Extracorporeal shockwave therapy for the treatment of chronic diabetic foot ulcers: a clinical perspective.

Kenneth Craig

Director – Kompass Centre for Shockwave Therapy and Research, Auckland.

Introduction

Amputations are the consequence of chronic unresponsive diabetic foot ulcers due to small vessel occlusions and the persistent limb ischemia, compounded with neuropathy and infection.1,7,14,15

Despite the available guidelines of of this discipline, the management and treatment of diabetic ulcers remain highly challenging and success is somewhat limited. Extracorporeal shockwave therapy

(ESWT) has been used for the treatment of chronic diabetic and shows promise.

Aim

To highlight ESWT as a treatment option and encourage the initiation of a local trial to further assess its efficacy for the treatment of chronic and complicated diabetic ulcers.

Discussion

The cause of diabetic ulcers are multifactorial and its management requires a multidisciplinary approach with the primary goal being the control of blood sugar levels and to avoid the associated

complications. However, the complex and recurrent refectory chronic foot ulcer that responds inconsistently to various surgical and non-surgical treatments may inevitably lead to amputations.

Therefore chronic diabetic foot ulcers remains as a complex and challenging medical entity.

Although the exact mechanism of ESWT is yet to be fully elucidated, research have demonstrated that a dose dependant ESWT stimulus triggers a favorable neurobiocellular and chemical process

that regulates regional hemodynamics, inflammation, neuronal signaling, growth factor proliferation,6,7,10,11,12,13,14,15 while having antibacterial properties.4

Investigations conducted on both acute and chronic soft tissue wounds, and diabetic ulcers by Mittermayr et, al. (2011), Moretti et, al. (2009), Saganni et, al. (2008), Wang et, al. (2008) and Schaden

et, al. (2007) all demonstrated ESWT to be and effective and viable treatment option when dealing with complex and resistant wounds and ulcers. A study conducted by Wang and colleagues (2011)

found ESWT to be more effective compared to hyperbaric oxygen therapy (HBOT) for the treatment of chronic diabetic ulcers. ESWT treated ulcers demonstrated significant improvements in blood flow

perfusion rates and cellular activity resulting in better healing compare dto HBOT treated ulcers.14,15

Conclusion

ESWT offers a non-invasive, minimal risk and readily applicable treatment modality which accelerates tissue repair and provides an effective treatment response. Its favorable risk-benefit ration and

proposed mechanism of action such as the stimulation of angiogenesis and proliferation of various progenitor factors such as vascular endothelial growth factor (VEGF) 2, 5,6,7,9,10,11,12,13,14,15 suggest that

its is a viable treatment option for chronic diabetic ulcers.

Reference

1. Boulton A. Medical Treatment of Symptomatic Diabetic Neuropathy. Immunology, Endocrinology & Metabolic Agents in Medicinal Chemistry. 2007; 7, 79 – 86.

2. Carmeliet P & Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature. 2005; 436(7048): 193 – 200.

3. Gale, E. A. M. Glucose control in the UKPDS: what did we learn? Diabetic Medicine. 2008; 25(S2) 9 -12.

4. Gerdesmeyer L, von Eiff C, Horn C, et, al. Antibacterial Effects Of Extracorporeal Shock Waves. Ultrasound in Med. & Biol. 2005; 31(1): 115 – 119.

5. Lopes PFR, Lisboa BCG, Frattini F, Almeida FM, et. al, Enhamcement of sciatic nerve regenaration after vascular endothelial growth factor (VEGF) gene therapy. Neuropathology and Appliced Neurobiology. 2011; 37: 600 – 612.

6. Mittermayr R, Hartinger J, Antonic V, et al. Extracorporeal Shock Wave Therapy (ESWT) Minimizes Ischemic Tissue Necrosis Irrespective of Application Time and Promotes Tissue Revascularization by Stimulating Angiogenesis. Ann Surg 2011;253:1024–1032.

7. Moretti B, Notarnicola A, Maggio G, Moretti L, Pascone M et, al. The management of neuropathic ulcers of the foot in diabetes by shock wave therapy. BMC Musculoskeletal Disorders. 2009; 10:54 doi:10.1186/1471 – 2474/10/54.

8. Nortanicola A, Morreti L, Tafuri S el al. Shockwave therapy in the management of Complex Regional Pain Syndrome of the femoral condyle of the knee. Ultrasound Med Biol. 2010; 36(6):874-9.

