Use of Negative Pressure Wound Therapy for the Treatment of Venous Leg Ulcers

NPWT entered the lexicon of wound care in the United States in 1997.¹ In 2000, KCI initiated 2 trials to evaluate the use of NPWT in the management of VLU. Although well designed, these 2 trials (1 with STSG, 1 without) were only presented once as abstracts and only the trial with STSG was published. The results of these company-sponsored trials were supportive of NPWT in the management VLU with compression as well as with and without STSG; however, both trials terminated early and thus, upon trial closure were not significantly powered to provide conclusive evidence in support of NPWT for VLU.^2,3 Both of these trials were presented at the Second World Union of Wound Healing Societies, July 8-14, 2004, in Paris, France.² A Cochrane review published in 2015 concluded that despite some literature suggesting that NPWT may reduce time to healing when used with punch skin graft transplants, there was limited rigorous RCT evidence exhibiting clinical effectiveness of NPWT as an adjunct in the treatment of leg ulcers, and there was no RCT evidence on its use as a primary treatment for VLUs.⁴

Independent of the lack of evidence for the effect of NPWT on time to healing, the goals of NPWT in the management of VLUs are varied. NPWT does not change the underlying pathophysiology of the disease; it affects only the wound surface, not the obstruction or venous reflux in the deep or superficial system. The CEAP classification is an internationally accepted classification system to standardize diagnosis and treatment of chronic venous disorders.⁵ Before initiating NPWT it is necessary to make an image-based diagnosis and determine the patient’s CEAP classification. In addition, based upon recent publications, underlying venous abnormalities that can be corrected—such as superficial venous reflux or deep venous occlusion—should be treated in order to improve healing and to reduce the chance of venous ulcer recurrence.⁶

The 4 primary reasons for use of NPWT in the management of VLUs are promotion of granulation tissue development, wound bed preparation prior to placement of tissue graft, exudate management, and as a bolster over tissue graft. NPWT technology can be used in many ways. In this review, the published evidence for NPWT for these desired outcomes is evaluated and the evidence discussed based on the unique ways in which NPWT is delivered, whether traditional NPWT, disposable or suNPWT, or NPWTi.

Traditional NPWT works by causing tissue deformations at both the macroscopic and microscopic level. At the macroscopic level (macrodeformation), NPWT promotes tissue granulation by exerting a subatmospheric pressure that contracts the wound.^7,8 This contraction pulls the edges of the wound closer together, which facilitates size reduction as the wound heals. At the microscopic level (microdeformation), NPWT exerts cellular and molecular effects. Mechanical stress from wound suction promotes perfusion to the wound edges. Improved flow increases oxygen and nutrient delivery to the tissue edges, which may promote angiogenesis. Suction coupled with the presence of a fluid canister also allows for the consistent removal of wound exudate and infectious material from the wound bed, which helps decrease edema. Together, macrodeformation, microdeformation, and the continuous removal of exudate help facilitate cell proliferation and promote granulation tissue formation for wound closure.^7,8 NPWT can be a highly effective treatment method for promoting granulation tissue formation and reducing wound area in VLUs despite the presence of exudate, large wound size, and the presence of infection.⁹

A portable, disposable alternative to traditional NPWT is suNPWT, which was developed in part to reduce the onus on the patient of carrying a large unit with them and of coping with the noise and attachments or plugs and the other limitations of always carrying a mechanical device. The primary goal of suNPWT is to improve the patient’s quality of life while providing the same benefits as the more cumbersome NPWT.¹⁰ An electrically powered pump is typically used in NPWT, but a mechanically powered device that uses a spring system to produce negative pressure is also available.¹¹ This silent, portable mechanical suNPWT system has demonstrated similar biomechanical properties as electrically powered systems and has shown comparable wound management outcomes. In general, whether electrically powered or not, suNPWT works in the same way as traditional NPWT. Depending on the manufacturer, differences exist in the amount of suction, the frequency of suction monitoring, the amount of fluid the system can handle, and the tissue interface. While the mechanism of suNPWT also involves the application of constant pressure to a wound bed to promote granulation tissue and wound closure, such devices either lack a canister or have a much smaller volume canister for fluid collection; thus, their use is limited to wounds with low levels of exudate.⁹ When indicated, however, suNPWT has been shown to stimulate granulation tissue formation and wound size reduction in the management of VLUs.¹²

