Extracorporeal Shockwave Therapy (ESWT) in an Outpatient Wound Care Clinic: Case Series Analysis of a Non-Invasive Technology in the Management of Chronic Wounds for Wound Bed Preparation

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Chronic wounds affect 6.5 million people in the US.¹ They contribute significantly to lower limb amputations, and every 20 seconds a limb is amputated somewhere in the world due to diabetes and diabetes-related complications including wounds.² Chronic wounds exert a heavy financial burden on the health care system. In the US, total Medicare spending estimates for all wound types range from $28.1 to $96.8 billion per year.³ When wounds fail to achieve significant healing after 4 weeks of the standard of care, reassessment of the underlying pathology and the need for advanced wound therapies should be undertaken.⁴ This is done through careful assessment that can include reevaluation of current wound care measures and ordering diagnostic tests. The diagnostic workup can include, but is not limited to, culture and sensitivities as well as vascular evaluation and prompt referral when indicated. It is not uncommon to see chronic wounds that are stagnant, despite what clinicians deem to be appropriate interventions and advanced modalities.

Often, this problem can arise from inadequate wound bed preparation, which is why it is important to do a holistic evaluation of patients. This can be accomplished by using the Wound Bed Preparation (WBP) paradigm. WBP is a paradigm to optimize chronic wound treatment.⁵ It was first introduced in the wound care setting in 2000 and is an assessment tool that is constantly updated.^6,7 It is a patient-based, holistic approach that takes into consideration patient concerns followed by proper evaluation and intervention targeted toward specific components of wound care, including moisture balance, debridement, and infection/inflammation.

Additionally, another helpful tool in the holistic evaluation of patients with chronic wounds includes the TIMEO2 principle (Figure 1). This stems from the modified TIME principle, which is a mnemonic for the management of nonviable or deficient tissue (T), infection or inflammation (I), prolonged moisture imbalance (M), and non-advancing or undermined epidermal edge (E). Correction of hypoxia (O2) is the last component of the mnemonic.⁸ As with the WBP paradigm, the TIMEO2 principle aims to identify and correct all underlying pathology that might be keeping a chronic wound at a non-healing stage.

There are many factors that can contribute to a delay in wound healing and the development of a chronic wound. These factors include hypoxia, bacterial infection (and virulence factors such as biofilm production), malnutrition, and constant unrelieved pressure causing mechanical damage, to name a few.^9,10,11,12 At a molecular level, failure of wound healing may result either from deficient supply or functional inhibition of growth factors.¹³

Extracorporeal shockwave therapy (ESWT) is a non-invasive and non-painful therapy that uses the application of shockwaves from outside the body in the form of acoustic waves. Most clinicians have heard of ESWT in the setting of lithotripsy as a treatment for renal calculi. ESWT was first used in vivo for the disintegration of renal and ureteric calculi in 1980, followed shortly by its use for gallbladder calculi in 1985. In 1988, these acoustic waves were tried successfully for the treatment of nonunion of long bone fractures in Germany.¹⁴ ESWT is now used in the treatment of a variety of orthopedic pathologies, including delayed healing of fractures, pseudoarthrosis, heel spurs, and pain relief in subjects with osteonecrosis of the hip. In a systematic review conducted by Willems et al, it was found that the average union rate after ESWT in delayed unions was 86%, in nonunions 73%, and in nonunions after surgery 81%.¹⁵  ESWT is an ongoing source of investigation for the management of pathologies of skin, bone, nerve, and muscle.

During ESWT, shockwaves are usually electro-hydraulically induced biphasic transient pressure changes characterized by a fast positive wave followed by a slower negative wave. The electrohydraulic method uses high-energy acoustic pressure waves that are nonthermal via an electric discharge inside a fluid. Once the acoustic energy reaches the tissue boundary, it is transformed into mechanical energy. It is thought that this is what stimulates the upregulation of important growth factors involved in wound healing.¹⁶ Today, ESWT is a valuable tool in the management of chronic wounds, difficult-to-treat wounds, diabetic foot ulcers, and burns. In the setting of wound healing, the application of ESWT is carried out utilizing proprietary forms of ESWT such as pulsed acoustic cellular expression (PACE), in which specially modulated shockwaves are delivered directly into the wound bed and periwound and penetrate deep inside the tissue to promote wound healing and closure (Sanuwave n.d.).¹⁷

