Physiological wound healing is a complex process. The primary goal of this temporally and regionally controlled series of events is to restore tissue integrity and function. In regard to the skin, the wound healing process encompasses a time period which depends on many factors and which may be divided into several consecutive phases . There is still no standardized, accepted consensus on the definition of chronic wounds. Along with duration, there are problems owing to the highly variable factors related to the pathophysiology. Most current classifications are based only on time. In the following, “chronic” refers to wounds which have persisted for more than eight weeks .
Even if there is scant scientific evidence on the effectiveness of wound care products in accelerating the healing of chronic wounds, there is consensus among experts in the field concerning the use of modern wound care products, especially in regard to improving quality of life . New discoveries in topical wound care have made the treatment of patients with chronic wounds more complex. Thus it was the aim of the working group for wound healing (AGW) of the German Society of Dermatology (DDG) to present a review article on the current, relevant aspects of topical, non-interventional wound care for use in daily practice.
Modern wound care
Before treatment of any patient with a chronic wound begins, the relevant underlying factors should be diagnosed and, whenever possible, treated. Wound healing may be promoted by topical wound care. The concept of moist wound care was pioneered by George D. Winter. In preclinical studies done in 1962, he showed that a moist wound milieu promoted wound healing .
At the beginning of wound therapy, it is often necessary to perform débridement, or at least to cleanse the wound. In addition to necrotic areas, fibrin, crusts, or dressing remnants must also be removed . For wounds that are to be cleansed when changing the wound dressing, Ringer solution or physiological saline solution are the cleansers of choice. Sterility is no longer ensured once the container has been opened. Solutions which do not contain preservatives must be used immediately. For practical purposes, it is often more feasible to use cleansing solutions which contain preservatives, such as polyhexanide, or which are completely used up in a single dressing change. Care should be taken to ensure that the solution has been warmed to body temperature .
The use of tap water is strongly debated among experts . The German law on the prevention of infection, and the recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) of the Robert Koch Institute (RKI), have unequivocally stated that only sterile cleansing liquids may be used for wound care. The use of tap water is only permissible in Germany if filters with a maximum pore size of 0.2 μm are used .
Patients rarely purchase such filters, given their expense. Yet, for doctor's offices and wound clinics, they represent a viable alternative if one wishes to continue using tap water.
Débridement should be as radical as necessary, but as gentle as possible. Treatment of chronic wounds often begins with mechanical débridement. Mechanical débridement using sterile compresses is often sufficient for removal of loosely adherent coatings, such as fibrin.
For painful wounds, in particular, one therapy option is to use a monofilament fiber product, which involves minimal pain. Firmly adherent coatings and necrotic areas usually have to be removed surgically. Other alternatives include biosurgical débridement with medicinal larvae or physical débridement with ultrasound, plasma, or laser. These methods are usually only offered by specialized wound care centers. In outpatient care, especially, autolytic techniques, such as hydrogels and proteolytic enzymes are used. For effective débridement, it is imperative to plan the necessary pain therapy in advance and to discuss it with the patient [4, 8].
Materials for modern wound care
In everyday practice, dressings are recommended as part of modern moist wound care for most chronic wound patients. No single dressing is optimal for all wound types (Table 1). In Germany, there are currently more than 1,000 different medical products for use in chronic wounds, and many manufacturers have their own declarations. This makes the steadily growing market for such products increasingly difficult to navigate (Figure 1). The following discussion focuses on only a few, widely used types of wound care products and briefly discusses their presumed modes of action [9-13].
|▸ Reasonable cost|
|▸ Conforms to body contours|
|▸ Atraumatic dressing changes|
|▸ Absorption of wound exudate (also with compression therapy)|
|▸ Permeable to oxygen, water vapor, and carbon dioxide|
|▸ Simple and complete removal|
|▸ Easy to apply|
|▸ Mechanical protection|
|▸ May be cut to size, or available in a variety of shapes and sizes|
|▸ Protection against microorganisms|
|▸ Sterile packaging|
|▸ Prevention of dehydration|
|▸ Contains hypoallergenic materials|
|▸ Contains non-toxic materials|
|▸ Thermal insulation|
Activated carbon wound care dressings are made up of fibers consisting of carbonized cellulose products. The compresses reduce odors and absorb endotoxins, and they also have bactericidal properties. They are thus especially suitable for foul-smelling wounds and ulcerated tumors.
The dressings are placed in the wound and fixed in place with compresses. Some of the products available cannot be cut to size, as this would leave activated carbon in the wound. For wounds with only a limited amount of exudate, the dressing should be moistened regularly. For wounds with a large amount of exudate, an absorbent secondary dressing should be used and the surrounding area should be protected against maceration, as currently activated carbon dressings can only absorb a small amount of moisture. The dressing should be changed every 1–3 days.
