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Contents
1 Wound assessment
Joseph E Grey, Stuart Enoch, Keith G Harding.
2 Venous and arterial leg ulcers
Joseph E Grey, Stuart Enoch, Keith G Harding.
3 Diabetic foot ulcers
Michael E Edmonds, A V M Foster.
4 Pressure ulcers
Joseph E Grey, Stuart Enoch, Keith G Harding.
5 Traumatic and surgical wounds
David J Leaper, Keith G Harding.
6 Uncommon causes of ulceration
Girish K Patel, Joseph E Grey, Keith G Harding.
7 Burns
Alex Benson, William A Dickson, Dean E Boyce.
8 Reconstructive surgery
Dean E Boyce, Kayvan Shokrollahi.
9 Wound dressings
Vanessa Jones, Joseph E Grey, Keith G Harding.
10 Infections
Brendan Healy, Andrew Freedman.
11 Non-surgical and drug treatments
Stuart Enoch, Joseph E Grey, Keith G Harding.
12 Recent advances and emerging treatments
Stuart Enoch, Joseph E Grey, Keith G Harding.
Index
ABC of wound healing
Wound assessment
Joseph E Grey, Stuart Enoch, Keith G Harding
Most wounds, of whatever aetiology, heal without difficulty.
Some wounds, however, are subject to factors that impede
healing, although these do not prevent healing if the wounds
are managed appropriately. A minority of wounds will become
chronic and non-healing. In these cases the ultimate goal is to
control the symptoms and prevent complications, rather than
healing the wound.
It is important that the normal processes of developing a
diagnostic hypothesis are followed before trying to treat the
wound. A detailed clinical history should include information
on the duration of ulcer, previous ulceration, history of trauma,
family history of ulceration, ulcer characteristics (site, pain,
odour, and exudate or discharge), limb temperature, underlying
medical conditions (for example, diabetes mellitus, peripheral
vascular disease, ischaemic heart disease, cerebrovascular
accident, neuropathy, connective tissue diseases (such as
rheumatoid arthritis), varicose veins, deep venous thrombosis),
previous venous or arterial surgery, smoking, medications, and
allergies to drugs and dressings. Appropriate investigations
should be carried out.
Wounds are not just skin deep, and accurate assessment is an essential part
of treatment
Local and systemic factors that impede wound healing
Local factors
x Inadequate blood
supply
x Increased skin tension
x Poor surgical
apposition
x Wound dehiscence
x Poor venous drainage
x Presence of foreign
body and foreign
body reactions
x Continued presence
of micro-organisms
x Infection
x Excess local mobility,
such as over a joint
Systemic factors
x Advancing age and general immobility
x Obesity
x Smoking
x Malnutrition
x Deficiency of vitamins and trace elements
x Systemic malignancy and terminal illness
x Shock of any cause
x Chemotherapy and radiotherapy
x Immunosuppressant drugs,
corticosteroids, anticoagulants
x Inherited neutrophil disorders, such as
leucocyte adhesion deficiency
x Impaired macrophage activity
(malacoplakia)
Areas of abnormal pressure
distribution in the diabetic foot.
Plantar ulcers are most commonly
seen under the hallux, on the first
and fifth metatarsal heads, and under
the heel
Some complications of chronic wounds
x Sinus formation
x Fistula
x Unrecognised malignancy
x Malignant transformation in the ulcer bed (Marjolin’s ulcer)
x Osteomyelitis
x Contractures and deformity in surrounding joints
x Systemic amyloidosis
x Heterotopic calcification
x Colonisation by multiple drug resistant pathogens, leading to
antibiotic resistance
x Anaemia
x Septicaemia
This is the first in a series of 12 articles
Causes of ulceration
x Vascular (venous, arterial, lymphatic, vasculitis)
x Neuropathic (for example, diabetes, spina bifida, leprosy)
x Metabolic (for example, diabetes, gout)
x Connective tissue disease (for example, rheumatoid arthritis,
scleroderma, systemic lupus erythematosus)
x Pyoderma gangrenosum (often reflection of systemic disorder)
x Haematological disease (red blood cell disorders (for example,
sickle cell disease); white blood cell disorders (for example,
leukaemia); platelet disorders (for example, thrombocytosis))
x Dysproteinaemias (for example, cryoglobulinaemia, amyloidosis)
x Immunodeficiency (for example, HIV, immunosuppressive therapy)
x Neoplastic (for example, basal cell carcinoma, squamous cell
carcinoma, metastatic disease)
x Infectious (bacterial, fungal, viral)
x Panniculitis (for example, necrobiosis lipoidica)
x Traumatic (for example, pressure ulcer, radiation damage)
x Iatrogenic (for example, drugs)
x Factitious (self harm, “dermatitis artefacta”)
x Others (for example, sarcoidosis)
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Assessing wounds
Size of wound
The size of the wound should be assessed at first presentation
and regularly thereafter. The outline of the wound margin
should be traced on to transparent acetate sheets and the
surface area estimated: in wounds that are approximately
circular, multiply the longest diameter in one plane by the
longest diameter in the plane at right angles; in irregularly
shaped wounds, add up the number of squares contained within
the margin of the outline of the wound from an acetate grid
tracing. These methods are the simplest, but it should be
recognised that they are not precise. However, they do provide
a means by which progress over time to wound closure can be
identified. Patient positioning, body curvature, or tapering of
the limbs will affect the accuracy of these techniques.
Edge of wound
Although not diagnostic, examination of the edge of the wound
may help to identify its aetiology in the context of the history of
the wound. For example, venous leg ulcers generally have gently
sloping edges, arterial ulcers often appear well demarcated and
“punched out,” and rolled or everted edges should raise the
suspicion of malignancy. A biopsy should be taken of any
suspicious wound.
Site of wound
The site of the wound may aid diagnosis; diabetic foot ulcers
often arise in areas of abnormal pressure distribution arising
from disordered foot architecture. Venous ulceration occurs
mostly in the gaiter area of the leg (see next article in this
series). Non-healing ulcers, sometimes in unusual sites, should
prompt consideration of malignancy.
Wound bed
Healthy granulation tissue is pink in colour and is an indicator
of healing. Unhealthy granulation is dark red in colour, often
bleeds on contact, and may indicate the presence of wound
infection. Such wounds should be cultured and treated in the
light of microbiological results. Excess granulation or
overgranulation may also be associated with infection or
non-healing wounds. These often respond to simple cautery
with silver nitrate or with topically applied steroid preparations.
Chronic wounds may be covered by white or yellow shiny
Laboratory investigations before treating a wound
Investigation Rationale
Haemoglobin Anaemia may delay healing
White cell count Infection
Platelet count Thrombocytopenia
Erythrocyte sedimentation rate;
C reactive protein
Non-specific markers of infection
and inflammation; useful in
diagnosis and monitoring
treatment of infectious or
inflammatory ulceration
Urea and creatinine High urea impairs wound healing.
Renal function important when
using antibiotics
Albumin Protein loss delays healing
Glucose, haemoglobin A1C Diabetes mellitus
Markers of autoimmune disease
(such as rheumatoid factor,
antinuclear antibodies,
anticardiolipin antibodies, lupus
anticoagulant)
Indicative of rheumatoid disease,
systemic lupus erythematosus, and
other connective tissue disorders
Cryoglobulins, cryofibrinogens,
prothrombin time, partial
thromboplastin time
Haematological disease
Deficiency or defect of
antithrombin III, protein C,
protein S, factor V Leiden
Vascular thrombosis
Haemoglobinopathy screen Sickle cell anaemia, thalassaemia
HIV status Kaposi’s sarcoma
Serum protein electrophoresis;
Bence-Jones proteins
Myeloma
Urine analysis Useful in connective tissue disease
Wound swab Not routine; all ulcers colonised
(not the same as infection); swab
only when clinical signs of infection
Left: Basal cell carcinoma with rolled edges. Right: Lymphoma
presenting as groin ulceration
Site of wound and type of ulcer
Site Type of ulcer
Gaiter area of the leg Venous ulcer
Sacrum, greater trochanter, heel Pressure ulcer
Dorsum of the foot Arterial or vasculitic ulcer
Shin Necrobiosis lipoidica
Lateral malleolus Venous, arterial, or pressure ulcer
or hydroxyurea induced ulceration
Plantar and lateral aspect of foot
and toes
Diabetic ulcer
Sun exposed areas Basal cell carcinoma; squamous cell
carcinoma
Left: Healthy granulation tissue in a hidradenitis
suppurativa excision wound. Right: Unhealthy
granulation tissue in a venous leg ulcer
Tracing a wound for measurement and measuring a wound
Wound edge characteristics
Edges Type of ulcer
Sloping Venous ulcer
Punched out Arterial or vasculitic ulcer
Rolled Basal cell carcinoma
Everted Squamous cell carcinoma
Undermining Tuberculosis, syphilis
Purple Vasculitic (such as pyoderma
gangrenosum)
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fibrinous tissue (see next article in this series). This tissue is
avascular, and healing will proceed only when it is removed.
This can be done with a scalpel at the bedside.
The type of tissue at the base of the wound will provide
useful information relating to expectation of total healing time
and the risk of complications—for example, bone at the base
may suggest osteomyelitis and delayed or non-healing.
Necrotic tissue, slough, and eschar
The wound bed may be covered with necrotic tissue (non-viable
tissue due to reduced blood supply), slough (dead tissue, usually
cream or yellow in colour), or eschar (dry, black, hard necrotic
tissue). Such tissue impedes healing. Necrotic tissue and slough
may be quantified as excessive (+++), moderate (++), minimal (+),
or absent (−).
Since necrotic tissue can also harbour pathogenic
organisms, removal of such tissue helps to prevent wound
infection. Necrotic tissue and slough should be debrided with a
scalpel so that the wound bed can be accurately assessed and
facilitate healing. Eschar may be adherent to the wound bed,
making debridement with a scalpel difficult. Further
debridement, as part of wound management, may be required
using other techniques.
Depth
Accurate methods for measuring wound depth are not practical
or available in routine clinical practice. However, approximate
measurements of greatest depth should be taken to assess
wound progress. Undermining of the edge of the wound must
be identified by digital examination or use of a probe. The
depth and extent of sinuses and fistulas should be identified.
Undermining areas and sinuses should be packed with an
appropriate dressing to facilitate healing. Undermining wounds
and sinuses with narrow necks that are difficult to dress may be
amenable to be laid open at the bedside to facilitate drainage
and dressing. Wounds associated with multiple sinuses or
fistulas should be referred for specialist surgical intervention.
Surrounding skin
Cellulitis associated with wounds should be treated with
systemic antibiotics. Eczematous changes may need treatment
with potent topical steroid preparations. Maceration of the
surrounding skin is often a sign of inability of the dressing to
control the wound exudate, which may respond to more
frequent dressing changes or change in dressing type. Callus
surrounding and sometimes covering neuropathic foot ulcers
(for example, in diabetic patients) must be debrided to (a)
visualise the wound, (b) eliminate potential source of infection,
and (c) remove areas close to the wound subject to abnormal
pressure that would otherwise cause enlargement of the wound.
This can be done at the bedside.
Infection
All open wounds are colonised. Bacteriological culture is
indicated only if clinical signs of infection are present or if
Bone at the base of a wound may suggest a protracted
healing time and the possibility of underlying
osteomyelitis
Maceration of the skin
surrounding a diabetic foot ulcer
Top: Necrotic tissue (black areas) in a pressure ulcer. Bottom: Slough at the
base of a pressure ulcer. Right: Eschar covering a heel pressure ulcer
Left: Digital examination of a wound. Right: Examining a wound with a
probe
Fistula in a diabetic foot
ulcer
Types of debridement
Sharp—At the bedside (using scalpel or curette)
Surgical—In the operating theatre
Autolytic—Facilitation of the body’s own mechanism of debridement
with appropriate dressings
Biological—Larval (maggot) therapy
Enzymatic—Not widely used; pawpaw (papaya) or banana skin used in
developing countries
Mechanical—Wet-to-dry dressings (not widely used in the UK)
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infection control issues (such as methicillin resistant
staphylococcus aureus (MRSA)) need to be considered. The
classic signs of infection are heat, redness, swelling, and pain.
Additional signs of wound infection include increased exudate,
delayed healing, contact bleeding, odour, and abnormal
granulation tissue. Treatment with antimicrobials should be
guided by microbiological results and local resistance patterns.
Pain
Pain is a characteristic feature of many healing and non-healing
wounds. Pain can be caused by both nociceptive and
neuropathic stimuli. Intermittent pain is often related to
dressing removal or recent application of new dressings and
may necessitate the use of analgesia before the dressing is
changed. Constant pain may arise as a result of the underlying
condition, such as ischaemia, neuropathy, tissue oedema,
chronic tissue damage (for example, lipodermatosclerosis),
infection, or scarring (for example, atrophie blanche). The
nature and type of pain should be identified and treated
appropriately. Pain assessment tools can help to assess the
nature and severity of pain. With recalcitrant pain, or pain that
is difficult to control, consider referral to a local pain team.
Non-healing wounds
Non-healing wounds have traditionally been defined as those
that fail to progress through an orderly sequence of repair in a
timely fashion. Such wounds are sometimes thought of as being
caused by neglect, incompetence, misdiagnosis, or
inappropriate treatment strategies. However, some wounds are
resistant to all efforts of treatment aimed at healing, and
alternative end points should be considered; measures aimed
at improving the quality of life will be paramount in these
instances.
Quality of life
Several studies have shown that patients with non-healing
wounds have a decreased quality of life. Reasons for this include
the frequency and regularity of dressing changes, which affect
daily routine; a feeling of continued fatigue due to lack of sleep;
restricted mobility; pain; odour; wound infection; and the
physical and psychological effects of polypharmacy. The loss of
independence associated with functional decline can lead to
changes, sometimes subtle, in overall health and wellbeing.
These changes include altered eating habits, depression, social
isolation, and a gradual reduction in activity levels. Many
patients with non-healing wounds complain of difficulties with
emotions, finances, physical health, daily activities, friendships,
and leisure pursuits.
Quality of life is not always related to healing of the wound.
It may be clear from the outset that wounds in some patients
will be unlikely to heal. In such patients control of symptoms
and signs outlined above—particularly odour, exudate, and
pain—may improve the individual’s quality of life. Additionally,
optimal chronic wound management will lead to a reduction in
the frequency of dressing changes, further enhancing quality of
life. In a minority of instances, seemingly drastic measures—
such as amputation in a person with chronic leg ulceration—
may need to be considered when the quality of life is severely
affected by the non-healing wound and its complications.
The drawing on page 285 is adapted from one provided by Wendy Tyrrell,
School of Health and Social Sciences, University of Wales Institute, Cardiff.
BMJ 2006;332:285–8
Wound exudate
x Wound exudate may be serous, serosanguinous, or sanguinous
x The quantity of exudate is usually classified as heavy (+++ (dressing
soaked)), medium (++ (dressing wet)), or minimal (+ (dressing dry))
x Excessive exudate may be due to wound infection or gross oedema
in the wound area and may complicate wound healing
x The exudate should be controlled with the use of dressings
appropriate for the level of exudate and any infection treated
x Barrier films applied to the surrounding skin help to prevent
further maceration (see the ninth article in the series)
x The oedematous leg should be raised when the patient is seated
The causes of malodorous wounds include infection
and the presence of necrotic tissue. Infection should be
treated with antibiotics. Odour associated with necrotic
tissue may be reduced by removal of the necrotic tissue
or use of agents impregnated with antiseptics or
charcoal . Treatment with topical metronidazole and use
of odour absorbing dressings may help to reduce odour
from fungating malignant wounds. Larval therapy may
also be helpful in the debridement of malodorous tissue
Clinical features of non-healing wounds
x Absence of healthy
granulation tissue
x Presence of necrotic and
unhealthy tissue in the
wound bed
x Excess exudate and slough
x Lack of adequate blood supply
x Failure of re-epithelialisation
x Cyclical or persistent pain
x Recurrent breakdown of wound
x Clinical or subclinical infection
Overgranulation may be a sign of infection or
non-healing
Further reading
x Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE,
Rodeheaver G, et al. Definitions and guidelines for assessment of
wounds and evaluation of healing. Arch Dermatol 1994;130:489-93.
x Izadi K, Ganchi P. Chronic wounds. Clin Plast Surg 2005;32:209-22.
x Falanga V, Phillips TJ, Harding KG, Moy RL, Peerson LJ, eds. Text
atlas of wound management. London: Martin Dunitz, 2000.
Stuart Enoch is a research fellow of the Royal College of Surgeons of
England and is based at the Wound Healing Research Unit, Cardiff
University.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: KGH’s unit receives income from many commercial
companies for research and education, and for advice. It does not support
one company’s products over another.
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ABC of wound healing
Venous and arterial leg ulcers
Joseph E Grey, Stuart Enoch, Keith G Harding
Venous ulceration
Venous leg ulceration is due to sustained venous hypertension,
which results from chronic venous insufficiency. In the normal
venous system, pressure decreases with exercise as a result of
the action of the calf muscle pump. When the muscles relax, the
valves in the perforating veins connecting the superficial to the
deep venous circulation prevent reflux and the pressure
remains low. The venous pressure remains high, however, in a
system where the valves are incompetent.
Up to 10% of the population in Europe and North America
has valvular incompetence, with 0.2% developing venous
ulceration. Forty to fifty per cent of venous ulcers are due to
superficial venous insufficiency and/or perforating vein
incompetence alone with a normal deep venous system.
There are many risk factors for venous ulceration. Recurrent
venous ulceration occurs in up to 70% of those at risk. Many
venous ulcers are painful, so appropriate pain relief and advice
should be given.
Examination
Ninety five per cent of venous ulceration is in the gaiter area
of the leg, characteristically around the malleoli. Ulceration
may be discrete or circumferential. The ulcer bed is often
covered with a fibrinous layer mixed with granulation tissue,
surrounded by an irregular, gently sloping edge. Ulcers
occurring above the mid-calf or on the foot are likely to have
other origins.
Pitting oedema is often present and may predate the ulcer.
It is often worse towards the end of the day. Extravasation of
erythrocytes into the skin occurs, resulting in the deposition of
haemosiderin within macrophages, which stimulates melanin
production, pigmenting the skin brown. In long term venous
insufficiency, lipodermatosclerosis occurs. This is characterised
by the dermis and subcutaneous tissue becoming indurated and
fibrosed with the lack of pitting oedema; the skin also becomes
atrophic, loses sweat glands and hair follicles, and becomes
variably pigmented (ranging from hypopigmented to
hyperpigmented). Severe lipodermatosclerosis may lead to
atrophie blanche—white fibrotic areas with low blood flow.
Lipodermatosclerosis often precedes venous ulceration. As a
result of lipodermatosclerosis, a rigid woody hardness often
develops, which at its worst may result in the leg resembling an
“inverted champagne bottle.” Venous eczema (erythema,
scaling, weeping, and itching) is also common and is distinct
from cellulitis.
Typical venous leg ulcer over the medial malleolus (left) and venous leg
ulcer over malleolus with a fibrinous base (right)
From left to right: Haemosiderin associated with a venous leg ulcer; lipodermatosclerosis; venous leg ulcer in area of atrophie blanche; wenous leg ulcer with
severe “champagne bottle” deformity of the leg
Risk factors for venous ulceration
Direct risk factors
x Varicose veins
x Deep vein thrombosis
x Chronic venous insufficiency
x Poor calf muscle function
x Arterio-venous fistulae
x Obesity
x History of leg fracture
Indirect risk factors
x All risk factors leading to deep vein thrombosis including
protein-C, protein-S, and anti-thrombin III deficiency
x Family history of varicose veins
x A history of minor trauma prior to the development of ulceration
may also be identified
Features of venous eczema and cellulitis
Venous eczema Cellulitis
Red, warm, painful, and tender
to touch
Red, warm, painful, and tender
to touch
Usually chronic Insidious (usually develops over
24-72 hours)
Diffuse and poorly demarcated Usually well demarcated
Increase in exudate No increase in exudate
Itchy Not itchy
Scaly Not scaly
Treated with topical steroids Treated with systemic antibiotics
This is the second in a series of 12 articles
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Management
Compression is the mainstay of venous ulcer management (see
also 11th article in this series). Graded compression, with
greatest pressure (about 40 mm Hg) at the ankle, tapering off to
lower pressure (about 18 mm Hg) below the knee, increases the
limb hydrostatic pressure and concomitantly reduces the
superficial venous pressure. Various compression bandage
systems are used. These include the single and multilayer elastic
banadage system, short stretch bandage, and elasticated tubular
bandages (for example, Tubigrip). Compression with pneumatic
devices (for example, Flowtron) has been used to promote
healing of venous ulcers in patients with oedematous legs.
Patients should be warned to remove the compression if
they notice any side effects (such as numbness, tingling, pain,
and dusky toes) and seek advice.
Sharp debridement of non-viable tissue may expedite
healing of venous ulcers and can be done in the primary care
setting. Surgery is normally indicated to correct superficial
venous disease in an attempt to prevent ulcers from recurring.
Shave therapy (excision of the whole ulcer) followed by skin
grafting, or skin grafting alone, may be useful in patients where
other treatments have failed.
Venous leg ulcers often become infected (see 10th article in
this series for how to detect signs of infection). The most
common organisms include Staphylococcus aureus, Pseudomonas
aeruginosa, and -haemolytic streptococci. Initially, these should
be treated empirically (with broad spectrum penicillin or
macrolide or quinolone antibiotics) until definitive culture and
sensitivities are available. Infection should be treated with a two
week course of antibiotics. Topical antibiotics should be avoided
owing to the risk of increasing bacterial resistance and contact
dermatitis. Associated venous eczema should be treated with
topical steroids and emollients. The eczema may be secondarily
infected and require systemic antibiotic therapy.
Once the venous ulcer has healed, it is essential that patients
follow simple advice aimed at preventing the recurrence of the
ulcer: this includes wearing compression stockings, skin care, leg
elevation, calf exercises, and adopting a suitable diet. The
reported annual recurrence rate of venous ulcers (20%) is
strongly influenced by patient adherence. Local “leg clubs”
(www.legclub.org) may help to reduce this rate.
Arterial ulceration
Arterial ulceration is due to a reduced arterial blood supply to
the lower limb. The most common cause is atherosclerotic
disease of the medium and large sized arteries. Other causes
include diabetes, thromboangiitis, vasculitis, pyoderma
gangrenosum, thalassaemia, and sickle cell disease, some of
which may predispose to the formation of atheroma. Further
damage to the arterial system occurs with concurrent
hypertension through damage of the intimal layer of the artery.
The reduction in arterial blood supply results in tissue hypoxia
and tissue damage. Thrombotic and atheroembolic episodes
may contribute to tissue damage and ulcer formation.
Choice of dressing
x Dressing choice will reflect the nature of the ulcer (see ninth article
in this series)
x The leg should always be raised when a patient is seated
x Patients should be encouraged, however, to remain active provided
they are wearing some form of compression system
Compression stockings
Class
Pressure at
ankle (mm Hg) Indication
I 14-17 Mild varicose veins
II 18-24 Prevention of recurrence of venous ulcers
on narrow legs and in slim patients and
for mild oedema
III 25-35 Chronic venous insufficiency and
oedema, and large heavy legs
Severe eczema
Very potent corticosteroid for 3-4 weeks
(such as clobetasol propionate); also emollient*
No eczema
Daily emollient*
*Such as aqueous cream or liquid and white soft paraffin (50/50)
Infected eczema
Combination of highly
potent corticosteroid;
antiseptic and
astringent agent such
as potassium
permanganate
(1 in 10 000);
and oral antibiotics
Mild eczema
Moderately potent
corticosteroid
for 3-4 weeks
(such as
clobetasone
butyrate);
also emollient*
Weeping eczema
As for infected
eczema,
but without
oral antibiotics
Guidelines for management of different categories of venous eczema.