At a molecular level, ESWT has been shown to increase the expression of proangiogenic genes such as eNOS, VEGF, CXCL5, CCL2, CCR2, and proangiogenic proteins VEGF and vWF.¹⁸ A study by Ching-Jen Wang et al suggests that ESWT may have the ability to improve wound healing by increasing angiogenesis and cell activity in the wound environment, normalizing the rate of apoptosis, and making positive changes to growth factor and cytokine levels.¹³ ESWT has been shown to reduce wound dimensions and healing time in chronic wounds and should be considered as a valuable tool for wound bed preparation in selected wounds.^19,20,21

Purpose

The aim of this small case series was to evaluate the effect of ESWT on complex chronic wounds in subjects with multiple comorbidities in a medically underserved outpatient wound care clinic setting.

Subjects

Subjects with chronic wounds presented to the outpatient wound care clinic in a medically underserved urban setting.  Only subjects who had wounds that were refractory to the standard of care for more than 30 days were considered for ESWT. ESWT has been approved for the treatment of chronic diabetic foot ulcers. In the case of subjects with non-diabetic wounds, off-label use was disclosed to the subjects, and patient consent was obtained noting this.

Initially, a total of 13 subjects were selected to undergo ESWT, and data for 18 wounds was gathered as part of normal wound care protocol. This discrepancy between subjects and wounds was due to cases of multiple wounds being treated on a single patient. After retrospectively analyzing the data previously collected, 3 subjects total and a total of 5 wounds were excluded, resulting in a total of 10 subjects and 13 wounds included in this retrospective case series.

The inclusion criteria for this study were patients over the age of 18 with one or more chronic wounds refractory to standard of care for more than 30 days. Exclusion criteria included patients who failed to follow up for the complete duration of treatment for any reason (eg, noncompliance, readmission).

Participants were divided into two groups. The first group was the “standard cohort,” which consisted of all patients and wounds. The second group was the “diabetic cohort,” which consisted of only those wounds that were related to diabetes. The standard cohort consisted of a total of 10 patients between the ages of 52 and 74 years; the diabetic cohort included 9 patients between the ages of 57 and 74 years.

All patients selected for ESWT  as a treatment modality had baseline wound measurements taken (length, width, depth, volume, and area in cm). Pictures of the wounds were also taken at the time of the initial visit. These patients received weekly treatments of ESWT for a maximum recorded duration of 12 weeks. Prior to each weekly treatment, wound measurements were reassessed and recorded. Wound beds were cleansed according to the standard of care. Pictures of the wounds were taken every 2 weeks.

Using patient record numbers, deidentified data was retrospectively extracted from these patients’ charts. The following information was obtained and recorded: age and sex of the patient, location of the wound, wound type, wound thickness/stage, involvement of tendon and/or bone, the onset of the wound, wound history, comorbidities, off-loading/pressure relief methods, hemoglobin A1C level when relevant, current wound care measurements, any record of vascular assessments or interventions, concurrent hyperbaric oxygenation therapy, and if any human cellular tissue-based products were applied. The authors also reviewed treatment dates with measurements, ESWT settings including number of shocks delivered, amount and type of exudate of the wound, percentage of wound granulated, percentage of slough/eschar on the wound, debridement done during visit, and pain scale.

For the purpose of retrospective analysis, only the following variables were used: sex, age, initial wound volume, number of weeks of ESWT, and involvement of tendon and/or bone.

Regarding the exclusion of subjects from this study, a total of 3 subjects and a total of 5 wounds were excluded. One of the subjects who was excluded had 2 wounds and was excluded since they received only 2 treatments and discontinued medical treatment on their end. Another patient was excluded due to only receiving one ESWT session secondary to being admitted to the hospital for management of other medical issues and, in fact, healed while admitted.

This study was deemed to be exempt from IRB review by the Baptist Health Research Department due to its retrospective nature and the deidentified data that was collected.

