Emerging Indications For NPWT

Negative pressure wound therapy (NPWT) is an established adjunctive treatment for chronic wounds with a robust body of support in the literature. These authors discuss emerging indications for NPWT, including the use of negative pressure with instillation, over closed incisions and in possibly enhancing the efficacy of split thickness skin grafts.

Negative pressure wound therapy (NPWT) is a well-known adjunctive modality for healing wounds. A device applies negative vacuum pressure either continuously or intermittently through a material one uses to pack the wound. A sealed disposable container collects the exudate removed from the wound environment. This technology is commonly in use in the setting of wound infection, tissue loss and as a supplement to postoperative soft tissue reconstruction.

The rise in the use of NPWT has led to the conception of numerous other innovations and applications, including the use of NPWT over closed incisions, as an aid to skin grafting and through the use of instillation therapy with NPWT. As NPWT has become readily available and cost-effective, the indications and utility of the modality continue to expand. Accordingly, let us take a closer look at a few of the emerging indications of NPWT and how the evidence supports its use in these settings.

Negative pressure wound therapy has greatly improved the treatment of complex wounds by enhancing the rate of wound healing. In part, this is due to early implementation of NPWT and a more rapid granulation of the wound bed, thereby facilitating more prompt wound coverage and closure.^1,2 We can attribute the beneficial effects of this therapy to the micro- and macro-deformations that occur at the wound surface, an interaction that occurs at the negative pressure foam and tissue interface. These interactions accelerate the wound healing cascade through increased angiogenesis, cellular migration and granulation tissue formation while removing excess interstitial fluid, thereby stabilizing osmotic gradients and reducing edema.^3-6

Although it is greatly beneficial to use NPWT in the setting of infection and extensive soft tissue loss, it is important to note that NPWT most usefully serves as an adjunctive therapy along with proper antibiosis, adequate debridement of infection, optimization of in-line blood flow and management of biomechanics. Once these other factors are in place, NPWT may serve as a temporary mode of wound coverage for the purpose of preparing the wound bed for eventual coverage with healing by secondary intention, delayed primary closure, skin grafting, local tissue rearrangement or the use of free tissue transfers.

Multiple studies have validated the use of NPWT for the purpose of encouraging wound closure in diabetic limb salvage. One such study conducted by Blume and colleagues is a multicenter randomized controlled trial of 335 patients with diabetic foot ulcers.⁷ The authors compared the efficacy of moisture-retentive dressings, which they termed advanced moist wound therapy (AMWT), against NPWT. In this study, the authors found a significantly higher proportion of patients receiving NPWT achieved 100 percent reepithelialization in comparison to those who received AMWT within the 112-day treatment period and experienced fewer secondary amputations. Armstrong and coworkers also showed that NPWT is equally efficacious for acute wounds (less than 30 days in age) and chronic wounds.⁸

Another area where NPWT has been of value is its use in patients who have sustained wounds secondary to burns. Prevention of poor outcomes and negative sequelae related to burn injury are important goals, particularly in relation to highly functional anatomic locations such as the extremities. Researchers have described NPWT as an effective modality in the management of second- and third-degree burns. Negative pressure is an adjunct to aggressive fluid hydration, control of infection, pain control, nutritional support, surgical debridement, escharotomy or surgical fasciotomy as required on a case by case basis. Prompt use of NPWT is vital in order to prevent evolution of the burn wound in the reversible area known as the “zone of stasis,” which correlates to the development of edema in the first 24 hours following injury.^9-11

Implementation of NPWT in burn wounds reduces exudate, promotes angiogenesis and granulation tissue formation, and has proven to be effective for wound healing and maintaining the functionality of hands following burn injury.¹² Stimulation of healthy granular tissue over exposed bone, muscle or tendon may reduce the need for complex soft tissue reconstructions. In addition to these benefits, there are the merits of decreased dressing changes with NPWT in comparison with standard dressings in this cohort.

