CHAPTER THIRTEEN: Wound Dressings

At the end of this chapter, the learner will be able to:

1. Define the function of primary and secondary dressings.

2. Describe the role of dressings in moist wound healing.

3. Select the appropriate primary dressing based on wound characteristics.

4. Select the appropriate secondary dressing based on patient function.

5. Determine when an antimicrobial dressing is needed for wound healing.

6. Describe the mechanism by which different antimicrobial dressings reduce bacterial burden.

Chronicles about the care and management of open wounds go back to early civilization’s use of natural remedies to treat injuries of unfathomable causes. One of the oldest medical manuscripts known to man is a clay tablet dated circa 2100 BC that contains a collection of prescriptions described as “three healing gestures,” which even in modern times is the basis for wound treatment.^1,2 These gestures were washing the wound, making plasters, and bandaging the wound.

The Ebers Papyrus, circa 1500 BC, detailed the use of lint, animal grease, and honey for the management of open wounds. The lint provided a fibrous base that promoted wound site closure, the animal grease provided a barrier to environmental pathogens, and the honey served as an antibiotic agent. The Egyptians believed that closing a wound preserved the soul and prevented the exposure of the spirit to “infernal beings,” as was noted in the Berlin papyrus. The Greeks, who had a similar perspective on the importance of wound closure, were the first to differentiate between acute and chronic wounds, calling them “fresh” and “nonhealing,” respectively. Galen of Pergamum, a Greek surgeon who served Roman gladiators circa AD 120 to 201, made many contributions to the field of wound care. The most important was acknowledgment of the importance of maintaining wound-site moisture to ensure successful wound closure.

There were limited advances that continued throughout the Middle Ages and the Renaissance, but the most profound advances, both technological and clinical, came with the development of microbiology and cellular pathology. In the 19th century, Pasteur advocated that wounds be covered and kept dry because he believed this would keep them “germ” free. The dressings developed at this time (made from cloth, cotton, and gauze) have dominated wound management in recent history, and in some countries, they continue to be the main products used.

The first manufactured dressings were probably Gamgee wadding and tulle gras. Gamgee discovered that degreased cotton wrapped in bleached lint would absorb fluids, and he introduced his first dressing in the 19th century. During the 1914-1918 war, Frenchman Lumiere developed cotton gauze that was impregnated with paraffin to prevent the dressing from sticking to the wound. Wound management technology did not progress significantly beyond these early developments until the 1960s when comparisons were made of wound healing in dry and moist environments.³

In 1962, Winter⁴ published his landmark paper about the effect of occlusion on wound healing. He made experimental wounds on the backs of domestic pigs, covered half of the wounds with occlusive film, and left the other half exposed to the air. The occluded, and hence moist, wounds had an epithelialization rate twice that of those left open to form a scab. The concept of moist wound healing was accepted, and a variety of dressings have become available since the late 1970s to deliver and maintain a moist healing environment. Although four plus decades have passed since this historical work documenting the benefits of moist wound healing and managing exudate, too often topical wound care still falls under the premise of “a priori,” based on how one was previously taught, on previous concepts, or on the way it has always been done.

A moist wound bed is the evidence-based standard of care for the management of open wounds; however, the “wet-to-dry” dressing (ie, packing a wound space with moist gauze and removing it after it has adhered to the wound bed) is still one of the most common treatments used today. In a retrospective descriptive study⁵ exploring the prevalence of wet-to-dry dressings ordered for care of open wounds healing by secondary intention, a chart review examined admission orders for 202 randomly selected Florida home care and health maintenance organization patients from 2002 to 2004. All subjects in the study had open wounds healing by secondary intention (42 partial-thickness and 160 full-thickness wounds). Wet-to-dry dressings accounted for 42% of wound care orders, followed by enzymatic (7.43%) and dry gauze (6.93%). Most wounds treated with wet-to-dry dressings were surgical (69%), followed by neuropathic ulcers (10%) and pressure ulcers (5.9%). Surgical specialists preferred wet-to-dry dressings (73%). Mechanical debridement was not clinically indicated in more than 78% of the wounds treated with wet-to-dry dressings. Therefore, wet-to-dry dressings were inappropriately ordered in these cases.⁵

In the often cited article from 2002, “Hanging Wet to Dry Dressings Out to Dry,”⁶ Ovington provides evidence that gauze dressings (whether dry or moistened with saline) are substandard for optimal wound care for several reasons, including increasing patient’s discomfort, impeding wound healing, and increasing the risk of infection.

Wet-to-dry debridement is not selective (see Chapter 12, Wound Debridement) and often also removes healthy tissues, thereby causing further tissue trauma and potentially significant pain upon removal (FIGURE 13-1).

The concept of using a wet-to-moist dressing to avoid this trauma may still cause injury. The dressing is prepared in the same manner as a wet-to-dry dressing except the gauze is applied with more moisture with the intent that it will remain moist until removal. Nevertheless, it may become a wet-to-dry dressing in practice. A study of the mechanism of action of saline dressings suggests that they function as an osmotic dressing.⁶ Normal saline is isotonic. As water evaporates from the saline dressing, it becomes hypertonic and fluid from the wound tissues is drawn into the dressing in an attempt to reestablish isotonicity. However, wound fluid is not merely water; it contains blood and proteins that may begin to form an impermeable layer on the dressing’s surface. At this point, fluid from the wound is unable to replace the fluid lost from the dressing by evaporation and the dressing dries out completely. Consequently, unless the dressing is changed frequently, or remoistened between dressing changes, it will still function as a wet to dry.

Additionally, cooling of the tissues at dressing changes may impede healing. Evaporation of water from a surface results in a reduction of temperature at that surface. Reduction in tissue temperature has multiple physiologic effects, including local reflex vasoconstriction and hypoxia, impairment of leukocyte mobility and phagocytic efficiency, and increased affinity of hemoglobin for oxygen—all of which not only impede healing but increase susceptibility to infection.⁶

Gauze dressings present no physical barrier to the entry of exogenous bacteria. An in vitro study showed that bacteria were capable of penetrating up to 64 layers of dry gauze, and moistened gauze provides even less of a barrier to bacterial penetration, again increasing the risk of infection. In a literature review of 3047 wounds, the overall infection rate for wounds dressed with moisture-retentive dressings was 2.6%, whereas the infection rate for gauze-dressed wounds was 7.1%.⁶

Wet-to-dry dressings may incur more labor for the clinician or caregiver and more costs for the health care system. In order for gauze to remain continuously moist to support optimal healing, it must be either changed frequently or remoistened with additional saline. This requires additional labor on the part of the clinician or the lay caregiver. Dressing changes two or three times a day used to be common. In today’s reimbursement climate, this practice is no longer feasible, not only from a reimbursement perspective, but also from the standpoint of best patient outcomes. In home health care, multiple dressing changes a day require the expense of extra travel, home visits, and post-visit time for documentation. Even without the expense of travel in acute or long-term care settings, frequent dressing changes still require time that could be used for other patient care tasks.

Assessment of the patient with an open wound involves a holistic approach and there are many facets of the evaluation that go beyond purely the physical makeup of the wound, for example, the appropriate diagnosis of the wound etiology, patient comorbidities, nutrition, and tissue oxygenation. Open wounds are dynamic and are continuously changing; therefore, dressing selection for optimal healing must also change. It is rare that a singular treatment plan for any given wound will remain the same throughout the healing process. Decision making relative to treatment is based on a thorough assessment of the patient and the wound at regular intervals so that timely changes in the care plan can be made. Specific wound and patient characteristics to be assessed that will drive treatment decisions are illustrated in TABLE 13-1.

Location

The location of the wound on the patient has less to do with the primary dressing (the dressing that is in contact with the wound bed) and more to do with how the dressing may be secured. Wounds located on the torso will require a dressing that is self-adhering, has an incorporated adhesive border, or is secured with additional tape. Wounds on the extremities can be secured with self-adhering dressings, gauze rolls, tubular bandages, or stretch net. The skin condition, patient activity level, potential trauma, possible contamination, and the desire to bathe or shower are also factors to be considered when selecting the secondary dressing.

Size

The size of the wound determines the size of the dressing required to adequately fill and cover the wound surface. Undermining or sinus tracts need to be loosely packed or filled, usually with the same primary dressing. All categories of dressings are available in a variety of sizes and shapes to accommodate the dimensions of most wounds. The outlier in the size consideration is the very large wound requiring frequent dressing changes (eg, a large surgical wound) in which case negative pressure wound therapy (NPWT) may accomplish more rapid reduction in wound size and allow more patient activity. (See Chapter 15, Negative Pressure Wound Therapy.) If wound healing is not the immediate or long-term goal, a better dressing selection is one that is cost-effective; requires less frequent changes; and manages exudate, odor and pain.

Tissue Type

The predominant tissue type and the exposure of vital structures such as bone, tendon, and muscle are key determinants of dressing selection. Healthy granulating wound beds and exposed viable structures need to be kept moist and protected from trauma. The presence of necrotic tissue requires a decision about appropriateness and type of debridement.

Exudate

The amount and type of exudate is a fundamental consideration in dressing selection. The optimal dressing material adequately manages wound drainage by wicking the exudate into a secondary dressing. This prevents pooling of exudate on the wound surface, which can become a nidus for bacterial growth as well as a source of leakage and maceration of the surrounding skin. A dry tissue bed requires hydration, a moist bed needs to be maintained, and a wet surface with large amount of exudate requires absorption. The exudate levels will also determine frequency of the dressing change.

Periwound Condition

A key goal of any dressing is to maintain the periwound skin and prevent maceration (ie, over-wetting), stripping/mechanical trauma, prevention and treatment of rashes, and prevention of tape irritation. A dressing that adequately manages exudate is the primary strategy for maintaining intact skin. The use of a barrier wipe or ointment also protects the skin from moisture as well as from trauma during tape removal. Silicone-backed dressings help prevent pain and trauma at dressing change and facilitate remodeling of the wound areas that have reepithelialized. A rash or blistering of the periwound area may be an indication of an allergic reaction to a particular dressing or tape; the location and distribution of the rash or blisters are a clue to the etiology. A true allergic reaction usually results in the presence of rash or blistering where the tape or irritating agent was in contact with the skin.

Blistering, especially on one side of dressing edge, is usually indicative of tape being applied with tension, thus resulting in a separation of the epidermis and dermis that subsequently fills with fluid, hence the blister.⁸ Applying tape without tension by anchoring in the middle and smoothing outward can prevent this.

Bacterial Burden

All wounds are contaminated. As bacterial levels rise, the potential for infection in the deeper tissue increases. Even in the absence of gross infection, wound healing can be affected by the increase of proteases, toxins, and other consequences of bacteria. The use of topical agents and dressings to reduce local bioburden can reduce the number of bacteria before they rise to a critical level and negatively influence wound healing. Multiple dressing options exist to address bacteria while still meeting the environmental needs of the wound. (See the section Antimicrobial Dressings at the end of this chapter.)

Pain

Every patient has an acceptable level of pain, and every treatment plan includes strategies to mitigate or eliminate pain to the extent possible, or at least to the patient’s acceptable level. A survey conducted in 2002 in 11 European and North American countries identified the top issues in wound healing as (1) preventing trauma to the wound surface and periwound skin and (2) preventing pain to the patient during dressing changes.⁹ Maintaining a moist wound bed, selecting a nonadherent dressing that is easy to remove, gentle cleansing, administering oral and IV pain medications at the optimal times, and using a topical anesthetic for procedures such as debridement are strategies that reduce the pain associated with both acute and chronic wound care. In some cases, having the patient don gloves and assist in the dressing removal can help minimize pain and reduce anxiety.

Support Needs

Topical care is only a part of the multifaceted approach to achieving wound healing. A thorough patient assessment to determine wound etiology and the appropriate supportive management is an integral part of the treatment plan. To that end, dressing choices are also determined by the supportive care or other medical interventions required to manage the underlying etiology and comorbidities. Examples include but are not limited to

• ▪ Patients with venous disease requiring compression wraps or patients with diabetic foot ulcers (DFUs) off-loaded with total contact casts require dressings that may be left in place until the compression or casts are removed.

• ▪ Patients with suspected or confirmed infection may require frequent observation of the wounds.

• ▪ Patients with periwound dermatitis being treated with topical steroids require dressings changed at the frequency needed for the reapplication of medications.

