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A Closer Look At Advances With NPWT
Negati
ve pressure wound therapy (NPWT) has been a proven technique for facilitating wound healing and the technology continues to evolve beyond the original negative pressure devices. These authors examine the efficacy of innovations in NPWT delivery, including NPWT with instillation.
Negative-pressure wound therapy (NPWT) has now been in use for decades as an effective adjunctive treatment of acute and chronic wounds. The primary benefits of NPWT are the promotion of wound healing and preparation of the wound bed for closure.
Clinicians first applied subatmospheric or negative pressure to wounds with soft tissue damage in open fractures.1 Since then, physicians have successfully used the technology to prepare the wound bed for delayed closure, skin grafts or flap closure. Negative pressure has also emerged in many wound healing protocols as an adjunct or bolster for skin grafts, biologic alternative tissue substitutes and as a dressing over high-risk wound closures.2-8
In 2011, Janis and colleagues described a modification of the reconstructive ladder that incorporated NPWT, stating that NPWT can be an adjunct to any other method of soft tissue reconstruction.9 They noted that NPWT may be especially useful for the common but problematic small wound with poorly vascularized tissue at its base. This includes wounds with exposed bone or tendon, which would have traditionally required a flap for closure.
Proposed benefits of NPWT include less frequent dressing changes and reducing exposure of the wound to contamination. In addition, NPWT offers possible economic value to the healthcare system through reduced infection rates, fewer hospital stays and fewer trips to the operating room.10-11
How NPWT Can Facilitate Diabetic Limb Salvage
The innovation of NPWT has both revolutionized and simplified the treatment of complex lower extremity wounds, including chronic wounds in patients with diabetes.6,8,12 
In 2013, the Cochrane Review published an analysis of the literature on NPWT for treating foot wounds in people with diabetes mellitus.12 It identified five randomized controlled trials with a total of 605 patients and focused on two studies comparing NPWT with standard moist wound dressings. The authors concluded that there is some evidence that NPWT is more effective than moist wound dressings in patients with diabetes but cautioned that these findings are uncertain due to the possible risk of bias in these studies.
The first of these notable studies compared NPWT to standard moist wound care after partial foot amputation.6 Seventy-seven wounds received NPWT and 85 received moist dressings until healing or completion of the 112-day treatment phase. Researchers found that more patients healed in the NPWT group (56 percent) in comparison to the control group (39 percent). The rate of wound healing was also faster in the NPWT group than in control patients. Importantly, NPWT patients were approximately 25 percent less likely than control patients to need a second amputation.6
The second randomized control trial included 342 patients and found that a greater percent of foot ulcers achieved complete closure with NPWT (43 percent) than with advanced moist wound therapy (29 percent) within the 112-day active treatment phase.8 They found a greater decrease in ulcer area with NPWT (-4.32 cm2) versus advanced moist wound therapy (-2.53 cm2) from baseline on day 28. Additionally, Kaplan-Meier median estimates for 76–100 percent granulation tissue formation were 56 days for NPWT and 114 days for advanced moist wound therapy.
A Closer Look At NPWT Principles
Clinicians widely embrace NPWT as one of the most commonly used devices for advanced wound therapy. However, the exact mechanism of action and its superiority over standard wound care protocols are not clearly established.13 Morykwas’ original animal studies found that mechanical forces induced by negative pressure on chronic wounds effectively remove excess interstitial fluid, increase local vascularity and stimulate granulation tissue formation to promote healing.14 
Researchers have proposed that NPWT decreases bacterial colonization and periwound edema while increasing immune response and angiogenesis to the wound margins.15-19 Decreased edema reduces tension on the microcirculation, increasing local blood flow and reducing the distance that oxygen and nutrients have to travel to the wound edge. One study reported a significant decrease in Gram-negative rods (e.g., Pseudomonas) in biopsy specimens harvested from NPWT-treated wounds but also noted more Staphylococcus aureus in NPWT-treated wounds.20
Both Saxena and Green demonstrated that as negative pressure draws wound tissues into the open pore foam dressing, it strains underlying cells, promoting cell division and granulation tissue formation.1,22 Multiple animal studies demonstrate that the wounds treated with 125 mmHg NPWT fill with granulation tissue significantly faster than wounds treated with more or less pressure.23
What You Should Know About Innovative NPWT Devices
The success and high demand of NPWT has led multiple manufacturers to develop and bring to market new and innovative devices. The Vacuum-Assisted Closure Therapy System (VAC Therapy, KCI), the most widely used electrically powered NPWT system today, was the first commercially available NPWT device and remains the most studied NPWT system.
