In a revealing discussion of lower extremity wounds and their complications, panelists at the Western Foot and Ankle Conference offered insights on peripheral arterial disease, limb salvage, amputation, debridement and negative pressure wound therapy.
What is the average profile of a patient who seeks a health care provider’s treatment for a wound? Drawing on U.S. Wound Registry data from 15,499 wounds in 8,611 patients, Caroline Fife, MD, cites some sobering statistics.1
The average patient age is 60.4, notes Dr. Fife. The average wound duration at consultation is 189 days and 54 percent of the patients were placed on systemic antibiotics at some point during their course of care.1 She notes patients have an average of six major comorbid conditions, such as coronary artery disease, renal failure and wounds that were not specifically diabetic foot ulcers (DFU) in patients with diabetes. In fact, 39 percent of patients with venous ulcers have diabetes. They are on an average of 12 medications. In addition, Dr. Fife says many patients on the registry smoked, approximately 10 percent are taking prednisone, approximately 10 percent are on dialysis or have had a renal transplant, and a very high percentage would be considered malnourished. These statistics reinforce that chronic wounds are actually a symptom of another disease or diseases.
Which Type Of Wound Debridement Is Best?
Wound debridement needs to address all factors contributing to chronic wound healing, emphasizes Alexander Reyzelman, DPM, FACFAS. These factors include biofilm, bioburden, exudate and necrosis. When choosing a method of debridement, he notes options include surgical, enzymatic, mechanical and autolytic debridement.
Surgical debridement is both selective and the fastest method, according to Dr. Reyzelman. He notes Steed and colleagues found that patients who received more frequent surgical debridement had higher rates of healing while Cardinal and coworkers found that serial surgical debridement facilitated both a higher rate of healing and a shorter time to healing.2,3 Dr. Reyzelman notes surgical debridement is not recommended in severely immunocompromised patients or those with bleeding disorders.
In enzymatic debridement, Dr. Reyzelman notes that naturally occurring proteolytic enzymes stimulate the breakdown of necrotic tissue. He says the technique is not selective and that the material digested by enzyme may provide a medium for bacterial growth. However, enzymatic debridement is painless, leads to minimal blood loss and requires no anesthetic. Ramundo and Gray found that enzymatic debridement via collagenase ointment is more effective than placebo for pressure ulcers, leg ulcers and partial-thickness burn wounds.4 They also noted equivalent healing between debridement with collagenase and papain-urea.4
As for autolytic debridement, Dr. Reyzelman notes it is selective and easy to perform, clinicians can perform it in any setting and there is little to no discomfort for patients. He says McFarland and Smith found that the judicious use of occlusive and semi-occlusive dressings can control exudate levels, and maintain a moist wound environment.5
Which type of debridement is most effective? Dr. Reyzelman notes there is currently no definitive evidence to suggest that one method of debridement is superior to another. He says while the rationale for using surgical debridement to remove devitalized, necrotic, infected tissue and expose healthier tissue seems logical, the evidence for its role in enhancing healing is deficient.6,7
“Our concept of debridement needs to evolve into an understanding that debridement occurs 24/7 and we need to provide an appropriate environment for this to occur,” concludes Dr. Reyzelman.
Cleansing The Wound Surface
Diabetic foot ulcers (DFU) are at a high risk for infection, says William Tettelbach, MD, who emphasizes the importance of thoroughly cleansing the wound. Citing data by Lavery and coworkers, Dr. Tettlebach says a lower extremity wound is the most common precipitating event for infection.8 Lavery and colleagues found that patients who develop a DFU infection are 56 times more likely to be hospitalized and 155 times more likely to have an amputation.8
When it comes to the microbiology of diabetic foot infection, Armstrong and colleagues found that of 112 DFUs, 89 percent of those cultured grew two or fewer organisms.9 Dr. Tettelbach says the authors noted that chronic DFUs or those with more severe infection tended to be more polymicrobial. In diabetic foot osteomyelitis, he notes that Staphylococcus aureus is the most common pathogen cultured from bone.10
Although antiseptics may be indicated for DFUs, Dr. Tettelbach says research has demonstrated that H2O2or iodine reduce the migration and proliferation of fibroblasts, and are accordingly poor choices that potentially slow healing.11 The authors found that at bactericidal levels, silver sulfadiazine and chlorhexidine had fewer detrimental effects on fibroblast activity and may increase the proliferation of fibroblasts. Sakarya and coworkers found that stabilized hypochlorous acid solution was effective for fibroblast and keratinocyte migration in comparison to povidone iodine.12 Selkon demonstrated that super-oxidized water is effective against bioburden.13
Proteases break down proteins into peptides and amino acids and Dr. Tettelbach notes that generally, different wound-related proteases act on the extracellular matrix and connective tissue proteins such as collagen, gelatin, proteoglycans and elastin.14 As he says, elevated protease activity can compromise the microvasculature of the wound, inhibit healing and facilitate microbial penetration into tissue.