The painful nature of burn wounds with intact nerve endings highlights the importance of minimizing the frequency of dressing changes in this population. However, in cases of burn injury in which NPWT can still be painful, one may need to titrate the amount of negative pressure. In these cases, clinicians should adjust it to 75 mmHg based on patients’ pain level.¹³

How Current Evidence Supports The Use Of NPWT With Instillation

Negative pressure wound therapy with instillation (NPWTi) is for wounds that benefit from application and removal of a topical solution in conjunction with the benefits of NPWT. The device functions in three phases: instillation of fluid, a pause to allow for the solution to soak (dwell time) and subsequent removal of the instilled fluid with continuation of negative pressure for a predetermined duration of time. Authors have suggested a variety of fluids for instillation, including 0.9% saline, 0.1% polyhexanide and 0.1% betadine (Prontosan, B Braun), betadine and Dakin’s solution, and acetic acid as well as antibiotic solutions.^14,15

Our group at MedStar Georgetown University Hospital conducted two studies regarding NPWTi. We undertook the first study in order to evaluate the effectiveness of NPWTi and if the length of dwell time had an effect on patient outcome.¹⁶ The study was a retrospective, cohort controlled study of 142 patients having serial debridement (more than two surgical debridements in the operating room during the patient admission). Seventy-four patients received standard NPWT, 34 patients received NPWT instillation with a six-minute dwell time and 34 received NWPTi with a 20-minute dwell time. The instillation fluid used in this study was Prontosan.

The results revealed a decreased hospital length of stay in the 20-minute dwell time group in comparison with standard NPWT and a decreased number of operating room visits with both the six-minute dwell time group with standard NPWT, and the 20-minute dwell time group with standard NPWT.¹⁶ We also found a decreased time to final surgical procedure during the hospital admission in the six-minute dwell time group with standard NPWT and in the 20-minute dwell time group with standard NPWT. There was no significant difference in outcomes between the six-minute and 20-minute dwell time groups, suggesting that an exact dwell time may not be of importance.

Our group also sought to assess the importance of type of installation fluid on the effectiveness of NPWTi by conducting a prospective randomized controlled trial of 100 patients with infected wounds who were admitted for serial debridement.¹⁷ Dwell time for both groups was 20 minutes and this was followed by two hours of continuous NPWT. Patients were randomly assigned to receive NPWTi by normal saline or Prontosan. There were no significant differences between the two groups for the number of operating room visits, length of hospital stay or the proportion of wounds that were closed during admission or remained closed at 30-day follow-up.

The results of the aforementioned studies suggest that although instillation is beneficial, the choice of instillate itself does not alter the patient’s outcome. Rather, the fluid dynamics provided by instillation, dwell period and removal of fluid may possibly have an influence on decreasing biofilm and may cause favorable deformation of the wound bed.

Another area of utility for NPWT with instillation is its use in the setting of hardware infection, particularly for the purpose of decreasing implant bioburden. There are many bacteria that produce factors such as adhesins that facilitate adherence of microorganisms to hardware by modulating surface tension and electrostatic forces to their advantage. In addition to the ability to adhere to hardware, bacteria also produce a protective matrix. This network allows bacteria to survive by entering a quiescent state to evade host immune response and interact via quorum sensing and gene transfer.¹⁸ Surgical debridement and systemic antibiotic therapy are paramount in these instances. Negative pressure instillation with a surfactant could also be of use in the setting of intact hardware to prevent adherence of organisms and thereby decrease biofilm production.

A multicenter, prospective, observational study of 32 patients with total knee and total hip arthroplasties examined the implant salvage rate following acute (within eight weeks of implant placement) and chronic (greater than eight weeks after placement) implant infection.¹⁹ Researchers used NPWTi (with Prontosan) in conjunction with surgical debridement, lavage and systemic antibiotics. At four to six months’ follow-up, the results showed a total implant retention rate of 86.4 percent with acute infection and 80 percent with chronic infection. However, this study used no control group so it is not possible to attribute the retention of the implant to utilization of NPWT with instillation itself.

