Low-Intensity Shock Wave Therapy for Fournier’s Gangrene
Low-intensity extracorporeal shock wave therapy in the postoperative management of Fournier’s gangrene – a case series of a new concept
Rassweiler JJ¹, Scheitlin, W², Agatep J³, Condero C³, Wolfgang Schaden⁴
- Chair of Urology and Andrology, Danube Private University, Krems, Austria
- Department of Urology, SLK Kliniken Heilbronn, Germany
- Department of Urology, East Avenue Medical Center, Manila, Philippines
- Ludwig Boltzmann Institute for Traumatology, Vienna, Austria.
OPEN ACCESS
PUBLISHED: 30 October 2024
CITATION: Rassweiler, JJ., et al., 2024. Low-intensity extracorporeal shock wave therapy in the postoperative management of Fournier’s gangrene – a case series of a new concept. Medical Research Archives, [online] 12(10). https://doi.org/10.18103/mra.v12i10.5801
COPYRIGHT: © 2024 European Society of Medicine.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI https://doi.org/10.18103/mra.v12i10.5801
ISSN 2375-1924
ABSTRACT
Objective: Fournier’s gangrene is an aggressive frequently fatal polymicrobial soft tissue infection of perineum and external genitalia requiring immediate surgical therapy. Postoperative management includes reconstructive surgery and wound healing. We report on the use of low-intensity extracorporeal shock wave therapy (Li-ESWT) in the postoperative management of wound healing following Fournier’s gangrene.
Keywords: Fournier’s gangrene, low-intensity extracorporeal shock wave therapy, wound healing, postoperative management.
Introduction
Fournier’s gangrene is an aggressive and frequently fatal polymicrobial soft tissue infection of the perineum, peri-anal region, and external genitalia (Fig. 1a). It is an anatomical sub-category of necrotizing fasciitis with which it shares a common etiology and management pathway.¹ ² Typically, there is painful swelling of the scrotum or perineum with sepsis. Examination shows small necrotic areas of skin with surrounding erythema and oedema. Crepitus on palpation and a foul-smelling exudate occurs with more advanced disease.³
Risk factors include diabetes mellitus, malnutrition, immunotherapy, alcohol abuse, recent urethral or perineal surgery, and high body mass index.¹ ³ The degree of internal necrosis is usually vastly greater than suggested by external signs. It requires immediate radical surgery with complete removal of affected tissue (Fig. 1b).
Once the sepsis is under complete control and the wound is clean, postoperative management usually includes mesh-graft and skin-flaps.³ ⁴ Both can be associated with secondary wound healing problems mostly requiring secondary surgical procedure (Fig. 2a). Moreover, the cosmetic results of mesh-grafts are not convincing, because it is not replacing the previous skin; in case of large excision of scrotal skin, the wound can only be covered by cutaneous flaps.⁴ Other alternatives of postoperative wound management have been tested, such as hyperbaric oxygen therapy, application of honey, and vacuum-techniques.³ ⁵ ⁶ ⁷ However, a recent meta-analysis did not prove any benefit on wound-healing compared to classical wound dressing.⁷
Among the strategies for chronic wound treatment, extracorporeal shock wave therapy (ESWT) has shown promise. Initially used for treating renal and ureteral calculi as extracorporeal shock wave lithotripsy (ESWL),⁸ ⁹ ESWT’s success in urology prompted exploration in other areas, including wound healing.¹⁰ ¹¹ ¹² ¹³ Unlike the use of shock waves for stone fragmentation (ESWL), for treatment of soft-tissue usually only low energy density is required. Thus, low-intensity shock wave therapy (Li-ESWT) is defined a less than 35 mJ/mm² per impulse.¹⁴
The primary mechanism of action of Li-ESWT is based on the so-called mechano-transduction in the respective cell thereby improving tissue circulation by stimulating the production of energy-rich nitric oxide (NO), leading to reduced muscle rigidity and improved biomechanical functioning, enhancing mobility and self-perception.¹⁵ ¹⁶ ESWT can also activate key factors involved in connective tissue repair, such as fibroblasts which may increase proliferation and expression of essential factors like TGF-beta-1 and collagen types I and III.¹⁷ ²¹
Based on these promising results we started to use Li-ESWT in the postoperative management of Fournier’s gangrene. We reported already early case studies.²² ²³ In this article, we want to present our mid-term experience in two centers in Europe and Asia with special emphasis on the evaluation of wound-healing process and the possible positive impact of stem cell stimulation.