Protease activity is one of the best available biochemical marker for predicting poor wound healing of both acute and chronic wounds, notes Dr. Tettelbach.15 He adds that localized bleeding following debridement stimulates the influx of alpha-2-macroglobulin, which acts as a protease inhibitor, reducing proteolytic activity.16 Collagen-based dressings, calcium alginate dressings and silver dressings are options to modulate proteases.17,18
What You Should Know About NPWT With Instillation
As negative pressure wound therapy (NPWT) evolves, Matthew Regulski, DPM, cites the efficacy of NPWT with instillation. He notes that Allen and colleagues showed NPWT with instillation to be effective without causing swelling whereas lavage caused swelling.19 Furthermore, Dr. Regulski says that in comparison with wounds that received continuous NPWT, Lessing and colleagues found that after seven days, wounds treated with NPWT with instillation had thicker granulation, a greater reduction in wound area and faster rate of wound fill.20
Dr. Regulski notes that Rycerz and coworkers found NPWT with instillation via VAC VeraFlo (Acelity) provided uniform wound coverage with irrigation solution and could reach areas that were tunneled or undermined.21 Similarly, Brinkert and coworkers found VAC VeraFlo to provide better granulation tissue than conventional VAC therapy.22
Kim and colleagues, in a study of 142 patients, found NPWT with instillation to be more effective than standard NPWT for chronic wounds requiring hospitalization.23 In another study, Dr. Regulski says the authors found NPWT with instillation with 0.9% normal saline may have the same effect as an antiseptic (0.1% polyhexanide plus 0.1% betadine) for infected wounds.24
A Guide To Effective Testing For PAD
The prevalence of peripheral arterial disease (PAD) increases with age, notes Monara Dini, DPM, and about half of patients with PAD are asymptomatic.25,26
As Dr. Dini notes, the ankle-brachial index (ABI) is a good test for PAD in patients with diabetes but medial calcification can occur in patients with diabetes or end-stage renal disease.27 The toe-brachial index (TBI) test is good in patients with diabetes as digital vessels are less affected by calcification but Dr. Dini notes the test requires a toe, which some patients with diabetes do not have. Healing is unlikely if toe pressure is less than 55 mmHg, according to Dr. Dini.
In regard to transcutaneous pressure of oxygen (TcpO2) and skin perfusion pressure (SPP), Dr. Dini notes the tests are not affected by arterial calcification and one can perform them at any level of the body. However, both tests have poor reproducibility and can be affected by factors such as edema and venous pressure. Yamada and colleagues found the SPP to be effective for predicting wound healing.28
Duplex ultrasound can visually evaluate the site and severity of vascular disease with a sensitivity of 80 percent and specificity of 98 percent, but the test is sensitive to small movements in patients, according to Dr. Dini. She notes that fluorescence angiography, initially approved for cardiology, is more in use today in podiatry.
Dr. Dini says indocyanine green angiography provides real-time assessment of perfusion and is reproducible. However, she says the test is expensive and only offers a depth of penetration of 5 mm. She notes a study by Braun and coworkers could not demonstrate levels of indocyanine green angiography parameters above which healing can be predicted, or below which non-healing could be predicted.29 Igari and coworkers found that the time elapsed from fluorescence onset to half the maximum intensity was the strongest parameter in indocyanine green angiography testing.30
Dr. Dini concludes that toe pressure is the gold standard for non-invasive testing to predict wound healing although she says there is no single perfect test for assessing foot perfusion in patients with PAD. She adds that perfusion-based techniques may have a better predictive value for wound healing and for planning revascularizations although current technologies are limited by reproducibility.
