Wound healing and treating wounds

Chronic wound care and management

Jennifer G. Powers, MD,a Catherine Higham, MD,b Karen Broussard, MD,c and Tania J. Phillips, MDd,e
Durham, North Carolina; Nashville, Tennessee; and Boston and Chestnut Hill, Massachusetts

In the United States, chronic ulcersdincluding decubitus, vascular, inflammatory, and rheumatologic
subtypesdaffect [6 million people, with increasing numbers anticipated in our growing elderly and diabetic
populations. These wounds cause significant morbidity and mortality and lead to significant medical costs.
Preventative and treatment measures include disease-specific approaches and the use of moisture
retentive dressings and adjunctive topical therapies to promote healing. In this article, we discuss recent
advances in wound care technology and current management guidelines for the treatment of wounds and
ulcers. ( J Am Acad Dermatol 2016;74:607-25.)

INTRODUCTION

In the United States, chronic wounds affect [6 million people, with increasing numbers anticipated
because of our aging population and the high prevalence of diabetes mellitus. A 2004 analysis found that
chronic wounds are the largest direct medical cost center of all human skin diseases, costing $9.7 billion
in the United States in 1 year alone.1 Chronic wounds can impact quality of life as profoundly as renal and
heart disease.2 Mortality for some patients with chronic wounds now rivals that of cancer patients.3

Healing wounds is historically one of the most basic and essential practices of human civilization. From
Egyptian papyri to the battlefields of Crimea, there are accounts of wound care from preventing infection
to creating bandages and homemade dressings with honey, grease, and lint.4 Today, there is a growing
body of literature to inform these and more technologically advanced practices. Once the underlying
disease has been addressed (see part I of this 2-part continuing medical education article and Table I),
wound bed preparation is a critical concept. Chronic wounds tend to be stuck in the inflammatory phase
of wound healing.5 To optimize wound healing, the wound should be clean, with a healthy granulating
base, and free of infection. Dressings should be chosen to keep the wound moist but not too wet or too
dry. If the wound fails to heal after addressing these issues, advanced technologies can be considered.
Tissue, infection, moisture imbalance, and edge advancement (TIME), which addresses important barriers
to wound healing, was developed in 2002 by a wound care consensus group. 6 We advocate following
TIME guidelines for the treatment of chronic wounds.

TISSUE

Key points

Removal of devitalized tissue is essential for wound healing to occur.

Debridement, which facilitates removal of this devitalized tissue, can be accomplished using surgical,
mechanical, autolytic, enzymatic, and biologic techniques.

Debridement
Debridement or removal of nonviable wound tissue is essential to good wound bed preparation (Table II).
Necrotic tissue found in chronic wounds can impair healing and impede keratinocyte migration over the
wound bed. Debridement can be performed using surgical, autolytic, enzymatic, biologic, or mechanical
methods. A 2013 study reviewing a variety of chronic wound types found that frequent surgical
debridement facilitated healing.7

Before debridement, a vascular assessment should be performed, especially for ulcers on the lower leg or
foot. Surgical debridement must be avoided in ischemic limbs and heel ulcers that are close to bone.8
Surgical debridement can be performed with scissors, scalpel, or curette, under topical, local, or general
anesthesia. Patients with peripheral neuropathy may not require any anesthesia. Surgical debridement is
rapid and effective but can sometimes damage viable tissue. Autolytic debridement occurs when a wound
is kept moist, allowing endogenous enzymes (eg, matrix metalloproteinases) to degrade nonviable
material from the wound bed. This is slow but less painful and more selective than surgical debridement.

Collagenase is the only commercially available enzymatic debriding agent in the United States.
Collagenase ointment (250 units/g) is derived from the bacterium Clostridium histolyticum and is most
effective for dry wounds with fibrinous slough lacking good granulation tissue, especially when surgical
methods are not ideal. In vivo studies have shown that collagenase increases endothelial cell and
keratinocyte migration.9 Enzymatic debriding agents are an effective alternative for removing necrotic
material from pressure ulcers, leg ulcers, and partial-thickness wounds.10-12 Biologic debridement using
medical grade maggots is a rapid and efficient debridement modality usually reserved for recalcitrant
fibrinous wounds. The powerful enzymes in their saliva dissolve necrotic tissue, which the maggots ingest.
This modality is infrequently used in the United States because of the associated pain and patient and
provider reticence.13 A recent randomized controlled trial found that subjects treated with larvae
experience more discomfort than subjects treated with hydrogel dressings.14

Mechanical debridement can be accomplished using a variety of modalities, including wet to dry
dressings, irrigation of wounds with hydrosurgery, ultrasonography, or high pressure wound irrigation.
These methods are nonselective and can be painful.