NPWTi involves the traditional NPWT system but includes the periodic instillation of topical wound solution to cleanse the wound bed. Instillation cycle time, volume, and negative pressure levels can be tailored to the wound. The foam dressings used in NPWTi are less hydrophobic than those used in traditional NPWT, which permits improved fluid distribution across the wound and removal of debris.¹³ NPWTi is suitable for use in severe VLUs with significant biofilms or preexisting infection, provided appropriate debridement and antibiotic treatment has been initiated.¹⁴  International consensus guidelines published in 2020 state, “in conjunction with appropriate wound care, such as debridement and systemic antibiotics, [NPWTi] may be used as an adjunct therapy…for [VLUs].”¹⁵ NPWTi does not replace debridement, but it can help with removal of exudate, loosened debris, and infectious material post-debridement.¹⁶ Topical antiseptic solutions and saline have both been used in infected or heavily colonized wounds.¹⁵ NPWTi has shown the faster creation of granulation tissue and more rapid reduction in the depth of the wound when compared to NPWT; this finding is independent of what irrigant is being used. The exact mechanism of this is not clear, however, it is noted that NPWTi does a better job of managing the wound bacterial burden.¹⁷

The unimpeded production of granulation tissue is essential for healing most wounds, including VLUs. Granulation tissue functions as the tissue matrix that promotes angiogenesis, reepithelialization, and eventual scar formation in a wound. In normal healing, local inflammation at the wound bed induces cytokines and growth factors that promote granulation and attenuate inflammation.¹⁸ The chronic inflammatory state and associated exudate in VLUs prevent appropriate granulation tissue production. This inflammatory state also predisposes to bacterial colonization and biofilm formation, further preventing wound healing.¹⁹

VLU has been noted to exhibit severe microangiopathy, which results in trophic changes in the skin. The initial increased ambulatory venous pressure is transmitted retrograde into the microvasculature of the skin at the ankle region.²⁰ Franzeck et al²¹ studied the changes in VLU cutaneous microvasculature using dynamic fluorescence video microscopy, fluorescence microlymphography, and tcPO₂ tension measurements in those with CVI compared to controls. While there was normal capillary density, morphologic characteristics, and tcPO₂ in those with mild CVI, there was increased fluorescent light intensity. This difference seen with fluorescence microscopy is due to greater transcapillary diffusion of fluorescein sodium, which serves as a marker of capillary leakage, in the CVI cohort. In the later, more severe stages of CVI (in patients with venous ulcers), capillary thrombosis leads to reduced capillary density. The body responds by enlarging the oxygen exchange surface area, and the remaining skin capillaries become tortuous, resulting in capillary tufts. However, this reduced capillary number results in decreased tcPO₂, which can be extremely low at the ulcer rim or atrophie blanche spots. Interestingly, it appears that fibrin cuffs are not a specific finding for venous ulceration and do not significantly impair oxygen diffusion.

Using fluorescence microlymphography, which permits visualization of the lymphatic capillaries of the superficial skin, it has been noted that in severe CVI the lymphatic capillary network at the medial ankle area is destroyed and the remnant lymphatic capillary fragments have greatly increased permeability.²¹ This is demonstrated by significant leakage of fluorescein isothiocyanate–dextran, which has a molecular weight of 150 000. These findings demonstrate the significant association between the lymphatic and venous systems in severe CVI.²¹ A system that acts at the wound and periwound area to enhance blood flow, improve lymphatic drainage, downregulate MMPs, and manage exudate would be beneficial. Studies have shown these properties to be associated with NPWT.^22-24

Since the first use of NPWT by Fleischmann et al²⁵ in 1993 on 15 patients with open fractures, resulting in rapid development of granulation tissue in the wounds, this therapy has been trialed on all wound types, including VLUs, with promising results. In 1997, Argenta and Morykwas²⁶ published their results of treating wounds with NPWT on 300 acute, subacute, and chronic wounds. Of the 175 chronic wounds studied, 31 were of venous stasis or vasculitis origin ranging in size from 6 cm² to 120 cm² and 90% had failed prior treatments. All these ulcers were treated with NPWT until adequate granulation tissue was obtained and then received STSGs. Of these, 90% were successfully closed after the first STSG and the 3 cases that did not close were attributed to lack of adherence to compression therapy. Vuerstaek et al²⁷ compared NPWT with conventional wound care methods in 60 patients with chronic leg ulcers. The median healing time was 29 days with NPWT compared with 45 days for conventional wound care (95% CI, 25.5–32.5 and 95% CI, 36.2–53.8, respectively; P =.0001). NPWT has been shown to address many of these issues created by the pro-inflammatory state and to help promote wound healing compared with other wound care techniques²⁸ (Figure 1).

