Use of Negative Pressure Wound Therapy With Instillation and Dwell Time in All Phases of Care for the Management of Complex, High-risk Wounds: Two Case Reports of Necrotizing Fasciitis

Necrotizing fasciitis is a rare and destructive clinical entity requiring aggressive surgical and medical management. Left untreated, mortality rates approach 100%; however, with prompt diagnosis and management, current rates have been reported to be around 20% to 30%.^1,2 The gold standard treatment involves radical debridement, judicious irrigation, and prompt administration of appropriate broad-spectrum antibiotics. 

Although lifesaving, treatment often leaves patients with extensive, full-thickness soft tissue defects that require reconstructive procedures such as skin grafting and free flaps. Without proper wound/graft management, these patients are at risk for requiring multiple grafting procedures due to graft or flap rejection and/or failure. Thus, it is in the best interest of both the health care system and patient to minimize unnecessary operative procedures by maximizing the success of completed interventions. Modern medicine has brought the advent of negative pressure wound therapy (NPWT), which has been shown to have great clinical benefit when used in traumatic and/or infected wounds.^3,4 It also has been proven to be significantly beneficial when utilized in skin graft management.⁵

Recently, the addition of instillation and dwell time (NPWTi-d) has expanded the scope of this technology. Negative pressure wound therapy with instillation and dwell time has successfully and safely been utilized in complex wound management, including in cases of necrotizing fasciitis.^6,7 However, no studies to date have examined its direct effects on grafts. Despite the lack of clinical or laboratory evidence, new expert consensus guidelines published in International Wound Journal recommended against the use of NPWTi-d in graft cases, citing the risk of instillation fluid causing the graft to drift from the wound bed.⁸ The authors postulate NPWTi-d could instead offer theoretical benefits in graft care. The purpose of this case report is to demonstrate the efficacy and safety of the utilization of NPWTi-d in all phases of care including after graft application as a bolster. The following 2 cases of lower extremity necrotizing fasciitis with high-risk wounds utilized NPWTi-d throughout all phases of care, including as a bolster.

Patient 1
A 57-year-old female with a past medical history significant for chronic obstructive pulmonary disease, cardiomyopathy, morbid obesity, and poorly controlled type II diabetes with associated peripheral neuropathy reported that a few weeks prior to presenting to the emergency department (ED), a broomstick fell and struck her left proximal tibia creating a superficial wound. Over the course of a couple weeks, the patient reported progressive expansion of erythema and edema. The superficial wound eventually ulcerated and began draining a cloudy fluid. Due to the absence of pain and systemic symptoms, the patient elected to attempt local wound care alone. However, she eventually injured her left leg again by falling onto a safety pin creating new wounds distally that quickly ulcerated and started draining. Shortly after this injury, she developed shortness of breath and felt increasing pain. Attempting to alleviate her discomfort, the patient smoked marijuana and methamphetamines. These both failed to improve her symptoms, so she decided to seek professional medical attention. 

In the ED, the patient was hypertensive (210/118 mm Hg), febrile (102.9^oF), and tachypneic (30 breaths per minute) with an oxygen saturation of greater than 98% on room air. A focused physical exam revealed an insensate left lower leg with proximal and distal wounds surrounded by areas of erythema. Wounds had active cloudy drainage; however, there was no gross purulence expressible (Figure 1). Cultures from the open lesions were obtained at bedside, and the patient was empirically started on vancomycin and cefepime. Inflammatory markers were found to be highly elevated, and initial basic chemistry panel revealed hyperglycemia, elevated creatinine levels, and lowered glomerular filtration rate. Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was calculated to be greater than 6. Presumptive diagnosis of necrotizing fasciitis was made, and the decision to operate emergently was made. 

Before transfer to the operating room, the patient experienced acute respiratory decompensation requiring intubation and resuscitation. Once she was stable enough for transfer, she was transported to the operating room for initial irrigation and debridement. Dishwater-like fluid was encountered with gross compromise of myofascial planes. Nonviable, avascular tissue was excised until healthy tissues were encountered. Negative pressure wound therapy with instillation and dwell time (V.A.C. VERAFLO Therapy; 3M + KCI) with a reticulated open cell foam dressing with through holes (V.A.C. VERAFLO CLEANSE CHOICE Dressing; 3M + KCI) were applied, and the patient was transferred to the intensive care unit. Three days later, an additional irrigation/debridement and NPWTi-d exchange was performed (Figure 2). Significant improvement of the soft tissues was noted.