Table I. Wound bed preparation according to the TIME guidelines

Jaringan Infeksi Kelembapan Wound edge

advancement
Key goals Removal of Recognition of Ensure adequate Create a wound bed
necrotic and/or wounds at high moisture of microenvironement
devitalized tissue risk of infection, wound bed and that promotes
and fibrinous malodor, delayed eliminate excess healing at the
slough healing, pain, exudate cellular level
excessive
exudate,
undermining
borders, and
friable tissue;
prevention and
treatment of
wound infection
 Key strategies Debridement Proper cleansing Moisture Biologic dressings
(surgical, of wound; retentive (epidermal dEpicel;
mechanical, or systemic dressings (films, dermal dBiobrane,
autolytic); antibiotics only foams, Integra, Oasis,
medical grade for deeper wound hydrocolloids, Dermagraft;
honey; moisture- infections; topical alginates, combination
retentive antibiotics and for hydrogrels, or dApligraf); topical
dressings superficial Promogran); becaplermin; horse
(enzymatic and infections; topical negative pressure chestnut seed
collagenase); iodine in low therapy extract; Vasculera;
biologic concentrations; hyperbaric oxygen
alternative therapy; and
antimicrobial hydrotherapy
agents (silver-
coated dressings,
medical grade
honey, or
Sorbact);
metronidazole gel
to reduce
malodor of
infected wounds

Table II. Methods of debridement

Type of debridement Approaches Clinical context

Surgical Removal of tissue with scissors Should be performed by a skilled
and scalpel practitioner only, faster results,
may require local anesthesia,
often needed for diabetic foot
wounds, and should be avoided
in ischemic limbs and heel ulcers
Mechanical Saline gauzed‘‘wet to dry’’ Less painful than surgical but
dressings may harm viable tissue
Hydrotherapy: pulsed lavage,
whirlpool debridement,
debridement pads with
monofilaments,
ultrasonographic debridement,
and atomized saline
Autolytic Endogenous enzymes (eg, Pain-free, ‘‘selective’’; slower
proteolytic, fibrinolytic, and than other methods
collagenolytic) interact with (improvement in 72 hours);
moisture retentive dressings; avoid in septic or
medical grade manuka honey immunocompromised patients
(via osmosis)
 Enzymatic Collagenase ointment; Faster than autolytic; selective,
discontinued (eg, papain, easy to use; may crosshatch over
streptokinase, and fibrinolysin- eschar with no. 15 or 11 blade;
desoxyribonuclease) avoid silver dressings; okay to
use with infected wounds or on
patients taking anticoagulants,
but may cause allergy/stinging
Biologic Larval therapy: Lucilia sericata, May require patient coaching
Phaenicia sericata, and Lucilia and can be painful
cuprina

INFECTION

Key points

Addressing local infection using cleansing agents and topical antimicrobials can improve healing

Cadexomer iodine has antimicrobial activity and is helpful in healing chronic venous ulcers and
decubitus ulcers

Dilute vinegar topical soaks may reduce recurrent bacterial colonization in chronic wounds, especially
for pseudomonas

In frequently infected wounds or those at high risk, silver-impregnated dressings may be given a two-
week trial period for efficacy.

For deep infection, systemic treatment is required.

In chronic wounds, bacteria may colonize the wound without impairing the healing process (colonization).
As the bacterial load increases to critical colonization, wound healing becomes impaired (local wound
infection). Infection may spread into surrounding tissues, resulting in deep infection, which may progress
to systemic infection (Fig 1). Infection may present as delayed healing, increased exudate, malodorous
discharge, undermined borders, friable tissue, increasing wound size, increased pain, and new areas of
slough (Table III).15 Addressing local wound infection using cleansing agents and topical antimicrobials
can improve healing. For deep or systemic infection, systemic treatment is required.