Similarly, mechanical suNPWT has demonstrated superior wound healing ability over advanced wound care protocols. In a comparative cohort study, Lerman et al²⁹ examined 63 patients with lower extremity ulcers of diabetic and venous origin, 21 of whom received mechanical suNPWT. Of the 21 wounds treated with suNPWT, 52% were VLUs. Outcomes were compared with 42 matched controls who had received advanced wound care, including skin substitutes and grafting. The authors found a 50% decrease in healing time with use of mechanical suNPWT compared with other treatments (P <.0001). It is important to note, however, that 25% of patients in the suNPWT group prematurely discontinued treatment for various complications such as severe maceration or allergic skin reaction of hydrocolloid dressing.

A small prospective pilot study (n = 12) evaluated suNPWT use in various wounds, including 9 VLUs.¹² Patients with VLUs were treated with 3-layer compression wrap. This study lacked a control group. Patients with VLU demonstrated a 32% reduction in wound size and increased granulation tissue. A small pilot study that evaluated suNPWT along with 3-layer compression wrapping in the management of 15 VLUs showed median surface area reduction from 2.1 cm² to 0.8 cm² (P =.022) and depth reduced from 3.0 mm to 0 mm (P =.005).³⁰ When compared with a similar historical cohort treated with compression alone, it was determined that the addition of suNPWT reduced time to healing from 6.3 weeks in the historical cohort to 4.3 weeks in the study by Wang et al³⁰ (P =.024).

In a much larger prospective controlled trial that included 101 patients with VLUs and 60 patients with DFUs, Kirsner et al³¹ demonstrated that use of suNPWT resulted in decreased wound area and wound depth at a faster rate than traditional NPWT. Additionally, the wound closure rate was higher with suNPWT than with traditional NPWT (45% and 22%, respectively). The authors concluded that suNPWT should be considered first-line therapy over traditional NPWT. One possible reason for this finding is that the pressure associated with NPWT has been demonstrated to reduce tcPO₂.³² While the smaller units with a less deformable foam dressing may well be associated with less reduction in tcPO₂, this has yet to be proved.

Although suNPWT was designed to be more user-friendly, less bulky, and quieter than traditional NPWT while providing similar wound healing outcomes, suNPWT has also exhibited some signs of superiority in animal and clinical studies. In a porcine model comparing traditional NPWT with suNPWT, the latter resulted in accelerated wound closure, reduced wound edge hyperproliferation, enhanced granulation tissue maturation, and increased epithelial migration.³³ It has been hypothesized that owing to the lack of filler and to evenly transmitted pressure across the wound bed and surrounding skin, periwound inflammation was significantly reduced with suNPWT. A study that used ex vivo human skin cultures to assess the mechanisms of action of suNPWT found that suNPWT caused less dermal-epidermal junction disruption, less damage to the tissue at the wound edge, and less activation of pro-inflammatory markers compared with traditional NPWT.³⁴

In a comparison of electrically powered NPWT with mechanical suNPWT, Armstrong et al³⁵ randomized 115 patients with diabetic or venous lower extremity ulcers to either treatment. Wound area was measured at 16-week follow-up. All VLUs were wrapped in multilayer compression therapy over the NPWT device. Despite larger initial wounds in the traditional NPWT group compared with the suNPWT group (9.95 cm² ± 11.38 standard deviation and 5.37 cm² ± 6.14, respectively; P =.0093), there was no significant difference in percentage wound area reduction after controlling for this difference. Patients who received mechanical suNPWT reported less overall interruption to daily activities; however, it is important to note that this group had smaller initial wound size and underwent more frequent dressing changes.