Quality of Life

Optimal wound management involves a holistic approach that considers patient wishes and lifestyle, work requirements, and activities of daily living. An important first consideration is the overall goal for the wound, for example, can it be healed? In the case of a patient with a terminal illness or a wound of the lower extremity with inadequate circulation, the goal may not be healing but pain and odor control, prevention of infection, and prevention of wound deterioration. The patient who desires or requires showering needs a waterproof dressing if showering with the wound exposed is not appropriate. The working patient needs a treatment plan that accommodates the working schedule and environment, as well as a dressing that can be camouflaged, hidden, or at least be presentable. In summary, the patient needs a dressing that will prevent the wound from interrupting daily life as much as possible.

There is no “one size fits all” for dressing selection for open wounds. There are literally thousands of dressings available considering the various categories, shapes, and sizes. Although the form (ie, the ingredients) of the dressing is important, the function, or how it will optimize the wound environment, is more essential in decision making. That being said, there is almost always more than one option available to meet the assessed needs of any wound. TABLE 13-2 describes the desired characteristics of an ideal wound dressing.

A myriad of dressing materials are available to meet the ever-changing needs of the open wound. The task of selecting the appropriate dressing can at times be daunting. There are numerous specialty dressings that create or enhance the wound environment to promote healing. Some have a singular function while others are combinations or composites possessing attributes of more than one category. Familiarity with the basic categories enables the clinician to understand the combination products.

Skin Protectants

Although they are not dressings per se, skin protectants are formulations designed to protect the skin from the effects of mechanical injury due to tapes and adhesives. Composed of a polymer and a solvent, when applied to the skin, the solvent evaporates and the polymer dries, thereby forming a visible transparent protective coating on the skin. When tapes or adhesives are applied over this coating, upon removal, this protective layer is lifted instead of layers of skin cells, thus avoiding mechanical injury to the epidermis. Skin protectants are available with and without alcohol, an important distinction when considering application to broken or irritated skin that is painful with alcohol. Skin protectors are available in foam applicators, wipes, and sprays (FIGURES 13-3, 13-4).

Contact Layer Dressings

Contact layers are single-layer woven net-type dressings that act as a barrier between the wound surface and a secondary dressing. Contact layers protect the wound bed from trauma while allowing wound exudate to pass through into a secondary or negative pressure wound dressing. Alternatively, contact layers may be used over medicated creams, ointments, or biologics such as growth factors or cell therapy products in order to protect them from the secondary dressing. Contact layers are made from nonadherent fabrics such as polyethylene and can be coated with silicone, oil emulsion, or petrolatum to prevent or minimize adherence (FIGURES 13-5 to 13-8).

The contact layer may be cut to fit the wound or allowed to overlap onto the adjacent skin. They are usually removed and reapplied with each dressing change; however, they can be left in place to avoid skin trauma while only changing the secondary dressing in the presence of larger amounts of exudate (eg, with radiation burns). Contact layers can be used for wounds of all types and any amount of exudate. Advantages and disadvantages are listed in TABLES 13-3 and 13-4.

Film Dressings

Film dressings, also referred to as transparent film dressings because of the ability to see through them, are polyurethane self-adhering membranes that are moisture vapor permeable, meaning that they allow gaseous exchange from the wound bed. Transparent films are waterproof and prevent contamination of the wound bed, yet water vapor is able to evaporate from the wound bed and oxygen is able to penetrate from the air. The amount of oxygen available is not in a quantity sufficient to support tissue growth, but enough to possibly mitigate growth of anaerobic bacteria if changed frequently.

Film dressings are thin and flexible and thus allow visualization of the wound and surrounding skin. They are frequently used on intact skin for protection from friction and moisture and to reduce shear. Placing transparent films over early skin changes such as Stage I pressure ulcers or suspected deep tissue injuries allow the clinician to frequently assess the site for progression or changes. Standard film dressings have no ability to absorb exudate thus are not indicated for draining wounds. There is, however, a film dressing that incorporates an acrylic polymer pad so that exudate transfers through perforations and into the absorbent pad and away from the wound surface (FIGURES 13-9 to 13-11).

Film dressings create an environment conducive to autolytic debridement by holding the body fluid onto the necrotic tissue. The natural enzymes in the fluid emulsify only the necrotic tissue so that it can be easily removed, usually after only 24 hours (refer to Chapter 12, Wound Debridement) (FIGURES 13-9 to 13-11).

Care must be taken when removing film dressings from intact fragile skin in order to avoid mechanical stripping. Use of a skin barrier wipe before applying the film helps protect the skin as well as increases the adherence of the dressing. Films are often used as secondary dressings and are the dressing material used with most NPWT devices. See TABLES 13-5 and 13-6 for advantages and disadvantages of transparent film dressings.

Hydrogels and Hydrogel Dressings

Hydrogels are water- or glycerin-based products that are either amorphous (defined as dispensed from a tube or impregnated into gauze dressings) or cross-linked polymers formed into three-dimensional sheets. Hydrogels are moisture-donating products that enable the most rapid hydration of a wound surface as compared to other categories of wound dressings. They may contain other ingredients such as alginate to increase viscosity or allow for small amounts of absorption, antimicrobial agents to address bioburden, and collagen or growth factors to enhance wound healing (FIGURES 13-12 to 13-15).

Amorphous gels are reapplied daily; sheet forms may offer extended wear time depending on the amount of exudate that collects beneath them. The periwound skin of a wound treated with hydrogels may need protection with a moisture barrier film or ointment to prevent overhydration or maceration. Hydrogels are used for dry wounds and are contraindicated for wounds that have visible exudate. See TABLES 13-7 and 13-8 for advantages and disadvantages of hydrogels.

Hydrocolloid Dressings

Hydrocolloids are wafer-type dressings composed of three layers: an inner slightly adhesive layer, a middle absorbent layer, and an outer semiocclusive layer. The middle absorbent layer contains combinations of gelatin, pectin, and carboxymethylcellulose with hydrophilic particles, which interact with wound fluid to form a gel mass over the wound bed and thereby maintain a moist environment, support autolytic debridement, and prevent trauma upon removal. The resulting gel is reported to be acidic, therefore, not conducive to bacterial growth; however, caution is advised in suspected or known wound infection as the resulting gelled dressing becomes occlusive in nature and may support bacterial proliferation. The outer layer of the hydrocolloid dressings is either film or foam based and does not allow contamination from the outside environment to reach the wound, nor does it allow exudate to strike through from beneath the dressing. Dressings that become soiled from incontinence may be cleaned but care should be taken to ensure that residual stool or urine does not remain trapped at the edge of the dressing (FIGURES 13-16 to 13-19).

As the middle layer of the dressing gels, the contained moisture is observable from the top of the dressing, thus enabling the clinician to assess the amount of exudate and determine the need for a dressing change. The gel will ultimately migrate toward the edge of the dressing and may leak out from the edge unless it has an adhesive border. The gelatinized exudate is fairly tenacious and sticky, thus can tear fragile skin during removal and cleansing. Hydrocolloids tend to have an odor upon removal, not to be taken as a sign of infection unless the odor remains after the wound has been thoroughly cleansed.

Hydrocolloid dressings are available in various shapes and sizes designed to fit and adhere on almost any anatomic location such as the sacrum, elbows, and heels. Hydrocolloid material is also available in pastes, rings, strips, and powders to fill cavities and creases, as well as for use under pectin ostomy appliances. Frequency of dressing changes is dependent on the particular manufacturers’ instructions for use, but is generally between 3 and 7 days. Shearing forces over areas such as the sacrum and coccyx may cause dressing edges to roll and require more frequent changes, although many newer versions have thin borders that adhere better without rolling. In addition, the dressing can be picture framed with tape. Hydrocolloid dressings can be used as protection from friction and trauma; however, they are not recommended to use over suspected deep tissue injury (SDTI) because the opaqueness prevents visualization of the skin beneath the dressings. Consequently, the evolution of the SDTI cannot be observed frequently. TABLES 13-9 and 13-10 list the advantages and disadvantages of hydrocolloid dressings.

Foam Dressings

Foam dressings, generally made from polyurethane with or without a film outer layer, are very absorbent and prevent “strike-through” or leakage of exudate. There are many differences between the various foam dressings, including thickness, fluid-handling capability, and ability to hydrate or absorb moisture. Foams are available with or without adhesive borders, as well as with standard adhesive or silicone as the adhesion material. The frequently-used silicone backing facilitates painless and atraumatic removal. Foam dressings are semiocclusive, thus allowing for gas and vapor exchange (FIGURES 13-20 to 13-22).

Foam dressings may be used in all wound types, and while indicated for wounds with moderate to large amounts of exudate, they are also suitable for wounds with little to no exudate, especially when used as a secondary dressing. The frequency of dressing change is 3 to 7 days depending on the amount of exudate or the frequency change required for the primary dressing when the foam is being used as a secondary. The moist environment created under the foam dressing can facilitate autolytic debridement. Foams may be used on infected wounds; however, they should be changed daily or according to manufacturer recommendations, especially if the foam contains an antimicrobial.

Foam dressings are available in anatomical shapes appropriate for problematic areas such as the sacrum, heels, and elbows. Bordered sacral foam dressings, specifically multilayered silicone-backed dressings, have been used successfully for prevention of sacral pressure ulcers and there is ongoing research addressing the mechanism of action for this purpose. See TABLES 13-11 and 13-12 for the advantages and disadvantages of foam dressings.

Absorbent Dressings

Calcium Alginates

Calcium alginate dressings are absorbent, biodegradable, nonwoven fibers that are derived from brown seaweed and composed of calcium/sodium salts of alginic acid and mannuronic and guluronic acids. Alginate dressings are available in fiber sheets or packing ribbon/strips and reportedly absorb 15 to 20 times their weight in wound fluid. When applied to a wound with adequate ambient wound exudate, the sodium ions in the exudate are exchanged for the calcium ions in the dressings, thereby forming a sodium alginate gel. This soft gel mass conforms intimately to the wound surface and creates a moist wound environment while continuing to absorb exudate until the dressing is saturated. As long as they remain moist, alginate dressings are easily removed atraumatically and painlessly from the wound bed. Occasionally fibers from the alginate will adhere to the wound bed and require removal with soft debridement or sterile forceps, in which case another dressing may be more appropriate.

Calcium alginates are indicated for moderate to highly exudating wounds of all types. The frequency of dressing change is dependent on the amount of exudate. Copiously draining wounds may need daily changes while wounds with less drainage may be left in place up to 7 days. Calcium alginate dressings tend to wick fluid laterally; therefore, protection of the skin immediately adjacent to the wound is necessary if the alginate dressing extends beyond the wound edge. Calcium is known to act as a clotting factor (factor IV); therefore, alginate dressings may be used as a hemostatic agent for minimally bleeding wounds, for example, after debridement or in the case of low platelets. Alginate dressings require a secondary dressing to manage excess drainage, to hold the dressing against the wound bed, and to protect from external contaminants.

Hydrofiber Dressings

Hydrofiber dressings are soft, sterile dressings composed of sodium carboxymethylcellulose. They are able to absorb large amounts of wound exudate, which transforms the dressing into a soft gel, creating a moist wound healing environment and supporting autolytic debridement. Hydrofibers are used in similar wounds as calcium alginates but are technically in a category by themselves due to their composition, features, and mechanism of action. They do tend to wick only vertically so that any excess dressing overlapping onto the periwound skin does not become wet with exudate. The nature of the dressing creates a soft, conformable gel mass that maintains intimate contact with the wound bed. Thus if they adhere to a dry wound bed, they can be rehydrated and easily removed. See TABLES 13-13 and 13-14 for advantages and disadvantages of these absorbent dressings (FIGURES 13-23 to 13-28).

Specialty Absorptive Dressings^10-16

Gauze and gauze products are not covered specifically in this chapter because they are rather generic in nature. One example is the abdominal pad, a larger absorbent dressing used as a secondary wound cover over filler products to absorb exudate and provide padding for the wound. There are similar multilayered dressings that combine a nonadherent layer to mitigate adherence to the wound bed with varying layers of absorbent materials to wick (and often gel) exudate for higher levels of absorbency. A common example of this construction is also seen in most baby diapers. Some are available in larger sizes (eg, 24 × 36 inches) for use with overwhelming tissue loss and burns (FIGURE 13-29).