Alginate products consist of a loose dressing structure made up of fibers which are composed of red or brown algae. After contact with sodium salts present in the blood or in wound secretions, the alginate fibers absorb the secretions to form a moist hydrophilic gel; bacteria and detritus are enclosed in the gel structure. The speed and amount of gel formation depend on the amount of exudate absorbed and the fiber weave. Alginates are capable of absorbing up to 20 times their own weight. Depending on the product, calcium, zinc, or manganese is supplied to the wound milieu. Alginates are used for deep, jagged, or heavily exuding wounds, either for wound cleansing or to promote granulation. Given that alginates also have hemostatic effects, they are also suitable for achieving hemostasis, for instance, following surgical débridement.
Depending on the type of wound and the amount of exudate, either dry or moist alginate is applied. Compresses may be placed in deep wounds and pocket wounds; tamponade may also be used. For heavily exudative wounds, it is advisable to use an absorbent secondary dressing for example a superabsorber. For clinically infected wounds, the dressing should be changed daily. For all other wounds, a new dressing should be placed every 2–5 days, depending on the amount of exudate.
Biosurgery refers here to the treatment of wounds with medical grade maggots. Species that are suitable for use in biosurgery include larvae belonging to the Lucilia sericata (gold fly), as they are capable of performing highly selective débridement.
Biosurgical débridement does not cause bleeding, and is associated with minimal or no pain. Fly larvae have the potential for lysis of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The larvae are placed directly on the wound. If free-roaming larvae are used, a cage must be built around the wound using the net that comes with the larvae and gel strips or stoma paste. Nowadays, fly larvae are more common; these come contained in a BioBag. Depending on the wound shape, the bag should be moved every day, as it is only effective on the area over which it is directly placed. Highly absorbent compresses should be used as a secondary dressing. The dressing should be changed after 3–5 days.
Chitosan is a biopolymer that is derived from chitin. It is available in wound dressings or as a spray. It is believed to promote various aspects of wound healing, given its positively charged surface. Chitosan products may be used in all phases of wound treatment, after adequate débridement has been performed. They may also be used for achieving hemostasis after surgical débridement.
The wound dressing should be cut to size before being placed on the wound. When using the spray, it must be allowed to dry for at least 90 seconds before applying the secondary dressing. Depending on the type of product, the dressing should be changed every 1–3 days.
Honey wound care preparations come in tubes or as impregnated dressings. The osmotic effect, leading to wound dehydration, and low pH values, as well as the release of small amounts of hydrogen peroxide and methylglyoxal, explain its antimicrobial properties as well as the often severe pain reported during treatment.
Given that honey is a natural product, its effectiveness varies depending on the source of the product and the processing methods used. Honey-based products are used for wounds with a small amount of exudate for osmotic débridement and elimination of bacteria. These products should be applied to the wound only, taking care to avoid the surrounding area. How often to change the dressing depends on how quickly the honey is diluted by the exudate. Honey is water-soluble and can be washed off during dressing changes, which are done every 1–3 days.
Hyaluronic acid wound dressings are available as gel, fiber compresses, microgranules, and sprays; hyaluronic acid products may also be used for tamponade. Hyaluronic acid forms a hydrophilic gel upon contact with wound exudate. Products containing hyaluronic acid are often used for wounds with a large amount of exudate to promote granulation and for wound cleansing.
Depending on the type of wound and amount of exudate, hyaluronic acid may be applied in its dry form, or combined with Ringer solution; gel formation is absolutely essential for the release of hyaluronic acid. The wound should be covered with a secondary dressing. The dressing should be changed after 1–3 days.
Hydrofibers or aqua fibers are composed of sodium carboxyl cellulose. Fluid absorption occurs vertically only; no fluid should be released horizontally. This is intended to avoid maceration about the wound margins. Hydrofiber dressings can rapidly absorb up to 40 times their weight in exudate.
After absorbing the wound exudate, the fibers rapidly transform into a firm, transparent gel. Hydrofiber products may be used for wounds with a large amount of exudate to promote granulation and for wound cleansing. The hydrofiber dressing is placed on the wound and may extend over the wound margin. The wound should be covered with a secondary dressing. The dressing should be changed after 1–3 days.
Hydrogels are preparations that contain up to 95 % water, along with organic additives such as pectin and starch, or gelling agents. Generally, a tube or syringe is used to place the gel in the wound. Hydrogel sheets, which are placed on semi-permeable films, are available for wound therapy. Hydrogels can provide moisture to the wound as well as absorb excess wound exudate. They are especially suitable for dry wounds to facilitate autolytic débridement.
