In addition to assessing the mechanisms and impact of negative pressure wound therapy (NPWT) in lower extremity wound care, these authors discuss the advent of fluid installation therapy in thwarting complications, recent literature on the use of the modality for closed incision sites and wounds secondary to traumatic fractures, and the potential of portable NPWT for small wounds.
In 2011, an estimated 366 million people worldwide had diabetes and this number is expected to increase to 552 million by 2030.1 In the United States, diabetes affects 25.8 million people (8.3 percent of the population) with more than 60 percent of non-traumatic lower limb amputations occurring in patients with diabetes.2
Of these amputations, 85 percent are preceded by a foot ulcer and the risk of developing a foot ulcer during the lifetime of a person with diabetes can be as high as 25 percent.3 The management of these foot wounds, with the ultimate goal of amputation prevention, remains one of the great challenges faced by the multidisciplinary foot care team today.
Over the past 20 years, negative pressure wound therapy (NPWT) has proven to be a safe, effective modality for the treatment of diabetic foot ulcers. Most commonly delivered by a Vacuum Assisted Closure device (VAC therapy, KCI), the NPWT system consists of a reticulated, open cell foam, covered with a semi-permeable adhesive drape, and connected to a negative pressure therapy unit via evacuation tubing.
The foam, engineered to apply a uniform pressure throughout the entire wound bed, comes in several varieties including: polyurethane ether; polyurethane ether with microbonded metallic silver impregnated into the foam; and white, pre-moistened, hydrophilic polyvinyl alcohol foam. The negative pressure unit is typically at 125 mmHg on a continuous or intermittent setting.4,5
In 1997, Morykwas and colleagues reported a fourfold increase in blood flow to the subcutaneous tissue and muscle of Chester pigs when applying VAC therapy at 125 mmHg over 15-minute intervals.6 During the same interval, however, the blood flow values decreased to below baseline at pressures greater than 400 mmHg. The authors also found that the increase in local blood flow subsided after a period of five to seven minutes but an “off” interval of two minutes was sufficient for re-establishing the increase in blood flow. This represents the concept behind intermittent pressure.
Timmers and co-authors applied VAC therapy to the healthy, intact forearm skin of 10 healthy volunteers and measured the response of cutaneous blood flow to different values of negative pressure between 25 and 500 mmHg.7 The authors reported a significant increase in cutaneous blood flow at a negative pressure of 300 mmHg, more than double the pressure used in previous studies. In fact, even at negative pressures approaching 500 mmHg, they found no decrease in the baseline blood flow.
In 2005, Armstrong and Lavery reported on the results of a multicenter, randomized clinical trial comparing the proportion and rate of wound healing in 162 patients with diabetic wounds secondary to partial foot amputation and evidence of adequate perfusion.8 The patients were randomly assigned to two groups, one of which received NPWT while the other group had standard moist wound therapy. The study, which took place over a period of 16 weeks in 18 study sites, found that treatment with NPWT resulted in a higher number of healed wounds (56 percent versus 39 percent) as well as a faster rate of wound healing. Furthermore, the group receiving NPWT demonstrated an increase in the rate of granulation tissue formation as well as a potential trend toward a reduced risk of re-amputation.
Blume and colleagues reported similar results in an even larger study published in 2008.9 Over a period of 16 weeks, the authors demonstrated that a greater proportion of diabetic foot ulcers achieved complete closure with NPWT (43.2 percent versus 28.9 percent) and that patients receiving NPWT required fewer amputations.