In an RCT published in 2015, Marston et al³⁶ randomized 40 patients with VLUs to either traditional NPWT or mechanically powered suNPWT and found significantly greater wound size reduction with suNPWT. Although initial wound size was larger in the traditional NPWT group than in the suNPWT group (11.60 cm² ± 12.12  and 4.85 cm² ± 4.49, respectively), by 90 days complete wound closure was achieved in 57.9% of patients treated with mechanical suNPWT (11 of 19) and 38.15% of those treated with traditional NPWT (8 of 21) (OR, 2.23; 95% CI, 0.63–7.93). These 2 RCTs reported comparable adverse events for both treatment arms, but they highlighted trends toward fewer allergic reactions and wound infections with suNPWT, which was thought to be attributable to its hydrocolloid dressing.^35,36

It is important to note that with suNPWT, the dressing facing the wound can differ considerably between devices. In most cases, such dressings are not a reticulated open cellular conformable foam. The nonpowered (mechanical) NPWT units do have such a foam, while the other units have a direct wound interface with a fixed porosity; at times these dressings may have trouble with the viscosity of the fluid draining from the open VLU. Fundamentally, the difference in size of the aperture of the contact surface to the wound and the surface tension of the fluid being aspirated can cause dressings with a highly engineered but smaller pore size primary interface to not aspirate fluid effectively.

NPWTi has also outperformed traditional NPWT in a few animal and human trials. In a porcine model, Lessing et al¹⁷ treated full-thickness wounds with either traditional NPWT or NPWTi. Biopsy samples were taken after 7 days for histological analysis to examine granulation tissue thickness and overall edema. The wounds treated with NPWTi exhibited a significant increase in granulation tissue thickness compared with those treated with traditional NPWT (P <.05).

In a small prospective RCT (n = 48) comparing traditional NPWT and NPWTi using normal saline on extremity ulcers, Giri et al³⁷ reported mean reduction in wound size between day 1 and day 10 of 28.8% with NPWTi and 19.8% with NPWT (P <.05). These results suggest that NPWTi may be better than traditional NPWT for the management of lower extremity ulcers. To date, the only other prospective trial to evaluate wound area reduction by comparing NPWTi with traditional NPWT involved patients with postoperative diabetic foot wounds.³⁸ There was no statistically significant difference in outcomes between the 2 groups in that study.

In a large retrospective case-control study, Brinkert et al³⁹ evaluated the outcomes of 131 patients with complex wounds adjunctively treated with NPWTi using saline. Forty-six patients (35%) had previously been treated with traditional NPWT prior to initiation of NPWTi. Ostensibly, those patients had not responded well to NPWT alone. They responded much more favorably to NPWTi. Surgical closure by means of skin graft, tissue flap, or primary closure was achieved in 98% of wounds after treatment with NPWTi.

NPWT has long been recognized as a good way to prepare a wound bed and reduce wound bed depth, but it is rarely used for wound closure. The aforementioned studies of NPWT use in VLUs seem to support its use, especially use of suNPWT for wound bed preparation prior to wound bed closure with STSG or other grafting. NPWTi should be reserved for larger wounds that may require hospitalization for systemic antibiotic therapy, and/or for pain control.

Wound bed preparation is especially important with chronic VLUs, which have stalled in the healing process and are trapped in a pro-inflammatory state that impedes the natural progression to healing. The focus of wound bed preparation is on removal of exudate and infectious materials and reduction of bioburden while promoting improved perfusion and granulation tissue formation.^28,40,41 Wound bed preparation also involves decreasing the bacterial burden of chronic wounds, which many studies report is an important attribute of adjunctive NPWT.^1,13,16,42 Consensus guidelines written by experts have consistently supported the use of NPWT for both wound bed preparation and as a bolster over STSG.^15,43

Vuerstaek et al²⁷ compared NPWT alone (n = 30) with conventional wound care techniques (ie, local wound care and compression therapy [n = 30]) in 60 patients with complex ulcers. Wound bed preparation was faster in the NPWT group, taking only 7 days compared with 17 days for conventional care (P =.005), which is a 58% reduction in median preparation time. In patients who went on to STSG, time to complete healing was 29 days (95% CI, 25.5–32.5) for patients who received NPWT compared to 45 days (95% CI, 36.2–53.8) for the control group. In a study of NPWT in the management of VLU in patients with postthrombotic syndrome, Tekin et al⁴² showed efficient reduction of bioburden. Negative wound cultures were observed after a mean 12.1 days of NPWT, and no patients required further antibiotics after treatment with NPWT.

As mentioned previously, NPWT alone has shown success in managing VLUs even in the presence of infection; however, NPWTi may result in reduced bioburden, resulting in an improved wound bed. Gabriel et al⁴⁴ compared prospective data of 15 patients with complex, infected wounds treated with NPWTi and matched them with retrospective data from 15 patients treated with moist wound care. Decreased bioburden and reduced time to wound healing were achieved with NPWTi. Goss et al¹⁶ noted a significant reduction in bioburden after debridement of VLU followed by NPWTi with quarter strength Dakin solution; bioburden increased after debridement and NPWT alone.