Material and Methods
PATIENTS:
This is a two-institutional pilot study of case series (SLK Kliniken Heilbronn, Germany, East Avenue Medical Center, Manila, Phillipines): From November 2021 to November 2022, eight men (age 27-68 years) were admitted with severe Fournier’s gangrene requiring complete excision of the scrotal and perineal skin (Fig. 1-4). They were all treated in the Intensive Care Unit (ICU) for 10-14 days (Table 1). Wound dressing was applied every other day.
TREATMENT GROUPS:
The data of all patients are summarized on Table 1.
Case Series 1:
Once granulation of the wound started, we usually closed the wound by use of skin flap from the surrounding area. This was performed in the first three patients. Unfortunately, all three showed incidence of secondary surgical procedure in the respective half of the wound in the follow-up (Fig. 1-4). Instead of a second surgical procedure we treated the patients by Li-ESWT.
Fig. 1: Li-ESWT for postoperative management of Fournier’s gangrene – stimulation of wound healing after failure of closure with skin flaps.
a) Initial presentation of patient with severe Fournier’s gangrene (acute necrotizing fasciitis) in the genital and perineal area.
b) Radical excision of the involved tissue finally resulting to a wound area of 74.9 cm².
c) Secondary healing after closure of the defect with skin flaps with an open wound area of 35.3 cm².
d) Closure of the wound 9 weeks (= 63 days) after Li-ESWT (2000 impulses, 3 Hz, 12 sessions) with a remaining wound area of 9.5 cm² corresponding to a re-epithelization speed of 0.41 cm²/d.
Fig. 2: Li-ESWT for secondary management of Fournier’s gangrene – stimulation of primary wound healing prior to application of mesh-graft.
a) Situation after radical excision of the involved tissue with an open wound area 81.7 cm².
b) Significant closure of the wound with granulating tissue of the left testis after 9 weeks (= 63 days) following Li-ESWT (2500 impulses, 4 Hz, 9 sessions) resulting in a remaining wound area of 40.8 cm². Thiscorresponds to a re-epithelization speed of 0.65 cm²/d.
c) Situation following placement of mesh-graft.
Table 1: Li-ESWT in the postoperative management of Fournier’s gangrene – Patients data and outcome
| Indication | N | Energy flux density (mJ/mm²) | Frequency (Hz) | Impulses per session | Sessions | Size of Lesion prior ESWT (cm²) | Size of Lesion after ESWT (cm²) | Time interval (d) | Re-epithelisation speed (Δ cm²/d) | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Case 1: Failure of primary skin flap | 3 | 0.25 | 3 | 2000 | 12–15 | 18.7 30.3 35.3 |
8.6 6.8 9.5 |
42 56 63 |
0.24 0.42 0.41 |
Complete healing of secondary skin defect No surgery required |
| Case 2: Reduction of wound surface prior to mesh graft | 2 | 0.25 | 3 | 2500 | 9 | 81.7 99.7 |
40.8 55.3 |
63 56 |
0.65 0.79 |
Significant reduction of wound surface Granulomatous tissue covering left testicle |
| Case 3: Restoration of resected tissue | 3 | 0.25 | 3–4 | 3000 | 6–18 | 99.0 55.9 84.3 |
0.0 0.0 0.0 |
150 120 150 |
0.66 0.47 0.56 |
Complete healing of wound with restoration of local tissue (penile skin, scrotal skin, Granulomatous tissue covering the wound |
Case Series 3:
Based on our good experiences with the case series 1 and 2, we treated further three patients with complete necrosis of the scrotal and penile skin requiring radical excision primarily with Li-ESWT according to the protocol (Fig. 3, Fig. 4). Obviously, there was not much tissue available for adequate plastic surgery of penile and scrotal skin.