While there are several factors that may explain the success of NPWT, there is no consensus regarding the dominant mechanism. Rather, the combination of a moist wound healing environment, active removal of exudate and infectious materials, maintenance of adequate wound temperature, and physical stimulation of cells created by NPWT along with increased tissue perfusion all contribute to improved wound healing.10 When a wound bed is moist, this maintains the lateral voltage gradient and there is a greater potential for wound healing.10
Furthermore, researchers have shown that wounds with excessive exudate contain an increased number of matrix metalloproteinases (MMPs), which degrade the adhesion proteins necessary for wound repair while an increase in interstitial pressure may occlude the surrounding microvasculature and lymphatics, thus depriving the tissue of vital nutrients and oxygen.10,11
For some time, it has been widely accepted that infection may be detrimental to wound healing. In their study, Morykwas and co-workers were able to demonstrate a significant reduction in the number of organisms between days four (108) and five (105) in wounds receiving treatment with NPWT.6 However, Weed and colleagues, in a retrospective review of 25 patients, actually found an increase in the bacterial bioburden of 43 percent of wounds treated with NPWT over an average of 12.8 weeks.12
While quantitative bacteriology may not be the ideal method to measure a patient’s response to colonization, it is worth noting and discussing. Future works might delve deeper into both the specific microbiome and virulence factors secreted by that microbiome.
Besides the potential for wound colonization during prolonged periods of NPWT, there may be maceration of the wound, which could necessitate the temporary or permanent discontinuation of NPWT. In a 2002 case report, Chester and Waters reported that the closed, air-free environment created by NPWT led to a progressively worsening anaerobic wound infection in a 76-year-old man who developed sepsis following a groin wound dehiscence while undergoing treatment with NPWT.13
Although similar cases in the literature are unreported, it serves as a stark reminder that clinicians must carefully monitor all patients receiving NPWT for systemic changes as well as changes to the overall presentation of the wound.
Fluid instillation therapy, as delivered by NPWT, has shown a great deal of promise in avoiding many of these potential complications. Otherwise known as “wound chemotherapy,” a couple of different systems currently facilitate this process. The VAC Instill Therapy Unit (KCI) allows for separate infusion and vacuum periods via two different ports. The SVED negative pressure device (Innovative Therapies) provides simultaneous infusion and NPWT.14-16
While the VAC Instill Therapy Unit is more accessible than the SVED system in most clinical settings, its “hold” cycle — during which fluid infuses into the foam and NPWT pauses — may result in maceration and a loss of seal.14 Recent modifications to the updated KCI instillation system may have improved the seal.
Researchers have studied fluids such as Dakin’s solution (sodium hypochlorite), insulin, doxycycline, Dilantin (phenytoin), diluted Betadine, lactoferrin and biguanide antiseptics for their potential application to fluid instillation NPWT.14-16 The instillation of Dakin’s solution may prevent wound maceration and colonization, and researchers have shown that insulin-like growth factor increases the rate of wound healing.14,16 Furthermore, doxycycline is antimicrobial and is a competitive inhibitor of MMPs as well as tissue necrosis factor-a.15 This tetracycline antibiotic may also reduce inflammation in the wound by decreasing nitric oxide synthesis.15
Another way in which NPWT works to improve wound healing can be explained by the law of tension stress. As the clinician applies NPWT, the wound bed experiences a negative, deforming force, which stretches individual cells and results in increased cell proliferation and angiogenesis.10,17
In 2004, Saxena and colleagues reported that finite element modeling of VAC therapy was able to produce strains consistent with the levels needed for promoting cellular proliferation in vitro.17 Researchers have investigated the notion that micromechanical forces are able to induce cell proliferation and division with respect to the use of tissue expanders for reconstructive plastic surgery, and distraction osteogenesis for bone lengthening.10,17,18
More recently, the use of NPWT has expanded beyond the treatment of diabetic foot ulcers. Negative pressure wound therapy improves the take of split-thickness skin grafts by acting as a bolster and preventing an accumulation of fluid beneath the graft site.10 In 2004, Moisidis and co-workers found that the take for split-thickness skin grafts subjected to NPWT was qualitatively improved in 50 percent of the cases they studied.19
Researchers have also studied the benefits of NPWT with respect to the healing of wounds secondary to traumatic, open fractures. In 2009, Stannard and colleagues reported on the results of a prospective, randomized study in which 58 patients with 62 open fractures received either standard wet-to-dry dressings or NPWT.20 The authors found that the group treated with NPWT was one-fifth as likely to develop an infection as the control group, suggesting that NPWT may be an effective adjunct in the treatment of severe, open fractures.