When Do You Amputate And When Do You Salvage The Limb?
When facing a patient with a severe diabetic foot ulcer, how does one decide whether amputation or limb salvage will be better for a patient? Jonathan Labovitz, DPM, notes that researchers have established that limb salvage consists of preserving the ankle joint and avoiding major amputation.31 As he says, minor amputations are considered successful limb salvage.
Dr. Labovitz cites data noting a higher mortality rate and less potential for rehab in patients with an index major amputation in comparison with those who had an index minor amputation.32
In a study by Evans and coworkers, patients who had limb salvage had a 20 percent mortality rate at two years in comparison with a 52 percent mortality rate in patients with a transtibial amputation, notes Dr. Labovitz.33 In addition, he notes a five-year mortality rate of 43 percent for those with a DFU without a lower extremity amputation in contrast with a 47 percent rate in those with a DFU with a lower extremity amputation.34
Can minor amputations facilitate successful limb salvage? Dr. Labovitz says Chu and colleagues found that long-term outcomes from toe amputations were poor.35 For first ray amputations, Borkosky and coworkers noted about 20 percent of patients required a more proximal amputation.36 Following a transmetatarsal amputation, Thorud and colleagues found patients frequently needed reoperation, re-amputation and major amputation.37 Finally, Faglia and coworkers considered the Chopart amputation to be a successful limb salvage procedure, notes Dr. Labovitz.38
How does function factor into the decision of limb salvage or amputation? Dr. Labovitz says Attinger and colleagues considered preserving function to be the primary goal of limb salvage and reconstructive surgery should try to achieve a plantigrade, stable, ulcer-free foot.39 The authors note higher energy costs of ambulation after more proximal amputations.
Dr. Labovitz says clinicians should assess functional results to determine a successful outcome. He advises looking at mobility, physical ability and/or the return of independence for patients. When it comes to mobility, Larsson and colleagues found after an index minor amputation preceded by a DFU, 70 percent of patients could walk more than 1 km at one year and 93 percent returned to living independently.32 Dr. Labovitz notes that after an index major amputation preceded by a DFU, just 19 percent of patients could walk more than 1 km at one year and 61 percent returned to independent living.
What about function in patients who have had amputations? Dr. Labovitz points out that major amputation may provide better function than a longer stump that is biomechanically unstable with one study noting that 75 percent of patients who had a below-knee amputation were ambulatory with a prosthesis.40
Energy expenditure following a lower extremity amputation is controversial, notes Dr. Labovitz. He notes Waters and coworkers found that when preserving function is a goal, surgeons should amputate at the lowest level as patients with lower levels of amputation performing better in regard to gait and energy.41However, Göktepe found no differences in energy efficiency in the walking of partial foot amputees in comparison to those with higher level amputees.42
Quality of life is another concern post-amputation, notes Dr. Labovitz. He cites several studies that have noted a link between depression and the complications of diabetes.43-45 Furthermore, Wukich and Raspovic noted patients who have had successful limb salvage are more afraid of amputation than death.31
Ultimately, Dr. Labovitz argues that limb salvage is preferable as it offers a greater opportunity for a functional limb and better quality of life. He stresses considering the entire patient, especially behavior, cognitive ability and family/community support.
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8. Lavery LA, Armstrong DG, Wunderlich RP, et al. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006;29(6):1288-93.
9. Armstrong DG, Liswood PJ, Todd WF. 1995 William J. Stickel Bronze Award. Prevalence of mixed infections in the diabetic pedal wound. A retrospective review of 112 infections. J Am Podiatr Med Assoc. 1995;85(10):533-7.
10. Senneville E, Melliez H, Beltrand E, et al. Culture of percutaneous bone biopsy specimens for diagnosis of diabetic foot osteomyelitis: concordance with ulcer swab cultures. Clin Infect Dis. 2006; 42(1):57–62.
