Chronical wounds - The effect of stochastic electrical noise on hard-to-heal wounds

Clinical Impact

Bioelectrical Signal Therapy treatment resulted in substantial improvement in tissue viability in selected “worst case scenario” patients where wounds had been present for many months or years and had not responded to standard or advanced (tissue bioengineering) treatments.

Introduction

An easy to use, non invasive, painless treatment on a selected series of patients with hard-to-heal wounds that had undergone standard treatment without showing improvement over 1.5 to 20 years.

The use of electrical stimulation as an adjunct treatment for chronic wounds such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs) and pressure ulcers (Pus) has been explored. Moreover, the recent international pressure ulcer guidelines (EPUAP and NPUAP) rated electrical stimulation as the only treatment for pressure ulcers (PUs) with the highest strength of evidence.


Certain electrical currents, mainly direct current (DC) or pulsed monophasic waveforms, have the ability to attract opposite (positive) charged particles to a wounded tissue when applied. This mechanism is known as Galvanotaxis, a directional migration of various types of cells, such as endothelial cells and keratinocytes, which enhance re-epithelialisation. Other electrical currents, such as alternating current (AC), have been reported to activate cutaneous sensory nerves, which mediate increased blood flow and the sensation of the injured tissue around wounds.

A wide range of studies (from computer models to human experiments) has demonstrated that low-level mechanical or electrical noise presented directly to sensory neurons can significantly enhance their ability to detect weak stimuli. This phenomenon of noise improving sensory performance is termed STOCHASTIC RESONANCE. which might affect tissue repair at the molecular and cellular level.


BST (Bioelectrical Signal Therapy) is a computerized electrical stimulation of electrical noise combined with a pulse train (Fig. 1). This specific mode of electrical stimulation activates sensory nerves in humans via stochastic resonance.  The BST system applied on a wound

The increased sensory activity has been shown to accelerate epithelial and vascular growth and cell proliferation on the border of the wounds.

While BST therapy has been validated for the treatment of PUs, it has not been tested in difficult to-treat, long-standing (1.5—20 years’ duration), intractable chronic wounds where other standard treatment methods have failed. This study therefore sought to explore its effectiveness on recalcitrant ulcers of various aetiologies.

Open-label observational case series aimed to evaluate the effect of the Bioelectrical Signal Therapy (BST) device on the treatment of hard- to-heal (recalcitrant) wounds.

Objective

Evaluation of the effect of electrical stochastic noise stimulation on hard-to-heal wounds.

Method & Materials

The study group was comprised of nine patients (three males and six females), with a total of 11 ulcers that had not healed, despite of being treated with other standard methods (ulcer duration range: 18 months to 20 years). Median patient age = 75. Treatment was delivered for 30 minutes. three times a day for 60 days.

The study was conducted at the Difficult Wounds Unit, San Luca Hospital, Turin, Italy.

Subjects (regardless of the setting) were treated with BST for 30 minutes, three times a day. Standard wound care, including pressure relief, debridement and/or antibiotics, and compression therapy were administered as appropriate. Dressings used during the study period included hydrocolloids. hydrogeLs, foams or alginates.

Treatment with BST was given for 60 days and a follow-up observation continued for a further 30 days (patients were observed during the follow-up period each week for recurrence and/or progression of wound healing).

When treatment was given in the home settings. the patients operated the device by themselves (briefly, by connecting the electrodes wire to the device).

The device is a BST device (Lifewave, Israel), equipped with a single channel electrical stimulator and a pair of soft surface electrodes which arc placed 2—5 cm of the wound, on the healthy skin surrounding the wound. Since the BST stimulation is based on alternating current rather than DC, there is no need to place the electrodes on the wound. If the peri-wound was macerated, the electrodes were placed 5cm away from the wound.

The electrical stimulator had an embedded computer (ATmega 128, 16MHz, 8-bit microcontroller, Annel Corp. San Jose, CA, USA), stimulation circuits, and user controls. The electrical output was a low-intensity current (maximal current density of O.3mA r.m.s/cm2) is used in wou before treatment (a) and after day 60 (b)nd care to avoid damaging healthy tissue.
The stimulation mode is a low-frequency (2Hz) periodic pulse sequence composed of two integrated waveforms; a rectangular pulse train and a stochastic (random) signal (Fig 2). Following the digital synthesis and integration of the two signals (and their conversion to analogue signals), the integrated waveforms are filtered by a low pass filter at 2500Hz. The output of the rectangular pulse train is a periodic biphasic pulse which has maximum amplitude of 12± 1 volts (on 2 kilo ohms) and pulse duration of 4 milliseconds.

This combination of stochastic signal with the rectangular pulses enables the stimulation of sensory nerves.  

 

Data Analysis

Study results were summarized using descriptive statistics. For each subject, the overall percentage area of the wound heal (between 0% and 100%, the mean and standard deviation) were calculated.

Results

Stochastic white noise applied to hard-to-heal ulcers for 60 consecutive days reduced the wound surface area to less than half its original size in eight out of the nine subjects. by an overall mean closure rate of 82.5% (SD=25.2%).
Full closure was achieved for 4 patients (five ulcers). In three of these five ulcers, complete closure was observed between 45 to 60 days of treatment. The remaining two ulcers healed at 90 days (30 days after the end of treatment). Patient number nine, who had an 18-month-old post-surgical lesion, achieved complete closure after 45 days and stayed healed.
Ulcers in three patients reduced in size with signs of epithelialisation.
Three patients (no. 3,4,6) made good progress, with the ulcers reducing in size and showing increased epithelialisation (Fig. 2). Treatment was stopped in patient 7 due to an allergic skin reaction around the electrode contact site.

Discussion

The ability of BST to stimulate healing of hard-to-heal ulcers was particularly evident in that five patients achieved complete wound closure, 55.5%. These include grade IV pressure ulcers, post-actinic. ischaemic and postsurgical ulcers, whose duration ranged from 18 to 46 months.

A poor response to treatment was observed in the remaining subject, who has paraplegia and had a grade III PU on his lateral malleolus, was the only patient whose ulcer surface area did not reduce, showing only improved granulation. Defective wound healing associated with paraplegia has been reported by others, indicating the role of sensory nerves in the wound healing process.

No adverse effects were noted, even though one patient stopped the treatment due to a skin ‘allergy’ to the electrodes (a side-effect outlined by the manufacturer). We believe, therefore, that the use of this electrical current can be applied in a comfortable manner that is relatively painless and has minimal safety concerns.

CONCLUSIONS

This open-label observational case series provides preliminary indication of the possible role of stochastic resonance in 4ound healing.
BST treatment resulted in substantial improvement on tissue viability.

 before treatment (a) and after day 60 (b)

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