TREATMENT PROTOCOL USING LOW-ENERGY SHOCK WAVE THERAPY:
All patients were treated with Li-ESWT using the electromagnetic device Duolith SD1 ultra (Storz-Medical, Taegerwilen, Switzerland). This device delivers focused shock waves to human tissue generated by an electromagnetic cylinder and focused by a paraboloid reflector. The -6dB lateral focal zone depends on the energy setting and was 4 mm resulting to a focus volume of 0.5 cm³. The positive shock wave pressure was 24 MPa at a energy density of 0.25 mJ/mm². The focal depth can be regulated by use of different coupling devices (i.e. stand-offs). We used the stand-off which we use for treatment of erectile dysfunction and Peyronie’s disease, which has a depth of 5–8 mm. We applied three times weekly (Monday, Wednesday, Friday) 2000–3000 shock waves at 3–4 Hz with an energy flux density of 0.25 mJ/mm² distributed equally on the rims of the wound (Fig. 3a; Table 1). Low-intensity shock wave therapy is defined to use shock waves at an energy flux density of lower than 35 mJ/mm² per impulse.¹⁴ The treatment was well tolerated with no need of anesthesia or analgesia.
PLANIMETRIC ASSESSMENT OF RE-EPITHELIZATION
Based on the existing picture taken at several times before and after Li-ESWT we performed planimetric assessment of the wound area at the respective time. This allowed us to calculate the re-epithelization speed (cm²/d) = Wound area prior ESWT – Wound area at end of treatment / days of treatment and observation (Table 1). These results were compared with experimental and clinical data in the literature.
Results
Case Series 1:
In three cases, we treated secondary healing of skin-flaps with an open wound area ranging from 18.7 to 35.3 cm². All wounds showed a dramatic progress in the healing process with almost complete healing by the local skin (open wound surface 6.8 to 9.5 cm² after 7–9 weeks (Fig. 1) corresponding to a re-epithelization speed of 0.24 to 0.42 cm²/d. No further surgical procedure was required.
Case Series 2:
Both cases (initial wound area 81.7 and 99.7 cm²) responded very well on the Li-ESWT-treatment starting with intensive granulation tissue covering the wound after 8–9 weeks with significant reduction of the surface from the periphery by the local skin (wound area 40.8 and 55.3 cm²) corresponding to a re-epithelization speed of 0.65 and 0.79 cm²/d. At that stage we placed a mesh-graft, which healed in without any further complications (Fig. 2c) and was much smaller than the initial size of the wound.
Case Series 3:
Finally, we were able to close all three open wounds (initial wound area 55.9 to 99.0 cm²) completely only by use of Li-ESWT. This wound repair did not occur just as fibrous tissue. It started with decrease of the wound area from the rims and formation of granulation tissue covering the wound (Fig. 4b) respectively cleaning of the wound (Fig. 3b). Further on, the excised scrotal skin was completely restored as scrotal tissue and the penile skin accordingly providing an optimal cosmetic result after 5 and 9 months (Fig. 4c, 4d). The patient in Manila received only 6 sessions of Li-ESWT leading basically to the same result (Fig. 3c). This corresponded to a re-epithelization speed ranging from 0.47 to 0.66 cm²/d.
In summary, the observed re-epithelization speed varied between 0.24 and 0.79 cm²/d depending mostly on the size of the defect when starting the treatment. (Table 1).
Fig. 3: Li-ESWT for secondary management of Fournier’s gangrene – Technique of Li-ESWT and follow-up of patient treated exclusively by Li-ESWT.
a) Application of 2000–3000 Shock Waves on the rim of the wound using the handpiece of the Duolith SD (Storz-Medical, Taegerwilen, Switzerland) with 0.25 mJ/mm² at 3–4 Hz three days weekly. The wound area was 99.0 cm².
b) Significant improvement of the wound healing after 6 weeks, Complete cleaning of the wound.
c) Complete closure of the wound 5 months (= 150 days) corresponding to a re-epithelization speed of 0.82 cm²/d after Li-ESWT (3000 impulses, 4 Hz, 6 sessions).