Another trend that has been gaining popularity in recent years is the use of NPWT over closed incision sites. As previously discussed, NPWT reportedly increases local tissue perfusion, reduces edema, increases the rate of granulation tissue formation and promotes cellular proliferation through micromechanical forces. When one applies NPWT over a clean, closed incision, the modality acts to protect the wound bed and creates a splinting effect on the surrounding soft tissue.21 Furthermore, this eliminates the need for frequent dressing changes on high-risk incision sites and authors have shown that the incidences of dehiscence and infection are lower.22,23
Various authors have reported the use of NPWT over closed incision sites in cases of coronary artery bypass grafting, abdominal hysterectomy, revisional hip arthroplasty, transmetatarsal amputation and high-risk fractures of the lower extremity.21-23 Researchers have reported using a pressure setting of 75 to 125 mmHg, typically applying a non-adherent dressing between the incision site and foam layer. The Prevena™ Incision Management System (KCI) is a device specifically designed for applying NPWT over closed incision sites. The compact system has a 45 mL canister and includes a semi-permeable incision dressing impregnated with ionic silver.24
In a prospective, randomized, multicenter clinical trial published in 2012, Stannard and co-authors were able to demonstrate a decreased incidence of wound dehiscence and infection in postoperative tibial plateau, pilon and calcaneal fractures treated with closed incision NPWT.23 In this study based on 249 patients, with an even distribution of 263 tibial plateau, pilon and calcaneal fractures, the authors found that the relative risk of developing an infection was 1.9 times higher in patients treated with standard postoperative dressings in comparison to those receiving closed incision NPWT.
Another recent breakthrough in NPWT has been the development of the Smart Negative Pressure (SNaP®) Wound Care System (Spiracur), a novel portable device that utilizes specialized springs to deliver NPWT without the need for an electrically powered pump. In contrast to the electrically powered NPWT systems, the SNaP System is designed for smaller wounds and is fully disposable. The system is silent throughout its operation and is readily available for “off-the-shelf” use, obviating the need for costly and time-consuming rental agreement. The patient may wear the device, roughly the size and weight of a cell phone, beneath his or her clothing. The SNaP system consists of a cartridge, a hydrocolloid dressing layer with an integrated nozzle and tubing, and a wound interface layer made of either foam or gauze. The cartridge, which doubles as the storage canister (60 mL capacity), can deliver negative pressures of 75, 100 and 125 mmHg.25-27
In a prospective, multicenter, randomized controlled study, Armstrong and colleagues compared the SNaP Wound Care System to the VAC therapy system for the treatment of chronic lower extremity wounds.28 Over a period of 16 weeks and in 17 study centers, 115 patients with non-infected, non-ischemic, non-plantar lower extremity diabetic and venous wounds received treatment with either the SNaP System or the VAC therapy system. The results showed that at four, eight, 12 and 16 weeks, with respect to percent decrease in wound area, the patients treated with the SNaP system demonstrated non-inferiority to the patients treated with VAC therapy.
Furthermore, the study authors reported that the effect of the SNaP system in promoting complete wound closure was not significantly different than VAC therapy. The mean application time for the SNaP system was significantly shorter than that for VAC therapy, and patients treated with the SNaP system reported improved activities of daily living, less interruption in sleep and better comfort in social situations.
A battery-powered version of the KCI device (VAC Via) is also available with the intention of providing a smaller form factor like the non-electrically-powered SNaP device.