Cleansing

Wounds can be cleaned with either normal saline or tap water.16-18 Detergents, hydrogen peroxide, and
concentrated povidone-iodine solutions should be avoided because of tissue damage and toxicity.19-21
Cleansing wounds in dilute vinegar 0.5% acetic acid can have significant antimicrobial effects, particularly
in chronic wounds that are prone to frequent infection with Pseudomonas aeruginosa (Fig 2).22 One study
found that a 10-minute soak with 0.5% acetic acid is bactericidal against Gram-positive and -negative
isolates from wounds.23 This should be used for short periods of time until the wound is clean.

Table III. Infection in chronic wounds

Systemic signs of infection Local signs of infection

 Malaise, anorexia, fever, and chills Poor healing, rapid increase in wound size,
increased fibrinous coverage, increased friable
granulation tissue, increased wound exudate,
malodor, increased pain or tenderness to
palpation, and frank pus or abscess formation

Fig 2. Dilute vinegar preparation (0.5% acetic acid soak).

Antimicrobial agents

Topical antimicrobials are preferred over systemic antimicrobials for superficially infected wounds given
direct targeting of the bacterial burden and the concern for development of resistance with systemic
treatments. However, bacterial resistance to topical agents can occur, and they should be discontinued
once the wound is clean.6 Topical antibiotics, such as gentamicin and neomycin, frequently cause allergic
contact dermatitis in chronic wounds and should be avoided.24 They offer no benefit in the rate of
infection or healing time in surgical wounds compared to petroleum jelly.24-26 While concentrated
povidone iodine is cytotoxic, low concentrations have broad-spectrum antimicrobial activity without
inhibiting cell growth. Cadexomer iodine is compounded into gel beads that release low concentrations
of iodine into the wound over time. This is bactericidal against some resistant strains of bacteria, such as
methicillinresistant Staphylococcus aureus (MRSA),27 and may improve the healing of chronic venous leg
ulcers (VLUs) and decubitus ulcers.

Topical metronidazole gel has been shown in 3 randomized controlled trials to be effective at reducing
malodor in fungating malignant wounds or sites prone to anaerobic growth.30-32

Silver is thought to bind to bacterial cell membranes, interfere with bacterial electron transport, bind to
bacterial DNA, and bind up key building blocks in the cell. It is toxic to bacteria, including MRSA, and fungi
in vitro. The 2012 international consensus guidelines on the use of silver-containing products recommend
that silver dressings be used for wounds that are infected or at high risk of becoming infected for a 2-week
trial period. If a silver dressing proves to be insufficient after 2 weeks, more aggressive therapies, such as
systemic antibiotics, may be indicated.33 A meta-analysis of randomized controlled trials that included
both infected and infection-free chronic ulcers has shown that silver-impregnated dressings are superior
to nonsilver dressings in reducing wound size, but the data for complete wound healing and healing rate
are more equivocal.34,35

Medical grade manuka honey from New Zealand and Australia is thought to have both peroxide and
nonperoxide antibacterial activity that can inhibit [50 species of bacteria.36 Manuka honey is available
both as a topical preparation or honey-impregnated dressings (MediHoney; Derma Sciences, Princeton,
NJ). A recent Cochrane review discussed low-quality evidence showing quicker healing of partialthickness
burns compared to conventional treatments and infected postoperative wounds more quickly than
antiseptics and gauze.37

Topical agents can reduce superficial wound infection, but systemic antibiotics should be used in patients
with deep or systemic infection.

MOISTURE BALANCE

Key points

Adequate moisture balance promotes keratinocyte migration and wound healing

A dressing that will keep the wound moist but not too wet or too dry should be chosen

While there are multiple types of moisture retentive dressings, the 5 basic categories are films, foams,
hydrocolloids, alginates, and hydrogels

Negative pressure therapy appears to be effective in postsurgical wounds.

Moisture-retentive dressings

Moisture balance entails selecting the appropriate dressing to absorb exudate yet keep the wound moist.
There are a wide variety of wound dressings, ranging from over the counter adhesive bandages to complex
biologic dressings engineered with neonatal keratinocytes.