Application of ESWT

ESWT in the form of focused electro-hydraulic acoustic pulses was applied using the dermaPACE system (Sanuwave). This system is an advanced wound care device that utilizes PACE technology, a proprietary form of focused, extracorporeal shockwaves.²²

The device itself consists of a probe or applicator that is attached to a control console via a 6-foot-long cable. There is also a footswitch that controls the delivery of the acoustic pulses. Both the applicator and the probe are meant to be reusable; sterile probe sleeves are used to cover the applicator during use with each patient to prevent cross-contamination. The device probe is like that of an ultrasound probe in that ultrasound gel is utilized to properly transfer acoustical waves to the area being treated.

The manufacturer recommends escalating a specific number of shockwave pulses per treatment based on wound area, with an additional 2 cm peri-wound area to be included. Dosing recommendations are shown in Figure 2.

The ESWT treatment in this study consisted of a selection of an appropriate number of shockwaves based on the measurements taken during that specific visit. The patients were informed about the noninvasive nature of the procedure, including the fact that no pain is typically associated with the treatment. Therefore, no analgesia was applied prior to their treatment and all patients reported that they tolerated ESWT well. Patients were also informed that the procedure would take somewhere between 2 and 8 minutes, depending on their recommended dosage and wound area to be treated, and that the acoustic waves associated with the device would make a loud noise for which the patient, clinician, and personnel were all  provided appropriate hearing protection. Anticipatory guidance regarding the shockwave sensation to the area treated was also given. Patients were given the opportunity to clarify any questions prior to initiation of each ESWT session.

Prior to starting the treatment, all dressings and products on the wounds were removed. The wounds were cleansed with normal saline, as per clinic protocol, and evaluated for any signs of infection. Routine measurements and photographs were taken.

Once the appropriate dosage was selected based on the wound measurements, the applicator was shaken 2 to 3 times; as per the manual, this helps to ensure that there is an even suspension of solids in the liquid-filled probe head.  Ultrasound gel was applied both to the tip of the applicator and the area to be treated. The sterile probe sleeve was then applied to the applicator. The probe was then placed firmly on the area to be treated, and the applicator was moved evenly and gently throughout the area in the pattern recommended by the manufacturer (Figure 3). Care was taken to create an angle that was no greater than 30° throughout the application process (Figure 4). The foot switch was utilized to deliver these shocks.

Statistical Analysis

A retrospective analysis of the data set was conducted in 2 separate phases. The first phase consisted of an analysis of all available data, including both diabetic and non-diabetic wounds (“standard cohort”). The second phase consisted of analyzing data pertaining to only the diabetic wounds in the data set (“diabetic cohort”).  

To determine the appropriate sample size for the study, the authors conducted a power analysis using the software G*Power (version 3.1.9.6). The analysis showed that a sample size of 67 was needed. For the Pearson correlation analysis, an a priori power analysis was conducted based on a moderate effect size of 0.3, a significance level of 0.05, and a power of 0.8.

A Pearson correlation test was conducted between the total number of ESWT weeks needed for complete wound closure and the initial wound volume for both the standard and diabetic cohorts.

The authors conducted a linear regression analysis using data from both the standard and diabetic cohorts to investigate whether there was a correlation between tendon/bone involvement and the total number of ESWT weeks required to achieve complete wound closure.

Statistical software IBM SPSS Statistics (version 27) was utilized in the analysis of the data set.

For statistical analysis, N refers to the number of wounds and not the number of participants, as there were participants with multiple wounds.

According to the power analysis conducted, the required sample size was 67. The actual sample size for this study was 13.

Data on a total of 10 subjects and 13 wounds were analyzed. Out of these wounds, 12 of them healed completely by or before week 12 of ESWT. The remaining “improved wound” demonstrated significant wound dimension reduction during the first 12 weeks of treatment and was the case of a lower extremity wound that completed 17 ESWT treatments prior to stalling. The decision was made to discontinue treatment and apply a short series of piscine xenografts. After only 3 applications of these xenografts the wound healed, which strongly suggests that the ESWT performed well at preparing the wound bed for further treatment with an advanced modality.
 