Collagen Dressings

Collagen is the primary protein in human tissues and is necessary for wound healing and repair. Research about and evidence for the use of collagen dressings in wound healing has proliferated in recent years as the role of topically applied collagen has been better understood. Because of its chemotactic effects, collagen plays an important role in each of the wound healing phases. It attracts cells needed for healing (eg, fibroblasts and keratinocytes) to the wound and then provides temporary scaffolding for these cells. Additionally, chronic wounds are known to have higher levels of matrix metalloproteases (MMPs) and a reduced number of the MMP inhibitors (TIMPs). When MMPs are present in a wound bed at too high a level, for too long a time, and in the wrong places, they begin to degrade proteins that are not their normal substrates. This can result in “off-target” destruction of proteins (eg, growth factors, receptors, and ECM proteins that are essential for healing) and thus impair the healing process.^17-18 Adding topical collagen to a wound provides an alternate collagen source that can be degraded by the high levels of MMPs as a sacrificial substrate, leaving the endogenous native collagen to continue normal wound healing and to protect other proteins such as growth factors.^17-18 (FIGURES 13-30 to 13-32).

There are variations in collagen dressings, including the source from which the collagen is harvested. Collagen is basically the same regardless of the source; it can be derived from any animal source because there is no difference between species. Current collagen dressings are derived primarily from bovine collagen, and fewer from porcine or ovine sources. Most of the other categories of dressings are used to interact with wound fluid and impact moisture balance in some way. Although some collagen dressings are powdered and/or combined with additional material (eg, alginate) to provide some absorption, most collagen dressings are intended to interact with the wound at the cellular level and are biodegradable; therefore, they have a minimal impact on fluid balance. Frequency of dressing change, which varies from 2 to 7 days, is dependent on the formulation of the collagen product and the amount of wound exudate. Collagen products are only placed on clean and/or granulating parts of the wound, not on slough or eschar. The collagen attracts the cells to which it is adjacent, so if epithelial migration is the goal, the dressing needs to connect with the skin at the edge of the wound. Most products are more effective if moistened with normal saline at the time of application, and are covered with a secondary dressing that will prevent desiccation of the material. Manufacturers’ instructions are advised for optimal results with each product. Advantages and disadvantages of collagen dressings are listed in TABLES 13-15 and 13-16.

Miscellaneous Dressings

The previously described dressing categories are the more standard, with multiple sizes, types, and brands within each category. Knowledge of the category functions enables the clinician to understand combination dressings (also referred to as composites), which have attributes of more than one dressing type and serve to be all inclusive. Combination dressings manage exudate as well as provide absorption, coverage, and security. Many of these dressings can be applied by one clinician and are thus less labor intensive. They may be as simple as a transparent film or tape sheet with a central pad for coverage and minimal exudate absorption, or as complex as an antimicrobial hydrofiber with a bordered foam covering. These dressings tend to be more expensive, but can be cost-effective if the frequency of changing the dressing can be reduced.

Other dressings fall into “stand-alone” categories and are unique in their attributes and mechanism of action. They may be considered niche products by some, yet are mainstays of other practices. Following are a few of these specialty dressings:

Drawtex Hydroconductive Dressings¹⁹

Drawtex (Steadmed Medical, Ft Worth, TX) is a unique primary dressing with a combined mechanism of action. The dressing is composed of a variety of different fibers collectively referred to as LevaFiber technology. This technology is not medicated and has been shown clinically to lift and draw exudate, wound debris, bacteria, and harmful MMPs into the dressing through a combination of capillary, hydroconductive, and electrostatic activities. Exudate is dispersed vertically and horizontally, thereby locking it into the dressing fibers. The exudate then transfers into a secondary dressing. Drawtex is indicated for all types of wounds, especially wounds with moderate to heavy exudate including, but not limited to, burns (superficial and partial thickness), amputations, postoperative wounds, venous leg ulcers (VLUs), pressure ulcers, cavity wounds, DFUs, Buruli ulcers, and complex surgical wounds (FIGURES 13-33 to 13-35).

Procellera²⁰

Numerous physical modalities have been used in attempts to augment the healing process, including ultrasound, low-energy light therapy, and electrical stimulation. There is good clinical evidence supporting the use of electrical stimulation; it has been shown to benefit tissue repair in a variety of wound types and is used extensively for multiple indications in the practice of physical therapy (see Chapter 14, Electrical Stimulation). Procellera (Vomaris Wound Care, Inc, Chandler, AZ) is a unique antimicrobial wound dressing with wireless microcurrent technology that provides an advanced wound healing solution for the management of wounds. Silver and zinc are applied on the device surface in a dot matrix pattern, creating multiple microbatteries. In the presence of moisture, which may come from wound exudate or exogenously applied saline or hydrogel, low-level microcurrents are generated at the device surface. These reactions occur without an external power source or accessories. Procellera antimicrobial dressing is indicated for partial- and full-thickness wounds such as pressure ulcers, venous ulcers, diabetic ulcers, burns, surgical incisions, donor and/or recipient graft sites, and so forth. The dressing may be left in place for up to 7 days; more frequent dressing changes may be needed with high exudate levels (FIGURES 13-36, 13-37).

Enluxtra Self-Adaptive Dressing²¹

The Enluxtra Self-Adaptive Wound Dressing (Osnovative Systems, Inc, Santa Clara, CA) adapts to continuously changing wound conditions and emerging requirements that may have been unknown or unpredictable when the dressing was first applied. The dressing material is designed to change its properties according to the feedback from underlying wound tissues. Thus the dressing dynamically balances the evolving moist wound environment and provides hydration or absorption depending on the instantaneous needs of wound and periwound skin. Dry areas of the wound stay properly hydrated, fluid from exuding areas is absorbed and locked in, and periwound skin is protected from maceration. The dressing is indicated for all wound types and all exudate levels and is changed based on the amount of exudate; however, it may be left in place for up to 7 days (FIGURE 13-38).

X-Cell²²

X-Cell (Medline Industries, Inc, Chicago, IL) is another dressing that can either absorb exudate or hydrate tissue depending on the moisture level of the tissue it is covering. Composed of hydrofiber partially saturated with saline, it is moist enough to be soothing to inflamed and painful wounds and yet able to absorb small amounts of exudate. Because it is nonadherent, dressing changes are less painful and not destructive to underlying fragile tissue such as tendon, muscle, or new granulation. X-cell is available in sheets, making it ideal for flat wounds such as partial thickness burns, vasculitic wounds, venous wounds, skin tears, and flat traumatic wounds. It is also available with 0.3% polyhexamethylene biguanide (PHMB), a broad-spectrum antimicrobial. When applying X-Cell, it is recommended to extend the dressing over the wound edges, thus it functions like a blister, sealing the wound bed from contaminants and in the case of a dry wound, enhancing autolytic debridement (FIGURE 13-39).

Gold Dust ²³

Gold Dust (Southwest Technologies, Inc, Kansas City, MO) is a highly absorbent hydrophilic polymer capable of absorbing large amounts of exudate and retaining the exudate in the matrix even under high pressures. The dressing fills and conforms to the wound bed, thereby creating and maintaining a moist wound environment. Gold Dust may be used as dry granules on highly exudating wounds; however, the wounds must be monitored for the potential of overdrying the tissue. If the wound contains low to moderate exudate, the dressing may be premoistened prior to application. Upon application, either moist or dry, patients may experience a burning or stinging sensation. Frequency of dressing change is driven by the level of exudate in the wound and may range from daily to up to 7 days. Gold Dust is indicated for all wound types with heavy drainage.

Biologics

The field of wound care began a journey into the use of biological devices beginning in the late 1990s, and today has seen a significant expansion in options for actively enhancing the wound healing process. The plethora of wound dressings that are available balance the local wound milieu to create an ideal environment for the wound healing, but with the exception of collagen,^17-18 these specialty dressings do not directly interact with cells or impact cellular activity.

A biologic is a device or product that in its natural state is a contributor to the wound healing process and thereby manipulates the process when applied topically to an open wound. Of critical importance is that all of these devices are used in the well-prepared wound—one that is free of necrotic tissue, has an acceptable low level of bioburden, and has adequate blood supply to support wound healing. An understanding of the indications and contraindications with each device is essential.

The materials used to produce biological dressings may be derived from human or animal tissue and may undergo extensive or minimal processing to manufacture the finished product. Consequently the extent of processing and the source of the material used in the product also determine the regulatory pathway required before the product can be marketed.²³ The regulatory and approval processes vary greatly and are covered in great detail here. For the purposes of basic understanding, however, the types of approvals fall into three basic categories with the Food and Drug Administration (FDA): Premarket approval, HCT/Ps, and 510(k).

Premarket Approval²³

Premarket approval (PMA) is the required process of scientific review to ensure the safety and efficacy of Class III devices. Class III devices support or sustain human life; are of substantial importance in preventing impairment of human health; or present a potential, unreasonable risk of illness or injury. As a result, clinical and safety data are required by the FDA for the device to be used as a wound treatment. At this time there are only three products used in chronic wound management that have received this type of approval—two cellular products are Apligraf (Organogenesis, Inc, Canton, MA) and Dermagraft (Shire Regenerative Medicine, Inc, San Diego, CA), and a recombinant platelet-derived growth factor gel, REGRANEX (becaplermin) Gel 0.01% (Healthpoint Biotherapeutics, Ft Worth, TX).

Cellular Therapies

The delivery of cells to an open wound to induce healing is now relatively commonplace, with some products in existence since the late 1990s. Directed cell therapy, most notably stem cell therapy, has become a more significant portion of the current thrust of regenerative therapy research, with the ability to create a true dermis with skin appendages being the gold standard of chronic wound healing.²⁴ This discussion focuses on living cell therapies currently in use.

Two products are created from living cells and cultured in the laboratory to create sheets of cells cultivated on a mesh. Although these products are termed skin substitutes or living skin equivalents, these terms are not used by the FDA and are technically incorrect as they relate to the mechanism of action of the products. They are not skin grafts; they do not “take” as does an autologous skin graft. The product does not persist in the wound bed, does not become vascularized, and does not promote ingrowth of the recipient cells into the device. Application of these cell therapy products onto a well-prepared wound bed creates an environment in which the cultivated cells deliver cytokines and growth factors that subsequently trigger a healing response from the recipient site. The cytokines and growth factors induce the tissue to granulate and close as it would in a more normal healing process. The two cell therapy products currently available are Apligraf and Dermagraft.

Apligraf²⁵ is a bilayered, living cell-based product that has FDA approval for the treatment of both VLUs and DFUs. Like human skin, Apligraf consists of living cells and structural proteins. The lower dermal layer combines bovine type 1 collagen and human fibroblasts (dermal cells), and the upper epidermal layer is formed by promoting human keratinocytes (epidermal cells) first to multiply and then to differentiate and replicate the architecture of the human epidermis. The human keratinocytes and fibroblasts are derived from neonatal foreskins. Unlike human skin, Apligraf does not contain melanocytes, Langerhans cells, macrophages, lymphocytes, or other structures such as blood vessels, hair follicles, or sweat glands. When applied, it provides a temporary barrier function. Individually, the two cell types produce a combination of cytokines and growth factors found in human skin, and in addition, the two cell types release signals that influence the function of the other cell type.

Apligraf is shipped in a sealed bag, under controlled temperature and on a nutrient medium to keep the cells viable until use. The bag is opened no longer than 15 minutes prior to application to the wound. The product is lifted from the tray and fenestrated with a scalpel to allow for passage of exudate as well as to enable intimate contact with the wound bed. It is secured to the surrounding skin, covered with a contact layer, and then anchored with a dressing appropriate for the exudate level of the wound. The initial dressing is removed after 1 week for assessment of the wound progress. Apligraf can be reapplied up to five times to facilitate healing, although in clinical trials patients usually required between three and four applications for complete wound healing. Since Apligraf is indicated for VLUs and DFUs, it should be used in conjunction with standard care for those wound types, including compression for the patient with a VLU and off-loading and glucose control for the patient with a DFU (FIGURE 13-40).

Dermagraft²⁶ is a cryopreserved, human fibroblast-derived dermal substitute containing fibroblasts, extracellular matrix, and a bioabsorbable polyglactin mesh scaffold. The fibroblasts, which are obtained from human newborn foreskin tissue, are placed on the scaffold and then proliferate and produce human dermal collagen, matrix proteins, growth factors, and cytokines. The process creates a three-dimensional human dermal substitute with metabolically active human cells. Dermagraft does not contain macrophages, lymphocytes, blood vessels, or hair follicles.

