Management of Acute and Chronic Wounds Using Negative Pressure Wound Therapy With Instillation and Dwell Time: A Retrospective Review of a 100-Patient Cohort in Padova, Italy

The presence of devitalized tissue and slough in an open wound can be a contributing factor in a prolonged inflammatory response and delayed wound healing.¹ Owing to its viscous texture, slough can be difficult to separate from healthy tissue. One method by which slough and soft infectious materials can be gently removed from the wound bed is negative pressure wound therapy with instillation and dwell time (NPWTi-d), which enables automated delivery of topical solutions to remove exudate and debris from the wound surface.² Desired therapeutic outcomes of NPWTi-d include wound cleansing, promotion of granulation tissue growth, and wound bed preparation for closure.^3-5 This study examines the use of NPWTi-d in a heterogeneous cohort of patients receiving care for various wound types at a hospital in Padova, Italy. Key healing outcomes in each wound category are reported.

This study is an observational retrospective review of 100 patients with wounds managed with NPWTi-d (V.A.C. VERAFLO Therapy; 3M) from January 2013 through December 2017. Deidentified data were collected from medical records from a single institution. Patient consent to treatment was acquired in accordance with institutional and governmental guidelines. This study did not require other informed consent or ethical approval.

Application of NPWTi-d was prescribed in accordance with patient comorbidities, wound characteristics, and current institutional practice. Negative pressure settings ranged from −75 mm Hg to −125 mm Hg, with a dwell time of 3 minutes to 10 minutes and a cycle length of 2 hours to 3.5 hours (Table 1). Initially, normal saline was instilled in 30 cases, 0.25% acetic acid in 20 cases, and 0.05% sodium hypochlorite in 50 cases (this concentration is the only one available at the present hospital; use of Dakin solution 0.125% was not possible) (Table 1). Acetic acid (0.25%) was used for patients who initially presented with signs of infection with Pseudomonas species (abundant blue-green exudate). Sodium hypochlorite 0.05% was used for patients with complex wounds or signs of infection with non-Pseudomonas species (only serosanguinous exudate was present). Normal saline was used for patients with simple wounds, delicate skin, or previous reaction to topical antiseptic solutions. In 2 patients, acetic acid was later changed to 0.05% sodium hypochlorite solution; 1 patient experienced discomfort as a result of the initial application of acetic acid, and the other was switched after the bacterial swab cultures confirmed the clearance of Pseudomonas. In 1 patient, instillation with 0.05% sodium hypochlorite was changed to normal saline after evidence of skin irritation. Dressing changes were performed every 72 hours (including on weekends) or as necessary. Swab samples were collected for microbial testing before and after application of NPWTi-d. Debridement and administration of culture-specific antibiotics for 7 days were performed as necessary. To avoid bias, patients treated with a reticulated open-cell foam dressing with through holes were excluded.

For statistical analysis, data were divided into subgroups based on sex, instillation solution, wound size, and wound etiology. Microsoft Excel was used for all descriptive statistics. Statistical analysis for significance of wound surface area reduction was performed with a Wilcoxon signed-rank test using SAS (SAS Institute), with significance defined as P less than .05.

Patient and wound characteristics

The study population included 100 patients (53 male, 47 female) with a mean age of 63 years (range, 22–95 years). The most common comorbidities were diabetes (40.0%), peripheral vascular disease (36.0%), hypertension (35.0%), and coronary disease (24.0%) (Table 2).

Wounds managed with NPWTi-d were classified into 1 of 8 categories based on etiology, with the most common wound types being peripheral vascular ulcer (28.0%), surgical wound (21.0%), and dehiscence (16.0%) (Table 3). Nearly two-thirds (61.0%) of the wounds were located on the lower limb; the pelvic area was the second most common wound location (23.0%).

Treatment outcomes

Wound management with NPWTi-d continued for a median duration of 11 days (range, 1–35 days). The patient treated for only 1 day stopped the therapy because of a general deterioration of health unrelated to NPWTi-d; no improvement in wound healing was noticed. Overall, wound surface area decreased in 75 patients (75.0%) throughout the duration of NPWTi-d. In the remaining 25 patients (25.0%), there was no difference in surface area. These 25 patients presented without a common wound etiology—among them were 10 peripheral vascular ulcers, 7 traumatic wounds, 3 dehiscences, 2 surgical incisions, 1 diabetic foot ulcer, 1 radiodermatitis injury, and 1 peripheral gangrenous wound with sepsis. In the entire 100-patient population, the median wound surface area decreased from 45.0 cm² before NPWTi-d to 35.0 cm² after NPWTi-d (P <.0001) (Table 4). This decrease in surface area remained significant in both males and females (P <.0001) and based on patients initially receiving instillation with 0.05% sodium hypochlorite (P <.0001), acetic acid (P =.0002), or normal saline (P <.0001). A significant decrease was also observed in small- (< 250 cm²; P <.0001) and medium-sized (250–500 cm²; P =.031) wounds. There was a nonsignificant decrease in the median surface area of large wounds (>500 cm²), from 888 cm² before NPWTi-d to 594 cm² after (P =.250). All the large wounds were positive for gram-negative bacteria, but no other common features were present. A significant reduction in wound area was observed in 5 wound types: peripheral vascular ulcer, surgical wounds, dehiscence, trauma, and pressure ulcer (P <.05) (Table 4).