Arrows indicate direction of possible change in condition of eczema
Unna’s boot, a wet zinc oxide bandage applied from toes
to knee and covered with elastic compression bandage,
is commonly used in the United States. The
surrounding skin, however, can develop contact
dermatitis, and this type of bandaging may fail to
control high levels of exudate from the ulcer
Unhealthy venous leg ulcer before debridement (left) and sharp
debridement of venous leg ulcer (right)
Arterial ulceration often occurs after seemingly trivial
trauma or as the result of localised pressure
Compression stocking
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Peripheral vascular disease is most common in men older
than 45 and women older than 55, and patients may have a
family history of premature atherosclerotic disease. Modifiable
risk factors for peripheral vascular disease include smoking,
hyperlipidaemia, hypertension, diabetes, and obesity, with
associated decreased activity. Patients may also have a history of
generalised vascular problems, such as myocardial infarction,
angina, stroke, and intermittent claudication.
Examination
Arterial ulceration typically occurs over the toes, heels, and
bony prominences of the foot. The ulcer appears “punched
out,” with well demarcated edges and a pale, non-granulating,
often necrotic base. The surrounding skin may exhibit dusky
erythema and may be cool to touch, hairless, thin, and brittle,
with a shiny texture. The toenails thicken and become opaque
and may be lost. Gangrene of the extremities may also occur.
Examination of the arterial system may show a decreased or
absent pulse in the dorsalis pedis and posterior tibial arteries.
There may be bruits in the proximal leg arteries, indicating the
presence of atherosclerosis.
Patients with arterial ulcers have a reduced capillary refill
time. With normal capillary refill, after compression of the great
toe or dorsum of the foot for a few seconds, the skin colour
should return to normal in less than two to three seconds. Delay
in return of the normal colour is indicative of vascular
compromise. A delay of more than 10 to 15 seconds in return
of colour after raising an ischaemic leg to 45 degrees for one
minute (Buerger’s test) indicates vascular compromise.
The ankle brachial pressure index is helpful in identifying
peripheral vascular disease in the absence of non-compressible
vessels resulting from vessel calcification (for example, diabetes)
or tissue oedema. A duplex ultrasound scan will give further
information—on arterial occlusion, stenosis, and areas of diffuse
and continuous atheromatous disease. Arteriography is the
ideal investigation in preoperative planning, allowing direct
assessment of the vascular anatomy of the lower limb.
Management
Increasing the peripheral blood flow by, for example,
reconstructive surgery (for diffuse disease) or angioplasty (for
localised stenosis) is the intervention most likely to affect the
healing process in arterial ulceration. Operative indications for
chronic ischaemia include non-healing ulceration, gangrene,
rest pain, and progression of disabling claudication.
Pain with arterial ulceration
x Pain may be present at rest and may be alleviated by hanging the
foot over the side of the bed or sleeping in a chair
x Pain usually begins distal to the obstruction, moving proximally as
ischaemia progresses
x The ulcer itself is often painful
Features of venous and arterial ulcers
Venous Arterial
History History of varicose veins,
deep vein thrombosis,
venous insufficiency or
venous incompetence
History suggestive of
peripheral arterial disease,
intermittent claudication,
and/or rest pain
Classic site Over the medial gaiter
region of the leg
Usually over the toes, foot,
and ankle
Edges Sloping Punched out
Wound bed Often covered with
slough
Often covered with
varying degrees of slough
and necrotic tissue
Exudate level Usually high Usually low
Pain Pain not severe unless
associated with excessive
oedema or infection
Pain, even without
infection
Oedema Usually associated with
limb oedema
Oedema not common
Associated
features
Venous eczema,
lipodermatosclerosis,
atrophie blanche,
haemosiderosis
Trophic changes;
gangrene may be present
Treatment Compression is mainstay Appropriate surgery for
arterial insufficiency;
drugs of limited value
Interpreting ankle brachial pressure index
Index
Signs and
symptoms
Severity of
disease Action
≥ 0.7-1 Mild
intermittent
claudication, or
no symptoms
Mild arterial
disease
Reduce risk factors and
change lifestyle: stop
smoking, maintain
weight, exercise
regularly, consider
antiplatelet agent
0.7-0.5 Varying degrees
of intermittent
claudication
Mild to
moderate
arterial
disease
As for index ≥ 0.7-1,
plus referral to
outpatient vascular
specialist and possible
arterial imaging
(duplex scan and/or
angiogram)
0.5-0.3 Severe
intermittent
claudication
and rest pain
Severe
arterial
disease
As for index ≥ 0.7-1,
plus urgent referral to
vascular specialist and
possible arterial
imaging (duplex scan
and/or angiogram)
≤ 0.3 or
ankle
systolic
pressure
< 50 mm
Hg
Critical
ischaemia (rest
pain > 2 weeks)
with or without
tissue loss (ulcer,
gangrene)
Severe
arterial
disease; risk
of losing
limb
Urgent referral to
vascular emergency
on-call team and
possible surgical or
radiological
intervention
An index of 1 to 1.1 is considered to be normal. The data in the table should be
used as an adjunct to the clinical findings. Erroneous readings may be the result
of incompressible arteries secondary to presence of calcification or presence of
tissue oedema. Patients may present with an arterial ulcer even with a normal
index. Patients may present with an acutely ischaemic limb either due to an
embolus or a thrombus (“acute on chronic” ischaemia) and should be referred
as an emergency to a vascular specialist or emergency department for urgent
intervention to prevent imminent limb loss.
Top left: Dry gangrene of great toe
in a patient with peripheral vascular
disease with line of demarcation
covered with slough. Top right: Wet
gangrene of forefoot and toes in a
patient with arterial disease, with
soft tissue swelling due to infection.
Left: Arterial ulcer over lower leg,
with associated skin changes typical
of arterial disease
Practice
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The patient should stop smoking, and control of diabetes,
hypertension, and hyperlipidaemia should be optimised.
Patients may find benefits from sleeping in a bed raised at the
head end. Patients should follow simple advice on foot and leg
care. Walking is beneficial.
Infection can cause rapid deterioration in an arterial ulcer,
and treatment with systemic antibiotics (along the lines for
venous ulceration outlined above) should be started. Patients with
rest pain or worsening claudication, or both, and a non-healing
ulcer should be referred to a vascular surgeon; opioid analgesia
may be necessary during the wait for surgery. It is not appropriate
to debride arterial ulcers as this may promote further ischaemia
and lead to the formation of a larger ulcer.
Choice of wound dressings will be dictated by the nature
of the wound. Vasoconstrictive drugs such as non-selective
blockers should be avoided. (See 11th article in this series for
more information on drug treatment.)
Ulceration of mixed aetiology is not uncommon: patients
may have a combination of venous and arterial diseases,
resulting in ulcers of mixed aetiologies, which will limit the
degree of compression (if any) that can be used.
Further reading
x Simon DA, Dix FP, McCollum CN. Management of venous leg
ulcers. BMJ 2004;328:1358-62.
x Barwell JR, Davies CE, Deacon J, Harvey K, Minor J, Sassano A,
et al. Comparison of surgery and compression with compression
alone in chronic venous ulceration (ESCHAR study): randomised
controlled trial. Lancet 2004;363:1854-9.
x Cullum N, Nelson EA, Fletcher AW, Sheldon TA. Compression for
venous leg ulcers. Cochrane Database Syst Rev 2001;(2):CD000265.
x Williams DT, Enoch S, Miller DR, Harris K, Price PE, Harding KG.
The effect of sharp debridement using curette on recalcitrant
non-healing venous leg ulcers: a concurrently controlled
prospective cohort study. Wound Rep Regen 2005;13:131-7.
x Morris PJ, Malt RA. Oxford textbook of surgery. 2nd ed. Oxford:
Oxford University Press, 2001.
x Burnand KG, Young AE, Lucas JD, Rowlands B, Scholefield J.
The new Aird’s companion in surgical studies. 2nd ed. Edinburgh:
Elsevier Churchill Livingstone, 2005.
x Nelson EA, Bell-Syer SE, Cullum NA. Compression for preventing
recurrence of venous ulcers. Cochrane Database Syst Rev
2000;(4):CD002303.
x Gohel MS, Barwell JR, Earnshaw JJ, Heather BP, Mitchell DC,
Whyman MR, et al. Randomized clinical trial of compression plus
surgery versus compression alone in chronic venous ulceration
(ESCHAR study)—haemodynamic and anatomical changes. Br J
Surg 2005;92:291-7.
Guidelines for patients on protecting lower limbs and feet
x Examine the feet daily for broken skin, blisters, swelling, or redness
x Report worsening symptoms—for example, decreasing walking
distance, pain at rest, pain at night, changes in skin colour
x Keep the skin moist with, for example, 50/50 white soft paraffin
and liquid paraffin mix
x Never walk barefoot
x Ensure shoes are well fitting and free of friction and pressure
points; check them for foreign objects (such as stones) before
wearing; and avoid open toed sandals and pointed shoes
x Give up smoking
x Take regular exercise within limits of pain and tolerance
Ulcer over medial malleolus of mixed arterial and venous aetiology, with
lipodermatosclerosis and breakdown of scar over saphenous vein harvesting
site (for cardiac bypass grafting)
The table on interpreting the ankle brachial pressure index is adapted
from Beard JD, Gaines PA, eds. Vascular and endovascular surgery. 3rd ed.
London: WB Saunders, 2005.
Stuart Enoch is research fellow of the Royal College of Surgeons of
England and is based at the Wound Healing Research Unit, Cardiff
University.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:347–50
Memorable patients
Prisoners of war
The 50th anniversary of VE day threw up a crop of veterans, all
suffering the effects of lifelong smoking. Two were unworried
about the prospect of surgery. They had had a good war and were
enjoying half a century of borrowed time. One, captured in north
Africa, had been paraded before Rommel. A British submarine
had attacked the ship taking him to Europe and imprisonment.
Rescued from near drowning, he was thrust back into a
succession of advancing front lines through Europe. The other
showed his neck and chest scars. Bayoneted and left for dead, he
was found in the ruins of Arnhem, nursed back to life, and spent
the remainder of the war behind barbed wire.
A third was the antithesis. He had been captured in 1939 and
spent five sterile, comfortless, austere, and miserable years in
prisoner of war camps. Those years were to be a metaphor for the
rest of his life. There were no experiences of derring-do to share,
no reunions with old comrades in arms, and no parades on the
50th anniversary to show a chest full of medals. His illness was
just further evidence of the lousy hand he had been dealt.
We almost missed the significance of the note on beri-beri in
the record of a fourth. VE day meant nothing to him, nor would
VJ day be cause for celebration. We warned him of the potential
for flashbacks and tried to ensure that he did not misconstrue his
perioperative experience as punishing, brutal, or inhumane.
Ian D Conacher consultant anaesthetist, Freeman Hospital, Newcastle
upon Tyne (i.d.conacher@btinternet.com)
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ABC of wound healing
Diabetic foot ulcers
Michael E Edmonds, A V M Foster
Diabetic foot ulcers can be divided into two groups: those in
neuropathic feet (so called neuropathic ulcers) and those in feet
with ischaemia often associated with neuropathy (so called
neuroischaemic ulcers). The neuropathic foot is warm and well
perfused with palpable pulses; sweating is diminished, and the
skin may be dry and prone to fissuring. The neuroischaemic
foot is a cool, pulseless foot; the skin is thin, shiny, and without
hair. There is also atrophy of the subcutaneous tissue, and
intermittent claudication and rest pain may be absent because
of neuropathy.
The crucial difference between the two types of feet is the
absence or presence of ischaemia. The presence of ischaemia
may be confirmed by a pressure index (ankle brachial pressure
index < 1). As many diabetic patients have medial arterial
calcification, giving an artificially raised ankle systolic pressure,
it is also important to examine the Doppler arterial waveform.
The normal waveform is pulsatile with a positive forward flow
in systole followed by a short reverse flow and a further forward
flow in diastole, but in the presence of arterial narrowing the
waveform shows a reduced forward flow and is described as
“damped.”
Neuropathic foot ulcer
Neuropathic ulcers usually occur on the plantar aspect of the
foot under the metatarsal heads or on the plantar aspects of the
toes.
The most common cause of ulceration is repetitive
mechanical forces of gait, which lead to callus, the most
important preulcerative lesion in the neuropathic foot. If
allowed to become too thick, the callus will press on the soft
tissues underneath and cause ulceration. A layer of whitish,
macerated, moist tissue found under the surface of the callus
indicates that the foot is close to ulceration, and urgent removal
of the callus is necessary. If the callus is not removed,
inflammatory autolysis and haematomas develop under the
callus. This leads to tissue necrosis, resulting in a small cavity
filled with serous fluid giving the appearance of a blister under
the callus. Removal of the callus reveals an ulcer.
A foot ulcer is a sign of systemic disease and should
never be regarded as trivial
Left: Neuropathic foot with prominent metatarsal heads and pressure points
over the plantar forefoot. Right: Neuroischaemic foot showing pitting
oedema secondary to cardiac failure, and hallux valgus and erythema from
pressure from tight shoe on medial aspect of first metatarsophalangeal joint
Left: Hand held Doppler used with sphygmomanometer to
measure ankle systolic pressure. Right: Doppler waveform from
normal foot showing normal triphasic pattern (top) and from
neuroischaemic foot showing damped pattern (bottom)
Left: Callus removal by sharp debridement. Right: Whitish,
macerated, moist tissue under surface of callus, indicating
imminent ulceration
Left: Blister under a callus over first metatarsal head. Centre:
The roof of the blister is grasped in forceps and cut away,
together with associated callus. Right: Ulcer is revealed
underneath
This is the third in a series of 12 articles
Left: Neuropathic foot with plantar ulcer surrounded by callus. Right: Ulcer
over medial aspect of first metatarsophalangeal joint of neuroischaemic foot
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Neuroischaemic foot ulcer
Neuroischaemic ulcers are often seen on the margins of the
foot, especially on the medial surface of the first
metatarsophalangeal joint and over the lateral aspect of the fifth
metatarsophalangeal joint.They also develop on the tips of the
toes and beneath any toe nails if these become overly thick.
The classic sign of preulceration in the neuroischaemic foot
is a red mark on the skin, often precipitated by tight shoes or a
slip-on shoe, leading to frictional forces on the vulnerable
margins of the foot.
The first sign of ischaemic ulceration is a superficial blister,
usually secondary to friction. It then develops into a shallow
ulcer with a base of sparse pale granulation tissue or yellowish
closely adherent slough.
Management
Wound control
In the neuropathic foot, all callus surrounding the ulcer is
removed with a scalpel, together with slough and non-viable
tissue. It is always important to probe the ulcer as this may
reveal a sinus extending to bone (suggesting osteomyelitis) or
undermining of the edges where the probe can be passed from
the ulcer underneath surrounding intact skin.
In the neuroischaemic foot, slough and dried necrotic
material should be removed from the ulcer by sharp
debridement. Debridement should be cautious if the foot is very
ischaemic (pressure index < 0.5) as it is essential not to damage
viable tissue.
Some ischaemic ulcers develop a halo of thin glassy callus
that dries out, becomes hard, and curls up. These areas need to
be smoothed off as they can catch on dressings and cause
trauma to underlying tissue. If a subungual ulcer is suspected,
the nail should be cut back very gently or layers of nail pared
away, to expose and drain the ulcer. Maggot therapy is
sometimes used in debridement, especially with neuroischaemic
ulcers.
Vacuum assisted closure may be used to achieve closure of
diabetic foot ulcers and wounds that have been debrided. This
technique is increasingly used to treat postoperative wounds in
a diabetic ischaemic foot, especially when revasularisation is not
possible.
Mechanical control
In neuropathic feet the overall aim is to redistribute plantar
pressures, wheareas in neuroischaemic feet it is to protect the
vulnerable margins of the foot. Semicompressed adhesive felt
padding may be used to divert pressure, especially from small
ulcers in neuropathic feet. The most efficient way to redistribute
plantar pressure is to use a total contact cast (treatment of
choice for indolent neuropathic ulcers), a prefabricated cast
such as Aircast, or a Scotchcast boot.
If casting techniques are not available, temporary shoes with
a cushioning insole can be supplied. When the neuropathic
ulcer has healed, the patient should be fitted with a cradled
insole and bespoke shoes to prevent recurrence. Occasionally,
extra-deep, “off the shelf” orthopaedic shoes with flat
cushioning insoles may suffice in the absence of areas of very
high pressure.
As ulcers in neuroischaemic feet usually develop around the
margins of the foot, a shoe bought from a high street shop may
be adequate provided that the shoe is sufficiently long, broad,
and deep and fastens with a lace or strap high on the foot.
Alternatively, a Scotchcast boot or a wide-fitting, off the shelf
shoe may be suitable.
Top: Shoe with no proper
fastening and with a narrow toe
box (left); red marks on toes
after wearing unsuitable shoes
(right). Left: New ischaemic
ulcers resulting from bullae on
lateral margin of foot
The ulcer should be cleansed and dressed with an
appropriate dressing (see ninth article in this series)
Left: Ischaemic ulcer with halo of thin glassy callus. Right: The
halo has been cut away without causing trauma
Left: Vacuum assisted pump sponge attached to plantar aspect
of foot. Centre: Pump sponge being removed from foot.
Right: Healed wound
Top (left to right): Total contact cast;
Aircast prefabricated cast; Scotchcast
boot. Left: A suitable shoe bought in
the high street may be sufficiently
roomy to avoid pressure
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Pressure ulcer in the diabetic foot
All patients with neuropathic or neuroischaemic feet are at risk
of pressure ulcers, especially of the heel. Pressure over heel
ulcers can be off-loaded by “pressure relief ankle foot orthoses.”
This orthosis is a ready-made device that has a washable fleece
liner with an aluminium and polyproprylene adjustable frame
and a non-slip, neoprene base for walking. It is used to relieve
pressure over the posterior aspect of the heel and maintain the
ankle joint in a suitable position, thus preventing pressure
ulceration, aiding healing, and preventing deformity.
Vascular control
If an ischaemic ulcer has not shown progress in healing despite
optimum treatment, then it may be possible to do duplex
ultrasound and angiography. This should be done if any or all
of the following are present:
x An ankle brachial pressure index of < 0.5 or a damped
Doppler waveform
x A transcutaneous oxygen (reflecting local arterial perfusion
pressure) of < 30 mm Hg
x A toe pressure of < 30 mm Hg.
Duplex ultrasound and angiography may show areas of
stenoses or occlusions suitable for angioplasty. If lesions are
too extensive for angioplasty, then arterial bypass may be
considered.
Another manifestation of ischaemia is dry gangrene,
particularly in a toe. Dry gangrene usually results from severe
ischaemia secondary to poor tissue perfusion from
atherosclerotic narrowing of the arteries of the leg. Ideally, the
ischaemic foot should be revascularised and the digital necrosis
be removed surgically, but if revascularisation is not possible,
the gangrenous parts of the toes may be allowed to
“autoamputate” (drop off naturally).
Microbiological control
When an ulcer is present, there is a clear entrance for invading
bacteria. Infection can range from local infection of the ulcer to
wet gangrene. Only half of infection episodes show signs of
infection. In the presence of neuropathy and ischaemia, the
inflammatory response is impaired and early signs of infection
may be subtle.
Deep swab and tissue samples (not surface callus) should be
sent for culture without delay and wide spectrum antibiotics
given to cover Gram positive, Gram negative, and anaerobic
bacteria. Urgent surgical intervention is needed in certain
circumstances.
Pressure relief ankle/foot orthosis for
use with heel ulcers
Left: Angiogram showing occlusion of anterior tibial
artery and stenosis of tibioperoneal trunk. Right:
Post-angioplasty anterior tibial flow has been restored and
tibioperoneal stenosis dilated
Left: Necrotic fifth toe and necrotic apices of the first, third, and fourth
toes undergoing podiatric debridement. Right: Autoamputation six
weeks later, after regular debridement
Local signs of wound infection
x Granulation tissue becomes increasingly friable
x Base of the ulcer becomes moist and changes from healthy pink
granulations to yellowish or grey tissue
x Discharge changes from clear to purulent
x Unpleasant odour is present
Left: Deep ulcer with subcutaneous sloughing visible. Centre: Extent
of debridement necessary to remove all necrotic tissue down to
healthy bleeding tissue. Right: Wound has healed at 10 weeks
Indications for urgent surgical intervention
x Large area of infected sloughy tissue
x Localised fluctuance and expression of pus
x Crepitus with gas in the soft tissues on x ray examination
x Purplish discoloration of the skin, indicating subcutaneous necrosis
Left: Increased friable granulation tissue. Right: Base of ulcer has areas of
yellowish to grey tissue
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In neuropathic feet, gangrene is almost invariably wet and is
caused by infection of a digital, metatarsal, or heel ulcer that
leads to a septic vasculitis of the digital and small arteries of the
foot. The walls of these arteries are infiltrated by polymorphs,
leading to occlusion of the lumen by septic thrombus. Wet
gangrene may need surgical intervention.
Wet gangrene caused by septic vasculitis can also occur in
neuroischaemic feet, although reduced arterial perfusion due to
atherosclerotic occlusive disease is an important predisposing
factor. Gangrenous tissue should be surgically removed and the
foot revascularised if possible.
Metabolic control
Wound healing and neutrophil function is impaired by
hyperglycaemia, so tight glycaemic control is essential. Patients
with type 2 diabetes suboptimally controlled with oral
hypoglycaemic drugs should be prescribed insulin.
Hyperlipidaemia and hypertension should be treated. Patients
should stop smoking. Those with neuroischaemic ulcers should
take statins and antiplatelets. Diabetic patients with peripheral
vascular disease may also benefit from an angiotensin
converting enzyme inhibitor to prevent further vascular
episodes.
Education
Patients who have lost protective pain sensation need advice
on how to protect their feet from mechanical, thermal, and
chemical trauma. Patients should be instructed on the
principles of ulcer care with emphasis on the importance of
rest, footwear, regular dressings, and frequent observation for
signs of infection. They should be taught the four danger signs:
swelling, pain, colour change, and breaks in the skin.
Left: Vein bypass seen passing across ankle to the dorsalis pedis artery.
Centre: Infected ulcer with cellulitis. Right: Wet necrosis from infected
toe ulcer
Left: Plantar view of infection after puncture wound that
led to wet necrosis of the forefoot requiring amputation
of four toes and their adjoining metatarsal heads. Right:
Full healing of the large post-surgical tissue defect took
six months
Oral hypoglycaemic agent found
within the patient’s shoe at annual
review
Members of the multidisciplinary team
x Physician
x Podiatrist
x Specialist nurse
x Orthotist
x Dietitian
x Radiologist
x Vascular surgeon
x Orthopaedic surgeon
Further reading
x Edmonds M, Foster AVM, Sanders L. A practical manual of diabetic
foot care. Oxford: Blackwell Science, 2004.
x Bowker JH, Pfeifer MA, eds. Levin and O’Neal’s the diabetic foot. 6th
ed. St Louis: Mosby, 2001.
x Boulton AJM, Connor H, Cavanagh PR, eds. The foot in diabetes. 3rd
ed. Chichester: Wiley, 2000.
x The International Working Group on the Diabetic Foot.
International consensus on the diabetic foot. 2003 (www.iwgdf.org/
concensus/introduction.htm)
x Veves A, Giurini JM, Logerfo FW, eds. The diabetic foot. Medical and
surgical management. Totowa, NJ: Humana Press, 2002.
x National Institute for Clinical Excellence. Type 2 diabetes. Prevention
and management of foot problems. London: NICE, 2004.
(www.nice.org.uk/pdf/CG010NICEguideline.pdf)
Left: Thermal trauma from convection heater. Right: Ulceration after
use of foot spa
Successful management of diabetic feet requires the
expertise of a multidisciplinary team that provides
integrated care, rapid access clinics, early diagnosis, and
prompt treatment. Patients will need close follow-up for
the rest of their lives
Michael E Edmonds is consultant physician and A V M Foster is chief
podiatrist at the diabetic foot clinic at King’s College Hospital,
London.