In an animal model, Allen et al⁴⁵ compared adequacy of cleansing, soft tissue damage, and susceptibility to environmental cross-contamination with low-pressure lavage versus with NPWTi. Both techniques properly cleansed wound debris, but 3-dimensional imaging revealed significantly more edema with lavage, suggesting tissue damage, whereas swelling was reduced with NPWTi. The wounds were inoculated with fluorescent bacterial particles prior to treatment and the environment assessed for cross-contamination. Low-pressure lavage aerosolized 50% of the bacterial particles but NPWTi did not, indicating that NPWTi is a much more sanitary means of cleansing wounds in the health care environment.⁴⁵

In a review of NPWTi in dermatology, Müller et al¹³ anecdotally discussed treatment of a circumferential postthrombotic leg ulcer colonized with Pseudomonas aeruginosa. The authors previously had been unable to eradicate the bacteria with other conservative treatments, but with NPWTi using a polyhexanide solution the infection was cleared in 9 days and a healthy granulation bed developed throughout the ulcer. In 2010, Raad et al⁴⁶ demonstrated the sterilization of massive VLUs with an aggressive hospital-based plan that involved NPWTi and sodium hypochlorite solution (Figure 2). The same institution later used this algorithm, where Yang et al⁴⁷ demonstrated a viable clinical outcome for large VLUs (>100 cm²) (Figure 3). High wound closure rates were achieved in a small group of patients with ulcers treated with 7 days of NPWTi followed by STSGs, with 4 additional days of NPWT bolster over the graft. Between these 2 publications the actual mechanism of NPWTi physically changed as the machines were updated. Therefore, the most recent publication has setting recommendations based on the following: the installation volume in cubic centimeters is equal to 20% of the wound area; for example, for a wound measuring 100 cm² the installation volume is 20 mL. The instillation is allowed to dwell on the wound for 10 minutes with a negative pressure cycle of −125 mm Hg for 3.5 hours.

As noted previously, wounds that are recalcitrant to NPWT are “jump-started” by NPWTi.⁴⁸ The exact mechanism for that is unclear, although several have been suggested.^15,16 It should be noted that in theory, NPWTi can be performed in an LTAC setting. However, in the majority of literature on NPWTi for the closure of VLU, the treatment algorithm usually involves debridement followed by NPWTi for 7 days and then closure. Therefore, although the logistics of treating the VLU in the inpatient setting, transferring the patient to an LTAC setting, and readmitting the patient are cumbersome, it is possible to do so.

Few published studies have focused on the use of suNPWT for wound bed preparation. Hampton⁴⁹ demonstrated that the use of suNPWT resulted in an average weekly reduction in size of 21% in 9 patients with nonhealing VLUs. A study in which suNPWT was used in the management of hard-to-heal wounds (including 12 VLUs) in 52 patients found a statistically significant improvement in the healing trajectory as well as a cost reduction.⁵⁰ The previously discussed study by Kirsner et al³¹ included the largest cohort of VLUs treated with suNPWT (n = 101). Using the modified Bates-Jensen wound assessment tool, which accounts for exudate, granulation, undermining, and periwound health, those authors noted that the suNPWT group had a statistically significant greater change in scores compared with the traditional NPWT group, indicating better wound bed preparation with suNPWT.

Many suNPWT devices have a 2-week battery life. Since from a cost prospective a new device needs to be provided at 2-week intervals, 2 weeks of outpatient therapy followed with eventual grafting or other tissue-based therapy make sense. Schwartz et al¹² demonstrated that the reduction in primary wound depth and area resulting from suNPWT in patients with VLU occurred in the first 2 weeks of therapy. Little enhanced effect was noted with an additional 2 weeks of therapy.

There appears to be a benefit to using NPWTi in the management of very large (>100 cm²) leg ulcers and/or infected wounds, but hospitalization is required. If the goal is to close the wound using skin grafts, the treating physician should consider preparing the wound bed with NPWT, suNPWT, or NPWTi. For wounds smaller than 12 cm², it is best to exhaust more traditional methods of wound preparation prior to grafting before resorting to any form of NPWT.