The following week, the patient underwent a final irrigation/debridement where tissues were deemed ready for soft-tissue coverage. Thus, split-thickness skin graft (STSG) application was performed with a NPWTi-d bolster. The NPWTi-d bolster was changed at bedside on postoperative day 5 with greater than 90% graft viability (Figure 3), and within a few days, she was transitioned to medical honey and soft dressings. She was discharged home against medical advice after refusing intravenous and oral antibiotics. Despite this, at her most recent follow-up, the patient’s wounds were found to have completely healed without complication (Figure 4). She remains ambulatory and has returned to her prior level of activity, umpiring for little league baseball.

Patient 2
The second patient was a 64-year-old female with a past medical history significant for hypertension and hyperlipidemia. The surgical history was significant for multiple uncomplicated gynecologic procedures, and the patient denied recent drug or alcohol use. One week prior to admission, the patient reported dropping a knife onto the dorsum of her second toe creating a superficial wound over the distal interphalangeal joint. Progressive erythema, edema, and pain developed over several days before the patient sought medical treatment at an urgent care clinic. The patient was diagnosed with cellulitis, prescribed a course of cephalexin and doxycycline, and instructed to follow-up with an orthopedic surgeon. Despite compliant oral antibiotic use, the erythema and edema continued to progress with eventual development of blisters on the dorsum of the foot. When the patient was seen for her follow-up at an orthopedic surgery clinic, concern for developing necrotizing fasciitis was raised, and the patient was immediately transferred to the ED for appropriate work-up and management.

Laboratory work-up in the ED revealed leukocytosis, hypokalemia, elevated C-reactive protein/erythrocyte sedimentation rate, and anemia. The LRINEC score was calculated at 6. On physical examination, the patient was afebrile with vital signs within normal limits. The patient denied fevers or other constitutional symptoms. Focused physical examination of the right leg demonstrated a neurovascularly intact extremity with ascending erythema/edema and multiple hemorrhagic bullae (Figure 5). Open skin lesions over the distal interphalangeal joint of the second toe and proximal tibia were noted; however, there was no expressible purulence/exudate from the wounds. She was tender to palpation to the entire right lower extremity distal to the knee. Preliminary diagnosis of necrotizing fasciitis was made. Bedside wound cultures were obtained, the infectious disease team was consulted, and the patient was started on prophylactic vancomycin, clindamycin, and meropenem. She then was transported to the operating room for emergent necrectomy and irrigation. 

In the operating room, necrectomy was performed with extensive removal of nonviable tissues. Dishwater-like fluid was encountered and tracked along fascial planes beyond cutaneous erythematous margins. Intraoperative cultures and tissue samples were taken, and excisional debridement was carried out until only vascular and viable tissues remained. Copious irrigation was performed and hemostasis achieved (Figure 6). Negative pressure wound therapy with instillation and dwell time with the ROCF-CC dressing was applied with a 10-minute dwell time cycled every 3 hours and suction set to -125 mm Hg. Wound cultures ultimately returned negative (likely due to previous antibiotic exposure); however, final fascial tissue histology confirmed the presence of necrotizing fasciitis. 

On postoperative day 3, the patient underwent repeat irrigation/debridement and NPWTi-d exchange. After a few additional days, final irrigation/debridement was performed with evaluation of the wound to determine if it was amenable to skin grafting. Vastly improved tissues were encountered, so repeat cultures/tissue samples were obtained, copious irrigation was performed, and STSG application with an NPWTi-d bolster was done (Figure 7).  

The rest of this patient’s hospital course mirrored the previous patient with a bedside NPWTi-d bolster exchange on postoperative day 5 (Figure 8) and eventual transition to medical honey and soft dressings. There was greater than 90% graft viability without requirement for additional debridement/irrigation. The patient then was discharged to home on a multi-week course of cephalexin and doxycycline per infectious disease recommendations. The wounds went on to heal without complication (Figure 9); the patient resumed her previous levels of activity. 