Hydrogels may also be combined with various other dressing materials, in order to keep these – or other structures (such as exposed tendons) – moist. The hydrogel sheets are applied in 3–5 mm thick layers, and are then covered with impregnated gauze or semi-permeable film dressings. The dressing is changed every day for débridement; during the granulation phase, the dressing should be changed every 2–3 days.
Hydrocolloid dressings are made of a polyurethane film or foam, on which there is a self-adhesive mass made of elastomers and adhesives, with particles that are capable of swelling to absorb large amounts of exudate (such as gelatin, carboxymethyl cellulose, or pectin). As it absorbs the wound exudate, the hydrocolloid mass liquefies to form a viscous gel. Hydrocolloids are used mainly for superficial wounds, with little exudate, to promote granulation or epithelization.
Self-adhesive hydrocolloid dressings may also be applied without a secondary dressing; these conform to body contours. The dressing should extend 2–3 cm beyond the wound margin to ensure that it adheres sufficiently without leading to maceration of intact skin. Depending on the amount of exudate, hydrocolloid dressings may be left on the wound for 3–5 days.
Impregnated gauze dressings are fiber nets which are coated with ointments, hydrocolloid, silver, or silicone. The impregnation prevents the dressing from sticking to the wound base. This type of dressing is primarily used for acute wounds, temporary coverage of chronic wounds, and to prevent the adhesion of other dressing materials. For chronic wounds, impregnated gauze is generally unsuitable for use as the sole wound dressing.
Depending on the wound and the product, the dressing should be changed after 1–7 days.
Collagen wound care products are currently available in fleece, powder, or sponge form. Different mechanisms of action have been described, especially concerning modification of the pro-inflammatory wound milieu through protease binding.
Collagen may be used for the promotion of granulation and epithelization, especially in previously stagnant wound healing. Due to their hemostatic properties, they are also used after surgical débridement. They are applied as a dry or moist dressing to the wound surface, extending to the wound margin. A secondary dressing should be placed over the collagen dressing. Depending on the product used, the dressing should be changed after 1–5 days. Most of the collagen will have been absorbed by the time of the dressing change; it is usually only necessary to rinse off any remaining residue.
Foam dressings are made of non-irritating polyurethane foam. The surfaces may be coated for example, with silicone or heat-treated. Foams may be used for moderately or strongly exuding wounds to promote granulation and epithelization. If the dressing does not come with adhesive border or an additional superabsorber, it may be cut to size; the wound dressing should extend at least 2 cm over the wound margin. The dressing should be in direct contact with the wound bed.
Depending on the amount of exudate, the wound dressing should be changed after 1–7 days.
Wound products may contain silver in the form of silver ions, elementary silver, nanocrystalline silver, or anorganic silver complexes. Silver ions are either firmly attached to the dressing materials or they are released after contact with wound exudate. Silver ions form complexes with bacterial proteins, which lead to damage of the cell membrane, enzymes, or DNA, and irreversibly damage the bacteria.
Wound dressings containing silver are often used in patients with infected wounds. Depending on which materials the silver is attached to, the size of the dressing may be modified to fit the individual wound. In wounds with little exudate, the dressing should be moistened regularly. Depending on the product, the dressing should be changed after 1–7 days.
Polyacrylate super-absorbers consist of neutralized, cross-linked polyacrylic acid molecules. They can absorb up to 100 times their own weight and store the exudate in their polymer structure.
Polyacrylate super-absorbers inhibit excessive protease activity and normalize the wound micromilieu. They thus support wound cleansing and the formation of granulation tissue. Depending on the amount of exudate, the dressing should be changed after 1–3 days.
Proteolytic enzymes enable selective débridement, which may be accomplished without pain or bleeding. They are safe, quick and easy to apply. Yet treatment can take a very long time. If the wound margin is not protected, maceration of the surrounding area may occur. At present, an ointment with collagenase, and a gel with streptodornase/streptokinase are available.
The preparations are applied, after mechanical wound cleansing, in 2–5 mm layers. They should be covered with non-adhesive dressings. Depending on the chosen preparation, the wound dressing should be changed after 12–24 hours.
There are many other products which do not clearly belong to one of the aforementioned groups. Of particular interest are advanced wound care products which are also declared as wound (kick)starters. These are a new, highly diverse group of therapies for use in wound treatment. Their primary aim is to actively influence the wound milieu.