There have been no randomized prospective clinical studies that quantitatively evaluated whether NPWTi is superior to standard NPWT or if a type of instillate is more effective in the setting of infected surgical hardware with reducing bioburden. At our institution, we have typically removed infected hardware and utilized NPWTi with normal saline in order to intermittently lavage and evacuate any possible remaining bioburden while we await culture results prior to further therapy.

In the setting of soft tissue infection with underlying or exposed hardware that we cannot remove, we have had favorable results using NPWT instillation with Prontosan. We utilize what has been described as the “German experience,” placing the foam in direct contact with the hardware. We temporarily close the surrounding soft tissue with retention sutures and drape it in the conventional manner. The purpose of doing so is to decrease the risks associated with hardware explantation, particularly if removal will result in osseous instability. Further work is required before evidence-based recommendations can provide guidance in this regard.

Key Insights On Incisional Negative Pressure Wound Therapy

A more recent indication of NPWT is the use of the modality over closed surgical incisions. Research has shown the technique of closed incisional negative pressure wound therapy (iNPWT) to be an effective way to reduce surgical site infection in comparison to standard dressings.²⁰

Researchers have assessed iNPWT in the setting of high-energy lower extremity trauma through a multicenter prospective randomized controlled trial, which included patients who had open reduction and internal fixation (ORIF) following closed tibial plateau, pilon and calcaneal fractures.²¹ The study had two treatment groups with one group receiving iNPWT set at -125 mmHg and the other group utilizing a standard dressing. Following ORIF, incisional NPWT and standard dressing changes occurred on postoperative day two and every one to two days thereafter until wound drainage was minimal. Between the two groups, there were significantly fewer surgical site infections and less wound dehiscence in the iNPWT group. Of note, calcaneal fractures were the most common fracture type to develop wound dehiscence.

The iNPWT method is also in wide use in total joint surgery. A retrospective study compared iNPWT to standard dry dressing following total ankle arthroplasty by a single surgeon through an anterior incision.²² There were two study cohorts of 37 patients each. In the active treatment group, patients had continuous negative pressure at -80 mmHg for a period of six days postoperatively. The study revealed that the standard dressing cohort had significantly more wound healing problems that were defined as presence of wound dehiscence, eschar or drainage over three weeks postoperatively. No significant difference was evident in surgical site infections between the two groups in this study.

An international multidisciplinary consensus states that the majority of evidence supports the use of closed iNPWT for the use of decreasing wound dehiscence, surgical site infection, hematoma or seroma formation.²³ Although this technique may not be warranted for all surgical incisions, one can particularly consider iNPWT for those who are at a higher risk of developing surgical site infection, such as those with obesity (BMI > 30), uncontrolled diabetes mellitus (hemoglobin A1c > 8% or perioperative glucose > 200 mg/dL), or when there is prolonged surgical time, tobacco use and corticosteroid use.^24,25

At our institution, we frequently utilize incisional NPWT. We have found it most beneficial in reducing postoperative surgical site complications including seroma or hematoma formation, maceration at the incision site, postoperative edema, and minimizing tension across the incision to reduce postoperative scarring.²⁶

With the advent of portable devices, one can administer iNPWT on an outpatient basis following surgery. For total joint or trauma surgery, one typically removes the device seven days from the time of surgery during the first postoperative visit and applies a dry dressing and splint or cast. For the purpose of a limb salvage procedure, remove the portable device on postoperative day seven. One may eventually reapply the portable device depending on the clinical examination of drainage and reevaluate the device at further clinic follow-up.

How NPWT Can Aid With STSG Coverage

Split thickness skin grafts (STSG) serve as a useful way to obtain coverage over wounds that are not amenable to primary or delayed secondary closure. Many factors play a role in successful graft take, including optimized host factors, adequate blood flow, eradication of infection and adequate protection of the graft. Failure of a graft most often occurs secondary to shear forces that disrupt neovascularization, seroma or hematoma formation (which prevents adequate contact with the native tissue base), and infection.