Moisture-retentive dressings (MRDs) have moisture vapor transmission rates (MVTRs) of\35 g/m2 / hr to
allow for moist wound healing. For acute wounds, the benefits of MRDs have been clearly proven in
clinical trials.38 A systematic review of 99 studies on MRDs also showed their clinical benefit in chronic
wounds.39 Initial healing rates with these dressings plus compression is faster than compression alone in
venous ulcers.40 These dressings are also cost effective in chronic VLU care considering all factors (eg,
cost for materials, nursing, and travel time).41

The 5 basic types of MRDs are films, foams, hydrocolloids, alginates, and hydrogels (Table IV). Films are
thin, elastic transparent sheets of polyurethane that adhere with acrylic to skin but are gas permeable.
Films are the choice dressing for donor sites of split-thickness skin grafts and may also be used in acute
surgical wounds.42 Foams are bilaminate dressings composed of hydrophobic polyurethane foam sheets
with a hydrophilic surface to prevent leakage and bacterial contamination. These can provide padding
over bony prominences43 and are suitable for mild to moderately exudative wounds. The removal of foam
dressings may require soaking with saline solution if the wound is not very exudative.43

Hydrocolloids are soft conformable dressings composed of an adhesive matrix containing

carboxymethylcellulose, pectin, and gelatin attached to a foam or polyurethane film backing. Wound
exudate interacts with the hydrocolloid to form a yellow gel, promoting autolytic debridement. These
dressings conform well, allowing for easy adoption by patients, and they are helpful for wounds with mild
amounts of exudate. Because they are waterproof they can be worn while bathing or swimming but may
create maceration around the edges. In several meta-analyses, wounds treated with hydrocolloid
dressings showed statistically significant improvement compared to sterile gauze.44-47 Hydrocolloids
should be applied with generous margins to avoid rolling corners and, once placed securely, may be left
for 2 to 4 days. To avoid maceration, a layer of petroleum jelly or zinc oxide paste can be applied around
the wound margins.

Alginates are highly absorbent dressings comprised of cellulose-like polysaccharides derived from algae
or kelp. They can exchange calcium for sodium to absorb fluid and also have hemostatic properties. They
are dry fluffy sheets that become moist as they absorb drainage.48 Alginates are ideal for heavily
exudative wounds and should not be used for dry or minimally exuding wounds.49

Hydrogels are composed of 96% water inside a cross-linked hydrophilic polymer network. They are
available as liquid gels, which can be squirted into a wound, or as sheets that can be placed on the wound
surface. They are best suited for dry, necrotic wounds. They can be cooling and soothing for patients,
especially if the wound is painful.50

Dressing placement

Some dressings are adherent, such as hydrocolloids and films; others require a secondary dressing to keep
them in place. This can be accomplished with a gauze wrap followed by an elastic compression wrap, such
as an ACE or Coban bandage (3M, Minneapolis, MN). If more compression is desired, an Unna boot or
multilayer compression wrap (Fig 3) can be used.51 Unna boots have zinc oxide impregnated into rolled
gauze that can be applied with the knee flexed and wrapped tightly, overlapping each layer by 50% with
each turn, to create a smooth, firm compression wrap that ends just below the knee.52