By interacting with the wound, they are intended to alter the wound milieu or wound surface. Advanced wound care products are used in chronic wounds which, despite optimal, causal therapy, remain hard-to-heal.
The aim of products containing collagen and cellulose (PromogranTM; Systagenix), nano-oligosaccharide factor (NOSF, UrgoStartTM; Urgo), or polyhydrated ionogens (PHI-5, TegadermTM Matrix; 3M), is to directly reduce matrix metalloproteinases (MMPs) [14, 15]. A test procedure is also currently offered (WoundchekTM; Systagenix) for detecting increased levels of various proteases (increased protease activity [EPA]). Currently used growth factors include platelet-derived growth factor (PDGF), which is available as a gel (RegranexTM; Janssen-Cilag) for the treatment of diabetic foot syndrome, as well as epidermal growth factor (EGF), which comes in a wound dressing (NeodermTM; Trimedicales) . Another new, innovative product uses porcine hemoglobin in the form of a spray (GranuloxTM; Sastomed), which may be applied directly to the wound surface, along with conventional wound products. The spray is supposed to transport oxygen from the air into the wound, and is thus suitable for all types of hypoxic wounds . There is also a paste, containing modified starch (poloxamer) that is intended to reduce wound pH levels (CadexomerTM; Smith&Nephew) . Other products contain, e.g., the extracellular matrix protein (ECM) amelogenin (XelmaTM; Mölnlycke) , coagulation factor XIII (FibrogramminTM; CSL Behring) , the analgesic ibuprofen (Biatain IbuTM; Coloplast) , tensides (PolymemTM; Mediset), or negatively charged microspheres (PolyHealTM; Mediwound).
Many of the underlying ideas, and the therapeutic approaches, related to these wound care products are very interesting. One may expect that, in the future, more solid recommendations for their targeted use may become available. At present, there is still lacking scientific data and high quality and controlled clinical trials are required to proof their clinical effectiveness[11-13].
Contact allergens in wound therapies
The current literature contains several reports of an increased incidence of contact sensitization in patients with chronic wounds, compared to the normal population. In patients with chronic venous leg ulcers, contact sensitization rates of up to 80 % have been cited. The most commonly identified contact allergens among these patients are wool wax alcohols (18–33 %), followed by aminoglycoside antibiotics and balsam of Peru . There are also increasing numbers of reports of contact sensitization to products which are used directly for wound treatment (Table 2) .
|▸ Colophonium (up to 14 % of all patients)|
|▸ Polyisobutyl derivatives (rarely)|
|▸ Carboxymethyl cellulose (rarely)|
|▸ Propylene glycol (up to 18 % of all patients)|
|▸ Fatty gauze|
|▸ Wool wax alcohols (up to 35 % of all patients)|
|▸ Arlacel 83 (rarely)|
|▸ Antimicrobial therapies|
|▸ PVP iodine (up to 20 % of all patients)|
|▸ Neomycin (up to 20 % of all patients)|
|▸ Cetyl stearyl alcohol (up to 17 % of all patients)|
|▸ Gentamicin (up to 10 % of all patients)|
|▸ Benzoyl peroxide (up to 4 % of all patients)|
|▸ Cocamidopropyl betaine (up to 3 % of all patients)|
It is important when selecting test substances for patch testing to also include wound dressing products.
Negative pressure wound therapy
Negative pressure treatment, or vacuum therapy, refers to various systems which use an electronic control unit to apply a specific suction level to the tissue. A primary use for negative pressure wound therapy in the treatment of patients with chronic wounds in dermatology is wound bed preparation, with the aim of promoting granulation.
In addition, negative pressure therapy can also promote various aspects of wound healing, e.g., reduction of edema, wound cleansing, or mechanical elimination of bacteria and wound secretions. The option of using the system with instillation allows for cleansing (also with antiseptics) without removing the dressing; hence, negative pressure therapy may also be used in clinically infected wounds. Disadvantages of negative pressure therapy include the odor, irritation of the area around the wound, and the sometimes considerable pain associated with treatment. The most important requirement for its use is that negative pressure may be applied with an airtight seal. Current negative pressure therapy systems consist of a sterile, replaceable sponge or coated gauze, and a non-collapsible tube system with a suction pump unit which generates negative pressure according to individual patient needs. Chronic wounds are usually treated with suction levels of 75–125 mmHg. The surrounding skin should be protected against maceration. Protective polyacrylate or silicone films may be placed over the skin as a protective measure. For chronic wounds, negative pressure therapy devices may be left in place for 2–5 days. If pain occurs when the dressing is changed, one may apply fatty gauze under the sponge or reduce the suction level or time [24, 25].