Dermagraft is packaged with a saline-based cryoprotectant that contains bovine serum and 10% dimethylsulfoxide (DMSO). The directions for use include specific thawing, rinsing, and application steps. It is recommended to use within 30 minutes of thawing; any unused product is discarded and a new package used for each application. A nonadherent contact layer is applied over the Dermagraft, followed by a dressing to bolster the device in place and provide for a moist environment. The first dressing change takes place after approximately 72 hours. The subsequent dressing changes would then be determined by the provider. Dermagraft is indicated for DFUs and is used in conjunction with the appropriate off-loading and glucose control (FIGURE 13-41).

Growth Factors

Growth factors (GFs) are small proteins produced by multiple cells and act as signals to allow cells to communicate with one another. GFs specifically stimulate the migration and proliferation of cells, and thus the formation of new tissue. Many cell types are involved in wound healing, including platelets, macrophages, and fibroblasts. Platelets are the first cellular components to invade the wound site and initiate the wound healing process by releasing stored growth factors.

One specific growth factor that is available for topical application on a well-prepared wound is a recombinant platelet-derived growth factor (PDGF). REGRANEX Gel²⁶ is formulated with 0.01% becaplermin, a recombinant human platelet-derived growth factor (rh PDGF-BB), in aqueous sodium carboxymethylcellulose-based gel for topical administration. At this time, it is the only FDA-approved topical agent with PDGF. When applied to a well-prepared wound bed, REGRANEX Gel promotes the recruitment and proliferation of chemotactic cells, thereby stimulating the wound healing process and aiding formation of granulation tissue.

REGRANEX Gel²⁷ is indicated for the treatment of lower extremity diabetic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. It is an adjunct to, and not a substitute for, good wound care practices, and is contraindicated in patients with known neoplasm(s) at the site(s) of application. Additionally, malignancies distant from the site of application have been reported in both a clinical study and postmarketing use. Therefore, REGRANEX Gel should be used with caution in patients with a known malignancy.

Regranex is available by prescription only; it is applied daily in a thin layer to a clean wound bed and covered with a moist dressing. Based on the clinical trials, the package insert recommends a second dressing change daily to reapply the moist dressing. In this author’s experience, the second dressing change is not necessary as long as the wound bed can remain moist; however, this is considered off-label use and must be determined by the prescriber.

HCT/Ps²³ (Human Cells, Tissues, and Cellular and Tissue-Based Products)

Human tissue can be obtained from human donors, processed, and used exactly in the same role in the recipient—skin for skin, tendon for tendon, bone for bone. These uses are regulated as HCT/Ps as long as the proposed clinical use and manufacturing methods are consistent with definitions of homologous use (meaning the device is used for the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic functions in the recipient as in the donor) and minimal manipulation (meaning the processing does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement). Registration as an HCT/Ps establishes donor eligibility, current good tissue practice, and other procedures to prevent the introduction, transmission, and spread of communicable diseases by the device.

There are many human cellular products used in chronic wounds that are derived directly from human tissue versus being cultured in the laboratory. They are regulated via the HCT/Ps process, and most manufacturers are registered with the FDA as a tissue establishment and accredited by the American Association of Tissue Banks (AATB). The source of the devices vary and include, but are not limited to, cadaveric preserved skin, human amniotic tissue, and processed acellular dermal matrices. Just as all of the biologic products, HCT/Ps are designed to stimulate healing of chronic wounds in a well-prepared wound bed.

510(k)

A 510(k) is a premarketing submission made to the FDA to demonstrate that the device to be marketed is as safe and effective (ie, substantially equivalent to) as a legally marketed device that is not subject to PMA. All wound dressings fall into this category, and a small percentage require clinical data for approval. The approval process, however, is far less stringent than the PMA process.

Collagen, as the basic structural material of the body, is a biologically derived material that is recognized by human tissue cells regardless of the source. The products are derived from porcine, bovine, equine, and ovine sources. As a result, all collagen products are approved via the 510K process; however, some have provided additional clinical data elevating them to a level in the biologic category. These products are collectively referred to as acellular tissue matrices, and when applied to a well prepared wound bed, influence cellular migration, provide a scaffolding for temporary cellular attachment, and act as a sacrificial substrate for excessive MMPs, thereby mitigating the hostile environment in chronic wounds. Inclusion in the biologic category results in direct reimbursement outside of the surgical dressing policy of the Centers for Medicare and Medicaid Services (CMS), which is guided by local coverage decisions and managed by federal and state payers, as well as private insurance companies.

Clinical use of these active devices has increased in recent years largely due to enhanced education, recognition that advanced treatments expedite wound healing and lead to better patient outcomes, and acknowledgement that the earlier an advanced therapy is initiated, the sooner the wound is likely to heal. Accelerating the healing of a chronic wound is critical, as complication risks and costs increase over time.^28,29

Acute wounds in healthy patients with low comorbidities will usually progress through the wound healing cascade in a timely manner; however, a delay in healing and subsequent development of a chronic wound requires complex wound assessment and intervention. The changes associated with chronic wound development often involve alterations in one of three primary categories, including systemic and cellular changes, macrovascular or microvascular ischemia, and the negative effects of bacterial bioburden. These challenges highlight the fact that selection of one antimicrobial dressing, or any single therapeutic intervention, will not result in wound healing alone.³⁰ Instead, systemic management of known comorbidities and wound bed preparation are necessary to ready the wound bed for healing.

Sibbald³¹ et al first described the TIME model for wound bed preparation, which involves removal of devitalized Tissue, reduction of Infection/inflammation, Moisture management, and prevention of Edge rolling or epibole. Therefore, the wound clinician approaches wound bed preparation holistically and determines the amount and type of debridement necessary, the methods by which to reduce bioburden and proinflammatory local wound mediators, the optimal dressings to maintain adequate moisture levels and normothermia, as well as to provide adequate wound filling. Each decision involves an evaluation of the available evidence, professional experience, and the ability of the patient’s resources to obtain and provide the necessary care. Wound care is never straightforward like the testing of a dressing in a laboratory, but instead is a mixture of science and real-world circumstances.

The use of antimicrobial wound care products has received a great deal of scrutiny with some literature suggesting there is no evidence for the use of these products in wound care. However, it is important to understand that the selection of an antimicrobial agent is not meant to bring about wound healing. An antimicrobial dressing may be selected for treatment or palliation in order to

• ▪ Reduce the bacterial burden of a wound

• ▪ Decrease pain associated with care

• ▪ Diminish wound odor

• ▪ Potentially interrupt bacteria biofilms

A best practice statement³² described this misunderstanding and points out that these misconceptions are related to Cochrane-style systematic reviews, which are devoid of the proper evidence-based usage of antimicrobial dressings, insufficient study follow-up, and unreasonable end points such as time to complete wound healing. Additionally, Sackett³³ et al point out that evidence-based medicine is not restricted to RCTs and meta-analysis, but an evaluation of all available external evidence to answer the question at hand. Further, an important potential benefit of antimicrobial dressings is to reduce the use of systemic antibiotic therapy that is prone to bacterial resistance. Landis³⁴ et al states that one in four persons with a chronic wound receives antibiotic therapy at any given time and that over 60% have received these medications in the last 6 months. The overuse and abuse of antibiotics reflects the lack of practitioner knowledge surrounding proper management of complex chronic wounds. With these concepts in mind, it is necessary to examine the levels of bacterial influence in the wound milieu, the products available for bacterial control, and how topical antimicrobial agents can be utilized appropriately.

Infection in humans is generally the result of bacteria, fungi, viruses, or protozoa.³⁵ The term bioburden is utilized in varying connotations to refer to the effect of organisms within a wound bed that influence wound healing. All chronic wounds have some level of bacterial bioburden; however, the presence of bacteria does not indicate infection. In general, clinicians classify the range of bacterial influence using the terms contamination, colonization, critical colonization, and infection (defined in TABLE 13-17). These terms attempt to classify the amount and the activity of the bacteria within the wound. Contamination and colonization do not always require direct intervention and principles of autolytic wound healing are likely sufficient. However, as the wound reaches critical colonization, subtle clinical changes occur that influence the healing trajectory. Infection has occurred if these replicating organisms move from the superficial to the deep tissues, invade tissues not involved with the area of injury, and induce evidence of host injury.³⁴

Previous studies have attempted to discover the number of bacterial inoculums at which critical colonization occurs, with some sources indicating a level of 10⁵ colony forming units (CFUs) per gram of tissue for some bacterial species; however, this quantification can be misleading. The pivotal concerns include the diversity of bacteria present, the virulence, the presence of a particular species, the expression as planktonic versus biofilm phenotype bacteria, and the host’s immune system ability to resist infection^36,37 Authors describe a negative association with bacteria found in chronic wounds and poor wound healing, especially when gram-negative bacteria, proteus, E coli, bacteriodes, β-hemolytic strep, and pseudomonas are present.³⁸ In a study by Dalton et al, pseudomonas was noted to overrun the wound environment, even when only beginning as 1% of the total inoculums; it quickly grew to 100% of the population in 48 hours.³⁹ Similarly, the authors reported that pseudomonas was often found at the leading edge of infection related to both its bactericidal proteases, as well as its superior motility.³⁹ Additionally, its pathogenicity may be more prevalent in certain populations, climates, and developing countries.⁴⁰ Staphylococcus aureus, on the other hand, is equally pathogenic because it possesses the capability of producing a wide variety of toxins and enzymes with the ability to block phagocytosis, degrade collagen matrices, provide antibiotic resistance, and lyse and destroy host cells, all of which lead to abscess formation.³⁴ While single genera planktonic bacteria are able to induce acute infection, chronic wounds often demonstrate synergistic bacterial relationships, such as those found in mature biofilms, which is discussed later in this section.

The total number of bacteria present is likely irrelevant for the wound care practitioner. First, the number of bacteria cannot be determined by physical assessment and traditional swab cultures are unable to fully identify the vast diversity of organisms. In addition, available laboratory evaluation largely ignores the significance of anaerobes. Newer technologies and methods for identifying a wide range of aerobes and anaerobes are available, such as molecular modeling, which have been found to be far superior to current techniques. Dowd et al⁴¹ described a study in which swab culturing found only 12 different bacterial genera, while the same wound revealed up to 106 bacterial genera, most of them facultative anaerobes which are not normally detected with standard approaches. However, these advanced methods remain technically challenging and are not currently available to all clinicians. Because of this, more subtle assessment findings may provide the most beneficial clue as to changes in the wound environment and the detrimental rise in wound bioburden.

Wounds are assessed for etiology, quality and amount of granulation tissue, percentage of nonviable tissue present, condition of the wound edges, presence and amount of exudate, total surface area, and presentation of the surrounding intact skin. While acute infection in a healthy individual displays the classic signs and symptoms of erythema, induration, edema, pain, suppuration, and fever, these findings are often either reduced or absent in the patient with poor perfusion or an incompetent immune system.³⁴ However, the clinician again must utilize keen assessment skills because subtle changes in wound bed appearance may represent alterations in nutrition, inappropriate systemic or local inflammatory states, inadequate perfusion, or medications, all of which may mimic changes seen with an increase in bioburden.

Two pneumonics have been developed to distinguish between critical colonization and infection in a chronic wound. NERDS and STONES provide characteristics that can help differentiate between a wound that has critical colonization (NERDS) and absolute infection of the wound bed and surrounding tissue (STONES). The superficial presence of microbes (NERDS) may be treated with topical antimicrobials since the bacteria are on the surface of the wound bed; however, the deeper infection (STONES) will need to be treated with systemic antibiotics (TABLE 13-18). The differential diagnosis is made clinically; swab cultures may be used to identify the bacteria and determine drug sensitivity.⁴² Fife et al⁴³ stated that these secondary signs had greater sensitivity than the classic symptoms (0.62 and 0.38, respectively), with increasing pain and wound breakdown often sufficient enough to indicate infection. It is in these circumstances that the authors suggest that early and liberal use of topical antimicrobials may reduce bioburden and localized infections.