The ABC of wound healing is edited by Joseph E Grey
(jeg@petravore.freeserve.co.uk), consultant physician at the University
Hospital of Wales, Cardiff, and honorary consultant in wound healing
at the Wound Healing Research Unit, Cardiff University; and by Keith
G Harding, director of the Wound Healing Research Unit, Cardiff
University, and professor of rehabilitation medicine (wound healing)
at Cardiff and Vale NHS Trust. The series will be published as a book
in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:407–10
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ABC of wound healing
Pressure ulcers
Joseph E Grey, Stuart Enoch, Keith G Harding
A pressure ulcer is defined by the European Pressure Ulcer
Advisory Panel as an area of localised damage to the skin and
underlying tissue caused by pressure, shear, or friction, or a
combination of these. Pressure ulcers are caused by a local
breakdown of soft tissue as a result of compression between a
bony prominence and an external surface.
They usually develop on the lower half of the body: two
thirds around the pelvis and a third on the lower limbs, with
heel ulceration becoming more common. Elderly people are
the most likely group to have pressure ulcers; this is especially
true for those older than 70, up to a third of whom will have
had surgery for a hip fracture. Those with spinal injuries form
another distinct group, in whom the prevalence is 20%-30%
one to five years after injury.
Most pressure ulcers arise in hospital, where the prevalence
among inpatients is 3%-14%, although it can be as high as 70%
in elderly inpatients with orthopaedic problems. The incidence
of pressure ulcers in hospitals is 1%-5%. In patients who are
confined to bed or to a chair for more than one week, the
incidence rises to almost 8%. In long term healthcare facilities
1.5%-25% of patients develop pressure ulcers. Almost a fifth of
pressure ulcers develop at home and a further fifth in nursing
homes. The prevalence of pressure ulcers in nursing homes is
not much higher than in hospitals. Pressure ulceration in
elderly patients is associated with a fivefold increase in
mortality, and in-hospital mortality in this group is 25%-33%.
Estimates of the cost of pressure ulceration to the NHS range
from £180m ($318m; €265m) to nearly £2bn a year.
Pathogenesis
The four main factors implicated are interface pressure, shear,
friction, and moisture.
When pressure of short duration is relieved, tissues
demonstrate reactive hyperaemia, reflecting increased blood
flow to the area. However, sustained high pressure leads to
decreased capillary blood flow, occlusion of blood vessels and
lymphatic vessels, and tissue ischaemia.
These changes are ultimately responsible for necrosis of
muscle, subcutaneous tissue, dermis and epidermis, and
consequent formation of pressure ulcers. An external pressure
of 50 mm Hg may rise to over 200 mm Hg at a bony
prominence, leading, with time, to deep tissue destruction,
which may not be evident on the surface of the skin. Regular
relief from high pressures in the at-risk patient is essential to
prevent pressure ulceration.
Shear force is generated by the motion of bone and
subcutaneous tissue relative to the skin, which is restrained from
moving due to frictional forces (for example, when a seated
patient slides down a chair or when the head of a bed is raised
more than 30°). In such circumstances the pressure needed to
occlude the blood vessels is greatly reduced. In elderly patients,
a reduced amount of elastin in the skin predisposes to the
adverse effects of shear.
Friction opposes the movement of one surface against
another. Frictional forces may lead to the formation of
intraepidermal blisters, which in turn lead to superficial skin
erosions, initiating or accelerating pressure ulceration. Such
This is the fourth in a series of 12 articles
Most pressure ulcers are avoidable
Supine position
Prone position
Lateral position
Heels Sacrum Elbows Scapulae Back of
head
Cheek
and ear
Acromion
process
Acromion
process
Ear
Breasts
(women)
Genitalia
(men)
KneesToes
RibsMalleous Greater
trochanter
Medial and
lateral condoyle
Common sites of pressure ulceration in individuals at risk of ulceration
Sustained
high pressure
Cell (and tissue)
death
Oedema
Increased capillary permeability
Fluid escapes
into extravascular
space
Decrease in
capillary flow
Ischaemia
capillary thrombosis,
and occlusion of
lymphatic vessels
Pathophysiology of pressure ulceration
Shear force generated—for example, when a patient slides down a bed
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forces occur, for example, when a patient is dragged across a
bed sheet or as a result of ill fitting prosthetic devices or
footwear.
An excessively moist environment caused, for example, by
perspiration, urinary or faecal incontinence, or excessive wound
drainage increases the deleterious effects of pressure, friction,
and shear. It also causes maceration of the surrounding skin,
which compounds these factors. Friction and moisture exert
their greatest effects in areas of high pressure: the effects of
friction are up to five times worse if moisture is present.
Classification
Among the various classification schemes for pressure
ulceration, the one developed by the European Pressure Ulcer
Advisory Panel (EPUAP) uses a simple, four grade classification.
No “ideal” classification system exists; the EPUAP’s grade 1
ulceration, for example, may be difficult to detect in people with
darkly pigmented skin. Eschar (dried, black, hard, necrotic
tissue) covering a pressure ulcer prevents accurate grading.
Undermining of adjacent tissue, and sinus wounds, commonly
occur and can affect grading as well as healing.
Prevention and treatment of pressure
ulcers
Risk factors
Age alone is not a risk factor; rather, it is the problems common
in elderly people that are associated with pressure ulceration.
These include hip fractures, faecal and urinary incontinence,
smoking, dry skin, chronic systemic conditions, and terminal
illness. The effects of all risk factors should be minimised
through their optimal management.
Immobility (the inability to reposition without help) and
limited activity are probably the major risk factors for pressure
ulcers and may occur for various reasons. Elderly people are
particularly prone to such problems. Sensory deficits give rise to
altered ability to perceive the pain and discomfort associated
with persistent local pressure, and this leads to reduced
frequency of repositioning.
Being confined to bed or to a chair significantly increases
the risk of pressure ulceration; appropriate pressure relieving
surfaces should be provided. Individuals with increased limb
tone (spasticity) may benefit from interventions such as
physiotherapy, muscle relaxants (for example, baclofen), nerve
block, or surgery. Care should be taken with the use of sedatives,
analgesics, and drugs that cause alteration in skin blood flow,
such as antihypertensives.
Friction forces generated—for example, when a patient is dragged across a
surface
From top left, clockwise: Grade 1 pressure ulcer over greater trochanter;
grade 2 pressure ulcers on a below-knee amputation stump due to an ill
fitting prosthesis; grade 4 pressure ulcer over the sacrum (with grade 2
pressure ulcers over buttocks); grade 3 pressure ulcer over lateral aspect of
calcaneum
Eschar covering calcaneal pressure ulcer
preventing accurate grading
Risk factors for pressure ulceration*
Acute illness—Increased metabolic rate and demand for oxygen
compromising tissues
Age—Chronic disease, cerebrovascular accident, impaired nutrition,
confined to chair or bed, faecal incontinence, fractured neck of
femur
Level of consciousness—Acute or chronic illness, medication (sedatives,
analgesics, anaesthetics)
Limited mobility or immobility—Cerebrovascular accident, spinal cord
injury (hemiparesis, paraparesis, quadriplegia), spasticity, arthritis,
orthopaedic problems (especially fracture neck of femur), patients
confined to chair or bed
Sensory impairment—Neuropathies (for example, diabetes), decreased
conscious levels, medication, spinal cord injury
Severe chronic or terminal disease—Diabetes, chronic obstructive
pulmonary disease, chronic cardiovascular disease, terminal illness
Vascular disease—Smoking, diabetes, peripheral vascular disease,
anaemia, anti-hypertensives
Malnutrition or dehydration
History of pressure damage
*Based on NICE guidelines for prevention of pressure ulcers
Classification of pressure ulcers by grade*
Grade 1—Non-blanchable erythema of intact skin. Discoloration,
warmth, induration, or hardness of skin may also be used as
indicators, particularly in people with darker skin
Grade 2—Partial-thickness skin loss, involving epidermis, dermis, or
both. The ulcer is superficial and presents clinically as an abrasion
or blister
Grade 3—Full-thickness skin loss involving damage to or necrosis of
subcutaneous tissue that may extend down to, but not through,
underlying fascia
Grade 4—Extensive destruction, tissue necrosis or damage to
muscle, bone, or supporting structures, with or without
full-thickness skin loss
*As defined by the European Pressure Ulcer Advisory Panel
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A correlation exists between the degree of malnutrition and
the extent and severity of pressure ulceration. In addition,
malnutrition slows the healing of pressure ulcers. Measures of
nutritional status predictive of pressure ulceration include a
recent decrease in body weight, decreased triceps skin-fold
thickness, and lymphocytopenia ( < 1.8x109
). Serum albumin
concentration may be used as a surrogate marker, though its
relatively long half life does not provide an accurate reflection
of nutritional status. More sensitive markers include serum
prealbumin and transferrin concentrations; testing for these,
however, is not routinely available.
Risk assessment
A systematic evaluation of risk factors will help to identify
patients at risk of pressure ulceration. These individuals should
be assessed regularly, and the risk assessment scales should be
used as an adjunct to, not a substitute for, clinical judgment.
Several risk assessment scales are currently used but vary in the
risk factors assessed. The guidelines from the UK National
Institute for Health and Clinical Excellence (NICE) state,
however, that the provision of pressure relieving devices should
also be based on cost considerations and an overall assessment
of the individual, not only on risk assessment scores.
Pressure relief
Regular inspection of the skin of patients at risk of pressure
ulcers should focus particularly on areas around bony
prominences. Excess moisture from, for example, urinary or
faecal incontinence, perspiration, or wound drainage should be
minimised. Patients confined to bed should be turned at least
every two hours, the frequency reflecting the type of support
surface used and the degree of risk.
Most patients are nursed on a standard hospital mattress.
However, those at risk may need to be nursed on a “static”
pressure relieving mattress or mattress overlay, which should
not be able to “bottom out”—that is, the mattress should not
provide less than 2.5 cm of support).
Dynamic mattresses, air-fluidised mattresses, and dynamic
overlays provide alternating pressure relief in a cyclical fashion.
They are suited to patients at high risk, including those in
whom contact of the pressure with the mattress is unavoidable,
those with very large or several ulcers, and those with
non-healing ulcers.
Direct (“kissing”) contact of bony prominences such as the
knees and ankles should be avoided by use of cushions or foam
wedges. Excess abnormal pressure on the heels should be
off-loaded using pressure relieving devices. The patient should
not be positioned on the femoral trochanter. Pressure and
friction should be minimised by maintaining the head of the
bed at less than 30° and using appropriate lifting devices rather
than dragging patients during transfer and repositioning.
When sitting in a chair or wheelchair, a patient at risk of
pressure ulcers should use a pressure relieving cushion to
reduce pressure, ensure good sitting balance, and provide
Nutritional support
x Nutritional support is critical in preventing and managing pressure
ulcers
x Patients at high risk and those with established ulceration should be
assessed and reviewed by a dietitian
x Supplementary feeding, either assisted or enteral (via a nasogastric
tube or a percutaneous endoscopic gastrostomy (PEG) tube) may
be necessary
x Supplementation with vitamins and trace elements should also be
considered
x Adequate hydration is essential
Minimum components of risk assessment scales*
x Age
x Mobility
x Activity
x Level of consciousness
x Nutrition
x Continence
x Skin status
x Illness severity
*Based on NICE recommendations, 2003
Components of three risk assessment scales*
Risk factor Norton Waterlow Braden
Mobility Yes Yes Yes
Activity Yes No Yes
Nutritional status No Yes Yes
Mental status Yes No Yes
Incontinence/moisture Yes Yes Yes
General physical condition Yes Yes No
Skin appearance No Yes No
Medication No Yes No
Friction/shear No No Yes
Weight No Yes No
Age No Yes No
Specific predisposing
diseases
No Yes No
Prolonged pressure No Yes No
Data from Flanagan M (J Wound Care 1993;2:215-8)
Left to right: Standard hospital mattress; Low tech (Repose) mattress
overlay; static mattress
Left: Dynamic mattress.
Right: Air-fluidised
mattress
Low tech (Repose) foot
protector
NICE recommendations for holistic assessment of patient
needing pressure relieving device
x Identified level of risk
x Skin assessment
x Comfort
x General health state
x Lifestyle and abilities
x Critical care needs
x Acceptability of the pressure relieving equipment to patient and
carer
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comfort. The patient should be encouraged to shift position
every 15-30 minutes. If they are unable to do this independently
they should be repositioned at least hourly. “Doughnut” or ring
cushions should not be used as they may exacerbate rather than
prevent the risk of ulceration.
Debridement and dressings
Necrotic or sloughy pressure ulcers should be debrided to
promote healing and to enable the stage of the ulcer to be
assessed accurately. Devitalised tissue can be removed at the
bedside by sharp debridement with a scalpel; local anaesthetic
may be needed. Formal surgical debridement may be necessary
for extensive grade 3 or 4 pressure ulcers. These ulcers may also
require plastic surgery to reconstruct the area. Dressings are the
mainstay of treatment of pressure ulcers. Other treatments,
including larval and vacuum assisted closure therapies, may be
beneficial (see penultimate article in the series).
Complications
All pressure ulcers will be colonised with bacteria. Only signs of
clinical infection should prompt bacterial culture to confirm the
organism and antibiotic sensitivities. Secondary bacteraemia or
septicaemia may complicate pressure ulceration, and each of
these conditions is associated with increased mortality.
Antibiotics are often started empirically, reflecting the site and
depth of the pressure ulcer. A chronic, indolent, non-healing
wound may reflect the development of underlying osteomyelitis,
the flora of which is often Gram negative or anaerobic
(treatment of infection is discussed in a later article). Rarely,
amyloidosis or malignancy may arise as a result of chronic
pressure ulceration.
The three figures on p 472 and the figure at the top of p 473 are adapted
from Grey JE, Harding KG. Principles and practice of geriatric medicine. 4th ed.
Chichester: Wiley (in press).
Stuart Enoch is research fellow of the Royal College of Surgeons of
England and is based at the Wound Healing Research Unit, Cardiff
University.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:472–5
Pressure relieving cushions
Dressing types suitable for the treatment of pressure ulcers
pressure ulcer grade
Grade Dressing type
Grade 1, minimally exuding grade 2 Semipermeable film
Low to moderately exuding, non-infected
grades 2-3
Foams
Low to moderately exuding grades 2-4 Hydrogels
Low to moderately exuding grades 3-4 Hydrocolloids
Moderate to highly exuding grades 2-4 Alginates
Moderate to highly exuding grades 2-4 Hydrofibres
Further reading
x European Pressure Ulcer Advisory Panel. Pressure ulcer prevention
guidelines. www.epuap.org/glprevention.html
x Pressure relieving devices. Clinical guidelines. 2003. www.nice.org.uk.
x Pressure ulcer management. Clinical guidelines. 2005. www.nice.org.uk
x Cherry GW, Hughes MA, Ferguson MWJ, Leaper DJ. Wound
healing. In: Morris DJ, Woods WC, eds. Oxford textbook of surgery.
2nd ed. Oxford: Oxford University Press, 2001.
x Clark RAF. The molecular and cellular biology of wound repair. 2nd ed.
New York: Plenum Press, 1998.
x Glat PM, Longaker MT. Wound healing. In: Aston SJ, Beasley RW,
Thorne CHM, eds. Grabb and Smith’s plastic surgery. 5th ed.
Philadelphia, PA: Lippincott- Raven, 1997.
x Brem H, Lyder C. Protocol for the successful treatment of pressure
ulcers. Am J Surg 2004;188(Suppl 1A):9-17.
x Brem H, Jacobs T, Vileikyte L, Weinberger S, Gibber M, Gill K, et
al.Wound-healing protocols for diabetic foot and pressure ulcers.
Surg Technol Int 2003;11:85-92.
x Cullum N, McInnes E, Bell-Syer SE, Legood R. Support surfaces for
pressure ulcer prevention. Cochrane Database Syst Rev
2004;(3):CD001735.
x Langer G, Schloemer G, Knerr A, Kuss O, Behrens J. Nutritional
interventions for preventing and treating pressure ulcers. Cochrane
Database Syst Rev 2003;(4):CD003216.
One hundred years ago
Medicine and men of letters
It is a curious fact that great writers, speaking generally, have
been no lovers of the medical profession. This is doubtless the
reason why doctors for the most part cut so sorry a figure in
literature. Scribes of all sorts take a special pleasure in girding at
them. Shakespeare, indeed, used them gently, as though he loved
them. Although the medicine of his time was a tempting subject
for the satirist, his large mind saw the nobility of its aim, which to
less penetrating and sympathetic eyes was disguised by the
poverty of its outward apparel, and divined the possibilities of
development that lay hidden in the mass of error and superstition
of which it mainly consisted. But Petrarch wrote treatises against
medicine and its professors; Montaigne laughed at them; Molière
put them on the stage as fixed figures for the scorn of time to
point its finger at; Rousseau vilified them; Voltaire is the author of
the famous saying that the healing art consists in pouring drugs
of which the physician knows little into a body of which he knows
less; and Carlyle said he might as well confide his sufferings to the
hairy ear of a jackass as to that of a physician.
Is this attitude of mind due to intellectual superiority or simply
to the conceit and egotism which are pretty constant ingredients
in the composition of genius? To the doctor all men are equal;
they are simply cases, and the case of a costermonger may be
more interesting than that of a poet or a philosopher. Yet
philosophers and poets probably think that their ailments should
be treated as exceptional because they who suffer from them are
exceptional persons. Flaubert—himself, by the way, the son of a
distinguished surgeon—is said to have hated doctors because they
treated him as a bourgeois. (BMJ 1905;i:609)
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ABC of wound healing
Traumatic and surgical wounds
David J Leaper, Keith G Harding
Management of traumatic and surgical wounds has had a
chequered history. For example, in 1346 at the Battle of Crécy,
France, foot soldiers were issued with cobwebs to staunch
haemorrhage caused by trauma. Two centuries later, the
eminent surgeon Ambroise Paré (1510-1590) rejected boiling
oil as a primary dressing after amputation, preferring a mixture
of oil of turpentine, rosewater, and egg.
Classification
Surgical incisions—Surgical incisions cause minimal tissue
damage. They are made with precision in an environment
where aseptic and antiseptic techniques reduce the risk of
infection, with the best of instruments and the facility to control
haemostasis. Penetrating trauma may involve minimal damage
to skin and connective tissue, though deeper damage to vessels,
nerves, and internal organs may occur.
Lacerations—Lacerations are caused when trauma exceeds
intrinsic tissue strength—for example, skin torn by blunt injury
over a bony prominence such as the scalp. Tissue damage may
not be extensive, and primary suturing (see below) may be
possible. Sterile skin closure strips may be appropriate in some
circumstances—for example, in pretibial laceration, as suturing
causes increased tissue tension, with the swelling of early
healing and inflammation leading to more tissue loss.
Contusions—Contusions are caused by more extensive tissue
trauma after severe blunt or blast trauma. The overlying skin
may seem to be intact but later become non-viable. Large
haematomas under skin or in muscle may coexist; if they are
superficial and fluctuant they can be evacuated with overlying
necrosed skin. Ultrasound scanning or magnetic resonance
imaging may help to define a haematoma amenable to
evacuation. Extensive contusion may lead to infection (antibiotic
prophylaxis should be considered in open wounds) and
compartment syndromes (fasciotomy will be needed to
preserve a limb).
Large open wounds—Such wounds may be left to heal “by
secondary intention” (that is, the wound heals from the base
upwards, by laying down new tissue) or with delayed skin
grafting, depending on the extent of the residual defect.
Exploration of a traumatic wound is needed if there is a
suspicion of blood vessel or nerve damage, with attention to
fractures and debridement of devascularised tissue and removal
of foreign material.
Abrasions—Abrasions are superficial epithelial wounds
caused by frictional scraping forces. When extensive, they may
be associated with fluid loss. Such wounds should be cleansed to
minimise the risk of infection, and superficial foreign bodies
should be removed (to avoid unsightly “tattooing”).
Management
Surgical wounds are made in optimum conditions with full
anaesthetic and operating theatre support; traumatic wounds
are not, and they may be associated with much more serious
underlying injury. Triage and resuscitation may be needed
before definitive wound management is started.
Although the 16th century French
surgeon Ambroise Paré could
successfully dress a wound, he felt
that only God could heal it
Wounds usually involve some loss or damage to an
epithelial surface (usually skin) but may also include
damage to underlying connective tissue, which may
occur without epithelial loss
Pretibial laceration showing treatment with sterile
skin closure strips
Types of traumatic and surgical wounds
Type of
wound Result Cause
Incision Penetrating Surgical (rarely, trauma)
Laceration Torn tissue Usually trauma
Contusion Extensive tissue
damage
Usually trauma; skin may be
intact
Abrasion Superficial epithelial Usually trauma
Combination Usually severe trauma Life threatening
In England, triage and resuscitation should be done
following the Advanced Trauma Life Support
guidelines of the Royal College of Surgeons of England
(www.rcseng.ac.uk)
This is the fifth in a series of 12 articles
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Arterial bleeding is easy to recognise—pulsatile and bright
red—provided it is overt, but if it is hidden from view (for
example, the result of a penetrating injury of the aorta) it may
lead to profound unexpected haemorrhagic shock. Early
exploration and repair or ligation of blood vessels may be
required. Venous haemorrhage is flowing and dark red, and can
be controlled by adequate direct pressure. Even large veins may
spontaneously stop bleeding after this measure. Capillary
bleeding oozes and is bright red; it can lead to shock if injury is
extensive and it should not be underestimated.
The risk of infection in traumatic wounds is reduced by
adequate wound cleansing and debridement with removal of
any non-viable tissue and foreign material. If severe
contamination is present, broad spectrum antibiotic prophylaxis
is indicated and should be extended as specific therapy as
recommended for surgical wounds that are classed as “dirty” or
when there are early signs of infection. Traumatic wounds need
tetanus prophylaxis (parenteral benzylpenicillin and tetanus
toxoid, depending on immune status). Strong evidence supports
the use of antibiotic prophylaxis and treatment for surgical
wounds that are classed as “clean contaminated” or
“contaminated.” The value of antibiotic prophylaxis in “clean”
wounds is controversial but is widely accepted in prosthetic
surgery (such as hip and knee replacement and synthetic
vascular bypass surgery).
Wounds from explosions and gunshot
When the source of the wound is high velocity (for example, an
explosion or gunshot), it causes more damage because of the
dissipation of kinetic energy (kinetic energy = Ymv2
, where m is
the mass of the bullet or shrapnel and v its velocity). In addition
to gross skeletal injury, soft tissues (such as muscles of the thigh)
develop cavitation ahead of the bullet track. These tissues are
rendered ischaemic and there may be a large exit wound.
Behind the missile there is a sucking action that deposits
clothing or dirt in the wound. Together with ischaemia, this
contamination provides an ideal culture medium for anaerobic
organisms (such as Clostridium perfringens, which can lead to gas
gangrene).
These wounds need extensive debridement down to viable
tissue and should be left open until healthy granulation tissue has
formed; repeated debridement may be necessary. Even after
extensive debridement, infection may develop, requiring
antibiotic treatment. Where there is doubt or an obvious crush
injury, fasciotomy can prevent systemic complications, including
infection. After debridement, delayed primary or secondary
suturing may be done, with or without reconstructive surgery (see
eighth article in this series). Alternatively, if the combination of
wound contraction and epithelialisation will leave an acceptable
cosmetic appearance, a wound may be left to heal by secondary
intention. Human and animal bites are traditionally managed in
this way, but primary closure can be done after wound
debridement and excision of non-viable tissue.
Methods of wound closure
For primary closure, the technique of closure, the suture
material, and the type of needle or appliance all need to be
considered.