Despite advances in research and ongoing clinical trials, the worldwide diabetes epidemic shows little sign of slowing down. Through a combination of increased tissue perfusion, removal of exudate and infectious materials, and physical stimulation of cells, NPWT reportedly increases granulation tissue formation and accelerates healing in patients with diabetic foot wounds.8,9 Negative pressure wound therapy may also improve the quality of life of patients with diabetic foot ulcers and may reduce the overall cost of treating these patients.10
Researchers have demonstrated that the instillation of fluids such as Dakin’s solution, insulin and doxycycline, which reportedly promote wound healing, may provide an added benefit of NPWT by reducing maceration via infusion of these solutions directly into the wound bed.14-16 Through the application of NPWT to post-traumatic wounds, skin grafts and, more recently, over closed incision sites, the current indications for the modality are greater than ever, and the results are promising. While the electrically powered NPWT systems most commonly used today can be difficult to procure in the outpatient setting and provide limited mobility due to their size and power source, a novel, portable system such as the SNaP system may help to remedy these issues.
Over the past 20 years, NPWT has emerged as a critical tool for foot and wound care specialists throughout the world. Over the next 20 years, the impact it will have for patients is immeasurable.
Dr. Armstrong is a Professor of Surgery at the University of Arizona College of Medicine in Tucson, Az. He is the Director of the Southern Arizona Limb Salvage Alliance (SALSA).
Dr. Isaac is the Chief Resident in the Podiatric Medicine and Surgery Residency (PM&S-36) at St. Barnabas Medical Center in Livingston, N.J. He is also an incoming Clinical Instructor in the Department of Surgery at the University of Arizona College of Medicine and Fellow at SALSA.
1. International Diabetes Federation. IDF Diabetes Atlas, 5th edn. Brussels, Belgium: International Diabetes Federation, 2011. http://www.idf.org/diabetesatlas 
2. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
3. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293(2):217-28.
4. Jeffries LC, Rodriguez RH, Belczyk R, Zgonis T. Negative pressure wound therapy for the complicated diabetic foot wounds. In: Zgonis T, ed. Surgical reconstruction of the diabetic foot and ankle. Philadelphia, PA: Lippincott Williams & Wilkins; 2009: 119-128.
5. Blitz NM. Vacuum assisted closure in lower extremity reconstruction. In: Dockery GL, Crawford ME, eds. Lower extremity soft tissue and cutaneous plastic surgery. Edinburgh, UK: Saunders; 2006: 343-358.
6. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38(6):553-62.
7. Timmers MS, Le Cessie S, Banwell P, Jukema GN. The effects of varying degrees of pressure delivered by negative-pressure wound therapy on skin perfusion. Ann Plast Surg. 2005;55(6):665-71.
8. Armstrong DG, Lavery LA; Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet. 2005;366(9498):1704-10.
9. Blume PA, Walters J, Payne W, Ayala J, Lantis J. Comparison of negative pressure wound therapy using vacuum-assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a multicenter randomized controlled trial. Diabetes Care. 2008;31(4):631-6.
10. Andros G, Armstrong DG, Attinger CE, Boulton AJ, Frykberg RG, Joseph WS, Lavery LA, Morbach S, Niezgoda JA, Toursarkissian B; Tucson Expert Consensus Conference. Consensus statement on negative pressure wound therapy (V.A.C. Therapy) for the management of diabetic foot wounds. Ostomy Wound Manage. 2006 Jun;Suppl:1-32.
11. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol. 1993;101(1):64-8.
12. Weed T, Ratliff C, Drake DB. Quantifying bacterial bioburden during negative pressure wound therapy: does the wound VAC enhance bacterial clearance? Ann Plast Surg. 2004;52(3):276-9; discussion 279-80.
13. Chester DL, Waters R. Adverse alteration of wound flora with topical negative-pressure therapy: a case report. Br J Plast Surg. 2002;55(6):510-1.
14. Giovinco NA, Bui TD, Fisher T, Mills JL, Armstrong DG. Wound chemotherapy by the use of negative pressure wound therapy and infusion. Eplasty. 2010 Jan 8;10:e9.
