Negative Pressure Darwinism: Survival of the Fittest Paradigm

The use of negative pressure for wound healing has been based on a set of parameters and devices that until recently were combined into a single paradigm. Despite historical and more recent evidence providing viable alternative considerations, it is only recently that this paradigm and its tenets have come into question. As the understanding of the limits of the current paradigm and specific instances of its benefits and drawbacks are identified, shifts in the paradigm must take place if the therapy is to evolve, develop, and continue to be efficacious. The pertinence of the concept of survival of the fittest is used to explore the need for a paradigm shift in negative pressure wound therapy.

The field of negative pressure wound therapy (NPWT) has had a dramatic expansion in terms of technologic reproduction, but there is a question as to whether there has been a definitive and identifiable change in the conceptualization, applications, and outcomes as newer versions are considered and enacted.

In 1997, the first commercial incarnation of NPWT entered the market. With it came concepts within this new paradigm that at first were met with skepticism. These included: using an open cell polyurethane foam inserted into a non-sterile wound for a period exceeding 23 hours without changing it; sealing the wound with a plastic film that “prevented the air from getting to the wound”; attaching a tube to the sealed foam/wound that allowed for a direct connection with the outside; keeping the drainage in an attached container for more than 24 hours without emptying it, and many other then controversial considerations. Despite these early concerns, the success of the technology and paradigm(s) it created led to major advances in wound healing and subsequent commercial success. It can be shown that there were earlier recorded uses of negative pressure; however, the creation and acceptance of this particular paradigm was due to its multi-factorial considerations such as the level of suction, wound contact medium, method of application, and of course, the pump technology, which led to improved healing outcomes.

An upstart company, led by a 2004 legal victory, forced the door open and allowed a limited juxtaposition of technologies and a challenge to the established paradigm. Since there is now a variation on an established technology, the terms “gold standard” and “perfect” must be evaluated and considered. For a technology and/or paradigm to be perfect it must have no shortcomings, no faults—in essence it is a one size fits all technology. In contrast, the term gold standard recognizes the temporal advantages and benefits of a given paradigm. It recognizes that at a given time, in a given place, under a given set of circumstances, that the paradigm was the best available. It allows for a change in any of these variables, but more importantly, recognizes that the changes in these and other variables allow for changes in the paradigm with an equal potential for improvement or worsening.

With these concepts in mind, the progression of scientific technologies must follow the basic tenets of British economist Herbert Spencer who transitioned from Charles Darwin’s biologic theories of natural evolution to that of sociologic, and subsequently economic events. It was he who coined the phrase “Survival of the Fittest” in his book Social Statics. Technology must be adaptable. “The more adaptability, the greater the viability.”¹ The question before us is simple: Is the initial and prevalent NPWT paradigm perfect or the gold standard? If “perfect,” then why should there be any other viable alternatives expected to survive? If the “gold standard,” then it is mandatory to consider, explore, create, and test alternatives to all aspects of the paradigm. It would be unrealistic to preconceive which of them could/would remain unchanged, hence, “perfect.”

The first consideration must look at the conundrum of perfect versus the gold standard in NPWT devices and technologies. In order to be perfect, the paradigm would have to consist of the following:

• Be universally available
• Easy to apply
• Easy to remove
• Cause no pain
• Be adaptable to all patients
• Be appropriate for all wounds
• Be cost effective
• Allow for variations in all wound and patient parameters
• Have no complications
• Have universally complete healing outcomes.

Since achieving this is tantamount to reaching infinity, the next best thing and the obvious conclusion that can realistically be reached is that the current paradigm is at best the gold standard. The considerations now shift to identifying those aspects of the gold standard paradigm that can be changed potentially for the better with the ultimate goal of reaching perfection.

The first component of the paradigm to be considered with respect to the aforementioned tenets of a perfect NPWT product is what I call “the wound contact medium,” or in the case of the current paradigm, open cell polyurethane foam. At the time of the writing of this article, there are two companies with NPWT paradigms and products based on this wound contact medium (Kinetic Concepts, Inc. San Antonio, Tex; Innovative Therapies, Inc. Gaithersburg, Md).