Prior to the initiation of NPWTi-d, bacterial infections were detected in 72 cases (72.0%) (Table 5). Of these, more than 1 microbe was detected in 33 patients (45.8%) and multidrug-resistant organisms were detected in 11 patients (15.3%). At the conclusion of NPWTi-d, in conjunction with the appropriate administration of systemic antibiotics for 7 days, qualitative swab analyses of 46 cases (46.0%) were positive for bacterial persistence. The largest difference occurred in surgical wounds (preoperatively positive for Morganella morganii and/or Pseudomonas aeruginosa), in which bacterial presence declined from 71.4% to 19.0%; all wounds in which bacteria was detected preoperatively achieved closure by the end of the study. The highest infection rates after administration of antibiotics and NPWTi-d were noted in wounds treated with acetic acid (70.0%), in peripheral vascular ulcers (75.0%), and in pressure ulcers (71.4%); the closure rates for these groups were 90.0%, 89.3%, and 92.9%, respectively (Table 5). 

Wound closure was achieved in 91 patients (91.0%) (Table 5). Of these, 39 (42.8%) were closed by skin grafts, 24 (26.4%) were closed by local flaps, 23 (25.3%) were closed via surgical revision or sutures, and 5 (5.5%) were closed using free flaps. In 3 patients, wound healing was complicated by a general deterioration of the patients' health. Two wounds remained recalcitrant, and amputation was performed in 4 patients. Among patients whose wounds were positive for bacteria persistence at the conclusion of NPWTi-d with antibiotics, the closure rate was 91.3%. In these patients, hydrosurgical debridement was performed along with treatment with a two-step porcine dermal substitute for 14 days prior to final reconstruction. 

Case study

A 41-year-old male with paraplegia resulting from spinal tuberculosis presented to the Department of Plastic Surgery with multiple pressure ulcers. The patient was cachectic and had ulceration at the trochanteric (Figure 1), ischiatic, and calcaneal areas. The stage 4 trochanteric ulcer was managed with debridement involving the coxofemoral joint (Figure 2) and immediate reconstruction using a tensor fascia lata myocutaneous flap (Figure 3, Figure 4). Unfortunately, partial flap necrosis and dehiscence occurred (Figure 5). Analysis of bacterial swab cultures detected the presence of P aeruginosa. Debridement was performed to completely remove the necrotic tissues, and systemic antibiotics were administered during the course of NPWTi-d, which was initiated with instillation of 80 mL of acetic acid, followed by a 10-minute dwell time and 3.5-hour cycles of negative pressure at –125 mm Hg (Figure 6). After 17 days, swab analysis was negative for the presence of bacteria, and 3 days later, debridement and flap revision were performed (Figure 7). The wound remained closed and stable at 6-month follow-up (Figure 8). 

In this cohort of 100 patients, NPWTi-d was a versatile modality used to cleanse a diverse range of wound types in various anatomic locations. In the 2004 article in which its use was first reported, Wolvos⁶ suggested NPWTi-d could be used in cases in which wounds are covered with slough or exudate preventing advancement to the next stage of wound healing. This proposal was subsequently supported in a study by Gabriel et al⁷ comparing 15 patients with complex, open, infected wounds receiving NPWTi-d and 15 control patients with matching wounds receiving standard moist wound care. Although both groups received appropriate antibiotics, time to infection clearance and wound closure were significantly shorter in patients treated with NPWTi-d (P <.001 for both). As reported in these and other publications, NPWTi-d may sometimes be used in the setting of unchanged wound status after an initial application of conventional NPWT.⁸ 

Multiple studies have examined the advantages of NPWTi-d over NPWT as part of a treatment plan with debridement and antibiotics, particularly in patients with infected wounds. In a retrospective, historical, cohort-control study comparing the outcomes of 142 patients with infected wounds who received either conventional NPWT or NPWTi-d with a polyhexanide solution, Kim et al² observed that patients in the NPWTi-d group had fewer operating room visits, a shorter length of hospital stay, a shorter time to final surgical procedure, and a higher rate of wound closure. Likewise, in a retrospective cohort-control study examining differences among 82 patients with infected or critically colonized extremity and trunk wounds receiving NPWT or NPWTi-d using saline or a polyhexanide solution, Gabriel et al⁹ found that patients who received NPWTi-d underwent fewer debridements in the operating room and had a shorter hospital stay, length of therapy, and time to wound closure. 

