Does NPWT With Instillation Have A Viable Role In The Wound Healing Process?

Can negative pressure wound therapy with instillation (NPWTi) have an impact in facilitating wound healing? Offering insights from their experience and key initial findings from the current literature, these authors take a closer look at the effects of biofilm in chronic wounds and the possible roles of instillation in reducing bioburden and improving healing in cases involving exposed hardware.

Negative pressure wound therapy with instillation (NPWTi) has been indicated mainly for compromised wounds due to a heavy load of bioburden, which physicians could eradicate more efficiently with the application and removal of a topical solution.

The negative pressure device has three main phases: instillation of fluid of choice; a pause in the ingress and egress of fluid from the wound bed (dwell time); and removal of all the instilled fluid with continued negative pressure for a preset amount of time. Authors have suggested a variety of fluids for instillation, including 0.9% saline, 0.1% betadine (Prontosan, B Braun), 0.1% polyhexanide and acetic acid as well as antibiotic solutions.¹

The addition of an instilled topical wound solution to NPWT is designed to facilitate regular wound cleansing to help improve the outcomes in some complex wounds but the addition of instillation to NPWT adds a level of complexity to the wound care process.2 Throughout the instillation process, a topical solution soaks the wound bed and dwells for a preset amount of time to remove the wound fluid.

Researchers have shown that physicians may use NPWT with instillation to prepare the wound bed between operative debridements to obtain a less contaminated wound bed as well as enhance granulation tissue.² One could utilize this technique for more complex wounds to limit the number of trips to the operating room in comparison to the conventional NPWT without instillation.

Our team at MedStar Georgetown University Hospital has conducted two prior studies regarding NPWTi to evaluate its effectiveness and assess if the length of dwell time had an effect of patient outcome.^1,3 One study was a retrospective cohort-controlled study of 142 patients having at least two surgical debridements utilizing Prontosan.³ The results showed a decreased length of hospital stay in the 20-minute dwell time group in comparison with the standard NPWT and decreased surgical debridements in the six-minute and 20-minute dwell time groups, both utilizing NPWT.

Given the wide range of specialties that have reported use of NPWTi, such as general, vascular, podiatric, plastic and orthopedic surgeons, there is still some relatively unknown information with regard to the clinical and technical use of the instillation units. It is important that we address this knowledge gap to ensure that providers are able to utilize NPWTi when the indications are present without having the added hesitation of not applying the instillation portion simply because the hospital inpatient care team (i.e. nursing) is not familiar with the instill portion of the NPWT unit.

Another important note that one should not overlook is that NPWTi is just one piece of the puzzle of effective and efficient wound healing in the setting of infection and severe soft tissue loss. One must ensure proper antibiotic coverage, patent blood flow to the area of concern, adequate surgical debridements and sufficient offloading to maximize healing potential.

Many studies have shown the positive effect of NPWT alone without instillation but more research is needed to properly evaluate the bacterial bioburden of the subjacent wound. Glass and colleagues conducted a systematic review of Medline, Embase, PubMed and Cochrane databases evaluating bacterial load under NPWTi.⁴ There is evidence that NPWT exhibits species selectivity, which suppresses the proliferation of non-fermentative Gram-negative bacilli, which in turn has implications for the use of NPWT where highly virulent strains of Gram-positive cocci have been isolated.

How The Current Evidence Supports NPWT With Instillation For Reducing Bioburden

The presence of bioburden in chronic wounds remains a major challenge. The detection of biofilm-protected bacteria is not a well-established process that we can extrapolate to all settings and the current general ability to identify the presence of biofilm is limited.^5,6 There have been implications that one can only extract qualitative results with direct molecular detection methods that do not provide quantitative data.⁷ Whereas 10⁵ CFU/g is the commonly acknowledged quantity of planktonic bacteria defining clinical infection, such a threshold has yet to be established for biofilm-protected bacteria reduction to evoke a positive clinical outcome.⁷

There are no therapeutic means to reduce biofilm other than detection. Not only do bacteria-produced glycoproteins and polysaccharide matrices limit antibiotic penetration, they also change the pharmacokinetics of antibiotic-degrading enzymes such as beta lactamases.⁸ Biofilm-protected bacteria have been known to have extremely slow growth rates and this quality makes them essentially resistant to antimicrobials.

In theory, NPWT disrupts biofilm when one removes the sponge from the wound bed, making it important to highlight the need for more frequent NPWT sponge exchanges throughout the course of therapy.⁹ With the addition of instillation fluid, this may further assist in disrupting the existing bioburden.

This leads us to the topic of which fluid we should use for NPWT instillation. Our group also conducted a prospective randomized controlled trial of 100 patients with infected wounds.¹⁰ Dwell time was preset at 20 minutes for both the normal saline and Prontosan group. Patients were randomly assigned to each group and there were no significant differences between the two groups for length of stay, the number of surgical debridements or the 30-day follow-up rate of healed wounds after discharge from the inpatient ward.