Many NPWT devices are similarly configured to the VAC Therapy System but manufacturers often differentiate the new systems with improved portability, ease of use and patient comfort. Authors have advocated the use of gauze-based NPWT as an alternative to foam as one way to improve comfort during dressing changes.24,25 In a prospective study of 131 patients, Dunn and colleagues found that gauze-based therapy was indeed effective to reduce wound volume, manage exudate and infection, and improve wound bed quality and granulation.26 To date, there are no studies comparing gauze to foam-based NPWT. 
The Smart Negative Pressure (SNaP) Wound Care System (Spiracur) introduced the advent of mechanical power instead of electrical power to generate subatmospheric pressure. This single-use, portable device uses specialized springs to generate a preset continuous subatmospheric pressure level similar to the VAC Therapy system.27-29 According to the manufacturer, the SNaP Wound Care System is fully disposable and silent throughout its operation, and is available for “off-the-shelf” use.28,29
Armstrong and coworkers performed a randomized controlled trial comparing the effectiveness of the mechanically powered SNaP wound care system with the electrically powered VAC Therapy system for the treatment of non-infected, non-ischemic, non-plantar lower extremity diabetic and venous wounds.30 They found no significant difference in wound size reduction or complete wound closure during 16 weeks of treatment with either device.
How Effective Is NPWT With Instillation?
One of the latest innovation trends in negative pressure is NPWT with instillation. This combines irrigation and lavage of the wound with subsequent fluid removal via negative pressure at automated, timed, repetitive intervals while the foam dressing remains in place. Advanced technology combining the VAC Ulta (KCI) NPWT system with VAC VeraFlo Therapy (KCI) maintains minimum negative pressure between periods of fluid instillation to prevent fluid accumulation and leaks.
Although infusion or “wound chemotherapy” as an adjunct to NPWT is a relatively new concept, preliminary studies suggest that the combined mechanisms may create a synergistic effect on wound healing.31-33 Fleischmann and colleagues first described NPWT with instillation in a 1993 study of non-infected open fractures.34 Since then, several investigators have proposed that NPWT with instillation could be indicated over standard NPWT for wounds with high levels of exudate and bioburden because of the irrigation phase’s potential ability to remove infectious and nonviable material, enhancing wound bed preparation.31,33-35
The irrigation and dilution of infected wounds is standard practice and there are many solutions to decrease bacterial load in wounds. The ideal solution combines the ability to disrupt biofilm and kill bacteria without cellular toxicity or delay in the wound healing process. Authors have investigated several irrigation solutions with NPWT and instillation, but no single agent has demonstrated superiority.31-41
Phillips and colleagues used a porcine model to study the reaction of a Pseudomonas aeruginosa biofilm to NPWT and instillation with six different instilled solutions: saline, povidone iodine, chlorhexidine gluconate, polyhexamethylene biguanide, polydiallyldimethylammonium chloride or a novel antimicrobial solution.38 They found that the novel antimicrobial solution, polyhexamethylene biguanide, polydiallyldimethylammonium chloride and povidone iodine solutions significantly reduced bacterial load of the Gram-negative biofilm in comparison with saline. 
On the other hand, another recent porcine study of full-thickness excisional wounds inoculated with Pseudomonas aeruginosa compared healing with standard negative pressure wound therapy, NPWT and instillation with normal saline, and NPWT and instillation with polyhexanide biguanide and a control.39 They found similar rates of improved healing with NPWT instillation, using both solutions and standard NPWT over control-treated wounds. Bacterial load improved with NPWT over controls. Negative pressure instillation further reduced bioburden over control and NPWT-treated wounds. The authors concluded that given these improvements in bioburden, NPWT and instillation with either normal saline or polyhexamethylene biguanide may be ideal for wounds associated with infection.
Lehner and coworkers conducted a multicenter prospective, non-randomized study using NPWT instillation with polyhexanide in the treatment of infected orthopedic implants.40 They found that the combination of surgical debridement with lavage, systemic antibiotics and NPWT with instillation resulted in the ability to retain the implant in 86 percent of patients with acute infections and 80 percent of patients with chronic infections.
Brinkert and coworkers conducted a prospective study using NPWT and instillation with normal saline in 131 patients with infected or complex wounds.41 After initial debridement and subsequent NPWT and instillation, they noted that 98 percent of wounds were closed at an average of 12 days. While the study authors were satisfied with their results, they noted that instillation of an antiseptic may be beneficial when biofilm is bacteriologically documented or when a zone of exposed material (osteosynthetic/prosthetic) is visible in the wound.