Other physical treatment methods which may be used in patients with chronic wounds include electrostimulation therapy, extracorporeal shock wave therapy, hyperthermia, laser therapy, plasma therapy, ultrasound, or water-filtered infrared-A radiation .
Bacteria and infections
A prerequisite for efficient wound healing is the elimination, or avoidance, of clinically relevant wound infections. One should take into account that nearly every chronic wound is contaminated or colonized with microorganisms, and that this is generally clinically unproblematic. The diagnosis of a clinically relevant wound infection should thus be based on the corresponding clinical findings with the cardinal symptoms of tumor, calor, dolor, rubor, and functio laesa. In patients with suspected systemic infection, a blood count should be obtained. In many patients with chronic wounds, both CRP and ESR are elevated, even when they do not have an infection. Other diagnostic criteria include a fever and chills. With a few exceptions, systemic antibiotic therapy should only be given if there is a systemic infection.
In chronic wounds, a bacterial smear should be taken, whenever possible, from the wound surface for example using the “Essener Rotary” technique). The “Essener Rotary” technique involves applying gentle pressure to take the bacteriological smear from the wound surface, moving from the outer edge inward in a circular fashion to obtain a representative sample of bacteria for identification . For deep wounds, extensive soft tissue infections, or in the framework of surgical intervention, biopsies should be taken from clinically suspicious areas.
Polyhexanide (polyhexamethylene biguanide, PHMB) belongs to the biguanide substance class. Along with wound cleansing solutions containing preservatives, polyhexanide is also now increasingly found in hydrogels and wound dressings as a first-line substance for use in antimicrobial wound therapy. Thus, in clinical use, it is also more feasible to ensure the contact time of ten minutes. Polyhexanide should not be used on exposed cartilage, in the inner ear, or the CNS
In Germany, octenidine is found in medications as octenidine dihydrochloride. A clear solution, octenidine with 2 % phenoxyethanol is the first-line choice for antimicrobial treatment of chronic wounds. The contact time for octenidine is at least two minutes. There is also a hydrogel preparation which may be left in place for 24 hours. The octenidine solution should not be injected with pressure into the tissue, as this can lead to necrosis. In addition, octenidine should not be used at the same time as povidone iodine, because iodine radicals may be released which can irritate the tissue and cause discoloration.
Preparations containing povidone iodine (polyvinylpyrrolidone [PVP] iodine) have long been central to treatment in Germany of patients with acute, post-traumatic wounds, as well as for preoperative preparation. Problems include the high rate of contact sensitization, discoloration of wounds, which makes evaluation of the wound difficult, and potential inactivation due to blood, pus, and wound exudate. In hard-to-heal wounds, with Gram-negative bacterial such as Pseudomonas aeruginosa, it may be advisable to briefly use PVP iodine [2, 5, 27-29]. Studies have also shown that PVP iodine preparations can effectively neutralize proteases and thus possibly have a positive influence on the wound healing process .
Pain is a complex subjective, perceptual phenomenon, which is influenced by numerous physiological, psychological, emotional, and social factors. Pain leads to a diminished quality of life, has a negative effect on patient compliance, and is an independent risk factor in delayed wound healing. Most patients with chronic wounds report having at least temporary pain due to their wound. Pain intensity may be evaluated using various scales. In Germany, the visual analogue scale (VAS) is the most widely used.
It is important when measuring pain to determine actual pain as well as pain between dressing changes. For values ≥4, improved pain therapy and avoidance of pain should be the goal. For patients with painful wounds, one must seriously consider whether continuous systemic pain therapy, in accordance with the analgesic ladder of the World Health Organization (WHO), may be advisable .
Using other measures is also often helpful, if changing the dressing is painful. Firmly adherent dressings can be removed almost painlessly if they are soaked for at least 30 minutes prior to removal in Ringer solution. Crusts may be softened using compresses soaked in olive oil or ointment and removed atraumatically using a wooden spatula. Local anesthetics in the form of lidocaine and prilocaine cream are suitable as supportive therapy. The cream should be applied to the wound for at least 60 minutes before cleansing is performed . The effectiveness may be increased by using occlusion with semi-permeable films. There are also wound dressings available which release low-dose ibuprofen . Morphine hydrogels are often highly effective; these may be applied directly to the wound and left in place for 24 hours (Table 3) .
|▸ Morphine hydrochloride trihydrate||0.1 g|
|▸ Ethylenediamine tetra-acetic acid sodium salt||0.1 g|
|▸ Hydroxyethyl cellulose 400||4.5 g|
|▸ Lavasept concentrate 20 %||0.2 ml|
|▸ Purified water EuAB||ad 100.0 g|