Biofilm

For years topical application and systemic administration of antibiotics have been utilized because of their bactericidal effects on planktonic bacteria. These mitotically active and vulnerable bacteria can be targeted and killed with the right corresponding antibiotic, antiseptic, or antimicrobial dressing. However, some bacteria and fungi have the capability of inducing a radical change in their phenotype following attachment to the wound surface. These bacteria can express over 800 new proteins within hours, thereby protecting themselves in an extracellular polymeric matrix that provides a protective encasement for a variety of genotypes, with upward of 17 genera of aerobes and anaerobes in each wound.^44,45 The bacteria irreversibly attach to the wound surface, become mitotically senescent within the biofilm base, and have enhanced resistance to the host’s antibodies as well as innate phagocytosis. This is described by Phillips⁴⁶ et al, who explain that resistance is due to limited diffusion of the microbial molecules through a dense and negatively charged matrix, with special bacterial efflux pumps in the cell membranes to pump out antimicrobial agents, with or without the secretion of enzymes that bind or inactivate antimicrobial agents; the lack of a mitotically active base; and areas lacking oxygen that allows for the proliferation of anaerobes (FIGURE 13-42).

Therefore, the development of this bacterial biofilm results in a chronic state of inflammation for the host, which cannot be removed with the routine use of wound cleansing or antibiotics. In fact, the minimum concentrations of many antibiotics needed to eliminate a biofilm may be thousands of times the standard dose and exceeds the maximum prescription dose available.^46,47 While biofilms are microscopic in size, the bedside clinician may suspect the presence of biofilm-encased bacterium in 90% of nonhealing chronic wounds.^49,50 Additionally, when the biofilm grows undeterred it may become detectable to the naked eye, such as seen in dental plaque or the development of a dense, slimy membrane.

The inability to remove biofilms through systemic antibiotics and topical antimicrobial therapies highlight the need for repetitive and multimodal debridement.^44,50 Both sharp and ultrasonic debridement are often indicated on a twice weekly basis, given the speed at which the biofilm may fragment and resurface the wound bed within 48 hours.⁵¹ Debridement serves two major purposes: (1) the physical detachment of the biofilm and its strong adhesion molecules and (2) destruction of the dense outer layer, thus allowing exposure of the bacteria inside the biofilm to antimicrobial agents. Attinger and Wolcott⁴⁹ describe the clinical significance of this being the ability to combine polymerase chain reaction (PCR) sequencing to direct therapy and select antimicrobials to remove the biofilm from the wound bed.

With specific biofilm-based infections, such as chronic osteomyelitis or prosthetic implant infection, wound healing may not be possible with surface debridement and antimicrobial agents alone. While acute osteomyelitis may be treated and resolve with early identification and antibiotic therapy, recalcitrant osteomyelitis results from poor tissue perfusion that fails to supply antibiotics, as well as biofilm formation. Removal of the infected bone and/or the prosthetic implant is necessary, as described in detail by Roy and colleagues.⁵² For the bedside clinician, wound assessment with the finding of exposed bone has been shown to have a positive likelihood ratio (LR) of 9.2 for osteomyelitis, and the finding of a jagged feel to the bone when probed has been shown to carry a prevalence of over 60%.⁵³ While imaging studies remain the primary diagnostic, laboratory data including erythrocyte sedimentation rate (ESR) can be used to diagnose osteomyelitis in DFUs, especially when the result is over 70mm/h.⁵³ However, the clinical finding of exposed bone in an open wound indicates the need for more vigilance (FIGURE 13-43A-C).

The essential components of treating an acute wound include thorough irrigation, appropriate dressing selection, prevention of infection, assessment for surgical intervention for wound coverage and closure, and off-loading. In the chronic wound, further diagnostic evaluation is indicated, and it should not be assumed that simple wound care is sufficient. If a wound with considerable depth granulates and closes, but then continues to reopen with findings of a sinus track or purulent discharge, surgical intervention is most likely indicated.

Categories and Considerations for Antimicrobial Use

Wound care practitioners have multiple antimicrobial products available for standard care. Six major categories include the following: (1) antibiotics, (2) antimicrobial peptides, (3) antibiofilm agents, (4) antiseptics, (5) disinfectants, and (6) topical antimicrobial dressings.

Antibiotics

Antibiotics have decreased in popularity as first-line treatments for management in wound care secondary to the rise of bacterial resistance. While the method of action varies, antibiotics generally have one defined target, thereby limiting their effectiveness against multiple pathogens.⁵⁴ It is agreed that systemic antibiotics should be avoided without evidence of true clinical infection, and topical antibiotics should be similarly avoided when treating infections because they may cause hypersensitivity reaction, lead to super infections, and encourage resistance.³⁶ Antibiotics should not be abandoned, rather reserved for situations where advancing clinical infection is present, highly virulent organisms exist in the wound bed, or the host’s immune response is severely compromised, such as in DFU infections. The detailed investigation of antibiotic use in wound care is beyond the scope of this chapter.

Antimicrobial Peptides

Two new categories of antimicrobials are entering the wound care market and include antimicrobial peptides (AMPs) and antibiofilm agents. The discovery of AMPs in the 1990s further enhanced understanding of the inflammatory phase of wound healing, offering an additional option to ward off the increase of antibiotic resistance. More importantly, AMPs were found to induce proteoglycan expression and thereby impact keratinocyte migration, angiogenesis, and creation of the ECM.⁵⁵ These peptides are typically found in polymorphonuclear leukocytes and epithelial cells in eukaryotes and have broad-spectrum bactericidal action against a range of organisms, show rare resistance, and can work in tandem with other antimicrobial agents.³⁶ Clinical trials are underway for a new drug, pexignan,⁵⁶ which is awaiting FDA approval for use in infected DFUs. Previous studies have already explored the potential constructs from which these peptides could be delivered to the wound bed as well as their potential benefit against resistant organisms.^57,58 As of now, these products are not available to the wound care practitioner commercially, but offer hope for improving infection management in the future.

Antibiofilm Agents

The next product awaiting widespread use in the clinical arena involves a novel antibiofilm/antimicrobial agent, Dispersin B.⁵⁹ Kaplan et al described the use of exogenously applied deoxyribonucleases on the aggressive adhesion of a biofilm exopolymeric matrix by preventing biofilm formation or by detaching existing biofilms of S aureus and S epidermidis. Moreover, this antibiofilm agent has been combined with triclosan (a broad-spectrum antiseptic) to illustrate synergistic antimicrobial and antibiofilm capability against S aureus, S epidermidis, and E coli. An in vitro study by Darouiche et al⁶⁰ compared catheters coated with dispersin B plus triclosan against catheters coated with chlorhexidine and silver sulfadiazine and found that the antibiofilm agent more significantly reduced bacterial colonization and demonstrated prolonged antimicrobial activity (p <0.05). This combination has also shown promise in in vitro studies against resistant bacterial biofilms versus currently available topical antimicrobials such as cadexomer iodine and silver gel.⁶¹ These in vitro studies warrant the need for increasing in vivo evaluation to determine how these products should be utilized in the future.

Antiseptics

Topical antiseptics are antimicrobial agents that reduce the number of microorganisms and may be seen as an adjunct to infection control. Whereas antibiotics have a specific method of action, antiseptics utilize multiple targets to inhibit or kill organisms and have a larger spectrum of activity against bacteria, fungi, and viruses. Categories include alcohols (ethanol), anilides (triclocarban), biguanides (chlorhexidine), bisphenols (triclosan), choline compounds, iodine compounds, silver compounds, peroxygens, and quaternary ammonium compounds.³⁰ These compounds may be in hand soaps, pre-surgical skin preparations, and some wound cleansers. The use of antiseptics in the open wound has previously been viewed with great scrutiny due to the risks of cytotoxicity and the potential for repetitive tissue trauma during their use³⁸; however, this greatly depends on which product is used and more importantly, how it is used by the wound care practitioner. For example, while most experts agree that continuously packing a wound with dressing materials saturated in cytotoxic antiseptics is not appropriate wound care, the short-term use of an antiseptic as part of wound irrigation is often found to be very effective in practice. More importantly, wound care clinicians continue to use antiseptics because of the clinical benefit they see, even if in vitro data do not support their use in all circumstances. Cytotoxic effects can be seen with many approved topicals, including silver, but detrimental effects are generally a result of exposure time and overall concentration.⁴³ Generally, antiseptics are used when the clinician perceives the need to reduce the level of bioburden as the number one priority or visualizes signs of infection. The selected antiseptic is either one with broad-spectrum capability or with a specific effect on a known pathogen, such as acetic acid on pseudomonas.

Antiseptics may also be utilized for specific wounds, such as large total body surface area burns that are prone to detrimental colonization from a variety of organisms that can lead to sepsis, a leading cause of morbidity and mortality. However, guidelines by the US Health and Human Services historically recommend these products not be used in pressure ulcers and suggest alternatives such as normal saline.⁶² Luckily, compromise can be reached in these differing opinions as newer noncytotoxic antiseptics are available, such as superoxide water solutions (Microsyn, Oculus Innovative Sciences, Petaluma, CA), PHMB irrigations (Protosan, B Braun, Bethlehem, PA), and even diluted and stabilized sodium hypochlorites and hydrochlorous acid (Anasept, Anacapa Technologies, San Dimas, CA; Vashe Therapy, Puricore, Malvern, PA). These products provide the benefits of bioburden reduction without injury to the host cells. A systematic review⁴⁰ described two small, single-center randomized controlled trials looking at the use of superoxide water versus povidone iodine and soap and water and found that patients with infected DFUs had greater odor reduction, reduction of cellulitis, and improved granulation tissue with the superoxide water solution.

Thus far systematic reviews have failed to identify evidence to recommend one specific cleansing solution or technique for wound management over another.⁶³ However, a best practice statement for the use of topical antiseptics and antimicrobial agents in wound care³² agreed that there are clinically justified circumstances where antiseptics can be utilized for well-defined, short-term time periods, and as part of a wound care plan that involves serial debridement and biofilm prevention and removal strategies. How a wound is irrigated and cleansed needs careful attention, and not just with what it is cleansed. Normal saline is still the most recommended wound irrigation for its ability to remove bacteria from the wound bed. This is not because of its chemical structure; saline is not antimicrobial. Yet when utilized properly, saline is capable of removing bacteria with the right amount of pressure.⁶⁴ Moreover, Fernandez and Griffiths⁶⁵ showed that potable water, or tap water, was as effective in wound irrigation as saline and suggest that there is no evidence that it increases risk of infection.

Disinfectants

Disinfectants are chemicals that are used primarily to kill microorganisms on surfaces or devices and are an integral part of infection control in medical facilities. They are, however, generally harmful to humans and should not be used topically or in open wounds. While the active agents in these solutions may be familiar to other topical antiseptics, the pH, concentration, and chemical additives warrant that they should never be used for wound care.

Topical-Antimicrobial Wound Dressings

Selection of a wound care dressing is based on far more than reduction of bioburden. The decision and selection is multifactorial, with the clinician asking these questions: How can I dress this wound so as to manage the exudate or moisture level, decrease the frequency of changes, decrease the pain of the patient, decrease the risk of trauma to the wound bed, and adequately pack the dead space? Is an antimicrobial necessary? Can my patient afford these dressings after discharge? In some cases, the antimicrobial selected is related to its known effect against certain pathogens. In other cases, selection is more related to the dressing construct and delivery method of the agent into the wound, and how it manages the other considerations listed above. The decision may be made based on the clinician’s personal experience with a particular agent in the specific wound type that is being assessed. Finally, any patient allergies need to be factored into the selection.

While researchers and companies are scrambling to provide bedside point-of-care testing to guide the bedside clinician with real-time biofeedback to influence the plan of care, much of wound care selection is a mixture of science and art. It is important for the nonclinician or bench researcher to understand that the bedside clinician is not blindly guessing on the plan of care in a laissez-fare fashion. Instead, the wound care practitioner uses keen assessment skills, history and physical assessment, laboratory data, experience, and craftsman-like creativity to improve outcomes. Further, in vitro data are not real world clinical reality, where nonclinical parameters such as availability and affordability also influence practice. According to Gethin,³⁵ dressings should be selected per the specificity and efficacy of the agent, potential cytotoxicity to human cells, effect on resistant bacterial strains, allergenicity, cofactors of the wound based on size and exudate, and total bacterial load.

