypertension, hypercoagulable state with deep vein thrombosis, decreased right ventricular ejection fraction, and Hodgkin lymphoma underwent 4 years of recurrent therapy for a difficult trauma wound. The patient had palpable pulses and intact protective sensation via monofilament. During this period, glycosylated hemoglobin was 6.9%. Treatment included sharp debridement and application of custom topical antimicrobial cream with routine wound dressing changes. The patient underwent 11 weeks of concomitant UHF-ES treatment. The VAS pain score decreased from 2 to 0. The wound had 4.04% closure per week prior to using UHF-ES and 4.13% closure per week with the addition of UHF-ES (Figure 6).
Case 7
A 57-year-old female with a medical history of hypothyroidism, hypertension, immunodeficiency secondary to chronic corticosteroid therapy, and pyoderma gangrenosum presented in 2015 for evaluation and treatment of a right anterior leg wound (secondary to insect bites) that had been present since 2002. The patient underwent systemic treatment with human immune globulin and local treatment with topical clobetasol propionate to modulate the autoimmune reaction. The patient demonstrated excellent perfusion with palpable pulses and brisk CFT. The patient had undergone continuous wound care, including repeat autologous STSG and serial applications of biologic skin graft substitutes. During the period of observation, treatment consisted of daily application of custom topical antimicrobial cream and marginal clobetasol with nonadherent dressings. The patient received additional UHF-ES treatment for 11 weeks. The VAS pain score decreased from 6 to 1. The wound had 1.85% closure per week prior to using UHF-ES and 2.67% closure per week with the addition of UHF-ES (Figure 7).
Case 8
An 87-year-old female with a medical history of squamous cell carcinoma and radiation therapy presented in September 2017 with a painful right distal anterior leg wound secondary to tumor excision and radiation therapy received in May 2017. The patient underwent continuous treatment, including serial sharp debridement, serial biologic skin graft substitutes, hyperbaric oxygen therapy (HBOT), and antimicrobial alginate dressings. During the period of observation, treatment consisted of antimicrobial alginate dressings and light serial debridement. The patient then underwent 8 weeks of UHF-ES in conjunction with the prior treatment. The VAS pain score decreased from 3 to 0. The wound had 0% closure per week prior to using UHF-ES and 6.99% closure per week with the addition of UHF-ES (Figure 8, Figure 9).
Case 9
A 35-year-old male with a medical history of morbid obesity, chronic anticoagulation, and PAD status after lower extremity arterial bypass surgery presented in June 2017 for evaluation and treatment of a chemical burn wound on the dorsal right foot sustained 4 months prior. The patient demonstrated palpable pulses and brisk CFT on extremity examination. Wound care treatment included HBOT, STSG, serial sharp debridement, and topical antimicrobial alginate dressings. During the period of observation treatment consisted of antimicrobial alginate dressings and serial debridement. The patient underwent 8.5 weeks of additional UHF-ES treatment. The VAS pain score decreased from 3 to 0. The wound demonstrated 4.71% closure per week prior to UHF-ES and 7.84% closure per week with the addition of UHF-ES (Figure 10).
Discussion
In recent decades there has been rapid advancement in treatment modalities designed to improve pain control and the rate of wound healing, decrease complications, and facilitate more effective healing strategies. Recent breakthroughs include advanced dressings,14–16 bandaging,17 ultrasonic therapy,18,19 negative pressure wound therapy,20,21 and HBOT.22
Electrical stimulation therapy has demonstrated effective disruption of surface biofilms, inhibiting the growth of various pathogenic bacterial organisms; augmentation of fibroblast function; reduction in the rates of infection; and the imitation of a healthy bioelectrical environment lost in chronic wounds.23–26
Several randomized controlled trials have demonstrated significant improvement in the rate of wound healing with various periwound ES modalities. Peters et al27 demonstrated a significant difference in wound healing (P = .058) with the active treatment of 20 patients with diabetic foot ulcerations using 50-V direct current treatment for 8 hours nightly for 12 weeks vs placebo (20 patients) using identical functioning equipment but no current. Houghton et al28 reported a 44% reduction in wound area in 16 patients treated with high-voltage pulsed current therapy and a 16% reduction in wound area in 18 patients treated with placebo therapy for 45 minutes 3 times per week for 4 weeks. Salzberg et al29 demonstrated a healing rate of 14 days in 9 patients treated with ES vs 35 days in 10 patients who underwent placebo therapy to treat pressure ulcers with localized pulsed electromagnetic field therapy (P = .007).