As we previously stated, NPWT may be an adjunctive therapy following surgical debridement of an acute or chronic wound in order to stimulate angiogenesis and granulation tissue formation, both of which aid in preparing the wound base for skin grafting. To assist further with the process of wound bed preparation, one can use NPWT with tissue biologics such as dermal substitutes and collagen matrices. This can hasten the maturation period when one places these modalities over exposed bone and tendon.^27-29

Negative pressure wound therapy can also play a critical role in securing skin graft take postoperatively. In a retrospective study of 50 burn patients who received STSG along with portable NPWT as a bolster dressing, Mushin and colleagues evaluated the efficacy of treatment.30 Physicians set the NPWT at -125 mmHg and removed the dressing on day five postoperatively during their first clinic follow-up. Results from this study revealed an average time to heal of 16 days and average graft take of 99.2 percent with one patient requiring repeat STSG.

A prospective randomized controlled study involved the application of 40 STSGs for 30 burn patients.³¹ Authors investigated if the application of NPWT following STSG increased graft take in comparison to conventional dry dressing. Twenty-one of the grafts were covered with NPWT set at -80 mmHg while the other 19 grafts served as the control group with conventional dressings. The study authors inspected all grafts on day four, at which point NPWT dressing use ended. The surgical team evaluated the grafts for percentage of graft take on day nine. The NPWT group had an average graft take of 96.7 percent while the control group had an average graft take of 87.5 percent.

Another prospective randomized controlled trial investigated this concept in 23 patients, eight of whom received only meshed STSG.³² The other 15 patients received STSG and NPWT after a previously unsuccessful trial of four weeks with skin graft and occlusive dressing. Of note, the study excluded patients with end-stage renal disease or poorly controlled diabetes. The negative pressure setting was -75 mmHg and dressing changes occurred after five days. Negative pressure continued at that time as long as there continued to be exudate formation. Although there was no significant difference in graft take, the NPWT group had significantly reduced pain after therapy in comparison to the conventional dressing group.
 
What The Future Holds For NPWT

Future considerations for instillation therapy will include culture-driven antibiotic instillation therapy to allow for local delivery, which could decrease the dose requirement for systemic administration and lessen the risk of adverse events such as nephrotoxicity. Furthermore, one could potentially employ advances in autologous stem cell therapy in the form of an instillate to deliver targeted regenerative therapy. A similar approach can occur with the delivery of chemotherapy as an instillate following surgical excision of malignancy. Further advances in biomedical engineering will dictate the use of molecular and stem cell biology for our patients.³³

Portable technology has allowed the continuation of NPWT in the outpatient setting. Future developments in telemedicine may allow remote monitoring of wounds in patients with portable NPWT devices that could send data regarding direct temperature measurement or measurement of wound dimensions to the practitioner.³³

Finally, modifications to NPWT devices for the purpose of delivering therapy to patients in developing countries are reportedly effective.³⁴ A further focus on making this cost-saving therapy available to patients globally regardless of socioeconomic status will be a large step in tackling this worldwide issue.

In Conclusion

The beneficial use of NPWT cannot be overstated. Its wide applicability and effectiveness make it a key adjunctive treatment for our patients, regardless of the extent or chronicity of the wound. Despite the therapy’s increasing use, much of the published literature relies on observational studies, making it difficult for diverse clinical applicability. The current evidence supports the adjunctive use of NPWT for its emerging indications and further work needs to occur to continue to guide the role of this modality in our clinical practice.

Dr. Ragothaman is a first-year resident in the Division of Podiatric Surgery at MedStar Washington Hospital Center in Washington, DC.

Dr. Elmarsafi is a Fellow in Diabetic Limb Salvage within the Department of Plastic Surgery at MedStar Georgetown University Hospital in Washington, DC.

Dr. Kim is a Professor in the Department of Plastic Surgery at MedStar Georgetown University Hospital in Washington, DC. He is a Fellow of the American College of Foot and Ankle Surgeons.

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