Various suturing techniques exist. Skin may be closed with
simple or mattress sutures using interrupted or continuous
techniques. Knots should not be tied tightly, to allow swelling as
a result of inflammation and to prevent necrosis at the skin
edge. Mattress sutures ensure optimal eversion at the skin edge
and appose deeper tissue, reducing the risk of formation of
haematoma or seroma. The subcuticular suture is the most
widely favoured technique for closing surgical skin wounds and
A tourniquet is rarely needed in traumatic bleeding—
control by direct pressure prevents irreversible
ischaemia and nerve damage
Categories of surgical wounds
Category Example
Recommendation
for antibiotics
Clean Hernia, varicose veins, breast None
Prosthetic surgery: vascular,
orthopaedic implants
Prophylaxis
Clean
contaminated
Elective cholecystectomy Prophylaxis
Contaminated Elective colorectal
operations
Prophylaxis
Dirty Drainage of abscess Treatment if spillage
Faecal peritonitis Treatment
Bomb blast and gunshot injuries should not be
sutured—primarily because of the high risk of infection
Streptococcal cellulitis complicating a leg wound (wound not shown)
Wounds to consider for open management
x Severe contamination (during laparotomy for faecal peritonitis)
x Old laceration ( > 12-24 hours; depends on amount of contusion)
x Shock (of any cause but usually haemorrhagic)
x Devitalisation (local poor tissue perfusion)
x Foreign body (either external or known dead tissue)
x Kinetic energy (in wounds caused by explosions; implies presence
of dead tissue and foreign material)
Interrupted
simple
Continuous
simple
Continuous
blanket
Interrupted and
continuous
horizontal
mattress
Interrupted
longitudinal
mattress
Halsted's stitch Left: Suture techniques in skin. Top right:
Simple and mattress closure. Bottom
right: Subcuticular closure
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has good cosmetic results. Arterial anastomoses and
arteriotomies are closed to ensure eversion, but gut anastomosis
conventionally has an inverted suture line.
The ideal suture material for a particular wound remains
controversial. Sutures that are absorbable (for example,
polyglactin or polydioxanone) clearly do not require removal.
Catgut should no longer be used as it causes an excessive tissue
reaction, which may predispose to infection. Such reactions are
less likely to occur with the use of synthetic polymers.
Non-absorbable sutures (for example, natural silk or synthetic
polymers such as nylon or polypropylene) need removal. The
monofilament polymers cause minimal tissue reaction and are
least likely to lead to secondary (exogenous) infection. Silk can
cause an intense tissue reaction, with an increased risk of
excessive scarring and of formation of a suture abscess; silk is
therefore no longer recommended.
Metal clips and staples are alternatives to conventional
suturing. Despite their need for removal, they are associated
with good cosmetic results and low infection rates. Disposable
applicators are expensive but allow rapid closure of long
wounds after prolonged surgical procedures. Some stapling
devices are sophisticated and allow safer surgery—for example,
for very low coloanal anastomosis.
Adhesive strips are useful for closing superficial wounds. In
emergency departments a child’s forehead laceration can be
closed without anaesthetic or tears. They allow for wound
swelling and are associated with low infection rates. Adhesive
polyurethane film dressings have a similar effect with sutured
wounds and provide a barrier to infection. The methacrylate
superglues are widely used for skin closure, particularly with
scalp wounds (though surrounding hair should be trimmed
first). Fibrin glues are relatively expensive but allow rapid
closure.
Modern suture materials are presented in sterile, single use
packets. Sutures are bonded on to hollow needles. Dispensing
with the eye of the needle results in a “shoulderless” needle,
permitting easier passage through, and less disruption of,
tissues.
Suture removal depends on the wound site. The role of
dressings to cover sutured wounds remains controversial.
Polyurethane dressings allow inspection and provide a bacterial
barrier. Island dressings allow absorbance of wound exudate
and lessen the risk of leakage.
Left: Final appearance of subcuticular closure with polypropylene closure.
Right: Final appearance of subcuticular closure with polyglactin closure
Left: Incision of neck closed with skin clips. Right: X ray showing stapled
low anterior resection: the gastrografin enema shows no leakage from the
anastomosis
Polyurethane film dressing over a wound after
subcuticular closure
1/4 circle 3/8 circle 1/2 circle
5/8 circle
1/2 curved
J needle
Compound
curve
Straight
Shapes of needle used in surgical and traumatic wound closure
Cutting needles for stitching skin
Round bodied needles for
peritoneum, muscles, and fat
Needles used for suturing the
abdominal wall
Cutting needles for aponeurosisCross
section
Needles used for suturing the bowel
The threads are swaged into the needles
Cross
section
Cross
section
Types of needles used for different surgical procedures. Straight needles and all hand needles are no longer recommended as they have an added risk of
causing needle stick injury and the passage of viruses through body fluids. Instrument mounted needles or, when appropriate (as in closure of abdominal
fascia), blunted needles should be used
Time to removal of non-absorbable sutures
Site of sutures No of days
Scalp and face 3-4
Upper limb 7
Lower limb 7-10
Trunk 10-14
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Hidradenitis suppurativa and pilonidal sinus wounds
Hidradenitis, an infection of apocrine sweat glands, affects
armpits and groins; pilonidal sinus, a tissue infection caused by
ingrowing hair, mainly affects the natal cleft.
Failed, repeated drainage of the abscesses requires complete
excision. The defect usually heals by secondary intention.
Initially, excision wounds are usually dressed with polymeric
foam. Once the wound has reduced in size, a topical
antimicrobial dressing (such as those that contain iodine or
silver) may be used. However, grafts or flaps are also used, either
as the primary treatment or for non-healing wounds. These
wounds often become infected and require prolonged
treatment to cover Gram positive and anaerobic organisms.
The picture of Ambroise Paré is published with permission from TopFoto.
David J Leaper is visiting professor of surgery at the Wound Healing
Research Unit, Cardiff University, Cardiff.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: DJL has received an educational grant for his
research group from Merck Sharp and Dohme and had expenses and a
fee paid by Ethicon for attending an advisory panel and for the making of
an educational film. For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:532–5
Excision wound in
hidradenitis suppurativa
Further reading
x Téot L, Banwell PE, Ziegler UE, eds. Surgery in wounds. Berlin:
Springer, 2004.
x Leaper DJ, Harding KG, eds. Wounds. Biology and management.
Oxford: Oxford Medical Publications, 1998.
x Bales S, Harding K, Leaper DJ. An introduction to wounds. London:
Emap Healthcare, 2000.
x Leaper DJ, Harding KG, Phillips CJ. Management of wounds. In:
Johnson C, Taylor I, eds. Recent advances in surgery. 25th ed. London:
Royal Society of Medicine, 2002.
x Leaper DJ, Low L. Surgical access: incisions and the management
of wounds. In: Kirk RM, Ribbons WJ, eds. Clinical surgery in general.
4th ed. Edinburgh: Churchill Livingstone, 2004.
x Leaper DJ. Basic surgical skills and anastomoses. In: Russell RCG,
Williams NS, Bulstrode CJK, eds. Bailey and Love’s short practice of
surgery. 24th ed. London: Arnold, 2004.
When I use a word
The very last word
What is the last word in the dictionary? Easy to answer, you might
think. But there is a problem. We talk blithely about “the
dictionary,” as if there was only one. But there are many, even
among monolingual dictionaries of English. And they don’t all
end with the same headword.
Samuel Johnson’s dictionary (1755) ends with zootomy,
“dissection of the bodies of beasts.” Not a great effort, but then he
wasn’t going for broke. Collins English Dictionary (sixth edition)
makes a better stab: Zyrian, the language spoken by the people of
the Komi, in the erstwhile Soviet Union. Zyrian belongs to that
curious group of languages, the Finno-Ugric (one of two
branches of Uralic, the other being Samoyed). Its main members,
despite the geographical divide, are Finnish and Hungarian; it
also includes Estonian, Vogul (or Khanti), Ostyak (or Mansi), and
the language of Sibelius’s Karelia.
The Chambers Dictionary (new ninth edition, 2003) does better
still: zythum, a kind of barley beer brewed by the ancient
Egyptians and others, from the Greek word zuthos (beer). And a
zythepsary is a brewery, got by adding hepsein (to boil). Hepsein
also meant to smelt metals and to digest food, reminiscent of
another Greek word, pepsis, meaning digestion or fermentation.
And the yeast in zythum was called zyme, which gives us enzyme,
a word that the Heidelberg physiologist Wilhelm Kühne
introduced in 1877 to describe substances such as pepsin.
The Oxford English Dictionary (second edition) takes us further
still: zyxt, which turns out to be, wait for it, an obsolete Kentish
form of the second person singular present indicative of see. In
other words, zyxt is “seest [thou].”
Now the OED is pretty comprehensive, but Philip Gove’s
controversial Webster’s Third New International Dictionary (1961)
went one better: zyzzogeton, a genus of large American
leaf-hoppers having the pronotum tuberculate and the front
tibiae grooved (well that’s what the dictionary says).
No dictionary that I’ve seen has another candidate: zyzzya, from
Zyzzya fuliginosa, a marine sponge found in the South Seas. It
contains pyrroloiminoquinone alkaloids belonging to the
makaluvamine family, which inhibit the enzyme topoisomerase II
and so produce a cytotoxic action by cleavage of DNA. And
zyzzyposide (modelled on etoposide) would be a great name for
an anticancer drug.
However, this is trumped by The American Heritage Dictionary of
the English Language (fourth edition, 2000), which has unearthed
zyzzyva, any of various tropical American weevils of the genus
Zyzzyva, and by The Random House Unabridged Dictionary (1997)
with Z-zero particle, one of three particles, intermediate vector
bosons, that are thought to transmit the weak nuclear force.
Finally, turn to Mrs Byrne’s Dictionary of Unusual, Obscure and
Preposterous Words (yes really) of 1974. Mrs Byrne, a concert
pianist and composer, was Jascha Heifetz’s daughter, Josefa, so it
is not perhaps surprising that the last word in her dictionary is
musical: zzxjoanw, pronounced ziks-jo’-un and defined as a Maori
drum. But anyone with the least smattering of Maori would look
suspiciously at those zeds, the ex, and the jay. Here’s a sample of
the real thing, from the famous haka: “ Tenei te tangata
puhuruhuru nana mei i tiki mai whakawhiti te ra.” Zzxjoanw can’t
be Maori. In fact, it turns out (Word Ways, November 1976) to
have been invented by Rupert Hughes for inclusion in his Music
Lovers’ Encyclopedia of 1914, where he says that it is pronounced
“shaw” and means “1. Drum. 2. Fife. 3. Conclusion.”
To which one the only possible concluding response is “Pshaw,”
followed by a bout of heavy zzzz-ing.
Jeff Aronson clinical pharmacologist, Oxford
(jeffrey.aronson@clinpharm.ox.ac.uk)
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ABC of wound healing
Uncommon causes of ulceration
Girish K Patel, Joseph E Grey, Keith G Harding
This article describes some of the many rare causes of
ulceration. Rare causes that are more common in developing
countries—such as leprosy, fungal infections, Buruli ulcer, and
ulceration resulting from Kaposi sarcoma—are not covered
here.
Inflammatory disorders
Inflammatory disorders can lead to ulceration or impair healing
directly or through the effect of medication used to treat the
disorder; ulceration is a feature of many connective tissue
diseases. For example, ulceration develops in up to 10% of
patients with rheumatoid arthritis and is often painful. In
addition to the underlying disease, impaired healing can result
from anaemia, skin atrophy, dependent oedema, deformity,
neuropathy, microvascular disease, local factors, or the toxic
effects of drugs used in its treatment. Other associated
conditions such as vasculitis or pyoderma gangrenosum may
also lead to ulceration.
Ulceration in rheumatoid arthritis is usually of rapid onset
or enlargement, associated with pain (not relieved by raising or
lowering the leg), fever, malaise, arthralgia, and myalgia. The
ulcer may be multifocal and/or have an atypical location, tender
margin, and/or a violaceous or erythematous inflammatory
border.
Pyoderma gangrenosum
Pyoderma gangrenosum is characterised by the appearance of
lesions at the site of trauma (for example, venepuncture).
Surgical debridement of pyoderma gangrenosum often leads to
a worsening of the ulceration. The diagnosis of pyoderma
gangrenosum is primarily clinical but may be associated with
specific features on histology. The patient often has a history of
a painful sterile pustule or nodule with surrounding erythema,
which eventually ruptures and ulcerates. The ulcer has a
characteristic erythematous or violaceous overhanging edge.
The wound bed is often purulent and may extend to muscle.
Over half of cases of pyoderma gangrenosum are associated
with underlying active or quiescent systemic disease; these
include inflammatory bowel disease, seronegative rheumatoid
arthritis, and lymphoproliferative diseases. Treatment of
pyoderma gangrenosum is usually with immunosuppressants.
Necrobiosis lipoidica
Necrobiosis lipoidica commonly presents as a pretibial
yellowish atrophic plaque. It is often associated with diabetes
mellitus and has a propensity to ulcerate, usually as a result of
minor trauma. Typically, such ulceration is slow to heal, painful,
and often complicated by infection. In most cases the ulceration
Cutaneous necrosis
Blood flow
Vessel intima
Blood constituents
Common causes
Venous hypertension
Peripheral arterial disease
Diabetic foot ulceration
Inflammatory disorders
Connective tissue disease
Skin disease
Ulceration
Neuropathic
disease
Malignancy Metabolic Infection Iatrogenic Factitious
or non-
accidental
injury
Causes of ulceration, according to typical clinical presentation
Rheumatoid arthritis on dorsum of foot
with exposed tendon, and over medial
malleolus; such ulcers have a smooth,
irregular margin
Treatment of ulceration related to connective tissue
disease may require immunosuppressants, including
steroids and/or cytotoxic agents
Pyoderma gangrenosum over
posterior gaiter area of leg (note also
allergy to dressing on surrounding
skin)
Necrobiosis lipoidica
complicated by ulceration in
centre
This is the sixth in a series of 12 articles
Connective tissue disease associated with ulceration
x Rheumatoid arthritis
x Systemic lupus erythematosus
x Dermatomyositis
x Systemic sclerosis
x Sjögren’s syndrome
x Behçet’s syndrome
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will heal with good wound care and the use of potent topical
corticosteroids to the surrounding lesion.
Skin necrosis
Skin necrosis is a manifestation of tissue death that occurs as a
consequence of rapid ischaemia, often due to vessel occlusion.
The pattern and extent of necrosis varies according to the size
of the vessels affected. In the 1860s, Rudolf Virchow proposed
that thrombus formation is attributable to a change in three
components: blood flow, the vessel intima, and blood
constituents. This proposal (Virchow’s triad) provides a useful
framework to consider the causes of skin necrosis.
Blood flow
Rapid reduction in local blood flow that may arise from an
embolic event, severe chilblains, and Raynaud’s phenomenon
can present with dramatic digital necrosis. All patients with
Raynaud’s phenomenon should be advised not to smoke
cigarettes and to reduce caffeine intake. Both primary and
secondary Raynaud’s phenomenon may respond well to
conservative measures, including cold avoidance and treatment
with a long acting calcium channel antagonist or another oral
vasodilator. Topical vasodilators—for example, glyceryl
trinitrate—may also be of benefit. In severe chronic disease,
cervical sympathectomy can be done; in severe acute
necrotising disease, infusions with prostaglandin E1 or
epoprostenol (prostacyclin) can save digits.
Vessel intima
Calciphylaxis is characterised by painful, haemorrhagic skin
necrosis with a reticulate edge. Skin histology shows vessel
intramural hyperplasia, intravascular calcification, and
thrombosis. Calciphylaxis most often occurs in patients with
renal failure who are having dialysis or patients with
hyperparathyroidism, or idiopathically. Treatment consists of
analgesia, removal of calcium deposits at the site of any
ulceration, and control of predisposing factors.
Almost all types of vasculitis can present with skin necrosis.
In some cases, such as Wegener’s granulomatosis and classic
polyarteritis nodosa, they can be a cause of chronic ulceration.
Vasculitis is classified according to the size of vessel affected.
Medium sized vessel vasculitis presents with painful nodules
that may ulcerate. Small vessel vasculitis typically presents with
palpable purpura.
Blood constituents
Several coagulation factors are associated with skin necrosis and
are due either to genetic or acquired alteration in function.
Some syndromes are also associated with hypercoagulability.
Antiphospholipid syndrome is a heterogeneous group of
disorders characterised by the presence of autoantibodies
against various phospholipids, including lupus anticoagulant
and anticardiolipin. The disorder affects mostly females and
may be associated with systemic lupus erythematosus.
Antiphospholipid syndrome may present as a cause of multiple
arterial and venous thrombotic episodes, recurrent spontaneous
abortions, and the presence of livedo reticularis.
Antiphospholipid syndrome is a cause of livedoid vasculopathy,
a disorder characterised by painful ulceration in association
with livedo reticularis and atrophie blanche. Livedoid
vasculopathy has also been described as being associated with
factor V Leiden mutation. This progressive, painful, and
debilitating disease requires anticoagulation, plus drugs to treat
the underlying disease.
Topical PUVA (psoralens and ultraviolet A) therapy may
also have a role in necrobiosis lipoidica
Ulcerations due to Raynaud’s phenomenon over proximal interphalangeal
joint of index finger (associated with infection) and over distal
interphalangeal joint of middle finger
Left: Calciphylaxis showing calcium deposits in base of ulcer. Right: X ray of
same patient showing extensive subcutaneous calcification
Causes of vasculitis, classified according to size of vessel
affected*
Large vessel Medium vessel Small vessel
Giant cell
(temporal)
arteritis
Classic polyarteritis
nodosa
Wegener’s granulomatosis;
Churg-Strauss syndrome;
microscopic polyangiitis
Takayasu’s
arteritis
Kawasaki disease Henoch-Schönlein
purpura; essential
cryoglobulinaemic
vasculitis; cutaneous
leukocytoclastic angiitis
*Chapel Hill consensus conference, 1992.
Abnormalities of coagulation factors associated with skin
necrosis
x Protein C deficiency
x Protein S deficiency
x Antithrombin 3 deficiency
x Heparin cofactor 2 deficiency
x Homocystinaemia
x Raised prothrombin concentrations
x Factor 12 deficiency
x Factor V Leiden mutation
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Warfarin necrosis is an uncommon transient phenomenon,
which occurs at the start of warfarin treatment in the absence of
heparin. The condition affects mostly females, and individuals
are usually in their 50s or 60s. It typically involves sites
abundant in subcutaneous fat, such as breasts, hip, buttock, and
thigh. The use of warfarin results in a transient decrease of
vitamin K sensitive factors, including protein C, resulting in a
temporary hypercoagulable state, which spontaneously corrects
itself. Warfarin should therefore be continued.
Heparin necrosis is rare and may be caused by both
unfractionated and low molecular weight heparin. It is
associated with the formation of antibodies, leading to platelet
clumping. The continued use of heparin leads to greater
platelet clumping and emboli affecting both cutaneous and
internal organs. Skin necrosis occurs at injection and distant
sites. Heparin aggravates the condition, with potentially fatal
consequences, so it should be stopped immediately.
Malignancy
Many types of cancers, including metastases, present with skin
ulceration, including the commonest forms of skin cancer, basal
cell carcinoma, and squamous cell carcinoma. Although the
incidence of squamous cell carcinoma increases with age, it may
present in younger individuals with a genetic predisposition or
with a history of excessive exposure to ultraviolet light, of organ
transplantation, or of immunosuppressants (such as ciclosporin).
Squamous cell carcinoma may also develop in longstanding
chronic ulceration associated with burns, scalds, radiotherapy, or
venous disease (Marjolin’s ulcer). Features indicative of
malignancy include rapid enlargement of the lesion despite
conventional treatment; pain; bleeding; and often a rolled edge.
Squamous cell carcinoma arising in longstanding chronic ulcers
can exhibit a more aggressive phenotype, with a greater
potential to metastasise. In most cases of lower leg skin cancer
the preferred treatment is surgical excision. However, in cases of
substantial comorbidity or disseminated metastatic disease,
palliative treatment (radiotherapy and local wound care) may be
more appropriate.
Drug and iatrogenic causes
Hydroxycarbamide (hydroxyurea), used to treat
myeloproliferative diseases, may cause a painful, shallow, lower
leg ulcer, usually over the medial malleolus, up to 15 years after
start of treatment. Healing is normally only achieved when
hydroxycarbamide is discontinued.
Radiotherapy, used to treat benign and malignant diseases,
is associated with an endarteritis that may result in ulceration
and impair wound healing. Furthermore, after radiotherapy the
skin is at risk of ulceration as a result of chronic radiation
dermatitis, allergic contact dermatitis, squamous cell carcinoma,
and angiosarcoma.
Factitious
Factitious wounds and non-accidental injury can also present as
atypical wounds. Often the patient’s history is incongruent with
the clinical appearance of the wound. Further clues can be
gained from the pattern of the lesion and from a skin biopsy
(useful for excluding disease and for identifying the presence of
foreign material). Occasionally, admission to hospital is
necessary to verify the diagnosis. The management of such
cases invariably relies on a multidisciplinary approach involving
a liaison psychiatrist.
Purpura fulminans includes three different syndromes
(neonatal; associated with sepsis; and postinfective)
associated with widespread capillary and venule
thrombosis that present as purpura and skin necrosis.
Skin necrosis favours the extremities, particularly the
digits. Purpura fulminans is a complication of either
hereditary or acquired protein C or protein S deficiency
Infection
x -haemolytic Streptococcus pyogenes and Staphylococcus aureus are
responsible for many of the infections that can complicate existing
ulceration
x They may also in certain circumstances be the cause of ulceration.
-haemolytic streptococcus may lead to erysipelas, bullous cellulitis,
punched out ulceration (ecthyma) and necrotising fasciitis
x When the patient has a history of foreign travel, then Leishmania,
atypical mycobacterium, and deep mycotic infection should also be
considered as causes of ulceration
x In patients with AIDS or other immunosuppressive states,
ulceration may indicate infection with syphilis, tuberculosis,
bacillary angiomatosis, herpes simplex, or cytomegalovirus
infection
Left: Basal cell carcinoma presenting over medial aspect of knee; note
evidence of biopsy of centre of lesion and orange coloration (due to
dressing containing iodine). Right: Florid, ulcerating, necrotic squamous
cell carcinoma of lower leg
Marjolin’s ulcer—a squamous cell
carcinoma arising as a complication
of longstanding venous leg ulceration
Further reading
x Enoch S, Kupitz S, Miller DR, Harding KG. Dystrophic calcification
as a cause for non-healing leg ulcers. Int Wound J 2005;2:142-7.
x Enoch S, Miller DR, Harding KG, Price PE. Early diagnosis is vital
in the management of squamous cell carcinomas associated with
chronic non-healing ulcers: a case series and review of the
literature. Int Wound J 2004;1:165-75.
x Rovee DT, Maibach HI. The epidermis in wound healing. Boca Raton,
Fl: CRC Press, 2003.
x Falanga V, ed. Cutaneous wound healing. London: Martin Dunitz,
2001.
x Leaper DJ, Harding KG, eds. Wound: biology and management.
Oxford: Oxford Medical, 1998.
Girish K Patel is research fellow in wound healing and honorary
clinical tutor in dermatology, Cardiff University and Cardiff and Vale
NHS Trust.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:594–6
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ABC of wound healing
Burns
Alex Benson, William A Dickson, Dean E Boyce
About 250 000 people are burnt each year in the United
Kingdom. Of these, almost 112 000 attend an accident and
emergency department and about 210 die of their injuries. At
least 250 000 others attend their general practitioner for
treatment of their injury. A burn results in loss of epidermal
integrity of the skin; this article discusses the aetiology and
management of various types of burn injury.
Mechanisms of burn
Thermal injury
Flame—Accelerants such as petrol, lighter fluid, or natural
gas are often involved. The depth of flame burn is typically full
or partial thickness.
Scald—60% of burns in children are from scalds.
Non-accidental injury is rare but should be considered if there
are delays in presentation, inconsistencies in history, or an
unusual pattern of injury.
Contact—Contact burns often present as small burns on
extremities, but they can be serious in those not able to remove
themselves from the source of injury, such as elderly people,
children, disabled people, and those incapacitated by drugs,
alcohol, fit, or faint.
Flash—Flash burns are usually to the face and upper limbs
and are caused by an explosive ignition of a volatile substance.