15. Scimeca CL, Bharara M, Fisher TK, Giovinco N, Armstrong DG. Novel use of doxycycline in continuous-instillation negative pressure wound therapy as “wound chemotherapy." Foot Ankle Spec. 2010;3(4):190-3.
16. Scimeca CL, Bharara M, Fisher TK, Kimbriel H, Mills JL, Armstrong DG. Novel use of insulin in continuous-instillation negative pressure wound therapy as “wound chemotherapy.” J Diabetes Sci Technol. 2010;4(4):820-4.
17. Saxena V, Hwang CW, Huang S, Eichbaum Q, Ingber D, Orgill DP. Vacuum-assisted closure: microdeformations of wounds and cell proliferation. Plast Reconstr Surg. 2004;114(5):1086-96; discussion 1097-8.
18. Olenius M, Dalsgaard CJ, Wickman M. Mitotic activity in expanded human skin. Plast Reconstr Surg. 1993;91(2):213-6.
19. Moisidis E, Heath T, Boorer C, Ho K, Deva AK. A prospective, blinded, randomized, controlled clinical trial of topical negative pressure use in skin grafting. Plast Reconstr Surg. 2004;114(4):917-22.
20. Stannard JP, Volgas DA, Stewart R, McGwin G Jr, Alonso JE. Negative pressure wound therapy after severe open fractures: a prospective randomized study. J Orthop Trauma. 2009;23(8):552-7.
21. Stannard JP, Atkins BZ, O’Malley D, Singh H, Bernstein B, Fahey M, Masden D, Attinger CE. Use of negative pressure therapy on closed surgical incisions: a case series. Ostomy Wound Manage. 2009;55(8):58-66.
22. Gomoll AH, Lin A, Harris MB. Incisional vacuum-assisted closure therapy. J Orthop Trauma. 2006;20(10):705-9.
23. Stannard JP, Volgas DA, McGwin G 3rd, Stewart RL, Obremskey W, Moore T, Anglen JO. Incisional negative pressure wound therapy after high-risk lower extremity fractures. J Orthop Trauma. 2012;26(1):37-42.
24. Prevena™ Incision Management System Clinician Guide. KCI USA, Inc., San Antonio, TX. 2010.
25. Fong KD, Hu D, Eichstadt S, Gupta DM, Pinto M, Gurtner GC, Longaker MT, Lorenz HP. The SNaP system: biomechanical and animal model testing of a novel ultraportable negative-pressure wound therapy system. Plast Reconstr Surg. 2010;125(5):1362-71.
26. Lerman B, Oldenbrook L, Eichstadt SL, Ryu J, Fong KD, Schubart PJ. Evaluation of chronic wound treatment with the SNaP wound care system versus modern dressing protocols. Plast Reconstr Surg. 2010;126(4):1253-61.
27. Lerman B, Oldenbrook L, Ryu J, Fong KD, Schubart PJ. The SNaP Wound Care System: a case series using a novel ultraportable negative pressure wound therapy device for the treatment of diabetic lower extremity wounds. J Diabetes Sci Technol. 2010;4(4):825-30.
28. Armstrong DG, Marston WA, Reyzelman AM, Kirsner RS. Comparative effectiveness of mechanically and electrically powered negative pressure wound therapy devices: a multicenter randomized controlled trial. Wound Repair Regen. 2012;20(3):332-41.
For further reading, see “Inside Insights On Negative Pressure Wound Therapy” in the May 2007 issue of Podiatry Today, “Examining The Role Of NPWT In Limb Salvage” in the December 2009 issue or “Point-Counterpoint: Is Foam More Effective Than Gauze With Negative Pressure Wound Therapy?” in the July 2009 issue.
Also check out the DPM Blog “Building A Better ‘Mousetrap’ For NPWT” at http://goo.gl/Z7Lk2  .