Fig. 4:
Li-ESWT for secondary management of Fournier’s gangrene – Li-ESWT as single management of wound healing following radical excision of infected tissue after Fournier’s gangrene with long-term result.
a) Radical excision of the involved tissue with an open area of 84.3 cm².
b) Intermediate phase after 6 weeks with closure of the wound by granular tissue
c) Complete restoration of the wound by scrotal and penile tissue following 4 months (=120 days) after Li-ESWT (3000 impulses, 4 Hz, 18 sessions) corresponding to a re-epithelization speed of 0.70 cm²/d. No surgery required at all.
d) Final cosmetic result after 9 months with almost normal appearance of scrotal and penile skin.
Discussion
There have been several attempts to improve the wound healing after complete surgical excision in case of Fournier’s gangrene:
A more recent comparative case series suggested benefit for use of hyperbaric oxygen therapy in sixteen patients compared to twelve cases without use of such therapy in terms of reduced mortality and fewer debridement.³
A low-quality RCT with 30 patients found that use of honey-soaked dressings resulted in a shorter hospital stay (28 vs. 32 days) than dressing soaked with Edinburgh solution of lime.⁷ No evidence of benefit for use of negative-pressure (vacuum) wound therapy in Fournier’s gangrene was found.
Already in 1990, Haupt and Chavapil examined the effect of low-energy shock waves in an experimental lithotripter and concluded that low energy levels (14 vs. 18 kV) coincided with an increased vascularization.¹¹ More than ten years later, in 2007 Schaden et al. initiated the first clinical trials on Li-ESWT for wound healing.¹²
In the meantime, several experimental and clinical studies documented an accelerated tissue repair and regeneration in various wounds following Li-ESWT.¹⁶ ²¹ However, the complete biomolecular mechanism by which this treatment modality exerts its therapeutic effects remains still unclear. Shock waves’ primary physical effect is believed to be via mechanotransduction leading to cellular activation and downstream signaling. It has become evident, that only low-energy (energy flux density < 35 mJ/mm²) is required.¹⁶ Experimentally, ESWT’s effects on osseous, connective tissue and wound healing were examined in various mechanisms of action which have been initial neovascularization with ensuing durable and functional angiogenesis. Furthermore, recruitment of stem cells, stimulated cell proliferation and differentiation, and anti-inflammatory and antimicrobial effects as well as suppression of nociception are considered important facets of the biological responses to therapeutic shock waves.¹⁷ ²¹ ²³
Early studies of the group of Mittermayr and Schaden tried to evaluate the effect of Li-ESWT on “standardized” wounds using the donor situs of skin-grafts.¹⁵ They found a “faster complete epithelialization” with ESWT compared to the placebo group. The same was observed in clinical studies treating diabetic foot ulcers.²⁴ However, until now no re-epithelization speed has been calculated in the literature. There are several experimental trials dealing with wound healing and re-epithelization, but none of the studies used ESWT as a treatment option.⁶ ²⁶ ²⁸ We were able to calculate the re-epithelization speed based on the data provided by the articles (Table 2). However, such data cannot be compared with clinical data.