They are often due to use of accelerants to light a fire or gas
explosions.
Electrical injury
Low voltage—The energy imparted from 240 V usually gives
a deep burn in the form of a small entry and exit wound. Such
burns are commonly seen on the hands. If alternating current
crosses the myocardium, arrhythmias may arise. If the
electrocardiogram is normal and there is no history of loss of
consciousness, admission to hospital for cardiac monitoring is
not required.
High voltage—High tension burns occur with an injury
resulting from 1000 V or more. These catastrophic injuries
result in extensive tissue damage. Rhabdomyolysis and renal
failure may occur.
Flash—An arc of high tension current from a high voltage
power source may cause injury, without the current traversing
the body. Heat can damage exposed skin, and clothing may
ignite.
Chemical injury
Acids—Acids cause coagulative necrosis, denature proteins,
and are usually painful. Hydrofluoric acid penetrates tissues
deeply and can cause fatal systemic toxicity even in small burns.
Immediate copious lavage and treatment with topical calcium
gluconate gel is essential. Systemic calcium may be required as
hydrofluoric acid sequesters calcium with the burn.
Alkalis—Common household alkalis such as bleaches,
cleaning agents, and cement give a liquefactive necrosis. They
have the potential to penetrate tissues deeper than most acids
as further injury occurs as cells dehydrate and collagen and
protein are denatured. Often the onset of pain is delayed, thus
postponing first aid and allowing more tissue damage.
Aetiology of burn injuries (percentage)
Adults
x Flame (48)
x Scalds* (33)
x Contact (8)
x Electrical (5)
x Chemical (3)
x Friction (2)
x Sunburn (1)
Paediatric
x Scalds (60)
x Flame (25)
x Contact (10)
x Electrical (2)
x Chemical (2)
x Sunburn (1)
Adapted from UK manual for “Emergency Management of
Severe Burns” course. See “protocol” box next page
*Oil and water.
Clockwise from top left: Full thickness flame burn to the right arm,
torso, and face and neck (not shown); “pull over” scald (hot tea) to a
toddler; flash burn and erythema to face (note sparing of skin creases);
full thickness contact burn (patient was alcoholic and fell unconscious
against a portable heater)
Low voltage (240 V) electrical
burns to the finger pulps
Left: Cement burns to the dorsum of the toe. These burns may initially be
deemed superficial; persistence of the alkali within the skin can cause a
progressive full thickness burn. Right: Full thickness caustic soda burn
This is the seventh in a series of 12 articles
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Burn assessment
The severity of burn injuries is related to the depth of skin
involvement and the percentage of total body surface area
involved.
In the United Kingdom burns are classified as partial
thickness or full thickness, as these terms correspond to the
level of burn injury and the likelihood of healing without
surgical intervention.
Partial thickness burns are further categorised as superficial
or deep dermal. Superficial burns usually heal without surgery,
but deeper burns are likely to require excision and skin grafts.
Burn depth can progress without adequate first aid and
treatment such as appropriate fluid resuscitation and dressings.
Burn depth can be worsened by the presence of infection.
Superadded infection may lead to an increase in burn depth.
Classification of burn depth
Superficial burns
These usually heal within 14 days and leave minimal scarring.
Burn erythema may be described as skin redness and pain.
Erythema is not included in the assessment of the percentage of
total body surface area. With superficial dermal burns the outer
part of the dermis is injured; these burns characteristically have
blisters and are very painful.
Deep burns
These take a prolonged time to heal and do so with severe
scarring. All but the smallest areas of full thickness burn require
surgical intervention. In deep dermal burns the skin has fixed
capillary staining and has blotchy cherry red appearance. It
does not blanch with pressure and is typically insensate. Full
thickness burns have a leathery white or charred black
appearance (eschar). In people with dark skin, parameters other
than skin colour may need to be used.
Management of burn injuries
First aid
The person should be removed from the burning source
without endangering the rescuers. If clothing is alight, follow
the “drop and roll” procedure. When electricity is involved,
power should be turned off before administering first aid.
The burn should be cooled (or the toxin diluted) with
lukewarm running water for at least 20 minutes. This period
should be increased in those with chemical injury. Ice or very
cold water should be avoided, as blood flow to the affected area
will be reduced, and hypothermia induced, particularly in
infants and elderly people.
Patients are assessed and their treatment priorities
established on the basis of the severity of their injuries The
history of events leading to the burn will also alert those
treating the patient to the risks of coexisting injury. Inhalation
injury is potentially life threatening when burns have been
sustained in enclosed areas.
A Lund and Browder chart is useful in assessing the extent of
burn injury (the relative proportions of body areas differ in
children)
Top: Superficial dermal scald
(top). Bottom: Burn injury of
different depths (FT= full
thickness; DD = deep dermal;
SD = superficial dermal)
Indicators of depth of burn injury
Burn type Skin colour Blisters Capillary refill Sensation Pinprick Healing
Epidermal Red Absent Brisk Painful Bleeds Yes
Superficial dermal Pale pink Present (small) Brisk Painful Bleeds Yes
Mid-dermal Dark pink Present Slow May be painful Bleeds Usually
Deep dermal Dry blotchy red May be present Absent No pain No bleeding No
Full thickness Dry white/black Absent Absent No pain No bleeding No
The “drop and roll” procedure: get the person to drop
to the ground then help them to roll over to extinguish
the flames from burning clothing (the use of a wet
blanket may help)
Protocol for managing burn injuries*
A = Airway and cervical spine control
B = Breathing and ventilation
C = Circulation and haemorrhage control
D = Disability
E = Exposure and environmental control
F = Fluid resuscitation
*According to guidelines advocated in the course “Emergency Management of
Severe Burns,” run by the British Burn Association
(www.britishburnassociation.co.uk)
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Simple analgesia or opiates should be used. Covering the
burn and cooling with water will also provide some pain relief.
Dressings
Polyvinyl chloride sheeting (“clingfilm”) or sterile cotton
sheeting may be used initially. These are simple to use and allow
wound inspection so that definitive assessment can be
performed. Sterile burn cooling gels are also available.
Minor burn injury
Debridement
Burn debris should be removed with mild soap and water,
sterile saline, or a topical antiseptic solution before dressings are
applied. The dead skin of open blisters should be removed, and
large or friable blisters should also be “deroofed” (the outer
layer removed). Small blisters may be left intact. Antibiotics are
not routinely prescribed in minor burns. The tetanus status of
the patient should be checked.
Dressings
In the simple, clean, partial thickness burn, dressings such as
paraffin gauze (for example, Jelonet), chlorhexidine
impregnated gauze (Bactigras), or similar dressings such as soft
silicone (Mepitel) or soft polymer (Urgotul) can be used with an
overlying gauze pad. Hydrocolloid dressings are particularly
good for use on hands and other small areas of superficial or
partial thickness burns, although they leave a “skim” of exudate
that needs to be removed to allow appropriate assessment of
the wound. In bigger burns, several layers of dressing are usually
required to absorb exudate and to prevent shear or friction of
the skin.
Dressings such as alginate adhere to the wound and should
be reviewed after 24 hours. At this point only the secondary
dressing immediately overlying the alginate needs to be
replaced. Once the wound is healed, the alginate separates off.
If there is excessive exudate or a full thickness burn, the
dressing fails to stick, indicating the necessity for further
assessment. These properties also make alginate dressings
useful for donor sites after skin graft harvest.
Major burn injury
A major burn should be managed according to the guidelines
advocated in the British Burn Association’s Emergency
Management of Severe Burns course. Transfer of these patients
needs careful planning and communication with the burns
team. In a patient with multiple injuries, the most obvious injury
may be their burn, but careful assessment and treatment of
other injuries is vital before burn management. All patients with
facial burns or suspected of having inhaled smoke or hot gases
should be assessed by an anaesthetist before being transferred
to a specialist unit , as early intubation may be required.
Deep or full thickness burns make the skin inelastic and act
like a tourniquet. They should be released by escharotomy to
prevent respiratory embarrassment (of the chest and abdomen)
or vascular compromise of the limbs. This may need to be done
before transfer to a specialist unit.
Fluid resuscitation is indicated after a serious burn ( ≥ 10%
of total body surface area in children and ≥ 15% in adults). The
British Burn Association recommends the use of the Parkland
formula, but intravenous fluids should also be guided by the
patient’s response to resuscitation.
Surgical debridement of the major burn is influenced by the
fitness of the patient to undergo a procedure and the depth and
location of the burn. Excision of the burn may be required.
Reconstruction is often done with split skin grafts taken from
the patient in single or multiple stages. This may be combined
All burns are susceptible to infection. Silver based
products have traditionally been used to treat burns,
including silver sulfadiazine (Flamazine) and silver
sulfadiazine plus cerous nitrate (Flammacerium)—the
latter available only on a named patient basis in the UK.
However, the use of these preparations makes
subsequent assessment difficult. Ideally, they should not
be applied without discussion with the burns team
Criteria for referral to a burns centre
x Associated airway injury
x Partial thickness burns < 5% of total body surface area in a child
x Partial thickness burns < 10% of total body surface area in an adult
x < 1% full thickness burn
x Partial or full thickness burns to face, perineum, external genitalia,
feet and hands, and over joints
x Circumferential injury
x Chemical and electrical burns
x Extremes of age
x Non-accidental injury
x Comorbidity
x Non-healed burn three weeks after injury
Repeated review of the burn wound and multiple
dressing changes are unnecessary. A change of
dressings and wound review after 48 hours is usual.
Further changes are guided by the rate of healing, but
are generally needed at intervals of two to three days.
More frequent change of dressing is needed if there is a
high volume of exudate or evidence of infection
Escharotomies to the chest to allow respiratory expansion
Fluid resuscitation guide based on Parkland formula
Calculations are guidelines only and refer to fluid required from the
time of burn injury, not the time of presentation. Volumes refer to
fluid resuscitation for the first 24 hours: half is given in the first 8
hours, and half over the subsequent 16 hours
Resuscitation formula for adults
x 3-4 ml Hartmann’s solution/kg body weight/% total body surface
area
Resuscitation formula for children
x 3-4 ml Hartmann’s solution/kg body weight/% total body surface
area, plus maintenance fluids (4% glucose in 0.25N saline or 0.2N
saline)
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with cadaveric skin if the patient has insufficient donor skin.
Artificial skin substitutes are being increasingly used with good
results (see a later article in this series). Several layers of
dressings are used to minimise shear at the site of skin grafting.
These should not be too tight as swelling often occurs after a
burn injury.
Once a burn has healed, the area should be regularly
moisturised and protected from the sun by sunblock cream or
clothing. Physiotherapy may be required to prevent burn
contractures.
Alex Benson is specialist registrar in plastic surgery in the Mersey
Regional Plastic Surgery Unit, Whiston Hospital, Liverpool. William
A Dickson is consultant burns and plastic surgeon and Dean E Boyce
is consultant hand and plastic surgeon in the Welsh Centre for Burns
and Plastic Surgery, Morriston Hospital, Swansea.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Top: Full thickness
burns of the abdomen
have been excised and
closed with split
thickness skin grafts.
Bottom: Artificial skin
substitute used to cover
full thickness burn
Prevention of burns is key: the main improvement in
reduction of burns in the UK over the past 40 years has
been the introduction of legislation to reduce the
flammability of clothing, furniture, and fireworks and
of proper labelling of inflammable materials
Competing interests: For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:649–52
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The Napsterisation of learning
At BMJ Learning, we like to think that we are creating something
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learners rather than lecturing them. But critics of BMJ Learning
would say that it is still a large compendium of learning resources
that learners must work their way through. Certainly the internet
enables us to communicate large amounts of new and easily
updated knowledge quickly and easily—but that is just using a
small part of its potential.
In 2000, just as dot com was turning into dot bomb, Shawn
Fanning founded Napster—a system whereby internet users could
share music files. It is an idea that is now changing the face of the
internet. There is no large behemoth bestowing resources or
wisdom from on high—rather it is about putting people in touch
with each other. How can this help with learning? Well, no
learning resource, no matter how big, can answer all possible
questions. Our recent module on hepatitis B gives an overview on
recent advances on how best to treat patients with this infection.
But what if you are caring for a patient with hepatitis B who also
has hepatitis C and who is intolerant of interferon and who
doesn’t like taking drugs anyway? Our learning module won’t be
able to answer such a specific question, and it is likely that no
learning resource will be able to do so. So what do you do? You
could ask your colleagues down the hall, but what if they don’t
know either?
Another option is to go online and ask a colleague. The new
discussion forum that we have added to www.bmjlearning.com
enables you to do exactly that. Like the Napster model, it is a peer
to peer system that puts end users in touch with each other.
Learners and teachers have always shared with each
other—lecture notes, presentations, quotes, etc—and a learning
forum enables you to do just that, but with thousands of potential
colleagues rather than just one. You will also get the question that
is important to you answered—rather than the question that is
important to the author.
Critics of peer to peer systems say that they can result in chaos
and that you cannot guarantee that the answer to your question is
correct. But, as Donald Clarke of EPIC says, “regular internet
users accept the trade-off between chaos and usefulness.”1
In
addition, we moderate our forum to ensure that the postings are
of high quality and that users respect patient confidentiality. Also
a form of natural selection ensures that the best postings are the
ones that everyone sees while the poor ones gradually fade from
view. As the peer to peer gurus say, we now have “connection as
well as collection.”1
Kieran Walsh clinical editor, BMJ Learning
(bmjlearning@bmjgroup.com)
1 Clark D. White paper: Napsterisation of e-learning (P2P). www.epic.co.
uk/content/resources/white_papers/p2p.htm (accessed 6 Dec 2005).
Further reading and resources
x Herndon D. Total burn care. 2nd ed. London: Saunders, 2002.
x National Burn Care Review. National burn injury referral
guidelines. In: Standards and strategy for burn care. London: NBCR,
2001:68-9.
x Burnsurgery.org (a website designed to be a comprehensive
educational tool for burn care professionals worldwide)
www.burnsurgery.org
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on combined cardiovascular events. Neither RCTs nor
cohort studies showed significantly increased risks of
cancer or stroke with higher intake of omega 3, but
there were too few events to rule out important effects.
Strengths and weaknesses
The largest studies reviewed had greater potential for
bias than some of the smaller ones. We hoped that pool-
ing studies at low risk of bias might provide enough
power to inform us of effects on health, but this was not
the case. Similarly, analysis of the effects of omega 3 on
rarer outcomes such as stroke had insufficient power to
detect clinically important effects. Unlike previous meta-
analyses, we reviewed systematically the effects of omega
3 fats on mortality, cardiovascular disease, cancer, and
bleeding events and analysed all relevant RCTs and pro-
spective cohort studies. We also accounted for differ-
ences in study quality and examined the effects of long
chain and short chain omega 3 fats in a wide group of
participants; this provides high quality evidence to guide
policy and practice.
Other studies
Our findings differ from those of a recent systematic
review by Bucher et al,3
which reviewed trials assessing
the effects of long chain omega 3 fats over at least six
months in patients with coronary heart disease and
found significant protection from mortality and
sudden death. It did not include the large recent study
by Burr et al.4
Possible explanations for the differences in results
between this and the Bucher review rests on our
inclusion of the study by Burr et al. These are that this
RCT had the longest follow-up of all RCTs and the
harmful effects of methylmercury could be cumulative;
the study was the only RCT that specifically enrolled
men treated for angina; omega 3 from oily fish has a dif-
ferent effect to fish oil supplements (but this was found
not to explain the differences); the effect of omega 3 fats
on cardiovascular disease is smaller than previously
thought; or that its beneficial effect is limited to a specific
group (such as patients after myocardial infarction or
with heart failure) (see bmj.com). Two other systematic
reviews were less comprehensive than ours.6 7
Interpretation
It is not clear whether long chain or short chain omega
3 fats (together or separately) reduce or increase total
mortality, cardiovascular events, cancer, or strokes. Our
findings do not rule out an important effect of omega
3 fats on total mortality, as robust trials at low risk of
bias reported few deaths. The source (dietary or
supplemental) and dose of omega 3 fats did not seem
to affect the effectiveness of long chain omega 3 fats.
UK guidelines encourage the general public to eat
more oily fish, and higher amounts are advised after
myocardial infarction (supported by trials after
myocardial infarction). This advice should continue at
present, but the evidence should be reviewed regularly.
It is probably not appropriate to recommend a high
intake of omega 3 fats for people who have angina but
have not had a myocardial infarction.
Thanks to Theresa Moore and Margaret Burke from the
Cochrane Heart Group, and to all of the authors of primary
studies who helped us build up the data. This paper is based on
a Cochrane review accepted for publication in The Cochrane
Library (see www.TheCochraneLibrary.net for information).
Contributors: See bmj.com.
Funding: A northwest research and development research
fellowship (UK Department of Health) and the British Dietetic
Association.
Competing interests: NEC has received fees for speaking from
Solvay Healthcare, who market Omacor.
Ethical approval: Not required.
1 Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic west
coast Eskimos. Acta Med Scand 1972;192:85-94.
2 Nettleton JA. Omega-3 fatty acids: comparison of plant and seafood
sources in human nutrition. J Am Diet Assoc 1991;91:331-7.
3 Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty
acids in coronary heart disease: a meta-analysis of randomized controlled
trials. Am J Med 2002;112:298-304.
4 Burr ML, Ashfield-Watt PA, Dunstan FD, Fehily AM, Breay P, Ashton T, et
al. Lack of benefit of dietary advice to men with angina: results of a con-
trolled trial. Eur J Clin Nutr 2003;57:193-200.
5 Hooper L, Thompson RL, Harrison RA, Summerbell CD, Moore H,
Worthington HV, et al. Omega 3 fatty acids for prevention and treatment
of cardiovascular disease. Cochrane Database Syst Rev 2004;4:CD003177.
6 Wang C, Chung M, Balk E, Kupelnick B, DeVine D, Lawrence A, et al.
Effects of omega-3 fatty acids on cardiovascular disease. Rockville, MD: Agency
for Healthcare Research and Quality, 2004. Evidence Report/
Technology Assessment 94. www.ncbi.nlm.nih.gov/books/
bv.fcgi?rid = hstat1a.chapter.38290 (accessed 13 Mar 2006).
7 Scientific Advisory Committee on Nutrition. Advice on fish consumption:
benefits and risks. London: Stationary Office, 2004. www.food.gov.uk/
multimedia/pdfs/fishreport200401.pdf (accessed 13 Mar 2006).
(Accepted 1 February 2006)
doi 10.1136/bmj.38755.366331.2F
What is already known on this topic
A systematic review of randomised controlled
trials in coronary heart disease showed reduced
mortality in patients taking supplemental long
chain omega 3 fats
What this study adds
This systematic review assessed the health effects
of long chain and shorter chain omega 3 fats
(together or separately) on total mortality,
cardiovascular events, cancer, and strokes in a wide
group of participants and found no evidence of a
clear benefit of omega 3 fats on health
Corrections and clarifications
ABC of wound healing: Burns
We failed to spot an obvious error in this article by
Alex Benson and colleagues (BMJ
2006;332:649-52, 18 Mar). In the box titled
“Criteria for referral to a burns centre” (p 651), the
three “less than” symbols (for proportion of total
body surface area affected by partial or full
thickness burns) should of course have been “more
than” symbols.
Call to scrap import tariffs on pharmaceuticals in global
WTO talks
In this news article by John Zarocostas, we wrongly
stated that a proposal calling for an end to import
tariffs was circulated during talks in Doha, Qatar
(BMJ 2006;332:508, doi:10.1136/
bmj.332.7540.508-c). In fact the talks were in
Geneva.
Obituaries: Kenneth Herbert Walter
In this obituary, we wrongly spelt Kenneth Walter’s
name as Walker (BMJ 2006;332:671, 18 Mar). We
have not been able to discover how we made this
mistake, but we do apologise.
Research
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ABC of wound healing
Reconstructive surgery
Dean E Boyce, Kayvan Shokrollahi
Many surgical options are available to a reconstructive surgeon
when faced with a difficult wound. However, any decision about
management should be holistic and take into account factors
such as the occupational circumstances of the patient and likely
period of time off work, comorbidity, likelihood of success,
donor morbidity, functional outcome, and the risks of surgery
and anaesthesia. The basic principles of wound management
apply to all wounds.
The “reconstructive ladder”
Reconstructive surgeons use the concept of a “reconstructive
ladder”—the more problematic the wound, the higher up the
ladder the surgeon has to climb. Simple wounds may be closed
by primary suturing, sometimes in the primary care setting. But
others may require complex reconstruction, including free
tissue transfer, in hospital.
All traumatic wounds should undergo debridement and
thorough irrigation before primary closure. The aim of
debridement is to remove all potentially contaminated and
devitalised tissue along with foreign material. Primary suture
may not be indicated in heavily contaminated wounds, where
the risk of infection is high. In such cases the wound should be
debrided, with “delayed closure” carried out later. Occasionally,
wounds may be allowed to heal by secondary intention, where
areas of skin loss are initially replaced by granulation tissue. The
skin defect continues to heal as a result of proliferation or
migration of epidermal cells within and around the wound and
by contraction of the wound by specialised cells (myofibroblasts)
within the granulation tissue. Healing by secondary intention is
slow and may lead to contractures, scarring, and restriction of
movements.
Where skin defects are too large for skin apposition, and
healing by secondary intention is inappropriate, skin grafts may
be used. Free skin grafts are taken from another part of the
body and rely on revascularisation from a healthy, well
vascularised wound bed. Grafts will not be successful on
non-vascularised beds, such as exposed bone or tendon.
Split skin grafts consist of the epidermis and a variable
amount of dermis. They are usually harvested from the thigh
using a specially designed knife or powered dermatome. The
donor area will heal within 10-14 days from remaining dermal
adnexal structures. Such grafts are the mainstay of treatment of
large wounds such as burns. Full thickness grafts consist of the
epidermis and dermis and offer several advantages, but are size
limited as the donor area must be directly closed.
Expansion of local skin using subcutaneous tissue
expanders is a method of increasing the amount of skin locally
available. A tissue expander is placed beneath the skin and
inflated at weekly intervals by injecting saline through a remote
port. The overlying tissue expands in response to mechanical
force. Epidermal thickness increases as a result of cellular
hyperplasia. The dermis also undergoes increased fibroplasia,
with realignment of collagen fibres and disruption of elastic
fibres. This also results, however, in a reduction in dermal
thickness and separation of dermal appendages, such as hair
follicles.
The surgical management of problem wounds generally
aims to obtain rapid wound closure with the simplest
method and with minimal compromise of cosmesis and
function
Free flap
Pedicled flap
Random pattern flap
Tissue expansion
Full thickness graft
Split thickness graft
Delayed closure
Primary closure
Dressings
The “reconstructive ladder” is used by reconstructive surgeons to assess the
complexity of treatment required
A finger injury is irrigated
with saline before
debridement and closure
Harvesting a split thickness skin graft using a hand held knife
A tissue expander has been used to expand the right side of the scalp to
reconstruct the wound left after excision of a congenital melanocyic naevus
This is the eighth in a series of 12 articles
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Many wounds, such as fracture sites and exposed bone or
tendon, are not suitable for grafting, and techniques further up
the reconstructive ladder, such as a flap reconstruction, must be
used. A flap is a unit of tissue that can be moved to cover a
wound while surviving on its own vascular supply. Random
pattern flaps rely on random cutaneous vessels for their blood
supply.
Greater lengths of flap can be used by including the
underlying deep fascia and also by including a perforating
blood vessel in the base of the flap. In some circumstances
better cosmesis may be obtained by raising the flap as fascia
only, leaving the overlying skin behind. “Islanding” a flap on its
vascular pedicle allows even greater pedicle length and thus
greater mobility and versatility. Occasionally no options are
available for local wound cover, and tissue has to be harvested
from elsewhere around the body by using microvascular
techniques. This transfer of tissue, known as a free flap,
represents the top rung of the reconstructive ladder. Any tissue
that can be isolated on a suitable vascular pedicle can be used,
and it may include muscle, skin, fascia, fat, nerve, and bone.