Tendon and bone involvement

The presence or absence of tendon and/or bone involvement was recorded for each individual wound. In the standard cohort, 53.8% (n=7) of the subjects had tendon/bone involvement while 46.2% (n=6) did not have tendon/bone involvement. In the diabetic cohort, 7 subjects had tendon/bone involvement and 5 did not have tendon/bone involvement.
 

Number of ESWT weeks needed for complete wound closure

For the standard cohort, the minimum number of weeks of ESWT required for complete wound closure was 3 weeks, while the maximum was 11 weeks. The mean number of treatment weeks was 6.77, with a standard deviation of 2.803.

In the diabetic cohort, the minimum number of weeks of ESWT for complete wound closure was also 3 weeks and the maximum was 11 weeks. The mean number of treatment weeks was 7, with a standard deviation of 2.796.
 

Initial wound volume

For the standard cohort, the initial wound volume ranged from a minimum of 0.018 cm³ to a maximum of 13 cm³, with an average of 1.64462 cm³ and a standard deviation of 3.508958 (Table 1). In the diabetic cohort, the initial wound volume ranged from a minimum of 0.018 cm³ to a maximum of 2.240 cm³, with an average of 0.69833 cm³ and a standard deviation of 0.856168 (Table 2).
 

Statistical analysis for standard cohort

A Pearson correlation test was conducted between the total number of ESWT weeks needed for complete wound closure and the initial wound volume (Table 3). The result of this correlation was nonsignificant (r = -.225, P =.459).

To determine if initial wound volume was a predictor of the total number of ESWT weeks necessary for complete wound closure, a linear regression analysis was conducted (Table 4). Initial wound volume explained about 5% of the variance in total ESWT weeks, R²= .051. Per the Omnibus test, the model did not demonstrate goodness of fit (F (1,11) =.589, P =.459). The coefficient for wound size was -1.357, meaning that a 1 unit increase in wound volume results in a 1.357 reduction in the number of weeks of ESWT until complete wound closure. 

To determine if there was a point-biserial correlation between tendon/bone involvement and the total number of ESWT weeks needed to complete wound closure, a Pearson correlation test was conducted (Table 5). The result was nonsignificant (r = -.251, P =.408).

Statistical analysis for diabetic cohort

A Pearson correlation test was conducted between the total number of ESWT weeks needed for complete wound closure and the initial wound volume (Table 6). The result of this correlation was nonsignificant (r = .283, P =.373).

To determine if initial wound volume was a predictor of total number of ESWT weeks necessary for complete wound closure, a linear regression analysis was conducted (Table 7). Initial wound volume explained about 20% of the variance in total ESWT weeks (R²= .203). Per the Omnibus test, the model did not demonstrate goodness of fit (F (2,9) = 1.14, P =.361). The coefficient for initial wound volume was .798, meaning that a unit 1 increase in wound size wound resulted in a .798 increase in number of ESWT weeks needed for complete wound closure.

To determine if there was a correlation between tendon/bone involvement and the total number of ESWT weeks necessary for complete wound closure, a Pearson correlation analysis was conducted (Table 8).  There was no significant correlation (r = -.379, P =.225).

Case Reports

Case 1

A 54-year-old male presented to the outpatient wound care clinic for evaluation of a nonhealing, Wagner grade 3 ulcer. The patient had previously undergone surgical excision, debridement, and secondary closure. He had subsequently developed osteomyelitis of the first metatarsal head. Soon after that, the patient experienced surgical wound dehiscence followed by failure to heal with standard wound management. This patient was treated with 6 weeks of ESWT in the outpatient wound care clinic and achieved complete closure within this time frame (Figure 5).

Case 2

A 56-year-old male with a history of severe peripheral vascular disease presented to the wound care clinic with flap necrosis post-partial amputation of the first right metatarsal. The patient had previously undergone 2 angioplasties to address the vascular issues. There was no underlying osteomyelitis. This patient’s wound achieved complete wound closure after 10 weeks of ESWT and standard wound care (Figure 6).