The difference between open-cell and closed-cell polyurethane foams is that these two types of polyurethane foams have different R-values, permeability, strength, and costs.² Interestingly, the scientific jargon used to legitimize the use of foam as a wound healing adjunct can also explain other aspects and uses “…the influence of pneumatic damping caused by friction between the gas within the open-celled foam and matrix polymer.”³ A continuous shape function is introduced to characterize the piecewise continuous stress-strain characteristic of flexible, open-cell foam. The new model is able to predict the dynamic performance of a seat cushion with fidelity. This statement pertains not to wound healing, but to the performance of an automobile seat cushion.³

The ongoing evaluation of paradigm safety is always a concern, and there are several with the current gold standard. The Materials Safety Data Sheet (MSDS) on open-cell foam clearly states, Eye Contact: Flush eyes with water for at least 15 minutes. Consult a physician. Skin Contact: Wash affected area with soap and water. If irritation persists, consult a physician. Inhalation: Remove to an uncontaminated area; administer oxygen if necessary. If victim has stopped breathing, begin CPR. Get medical attention. Ingestion: If swallowed, give water or milk and induce vomiting. Get immediate medical attention. Precautions to be taken in handling: Avoid eye contact and prolonged or repeated skin contact. Workers should thoroughly wash hands with soap and water prior to eating, drinking, smoking, and using lavatory.⁴

A review of the Manufacturer and User Facility Device Experience Database (MAUDE) reports on foam used in NPWT identified 22 incidents reported from 1/1/08 to 8/22/08. These included bleeding, retained foam, foam so intimate it required hospitalization and surgery to remove, hospitalizations due to pain, bleeding, need for exploration, etc.⁴ It is important to recognize that these events have appeared numerous times in prior databases despite more than 11 years of the paradigm’s gold standard status. Moreover, the US Food and Drug Administration (FDA) has mandated that there must be a non-adherent, interpositional layer between the foam and any viscera, and that the foam cannot be placed on any exposed vessels.⁵

The ultimate questions must identify the risks and the benefits of using foam in a given patient on a given wound. Is a paradigm shift necessary? What else can be considered to improve on the gold standard?

I have adopted the term “porous, non-adherent wound contact layer” to define and identify those materials and dressings potentially suitable for use as an interface with negative pressure. Presently, there is a trend toward using AMD (polyhexamethylene biguanide [PHMB]) gauze due to its availability, ease of use, overall familiarity in the wound care field, and studies documenting its antimicrobial efficacy.⁶ MAUDE database has no reported incidents on gauze. The MSDS for AMD gauze identified the following regarding Respiratory Protection, Hand Protection, Eye Protection, and Body Protection: “No specific measures necessary.” The only caveat was that in case of eye contact, “flush eyes with plenty of water for 1–2 minutes” but no specific eye protection was warranted with use. Is this evidence sufficient to consider a paradigm shift?⁷

Some of the hardest fought and yet simplistic arguments pertain to the differences in the suction that the various technologies produce. For example, the argument that suction generated from one device promotes wound healing, while suction from another device simply removes drainage is one of illogical thinking. A scientific explanation to support these claims has yet to materialize and cannot be found in the literature.

NPWT characteristics. To make the argument understandable, there must be defining characteristics for NPWT in which all paradigms should fit. Characteristics that are generally accepted:

• Promote moist wound environment
• Increase capillary and venous engorgement bringing fresh blood flow into wound
  • An increase in growth factors      
  • The promotion of white cells and fibroblasts within the wound
• Remove edema and restore normal fluid balance in tissues reducing tissue hypoxia in early stages of inflammation
• Promote increased lymphatic and venous drainage through changes in pressure on lymphatics and colloid osmotic pressure
• Remove healing inhibitory “waste products” (in wound drainage) in contact with wound
• Negative pressure brings tissue together (coaptation), which facilitates natural tissue adherence and increases healing
• Cellular membrane distension causes intracellular elements to send an injury current pattern to the cell nucleus causing secretion of pro-healing factors including angiogenic factors.⁸

At a minimum, these characteristics define the presence of NPWT. Therefore, any system that meets the criteria of this paradigm must be considered to be a negative pressure-generating wound therapy system. Since wounds do not have the ability to discern the differences between NPWT technologies, their response is based solely on the presence of this force. Thus, the paradigm of having only one entity with the ability to create the necessary negative pressure to promote healing is nonviable.