Changing an NPWT dressing on a VLU can be quite painful. Different means of managing dressing changes have been described. In 2 publications by the senior author (JL)^46,47 describing use of NPWTi, the NPWT device was changed only after a neuraxial block had been administered or in the operating room. Wolvos et al⁵¹ described using instillation of lidocaine when using NPWTi. The authors of this review use a tumescent lidocaine mixture if doing this. This mixture is used in endovenous procedures and consists of 440 mL of normal saline, with 60 mL of 1% lidocaine and 24 mL of sodium bicarbonate. Other physicians inject lidocaine directly into the foam and let it indwell. The authors of the current manuscript have no experience with this. However, when using NPWT in the management of VLUs the authors of the current manuscript believe it is paramount to ensure there is a nonstick contact layer between the foam and the open wound.

Drainage and exudate from a chronic VLU can be a significant quality of life issue for many patients. While strike-through of the compression dressing is of great concern to the patient, it is usually less so to the practitioner.⁵² Multiple highly absorbent dressings are available to the clinician to combat these issues. Whether using NPWT or other highly absorbent dressings, the practitioner must be sure to use a good skin preparation surrounding the wound to reduce periwound maceration.

However, in VLUs these fluids are known to contain a host of negative factors. The infiltration of T lymphocytes and macrophages found at the margin of VLUs results in upregulation of intracellular adhesion molecule-1⁵³ and vascular cell adhesion molecule-1⁵⁴ by the affected blood vessel, consistent with the chronic inflammatory response. There is further enhanced expression of leukocyte-associated adhesion molecules, lymphocyte function–associated antigen 1, and very late activated antigen 4 by cells in the microvasculature. Pericapillary fibrin cuffs are composed of actin, type IV collagen, extravasated factor XIIIa and α2-macroglobulin.⁵⁵ Transforming growth factor β expression is also noted.⁵⁶ Nonhealing ulcers have notably increased proteolytic activity, in part owing to high levels of neutrophil elastase, MMPs, urokinase-type plasminogen activator, and extracellular MMP inducer (ie, CD147), as well as decreased activity of tissue inhibitors of MMPs.⁵⁷

Thus, it seems as though a therapy such as NPWT, which has some ability to remove and sequester this fluid and exudate away from the wound bed and in some cases has been observed to downregulate some of these pathways, could be beneficial.²² The ability of NPWT to remove fluid from the wound is often cited, and that function is evident when systems with canisters are used. However, surprisingly little is written about what is in those canisters.^58-60 As of this writing, it is possible to confirm only that NPWT removes fluid and acts as a barrier to strike-through. It is quite difficult to demonstrate improvement in quality of life with NPWT compared with highly absorbent dressings alone. Kirsner et al³¹ demonstrated that patients prefer an suNPWT unit to traditional NPWT; however, that was because of the perceived manageability of suNPWT, not its contribution to fluid management.

Because most portable suNPWT devices lack a canister, wound characteristics and exudate levels are a concern. Hurd et al⁶¹ conducted a prospective 8-week study of 326 patients that included only 21 VLUs. The patients received suNPWT at home and were retrospectively compared with patients whose wounds were treated with traditional NPWT. Data on wound area and exudate levels were gathered weekly by visiting nurses. Although nearly all (91%) of the suNPWT cohort had wounds with low to moderate exudate, 26 patients (8%) still had to discontinue treatment owing to excessive exudate with an insufficient cannister. This was not a complication in the traditional NPWT group of which 89% were wounds with moderate or high levels of exudate. For those who were able to continue suNPWT, 68% healed within the 8-week study period, which was similar to the traditional NPWT group.

Based on the current literature, it seems that NPWT could be used as an exudate management strategy only after the failure of highly absorbent dressings. Even in that limited context, NPWT should be used with a primary focus on wound bed preparation.

It is well recognized that NPWT can have a positive effect as a bolster dressing over STSGs, and in many health care settings such use of NPWT has become standard practice. STSGs may have a higher rate of, more complete, and more rapid closure of VLUs than xenografts, non-autologous allografts, and other nonbiologic grafts. Molnar et al⁶² recommended fixation of a biosynthetic graft with NPWT for 4 to 11 days prior to STSG. Other researchers have shown that fetal bovine collagen can be affixed with NPWT prior to STSG.^63,64 The theoretical advantages of using NPWT as a bolster over skin grafts are that it removes fluid and exudate and provides a barrier against external contaminants.⁴⁰ There is also the theoretical advantage of decreasing the time to adequate inspissation and imbibition.