Case 3

A 63-year-old male with a history of severe peripheral vascular disease presented to the outpatient wound care clinic with a nonhealing wound on the lateral aspect of the right foot. This patient had previously gone through 2 angioplasties and a bypass surgery to address his peripheral vascular status. There was a noticeable improvement as early as week 3 of ESWT. After 8 weeks of ESWT, there was a significant reduction in wound size and evidence of epithelization (Figure 7).

This small case series did not show statistical significance, but findings of improvement of chronic wounds in patients with tendon and bone exposure with ESWT may need to be studied further. ESWT is not approved by FDA for wounds with tendon and bone exposure at the present time, as current guiding clinical studies were not done in patients with wounds with tendon and bone exposure.^19-21 The small cohort of patients required a mean of 6.77 ESWT treatments (one per week), with a standard deviation of 2.803, for healing complex wounds. In the present small case series, ESWT was used once a week, while in the phase III trial it was applied 4 times over a 2-week period and up to 8 times over 12-week period.

This small case series showed a significant reduction in wound measurements and improvement in wound healing outcomes after ESWT and standard wound care, consistent with published research with ESWT.^19-21 ESWT could be a valuable tool in wound bed preparation for chronic wounds. Further research and studies with a larger sample size are needed to validate these findings. Despite the lack of statistical significance within the present small case series, it seemed that the patients with tendon/bone involvement healed faster after ESWT than those without tendon/bone involvement. This concept is thought-provoking and deserves further investigation.

There are several limitations to this study. The first and most noticeable is the small sample size. The P values and correlations provided are not representative of the population. As per the power analysis, the required sample size of was 67; this study’s sample size of 10 was well below that requirement. Second, the authors are unable to account for confounding variables such as smoking, comorbidities, medications, etc. The data used in this case series data that was collected in part by a different researcher. The electronic health records system was exchanged during the middle of the study time frame, resulting in the loss of some data.

Real-world clinical data is invaluable to clinical practice. The goal of this study was not only to relate the effect of ESWT on wound dimensions and healing time but also to encourage wound care clinicians around the globe to participate in small-scale studies within their own practices and even to participate in larger collaborations with other clinicians around the country to come to solid conclusions about new modalities in wound healing.

ESWT has been shown to be beneficial in diabetic foot ulcers in several studies.^22,23,24 The current study was done to better understand ESWT’s role as an adjunct tool for wound bed preparation in the setting of difficult-to-heal wounds. This small case series did not show statistical significance, but findings of improvement of chronic wounds in patients with tendon and bone exposure with ESWT may need to be studied further. The small cohort of patients required a mean of 6.77 ESWT treatments (one per week), with a standard deviation of 2.803, for healing complex wounds. ESWT has the potential to reduce the cost and time associated with wound healing. It is a painless, noninvasive technology that is easy to use and poses little risk to patients. Its application is quick and can be done in the office or outpatient setting.

Acknowledgments: We would like to acknowledge Dr. David Fike for his time and patience in the setting of SPSS software education and statistical analysis. We would like to thank Dr. Gabriela Gutierrez-Zamora Velasco for her support and guidance on statistical work.

Authors: Denise Nemeth, MPAS, CWS; and Jayesh Shah, MD, MHA

Affiliation: University of the Incarnate Word School of Osteopathic Medicine

Correspondence: Denise Nemeth, MPAS, CWS, 7615 Kennedy Hill Dr, San Antonio, TX 78235; nemeth@student.uiwtx.edu

Disclosure: Dr. Shah is a shareholder in Sanuwave.

1. Sen CK, Gordillo GM, Roy S, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763-771. doi:10.1111/j.1524-475X.2009.00543.x

2. Cassidy B, Reeves ND, Pappachan JM, et al. The DFUC 2020 dataset: analysis towards diabetic foot ulcer detection. touchREV Endocrinol. 2021;17(1):5-11. doi:10.17925/EE.2021.17.1.5

3. Nussbaum SR, Carter MJ, Fife CE, et al. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds. Value Health. 2018;21(1):27-32. doi:S1098-3015(17)30329-7

4. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle). 2015;4(9):560-582. doi:10.1089/wound.2015.0635

5. Sibbald RG, elliott JA, persaud-jaimangal R, et al. wound bed preparation 2021. wound healing southern africa. 2021;14(2):52-62. accessed january 18, 2022. https://Search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=154447848&site=ehost-live. .