Current evidence regarding the use of antimicrobials is flawed and leads to erroneous recommendations.⁶⁶ When studying a topical antimicrobial meant for short-term use, such as silver, looking at its capability to influence time to wound healing is scientifically unsound.³² In the truest form of a randomized controlled trial, one intervention should be investigated until the primary outcome is achieved. However, Gottrup⁶⁷ describes how this is not possible in wound management secondary to changes in the wound bed that may indicate that the particular intervention is no longer appropriate, multiple modalities are needed, or the healing trajectory is too prominently guided by underlying comorbidities. Further, the author states that the often-used primary outcome of complete wound closure should never be used as a “gold standard” because no therapy could ever be considered efficacious with this parameter. Additionally, no topical antimicrobial has the potential of reducing the systemic contributors to poor wound healing, such as nutrition and disease.³⁵ Many experts agree with these sentiments and add that the majority of systematic reviews looking at antimicrobials have inadequate sample sizes, short follow-up periods, non-random allocation of treatment groups, non-blinded assessment of outcomes, and insufficient delineation between the control and experimental groups.^{30,32-33,36,67-69}

With that in mind, the most commonly used antimicrobials will be evaluated based on their mechanism of action to reduce bacterial bioburden as well as the practical considerations that influence their use.

Silver

Silver dressings may be the most popular selection for the reduction of wound bioburden, in large part due to its history. The first reports of silver being used as an antimicrobial agent were in the days of Hippocrates, until it lost favor with the advent of antibiotics during World War II.⁷¹ With increasing resistance to antibiotics, silver provides a viable option for the reduction of bioburden and the control of localized infection. One of the major reasons silver is so readily used is because of the wide variety of dressing delivery types that are available. Silver is provided in amorphous hydrogels, sheet hydrogels, alginates, hydrofibers, foams, silicones, contact layers, wound powders, ointments, negative pressure foams, and irrigations in the form of silver nitrate solutions. As described by Mooney et al,⁷¹ silver’s broad-spectrum antimicrobial ability is not in question, but the choice of dressing is more dependent on the characteristics of the particular carrier dressing, the way silver is delivered to the wound bed, and the needs of the wound following assessment. An International Consensus Document⁷² prepared by a group of experts discusses the appropriate use of silver in wound care and describes the function of various silver forms. The document states that the metallic form of silver is unreactive and does not have a bactericidal effect but must ionize to its active form, usually through contact with wound exudate. The silver must either be in contact with the wound bed to kill organisms on the surface or be in an absorbent carrier dressing that will reduce the bioburden by destroying bacteria absorbed into the dressing through the wound exudate. The authors caution the clinician to beware of false claims regarding the amount of silver loaded into a particular dressing as this does not correlate to the amount of silver delivered to the wound bed. The discrepancy is a result of inactivation by levels of wound chloride and proteins.

The benefit of silver is its ability to affect multiple sites within the bacterial cells, such as binding to bacterial cell membranes, interfering with binding proteins and energy production within the cell, decreasing enzyme function, and providing DNA and RNA transcription inhibition.⁷² The multimodal approach to bacterial death makes silver effective, but also at very low risk to bacterial resistance.⁷³ Additionally, silver may increase the sensitivity of a biofilm to antibiotics as well as alter its adhesion to the wound bed.⁷⁴

In order to realize its total bactericidal potential, silver must have a controlled and sustained release. In other words, the bacteria must be exposed to a sufficient concentration of silver ions over time without causing tissue toxicity.⁷⁵ The ability for the dressing to conform, remain in place, and provide consistent coverage of the wound bed is necessary in order to achieve antimicrobial reduction. While silver appears in many dressings, its quantity, chemical form, delivery, release, and ability to conform influence the outcomes observed at the wound site.^76,77

Another benefit from silver involves the potential for reducing inflammation. Hoeskstra⁷⁸ reported a histological comparison between two dressings and showed a reduction in inflammation between the silver hydrofiber group and a tulle gauze control. This finding has similarly been reported in burn management⁷⁹ and via review of literature by an expert panel.⁷² It is unclear, however, whether the anti-inflammatory effects of silver are directly related to the resultant reduction in wound bioburden or through some additional unknown mode of action.

Secondary symptoms of wound management are also of importance to the care provider. Dressing construction and function assist with the reduction of pain and trauma to the wound bed during dressing changes. The impact of pain and stress on wound healing is of concern, and dressings capable of delivering silver to the wound bed without adhering to the wound surface are advised in order to decrease pain and prevent trauma to the surface. This will assist in stopping the cycle of repetitive trauma and wound pain, as described by Krasner.⁸⁰ The use of silicone dressings, especially those impregnated with silver, has become very advantageous for these reasons. When compared to topical silver sulfadiazine, a silver impregnated silicone foam dressing showed a reduction in patient experience of pain at application (p = 0.02) and during wear (p = 0.048), decreased frequency of dressing changes (2.2 vs 12.4), and significantly reduced costs ($309 vs $513) in a multicenter randomized comparative trial.⁸¹ The reduction of cost and dressing change frequency was also noted to depend on dressing type in an RCT by Muangman et al.⁸² However, when levels of silver content and dressing construction type are similar, outcomes may be more comparable, as described in a study looking at silver alginates versus silver carboxymethylcellulose dressings.⁸³

Even when the efficacy of bioburden reduction is similar, secondary symptom control may differ based on dressing type. A study by Glat et al⁸⁴ showed no statistically significant difference in the rate of infection or time of reepithelialization in partial thickness burn wounds between silver sulfadiazine ointment and a silver hydrogel; however, the author identified less pain and increased patient satisfaction in the hydrogel group. Additional benefits described in RCTs and systematic reviews of silver include odor reduction, decreased wound exudate, and prolonged wear time.⁶⁹

Despite all of the aforementioned benefits of silver, it is not the dressing of choice for all wounds, nor is it intended to be utilized for the entire duration of the healing process. In fact, the use of silver is recommended for a limited time due to potential apoptosis of keratinocytes, fibroblasts, and leukocytes.^85,86 Silver can become cytotoxic to host cells if the dressing delivers large quantities of the ion to the wound and is used over extended periods of time, therefore silver dressings should be discontinued when signs of inflammation and critical colonization have resolved. Symptoms indicative of resolution include improved color and quality of granulation tissue, disappearance of periwound hyperemia, reduction in surrounding erythema, absence of purulence, decrease in pain, and decrease in purulent exudate. Similarly, when new epithelium appears along the wound edge with increasing granulation and contraction of the wound, proliferation should be supported with autolytic moist wound therapy. Most experts suggest a 2-week period of antimicrobial use, at which point the wound should be assessed and the determination made about continuation of current therapy, the need of further wound bed preparation, or the need for a different topical product.^32,43,54

Although silver is not indicated for use in wounds that show no evidence of increased bioburden or infection, there are times when prophylaxis may be appropriate. Again, a 2-week window may be considered for patients who are severely immunocompromised, wounds near contaminated areas such as the genitals, wounds with exposed bone, or wounds on extremities with poor circulation.⁸⁷

Interest has been shown recently in the use of silver dressings to prevent surgical site infection (SSI). SSI may occur within the organ space or as a deep SSI secondary to preoperative or postoperative adherence to prevention guidelines. In these infections, antimicrobial dressings may have little effect when applied topically; however, superficial SSI may also occur, especially in patients with systemic comorbidities that impair wound healing, and thereby increase the risk of deeper tissue infection. While SSIs are multifactorial, an RCT by Siah⁸⁸ showed a statistically significant difference in the amount of bioburden on postoperative incisions 5 to 7 days after surgery when using nanocrystalline silver compared with control. It is reasonable, therefore, to consider the use of silver dressings for prevention of infection in high-risk patients; however, more research is needed in this area. The NICE guidelines⁸⁹ found no statistical significance in the type of dressing used when looking at incidence of SSI; however, these dressings were standard dressings without antimicrobial constituents.

The final points of discussion regarding the use of silver involve safety. First, pediatric considerations for care should be considered before selecting silver dressings. A child’s skin is at risk for absorption of topical products leading to systemic toxicity.⁹⁰ Although silver has been reported in the literature as safe to use in pediatrics,^84,91 many studies focused on the end point of wound healing, decrease in pain, or length of stay rather than the risk of harm. The concern for toxicity as seen in in vitro studies has warranted further research in this vulnerable population.^92,93 Wang et al⁹⁴ showed that silver toxicity was a concern when examining pediatric burn patients and the use of nanocrystalline silver dressings. Not only were serum levels elevated, but they were closely proportional to the surface area of the wounds treated. An animal model raised question over deposition of silver in the major organs. In some cases, serum levels of silver have been noted to be 800 times greater than normal.⁹⁵ Dressings or topical agents providing adult dosages are not suitable for children; however, more research is necessary to determine the amount, length of use, and type of silver dressings that may or may not be safe for the pediatric population. Therefore, the patient’s age, the surface area of the wound, the amount of silver in the dressing, and its delivery are factors to be considered. Silver dressings are not advised for neonates, and the usage of such products in the pediatric population is limited to no more than 2 weeks.⁵⁴ A product with lower parts per million (ppm) concentration of silver and slow active release from the dressing, instead of high parts per million dressing that actively releases silver ions into the wound bed, are a better selection. These qualities are very product specific and overall caution is advised when considering these products for the pediatric population.

Controversy also exists regarding the use of silver wound dressings on patients having magnetic resonance imaging (MRI) studies. There are true concerns regarding the effect of MRI on medical products as metallic devices should never enter the MRI machine. However, wound care products are often not tested for MRI safety. Because silver is a metallic substance, many manufacturers will often issue warnings regarding its use near MRIs even if no testing has been performed. The concerns are for burns associated with response of the dressing to a magnetic field as well as for image disturbances. At this time, there is no universal recommendation for wound care dressings and MRI; therefore, manufacturer’s recommendations are to be carefully followed. A recent study⁹⁶ assessed silicone wound dressings with silver (Mepilex AG+ and Mepilex Border AG+, Molnlycke Healthcare, LLC, Norcross, GA) under 3-Tesla and found both dressings to be MRI safe. However, the authors caution that they only tested these two specific dressings, and therefore the results cannot be generalized across all product types. Clinicians are advised to check manufacturer’s recommendations for use before allowing patients to undergo an MRI with silver dressings in place (FIGURE 13-45A-C).

Honey

The use of medicinal honey has increased in popularity over the last several years; however, it is by no means the new-kid-on-the-block. The use of various forms of honey dates back thousands of years to the time of Dioscrodies,⁹⁷ Hippocrates⁹⁸ and descriptions on medical papyrus from 1325 BC.⁹⁹ However, the form of medical grade honey used today differs greatly from that of natural or culinary versions. Medical grade honey has two general sources: Leptospermum scoparium (manuka), which is derived from tea plants, and Leptospermum polygalifolium, which is jelly bush honey.¹⁰⁰ Both forms have specific qualities related to their processing that affect the bacterial count, pH, enzyme activity, and overall benefit in wound care.

Pieper¹⁰⁰ reports that while culinary honey uses heat to prepare the product for consumption, this invariably reduces the enzyme responsible for hydrogen peroxide production, whereas medicinal honey’s gamma radiation sterilization process allows it to retain its biologic activity. This biologic activity is multifactorial and relates to the unique blend of glucose, fructose, sucrose, water, amino acids, vitamins, minerals, and enzymes found in the final product.¹⁰¹ Honey is used for its many capabilities, for example, antimicrobial action, debridement action, anti-inflammatory properties, moist wound maintenance, low pH, and exudate absorption.

Honey is known to be an effective antimicrobial agent. The ability to reduce wound bioburden is directly dependent on the geographical, seasonal, and botanical source, as well as manufacturer processing and storage.¹⁰² Honey has been shown to have a polyantimicrobial effect on a broad spectrum of viruses, fungi, protozoa, and over 50 species of bacteria, including organisms such as Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE).^36,103 Honey has no risk of bacterial resistance and has been shown to be equal to antibiotics in the prevention of infection following eye surgery¹⁰² as well as capable of providing wound healing in pressure ulcers.¹⁰⁴ This versatility is enhanced through its availability in many forms, including gels, alginates, hydrocolloids, and solutions.