Despite these results, it is important to note that NPWTi-d is not indicated for managing infection, per the manufacturer’s instructions. However, the literature seems to suggest that NPWTi-d is helpful in the management of complex wounds, especially those that are contaminated or in need of cleansing. In 2012, Goss et al¹⁰ published the results of a single-center prospective randomized trial in which quantitative cultures were obtained preoperatively, postoperatively, and after 7 days of treatment with NPWTi-d or traditional NPWT. The authors¹⁰ reported a mean absolute reduction in bacteria equal to 10.6 × 10⁶ bacteria per gram of tissue in patients receiving NPWTi-d and a mean absolute increase in bacteria equal to 28.7 × 10⁶ bacteria per gram of tissue in patients receiving traditional NPWT. Yang et al¹¹ conducted a randomized clinical trial and reported a significant reduction (43%) in quantitative biofilm-protected bacteria in colonized leg and foot ulcers managed with NPWTi-d with 0.125% sodium hypochlorite without systemic antibiotics, compared with a mean 14% increase in such bacteria among wounds managed with NPWT without instillation. In the authors’ present patient population, NPWTi-d was used in conjunction with antibiotic therapy for 7 days when infection was detected, per 2013 international consensus guidelines¹² for use of NPWTi-d in infected wounds, which have since been updated.¹³ 

In the present study, the majority of patients receiving NPWTi-d experienced a significant decrease in wound surface area; a 91% closure rate was achieved. In addition, NPWTi-d was effective in delivering wound healing support using 3 different types of solutions, which were selected based on the wound characteristics and patient features. Wound surface area decreased in all major wound types, and in medium- and small-sized wounds. Although there was no significant reduction in wound surface area of very large wounds, there were few such wounds and the present results may not reflect outcomes of NPWTi-d usage in the general population. Also, the goals of therapy for large wounds may be different from those for medium- and small-sized wounds. Large wounds often require implementation of prolonged, multistep treatment plans to facilitate the creation of a healthy wound bed. In the current study, 100% of the large wounds were closed, using either a local flap or skin graft.

Within the different wound subgroups, the initial infection rate before NPWTi-d varied from 41.9% to 100%. With appropriate antibiotics, debridement, and NPWTi-d, the proportion of infected wounds decreased in all groups. The effect was not the same in all wound subgroups, however, which may indicate that NPWTi-d offers more benefit for some wounds (eg, peripheral vascular ulcers, surgical wounds) than others. However, even among wounds that were infected at the conclusion of NPWTi-d, the closure rate was high (91.3%). Additionally, the authors observed similar positive outcomes (significant reduction in wound area and high closure rate) between wounds undergoing NPWTi-d with normal saline and topical antiseptic solutions (ie, sodium hypochlorite, acetic acid). This suggests that the mechanism of NPWTi-d—removing infectious slough and materials from the wound site, instilling a topical cleansing solution across the wound surface, and applying negative pressure to the wound bed—may promote wound healing regardless of infection status. According to the literature,^3,5 and in the authors’ experience, a relationship between a specific topical solution and improved wound healing has not been documented. In the present case, the authors obtained improved wound healing using both saline and antiseptic solutions. It appears that the mechanism of NPWTi-d may be enough to stimulate wound healing regardless of the specific topical solution (saline or antiseptic) used, but further studies are required. 

This study is limited in that it lacks a comparative control group. All patients received NPWTi-d at a single health care center. Additionally, wide variation existed in patient age, comorbidities, and wound etiology and location. Wounds were not subcategorized as complex or high-risk, as was done in previously published studies. The wide variance of NPWTi-d settings could be another limitation; in the authors’ experience, these differences do not produce significantly different outcomes, even taking into account the possibility that single-day application or low intensity (eg, −75 mm Hg) may decrease efficacy. However, the diversity of the authors’ patient population and therapeutic regimen may provide insight into how NPWTi-d may benefit the typical patient requiring wound management. 

In summary, the records of 100 patients who underwent NPWTi-d at a single health care center were reviewed and the utility of NPWTi-d to promote wound healing under a variety of circumstances was reported. Over the course of NPWTi-d, important milestones in healing were achieved, including reduced wound surface area, improved bacteria bioburden control, and wound closure. Negative pressure wound therapy with instillation and dwell time provided biomechanical support, delivered sterile and antiseptic topical solutions to the wound surface, and laid the groundwork for potential additional benefit from concurrent therapies. In the authors’ experience, the presence of excessive exudate, highly adherent slough, and positive swab are fundamental for choosing NPWTi-d. Based on these results, NPWTi-d has become among the most used treatments at the authors’ institution, especially in the treatment of patients affected by chronic or acute wounds that are infected or at high risk of infection.

Authors: Franco Bassetto, MD; Eleonora De Antoni, MD; Sandro Rizzato, MD; and Carlotta Scarpa, MD, PhD

Affiliation: Clinic of Plastic Surgery, Department of Neurosciences, University Hospital of Padova, Padova, Italy

Correspondence: Franco Bassetto, MD, Head Clinic of Plastic Surgery, University Hospital of Padova,
Via Giustiniani 2, 35128 Padova, PD, Italy; franco.bassetto@unipd.it 

Disclosure: The authors disclose no financial or other conflicts of interest.