Closing Difficult Wounds

By Stephanie C. Wu, DPM, MS, Lawrence A. Lavery, DPM, MPH, and David G. Armstrong, DPM, PhD

Non-healing skin ulcerations of the lower extremities affect millions of people in the United States and impose tremendous medical, psychosocial and financial impact. These wounds may be secondary to a myriad of etiologies including pressure, metabolic, trauma, venous, arterial etiologies and diabetic neuropathy.1 The Wound Healing Society defines chronic ulcerations as wounds that have “failed to proceed through an orderly and timely process to produce anatomic and functional integrity, or proceeded through the repair process without establishing a sustained anatomic and functional result.”2 This prolonged and sometimes interrupted healing process affects the patient’s quality of life due to impaired mobility and substantial loss of productivity, and is a significant management challenge to healthcare professionals.3 The relapsing course may also be reflected in the astounding economic burden that chronic ulcerations have placed upon healthcare. The attributable cost for the treatment of chronic ulcerations has been conservatively estimated at $3.6 billion dollars per year.4 Medicare expenditures for lower-extremity ulcer patients were, on average, three times higher than expenditures for Medicare patients in general.5 In addition, a lack of immediate attention to these wounds can often serve as a prelude to serious health problems due to associated infections that may lead to amputations or induce life-threatening situations.1,6 Wound repair is an orchestra of highly integrated cellular and biochemical responses to injury.7 Certain pathophysiologic and metabolic conditions can alter this normal course of events, leading to delayed or impaired healing that may result in chronic, non-healing wounds.7,8 Integrating technological advances with our understanding of the complex cellular and biochemical mechanisms of wound healing has led to the development of various advanced wound healing modalities such as hyperbaric oxygen, topical growth factors, bioengineered skin and tissue equivalents, and negative pressure wound therapy (NPWT).7,9-13 What Studies Have Suggested About Using NPWT Negative pressure wound therapy (see “What You Should Know About NPWT” below) can often be both a catalyst to secondary wound healing and a bridge between debridement and definitive closure.24 The optimal subatmospheric pressure for wound healing, as shown in animal models, appears to be approximately 125 mmHg, utilizing an alternating pressure cycle of five minutes of suction followed by two minutes of no suction.29 Although the exact mechanism of the action of NPWT on wound healing is not clear, studies suggest that applying subatmospheric pressure may optimize blood flow, decrease local tissue edema, remove excessive fluid and pro-inflammatory exudates, facilitate the removal of bacteria from the wound, and promote a moist wound healing environment.24,29,30 In addition, researchers have noted the application of subatmospheric pressure helps increase the rate of cell division, angiogenesis, local elaboration of growth factors and subsequent formation of granulation tissue.22,24,29-31 In a simulated NPWT application on a computer wound model, Saxena, et. al., studied the effects of negative pressure-induced material deformations.32 They compared the morphology of deformation of the computerized wound model with histologic sections of wounds treated with NPWT. They demonstrated that most elements stretched by subatmospheric pressure experience deformations of 5 to 20 percent strain, which are similar to in vitro strain levels shown to promote cellular proliferation.32 Furthermore, they noted that the deformation illustrated by the computer wound model was similar in morphology to the surface undulations observed in histologic cross-sections of the wounds.32 Chen, et. al., examined the effects of NPWT on the microcirculation of full thickness wounds in rabbit ears and postulated that NPWT stimulates angiogenesis by promoting capillary blood flow velocity, increasing capillary caliber and blood volume, and stimulating endothelial proliferation. They also proposed that NPWT restores integrity of the capillary basement membrane and narrows endothelial spaces to decrease the permeability of blood vessels and wound edema.33 Clinical evidence that supports the use of NPWT has been based largely on anecdotal perception, case series, small cohort studies and weakly-powered randomized trials that constitute a considerable amount of publications but an overall low level of evidence.15-19 This is attributable in large part to difficulties encountered in clinical trials as well as in isolating study design variables.8 Recently, The Lancet published a multicenter, randomized, controlled trial that substantiates the use of NPWT in the treatment of complex diabetic foot ulcers.34 Several other ongoing clinical trials may quantify the reduction of wound size for NPWT. However, let us take a closer look at the currently published literature and the role of NPWT in facilitating the healing of chronic, difficult to heal wounds as well as the implication of these findings for clinical practice. What You Should Know About NPWT Since its introduction in the United States in 1997, NPWT has emerged as a commonly employed option in the treatment of complex wounds. Many clinicians have advocated the incorporation of NPWT into wound treatment regimens. Various researchers have noted that NPWT helps decrease the number of dressing changes, reduces the time between debridement and definitive closure, and reduces costs associated with a protracted course of hospital stay.14-25 Negative pressure wound therapy via Vacuum Assisted Closure (VAC Therapy System, Kinetic Concepts Inc.) is a non-invasive wound closure system that uses controlled, localized subatmospheric pressure to help promote healing in chronic and acute wounds. This subatmospheric or negative pressure can be conveyed either continuously