What The Authors’ Experience With NPWT Reveals
The Georgetown team approach to wound healing and limb salvage always starts with the same goals: maximizing blood flow, control of infection, correction of biomechanics and creation of a stable soft tissue envelope.42 Our standard operative approach for treatment of infected wounds is as follows: 1. Obtain deep wound culture specimens prior to debridement 2. Sharp excisional debridement of nonviable tissues 3. Pulse irrigation using 3 liters of normal saline 4. Redraping of the sterile field and the use of new surgical gloves 5. New surgical instruments and use of a separate, clean back table 6. Obtain deep wound culture specimens post-debridement 7. Application of NPWT/NPWT with instillation or closure. 
The patient typically goes back to the operating room for wound closure/coverage versus redebridement two to three days following the initial debridement based on the results of post-debridement cultures and the clinical appearance of the wound.
We recently published our early results of the impact of NPWT with instillation in comparison with standard NPWT in the adjunctive treatment of the acutely infected wound in an inpatient setting.33 This retrospective analysis included 142 patients who required hospital admission and at least two operative debridements with either NPWT or NPWT with instillation at the time of the initial operation. The study compared standard negative pressure with NPWT with instillation using six- or 20-minute dwell times of solution. As we described above, we applied NPWT or NPWT with instillation after the initial operative debridement and at each subsequent operating room visit until the wound was ready for closure or the patient was discharged from the hospital because the infection was cleared.
The instillation solution we used was Prontosan (B. Braun Medical). It provides a combined topical 0.1% polyhexanide (antimicrobial) and 0.1% betaine (surfactant). We set the NPWT at –125 mmHg continuous pressure and determined the volume of instillation by observing foam saturation through a change in color of the foam to a darker black. The negative pressure time was 3.5 hours for the six-minute dwell time group and two hours for the 20-minute dwell time group. The study included infected wounds of all anatomic locations and etiology, but most were on the lower extremity and were ischemic (23 percent), neuropathic (22 percent), surgical (23 percent) or decubitus (22 percent).
At the final analysis, 74 patients received standard NPWT, 34 received six-minute dwell time NPWT with instillation and 34 patients received 20-minute dwell time NPWT with instillation. We found statistically significant differences in the following outcomes.
1. The length of hospital stay between the standard NPWT group was higher (14.9 days) than in the group that received the 20-minute dwell time NPWT with instillation (11.4 days). 
2. There was a statistically significant difference between the operative visits for the standard NPWT group (3.0) and the group that received six-minute NPWT with instillation (2.4), and between the standard NPWT group and the group that received 20-minute NPWT with instillation (2.6).
3. There was a statistically significant difference between the time to final surgical procedure between the standard NPWT group (9.2 days) and the six-minute dwell time NPWT with instillation group (7.8 days), and between the standard NPWT group and the 20-minute dwell time NPWT with instillation group (7.5 days).
4. There was a statistically significant difference between the percentage of wounds closed (delayed primary, skin graft or flap) before discharge in the six-minute dwell time NPWT with instillation group (94 percent) in comparison with the standard NPWT group (62 percent)
Although the overall culture data showed no significant difference between the negative pressure and NPWT with instillation groups, there was a trend toward greater improvement in bioburden in the group receiving NPWT with instillation.To date, this is the only human study comparing traditional negative pressure and NPWT with instillation. Since these early results, we continue using NPWT with instillation to adjunctively treat inpatients with infected wounds. To better identify the effectiveness and most appropriate use of NPWT with instillation, we are currently conducting multiple prospective, randomized controlled studies comparing the effectiveness of negative pressure versus NPWT and instillation, and comparing NPWT and instillation with normal saline versus NPWT and instillation with Prontosan.
Negative pressure wound therapy will likely continue to play a vital role in wound healing as research and technology improve its ability to meet patient needs.
Dr. Oliver is a Diabetic Limb Salvage Fellow at MedStar Georgetown University Hospital in Washington, DC.
Dr. Garwood is a third-year resident with the INOVA Fairfax Residency Program in Falls Church, Va. Dr. Kim is an Associate Professor at the Georgetown University School of Medicine. He is a Fellow of the American College of Foot and Ankle Surgeons.
Dr. Steinberg is an Associate Professor at the Georgetown University School of Medicine. He is a Fellow of the American College of Foot and Ankle Surgeons.
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