11. Thomas GW, Rael LT, Bar-Or R, et al. Mechanisms of delayed wound healing by commonly used antiseptics. J Trauma. 2009;66(1):82-90; discussion 90-1.
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14. Neely AN, Brown RL, Clendening CE, et al. Proteolytic activity in human burn wounds. Wound Repair Regen. 1997;5(4):302–9.
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20. Lessing MC, James RB, Ingram SC. Comparison of the effects of different negative pressure wound therapy modes-continuous, noncontinuous, and with instillation-on porcine excisional wounds. Eplasty. 2013 Oct 1;13:e51. eCollection 2013.
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22. Brinkert D, Ali M, Naud M, et al. Negative pressure wound therapy with saline instillation: 131 patient case series. Int Wound J. 2013;10(Suppl 1):56-60.
23. Kim PJ, Attinger CE, Steinberg JS, et al. The impact of negative-pressure wound therapy with instillation compared with standard negative-pressure wound therapy: a retrospective, historical, cohort, controlled study. Plast Reconstr Surg. 2014;133(3):709-16.
24. Kim PJ, Attinger CE, Oliver N, et al. Comparison of outcomes for normal saline and an antiseptic solution for negative-pressure wound therapy with instillation. Plast Reconstr Surg. 2015;136(5):657e-64e.
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27. Andersen CA. Noninvasive assessment of lower extremity hemodynamics in individuals with diabetes mellitus. J Vasc Surg. 2010;52(3 Suppl):76S-80S.
28. Yamada T, Ohta T, Ishibashi H, et al. Clinical reliability and utility of skin perfusion pressure measurement in ischemic limbs–comparison with other noninvasive diagnostic methods. J Vasc Surg. 2008;47(2):318-23.
29. Braun JD, Trinidad-Hernandez M, Perry D, et al. Early quantitative evaluation of indocyanine green angiography in patients with critical limb ischemia. J Vasc Surg. 2013;57(5):1213-8.
30. Igari K, Kudo T, Toyofuku T, et al. Quantitative evaluation of the outcomes of revascularization procedures for peripheral arterial disease using indocyanine green angiography. Eur J Vasc Endovasc Surg. 2013;46(4):460-5.
31. Wukich DK, Hobizal KB, Brooks MM. Severity of diabetic foot infection and rate of limb salvage. Foot Ankle Int. 2013;34(3):351-8.
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36. Borkosky SL, Roukis TS. Incidence of re-amputation following partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy: a systematic review. Diabet Foot Ankle. 2012;3.
37. Thorud JC, Jupiter DC, Lorenzana J, et al. Reoperation and reamputation after transmetatarsal amputation: a systematic review and meta-analysis. J Foot Ankle Surg. 2016;55(5):1007-12.
38. Faglia E, Clerici G, Frykberg R, et al. Outcomes of Chopart amputation in a tertiary referral diabetic foot clinic: data from a consecutive series of 83 hospitalized patients. J Foot Ankle Surg. 2016;55(2):230-4.
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40. Brown BJ, Iorio ML, Klement M, et al. Outcomes after 294 transtibial amputations with the posterior myocutaneous flap. Int J Low Extrem Wounds. 2014;13(1):33-40.
41. Waters RL, Perry J, Antonelli D, Hislop H. Energy cost of walking of amputees: the influence of level of amputation. J Bone Joint Surg Am. 1976;58(1):42-6.
42. Göktepe AS, Cakir B, Yilmaz B, Yazicioglu K. Energy expenditure of walking with prostheses: comparison of three amputation levels. Prosthet Orthot Int. 2010;34(1):31-6.
43. Simon GE, Katon WJ, Lin EH, et al. Diabetes complications and depression as predictors of health service costs. Gen Hosp Psychiatry. 2005;27(5):344-51.
44. Egede LE, Ellis C, Grubaugh AL. The effect of depression on self-care behaviors and quality of care in a national sample of adults with diabetes. Gen Hosp Psychiatry. 2009;31(5):422-7.
45. Monami M, Longo R, Desideri CM, et al. The diabetic person beyond a foot ulcer: healing, recurrence, and depressive symptoms. J Am Podiatr Med Assoc. 2008;98(2):130-6.