9. Rosenstein JM & Krum JM. New roles for VEGF in nervous tissue – beyond blood vessels. 2004;187: 246 – 253.

10. Saginni R, Figus A, Troccola A et al. EXTRACORPOREAL SHOCK WAVE THERAPY FOR MANAGEMENT OF CHRONIC ULCERS IN THE LOWER EXTREMITIES. Ultrasound in Med. & Biol. 2008; 34( 8):1261–1271.

11. Schaden W, Thiele R, Kölpl C, Pusch M, Nissan A, et, al. Shock wave Therapy for Acute and Chronic Soft Tissue Wounds: A Feasibility Study. Jour. Surg Res. 2007; 143(1) 1 – 12.

12. Vardi Y, Appel B, Jacob G, Massarwi O & Gruenwald I. Can low-intensity Extracorporeal Shockwave Therapy Improve Erectile Function? A 6-Month Follow-up Pilot Study in Patients with Organic Erectile Dysfunction. European Urology.2010; 58: 243 – 248.

13. Vasyuk Y, Hadgegova A, Shkolnik E, et al. Initial Clinical Experience With Extracorporeal Shock Wave Therapy in Treatment of Ischemic Heart Failure. Congestive Heart Failure. 2010;16(5) 226 – 230.

14. Wang C-J, Kuo Y-R, Wu R-W, et al. Extracorporeal Shockwave Treatment for Chronic Diabetic Foot Ulcers. Journal of Surgical Research. 2008 May;152 (1)

15. Wang C-J, Wu R-W & Yang Y-J. Treatment of diabetic foot ulcers: A comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy. Diabetes Research and Clinical Practice. 2011; 92(2): 187 – 193.

Presented at the Annual Scientific Meeting of the New Zealand Society for the Study of Diabetes, Auckland 2012.

Figure 1. A. Pre-ESWT image: 57yr. Male patient with a chronic arterial pressure ulcer (>1yr duration), resistant to various topical treatments and dressings. 1st ESWT comprised of 800 impulses conducted at 100 impulses / mm² with and energy flux density level (EFDL) of 0.1mj /

mm². B. Image of lesion 2 weeks post ESWT and prior to 2nd administration of ESWT. 2nd ESWT comprised of 400 impulses conducted at 100 impulses / 1mm² at an EFDL of 0.1mj / mm². C. Soft tissue appearance at 4 weeks. No further ESWT was conducted. D. Complete

healing with and improved appearance of surrounding tissue at 6 weeks post ESWT.

*Treatment included debridement and moist dressing . A total of 208 patients were enrolled in this study with 156 (75%) patients achieving 100% re-epithelialization within a 44day period devoid of adverse reactions or complications TO ESWT. An electro-hydraulic device. Images

from Schaden et al 2007.

Figure 2. 53yr Female pre-ESWT (Left). Three (3) ESWT was administered at 72hr intervals. 100 impulses / 1mm² at an

EFDL of 0.04 mj / mm². Lesion at 52days post ESWT (Right).

* Treatment included debridement and sliver dressing. ESWT was administered using an electromagnetic device, Images

from Moretti et, al. 2009.

Figure 3. A plastic drape is place of the region of interest and ultrasound gel is used as the transmission medium for

the shockwave.

Before Treatment After Treatment Before Treatment After Treatment

ESWT GROUP n=44

HBOT GROUP n=40

ESWT GROUP n=44

HBOT GROUP n=40

Figure 4. Blood perfusion scan of the lower limb before and after treatments. ESWT group demonstrates significant

increase in perfusion rates after ESWT, HBOT shows insignificant change after HBOT. Images from Wang et, al.2011

Figure 5. Microscopic histopathological changes before and after treatments. ESWT Group demonstrates a significantly

higher cell proliferation, activity, and concentration vs HBOT Group. Images from Wang et, al. 2011.

*A single ESWT session was performed using an electro-hydraulic device. 500 impulses were administered at 0.23 mj/mm². HBOT was administered at 2.5 atmosphere absolute (ATA) for 90 mins, while 100% medical grade oxygen was inhaled via a mask.

After a single session of both ESWT & HBOT: ESWT Group yielded 57% (n=24) with a 100% completely heal ulcer vs 25% (n=10) in HBOT Group. ESWT Group yielded 32% (n=14) with ulcer healing of >50% vs 15% (n=6) in HBOT Group