Specific wounds
Pressure ulcers
When considering surgery for pressure ulcers, bear in mind
that the wound will recur if the original precipitant is still
present. Surgical intervention may sometimes be required, once
intrinsic and extrinsic factors have been resolved. Some units
have “outreach” pressure ulcer teams who will give treatment
and advice both in the community and on the wards. Surgery
should be a last resort and would consist of an “oncological”
debridement of the ulcer (including any areas of osteomyelitis)
and excision of bony prominences. Direct closure is usually not
possible, and a local closure using a fasciocutaneous or
myocutaneous flap is usually necessary.
Necrotising infections
Acute infections such as necrotising fasciitis can cause rapid
tissue loss in a very short time. They have polymicrobial
aetiology, and the classic Lancefield group A haemolytic
streptococci may be present in only 15% of cases. After
adequate resuscitation, appropriate antibiotics and prompt
surgical debridement of affected areas may be life saving, and
the patient would need a period of intensive support.
Significant tissue destruction can occur in minutes, highlighting
the importance of rapid debridement, and subsequently large
body surface areas may require surgical reconstruction, most
often with split skin grafts. Flap coverage may occasionally be
needed when the bed is not suitable for a graft.
Arterial ulcers
Peripheral vascular disease can be a primary cause of ulceration
and poor wound healing and is often a contributory reason for
poor healing of wounds from other causes. Bypass grafting or
angioplasty to improve arterial input to the distal limb can be
curative in itself or can be done to enable other forms of
Left to right: Excision of a tumour has left a defect on the nasal tip (the
flaps have been raised but not transposed); the flap is transposed into the
defect, and the adjacent flap is transposed into the donor area; final result.
This procedure is an example of a random patterned flap
Top: Defect on the back of the
hand showing exposed
fractures and destroyed
tendons (this is unsuitable for
skin grafting). Centre: At
reconstruction a distally based
adipofascial flap has been
raised using the radial artery
as a pedicle; the overlying
donor skin is closed primarily.
Bottom: The flap is inset and
covered by a split skin graft
Most wound types outlined in this section are discussed
in more detail in previous articles in this series
Left: Chronic trochanteric pressure ulcer excised. Right: Reconstruction
using a tensor fascia lata myocutaneous flap
Top: Necrotising fasciitis of
the groin after surgical
debridement. Bottom: Wound
closure with a split thickness
skin graft
Left: Compound tibial fracture. Right: Wound closure of the fracture using a
free latissimus dorsi muscle flap covered with a split thickness skin graft
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reconstruction that otherwise would fail (such as grafts or flaps).
Other indications for surgery include the debridement
ofnecrotic or infected tissue. In circumstances of chronic
non-healing, sepsis, or long term disability, amputation of digits
or limbs is often the best solution to enable rapid healing and
improve quality of life. With appropriate counselling from the
multidisciplinary team (surgeon, prosthetist, specialist nurses,
physiotherapist, occupational therapist, and general
practitioner), patients can make informed decisions about such
treatments. Prosthetists can advise the surgeon on the level of
amputation required taking into account the most up to date or
suitable artificial aids.
Diabetic foot ulcers
After proximal arterial disease has been excluded, hypertrophic
keratinous edges of ulcers are debrided and pressure points “off
loaded” (relieved of pressure) by use of appropriate orthoses,
although bony prominences and areas of osteomyelitis may
need to be excised. If, despite adequate treatment and graft or
flap closure, ulceration and infection recurs, amputation may be
the best treatment.
Pilonidal sinus and abscess
Chronic sinuses are excised down to the sacral fascia. The
wound is allowed to heal by secondary intention or closed with
the aid of “Z plasty” (a procedure involving transposition of two
interdigitating triangular flaps that elongate and change
direction of the common limb of the flap) or a local flap.
Non-melanoma skin cancer
Basal cell carcinoma and squamous cell carcinoma are the two
commonest types of skin cancer and are often characterised by
ulceration. In addition, squamous cell carcinoma can develop in
any chronic wound. Treatment of these lesions requires excision
with a suitable margin (typically 3 mm for basal cell and 5 mm
for squamous cell carcinoma). Preoperative microbiology
testing and perioperative antibiotics are recommended for
excision of ulcerated lesions, as such excisions are associated
with increased rates of surgical wound infection. Radiotherapy,
curettage, cryosurgery, and photodynamic therapy—as well as a
number of new topical treatments—may be used in the
treatment of basal cell carcinoma, but none of these procedures
can provide definitive histology or match adequate surgery in
terms of recurrence rates.
Hidradenitis suppurativa
Surgery entails excision of the affected area, leaving a large skin
wound. Primary closure of the wound is usually not possible.
Healing by secondary intention involves many weeks of
dressings and a substantial risk of scar contracture. Skin grafts
may be used, but these run the risk of resulting in scar
contracture and delayed healing. Flap reconstruction may result
in more rapid wound closure and a reduced risk of contracture.
Dean E Boyce is consultant hand and plastic surgeon and Kayvan
Shokrollahi is specialist registrar in plastic surgery in the Welsh
Centre for Plastic Surgery, Morriston Hospital, Swansea.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
Venous leg ulcers
x Surgery, if indicated, may include application of split skin graft on
to a healthy ulcer bed, pinch grafting (several small islands of
epidermis from a healthy donor site applied to the wound bed),
and excision of the ulcer and treatment with split skin grafts
x These techniques may enable more rapid healing than dressings
and compression alone. However, this is at the cost of a donor site
wound, which may be slow to heal because of infection or other
comorbidities, such as diabetes
x More complex procedures, such as coverage with a flap, may be
required if tendon or bone is exposed. Tissue engineered skin
substitutes have been used (see 12th article in this series), but this
technique remains an expensive and unconventional treatment
With a diabetic foot ulcer, amputation may be in the
form of a ray amputation, or an amputation at the level
of forefoot, midfoot, hind foot, or below the knee
Top left: Recurrent pilonidal disease (the patient had had 14 operations);
perforator based flap is marked; the circle indicates the site of the
perforator. Top right: Defect after excision to sacral fascia. Bottom left: Flap
transposed into defect. Bottom right: Disease-free one year after surgery
Defect after hidradenitis excision closed by an islanded V-Y flap based on
perforating vessels from the thoracodorsal artery
Further reading
x Hasham S, Matteucci P, Stanley PRW, Hart NB. Necrotising fasciitis.
BMJ 2005;330:830-3.
x Leaper DJ, Harding KG, eds. Wounds: biology and management.
Oxford: Oxford University Press, 1998.
x McGregor AD, McGregor IA. Fundamental techniques of plastic
surgery, and their surgical applications. 10th ed. London: Churchill
Livingstone, 2000.
x Téot L, Banwell PE, Ziegler UE, eds. Surgery in wounds. Berlin:
Springer, 2004.
The authors thank R Kannan, M S C Murison, D S Murray, T Potokar, G D
Sterne, and O G Titley for help in providing clinical photographs.
BMJ 2006;332:710–2
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ABC of wound healing
Wound dressings
Vanessa Jones, Joseph E Grey, Keith G Harding
Traditionally wet-to-dry gauze has been used to dress wounds.
Dressings that create and maintain a moist environment,
however, are now considered to provide the optimal conditions
for wound healing. Moisture under occlusive dressings not only
increases the rate of epithelialisation but also promotes healing
through moisture itself and the presence initially of a low
oxygen tension (promoting the inflammatory phase). Gauze
does not exhibit these properties; it may be disruptive to the
healing wound as it dries and cause tissue damage when it is
removed. It is not now widely used in the United Kingdom.
Occlusive dressings are thought to increase cell proliferation
and activity by retaining an optimum level of wound exudate,
which contains vital proteins and cytokines produced in
response to injury. These facilitate autolytic debridement of the
wound and promote healing. Concerns of increased risk of
infection under occlusive dressings have not been substantiated
in clinical trials. This article describes wound dressings currently
available in the UK.
Low adherent dressings
Low adherent dressings are cheap and widely available. Their
major function is to allow exudate to pass through into a
secondary dressing while maintaining a moist wound bed.
Most are manufactured in the form of tulles, which are open
weave cloth soaked in soft paraffin or chlorhexidine; textiles; or
multilayered or perforated plastic films.
They are designed to reduce adherence at the wound bed
and are particularly useful for patients with sensitive or fragile
skin.
Semipermeable films
Semipermeable films were one of the first major advances in
wound management and heralded a major change in the way
wounds were managed. They consist of sterile plastic sheets of
polyurethane coated with hypoallergenic acrylic adhesive and
are used mainly as a transparent primary wound cover.
Although they are impermeable to fluids and bacteria, they
are permeable to air and water vapour, the control of which is
dependent on the moisture and vapour transmission rate, which
varies depending on the brand. It is through this mechanism
that this dressing creates a moist wound environment.
Films are very flexible and are good for wounds on
“difficult” anatomical sites—for example, over joints. They are
unable to cope with large amounts of exudate, however, and
may cause maceration of the skin surrounding the wound bed if
they are used injudiciously.
Hydrocolloids
Sodium carboxymethylcellulose, gelatin, pectin, elastomers, and
adhesives are bonded to a carrier of semipermeable film or a
foam sheet to produce a flat, occlusive, adhesive dressing that
forms a gel on the wound surface, promoting moist wound
healing. Cross linkage of the materials used influences the
viscosity of the gel under the dressing. This gel, which may be
yellow and malodorous, may be mistaken for infection by the
Modern dressing technology is based on the principle of
creating and maintaining a moist wound environment
Characteristics of the ideal dressing
x Capable of maintaining a high humidity at the wound site while
removing excess exudate
x Free of particles and toxic wound contaminants
x Non-toxic and non-allergenic
x Capable of protecting the wound from further trauma
x Can be removed without causing trauma to the wound
x Impermeable to bacteria
x Thermally insulating
x Will allow gaseous exchange
x Comfortable and conformable
x Require only infrequent changes
x Cost effective
x Long shelf life
Low adherent dressings—suitable for use on flat, shallow
wounds with low exudates
Tulles—Bactigras, Jelonet, Paranet, Paratulle, Tullegras, Unitulle,
Urgotul
Textiles—Atrauman, Mepilex, Mepitel, NA Dressing, NA Ultra,
Tegapore, Tricotex
Left: Healthy venous leg ulcer suitable for dressing with low adherent
dressing. Right: Wound suitable for dressing with semipermeable film
Semipermeable films
Examples include Bioclusive, Mefilm, OpSite Flexigrid,* OpSite Plus,
Tegaderm
x Suitable for flat, shallow wounds with low to medium exudates
x Promote moist environment
x Adhere to healthy skin but not to wound
x Allow visual checks
x May be left in place several days
x Useful as secondary dressing
x Provide no cushioning
x Not for infected or heavily exuding wounds
*Not available on prescription in UK primary care.
Venous leg ulcer suitable
for dressing with
hydrocolloid
This is the ninth in a series of 12 articles
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unwary. Hydrocolloids are virtually impermeable to water
vapour and air and can be used to rehydrate dry necrotic eschar
and promote autolytic debridement. They are reported to
reduce wound pain, and their barrier properties allow the
patient to bathe or shower and continue with normal daily
activities without disturbing or risking contamination of the
wound. Caution should be exercised when using hydrocolloids
for wounds that require frequent inspection—for example, for
diabetic foot ulcers.
Hydrocolloid fibres are now available in the form of a
hydrophilic, non-woven flat sheet, referred to as hydrofibre
dressings. On contact with exudate, fibres are converted from a
dry dressing to a soft coherent gel sheet, making them suitable
for wounds with a large amount of exudate.
Hydrogels
Hydrogels consist of a matrix of insoluble polymers with up to
96% water content enabling them to donate water molecules to
the wound surface and to maintain a moist environment at the
wound bed. As the polymers are only partially hydrated,
hydrogels have the ability to absorb a degree of wound exudate,
the amount varying between different brands. They transmit
moisture vapour and oxygen, but their bacterial and fluid
permeability is dependent on the type of secondary dressing
used.
Hydrogels promote wound debridement by rehydration of
non-viable tissue, thus facilitating the process of natural
autolysis. Amorphous hydrogels are the most commonly used
and are thick, viscous gels.
Hydrogels are considered to be a standard form of
management for sloughy or necrotic wounds. They are not
indicated for wounds producing high levels of exudate or where
there is evidence of gangrenous tissue, which should be kept
dry to reduce the risk of infection.
Alginates
Alginates are produced from the naturally occurring calcium
and sodium salts of alginic acid found in a family of brown
seaweed (Phaeophyceae). They generally fall into one of two
kinds: those containing 100% calcium alginate or those that
contain a combination of calcium with sodium alginate, usually
in a ratio of 80:20.
Alginates are rich in either mannuronic acid or guluronic
acid, the relative amount of each influencing the amount of
exudate absorbed and the shape the dressing will retain.
Alginates partly dissolve on contact with wound fluid to form a
hydrophilic gel as a result of the exchange of sodium ions in
wound fluid for calcium ions in the dressing. Those high in
mannuronic acid (such as Kaltostat) can be washed off the
wound easily with saline, but those high in guluronic acid (such
as Sorbsan) tend to retain their basic structure and should be
removed from the wound bed in one piece.
Alginates can absorb 15 to 20 times their weight of fluid,
making them suitable for highly exuding wounds. They should
Hydrocolloid dressings (including hydrofibres)
Type of dressing Uses
Hydrocolloid sheets: Alione,
CombiDERM, CombiDERM
N, Comfeel,* Comfeel Plus,
Cutinova Thin,* DuoDERM
Extra Thin,* Granuflex,*
Tegasorb, Tegasorb Thin
Cavity or flat shallow wounds with low
to medium exudate; absorbent;
conformable; good in “difficult”
areas—heel, elbow, sacrum
Hydrocolloid paste: GranuGel
Paste*
May be left in place for several days;
useful debriding agent; may cause
maceration
Hydrofibre: Aquacel
(Hydrofibre), Versiva
Useful in flat wounds, cavities, sinuses,
undermining wounds; medium to
high exudate wounds; highly
absorbent; non-adherent; may be left
in place for several days; needs
secondary dressing
*Not available on prescription in UK primary care.
Hydrogels
Examples include Aquaform, Intrasite, GranuGel, Nu-Gel, Purilon,
Sterigel
x Supply moisture to wounds with low to medium exudate
x Suitable for sloughy or necrotic wounds
x Useful in flat wounds, cavities, and sinuses
x May be left in place several days
x Need secondary dressing
x May cause maceration
Hydrocolloid fibres (hydrofibres) are often used on
wounds where, traditionally, alginates have been used
Dry, sloughy leg wound
suitable for dressing with
hydrogel
Alginates
Examples include Algisite, Algosteril, Kaltostat,* Melgisorb, SeaSorb,
Sorbsan, Sorbsan SA,* Tegagen, Urgosorb
x Useful in cavities and sinuses, and for undermining wounds
x For all wound types with high exudates
x Highly absorbent
x Need secondary dressing
x Need to be changed daily
*Not available on prescription in UK primary care
Diabetic foot ulcer with
maceration to
surrounding skin suitable
for dressing with alginate
Foot wound complicated by
heterotopic calcification
suitable for dressing with
hydrofibres
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not be used, however, on wounds with little or no exudate as
they will adhere to the healing wound surface, causing pain and
damaging healthy tissue on removal.
Foam dressings
Foam dressings are manufactured as either a polyurethane or
silicone foam. They transmit moisture vapour and oxygen and
provide thermal insulation to the wound bed. Polyurethane
foams consist of two or three layers, including a hydrophilic
wound contact surface and a hydrophobic backing, making
them highly absorbent. They facilitate uniform dispersion of
exudate throughout the absorbent layer and prevent exterior
leakage (strike-through) due to the presence of a
semipermeable backing.
Polyurethane foam dressings are also available as a cavity
dressing—small chips of hydrophilic polyurethane foam
enclosed in a membrane of perforated polymeric film, giving a
loosely filled bag.
Silicone foams consist of a polymer of silicone elastomer
derived from two liquids, which, when mixed together, form a
foam while expanding to fit the wound shape forming a soft
open-cell foam dressing. The major advantage of foam is the
ability to contain exudate. In addition, silicone foam dressings
protect the area around the wound from further damage.
Antimicrobial dressings
Silver, in ionic or nanocrystalline form, has for many years been
used as an antimicrobial agent particularly in the treatment of
burns (in the form of silver sulfadiazine cream). The recent
development of dressings impregnated with silver has widened
its use for many other wound types that are either colonised or
infected.
Iodine also has the ability to lower the microbiological load
in chronic wounds. Clinically it is mainly used in one of two
formats: (a) as povidone-iodine (polyvinylpyrrolidone-iodine
complex), an iodophor (a compound of iodine linked to a
non-ionic surfactant), which is produced as an impregnated
tulle; and (b) as cadexomer iodine (a three dimensional starch
lattice containing 0.9% iodine). Cadexomer iodine has good
absorptive properties: 1 g of cadexomer iodine can absorb up
to 7 ml of fluid. As fluid is absorbed, iodine is slowly released,
reducing the bacterial load and also debriding the wound of
debris. This mode of action facilitates the delivery of iodine over
a prolonged period of time—thus, in theory, maintaining a
constant level of iodine in the wound bed.
Caution is required in patients with a thyroid disease owing
to possible systemic uptake of iodine. For this reason, thyroid
function should be monitored in patients who are treated with
iodine dressings.
Metronidazole gel is often used for the control of odour
caused by anaerobic bacteria. This is particularly useful in the
management of fungating malignant wounds. It may be used
alone or as an adjunct to other dressings.
Unwanted effects of dressings
Maceration of the skin surrounding a wound may occur if a
dressing with a low absorptive capacity is used on a heavily
exuding wound. If the dressing is highly absorptive then more
frequent dressing changes may be needed, in addition to
investigation and management of the cause of the exudate
(such as infection).
The ion exchange properties of some alginates make
them useful haemostatic agents, and as such they are
particularly useful for postoperative wound packing
Foam dressings
Type of dressing Uses
Adhesive sheets: Allevyn Adhesive,
Allevyn Lite Island, Allevyn Thin,
Allevyn Plus Adhesive, Biatain Adhesive,
Lyofoam Extra Adhesive, Tielle Plus,
Tielle Lite, Tielle
Non-adherent sheets: Allevyn,* Allevyn
Lite, Lyofoam,* Lyofoam Extra*
Flat, shallow wounds
(control of exudate
depending on type of
foam); give degree of
cushioning; may be left in
place for two to three days
Need secondary dressing
Allevyn Cavity, Allevyn Plus Cavity,
Cavi-Care
Cavity wound with
medium to high exudate
*Not available on prescription in UK primary care.
Venous leg ulceration
in background of
chronic oedema
suitable for dressing
with foam
Top left: Sloughy, infected
arterial ulcer suitable for
dressing with compound
antimicrobial dressing (silver
or iodine based). Top right:
Gangrenous foot suitable for
dressing with antimicrobial
iodine impregnated dressing.
Left: Malodorous malignant
melanoma ulcer suitable for
treatment with topical
metronidazole
Antimicrobial dressings
For use in all locally infected wounds
x Acticoat
x Actisorb Silver 200
x Aquacel Ag
x Arglaes
x Avance
x Inadine
x Iodoflex
x Iodosorb
x Metrotop Gel
Inappropriate use of dressings may lead to
unwanted effects
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The skin surrounding a highly exuding wound may be
further protected through the use of emollients (such as 50:50
mix of white soft paraffin and liquid paraffin) or the application
of barrier films (such as Cavilon). Conversely, use of a highly
absorptive dressing on a dry wound may lead to disruption of
healthy tissue on the wound surface and cause pain when
removed.
Allergic reactions are not uncommon: the dressing should
be avoided, and the allergy may need to be treated with potent
topical steroids. Tapes used to keep dressings in place are
common causes of allergy. Many dressings require secondary
dressings—for example, padding on highly exuding
wounds—which may make them bulky. Secondary dressings
should not be too tight, especially on patients with peripheral
vascular disease.
Competing interests: For series editors’ competing interests, see the first
article in this series.
Abdominoperineal resection wound treated with vacuum
assisted closure. The skin edges are protected with a barrier
cream to prevent maceration
Left: Allergy to dressing used to treat arterial leg ulceration. Note
erythematous skin with sharply demarcated edges corresponding to the
shape of the offending dressing. Right: Ulceration over the anterior aspect
of the ankle caused by inappropriately tight bandage
Vanessa Jones is senior lecturer at the Wound Healing Research Unit,
Cardiff University.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
BMJ 2006;332:777–80
“Seeing” is believing
“Your next batch of students arrive tomorrow,” the administrator
told me, “and one of them has a visual impairment.”
It turned out that 20 years previously he had had retinitis
pigmentosa diagnosed, and by the time he joined medical school
he was registered blind. My colleagues were sceptical about his
choice of profession, and we pondered how best to deal with this
situation and what impact his presence would have on the rest of
the team and the patients.
I met him the next day. Tall and elegant, he radiated a calm
confidence. Accompanying him every step of the way was his
guide dog, and a fellow medical student relayed the case notes to
him (forming “the trio,” as I soon called them). His history taking
skills turned out to be excellent, and he was able to extract
important information that had been missed by earlier students.
He picked up all the findings on palpation and auscultation. The
hepatic bruit is a specific sign of alcoholic hepatitis but can be
difficult to hear even for experienced hepatologists—but he never
missed one. During ward rounds, I was impressed by how well he
connected with his patients and how comfortable they seemed
with him. It was soon apparent that his presence was having a
positive and inspirational impact on the team, and “the trio”
became instantly recognisable in the hospital.
He relied on innovative ways to overcome his disability. For his
medical boards (equivalent to MRCP), he used a reader and
scribe. During the anatomy exam, his palpation skills helped him
to identify various parts on the cadaver. Since he had become
blind in adulthood, he did not read Braille and instead consulted
audiobooks and e-text. The most amazing development has been
JAWS, a computer program that allows him to “write” case notes,
search the internet, and respond to emails.
I had great respect and admiration for this remarkable medical
student and indicated that to him at our last meeting. To
overcome such personal hardship and, against all odds, choose to
study medicine required strength of character and conviction that
many of us lack. He graduated recently and is now training to be
a psychiatrist. Before I met him, if someone had asked my
opinion about a blind student training to be a doctor, I would not
have been optimistic. I guess “seeing” is believing.
Sumita Verma locum consultant, liver and antiviral unit, St Mary’s
Hospital NHS Trust, London (sumitaverma6@hotmail.com)
Further reading
x Choucair M, Phillips T. A review of wound healing and dressings
material. Skin and Aging 1998;6:(suppl):37-43.
x Hermans MH, Bolton LL. Air exposure versus occlusion: merits
and disadvantages of different dressings. J Wound Care
1993;2:362-5.
x Morgan DA. Wound management products in the drug tariff.
Pharmaceutical Journal 1999;263:820-5.
x Thomas S, Leigh IM. Wound dressings. In: Leaper DJ, Harding KG,
eds. Wounds: biology and management. Oxford: Oxford University
Press, 1998:166-83.
x Turner TD. Development of wound management products in
chronic wound care. In: Krasner D, Rodeheaver G, Sibbald RG, eds.
Chronic wound care: a clinical source book for healthcare professionals.
3rd ed. Wayne, PA: HMP Communications, 2001.
x Winter G. Formation of scab and the rate of epithelialisation of
superficial wounds in the skin of the young domestic pig. Nature
1962;193:293-4.
x Vermeulen H, Ubbink D, Goossens A, de Vos R, Legemate D.
Dressings and topical agents for surgical wounds healing by
secondary intention. Cochrane Database Syst Rev
2005;(4):CD003554.
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ABC of wound healing
Infections
Brendan Healy, Andrew Freedman
Despite optimal treatment some wounds are slow to heal. The
challenge clinically and microbiologically is to identify those
wounds in which healing is impaired as a result of infection or
heavy bacterial burden and in which systemic or topical
antimicrobial treatment will be of benefit.
