Comparing the Therapeutic Value of Negative Pressure Wound Therapy and Negative Pressure Wound Therapy With Instillation and Dwell Time in Bilateral Leg Ulcers: A Case Report

Introduction. Several reports state that negative pressure wound therapy (NPWT) with instillation and dwell time (NPWTi-d) is useful in the management of intractable ulcers. However, reports comparing the effects of NPWT and NPWTi-d in the same patient are lacking. Case Report. A 76-year-old man with intractable skin ulcers on both lateral malleoli presented to an outpatient clinic. Conservative treatment over a 3-month period had not been effective. The authors applied NPWT to the left leg and NPWTi-d to the right leg with fibular osteomyelitis to encourage granulation for 28 days. Thereafter, they covered both ulcers with split-thickness skin grafts. Negative pressure wound therapy was applied to the both legs for 1 week postoperatively. During periods in which NPWT and NPWTi-d were utilized, the patient received intravenous cefazolin sodium (1 g twice daily), lasting 7 days after skin grafting. Epithelization was completed in the NPWTi-d-treated ulcer in about 3 weeks and in the NPWT-treated ulcer in about 8 weeks due to the difficulty in healing his residual ulcers. In terms of the efficacy of granulation and debridement of infected granulation tissue, NPWTi-d demonstrated better results with increments in the washing amount. Also, NPWTi-d proved superior in terms of the survival status of the skin graft, the time until the residual ulcer disappeared, and the removal of latent bacteria. Conclusions. From this case report, the authors believe NPWTi-d may be more effective in cases with intractable ulcers associated with infection that need better granulation.

In more recent times, the concept of negative pressure wound therapy (NPWT) has been developed further into NPWT with instillation and dwell time (NPWTi-d). There are several reports on its usefulness in wound management of intractable ulcers.^1,2 However, there are only a few reports directly comparing the 2 therapies and no reports comparing both therapies in the same patient. Here, the authors report the case of a patient with bilateral intractable ulcers on the lateral malleoli treated with NPWT (V.A.C Therapy; KCI, an Acelity Company, San Antonio, TX) and NPWTi-d (V.A.C.Ulta; KCI, an Acelity Company).

A 76-year-old man with bilateral skin ulcers on his lateral malleoli was referred to our outpatient clinic (International University of Health and Welfare Hospital, Tochigi, Japan). His medical history included atrial fibrillation and polycythemia vera as past illnesses that were treated with oral medication. Pulsations of the bilateral dorsal pedis and posterior tibial arteries were weak on palpation. Physiological examination, including ankle-brachial index, skin perfusion pressure, and ultrasonic cardiography, revealed no abnormal findings. Computed tomography angiography demonstrated no significant stenosis in the bilateral iliac, femoral, and popliteal arteries above the knee; however, the flows in the dorsal pedis and posterior tibial arteries were weak and those in the fibular arteries were disrupted. Yet, the cardiologists found no indications for vascular intervention to improve the circulation. Magnetic resonance angiography demonstrated partial osteomyelitis of the right fibula confined to the lateral malleoli. Conservative treatment with irrigation, debridement, ointment (petroleum jelly-based material), and trafermin spray performed over a 3-month period had not been effective. With respect to the physical status, the patient could walk with a walking stick, perform daily tasks independently, consume a normal diet, and maintain a good nutritional status. From this, the authors believed the skin ulcer was due to peripheral arterial disease rather than pressure. The patient self-administered the aforementioned conservative wound care treatment at home. 

On admission, the patient presented with round bilateral ulcers, each measuring 2.5 cm in diameter, extending to the periosteum, and containing bacterial biofilm on the surface. He was prescribed intravenous prostaglandins along with resting his legs and continuation of the previously mentioned conservative treatment, but the ulcers did not resolve. Negative pressure wound therapy was applied on the left leg and NPWTi-d on the right leg, which had fibular osteomyelitis (Figure 1). Continuous negative pressure was set at -100 mm Hg on both devices. The volume of saline dripping for the initial irrigation (NPWTi-d) was set at 6 mL every 3.5 hours and the foam was dipped in saline for 10 minutes. Blood sampling demonstrated inflammation (C-reactive protein [CRP]: 5.8 mg/dL) and tissue cultures in the bilateral ulcers demonstrated positive results (3+, Staphylococcus aureus). The patient was treated with intravenous antibiotics. Foams were changed bilaterally with irrigation every 2 or 3 days. Data for the ulcer size, redness and maceration, good and poor granulation tissue formation (including bacterial biofilm), and time required for changing the systems were recorded (Table). In addition, the degree of inflammation by tissue culture and blood sampling on days 0, 10, 20, and 28 after the initial NPWT and NPWTi-d was evaluated. During NPWT and NPWTi-d, the patient was transported by a wheelchair with a plate keeping both legs elevated, walked to the toilet alone, and kept both legs in elevation and lateral malleoli offloaded using pillows while in bed.

On day 10, after initial NPWT and NPWTi-d, yellowish and poor granulation was found in both ulcers (Figure 2). The volume of saline (NPWTi-d) was increased to 10 mL every 3.5 hours. Redness and maceration were seen in the ulcer that was treated with NPWTi-d, and the skin around the ulcer was covered by a hydrogel. 

At 20 days post initial NPWT and NPWTi-d application, although good granulation tissue formation had started, poor granulation tissue (including biofilm) was still present in both ulcers. Therefore, the irrigation setting of NPWTi-d was increased to 16 mL every 1.5 hours and the time when foam was moistened with saline for 5 minutes. At this time, there was more granulation tissue formation on the NPWTi-d ulcer than the NPWT-treated left leg.