In a prospective RCT of 20 patients undergoing STSG who served as their own controls, patients’ wounds were split into 2 randomized arms and compared.⁴⁰ The portion of the wound receiving NPWT had equal or better take in 85% of cases. Sapino et al⁶⁵ reviewed graft take on leg wounds above the malleolus and below the knee; these wounds were not specifically venous in nature, but they were located in the same anatomic area as such wounds. The authors reviewed 92 patients, 23 of whom received compression wraps (standard of care) and 69 of whom received NPWT. The mean wound area was significantly larger in the NPWT group than in the compression group (55 cm² ± 7 and 24 cm² ± 6, respectively). The standard of care arm demonstrated a graft take rate of 72% ± 8 (mean ± standard error of the mean), compared with 92% ± 2 in the NPWT group, which was a significant difference (P <.05). Complete graft failure occurred in 4 of 23 patients in the compression wrap group and 2 of 69 patients in the NPWT group.

Carson et al⁶⁶ reported on 50 patients with heterogenous lower extremity wounds treated with STSG and NPWT. NPWT was applied over the STSG and left in place for 7 days. All skin graft sites were fully epithelialized after 11 to 24 days (mean, 17 days). Other studies have shown good graft take and prevention of mechanical graft displacement when NPWT was used in non-venous lower extremity wounds.⁶⁷ Yang et al⁴⁷ reported good graft take of STSG in massive leg ulcers after wound bed preparation with NPWTi; the protocol also included 4 days of NPWT bolster over the graft. There was 70% to 100% epithelialization observed in all 10 patients at 30 days after STSG, and at 6 months 8 of 10 patients had complete closure (Figure 4).

Very good outcomes have been achieved with suNPWT as a bolster over STSGs. Gabriel et al⁶⁸ demonstrated that the use of suNPWT with STSG could be both clinically effective and cost advantageous by expediting patient discharge. The authors evaluated 33 patients who received suNPWT and 25 who received traditional NPWT. On average, the patients who received suNPWT went home the same day, whereas the traditional cohort received inpatient care for 6 days. It is important to note that although this was a heterogeneous patient group, the mean graft take was equal for the 2 groups (98%). Sposato et al⁶⁹ demonstrated that suNPWT can be used in an inpatient setting with good graft take, while permitting ambulation. Seven of 9 cases had 100% graft take, while 1 had 95% take, and the seal was lost in 1 case, which required dressing removal and resulted in 80% take. Similar success was seen in case studies in which mechanical suNPWT was used as a bolster over STSG in the management of other nonhealing wounds: a medial ankle wound⁷⁰ and 2 forefoot amputation wounds of ischemic and diabetic origin.⁷¹  Cuomo et al⁷² identified 10 patients with chronic VLUs treated first with debridement and application of STSG before an suNPWT device was applied to the graft under compression. Dressing change was done every 2 days for 14 days. Eight patients completely healed within 90 days, and 2 patients had only 50% take. Anecdotally, the manuscript authors have successful experience using traditional NPWT for outpatient bolstering of STSG. In the experience of the authors of the current review, although logistically this would not be impossible, it would be quite difficult and impracticable.

NPWTi is not indicated over STSGs or any dermal substitutes because the instillation fluid could lift the graft off the wound bed. A bolster dressing is needed instead, which can be achieved with NPWT or compressive dressing.¹⁵

To date, NPWT is underrecognized as a useful adjunct in the management of VLUs. The literature has shown NPWT to be beneficial by primarily reducing wound area while promoting granulation tissue formation; thus, this therapy is a valuable adjunct in preparing the wound for either a cellular and tissue-based therapy and, more notably, for STSG. This is likely especially true for large VLUs. Although what is considered large may be somewhat arbitrary, it appears that the benefit of NPWT increases with wound size. Management of fluid and drainage appears to be a secondary reason to use NPWT.

Most clinicians who treat VLUs with adjunctive NPWT use it in conjunction with multilayer compression. It is well recognized that increasing venous return with multilayer compression is mandatory for good ulcer healing. Thus, in any setting other than the inpatient hospital setting, for most clinicians adjunctive NPWT is best used in addition to compressive dressing when treating VLUs. Some of the concerns with NPWT stem from the fact that in its initial iterations the tubing that was wrapped inside the multilayer wrap created a significant tissue deformity and, in some cases, created wounds (Figure 5). The tubing was eventually brought out of the of the compression wrap and attached to the dressing.³ Currently it is standard to create a bridge that tracks above the compression wrap. This premade dressing design is now available from some of the major manufacturers.⁷³

