Silver-Collagen Dressing and High-voltage, Pulsed-current Therapy for the Treatment of Chronic Full-thickness Wounds: A Case Series
Research suggests high-voltage, pulsed-current electric therapy (HVPC) is safe and effective for treating chronic wounds, and some data suggest silver- and collagen-based dressings may facilitate healing. A combination therapy utilizing both HVPC and silver-collagen dressing may present clinical advantages. To explore the effect of the combined therapy for chronic full-thickness wounds, a prospective, consecutive case series study was conducted. All participants were adults with wounds of at least 6 weeks’ duration.
After obtaining informed consent, patient and wound characteristics were obtained, wounds were assessed and measured, and patients received 2 to 3 HVPC treatments per week followed by application of the silver- and collagen-based dressing for a period of 2 weeks. Data were analyzed descriptively, and changes in wound size and volume from baseline were analyzed using Wilcoxon Signed Rank Test. The dressings were saturated with normal saline, used simultaneously during the 45-minute HVPC treatment, and left on top of the wound after treatment. The HVPC electro pads (stainless steel electrodes with a sponge interface) also were moistened with normal saline and the cathode placed on top of the wound. If the patient had more than 1 wound on the same leg, the anode was placed on the additional wound (otherwise over the intact skin nearby). Secondary dressings (eg, foam and/or gauze) were used as clinically appropriate, and a 4-layer compression wrap was used, if indicated, for patients with venous ulcers. Ten (10) patients (3 women, 7 men, 57.30 ± 9.70 years old with 14 wounds of 273.10 ± 292.03 days’ duration before study) completed the study and were included in the final analyses. Average wound surface area decreased from 13.78 ± 21.35 cm2 to 9.07 ± 16.81 cm2 (42.52% ± 34.16% decrease, P = 0.002) and wound volume decreased from 3.39 ± 4.31 cm3 to 1.28 ± 2.25 cm3 (66.84% ± 25.07% decrease, P = 0.001). One (1) patient was discharged with complete wound closure. No serious adverse events were noted, but a diagnosis of osteomyelitis in 1 patient and increased pain in a patient with significant Reynaud’s syndrome suggest clinicians should be cautious using HVPC in these instances. The combined intervention utilizing both HVPC and silver-collagen dressing was effective in the treatment of chronic full-thickness wounds in this patient population. Controlled clinical studies of longer duration are needed to further explore the safety, effectiveness, and efficacy of this treatment.
A wound that fails to heal properly in optimal conditions within 4 to 6 weeks is considered chronic.1,2 Chronic wounds can impair an individual’s functional status, restrict participation in employment and activities of daily living, and significantly decrease patient quality of life.3 Additionally, chronic wounds may lead to a number of costly complications including infection, amputation, and death.3 The healing of chronic wounds is often unpredictable. As a review4 indicates, healing processes can be interrupted or stalled in the sequence of biochemical and cellular events, and the risk of interruptions within the typical healing process becomes more common as the age of the patient increases and as the health condition of the patient decreases. In order to prompt transition of the chronic wound from a disrupted healing process, appropriate interventions are necessary. Currently, in clinical practice topical treatments constitute the mainstay of interventions in chronic wound care.5
Commonly used methods for the topical treatment of chronic wounds include various types of dressings, negative pressure wound therapy, debridement, local antibiotic therapy, and electric therapy.5 A review of the literature6 has shown high-voltage, pulsed-current electric therapy (HVPC) is effective in treating chronic wounds. In vivo animal experiments and in vitro study7-9 found HVPC can induce cellular electrotaxis, increase the production of vascular endothelial growth factor (VEGF) and fibroblastic growth factor (FGF), and activate VEGF receptors via VEGF and FGF (both stimulate angiogenesis and facilitate wound healing). Randomized, controlled trials (RCTs)10-12 also have found the use of HVPC in wound care to be promising. In a prospective, controlled trial (N = 16), Kloth and Feedar10 found HVPC accelerated the healing rate of Stage IV pressure ulcers compared to no treatment. In a similar prospective, controlled study (N = 17), Griffin et al11 reported HVPC induced significantly greater decrease in wound size than the placebo control in patients with a pelvic pressure ulcer. In a RCT, Franek et al12 found HVPC therapy provided to 33 patients produced better results than topical medication in 32 patients or Unna boot in 14 patients for healing venous leg ulcers.
Silver- and collagen-based dressings also are commonly used in chronic wound care. Silver is a toxic heavy metal that may cause protein denaturalization; however, silver-containing dressings are deemed safe based on a review of clinical trials13 because they allow only limited concentrations of silver ions to be present in the wound/dressing interface. According to a literature review,14 silver-based dressings have been found to possess antimicrobial activities and facilitate chronic wound healing.