or intermittently though the use of a sterile, latex free polyurethane or polyvinyl alcohol foam dressing. The clinician can fit the foam dressing at bedside to the appropriate size for each patient’s wound. One would then cover the dressing with an adhesive transparent drape to create an occlusive seal in order to contain the subatmospheric pressure at the wound site and promote wound healing. Overlaying the foam within the drape is a T.R.A.C. Pad® that is connected to a sophisticated track tubing device that accurately senses, monitors and maintains the prescribed pressure at the wound site. The tubing connects the T.R.A.C. Pad to a fluid collection canister, which is contained within a programmable, portable computer-controlled vacuum pump that creates negative pressure at the wound surface interface.26-28 Diabetic Wounds: Can NPWT Have An Impact? Diabetic foot ulceration is one of the most common complications associated with the disease and is notorious for its complexity and healing difficulties.35-37 Even for the most superficial wounds, treatment is frequently challenging with poor healing responses and high rates of complications.38 Numerous authors advocate the use of NPWT as a safe and effective adjunctive modality to help achieve a rapid granular bed and prevent further surgeries in this high-risk population.15,34,39,40 Armstrong, et. al., evaluated the efficacy of NPWT in the healing of 31 indolent diabetic foot wounds immediately following surgical debridement.15 They utilized a cessation of therapy protocol in which they discontinued NPWT when the wound bed approached 100 percent coverage with granulation tissue with no exposed tendon, joint capsule or bone.15 They noted that 90.3 percent of the wounds treated with NPWT healed at the level of debridement without the need for further bony resection in a mean of 8.1 + 5.5 weeks.15 In a randomized trial, Eginton, et. al., compared the wound healing efficacy of NPWT to conventional moist dressings in the treatment of large diabetic foot ulcers. They noted that NPWT decreased the wound volume (59 percent vs. 0 percent) and depth (49 percent vs. 8 percent) significantly more than moist gauze dressings.39 In a 16-week, 18-center, randomized clinical trial which consisted of 162 patients, Armstrong and Lavery noted that NPWT healed more wounds after partial foot amputation in patients with diabetes (56 percent) versus the standard of care (39 percent).34 Based on the time to complete closure, NPWT produced a faster rate of wound healing (p=0.005) with a faster rate of granulation tissue formation versus the standard of care (p=0.002).34 Is NPWT Effective For Pressure Ulcers? Pressure or decubitus ulcers occur most commonly over bony prominences in patients with diminished or absent sensation or in those who are debilitated, bedridden, emaciated or paralyzed. The alleviation of pressure is fundamental to the healing of these ulcers and several authors have found NPWT to be a useful adjunct to the standard pressure ulcer treatment.41-43 Smith, et. al., examined 281 patients with pressure ulcers who received either NPWT, alginate or hydrocolloid dressings.43 They noted that although most of the pressure ulcers showed some response to all of the wound healing modalities investigated, patients who received NPWT showed a greater response in all aspects of healing than those who received the other two treatment modalities.43 In a randomized trial, Wanner, et. al., compared the wound healing efficacy of NPWT to saline wet-to-dry/wet-to-wet dressing changes three times daily in 22 patients with pressure ulcers.41 They found the two methods to be equally effective in the formation of granulation tissue with no difference in the time required to reach a 50 percent decrease of the initial wound volume. However, the authors of the study also noted that NPWT was associated with reduced costs and improved patient comfort as dressing changes occurred every 48 hours as opposed to three times daily.41 Ford, et. al., evaluated the difference between NPWT and Curasol® (Healthpoint) in a randomized six-week trial in the healing of full-thickness pressure ulcers.42 They noted a mean reduction in ulcer volume of 42.1 percent with Curasol and 51.8 percent with NPWT.42 In addition, they noted that patients who received NPWT demonstrated favorable histological changes in both soft tissue and bone compared with patients who received the wound gel product. The authors pointed out that the NPWT group had a greater mean number of capillaries and a lower mean number of polymorphonuclearcytes and lymphocytes in comparison to the group treated with Curasol.42 Should NPWT Be Part Of The Treatment Regimen For Infected Wounds? The treatment of wounds caused by infection is often complicated by tissue viability and the size and location of the wound.44,45 When using NPWT in infected wounds, clinicians should proceed with caution as bacterial colonization of a wound is a recognized detrimental factor in the multifactorial process of wound healing. Some authors propose that NPWT’s closed wound healing environment may provide an ideal environment for the colonization of microorganisms. Others believe that NPWT enhances bacterial clearance to facilitate wound healing. Wongworawat, et. al., treated 14 wounds secondary to infection with NPWT for an average of 10 days with an average wound size reduction of 43 percent (from an average initial wound size of 70 cm2 to an average final wound size of 39 cm2.44 They noted that NPWT, since it is a closed system of treatment, has the added benefit of minimizing the exposure of staff and other patients to communicable diseases.44 Weed, et. al., retrospectively reviewed the charts of 25 patients who received NPWT with serial quantitative cultures and found that NPWT did not have a consistent effect of bacterial clearance.46 They observed that bacterial colonization increased significantly with NPWT and remained in a range between 104 and 106. However, despite their findings, the authors did note that