Table 2: Re-epithelization effects and wound-healing rates in animal studies
| Author | Model | Lesion | Treatment groups | Wound area at day 0 (cm²) | Wound area at final evaluation (cm²) | Time interval (d) | Re-epithelization speed (Δ cm²/d) | Comment |
|---|---|---|---|---|---|---|---|---|
| Negm et al.²⁶ 2022 | Wistar Rats | Excisional full thickness skin wound | Control Betadine-cream Rhofolinlin rich fraction-gel |
1.08 1.2 1.1 |
0.3 0.01 0 |
10 10 10 |
0.08 0.12 0.11 |
Treatment groups with inflammatory activity |
| Rowland et al.²⁷ 2022 | Wild type mouse | Skin punch biopsy | Male Female |
0.36 0.36 |
0.22 0.14 |
5 5 |
0.03 0.04 |
Females heal faster |
| Munoz et al.⁶ 2023 | Guinea pig | Circular burn injury | Control Honey-impregnated gauze |
0.78 0.78 |
n.a. n.a. |
n.a. n.a. |
n.a. n.a. |
Use of re-epithelization score |
| Le Kuiai et al.²⁸ 2018 | Diabetic mice Normal mice |
Circular punch | Control SJHY-formula Control SJHY-formula |
0.28 0.28 0.28 0.28 |
0.09 0.06 0.03 0.02 |
10 10 10 10 |
0.019 0.022 0.025 0.026 |
SJHY-Formula works only in diabetic mice |
Table 3: Comparison of Re-epithelization effects and wound-healing rates in clinical studies
| Author | Lesion | Treatment groups | Wound area at day 0 (cm²) | Wound area at day 7 (cm²) | Difference of Wound area (cm²) | Re-epithelization speed (Δ cm²/d) | Comment |
|---|---|---|---|---|---|---|---|
| Ottomann et al.²⁴ 2010 | Skin graft donor site of trauma patients | Defocused shock wave therapy 0.1 mJ/mm² DermaGold, MTS | n.a. | n.a. | n.a. | n.a. | Significant faster healing of the donor site 13.9 versus 16.7 d |
| Dymarek et al.²⁹ 2024 | Pressure ulcers Grade II and III | Radial ESWT (2 sessions) | 13.5 | 7.3 | 6.2 | 0.9 | Major skin cells, Keratinocytes, Fibroblasts are mechan |
There are only two recent clinical studies: Ottomann et al.²⁴ presented a randomized trial including 28 patients with acute traumatic wounds and burns requiring skin grafting of which 13 patients received standard topical the to graft donor sites with and 15 without defocused extracorporeal shock wave therapy (ESWT, 100 impulses/cm² at 0.1 mJ/mm²). They were able to show, that with a single treatment of ESWT, the donor site healed significantly faster (13.9 vs. 16.7 d). However, there are no data on the size of the wounds. Dymarek et al., presents data concerning re-epithelization following ESWT for pressure ulcers.²⁹ However, the interval between the second ESWT-session and evaluation was only seven days resulting to a decrease of the wound area from 13.5 to 7.2 cm² corresponding to a re-epithelization speed of 0.9 cm²/d. We observed a re-epithelization speed of maximal 0.79 cm²/d. Obviously, further studies are necessary to determine the base-lines for the re-epithelization speed as an instrument to compare different approaches on wound healing.
Even, if still only based on case studies, our experiences with complete restoration of different types of skin (i.e. perineal, penile, scrotal) following extensive tissue resection due to Fournier’s gangrene suggests, that the underlying mechanism for this is related to a stimulation of stem cells. Unlike the formation of superficial scar-like repair, when using skin grafts.⁴ Stem cell formation induced by shock waves has been already shown experimentally in different animal models, such as pelvic floor trauma or erectile dysfunction.³⁰ ³² A recent review article describes also possible clinical indications, such as cardiomyopathy. However, the authors did not mention skin repair in their article. In our opinion, the skin offers the unique opportunity to watch the progress of healing and tissue reastuaration as a model for the new concept of regenerative medicine.
However, further studies are necessary to confirm these anecdotal observations. Due to the low incidence of Fournier’s gangrene further multicenter studies should be initiated. Like in other indications of wound healing, these studies have to focus on treatment parameters (ie. number of impulses, energy flux density, number of sessions), but also on comparison of Li-ESWT with existing therapeutic modalities. Herein, the calculation of re-epithelization speed may become a crucial instrument.
Conclusions
The positive effect of Li-ESWT in the postoperative management of Fournier’s gangrene seems to be evident and could be reproduced in two continents. There are no negative side effects. Based on the obvious findings of complete restoration of different kinds of skin (i.e. perineal, penile, and scrotal) the underlying mechanism might be stem cell stimulation by mechano-transduction induced by low-intensity shock wave therapy. Nevertheless, further studies are necessary to confirm our casuistic findings and to determine the optimal treatment parameters of this rare disease. Here the re-epithelization speed may become an important parameter.
Conflict of Interest:
None
Acknowledgements:
None
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