Technique of application of NPWTi-d bolster for both cases
After extensive and thorough debridement and irrigation is performed, STSG placement is performed utilizing either staples or running-chromic gut sutures. In cases of necrotizing fasciitis, the authors often used a 2:1 ratio (as in the present cases) as the tissue defects tend to be extensive. A protective layer of a nonadhering dressing (ADAPTIC Non-Adhering Dressing; 3M + KCI) is placed over the underlying graft to prevent excess adhesion of the graft to the overlying sponge. The honeycomb contact layer sponge was applied over the nonadherent layer, and subsequent layers of the NPWTi-d system were applied per normal routine. In general, the authors prefer to halve the width of the thickest sponge, as they find using it directly out of the package adds unnecessary bulk to the dressing. Then, the NPWTi-d pad was applied to the center of the graft (if a combined instillation port/suction pad is utilized). However, when there are separate instillation ports and pads available, the authors place the instillation port at a nondependent position, and the pad at a dependent part of the NPWTi-d (as seen in Figure 7). The assist feature is used to determine the proper amount of instillation volume (just enough to shadow the sponge). The authors’ preference is to use a cycle setting of 10-minute dwell time every 2 to 3 hours depending on wound contamination with suction set to -125 mm Hg continuous. They also utilize iodine-impregnated adhesive dressings (Ioban Drape; 3M) to reinforce NPWTi-d units to reduce the potential risk for loss of seal and/or unit that is vital to maintain. The rationale behind this is that NPWT has been reported to be a physical barrier to outside bacterial contamination, and the authors found iodine-impregnated adhesive dressings to be a suitable reinforcement that may help decrease the odds of external bacterial colonization if the NPWT unit were to lose function.

The donor site is dressed with xeroform, moist gauze with epinephrine and normal saline solution, and a clear dressing that is removed on postoperative day 2. The entire extremity was overwrapped with cast padding, a splint to immobilize the extremity (to reduce shearing forces) was placed, and the final bandaging layer was applied.

Given the mortality rate and potentially devastating consequences associated with necrotizing fasciitis, prompt and aggressive treatment is recommended if there is any clinical suspicion.⁹ Radical debridement of clearly nonviable and compromised tissues (necrectomy) in tandem with an appropriate antibiotic regimen is gold standard treatment. Nevertheless, even with aggressive surgical and medical management, amputation rates of 50% and mortality rates of 29.3% have been reported.^10,11 

Frequently after amputation or radical debridement, patients are left with large tissue defects that require additional soft tissue procedures, ranging from split-thickness skin grafting to free flaps.^12,13 Exact rates of grafting procedures after necrotizing fasciitis debridement are poorly reported in the literature, but one study reported rates of over 20%.¹¹ Because of the relative rarity of these infections, the rates and factors associated with STSG success in necrotizing fasciitis cases are unknown. 

Nevertheless, research has revealed patient and wound-specific variables associated with overall graft success and failure. Regarding patient-specific characteristics, it is vital that providers consider and/or identify the presence of various patient comorbidities that may adversely affect graft outcomes. Studies indicate comorbid conditions, such as peripheral vascular disease, diabetes, and cardiovascular disease, significantly reduce the likelihood of STSG success.¹⁴ Thus, it is important patients be medically optimized before any attempt at soft-tissue coverage. 

After medical optimization, the next issue to consider is local wound factors and if the wound has the capacity to accept and heal a graft. Acute STSG failure is most commonly attributed to hematoma/seroma formation due to disruption of the imbibition phase of graft healing and mechanical prevention of graft adherence.¹⁵ Infectious causes are believed to be the next most common cause of acute failure and is the most common cause of late failure. Elevated bacterial load (quantified as ≥ 10⁵ CFU/g) in the wound bed has been identified as a significant risk factor for reduced graft uptake.¹⁶ In addition, both the quantity and type of bacteria matter. Specifically, Pseudomonas and/or Staphylococcus species have been found to have statistically significant adverse effects on graft take.¹⁷ By being aware of and identifying these wound- and patient-specific risk factors, providers can formulate treatment strategies that maximize patients’ potentials for good outcomes.  

Studies analyzing wound and graft care have been successful at identifying risk-factors associated with failure as well as discerning variables associated with increased graft success that can be capitalized on. One of these variables is the use of NPWT (during pre- and post-grafting wound management), and another is the presence of a clean wound bed (defined as a negative wound culture at time of the most recent debridement prior to grafting). 

Negative pressure wound therapy likely benefits wound healing and graft take through a few mechanisms. Firstly, NPWT promotes angiogenesis, indirectly improving the ability for the wound to combat infection. Secondly, the NPWT unit acts as a physical barrier to external sources of bacterial contamination. Finally, NPWT directly affects hematoma/seroma formation by continuous removal of excess wound exudate. Active removal of hematoma/seroma is hypothesized to decrease chances of both infection (by removing a possible nidus for infection) and graft nonadherence.¹⁸ Combined, these factors theoretically create a supportive environment for wound healing and graft take. 

The benefits of NPWT in graft management has been corroborated in the literature. A study by Turissini et al demonstrated an 80% graft failure reduction when NPWT was utilized, and another study revealed a decreased need for repeat grafting procedures when NPWT was used.¹⁹ Compelling evidence exists that supports the use of NPWT in wound management and graft care. Thus, the next logical step in graft care would be to further augment the benefits offered by NPWT and improve patient outcomes.