Staphylococci and streptococci are the most commonly
encountered pathogenic organisms in community acquired
superficial wounds. More unusual organisms may be found in
bite wounds, and these reflect the source of the bite. Pathogenic
organisms causing surgical wound infections vary according to
the anatomical site of surgery. Antibiotic resistant organisms,
such as methicillin resistant Staphylococcus aureus (MRSA), are
more commonly encountered, reflecting the hospital flora.
When to sample
It is inappropriate to swab all wounds: swabs should be taken
only from overtly infected wounds and from wounds that are
deteriorating, increasing in size, or failing to make satisfactory
progress despite an optimal environment for wound healing.
Indicators of wound infection include redness, swelling,
purulent exudate, smell, pain, and systemic illness in the
absence of other foci. Subtle signs of local wound infection
include unhealthy “foamy” granulation tissue, contact bleeding,
tissue breakdown, and epithelial bridging.
Types of sample
Superficial wound swabs—The ease of obtaining and
processing superficial wound swabs, combined with their
relatively low cost and non-invasive nature, make them in most
instances the most appropriate method for wound sampling.
Organisms cultured from a superficial swab may, however,
simply reflect the colonising bacterial flora and are not always
representative of the pathogenic organisms invading deeper
tissue. This is particularly relevant to deep surgical and deep
penetrating wounds in which infection from internal sources
may occur.
Tissue and pus—Tissue or pus, or both, should be collected
whenever possible, as growth from these samples is more
representative of pathogenic flora. These are amenable to
quantitative microbiological analysis and other techniques used
to improve the diagnostic yield. Tissue biopsy should always be
carried out when therapeutic debridement of the wound is
done, in cases of osteomyelitis, and when superficial sampling
methods have been ineffective.
Less invasive techniques—Less invasive sampling
techniques—such as dermabrasion and various absorbent
pads—have been developed. A wide range of products is
available, but no single method is used routinely yet.
Microbiological analysis
Semiquantitative analysis
Most laboratories will perform a semiquantitative analysis on
wound swabs. This entails grading bacterial growth as scanty,
light, moderate, or heavy. Semiquantitative analysis introduces a
bias towards motile and fast growing organisms.
Infection is a major source of failed wound healing
Management of bite wounds
x Carry out meticulous surgical debridement and cleansing of wound
x Send deep tissue specimens for microbiology testing
x Consider empirical treatment with antibiotics
x Consider tetanus prophylaxis
x Seek microbiological advice if bite was by exotic animal
Signs of wound infection
x Redness
x Heat
x Pain
x Swelling
x Exudate (purulent, serous, or serosanguinous)
x Odour
x Poor healing
x Contact bleeding
x Epithelial bridging
x Tissue breakdown
x Presence of unhealthy granulation tissue
x Systemic illness in the absence of other focus of infection
A charcoal swab preserves bacteria during transport to the laboratory
How to take a superficial wound swab
x Removal of superficial debris followed by swabbing of the wound
bed is considered to be the best way to obtain a superficial wound
swab
x Swabs containing transport media and charcoal should be used as
they help to preserve bacteria before laboratory analysis
x Timely delivery of the swab to the microbiology laboratory is
essential
Punch biopsy for
microbiological analysis
Semiquantitative analysis of swab showing light or scanty,
moderate, and heavy growth of Staphylococcus aureus
This is the 10th in a series of 12 articles
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Fastidious organisms such as anaerobes may be
under-represented. Semiquantitative counts have been shown to
correlate with quantitative tissue counts in both burn wounds
and diabetic foot ulcers.
Quantitative analysis
Bacterial load greater than 100 000 organisms or colony
forming units per gram of tissue or mm3
of pus is a predictor of
wound infection.
However, some wounds that are more heavily colonised will
heal spontaneously, and, conversely, some organisms are able to
cause serious infection at much lower levels of colonisation.
Infection depends on the pathogenicity of the organism, the
type of wound, and the host response.
Interpretation of results
Most wound swabs will yield bacterial growth. Growth of
bacteria from wounds is not synonymous with infection, and
treatment based on microbiological results alone is not
warranted.
Treatment
Wound infections in association with systemic illness, deep
invasion, or cellulitis require empirical systemic antibiotic
treatment while culture results are awaited. Choice of treatment
will depend on factors such as the type and site of wound;
previous microbiological results; and host factors such as drug
allergies. Clinicians must always be alert to the possibility of
necrotising fasciitis. A high level of suspicion followed by
prompt aggressive surgical debridement of devitalised necrotic
tissue is essential if the patient is to survive. Important clinical
markers include pain disproportionate to clinical signs,
anaesthesia over the infected area, and systemic illness.
Superficial wound swabs are not always representative
of the pathogenic organisms invading deeper tissue
Microbiological analysis
Type of analysis Suitable samples Advantages Disadvantages
Gram stain
Tissue, pus, or swab
transported immediately to
laboratory
Instant results; good
correlation with quantitative
counts
Poor sensitivity; no antibiotic sensitivity pattern
Quantitative culture Tissue, pus, dermabrasion
specimens, absorbent pad
specimens
Counts > 105
organisms or
colony forming units per
gram of tissue predict wound
infection
Invasive; labour intensive; costly
Semiquantitative culture All specimens Practical; can be carried out
on swab specimens; some
correlation with quantitative
analysis
Imprecise; bias towards motile/fast growing
organisms; sampling of superficial colonising
bacteria
Contamination Colonisation
Severity of clinical signs
Critical
colonisation
Local
infection
Systemic
infection
Contamination: Presence of non-replicating micro-organisms in wound – these
are rapidly cleared by host defences
Colonisation: Presence of replicating organisms adherent to wound bed without
causing cellular damage to host
Critical colonisation: Increasing bacterial burden. These wounds fail to heal but
may not manifest the classic signs of infection. The clinical signs and symptoms
of critical colonisation are delayed healing, pain/tenderness, increased serous
exudate, change in colour of the wound bed, friable granulation tissue, absent or
abnormal granulation tissue, and malodour
Local infection: Classic signs of infection (redness (erythema), warmth, swelling,
and pain) are present with or without surrounding cellulitis. Often described as
bacterial burden of >105 organisms per gram of tissue or mm3 of pus
Systemic infection: Increasing bacterial burden in the wound. If untreated, this
will result in systemic dissemination resulting in sepsis; progression may lead to
multiorgan failure and even death
Spectrum of interaction between bacteria and host
Left: Extensive cellulitis complicating laparotomy wound.
Right: Severely locally infected wound showing unhealthy
granulation tissue
Clinical markers of necrotising fasciitis*
Early presentation
x Pain (may be
disproportionate to
clinical signs)
x Cellulitis
x Swelling of the affected
region
x Induration
x Skin anaesthesia
x Fever
x Tachycardia
Late presentation
x Severe pain
x Skin discoloration (purple or black)
x Blistering
x Haemorrhagic bullae
x Crepitus
x Discharge of “dishwater” fluid
x Severe sepsis or systemic inflammatory
response syndrome
x Multiorgan failure
*From Hasham et al, 2005 (see Further Reading box)
Empirical antibiotic treatment of wound infection in
systemically unwell patient*
Type of wound Antibiotic
Wound infection Co-amoxiclav
Surgical wound
infection
Cefuroxime and metronidazole or co-amoxiclav
Bite wound Co-amoxiclav
Diabetic ulcer Co-amoxiclav and ciprofloxacin
Osteomyelitis Co-amoxiclav or ciprofloxacin and clindamycin
Necrotising
fasciitis
High dose benzylpenicillin plus clindamycin
(with or without ciprofloxacin)
MRSA infection
suspected
Vancomycin or linezolid
*Rough guide only. In general, treatment should be guided by discussion with
the local microbiology department. Choice of antibiotics will depend on
previous microbiology where available, previous antibiotic treatment, site of
surgery, and the local prevalence of MRSA.
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Treatment of locally infected wounds with topical antiseptics
such as silver compounds or iodine will be sufficient in most
instances. Topical treatment avoids the potential side effects of
systemic antibiotics, such as Clostridium difficile diarrhoea,
anaphylaxis, gastrointestinal upset, and, perhaps most
importantly, selection of resistant organisms. Systemic treatment
may be indicated if topical medication is unsuccessful.
In general, topical antibiotics are not recommended.
Reasons for this include inadequate penetration for deep skin
infections, development of antibiotic resistance, hypersensitivity
reactions, systemic absorption when applied to large wounds,
and local irritant effects leading to further delay in wound
healing. Short courses of silver sulfadiazine or topical
metronidazole can be useful, however, in certain
circumstances—for example, with burns and chronic ulcers.
Osteomyelitis associated with wound
infection
Osteomyelitis may develop after direct inoculation of bone from
a contiguous focus of infection. This can be a devastating
complication of wound infection, requiring specialist
intervention and management.
Diagnosis
The diagnosis of osteomyelitis should be considered in any
chronic wound that does not heal despite optimal treatment or
in any wound (especially in those with diabetes) that can be
probed to bone. Plain x rays of the affected area should be the
first line of investigation.
Radiographic changes, however, can lag behind the
evolution of infection by at least two weeks; a single, negative
plain x ray film does not, therefore, exclude osteomyelitis.
Magnetic resonance imaging is more sensitive than plain
radiography. Nuclear scintigraphy—either a technetium bone
scan or a labelled white cell scan—may also be helpful but
requires careful interpretation. It can be difficult to differentiate
osteomyelitis from chronic soft tissue infection.
Management
Antibiotics penetrate poorly into devitalised bone, and long
courses of antibiotics may be required. It is therefore important
to define the infecting organism(s) from the outset so that
antibiotic treatment can be targeted. Ideally, in the absence of
systemic illness, antibiotics should not be started before
microbiological sampling of the infected bone.
Surgery followed by prolonged intravenous antibiotic
treatment (generally a minimum of six weeks), is indicated in
selected patients. Periodic antibiotic treatment at times of
wound deterioration or of systemic illness may be appropriate if
cure is unachievable.
Surgery
Surgery enables debridement of all necrotic bone and tissue
and provides deep samples for microbiological analysis. In
some patients, surgery is not possible either because of the site
of the wound or because of the patient’s debility. Under these
circumstances, a prolonged course of antibiotics may be
warranted.
Antibiotic treatment
Choice of treatment is dependent on the antibiotic sensitivity
pattern of the infecting organism(s) along with antibiotic
properties, such as bone penetration, and host factors, such as
drug allergy. Combination therapy is often used to gain
maximal effect. Inflammatory markers (including C reactive
Necrotising fasciitis
Topical antimicrobial preparations
x Iodine releasing agents (povidone-iodine preparations,
cadexomer-iodine preparations)
x Potassium permanganate solution
x Silver releasing agents (composite silver dressings, silver
sulfadiazine)
x Topical antibiotic (metronidazole)
Left: Osteomyelitis in a chronic, non-healing sternotomy wound. Right:
Osteomyelitis arising at the site of a previous traumatic wound to the tibia,
previously healed by reconstructive surgery. The sinuses probe to bone
Four to six
week course of
antibiotics guided
by microbiology
Empirical antibiotic regime
started at induction, surgical
specimens to microbiology
Consider
prolonged course
of antibiotic
treatment
Swab wound and
start empirical
antibiotic treatment
Plain x ray
NoYes
Osteomyelitis suspected or can probe to bone
Is the patient systemically unwell?
Treat as soft tissue
infection. Consider
imaging again after
two to four weeks
Consider further
imaging to identify
extent of infection
Discuss with radiologist
and consider other imaging
(eg. MRI, bone scan)
NoYes
Is osteomyelitis proved?
Is osteomyelitis proved?
NoYes
NoYes
Is surgery indicated?
Algorithm for management when osteomyelitis is suspected or if the wound
can be probed to bone
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protein and erythrocyte sedimentation rate) and radiological
images can be used to monitor response.
Methicillin resistant Staphylococcus aureus
The incidence of MRSA wound infection and osteomyelitis is
increasing. Isolation of MRSA from a wound, however, does not
require treatment in the absence of clinical signs of infection.
Topical antimicrobial agents, such as iodine and silver
compounds, have activity against MRSA and may be used in
localised wound infection when there is no evidence of
invasion, cellulitis, or systemic upset.
In a systemically unwell individual, a glycopeptide
(vancomycin or teicoplanin) should be administered. In all cases
of MRSA osteomyelitis and in some MRSA wound infections a
second antistaphylococcal agent with good penetration to bone
and superficial skin sites should be added—for example, fusidic
acid or rifampicin. Both rifampicin and fusidic acid can cause
hepatitis and require regular monitoring of liver function tests.
With the exception of linezolid, evidence for the use of oral
antibiotics in MRSA infections is lacking. However, when oral
antibiotics are used, combinations are recommended to protect
against the development of resistance. Combinations of
rifampicin or fusidic acid with either trimethoprim or
minocycline have been used with some success. The
combination of rifampicin with fusidic acid is not advisable
because of the increased risk of hepatotoxicity.
Linezolid, an oxazolidinone, is a new agent active against
MRSA. It has excellent bioavailability, can be administered
orally, and has good skin and bone penetration. Linezolid is
generally well tolerated, but can cause bone marrow
suppression, and regular haematological monitoring is
therefore required. Linezolid use is currently limited by its high
cost.
Agents that may be available in the near future include
daptomycin, tigecycline, and dalbavancin.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
Radiological improvement will often lag behind clinical
improvement by up to six weeks
Pressure sore associated with MRSA osteomyelitis. Bone is visible at
the base of the ulcer
Further reading
x Hasham S, Matteucci P, Stanley PR, Hart NB. Necrotising fasciitis.
BMJ 2005;330:830-3.
x Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C,
Linezolid CSSTI Study Group. Linezolid versus vancomycin in
treatment of complicated skin and soft tissue infections. Antimicrob
Agents Chemother 2005;49:2260-6.
x Eron LJ, Lipsky BA, Low DE, Nathwani D, Tice AD, Volturo GA,
Expert Panel on Managing Skin and Soft Tissue Infections.
Managing skin and soft tissue infections: expert panel
recommendations on key decision points. J Antimicrob Chemother
2003;52(suppl 1):i3-17.
x Bisno AL, Cockerill FR 3rd, Bermudez CT. The initial
outpatient-physician encounter in group A streptococcal
necrotizing fasciitis. Clin Infect Dis 2000;31:607-8.
The figure showing the spectrum of interaction between bacteria and host
was supplied by J E Grey and Stuart Enoch.
Brendan Healy is specialist registrar in infection diseases and
microbiology, and Andrew Freedman is honorary consultant in
infectious diseases at University Hospital of Wales, Cardiff.
BMJ 2006;332:838–41
Do it yourself thermotherapy
A 75 year old man was found unconscious in his bath. He had
had a coronary bypass operation and pacemaker implanted
because of syncope with bradyarrhythmia, and, more recently,
prostate carcinoma with bone metastases had been diagnosed, for
which he was being treated with antiandrogens. Examination
revealed an unresponsive patient with a Glasgow coma score of
1-1-1, a rectal body temperature of 41.6°C, a blood pressure of
60/30 mm Hg, a heart rate of 60 beats/min, and a respiratory
rate of 20 breaths/min. Biochemical and cardiological
investigations did not identify the cause of coma, and the results
from a cerebral computed tomography were normal. After the
patient had been fully undressed and given saline infusions, his
body temperature dropped to 38°C, and his Glasgow coma score
became normal within 30 minutes.
At this point his wife told us that her husband had recently
been searching the internet for possible treatments for his
carcinoma. He had come across information on cooled
thermotherapy (TUMT, transurethral microwave
thermotherapy) for benign prostate hyperplasia and on
hyperthermia treatment for malignant diseases such as
melanoma, hepatocellular carcinoma, and metastasised breast
and colorectal carcinoma.
On the basis that such treatment would help him, he designed
and made a hyperthermia system from spare parts at home. He
fitted a large industrial garbage container with the heating
element of an old electric frying pan as well as a garden pond
pump for circulation. He took hot baths in this device for two
hours every other day. All went well until the day of admission,
when the water overheated and he lost consciousness.
He was discharged, well, after two days, insisting that he had
devised an excellent system apart from forgetting to install a
thermostat.
Jacqueline Buijs, Rinske Boersma department of internal medicine,
Atrium Medical Centre, Heerlen, Netherlands
(rinskeboersma@hotmail.com)
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ABC of wound healing
Non-surgical and drug treatments
Stuart Enoch, Joseph E Grey, Keith G Harding
Despite great strides in technological innovations and the
emergence of a wide range of treatments for wounds,
non-healing wounds continue to perplex and challenge doctors.
Various non-surgical approaches have been developed and
numerous drugs have been introduced to aid the management
of such wounds.
Non-surgical treatments
Bandages and hosiery
Compression bandages are used to treat lower limb ulcers
secondary to venous insufficiency (venous leg ulcers) and
lymphoedema. Single layer compression bandages (elastic) are
classified into four groups according to the predetermined
levels of compression they provide at the ankle. Inelastic
compression bandages (short stretch), when applied at full
extension, improve the calf muscle pump action and exert
higher pressures when the patient is upright (and walking) and
lower pressures at rest. They are useful in patients who are
adequately mobile. An elasticated tubular bandage (one to three
layers) may be useful to treat and prevent venous leg ulcers.
Multilayer compression bandaging, such as the four layer
method, is well established in the management of venous leg
ulcers. It consists of four layers—padding, a crepe bandage, and
classes 3a and 3b (UK classification) compression
bandages—applied from the base of the toes to knee. Ideally, it
should be left in place for four to seven days. Although effective,
the bulkiness of these layers may lead to non-compliance in
some patients. Its use is limited in heavily exuding ulcers as
repeated dressing changes may be needed.
Any form of debridement (sharp, mechanical,
autolytic (honey), enzymatic, or biosurgery (maggots))
Ulcer with slough and
non-viable or necrotic tissue
Compression bandages, intermittent
pneumatic compression device
Ulcer secondary
to lymphoedema
Medicated bandage such as zinc paste bandage
containing calamine, coal tar, or ichthammol
Venous ulcer
with eczema
Iloprost, glyceryl trinitrate,
calcium antagonists, corticosteroidsVasculitic
Appropriate compression bandagesVenous
TreatmentUlcers
Pentoxifylline, iloprostArterial
Vacuum assisted closureExudating cavity
Psoralen and ultraviolet light therapy, pentoxifyllineNecrobiosis lipoidica
Non-surgical and drug treatments to consider in the treatment of chronic
ulcers
Top left: Single layer elastic
compression bandage. Top right:
Inelastic (short stretch) compression
bandage. Left: Three layer
elasticated tubular bandage
Caution in use of compression bandages
x Appropriate clinical evaluation is essential before using any form of
compression treatment
x Injudicious use may lead to serious complications, including limb
gangrene
x Distal circulation of the limb should be carefully assessed and
peripheral vascular disease excluded
x Caution should be exercised in patients with peripheral neuropathy
Graduated compression hosiery (UK classes I to III) is
primarily used to prevent recurrence of venous leg
ulcers and to control symptoms associated with varicose
veins. The use of compression hosiery below the knee is
associated with increased patient adherence
This is the 11th in a series of 12 articles
Single layer compression bandages
Class (level of
compression) Indication Examples
3a (light (14-17
mm Hg))
To treat simple VLU Elset, Litepress
3b (moderate
(18-24 mm Hg))
To treat VLU and ulcers
secondary to lymphoedema
Tensoplus Forte,
Coban
3c (high (25-35
mm Hg))
As for class 3b plus gross
varicose veins in moderate sized
legs
Tensopres,
Setopress,
Surepress
3d (extra-high
(36-50 mm Hg))
To treat extensive VLU, ulcers
secondary to lymphoedema,
extensive varicose veins, and
post-thrombotic venous
insufficiency in patients with
very large and oedematous legs
Elastic web
bandages (blue
line or red line
webbing)
VLU = venous leg ulcer.
Left: Components of four layer bandage system. Right: Four layer bandage
system to treat venous ulcer (note class II compression stocking on right leg
for prevention of ulceration)
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Medicated bandages such as zinc paste bandages can be
useful in treating some leg ulcers. They can be left undisturbed
for up to a week. A zinc paste bandage containing calamine,
coal tar, or ichthammol can be used if there is associated venous
eczema. Medicated bandages provide no compression.
Intermittent pneumatic compression
Intermittent pneumatic compression is effective in treating
longstanding venous leg ulcers associated with severe oedema
that are refractory to conventional compression therapy alone.
Intermittent pneumatic compression provides compression
(range 20-120 mm Hg) at preset intervals (average 70 seconds)
through an electrically inflatable “boot” of variable lengths. It is
generally used two hours a day for up to six weeks. It improves
venous and lymphatic flow and is useful in patients with
comorbidities that limit mobility. It should be used as an adjunct
to, rather than a substitute for, conventional compression
therapy. Care should be taken in patients with cardiac failure.
Vacuum assisted closure
Vacuum assisted closure is a non-invasive, negative pressure
healing technique that is used to treat a wide range of chronic,
non-healing wounds.
The vacuum assisted closure device uses controlled
subatmospheric pressure to remove excess wound fluid from
the extravascular space, leading to improved local oxygenation
and peripheral blood flow. This promotes angiogenesis and
formation of granulation tissue, which are particularly useful in
deep cavitating wounds to expedite “filling” of the wound space.
Vacuum assisted closure is contraindicated in patients with
thin, easily bruised or abraded skin and in those with neoplasms
as part of the wound floor. Cost and patient adherence may be
issues of concern in some cases.
Hyperbaric oxygen
The use of hyperbaric oxygen has been recommended as an
adjunctive therapy to treat a variety of non-healing wounds (as
many non-healing tissues are hypoxic). Treatment is given by
increasing the atmospheric pressure in a chamber while the
patient is breathing 100% oxygen. Side effects such as seizures
and pneumothorax have been reported with hyperbaric
oxygen.
A systematic review of the Cochrane database, however, has
found insufficient evidence for its effectiveness in healing
chronic wounds, although it might have a role in reducing the
risk of major amputation in patients with diabetic foot ulcers
(see third article this series).
Biosurgery (myiasis)
Biosurgery uses sterile maggots (usually of the green bottle fly,
Lucilia sericata), which digest sloughy and necrotic material
from wounds without damaging the surrounding healthy tissue.
They have been shown in small scale trials to be useful in
the treatment of venous, arterial, and pressure ulcers. Some
patients complain of increased pain in the wound, and
psychological discomfort and aesthetics may be issues for some
individuals.
Other approaches
Other non-surgical approaches that have a scientific basis and
thus have been advocated in the treatment of chronic wounds
include radiant heat dressing, ultrasound therapy, laser
treatment, hydrotherapy, electrotherapy, electromagnetic
therapy, and PUVA therapy (psoralen plus ultraviolet A
irradiation).
However, few randomised controlled trials have studied the
effectiveness of these treatments.
Medicated bandage
Intermittent pneumatic
compression device
Diabetic foot ulcer suitable
for vacuum assisted closure
therapy (far left) and
vacuum assisted closure in
situ (left).
Left: Grade 4 sacral pressure ulcer suitable for vacuum assisted closure
therapy. Right: Vacuum assisted closure in situ
Further rigorous randomised controlled trials are
necessary to ascertain the type of ulcers that may
benefit from treatment with hyperbaric oxygen
Left: Pressure ulcer before debridement with larval (maggot) therapy. Right:
The same ulcer 12 days after debridement with larval therapy (with maggots
in situ)
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Drugs
Pentoxifylline, a methylxanthine that improves perfusion of
peripheral vascular beds, is useful in patients with ulcers
secondary to peripheral vascular disease. It improves capillary
microcirculation by decreasing blood viscosity and reducing
platelet aggregation. It may also inhibit tumour necrosis
factor- , an inflammatory cytokine involved in non-healing
wounds. Although mainly indicated for ulcers secondary to
peripheral vascular disease, pentoxifylline is useful in patients
with venous leg ulcer who cannot tolerate compression or in
whom compression is ineffective. It may also be beneficial in
rare but complex ulcers such as sickle cell ulcers, livedoid
vasculitis, and necrobiosis lipoidica.