According to a narrative review,15 the human body contains various types of collagen, which comprises 70% to 80% of the dermis (dry weight). Collagen provides structural support for cellular mitogenesis, differentiation and migration via synthesis, and release of inflammatory cytokines and growth factors.15 Because of these benefits,13-15 dressings containing silver, collagen, or both are widely used in chronic wound care.1
Various dressing brands with components of silver, collagen, or both are marketed. Reviews of the literature13-16 have found them effective. Additionally, in a recent case series study of recalcitrant wounds of various etiologies, Shah and Chakravarthy17 reported complete wound closure over 68 days of treatment in 15 out of 18 patients using a bovine-derived 100% native, type I collagen. In a prospective, comparative study of patients with venous leg ulcers or diabetic foot ulcers (N = 10), Manizate et al18 reported wound closure rates were 1.38 ± 1.44 cm2/week with bovine native collagen/ionic silver dressing and 0.79 ± 0.74 cm2/week with carboxymethylcellulose/1.2% ionic silver.
The use of HVPC and silver and/or collagen dressings has both a theoretical foundation and clinical research evidence.6-18 Thus, the combination therapy utilizing both HVPC and silver-collagen dressing is logical and may hold additional advantages in facilitating wound healing. However, little research evidence on the safety, efficacy and effectiveness of this combined therapy is available. The purpose of this case series was to explore the effect and safety of the combined therapy utilizing both HVPC and silver-collagen dressing in the treatment of chronic, refractory, full-thickness wounds.
Study Design and Methodology
A prospective, consecutive case series study was performed at the Daemen College Physical Therapy Wound Care Clinic, a subsidiary of the Daemen College Physical Therapy Department (Daemen College, Amherst, NY). Established in 2012 as a result of a grant secured from a private philanthropic organization, this clinic has been operating as an outpatient physical therapy clinic specializing in wound care and serving the Western New York community by offering treatment free-of-charge to patients for a 2-year period. In addition to providing patient care, clinical research on patient outcomes, effectiveness of treatment modalities, and patient response to dressings is ongoing. Patient participation in research is completely voluntary and is not a condition of receiving care. The study protocol was approved by the Daemen College Institutional Review Board; all participants provided written informed consent before study inclusion.
Participants. Inclusion criteria stipulated patients must be 21 years of age or older with a full- thickness wound of any type present for at least 6 weeks before study inclusion and nonresponsive to previous wound treatments (no improvement in wound surface area and depth of wound for 1 week or longer). Patients with vasculitis, hypergranulation tissue, unstable vital signs, or a known hypersensitivity to collagen and/or silver were excluded from participating in the study. Additionally, patients with visually identifiable redness and new onset of pain related to the wound (possible active infection) and patients who were taking antibiotics at assessment for study participation also were excluded.
Treatment protocol. Silver-collagen dressing (Puracol® Plus Ag+ MicroScaffold™ Collagen, Medline Industries, Inc, Mundelein, IL) that was saturated with normal saline was used simultaneously during 45 minutes of HVPC (RichMar Winner EVO ST4, Chattanooga, TN) treatment and was left on top of the wound after treatment. Electro pads (stainless steel electrodes with a sponge interface) were moistened using normal saline with the cathode on top of the wound; if the patient had more than 1 wound on the same leg, the anode was placed on the additional wound (otherwise over the intact skin nearby). Secondary dressings, which mainly include foams and gauzes, were used as adjuncts as clinically appropriate. An additional 4-layer compression wrap system was applied on patients with venous ulcers if the leg was compressible as judged from the ankle brachial index value and additional laser Doppler when needed. The same treatment protocol was applied to all patients during each visit. Participants were treated 2 to 3 times per week for 2 weeks.
Outcome measurement. During the study, the following data were collected at each patient visit: wound size (length and width) and depth were measured with regular paper ruler and Q-tip. Wound surface area was calculated (wound length times wound width); wound volume was calculated as wound surface area times wound depth. Photographs of the wound were taken during each visit to assess other characteristics (eg, color change and border); wound exudate and odor were noted if applicable. Additionally, patient age; gender; wound location, etiology, and duration before study participation; previous wound treatments; and medical history were documented.
Data collection and statistical analysis. Patient demographics and wound-related history data were collected and stored in the electronic medical record system at the clinic. Additional hardcopy documents related to the study were stored in the locked drawer at the clinic. Patient demographic data were summarized descriptively. Statistical analysis was performed using SPSS 19.0 software (SPSS Inc, Chicago, IL, USA) for Windows. Percentages, means, standard deviations (SD), and quantitative ranges were provided. Two-tailed significance testing at the <0.05 probability level was considered statistically significant for all analyses. Differences in wound surface areas and volumes were compared at study enrollment and at the end of the study using Wilcoxon Signed Rank Test. Wound surface area and volume reductions were described in percentages.