Table IV. Moisture-retentive dressings by type

Dressing type Description Advantages DisadvantagesBrand-names

Hydrocolloids Malleable sheets Stimulates Gel formation,
Duoderm
comprised of granulation tissue, drainage, and not
(ConvaTec),
waterproof gels or simple to apply, largely suitable for
NuDerm (Johnson
foams within and waterproof cavities & Johnson
polyurethane Medical), Comfeel
films; excellent for (Coloplast Sween,
mildly exudative Inc), Hydrocol
wounds (Dow Hickam),
Cutinova (Smith &
Nephew),
Replicare (Smith &
Nephew United),
and Tegasorb
(3M)
Alginates Consists of Absorbent, Not appropriate Algiderm (Bard),
polysaccharides confers for dry Algisite (Smith &
derived from kelp hemostatic woundsdmay Nephew), Algisorb
and algae; ideal benefits, and cause pain with (Calgon-Vestal),
 for highly suitable for use in dressing removal Algosteril
exudative wounds sinuses if too dry; can (Johnson &
require frequent Johnson Medical),
dressings changes Kaltostat
for wounds with (ConvaTec),
significant Curasorb (The
drainage Kendall Co),
Sorbsan (Dow
Hickam),
Melgisorb
(Molnlycke Health
Care), SeaSorb €
(Coloplast), and
Kalginate
(DeRoyal)
Hydrogels Cross-linked Stimulates Can result in skin Vigilon (CR Bard),
hydrophilic autolytic maceration if Nu-gel (Johnson &
polymer holding debridement and wound is highly Johnson Medical),
significant amount comfortable for exudative Tegagel (3M),
of water; excellent the patient FlexiGel (Smith &
for dry, necrotic Nephew), Curagel
wounds (The Kendall Co),
Clearsite (Conmed
Corp), Curafil (The
Kendall Co),
Curasol (The
Kendall Co),
Carrasyn
(Carrington
Laboratories),
ElastoGel (SW
Technologies),
Hypergel (Scott
Health Care),
Normgel (SCA
Hygiene
Products), 2nd
Skin (Spenco
Medical, Ltd), and
Transigel (Smith &
Nephew)
Films Thin layers of Provides barrier Poor drainage of Tegaderm (3M
elastic against bacteria, fluid, and removal Healthcare),
polyurethane; permeable to may be potentially Polyskin II (Kendall
used for donor gases, and allows damaging to Healthcare),
sites for for visualization of newly formed Bioclusive
splitthickness skin the wound epithelium (Johnson &
grafts Johnson Medical),
 Blisterfilm (The
Kendall Co),
Omniderm
(Omikron
Scientific Ltd),
Proclude
(ConvaTec),
Mefilm
(Molnlycke Health
Care), Carrafilm €
(Carrington Lab),
and Transeal
(DeRoyal)
Foams Bilaminate Absorbs and Can become Polymem (Ferris
dressings with retains moisture, adherent if Corp), Allevyn
hydrophobic prevents leakage drainage dries (Smith & Nephew
polyurethane of drainage and United), Biopatch
foam sheets with bacterial (Johnson &
a hydrophilic contamination, Johnson Medical),
surface; ideal for and easily shaped Curafoam (The
wounds over bony to accommodate Kendall Co),
surfaces, in body site of wound Flexzan (Dow
cavities, and mild Hickam),
to moderately Hydrasorb (Tyco/
exudative wounds Kendall Co),
Lyofoam
(ConvaTec), and
Mepilex
(M€olnlycke
Health Care)
Fig 3. Multilayer compression wrap

Fig 4. Negative pressure therapy on acute wound. (Courtesy of Mary Gloeckner, RN.)

Vacuum-assisted closure

Vacuum-assisted closure, or negative pressure therapy, has been used in chronic wound management,
including diabetic foot ulcers (DFUs), pressure ulcers, and in acute wounds, such as traumatic wounds,
surgical wounds, and flaps and skin grafts (Fig 4). The exact mechanism of action is unknown, but creation
of a moist environment, reduction of edema, reduction in size of the wound, stimulation of angiogenesis,
and the formation of granulation tissue have all been attributed to negative pressure therapy.53 One
prospective randomized trial found no difference in total bacterial load in wounds treated with vacuum-
assisted closure versus conventional moist gauze treatment; however, wounds treated with vacuum had
a significant reduction in surface area and increased rate of wound healing.54 A Cochrane review suggests
that negative pressure therapy may assist wound closure in patients with postoperative diabetic foot
wounds compared with moist dressings55; other postsurgical wounds may also benefit from negative
pressure therapy, but data are insufficient to support general use.56

EDGE OF WOUND

Key points

Biologic skin substitutes mimic the architecture of normal skin and activate healing cascades within the
patient

The 3 main categories of biologic skin substitutes include epidermal, dermal, and dermoepidermal
combination constructs.

Hyperbaric oxygen is most helpful in patients with diabetic foot ulcers

Becaplermin gel is approved by the US Food and Drug Administration for the treatment of diabetic foot
ulcers

Advancing the edges of any wound requires addressing not only local but also systemic factors.
Reepithelialization requires a well-vascularized wound bed, adequate oxygen and nutrients, control of
systemic diseases, such as diabetes mellitus, and treatment of underlying disease, such as chronic venous
insufficiency or arterial disease. A variety of devices from biologic dressings to hyperbaric oxygen
chambers and chronic disease management should be considered in these patients.