A prospective randomized trial conducted by Yang and colleagues showed a reduction in Pseudomonal and methicillin-resistant Staphylococcus aureus (MRSA) biofilms with sodium hypochlorite 0.125% while having little effect on Streptococcal and fastidious biofilms.¹¹ This indicates a need for a different agent if one has identified these species. This provides a new arena for innovative research on evaluating the different agents and their effects on multivariate bacterial species in order for us to be able to tailor the therapy to an individual patient. Medicine has started trending toward personalized medicine, which will provide better diagnosis, earlier interventions and more efficient treatment plans.

Pertinent Insights On Biofilm

Wolcott and colleagues showed that with frequent sharp debridement (every two or three days), there is effective eradication of formed biofilm.¹² Note that this provides an added challenge in the outpatient setting as the inpatient setting is recommended for proper management with NPWTi. The authors also found that 75 percent of the described macroscopic wound bed films contained microbial biofilms regardless of the patient’s comorbidities, location of the wound or which wound care regimen physicians utilized.¹²  

Multiple studies show that biofilm often live greater than 5 mm below the wound surface and often utilize dermal appendages as “safe harbors.” Evidence indicates that bacterial biofilms can chronically infect wounds and that they are present in the majority of chronic non-healing wounds.¹³ Biofilm protects microbes against topical and systemic antimicrobials in comparison to planktonic microbes. Our efforts with multiple operative debridements show that sharp debridement decreases the biofilm temporarily to expose them in the planktonic state. With sharp disruption, biofilm reforms to maturity within 48 to 72 hours.¹²

Singh and colleagues have evaluated the effect of NPWT with antiseptic instillation on biofilm formation in an in vivo model of infected spinal implants in comparison to traditional treatment methods.¹⁴ Five pigs had titanium rod implantation of their spinous processes followed by injection of 1 x 10⁶ of MRSA through the fascia at each site. Three pigs received NPWTi and the control group of two pigs received wet-to-dry dressings. The authors extrapolated the persistence of local infection utilizing tissue cultures. Mean bacterial counts showed statistical significance. Scanning electron microscopy between experimental and control groups exposed the presence of uniform biofilm across the control group instrumentation whereas the experimental group showed interrupted areas between the biofilm. Given that this is an in vivo porcine model, the authors have shown a reduction of the bacterial bioburden and interference with biofilm arrangement.

Currently, there is no consensus in the literature regarding proper indications on when to utilize NPWTi for chronic non-healing wounds with the presence of biofilm formation or when to remove infected hardware in these circumstances.

Using NPWT With Instillation When There Is Exposed Hardware

Currently, there is poor understanding of the role NPWTi has on reducing the biofilm present on surgically implanted hardware, which would allow clinicians to have a clear consensus regarding when to salvage or when to remove the infected hardware. When surgeons remove hardware, we risk losing stability if the construct has not fused whereas hardware retainment increases the risk of recurrent infection.¹

In a study conducted by Kenneth and colleagues, the authors cultured methicillin-sensitive Staphylococcus aureus (MSSA) biofilm on total knee arthroplasty materials and exposed total knee arthroplasty hardware to increasing doses of cefazolin.¹⁵ The authors used quantitative confocal microscopy and quantitative culture to measure viable biofilm. They continued to measure the minimum inhibitory concentration (MIC) after the biofilm’s exposure to different cefazolin concentrations. Changes in MIC would indicate genotypic features whereas unchanged MIC would suggest phenotypic behavior.

Lastly, the study authors employed quantitative reverse transcription-polymerase chain reaction to quantify the expression of bacterial levels between biofilm and planktonic bacteria after exposure to cefazolin for three hours.¹⁵ The authors deemed that antibiotics are incompetent at complete elimination of the biofilm from the surface of acute periprosthetic joints, suggesting that bacterial persisters are responsible for this phenotypic behavior and allowing biofilm a high tolerance to antibiotics.

There have been no studies marking the superiority of NPWTi versus traditional NPWT or if the type of instillate is more effective with the presence of infected surgical instrumentation and reducing bioburden. Our group regularly explants exposed hardware and employs NPWTi with normal saline to remove any remaining bioburden while we await a clean wound tissue culture for further treatment.

With regard to soft tissue infection with concealed hardware that we cannot explant, we have had encouraging results using NPWT instillation with Prontosan. We apply the NPWT sponge directly over top and close the surrounding soft tissue temporarily with retention sutures to maintain the integrity of the soft tissue so that as we are anticipating closure, we will have maximal skin rebound when attempting to close the wound primarily. We avoid removal of hardware if osseous stability is in question. More work is required before we can develop a treatment algorithm for exposed surgical hardware.

In Conclusion

We cannot overlook the valuable use of NPWT with instillation as it is an integral component to the treatment algorithm we utilize in treating our patients. Due to the lack of published literature highlighting the role of NPWT instillation in chronic non-healing wounds, one cannot surmise significant clinical application at this time. The current evidence has shown promise in the adjunctive use of NPWTi but more randomized, controlled clinical studies are needed to compare the safety and efficacy of NPWTi to standard NPWT as well as the implementation of a variety of fluids for the instillation with regard to the targeted microbe isolated from the wound. We have acknowledged the use of NPWTi and which circumstances we utilize instillation therapy but further research is necessary to provide concurrent practice guidelines.

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

Dr. Saeedi is a second-year resident within the Podiatric Surgery Residency Program 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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