Flow of study participation is presented in Figure 1. At the beginning of the study (July 18, 2013), 3 patients whose wound healing did not progress for more than 1 week at the clinic were directly included in the present study (cohort A). From July 18, 2013 to September 17, 2013, new patients with unhealed wounds who had not made clinical improvements at their treating physician’s office, wound clinics, or other health care facilities were referred to the present clinic for evaluation; among these patients, 9 were included in the present study (cohort B). Eleven (11) other potential patients were excluded from the present study for the following reasons: 2 patients with a full-thickness venous ulcer declined participation; 2 patients with a diabetic foot ulcer had unstable vital signs and were subsequently admitted to the hospital; 6 patients had a partial-thickness wound; and 1 patient had tissue hypergranulation.
In total, 12 patients participated in the study; none of the 12 patients showed signs and symptoms related to infection or were taking antibiotics at study inclusion. However, 2 patients were discontinued from the study after 2 treatments: 1 patient in cohort A developed excessive exudate and a strong foul odor as well as significant redness upon dressing removal; the wound under treatment had a 50+-year history and was caused by a motor vehicle accident. After study discontinuation, the patient was referred to a specialist and was diagnosed with chronic osteomyelitis. The other discontinued patient in cohort B experienced increased pain after 2 treatments; this patient had significant Reynaud’s syndrome. The remaining 10 patients who completed the 2-week study had 19 wounds in total; however, 5 wounds on 5 patients did not meet the inclusion criteria of wound duration of at least 6 weeks or full-thickness; these wounds were excluded from the present study. Consequently, 2-week outcomes data from 14 wounds (10 patients) were available.
The 10 participating patients had an average age of 57.30 ± 9.70 (range 41–67 years) and a wound history of 273.10 ± 292.03 (range 45–892) days before study participation (see Table 1). At baseline, the average wound surface area was 13.78 ± 21.35 cm2; after 2 weeks, the average was 9.07 ± 16.81 cm2 (a decrease of 4.71 ± 6.51 cm2, P = 0.002) (see Table 2). Wound volume also decreased significantly from 3.39 ± 4.31 cm3 to 1.28 ± 2.25 cm3 (a decrease of 2.09 ± 2.43cm3, P = 0.001). One patient was discharged after complete wound closure at study conclusion. One wound exhibited decreased wound volume but not wound surface; the other 13 wounds showed a decrease in both surface area and volume. Overall, wound surface area decreased by 42.52% ± 34.16% and volume decreased by 66.84% ± 25.07% in these 14 wounds. Thus, the combined intervention utilizing both HVPC and silver-collagen dressing was effective in the treatment of all of the 10 (100%) patients with 14 chronic refractory full-thickness wounds.
In addition to the adverse events in the 2 patients mentioned previously, other adverse events noted among the participants included the following: 2 patients had a local infection per physician diagnosis, confirmed with wound culture and treated with antibiotics during study; 1 patient was briefly hospitalized due to recurrent deep vein thrombosis (DVT); and 1 patient reported increased foul odor after application of the dressing. These patients resumed/continued their participation in the study without additional events. No other side effects were reported.
Despite extensive use of silver-based dressings in chronic wound care, research evidence using robust controlled models are not common, although a preponderance of in vitro antimicrobial studies has been conducted.13,14 In 1 of only a few RCTs (N = 34), Woo et al19 reported silver alginate powder could facilitate wound healing by decreasing bacterial burden using a foam dressing control. A review15 concluded a collagen-based dressing could facilitate wound healing; although high-quality clinical trials of collagen-based wound dressings are limited, collagen is widely considered safe and effective for wound healing15-18 and has no known side effects, according to a prospective, comparative study by Manizate et al.18 Results from the present study utilizing treatments containing both silver and collagen are consistent with these findings and demonstrated universal decrease in wound volume of all 14 wounds with minimal to no apparent treatment-related side effects. Nonetheless, it’s worth noting 2 patients withdrew from the study due to foul odor, drainage, or pain after 2 treatments; data on these 2 patients were not included in the final analyses.