Recent advances in NPWT have seen the introduction of instillation and dwell therapy (NPWTi-d). Recent expert consensus guidelines for NPWTi-d use by Kim et al⁸ recommend against its use as a bolster in biologic and/or skin grafts. It is argued that utilization of NPWTi-d may cause the graft to experience “lift-off” and ultimately compromise graft adherence and take. However, the expert recommendation and the argument against NPWTi-d as a bolster are opinion based, with no literature cited or supplied to support this theoretical risk.

The authors hypothesized that NPWTi-d does not create enough forceful lavage, nor does it instill a high enough volume to drown the graft (although it is possible to set high enough settings to do so). They believed that NPWTi-d could benefit grafts in highly contaminated fields, which seems to be supported by published literature. There is evidence that shows NPWTi-d reduces bacterial burden in high-risk wounds and disrupts bacterial biofilm formation on ex vivo porcine skin explants.^20,21 Furthermore, a study by Daeschlein et al²² found NPWTi-d utilizing polyhexanide solution before mesh (STSG) graft implantation greatly improved reepithelialization when compared to other solutions.High-level evidence for or against NPWTi-d use in graft management remains elusive with recommendations against its use as a bolster based on mostly theory, which may not translate to in vivo results. Thus, they chose to determine the possible feasibility and efficacy of NPWTi-d in vivo for skin graft management in complex, high-risk wounds. The goals were to show that instillation/dwell may be a useful adjunct in certain wounds and could improve graft take as well as reduce the amounts of required operative irrigation/debridements, reducing hospital costs. 

The authors believe the utilization of NPWTi-d as a skin graft bolster could improve graft take in certain high-risk wounds through a variety of means. They hypothesized during the suction phase that NPWTi-d still functions in the traditional sense and stabilizes the wound bed with uniform pressure, minimizes hematoma/seroma formation by consistent removal of excess exudate, and promotes angiogenesis through microdeformation and stimulation of local factors. By adding instillation and dwell, the graft success may increase through 2 mechanisms. First, instillation and dwell likely gently reduces bacterial bioburden within the wound via dilution and gentle lavage, therefore reducing the likelihood of infection and excessive inflammation. Second, instillation and dwelling helped dilute and remove any residual hematoma, seroma, and slough normally left unaddressed by NPWT alone, theoretically increasing graft adhesion and take. High-level evidence indicates saline irrigation can reduce the risk of seroma/hematoma formation in surgical wounds, so the authors believe it could also do so in traumatic wounds.²³

In both of the presented cases, NPWTi-d was utilized during all stages of wound management (pre- and post-graft application). Ultimately, despite both patients having significant risk factors associated with high rates of graft failure, there was near 100% graft take in both cases without the need for repeat debridement or grafting procedures. Both patients returned to their previous level of activity and had high levels of satisfaction. To the authors’ knowledge, these case reports are the first to report safe and efficacious use of NPWTi-d in direct STSG management as a bolster. Further high-level studies are needed to delineate the risks and benefits of NPWTi-d in wound and graft management. 

Soft-tissue defects associated with necrotizing fasciitis pose significant challenges to clinicians. In addition to being highly contaminated, these wounds have the additional burden of belonging to hosts with some degree of immunocompromise. These factors create an environment hostile to healing. Thus, it is imperative that surgeons work to gain an advantage whenever possible, which includes the implementation of technology such as NPWT and NPWTi-d. 

Negative pressure wound therapy and NPWTi-d use in wound care positively impacts wounds of all types, and classical NPWT has been shown to be beneficial in skin graft care. Clear indications and contraindications for NPWTi-d have not been as well established. Many of its risks and benefits remain theoretical, but studies are very promising. The present case reports of successful NPWTi-d utilization in 2 patients with high-risk necrotizing fasciitis wounds demonstrate the feasibility and potential benefit for its use in both wound and STSG management. 

Authors: Gordon Lee, MD; and Patrick Murray, MD

Affiliation: University of Hawai'i at Manoa John A. Burns School of Medicine, Honolulu, HI

Correspondence: Gordon Lee, MD, Resident, University of Hawai'i at Manoa John A. Burns School of Medicine, Orthopaedics, University of Hawaii Orthopaedic Residency Program, 1356 Lusitana Street, 6th Floor, Honolulu, HI 96813; glee7@hawaii.edu 

Disclosure: Dr. Murray is a speaker and paid consultant for 3M + KCI.