Timing of therapy. The timing of negative pressure application is another consideration in the spectrum. Even if one is to consider 24 hours as the gold standard, as a defined unit to compare other therapy timing regimens to, this allows for unique alterations:

• Constant: The machine operates for a 24-hour period (standard)
• Periodic: The machine operates for a period < 24 hours (6–8 hours) or more than one treatment period per 24 hours^9–11
• Intermittent: The suction alternates between on and off or lower/higher pressures • Continuous: A single pressure is maintained during a given treatment period.

This allows for 4 unique NPWT alternative timing schemes: constant/continuous, constant/intermittent, periodic/continuous, and periodic/intermittent. These have all been used to an extent either purposefully or accidentally (based on patient compliance and device/dressing reliability factors, among others). Additionally, the case evidence is sufficient to show that these timing combinations have resulted in wound healing.^12–31 The deciding factor as to which will result in the “best” healing is unlikely to ever be identified; however, the understanding of different and yet beneficial alternatives suggests that it is unlikely that the gold standard will be universally successful and the “best” in all situations. In this case as well, variability increases the potential for improved viability of a newer paradigm.

Pressure intensity. The paradigm must consider not just the timing of the applications of NPWT but also the intensity of the pressure. The variables regarding the optimal pressure to use have been oversimplified in the current gold standard of -125 mmHg to -150 mmHg when other factors are considered. The literature from early Russian scientists Usupov and Yepifanov³² using a rabbit wound model demonstrated that a pressure of -75 mmHg provided beneficial healing results, reduction in bacterial burden, and other parameters. They also identified tissue hemorrhage of previously coagulated vessels with negative pressures more than -120 mmHg to -125 mmHg.³² Additionally, Larichev reviewed all aspects of the Russian negative pressure therapy experience and propounded the need for these lower pressures during therapy as well as other currently novel ideas.³³ In contrast, Morykwas et al³⁴ identified pressures of -125 mmHg to -150 mmHg as ideal for their technology. This became an integral feature of the gold standard paradigm based on numerous factors, which include not just successful healing, but also marketing efforts.³⁴

In 2004, Wackenfors et al³⁵ evaluated varying negative pressures using an inguinal pig wound model. They used open-cell polyurethane foam as the wound contact medium and reported that different pressures should be used to obtain ideal healing for soft versus dense tissue injuries. They reported that the ideal pressures to promote healing and minimize adverse effects were 60 mmHg–80 mmHg for soft tissues and 80 mmHg–100 mmHg for denser tissues. They also reported that low negative pressure during treatment may be beneficial, especially in soft tissue, to minimize possible ischemic effects.³⁵

Timmers et al³⁶ evaluated the effects of high negative pressure. They evaluated the effects of polyurethane and polyvinyl chloride (PVC) open-cell foams on forearm skin of healthy volunteers. This limited study found a significant increase in cutaneous blood flow with both foams using -300 mmHg. The obvious criticisms of these findings surround the application of the foam to intact skin and the use of healthy volunteers.³⁶

A 2005 literature review³⁷ juxtaposed findings regarding NPWT techniques and other related factors, as reported in the previously mentioned studies.^32–36 The review found discrepancies between available articles regarding which pressures were best for the foam-based NPWT technologies. Additionally, when the foam deformation pressures were taken into account, it appeared that lower pressures were better for non-foam application (ie, less detrimental effects). The review also noted that negative pressure levels should reflect the types of tissue being treated, or higher pressures (comparatively) should be used to treat denser tissues such as muscle or fascia. Nonetheless, the foam incarnations have clung to the same gold standard pressures recommended for all tissues.³⁷

Robert Burton, a Scientist and Philosopher from the 1600s stated, “A dwarf standing on the shoulders of a giant may see farther than a giant himself.”³⁸ Despite marketing hype, ego, and braggadocio, there is clearly a place for both foam and non-foam applications of NPWT with each technology having proven efficacy under multiple circumstances, albeit not by double blind randomized studies. The conundrum facing practitioners now is not simply to identify those wounds and conditions that respond to the present gold standard, but rather those that do not. We may never achieve perfection but it is incumbent upon us to recognize that for each success of a given technique another failure awaits, as does another paradigm.

From the Wound Healing Center, Bedford, Illinois

Address correspondence to: Michael Miller, DO, The Wound Healing Center, 2900 16th Street Bedford, IN 47421; Phone: 812-798-2091; E-mail: doc@docmillers.com