The antimicrobial action of honey is a result of its ability to kill bacteria, as well as the capacity to regulate biologic activity within the wound. A major benefit is its low pH (3.5-4), which may move a chronic wound from a normally alkaline to an acidic environment, thereby producing a shift in the oxygen-hemoglobin disassociation curve. As described by Gethin,¹⁰³ this drop in wound pH leads to increased oxygen release, reduced toxicity of bacterial end products, enhanced removal of abnormal wound collagen, decreased protease activity, increased angiogenesis, increased macrophage and fibroblast activity, and enzyme regulation. Further, the biologic activity includes the regulation of the immune response because honey stimulates monocytes to release cytokines, stimulates B and T lymphocytes to activate phagocytes, contributes to therapeutic levels of hydrogen peroxide production, and reduces edema, thereby facilitating improved microcirculation of oxygen and nutrients.¹⁰⁰ Although these effects may not be visible, the actions likely explain the experience of seeing honey “jump start” a recalcitrant wound in clinical practice.

One of the major benefits of honey is the ability to both provide bioburden control and enhance debridement at the same time. A study by Gethin and Cowman¹⁰⁵ showed that honey was more effective at desloughing wounds with >50% necrotic tissue than standard hydrogel, leading to statistically significant faster healing rates and decreased time to epithelialization. Moreover, the authors state that while sharp and biologic debridement may be faster, honey may be superior to the autolytic or enzymatic debridement seen with hydrogel, collagenase, or cadexomer iodine.

Although the benefits of honey have been described in many studies, there remains conflicting evidence as to where honey fits in best practice. This is largely related to RCTs and Cochrane reviews that have pointed out that honey did not show any significant differences versus standard care, thus questioning its efficacy.^106,107 Some studies may limit the potential benefits of honey dressings through the selection of study samples. Often the wounds evaluated are nonnecrotic or without signs of infection and therefore the use of time-to-healing parameters negates the many potential benefits of honey. Additionally, secondary symptoms such as pain, odor, and frequency of changes are not factored in. Rogers and Walker^106,107 point out this discrepancy as they do not find sufficient evidence for the use of honey in leg ulcers, pressure ulcers or Fournier gangrene due to lack of available studies; however, they do support honey’s benefit in the management of partial thickness burns. This underlines the need for, as well as the difficulty of, proper research to test honey’s potential methods of action in wound healing.

There are potential adverse effects of using honey. First, stinging or burning pain has been reported after initial application of the dressing to the wound bed, most likely because of the osmotic and pH-lowering action of the dressing. These symptoms will often be transient; however, in some cases they persist and warrant a change in therapy. Unlike silver, Pieper¹⁰⁰ describes many studies showing safe and effective use of honey in children, but the author indicates the need to avoid its use in wounds requiring surgical debridement, following incision and drainage of an abscess, or when sensitivity to bee stings is present. While allergy to bee venom is a common fear with the use of honey products, and most clinicians will not select honey with a known bee allergy, no reports of anaphylaxis have currently been described with the use of medicinal honey.¹⁰⁸

Honey is increasing in its popularity because of its excellent debridement properties, especially following the lack of availability of papain-based enzymatic debriding agents. Whether the wound is dry or has copious exudate, honey may be utilized with a proper secondary dressing. The osmotic structure of the dressing acts to bathe the wound bed by drawing out peripheral edema in exudative wounds, by adding moisture with the gel form, or by trapping ambient moisture in the hydrocolloid version. Because of this balance, the absorptive alginate version can be used in dry wounds. The alginate may be easier to apply and thus preferable to gel forms that may drip out of the wound in response to gravity. Additionally, because of its theoretical benefits of anti-inflammatory/cytokine-regulating properties, honey may be preferable to a more expensive biologic dressing when treating chronic wounds. However, the actual clinical significance of this has not been tested (FIGURE 13-46A-C).

Cadexomer Lodine

Iodine was first discovered by Coutoius in 1811 and it took less than 50 years for it to be utilized in wound care.¹⁰⁹ Iodophors were well regarded for their ability to provide both bactericidal and bacteriostatic effects on a broad spectrum of bacterial species. Many iodine preparations exist, but not all are appropriate for wound care secondary to the cytotoxicity that may occur relative to its overall concentration, release, and solubility. Mertz et al¹¹⁰ stated that while iodine has been traditionally seen as an inhibitor of normal wound healing due to results of both in vitro and in vivo toxicity studies, the difference may lie in the components of iodine delivery. For example, povidone iodine includes active agents that improve its solubility and make the solution less damaging to host cells, and thus has been approved by the FDA for short-term use in the treatment of superficial and acute wounds.⁷⁹ Nevertheless, its interaction with the wound environment results in fast consumption, requiring the clinician to reapply the solution multiple times daily for the full antimicrobial effect.^109,110 This results in many undesirable consequences for the wound environment, including the need for frequent dressing changes that negatively affect normothermia; the potential for repetitive, rapid release of large concentrations of iodine into the wound bed; and secondary symptoms such as pain and wound trauma. In other words, iodine in and of itself is not the evil destroyer of the wound bed; however, the beneficial antimicrobial action of iodine needs to be controlled by the speed and amount of its release into the wound bed while maintaining its bactericidal action without inducing cytotoxicity, and it needs to be in a delivery vehicle that allows for less frequent dressing changes.

Cadexomer iodine (CI) solves this dilemma. Available in a paste or sheet dressing, (Iodosorb, Iodoflex, Smith and Nephew, Andover, MA), CI products have a three-dimensional, microspherical shape similar to a whiffle ball, with dextrin-based beads that allow controlled release of 0.9% iodine.¹⁰⁹ This structure can be thought of as an exchange system. As wound exudate is absorbed into the dressing, the starch carrier degrades and iodine is released into the wound bed. By doing so, CI has been shown to not inhibit or impair fibroblast function, but is extremely effective in killing broad-spectrum organisms. In fact, Danielsen et al¹¹¹ looked at the bacteriological efficacy of CI on VLUs colonized with Pseudomonas aeruginosa in an uncontrolled multicenter pilot study. They found that 65% of the wounds had negative cultures for Pseudomonas aeruginosa at 1 week and over 75% had negative cultures at 12 weeks.

In addition to improving wound healing potential by reducing bioburden, multiple researchers have found that CI has the ability to modulate the effects of macrophages to impact cytokine release and to increase growth factor production and activation in the chronic wound.¹¹² Specifically, CI was found to significantly increase the expression of interleukin-1-β, tumor necrosis factor alpha (TNFα), vascular endothelial growth factor (VEGF), and microRNA, thereby enhancing the inflammatory response to support angiogenesis.¹¹³ The combination of reducing wound pathogens and directly stimulating a refractory wound underscores the advantages of CI.

As previously discussed, biofilm phenotype bacteria (such as S aureus and P aeruginosa) pose a real threat to wound healing and infection. Almost all topical antimicrobials (including antibiotics, antiseptics, and concentrations of disinfectants) are unable to penetrate the polysaccharide matrix protecting the underlying pathogens. Cadexomer iodine is the exception.¹⁰⁹ Recent studies⁴⁸ investigated the ability for a wide variety of topical antimicrobials to penetrate biofilm inoculated on pigs ears. Of all the topical products tested, only CI was capable of penetrating the matrix and thus impact the bacteria present below the surface. While routine and frequent debridement is still necessary to ensure adequate removal, CI is useful in biofilm-based wound care, or in cases where a biofilm is suspected but aggressive debridement is not possible, for example, on a heavily anticoagulated patient.

Despite these benefits, CI is not without its own contraindications. CI should not be used on patients with a known allergy to iodine, dyes, or shellfish. Additionally, the starch encased structure of CI necessitates an adequate amount of exudate or moisture to stimulate breakdown and release of the iodine. Thus, dry wounds without exudate may not properly activate the dressing. Also, CI negatively interacts with exogenously applied collagenase for debridement; an alternate form of debridement or an alternate antimicrobial agent is required. As with all iodine products, caution is advised for use on children, patients with known thyroid dysfunction, and pregnant or lactating women. In addition, the amount of CI used relative to the size of the wound, the frequency of the application, and overall systemic absorption necessitate caution when considering its use in large surface area wounds, such as burns or surgical incisions (FIGURE 13-47A, B).

Polyhexamethylene Biguanide

Polyhexamethylene biguanide (PHMB) has been used for its antimicrobial effects as an environmental disinfectant, swimming pool additive, and contact lens irrigation; however, because of its high biocompatibility PHMB is also used in wound care products. PHMB is described as a heterodisperse mixture of polymers with a structure similar to those found in naturally occurring AMPs and with a similar effect on bacterial cytoplasmic membranes.¹¹⁶ The structure induces cell lysis by its mechanism of attaching and impairing the cell membrane, similar to the mechanism of some antibiotics. It is comparable to its closest chemical cousin chlorhexidine, having similar effects against bacteria such as Pseudomonas aeruginosa, while lacking the potentially damaging chlorobenzene group.¹¹⁷

PHMB is effective on both common wound pathogens and resistant organisms. Cazzinga et al,¹¹⁸ found that PHMB-impregnated foam showed a significant log reduction of Pseudomonas aeruginosa within the wound compared to standard gauze, and did not allow Pseudomonas to colonize the PHMB impregnated foam nor result in a reduction in normal flora. These results support one of the most common uses of PHMB as a preventative barrier dressing against infection in high-risk individuals.

An RCT by Wild et al¹¹⁹ investigated the effect of PHMB delivered by a constantly applied cellulose dressing versus intermittent use of impregnated swabs for the eradication of MRSA in pressure ulcers. Their results showed both applications of PHMB lowered the amount of MRSA present; however, the continuously applied cellulose dressing was more effective with a 100% reduction of MRSA on day 14 versus 67% reduction in the control. Both of these studies highlight the potential benefit of PHMB to reduce bioburden, but also focus on the fact that this substance is not released out of its delivery dressing.

Unlike some silver and iodine dressings, PHMB must be exposed to and in direct contact with the organisms for which it is designed to kill. Hence, once it is bound to a dressing material such as gauze, foam, or alginate, it can only affect bacteria that have been absorbed into the dressing construct.¹¹⁶ In the case of wound irrigations and solutions, time of exposure is the key determinant. Werner and Kramer¹²⁰ indicate that at least 10 to 15 minutes of exposure is necessary to induce the most antimicrobial effect. Therefore, PHMB in solution form is advised to stay in the wound bed during the cleansing process, or provide the agent as a continuous irrigation, for example, through the use of NPWT with instillation.¹¹⁵

Newer applications of PHMB into biosynthetic cellulose fibers have proven beneficial in managing the problem of PHMB binding as well as the moisture balance of the wound both in dry and wet environments. Biocellulose dressings provide unbound PHMB that is released into the surrounding wound fluid, rendering its antimicrobial action both within the dressing as well as at the wound interface.^121,122 The results further demonstrate that the qualities of the dressing may be as important as the antimicrobial agent inside. For biofilm-based wound care, PHMB may be utilized as a method to prevent reattachment of bacteria to the wound bed following debridement, but it is not the frontline choice for biofilm disruption. While a study involving 28 patients by Lenselink and Andriessen¹²³ showed a reduction in biofilm, the presence of biofilm was assumed and not clinically identified. Therefore, the results showing PHMB promoting wound healing via reduction of biofilm in this study must be questioned given the lack of appropriate identification, the small sample size, and the lack of a control group.

PHMB dressings are frequently used to reduce bioburden and secondary symptoms such as wound pain. Many dressing types contain PHMB, including gauzed-based systems (rolled gauze, drain sponges, island dressings, etc), foams, biocellulose dressings, and alginates. Most gauze-based NPWT systems utilize PHMB impregnated roll gauze to provide antimicrobial benefits without the risk of cytotoxicity. The roll gauze is similarly effective in the packing of deep cavity wounds or after trauma when the wound size requires the use of a product with adequate tensile strength and length to prevent the risk of retained foreign bodies. Sibbald et al¹²⁴ evaluated a PHMB foam dressing in a multicenter, prospective, double-blind RCT utilizing the NERDS and STONEES criteria for bacterial bioburden. They concluded that the PHMB foam significantly reduced bacterial burden compared to standard foam at week 4, as well as reduced wound pain at week 2 and week 4.