NPWT was associated with beneficial effects on wound healing in most cases.46 In a randomized trial, Moues, et. al., examined the effect of NPWT versus conventional moist gauze therapy on the bacterial load in 54 patients who required open wound management before surgical closure.47 Analogous to the work of Weed, Moues noted a significantly larger wound surface area mean reduction in patients treated with NPWT (3.8 percent/day) compared to the mean reduction in conventionally treated wounds (1.7 percent/day). However, they did not find a significant quantitative reduction of the bacteria load.47 While nonfermentative, gram-negative bacilli showed a significant decrease in wounds treated with NPWT, the researchers noted that Staphylococcus aureus showed a significant increase in these wounds.47 Researchers have also advocated the use of NPWT as an efficacious adjunctive treatment option in the care of musculoskeletal infections, specifically postoperative infections and osteomyelitis.22 As many as 12 percent of postoperative infections after osseous procedures are associated with the exposure of the hardware and implant.45 Incorporating NPWT as part of the treatment protocol may help enhance the rapidity of wound reduction and prevent such deleterious sequellae.45 When osteomyelitis is present, salvage of the foot and ankle is a challenging problem, especially in compromised hosts.48 Saltzman, et. al., utilized NPWT as part of a successful treatment regimen in eight patients with diffuse ankle osteomyelitis.48 What About High Energy Soft Tissue Injuries? The treatment of severe wounds of the extremities, characterized by large posttraumatic tissue loss, often represents a clinical problem that is difficult to resolve. This is especially true when the lesion is surrounded by large areas of ischemic dystrophic tissue with frequent exposure of bone and joint structures making amputation of the limb an inevitable outcome.49 In a consecutive non-randomized clinical study, Herscovici, et. al., evaluated the efficacy of NPWT in the healing of 21 patients with open high-energy soft tissue injuries and concluded that NPWT may be a viable adjunct for treating open high-energy injuries to help avoid the need for a free tissue transfer.50 In addition to the required microsurgical reconstruction of the extremity, Riccio, et. al., advocate the combination of NPWT with hyperbaric oxygen to help restore morpho-function, reduce hospitalization and synergize the successful treatment of posttraumatic wounds.49 Can NPWT Improve Graft Survival Rates? Negative pressure wound therapy allows for elective planning of definitive reconstructive surgery without jeopardizing the wound or outcome, and may be useful in the reconstruction of wounds.29 Using NPWT to help increase the rate of uptake of split-thickness skin grafts has been well documented.51,52 Numerous authors advocate that NPWT provides a safe and effective method for securing split-thickness skin grafts and significantly increases the skin graft success rate when used as a bolster over the freshly skin-grafted wound.29 Scherer, et. al., compared NPWT to bolster dressings in securing split-thickness skin grafts in 61 patients. They found the patients who received NPWT required significantly fewer repeat skin grafts (3 percent) compared to patients who received bolster dressings (19 percent).51 Carson, et. al., treated 70 patients with chronic, non-healing wounds with NPWT for a period of 30 months.52 Fifty of these patients received NPWT after undergoing skin graft procedures. The authors noted that NPWT, in addition to a protocol of general supportive and local wound care, resulted in a high rate of closure during an average of 48 days and achieved 100 percent of the skin graft uptake.52 In Conclusion Achieving closure in a complex, difficult to heal wound requires adequate perfusion, debridement, a moist environment, a reduction of bioburden and the correction of contributing medical diagnoses.13 Clinicians have observed that NPWT, a generally well-tolerated device with few contraindications or complications, appears to stimulate a robust granulation tissue response compared to other wound healing modalities.14,53 The concomitant use of NPWT with appropriate debridement and antimicrobial therapy may be an effective alternative to treating chronic, difficult to heal wounds.22,23,54 Future work in this area should include other clinical trials that may quantify the reduction of wound size for NPWT with an emphasis on cost efficacy, length of hospital stay as well as the patient’s quality of life. This will further enhance understanding and sharpen clinical decision making in the management strategies for difficult to heal ulcerations. Dr. Wu is the American Podiatric Medical Association/American Diabetes Association Senior Fellow at the Center for Lower Extremity Ambulatory Research (CLEAR) at the William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science in Chicago.   Dr. Lavery is a Professor in the Department of Surgery at Texas A&M Health Science Center College of Medicine. Along with Dr. Armstrong, Dr. Lavery is the Editor of the American Diabetes Association’s “Clinical Care of the Diabetic Foot.”   Dr. Armstrong is a Professor of Surgery, Chair of Research and Assistant Dean at the William M. Scholl College of Podiatric Medicine at the Rosalind Franklin University of Medicine in Chicago. He is the founder and Director of CLEAR, and is an immediate past member of the National Board of Directors of the American Diabetes Association. Dr. Armstrong is the co-Founder of the National Center for Limb Preservation in Chicago and the International Diabetic Foot Conference (DFCon), held annually in Los Angeles. For related articles, see “Combining VAC Therapy With Advanced Modalities: Can It Expedite Healing?” in the September 2005 issue of Podiatry Today and “Achieving Adjunctive Success With Wound Dressings” in the July 2003 issue. Also check out the archives at



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