Interestingly, suNPWT may not only be as good as traditional NPWT, it may be better in the management of VLUs. Reasons for this, cited by other authors, include but are not limited to the possibility of better adherence owing to decreased inconvenience³⁵ and the potential for decreased inflammation with suNPWT.³³ In addition, compared with traditional NPWT, suNPWT is associated with less disruption to the dermal-epidermal junction, less damage to the tissue at the wound edge, and less activation of pro-inflammatory markers.³⁴ Other authors have noted fewer allergic reactions and wound infections with suNPWT, which is thought to be attributable to its hydrocolloid dressing.³⁶ It has also been hypothesized that the reduction in the so-called stent effect of the bolster results in more evenly transmitted pressure across the wound bed and surrounding skin with suNPWT.³³

Few of the studies reviewed comment on the extent of debridement. Both Goss et al¹⁶ and Yang et al⁴⁷ defined the extensive surgical debridement performed before application of NPWTi (Figure 6). Presumably, most of the outpatient suNPWT involved moderate debridement. It seems that better outcomes can be expected in patients who undergo more aggressive, hemostatic initial debridement.

NPWTi is supported in wounds for which NPWT has been unsuccessful, in large VLUs, and in wounds with significant bacterial burden. After adequate wound bed preparation is achieved, either traditional NPWT or suNPWT is appropriate to use as a bolster over STSGs.

It is important to note that NPWT does not treat the underlying cause of a VLU. Rather, it is an adjunct to allow for reepithelialization, sometimes in the setting of massive ulceration. The primary treatment of VLU remains appropriate compression, with the potential benefit of early superficial venous intervention. Even with a combination of appropriate anatomic diagnosis (functional venous duplex ultrasonography), early venous intervention, NPWT, and grafting, long-term outcomes are reliant upon the venous intervention and concordance with compression, not with the use of NPWT. None of the NPWT studies reviewed purport any improvement in long-term outcomes; rather, they note improved acute wound closure rates.

While suNPWT appears to be equal to or, as some authors contend, superior to traditional NPWT in wound closure,³¹ wound bed preparation, and as a bolster over skin graft, it can also greatly improve patient quality of life. These portable devices improve autonomy and allow patients to return home sooner, reducing costs by shortening hospitalizations. Adequate data exist to support the use of suNPWT in the treatment algorithm for VLUs that do not reduce in size by 40% over 4 weeks of compression therapy, that are of more than 1 year’s duration, or are greater than 40 cm². Ultimately, suNPWT works well in conjunction with other important therapy measures necessary to treat patients with CVI. Negative pressure addresses many of the local wound care needs for VLUs, and concomitant compression therapy and physical activity is made easier with a smaller device.

This is a general review of the literature and is performed by a group from 1 institution, and is therefore prone to bias. There are not adequate studies with similar design or even similar endpoint questions to provide a more formal review of the literature such as a meta-analysis or systematic review. The senior author has been involved in multiple prospective randomized trials around NPWT, which provide both insights and potential bias. Overall, the attempt was to develop a comprehensive review of the potential benefits of NPWT, in its varying forms, for the treatment of VLUs. Non-English reviews and journal articles were not assessed, and not all publications are commented upon.

In summary, NPWT certainly has a role in managing larger VLUs. It would seem from a general utility standpoint that the real benefit of NPWT starts for ulcers that are at least 12 cm² and quite frankly greater than 40 cm². However, it must be noted that NPWT is only a portion of the algorithm of care. One must diagnose the underlying pathophysiology and try to modify it; in addition, compression should be used in conjunction with NPWT. The vast majority of the studies use NPWT in conjunction with compression, despite the fact that the US Food and Drug Administration has not commented on this combination therapy.

A potential algorithm could be aimed to address the patients who have ulcers greater than 40 cm² and do not progress by at least 40% wound area reduction at 4 weeks. This specific group may benefit from NPWT as a portion of wound bed preparation. This NPWT may only require 2 weeks of therapy to maximize outcomes. Certainly, it would appear that in VLUs greater than 100 cm² there is a potential role for NPWTi to help prepare the wound bed prior to application of STSG or a cellular and tissue-based product. suNPWT appears to be very effective for the wound bed preparation component or potentially even as a bolster.

In closing, suNPWT, NPWT, or NPWTi is not necessary to treat every VLU. However, while such therapy is the cornerstone of much of the treatment of deep diabetic foot wounds, postoperative wounds, and pressure-related injuries, this very important therapeutic modality should have a greater role in the treatment of the skin manifestations of venous ulcer disease than it currently does.