PHMB impregnated gauzes should be saturated with normal saline, sterile water, or potable water. Other antiseptic solutions such as sodium hypochlorite may cause a chemical reaction, which inactivates the PHMB and results in a nontoxic yellow stain. Patients with known adverse reactions to PHMB or chlorhexidine are excluded from use. Finally, because of the method of action of PHMB, it is generally recommended that it be used for prophylaxis or on critically colonized wounds, but not as the primary treatment in active wound infections (FIGURE 13-48A, B).¹¹⁶

PVA Foam with Gentian Violet and Methylene Blue

The antimicrobial action of methylene blue and gentian violet has long been described in the annals of science.^125,126 Possessing both a bactericidal, antifungal and broad-spectrum bacteriostatic effect, these components have been used to treat fungal infections, prevent infection, and assist with bacterial staining in laboratory studies. When combined with polyvinylalcohol (PVA) foam, it becomes a versatile wound care dressing termed methylene blue-gentian violet polyvinyl alcohol foam (MBGV-PVA).This dressing removes exudate from the wound bed while creating singlet oxygen and free radicals that directly impact the plasma membrane causing bacteriolysis.⁷⁷ Reduction or maintenance of wound bioburden is beneficial; however, the primary clinical advantage of this dressing is the action of its unique foam design. According to testing performed by the manufacturer, the movement of fluids throughout the patented pore design has an effect on the flow rate, which results in a negative pressure-like effect, with recorded pressures of 71.2 mmHg.¹²⁷ However, the clinical benefit of this claim has not been substantiated. Unfortunately, there is limited to no clinical research available on this product. The benefit is primarily assumed because of the known research on its antimicrobial agents and the physical action of the foam. However, the only available literature regarding its benefit involves case studies and poster presentations, which do not provide the necessary evidence to gauge its use over well-researched antimicrobial products.

Although clinical research evidence may be lacking, clinical benefit is seen in practice by the effect of MBGV-PVA on decreasing inflammation and pain, reducing fibrin wound covering, improving granulation tissue, and intriguingly, reducing wound edge epibole. These findings have been reported in multiple case series from different authors.^128,129 In addition, although products such as antiseptics, silver, and iodine may inhibit the effect of exogenous collagenases used for enzymatic debridement, PVA-MBGV does not.¹¹⁴ This permits combination therapy including reduction of necrotic tissue, entrapment of bacterial endotoxins, and decreased risk for infection.

The PVA foam itself is versatile and capable of being used in a variety of situations. The highly absorptive foam may be used in dry wounds, moist wounds, and excessively exudative wounds when a properly selected secondary dressing is applied. The moist foam will hydrate a dry wound bed when covered with a transparent film, will maintain moisture in a mildly exudative wound, and will achieve maximum absorption in exudative wounds when applied dry. Another benefit of MBGV-PVA foam is the ability to reduce hypergranulation tissue by the removal of excessive moisture from the wound base. Also, as the dressing allows for rapid evaporation of moisture vapor from the foam, it may be used in more creative ways. Since the foam becomes rigid and hard when dry, it can be used to provide antimicrobial protection as well as mild joint splinting, such as in the case of partial thickness burns over the fingers. By applying the dressing after necessary debridement in a moist state, the foam at the wound surface will stay moist enough for autolysis, while becoming rigid to support immobilization of the joint with an appropriate secondary wrap. The dressing can be subsequently rehydrated once daily to maintain a moist wound bed. Additionally, chronic wounds with rolled wound edges (epibole) have been shown to smooth out and elicit epithelialization in recalcitrant wounds.¹³⁰ Again, the lack of research in these areas questions the actual clinical benefit of this dressing over standard care, but clinical results and its use with debriding enzymes are promising (FIGURE 13-49A, B).

Dialkylcarbamoylchloride

Dialkylcarbamoylchloride (DACC) is a newly discovered antimicrobial dressing. The principles of hydrophobic interaction can be seen in daily life, such as how drops of oil may aggregate into one larger grouping when dropped into water, or how a pathogenic bacteria may grab hold of exposed and damaged collagen in an open wound.¹³¹ Microorganisms have the ability to attach to a denatured extracellular matrix through the interaction of their hydrophobic covering with cell surface proteins in the collagen known as hydrophobins.¹³² This method of surface attachment has been recently harnessed in the form of applying DACC, a naturally occurring hydrophobic fatty acid to various dressing constructs in order to utilize the principles of hydrophobic binding by allowing bandage fibers to stick to the hydrophobic covering of potential microbes in the wound bed.

Dressings containing DACC (Sorbact, BSN Medical, Charlotte, NC), also known generically as pathogen-binding mesh, are not technically antimicrobial, but they have a decided advantage over some of the other products discussed in this chapter—they have no chemical, pharmacological, or antimicrobial agents, thus erasing the concern for bacterial resistance or sensitivity. Silver, iodine, and other antimicrobials utilize multiple pathways to induce bacterial cell lysis (eg, binding to DNA, affecting efflux pumps, disrupting the cell membranes of microbes, denaturing proteins and displacing metallic cations in the bacterial cell wall).⁷⁷ In all of these cases, the bacteria are killed, and a resulting dump of endotoxins and cellular debris are released into the wound bed. This adds to the inflammatory response, risking the increase in inappropriate polymorphic neutrophil activation of MMPs.¹³³ To avoid these potentially disruptive insults to the wound environment, DACC-covered dressing fibers work instead to bind the microbes to the dressing, render them inactive, and then remove them whole. This concept of repetitive removal of microbes with each dressing change is similar to the concept of sequestration. The principle of trapping and removing bacteria in their intact state is one of the reasons that hydrofibers and alginates are effective in the reduction of wound bioburden.¹³⁴ In the case of dressings with DACC, however, there is no risk of bacteria re-release from an oversaturated dressing, and the dressing is capable of showing a large log reduction in bacterial load with subsequent dressing changes. A study by Gentili et al¹³⁵ used real-time PCR evaluations to study the bacterial bioburden in wounds with subsequent changes using DACC-coated dressings. The authors note that the bacterial load at the beginning of wound treatment was 4.41 × 10⁷ per mg of tissue and at the end of therapy 1.73 × 10⁵ per mg of tissue, or a 254-fold reduction in the bacteria present (p = 0.0243).

The ability of the dressing to bind to aerobic bacteria, fungi, and often pathogenic anaerobes is determined by the organism’s cellular surface hydrophobicity (CSH). The expression of CSH is often increased during periods of wound stress or as a result of the colonization of the wound environment.¹³⁶ This is an important concept when DACC dressings are used for wound care because irrigation must be properly performed and the wound environment assessed for appropriate levels of moisture. Common antiseptics and analgesics have the ability to reduce CSH expression, including eucteric mixture of local anesthetic (EMLA), which can eradicate CSH expression completely.¹³⁶ If CSH expression falls or is removed, DACC-coated dressings will lose their efficacy. Similarly, principles of hydrophobic binding require moisture to encourage the interaction between two hydrophobic surfaces. Thus, if a wound is dry and nonexudative, moisture may need to be added in the form of a hydrogel or the use of a secondary dressing that traps ambient moisture.¹³⁷

Other practical considerations for the use of hydrophobic-binding dressings include frequency of wound changes. As the dressings remove bacteria with each change, wounds with clinical signs of critical colonization or infection may require every 12- to 24-hour dressing changes to achieve a necessary reduction in wound bioburden with a concurrent application of an appropriate absorptive secondary dressing to manage exudate.¹³⁸ In cases of prophylaxis or no clinical signs of infection, a change in frequency of up to 4 days has been described.¹³¹ Because of the lack of chemical agents in this dressing, safe use in children has been reported. Meberg and Schoyen¹³⁹ performed a prospective randomized study on umbilical cord disinfection comparing a group using Sorbact (n = 1,213) with daily cleansing with 0.5% chlorhexidine in 70% ethanol (n = 1,228) and found no differences between the rate of infections in each group. No adverse reactions were reported in the Sorbact group. The versatility of DACC dressings have been evaluated to determine their benefit as wound fillers in NPWT. A pig model was utilized to study the efficacy of pathogen-binding mesh versus foam and gauze as related to granulation tissue formation, wound contraction, microvascular blood flow, and wound contraction.¹⁴⁰ The authors found that pressure transduction was similar between all of the products—wound contraction occurred more rapidly with foam products, pathogen-binding mesh showed more rapid granulation tissue formation than gauze and had similar fluid retaining qualities as foam. The adaptable qualities of these products are further supported by the idea that since the dressing is not loading any specific chemical or antimicrobial substance into the wound, the hydrophobic-binding dressings may be used longer than the 2-week challenge period suggested for other antimicrobials.¹⁴¹

The challenge of using hydrophobic DACC dressings is the relative lack of evidence suggesting when these dressings should be selected over traditional antimicrobials. Much of the current literature involves noncomparative, nonrandomized, uncontrolled studies utilizing subjective parameters to assess the benefit of a dressing used in a study population.¹³¹ For example, Bruce¹⁴¹ described a multicenter study of six centers across the UK and Ireland that evaluated Sorbact without a comparison group, using subjective assessment of the staff to determine if the dressing had an impact on wound healing, but they did not describe the methods used. A qualitative study of 50 patients was used to assess the efficacy of Sorbact using a questionnaire without description of a control group or methods used.¹³⁸ In other words, there is insufficient evidence to suggest when a dressing coated with DACC should be selected instead of any of the previously mentioned antimicrobials. It does, however, use a proven method of binding bacteria and appears safe with a low risk of adverse events and no possibility of resistance. Due to the potential versatility of its use, DACC/Sorbact dressings warrant more rigorous comparative examination (FIGURE 13-50A, B).

The use of topical antimicrobials demonstrates clear advantages over the misuse of antibiotic therapy in critically colonized and infected wounds. Due to their varying methods of action, the functional construction of the dressings selected and the abundance of competitive products on the market, selecting one product over another can be difficult in the clinical setting. Some products are known to be more efficacious on specific organisms, while others are more adept in dry versus moist wounds. However, the clinician should avoid the temptation of mixing these products together for any perceived benefit that may come from an antimicrobial cocktail. Cowan et al¹⁴² describe that in some cases mixing products can lead to problematic chemical reactions and inactivation of the dressings’ properties, essentially stating, more is not necessarily better.

Certain dressings are known to be harmful to the wound bed, for example, those containing disinfectants or heavy antiseptics with severely cytotoxic concentrations. Clinical considerations are a dressing’s intended use, its chemical makeup, the expected reaction by the host tissue, the frequency of changes, and the total time of safe usage.

The lack of understanding by practitioners in managing wounds is complicated by the exponentially growing base of knowledge found in the science of acute and chronic wound healing. As the scientific understanding continues to grow, so does the need to redefine how the complex differences of chronic wounds are identified. Some authors suggest current nomenclature focuses too much on wound chronicity and not enough on tissue condition, sparking the need for new terminology to assist with identification and care.¹⁴³

Until dissemination of new knowledge occurs within the health care community, the inappropriate use of dressings such as wet-to-dry gauze (which are known to inhibit wound healing, increase the costs of care, and increase pain) is still prescribed.¹⁴⁴ Moreover, the lack of wound care knowledge by the nonwound clinician may also lead to the inappropriate selection and use of antimicrobial dressings, when in fact they are not indicated.

In its best practice guidelines on wound infection,¹⁴⁵ the World Union of Wound Healing Societies (WUWHS) states that the risk of infection is elevated when there are any conditions that compromise the immune response or perfusion. Once those factors are identified, the proper management of infection requires much more than a dressing. Optimal care also treats systemic comorbidities, tracks necessary markers of inflammation, and assesses the reduction of wound bioburden as a necessary holistic approach. The authors describe recommendations for the use of antiseptics, antimicrobials, and antibiotics, stress the common theme of a 14-day treatment window, and recommend product selection that matches the presentation of the wound and the organisms present.

Silver, PHMB, CI, DACC, PVA-GVMB dressings, and honey have been found relatively safe to use with lower risks of resistance and cytotoxicity than antibiotics or antiseptics. However, there is a time and a place for all of these therapies to be utilized, and it is the responsibility of the clinician to make the best selection based on evidence based guidelines. Leaper⁶⁸ summarizes the need to consider the use of antiseptics and antimicrobial dressings in the prevention and management of chronic wound infections. These agents were previously disregarded due to concerns over their level of toxicity or research support; however, there is a lack of new antibiotic development. With increasing bacterial resistance, alternative measures need to be investigated. The fact that previous meta-analyses do not reflect the true use of antimicrobials should not prevent the use of these products, especially since these dressings have been shown to reduce the risk of infection and prevent biofilm formation.