6. Sibbald RG, Elliott JA, Persaud-Jaimangal R, et al. Wound bed preparation 2021. Adv Skin Wound Care. 2021;34(4):183-195. doi:10.1097/01.ASW.0000733724.87630.d6

7. Hess CT, Kirsner RS. Orchestrating wound healing: assessing and preparing the wound bed. Adv Skin Wound Care. 2003;16(5):246-9. doi:10.1097/00129334-200309000-00015

8. Shah JB. Correction of hypoxia, a critical element for wound bed preparation guidelines: TIMEO2 principle of wound bed preparation. 2011;3(2):26-32. doi:10.1016/j.jcws.2011.09.001

9. Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Front.Biosci. 2004;9:283-289. doi:10.2741/1184

10. Sun BK, Siprashvili Z, Khavari PA. Advances in skin grafting and treatment of cutaneous wounds. Science. 2014;346(6212):941-945. doi:10.1126/science.1253836

11. Bowers S, Franco E. Chronic wounds: evaluation and management. Am Fam Physician. 2020;101(3):159-166.

12. Powers JG, Higham C, Broussard K, Phillips TJ. Wound healing and treating wounds: xhronic wound care and management. J Am Acad Dermatol. 2016;74(4):607-625. doi:10.1016/j.jaad.2015.08.070

13. Wang CJ, Ko JY, Kuo YR, Yang YJ. Molecular changes in diabetic foot ulcers. Diabetes Res Clin Pract. 2011;94(1):105-110. doi:10.1016/j.diabres.2011.06.016

14. Raveendran K. ESWT is a force to be reckoned with. Int J Surg. 2015;24(PB):113-114. doi:10.1016/j.ijsu.2015.12.060

15. Willems A, van der Jagt OP, Meuffels DE. Extracorporeal shock wave treatment for delayed union and nonunion fractures: a systematic review. J Orthop Trauma. 2019;33(2):97-103. doi:10.1097/BOT.0000000000001361

16. Calcagni M, Chen F, Högger DC, et al. Microvascular response to shock wave application in striated skin muscle. J Surg Res. 2011;171(1):347-354. doi:10.1016/j.jss.2009.12.011

17. The dermaPACE® system. Sanuwave. April 6, 2021. Retrieved February 10, 2022.  https://Www.sanuwave.com/our-technology/the-dermapace-system/

18. Krokowicz L, Cwykiel J, Klimczak A, Mielniczuk M, Siemionow M. Pulsed acoustic cellular treatment induces expression of proangiogenic factors and chemokines in muscle flaps. J Trauma. 2010;69(6):1448-1456. doi:10.1097/TA.0b013e3181ddd067

19. Snyder R, Galiano R, Mayer P, Rogers LC, Alvarez O, Sanuwave Trial Investigators. Diabetic foot ulcer treatment with focused shockwave therapy: two multicentre, prospective, controlled, double-blinded, randomised phase III clinical trials. J Wound Care. 2018;27(12):822-836. doi:10.12968/jowc.2018.27.12.822

20. Galiano R, Snyder R, Mayer P, Rogers LC, Alvarez O, Sanuwave Trial Investigators. Focused shockwave therapy in diabetic foot ulcers: secondary endpoints of two multicentre randomised controlled trials. J Wound Care. 2019;28(6):383-395. doi:10.12968/jowc.2019.28.6.383

21. Omar MTA, Alghadir A, Al-Wahhabi KK, Al-Askar AB. Efficacy of shock wave therapy on chronic diabetic foot ulcer: a single-blinded randomized controlled clinical trial. Diabetes Res Clin Pract. 2014;106(3):548-554. doi:10.1016/j.diabres.2014.09.024

22. Sanuwave. https://www.sanuwave.com/our-products/energy-systems/dermapace-system/