Additional reports outline advanced wound healing with use of topical ES therapy bandages. In 2013, Whitcomb et al23 demonstrated a statistically significant increase in rates of closure of 38 wounds by adding a topical microcurrent-generating wound dressing device (P = .018). In 2016, Cole24 reported on the use of a silver-zinc coupled electroceutical dressing to heal wounds in 3 patients within 6 weeks after 2 years of prior failed treatments.
Chronic wound healing is often hampered by decreased tissue oxygenation. There are many reasons for decreased tissue oxygenation, and while intervention (where feasible) is paramount, there are many exogenous factors that may contribute to poor perfusion, including trauma, obesity, immobility, and chronic physiological stress. Prior studies of ES in wound healing have found upregulation of vascular endothelial growth factor.30,31 Multiple reports demonstrate improved perfusion to wound tissues after the use of ES.32 This increase is demonstrated in both arterial flow and venous flow and has been most notable in patients with known PAD.33 The influence of UHF-ES on local microvascular perfusion is beyond the scope of this study; however, 5 of the 9 patients (56%) demonstrated an observed increase of perfusion of periwound tissue.
Pain associated with wound care therapies has been correlated with increased stress reaction, which has been shown to delay healing.34,35 Use of ES, specifically transcutaneous electrical nerve stimulation (TENS), has been shown to improve acute and chronic pain. However, TENS treatments are time consuming and require the application of small electrodes to provide therapy for approximately 30 minutes at least twice daily.36
The aforementioned treatments differ from the present device in the level and type of current received, mechanism of delivery, and use type (multiuse vs single use); it delivers UHF current with a focal wand and is multiuse. The exact mechanism specific to the present device has yet to be elucidated. One hypothesized mechanism is the downregulation of inflammatory cytokines (eg, interleukin-1β, interleukin-6, tumor necrosis factor α) by suppressing a regulatory molecule for these cytokines (eg, high-mobility group box 1), as its release has been observed to correlate with conductive direction of the afferent nerves.37-39 Further research into this mechanism is ongoing.
Limitations
This study has many limitations. Further research is needed on both the study device and ES as advanced modalities in wound healing. All measurements and treatment modalities were directed by a single, direct–observer physician, which maintains a risk of bias in data collection and reporting. This study was originally designed to take place over the course of 8 weeks; however, 2 patients did not complete this total treatment time. An option for time to wound closure as the end goal of treatment was not provided. Although 2 patients had achieved complete wound healing as of the time of this writing, the majority of the wounds present at the beginning of the investigation remained open, but those wounds continued to demonstrate healing with the use of the UHF-ES device.
Conclusions
This study contributes to the literature on therapeutic modalities that can be beneficial in the healing of difficult-to-heal wounds. In the case of these 9 patients, the application of UHF-ES therapy with the aforemention study device in addition to the patients’ prior care regimens contributed to pain reduction and a statistically significant improvement in the rate of wound healing per week of treatment provided. Treatments that afford multimodal relief in wound healing (eg, pain relief, increased tissue perfusion, reduction in size) are of increased importance in the wound specialist’s armamentarium. The therapeutic modality reported herein deserves further scrutiny and higher-level study designs. This case series demonstrates preliminary evidence of the safety, efficacy, and ease of use of the UHF-ES study device as a viable, low-cost treatment for increasing the rate of closure for chronic wounds.
Acknowledgments
Authors: David Charles Hatch, DPM1,2; and Michael Lavor, MD2
Affiliations: 1Sage Research, Tucson, AZ; 2Saguaro Surgical, Tucson, AZ
Correspondence: David Charles Hatch, DPM, Director, Sage Research, 6422 E Speedway Boulevard, Suite 150, Tucson, AZ 85750; dchatchdpm@gmail.com; sage.research.az@gmail.com
Disclosure: The authors disclose no financial or other conflicts of interest.
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