Twenty-eight days after the initial NPWT and NPWTi-d applications, inflammation gradually decreased, and the amount of good granulation tissue increased (Figure 3). White blood cell counts were normal throughout therapy; however, CRP levels decreased gradually from 5.8 mg/dL (day 0 after initial NPWT and NPWTi-d) to 1.1 mg/dL (day 28 after initial NPWT and NPWTi-d). Both ulcers were covered with split-thickness skin grafts (NPWTi-d: 3.5 cm x 2.5 cm; NPWT: 2.5 cm x 2.5 cm). Negative pressure wound therapy was applied to both ulcers (negative pressure: -75 mm Hg) for 7 days postoperatively, and, thereafter, they provided conservative treatment with irrigation and ointment. During periods in which NPWT and NPWTi-d were utilized, the patient received intravenous cefazolin sodium at1g twice daily, lasting 7 days after skin grafting. For 10 days post skin grafting, he remained in bed with both legs elevated and lateral malleoli offloaded using pillows; subsequently, he was mobile using a wheelchair with a plate keeping both legs elevated and walked to the toilet until 16 days postop. Thereafter, he underwent rehabilitation to aid walking with a stick. In about 3 weeks, epithelization was completed in the NPWTi-d-treated ulcer, which demonstrated a good postoperative course (Figure 4A). Follow-up blood sampling and magnetic resonance angiography demonstrated no osteomyelitis of the right fibula in the NPWTi-d patient. In about 8 weeks, the NPWT-treated ulcer saw full epithelization because his residual ulcers were difficult to heal (Figure 4B). 

The patient provided written informed consent for the publication of this case report and use of images.

Negative pressure wound therapy has been widely used as an effective treatment for skin ulcers.³ Subsequently, a combination treatment with NPWT and irrigation was reported⁴ and because it improved the effectiveness of NPWT, it was developed commercially. Negative pressure wound therapy with instillation and dwelling can facilitate wound healing using NPWT with irrigation, including dripping saline, and periodic dipping and suction by negative pressure on the wound surface.^1,2

This case report compared the therapeutic outcomes of NPWT and NPWTi-d in the same patient, which included ulcer size, redness and maceration, formation of good granulation tissue, debridement of poor granulation tissue, the degree of removal of bacteria, and time required for changing the systems. Such a comparison of good granulation formation was reported in a previous study that was conducted on porcine ulcers.⁵ Similar studies in human ulcers have not been reported. 

The size of the NPWTi-d ulcer was enlarged 10 days after initial NPWT and NPWTi-d due to maceration. However, no maceration occurred thereafter and epithelization in both ulcers did not start during NPWT and NPWTi-d. The authors determined the difference in ulcer sizes was not significant. 

Redness and maceration were found in the ulcer treated with NPWTi-d until 10 days after initial NPWT and NPWTi-d. However, redness and maceration were not found in the NPWT ulcer until 10 days after initial NPWT and NPWTi-d. 

A previous report⁶ in which NPWTi-d was used in 5 cases for an average of 15 days reported that the wound infection improved and tissue culture results were negative following instillation of antibiotics in a saline solution in 2 cases.² In the present case, tissue culture results demonstrated no significant difference between the number of bacteria in either ulcer. However, the skin graft was well-taken and rapid epithelization was achieved in the NPWTi-d ulcer in comparison with the ulcer treated with NPWT. From this, the authors believe the potential effect for removal of bacteria was better with NPWTi-d.

Lessing et al⁵ reported a study on 12 porcine ulcers to compare the therapeutic value of good granulation formation in ulcers using NPWT and NPWTi-d, which demonstrated that NPWTi-d resulted in significantly better granulation tissue than NPWT. Also, a decrease in the viscosity of the wound discharge and effective removal of the infectious tissue with the use of NPWTi-d was reported.⁶ In the present case, 10 days following the initial applications, and after increasing the saline volume for irrigation, good granulation tissue began forming more in the NPWTi-d ulcer in comparison with the NPWT one. At 20 days following initial NPWT and NPWTi-d application, poor granulation tissue decreased in the NPWTi-d ulcer in comparison with the NPWT one.

Time required for changing the systems, including setting the saline irrigation, took 10 minutes for NPWT and 15 minutes for NPWTi-d initially; subsequently, it was 10 minutes in both systems. Both NPWT and NPWTi-d were mildly painful and stressful to the patient. 

Our report includes the findings from a single patient; therefore, further data from similar cases are needed to draw any significant conclusions.

Good granulation tissue formation and removal of poor granulation tissue was better in the NPWTi-d ulcer treated than the NPWT ulcer. Although tissue culture results were similar between the ulcers, considering the degrees of the skin graft take and time needed to achieve complete epithelization, removal of bacteria may have been more effectively performed with NPWTi-d. After protecting the surrounding skin with a wound-covering material, no redness and maceration was evident in either ulcer. In the NPWTi-d ulcer, despite the fibular osteomyelitis, the wound bed was well prepared and early wound healing was achieved. Thus, utilizing NPWTi-d may be useful for intractable ulcers with infection and ulcers that need sufficient granulation tissue formation. .

Authors: Yuichiro Uoya, MD¹; Naohiro Ishii, MD, PhD¹; and Kazuo Kishi, MD, PhD²

Affiliations: ¹Department of Plastic and Reconstructive Surgery, International University of Health and Welfare Hospital, Tochigi, Japan; and ²Department of Plastic and Reconstructive Surgery, Keio University, Tokyo, Japan

Correspondence: Naohiro Ishii, MD, PhD, Department of Plastic and Reconstructive Surgery, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara City, Tochigi 329-2763 Japan; ishinao0916@gmail.com 

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