The use of HVPC in the current study is well supported by research.6-9 Electric stimulation was reported in a narrative review6 to facilitate the production of collagen by fibroblasts and increase blood flow and capillary density. Both collagen production and blood supply are of great importance for the enhancement of granulation tissue growth in chronic wounds. Through RCTs,10-12,20 researchers found 45–60 minutes of HVPC more than 5 times a week is an effective therapy for pressure ulcers, nonhealing venous wounds, and diabetic foot ulcers. Nonetheless, more research is needed regarding wound healing using HVPC because wound healing plateaued in 2 patients from cohort A (they were managed with HVPC and other dressings before enrollment in this study) and various patients did not show continuous improvement with HVPC treatment in the previous studies.10-12,20
If wound healing has plateaued, whether to continue the use of the same treatment is a question for debate. In addition to efficacy concerns, it may be unethical from a human subject perspective. In the present study, the same treatment protocol was applied for 2 weeks and patients could be provided other dressings or treatments after the study if no responses were observed. Additionally, to optimize treatment outcomes, this combined therapy utilizing both HVPC and silver-collagen dressing was applied for the treatment of full-thickness wounds. The results of the present study demonstrated an average 42.52% decrease in wound surface area and a 66.84% decrease in wound volume during a 2-week study period, which suggests this combined treatment protocol may be effective.
With regard to side effects of the intervention, the etiology of the local infection in the 2 included patients remained unknown, most likely due to compromised immune function as a result of drug therapy or comorbidities. The patient who was hospitalized during the study due to DVT had transplantation of both a kidney and pancreas and had a long-term history of recurrent thrombosis, events not likely caused by the study intervention. Nonetheless, the foul odor may be caused by the breakdown of the silver/collagen-based dressing of the intervention.
Additionally, the discontinuation of treatment for the 2 patients from the study is worth noting; 1 was later diagnosed with chronic osteomyelitis, which may be a contraindication for electric therapy.21 Although the supporting research evidence for chronic osteomyelitis as one of the contraindications for electric therapy is still insufficient,21 clinicians should be cautious when applying HVPC to patients with chronic osteomyelitis. The other patient had uncontrolled Reynaud’s syndrome; clinicians may need to be vigilant regarding the use of silver/collagen-based dressing and/or HVPC in patients with simultaneous chronic wounds and Reynaud’s.
Although the majority of chronic wounds may stall in the inflammatory phase,1 the actual wound environment changes daily to weekly if not by hours or minutes. Thus, continuous monitoring of wound environment is needed. When wound healing plateaus, combined therapy using HVPC and silver-collagen dressing may facilitate the wound healing process.
The case series study design with a small sample size limits the generalizability of the study results. The effect of treatment for patients in cohort B who were newly examined and treated at the clinic may be due to a change in treatment clinics. Additionally, wound size and depth were measured with a regular paper ruler and Q-tip, which may not be reliable. Finally, patients were followed for only 2 weeks; thus, it is not known if ongoing treatment would have resulted in complete healing. Further investigation is warranted to better understand the treatment response and clinical utility of this combined intervention.
A combined intervention utilizing both HVPC and silver-collagen dressing was effective in the treatment of 14 chronic full-thickness wounds in 10 patients. After 2 weeks of treatment, a universal reduction in wound volume was observed in all of the 14 wounds. Although the results from this case series cannot be generalized to a larger population, these results are encouraging. Two potential limitations of using HVPC also should be noted. Specifically, clinicians should be cautious when applying HVPC to patients with chronic osteomyelitis or Reynaud’s syndrome. Controlled clinical studies are needed to evaluate the safety, efficacy, and effectiveness of this combined treatment modality. n
The authors thank the John R. Oishei Foundation and James H. Cummings Foundation for funding the Daemen College Physical Therapy Wound Care Clinic, Amherst, NY; Medline Industries Inc (Mundelein, IL) and Derma Sciences Inc (Princeton, NJ) for the wound care dressings; Corstiaan Brass, MD for his generous donation to the clinic and guidance in the management of patients; Michael Brogan, DPT, PhD for his leadership in the management and administration of the clinic; and Laura E. Edsberg, PhD for her kind suggestions during the draft of the manuscript.
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Potential Conflicts of Interest: The Medline Industries Corporation (Mundelein, IL) was 1 of the contributing entities supporting the free clinic over a 2-year period of time. The collagen product was donated to the clinic.
Dr. Zhou is a physical therapist, Daemen College Physical Therapy Wound Care Clinic and a clinical assistant professor, Department of Health Care Studies; Dr. Krug is a physical therapist, Daemen College Physical Therapy Wound Care Clinic; Dr. Stachura is a clinical assistant professor, Department of Physical Therapy; Dr. Niewczyk is an associate professor, Department of Health Care Studies; Dr. Ross is an assistant professor, Department of Physical Therapy; Ms. Tutuska is an assistant professor, Department of Health Care Studies; and Dr. Ford is an associate professor, Department of Physical Therapy, Daemen College, Amherst, NY. Please address correspondence to: Kehua Zhou, MD, DPT, LAc, Department of Health Care Studies, Daemen College, MailBox 144, 4380 Main Street, Amherst, NY 14226; email: email@example.com.