Iloprost, a prostacyclin analogue, is an established treatment
for intermittent claudication, severe limb ischaemia, and
prevention of imminent gangrene, and to reduce the pain and
clinical symptoms associated with Raynaud’s disease.
Intravenous iloprost is useful in promoting healing of arterial
ulcers and vasculitic ulcers secondary to connective tissue
diseases such as rheumatoid arthritis and scleroderma.
Antimicrobials including iodine based preparations and silver
releasing agents are used to treat infected wounds (there may be
a dose dependent effect). Antimicrobial agents target bacteria at
several level (cell membrane, cytoplasmic organelle, and nucleic
acid), thus minimising bacterial resistance. They can be used
either on their own or in conjunction with systemic antibiotics.
The many silver releasing agents, in dressing form, aim to
deliver sustained doses of silver to the wound. In addition to the
microbicidal effect of silver on common wound contaminants,
silver may also be effective against methicillin resistant
Staphylococcus aureus (MRSA).
Glyceryl trinitrate, a nitric oxide donor, is effective in the
management of chronic anal fissures when applied topically as
0.2% ointment. Nitric oxide causes vasodilatation, and
uncontrolled studies have suggested a potential role for glyceryl
trinitrate in treating chronic wounds of ischaemic aetiology,
including vasculitic ulcers. Headache, sometimes troublesome, is
the most commonly encountered side effect with glyceryl
trinitrate: lower concentrations may avoid this side effect.
Calcium antagonists such as diltiazem and nifedipine are
useful in treating vasculitic ulcers secondary to Raynaud’s
disease and connective tissue diseases. In Raynaud’s disease,
they restore blood flow to the digits and thus are useful in
treating ulcers and the prevention of necrosis in the extremities.
Non-surgical approaches that have been advocated for treating chronic wounds
Type Mechanism of action/principle Wound type Evidence; current status
Radiant heat dressing Improves tissue oxygenation and increases
subcutaneous oxygen tension
Mainly postoperative wounds;
diabetic ulcers; pressure ulcers
Limited evidence; not in
routine use
Ultrasound therapy Mechanical effect causing micromassage of tissue;
anti-inflammatory effect (due to reduction in
macrophages)
Pressure ulcers and VLU Limited evidence; not in
routine use
Laser Stimulates fibroblast activity and
collagen metabolism; promotes neovascularisation;
inhibits inflammation
VLU, diabetic ulcers, and burns Limited evidence; not in
routine use
Hydrotherapy Form of mechanical debridement; removes loosely
attached devitalised tissue and other cellular debris
from wound bed
Pressure ulcers, VLU, and other
chronic wounds containing
excess slough or necrotic tissue
Practised in USA, but not well
established in UK
Electrotherapy Stimulates body’s endogenous bioelectric system by
delivering therapeutic levels of electric current into
wound
TENS* is used to treat some
ischaemic ulcers, diabetic foot
ulcer, and pressure ulcers
Limited evidence; TENS*
used in specialist centres
Electromagnetic
therapy
Promotes cytokine synthesis in the topically applied
mononuclear cells (autologous)
Ischaemic ulcers, pressure ulcers,
and VLU
Limited evidence; not in
routine use
VLU = venous leg ulcer.
*Form of electrotherapy.
Arterial ulcer suitable for
pentoxifylline treatment
Left: Ulcers secondary to Raynaud’s disease suitable for iloprost therapy.
Right: Ulcer secondary to rheumatoid arthritis suitable for iloprost therapy
Infected wound suitable for topical antimicrobial therapy
Vasculitic ulcer suitable
for treatment with glyceryl
trinitrate
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Systemic corticosteroids are useful in treating ulcers secondary
to connective tissue diseases, including rheumatoid arthritis,
scleroderma, and other vasculitic disorders. They promote
healing by attenuating the excessive inflammatory response.
Long term use of corticosteroids, however, may have a
detrimental effect on healing. Patients taking long term, high
dose steroids should be offered bone protection with
bisphosphonates.
Zinc, an antioxidant, used in a paste bandage may be useful
in treating infected leg ulcers. Oral zinc sulphate treatment may
be beneficial in patients with chronic ulcers who have low
serum zinc levels.
Phenytoin, applied topically, promotes wound healing by
inhibiting the enzyme collagenase. It is effective in some low
grade pressure ulcers and trophic ulcers due to leprosy. The
possibility of systemic absorption and toxicity has limited its use.
Retinoids (derived from vitamin A) have an impact on
wound healing through their effects on angiogenesis, collagen
synthesis, and epithelialisation. Vitamin A is necessary for
normal epidermal maintenance. Although the value of retinoids
in chronic wounds is unclear, topical tretinoin (0.05-0.1%) has
been shown to accelerate re-epithelialisation of dermabraded
and chemically peeled wounds in humans, and partial and full
thickness wounds in animal models.
Analgesics are needed for many ulcers. They may range from
simple analgesics to opiates in individuals whose the pain is
severe. Pain from ulcers associated with neuropathy may benefit
from treatment with certain tricyclic antidepressants (such as
amitriptyline) or antiepileptic drugs (such as gabapentin).
Intractable pain may necessitate intervention by specialist pain
management teams.
Natural products
Honey, of the pasture and manuka varieties, has some
antibacterial action, inhibits excessive inflammatory response,
and promotes autolytic debridement. It is available as an
impregnated dressing or as a gel. Honey is used in the
treatment of a range of chronic wounds. Clinical data to
support its widespread use are limited, however, with
insufficient evidence on the type of wounds that may benefit
and the amount and duration of application required.
Many other natural products—including yoghurt, tea tree
oil, and potato peeling—have been used in various parts of the
world to treat ulcers with varying degrees of success; controlled
studies are lacking.
Drugs and agents that impair healing
Vasoconstrictors, such as nicotine, cocaine, adrenaline
(epinephrine) and ergotamine, cause tissue hypoxia by
adversely affecting the microcirculation, leading to impaired
wound healing. They should be avoided in patients with acute,
surgical, or chronic wounds. Little evidence exists to suggest
that immunosuppressants and antineoplastic drugs (such as
azathioprine, ciclosporin, cyclophosphamide, methotrexate)
affect wound healing in humans. Patients taking
immunosuppressants, however, have a slightly increased risk of
developing malignant ulcers. A biopsy should be taken if an
ulcer develops in these patients.
The photos of maggot therapy were provided by Dr S Thomas of
Zoobiotic, and the photo of the manuka bush was provided by Dr R
Cooper, University of Wales Institute, Cardiff.
Stuart Enoch is research fellow of the Royal College of Surgeons of
England and is based at the Wound Healing Research Unit, Cardiff
University.
Competing interests: For series editors’ competing interests, see the first
article in this series.
BMJ 2006;332:900–3
Effect of some commonly used drugs on wound healing
Class and name
of drug Effects
NSAIDs
Ibuprofen Affects inflammatory phase by inhibiting
cyclo-oxygenase production; reduces
tensile strength of wound
Colchicine Affects inflammatory phase; affects
proliferative phase by decreasing
fibroblast proliferation; affects
remodelling phase by degrading newly
formed extracellular matrix
Corticosteroids
(prednisolone)
Affects haemostatic phase by decreasing
platelet adhesion; affects inflammatory
phase by affecting phagocytosis; affects
remodelling phase by reducing fibroblasts
activity and inhibiting collagen synthesis
Antiplatelets (aspirin) Affects haemostatic phase by inhibiting
platelet aggregation; inhibits inflammation
mediated by arachidonic acid metabolites
Anticoagulants
Heparin Affects haemostatic phase by its effect on
fibrin formation; can lead to thrombus
formation by causing thrombocytopaenia
(white clot syndrome)
Warfarin Affects haemostatic phase by its effect on
fibrin formation; can cause tissue necrosis
and gangrene by release of atheromatous
plaque emboli in form of microcholesterol
crystals (blue toe syndrome)
Vasoconstrictors (nicotine,
cocaine, adrenaline)
Affects proliferative phase by inhibiting
neovascularisation and decreasing
granulation tissue formation; impairs
microcirculation and increases graft
rejection and ulcer necrosis
NSAID = non-steroidal anti-inflammatory drug.
Far left: Infected leg
ulcer suitable for
treatment with honey.
Left: Flowers from
Manuka bush from
which honey is
extracted
Further reading
x Cullum N, Nelson EA, Fletcher AW, Sheldon TA. Compression for
venous leg ulcers. Cochrane Database Syst Rev 2001;(2):CD000265.
x Berliner E, Ozbilgin B, Zarin DA. A systematic review of pneumatic
compression for treatment of chronic venous insufficiency and
venous ulcers. J Vasc Surg 2003;37:539-44.
x Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric
oxygen therapy for chronic wounds. Cochrane Database Syst Rev
2004;(1):CD004123.
x Eginton MT, Brown KR, Seabrook GR, Towne JB, Cambria RA. A
prospective randomized evaluation of negative-pressure wound
dressings for diabetic foot wounds. Ann Vasc Surg 2003;17:645-9.
x Karukonda SR, Flynn TC, Boh EE, McBurney EI, Russo GG,
Millikan LE. The effects of drugs on wound healing—part II.
Specific classes of drugs and their effect on healing wounds. Int J
Dermatol 2000;39:321-33.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
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ABC of wound healing
Recent advances and emerging treatments
Stuart Enoch, Joseph E Grey, Keith G Harding
The healing of acute wounds involves a complex and dynamic
series of events leading to the repair of injured tissues. These
events, triggered by tissue injury, involve four overlapping but
well defined phases: haemostasis, inflammation, proliferation,
and remodelling.
Haemostasis is secured by platelet aggregation and clot
formation. The inflammatory phase begins with the arrival of
phagocytic neutrophils and, later, macrophages at the wound
site; they are important sources of and substrates for growth
factors. The proliferative phase is characterised by the
formation of new blood vessels (angiogenesis), synthesis of
extracellular matrix components such as collagen, granulation
tissue formation, and re-epithelialisation. The extracellular
matrix is continually remodelled during the final phase; an
avascular scar is the end result of the healing process.
Chronic wounds may be arrested in any of the four phases;
commonly, however, disruption occurs in the inflammatory or
the proliferative phases. Many mediators—including
inflammatory cells, growth factors, proteases such as matrix
metalloproteinases (MMPs), and cellular and extracellular
elements—play important roles in different stages of the healing
process. Alterations in one or more of these components may
account for the impaired healing observed in chronic wounds.
Biological based treatments
Cryopreserved human cadaver skin (used in the UK), and
human amniotic membrane and frog skin (used in other parts
of the world) have long been used to treat wounds, particularly
burns. More recently, artificial “skin substitutes” and growth
factors have been developed to help achieve healing in chronic,
non-healing wounds of varying aetiologies. These treatments
target different stages of the healing process and, in the case of
skin substitutes, replace lost tissue.
Artificial skin substitutes, products of tissue engineering,
consist of a microengineered, biocompatible, polymer matrix in
combination with cellular and/or extracellular elements such as
collagen. Several growth factors (proteins involved in
coordinating and regulating various interrelated processes
during wound healing) produced by recombinant DNA
technology have also been developed to aid healing of such
wounds.
Days after wounding (log scale)
Maximumresponse
0.1 0.3 1 3 10
Early Late
30 100 300
• Epithelialisation
• Extracellular matrix
remodelling
• Increase in tensile
strength of wound
• Scar maturation
Phagodytosis
and removal of
foreign bodies
Phagocytosis
and removal of
foreign bodies
Neutrophils
Epithelialisation
and remodelling
• Fibroplast
proliferation
• Collagen synthesis
• Extracellular matrix
reorganisation
• Angiogenesis
• Granulation tissue
formation
• Epithelialisation
• Fibroblast
proliferation
• Collagen synthesis
• Extracellular matrix
reorganisation
• Angiogenesis
• Granulation tissue
formation
• Epithelialisation
MacrophagesMacrophages
Proliferative phaseInflammatory phase
Haemostaticphase
Growth factors
The four phases of acute wound healing
Composition of some tissue engineered skin substitutes
Product by type Content and description
Epidermal
Epicel, Laserskin Cultured epidermal autograft (sheet)
CellSpray Cultured epidermis in suspension form
BioSeed-S Keratinocyte-fibrin-glue suspension
LyphoDerm Lysate of cultured human keratinocytes,
comprising cytokines and growth factors
Dermal (acellular)
Integra Two layered skin substitute comprising
biodegradable matrix and bovine collagen, and
outer silicone layer
AlloDerm Processed human cadaver skin with acellular
dermal matrix and intact basement membrane
Biobrane Porcine dermal collagen bonded to
semipermeable silicone membrane
Dermal (cellular)
TransCyte Allogenic human fibroblasts cultured on nylon
mesh coated with porcine collagen
Dermagraft Allogenic human fibroblasts cultured on
bioabsorbable scaffold
Composite
Apligraf, OrCel Allogenic cultured skin containing keratinocytes,
fibroblasts, and bovine collagen
Tissue engineered skin substitutes in wound healing
Product Uses/advantages Disadvantages
Epicel,
Laserskin*
Permanent coverage for superficial and partial thickness
burns
2-3 week lag period between biopsy and obtaining epidermis;
lacks dermal component
Integra† Immediate permanent coverage for surgically excised full
thickness burns; reconstructive surgery
Requires healthy and non-infected wound base; in burns,
autograft is needed after 3-4 weeks for epithelial cover
AlloDerm† Intended to permanently cover full thickness burns and
deep ulcers; reconstructive surgery
In burns, may necessitate removal after 2-3 weeks; autograft is
needed for epithelial cover; not suitable for infected wounds
Biobrane† To cover extensive partial thickness burns and donor sites Temporary; not suitable for infected burn wounds
TransCyte‡ To cover surgically excised full thickness burns and
non-excised partial thickness burns
Temporary (may need skin grafting after 2-3 weeks); not suitable
for infected wounds and patients allergic to porcine collagen
Dermagraft‡ Non-healing diabetic foot ulcer and venous leg ulcer Not for infected wounds or ulcers with sinus tracts
Apligraf§ Non-healing diabetic foot ulcer and venous leg ulcer Not for infected wounds or patients allergic to bovine collagen
OrCel§ Acute and chronic deep dermal ulcers, partial thickness
burns and donor site wounds
Not for infected wounds or patients allergic to bovine collagen
*Epidermal; †Dermal, acellular; ‡Dermal, cellular; §Composite.
This is the last in a series of 12 articles
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Products targeting inflammatory phase
The production and activity of several proteases—including
metalloproteinases, serine proteases, and neutrophil elastases,
which are tightly regulated in acute wound healing—may be
altered in chronic wounds. Raised levels of such proteases can
be detrimental to wound healing, and products aimed at
counteracting their effect have been developed. One such
product is Promogran, which is designed to inactivate proteases
and also protect the host’s naturally produced growth factors. It
may be useful in the treatment of chronic wounds refractory to
conventional treatments, but it is not effective in infected
wounds or those with unhealthy wound beds.
Products targeting proliferative phase
Growth factors
Fibroblasts, the key type of cell in the healing process, are
attracted to the wound site by several growth factors, including
platelet derived growth factor (PDGF) and TGF- . They
proliferate and produce the matrix proteins fibronectin,
hyaluronan, and later, collagen and proteoglycans, all of which
help to construct the new extracellular matrix.
PDGF attracts keratinocytes and promotes the formation of
granulation tissue. Recombinant PDGF was developed to
expedite the proliferative phase. Becaplermin (as Regranex gel)
Selected growth factors in wound healing*
Growth
factor Wound healing related function Indication
VEGF Stimulates angiogenesis and collateral blood vessel
devlopment; accelerates granulation tissue formation
Has potential for use in diabetic ulcers; gene transfer encoding VEGF shown
to be effective in ischaemic legs and ulcers by formation of collateral blood
vessels
FGF Promotes fibroblast proliferation, matrix deposition,
wound contraction, and angiogenesis
Trials show that topical recombinant bovine FGF is effective in burns, donor
site wounds, and pressure ulcers
KGF Promotes proliferation and migration of
keratinocytes
Trials show that topical recombinant human KGF-2 (repifermin) is effective in
venous leg ulcers
EGF Stimulates keratinocyte differentiation, proliferation,
migration, and adhesion
Trials show that topical recombinant human EGF is effective in partial
thickness burns
PDGF Chemoattractant for neutrophils and fibroblasts;
stimulates fibroblast proliferation
Topical recombinant human PDGF-BB (becaplermin) shown to be effective in
diabetic foot ulcers
G-CSF Stimulates production of neutrophils; enhances
neutrophil and monocyte function; promotes
keratinocyte proliferation
Recombinant human G-CSF injected subcutaneously shown to be effective in
infected diabetic foot ulcers
GM-CSF Mediates epidermal cell proliferation Trials show that topical recombinant human GM-CSF enhances healing of
venous leg ulcers
HGF Recruits neutrophils, monocytes, and mast cells; has
mitogenic and morphogenetic properties
Topical recombinant HGF may accelerate healing of chronic venous leg ulcers
TGF- Attracts macrophages and fibroblasts to wound site;
stimulates angiogenesis and collagen metabolism
Trails show that recombinant human TGF- 2 is effective in diabetic foot ulcers
VEGF = vascular endothelial growth factor; FGF = fibroblast growth factor; KGF = keratinocyte growth factor; EGF = epidermal growth factor; PDGF = platelet
derived growth factor; HGF = hepatocyte growth factor; G-CSF = granulocyte colony stimulating factor; GM-CSF = granulocyte macrophage colony stimulating
factor; TGF- = transforming growth factor . *Only PDGF is licensed for commercial use in the United Kingdom.
Growth factors, including granulocyte colony
stimulating factor (G-CSF) and transforming growth
factor- (TGF- ), have also been used to target this
phase of healing. G-CSF, an endogenous haemopoietic
growth factor, induces terminal differentiation and
release of neutrophils from the bone marrow, enhances
neutrophil and macrophage function, and promotes
keratinocyte proliferation. Recombinant human G-CSF,
injected subcutaneously, has been shown to enhance
healing in infected diabetic foot ulcers.
TGF- is chemotactic for macrophages, induces the
production of collagen and fibronectin, and inhibits
metalloproteinase activity. TGF- 1 has been shown to
accelerate wound healing in animal models, and topical
application of TGF- 2 has been shown to be effective in
the healing of diabetic foot ulcers
Topical application of recombinant
platelet derived growth factor on a
diabetic foot ulcer
Left: Chronic venous leg ulcer suitable for protease inhibitor
dressing. Right: Infected diabetic foot ulcer, associated with
Charcot’s arthropathy, suitable for G-CSF treatment
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is the only growth factor currently licensed for commercial use
in the United Kingdom. A multicentre, double blind
randomised controlled trial in patients with chronic diabetic
foot ulcer showed topical PDGF to be superior to placebo in
promoting healing. Its effectiveness was further enhanced when
used in conjunction with debridement of the wound bed,
emphasising the importance of good basic wound care.
Fibroblast growth factor (FGF) and vascular endothelial
growth factor (VEGF) are active in this phase of repair. FGF
promotes fibroblast proliferation and collagen accumulation
and accelerates the formation of granulation tissue. VEGF plays
a crucial role in angiogenesis.
Cell and matrix based treatments
Autologous fibroblasts (that is, from the patient’s own dermis)
seeded onto a matrix derived from hyaluronic acid have been
shown to be useful in treating diabetic foot ulcers and venous
leg ulcers. Similarly, acellular collagen based matrices designed
to mimic the extracellular matrix have been successfully used to
treat chronic ulcers of varying aetiologies.
Loss of the dermal layer occurs frequently in deep ulcers and
burns. Allogenic fibroblasts, obtained from neonatal human
foreskin and cultured in vitro, have been used to provide the
dermal replacement in such wounds. They are seeded either on a
biologically absorbable scaffold (for example, Dermagraft) or on a
nylon mesh (for example, TransCyte). The proliferating
fibroblasts secrete collagen, matrix proteins, and growth factors
and promote healing. They are designed to provide dermal
replacement in a variety of wounds, though most evidence to date
comes from the treatment of diabetic foot ulcers and burns.
Processed human cadaver skin, in which the cells are
removed to leave a non-antigenic dermal scaffold (for example,
AlloDerm), was one of the first dermal replacement treatments.
Composite skin substitutes comprising allogenic keratinocytes
(epidermal equivalent) and fibroblasts (dermal equivalent) are
also effective in treating diabetic foot ulcers and venous leg
ulcers.
Products targeting epithelialisation and remodelling
Growth factors
Epidermal growth factor (EGF) plays a vital role in keratinocyte
differentiation, proliferation, migration, and adhesion. Topical
application of recombinant EGF is effective in inducing
epithelialisation of partial thickness burns and superficial
granulating wounds. Keratinocyte growth factor (KGF) also
induces proliferation and migration of keratinocytes.
Recombinant human KGF-2 induces proliferation of epithelial
cells and has been shown to enhance healing of venous leg
ulcers. Granulocyte macrophage colony stimulating factor
(GM-CSF), secreted by keratinocytes shortly after injury,
mediates epidermal cell proliferation in an autocrine manner.
Topical recombinant human GM-CSF is effective in the healing
of venous leg ulcers.
TGF- 3 causes reduced deposition of collagen during the
proliferative and remodelling phases, thus reducing scar
formation. Trials into the efficacy of TGF- 3 in the treatment of
hypertrophic scars are under way; the role of TGF- 3 in the
treatment of keloid scars is unclear.
Cell based treatments
Autologous keratinocyte grafts or suspension (obtained after
biopsy and culture of the individual’s own keratinocytes) and
allogenic cultured keratinocyte grafts are used to treat diabetic
foot ulcers, venous leg ulcers, and partial thickness burns. A
keratinocyte suspension in a fibrin sealant matrix has recently
been developed to aid adherence of the keratinocytes to the
Recombinant bovine FGF accelerates the formation of
granulation tissue and epidermal regeneration in
patients with pressure ulcers and burns. Topical VEGF
improves angiogenesis and granulation tissue
formation in ischaemic wounds in animal models.
Intramuscular gene transfer of VEGF has been shown
to improve the collateral circulation in patients with
peripheral vascular disease, leading to healing of
ischaemic ulcers
Venous leg ulcer suitable
for use of dermal or
composite skin substitute
Partial thickness burn
suitable for an epidermal
skin substitute
Wounds suitable for therapies aimed at the remodelling and
epithelialisation phases of wound healing
Left: Hypertrophic scar complicating healing of a sternotomy
wound. Right: Keloid scarring of acne in an adolescent
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wound bed (keratinocyte-fibrin-glue suspension). In addition, a
total lysate of cultured human keratinocytes—comprising
growth factors, cytokines, and matrix molecules, in a
hydrophilic gel—has been developed to treat non-healing
venous leg ulcers. The keratinocyte products are primarily used
in specialist centres in the treatment of chronic wounds and
burns.
Delivery of growth factors
Growth factors are currently delivered to the wound either
topically (such as platelet derived growth factor) or by
subcutaneous injections (such as granulocyte colony stimulating
factor). However, their effectiveness is limited owing to their
short half life and the presence of proteases in chronic wounds.
To overcome this, gene therapy (the transfer of nucleic acid) has
been investigated as a means of providing a longer lasting
source
Concerns about biological products
Lack of level 1 evidence
Randomised controlled trials are lacking for many biological
products, and the current evidence for many biological based
treatments is based on non-randomised prospective trials,
retrospective reviews, small case series (institutional or
personal), and isolated case reports. Furthermore in the case of
growth factors, there is little evidence on dose and duration of
treatment.
No trials have evaluated the effectiveness of two comparable
products (for example, dermal versus dermal skin substitute).
Large, multicentre double blind randomised trials are ongoing
for some of the products.
Transmission of diseases
Before human tissue is obtained for use in tissue engineered
skin substitutes, the donors’ medical histories are extensively
reviewed and blood samples are screened for a wide variety of
infectious diseases, including hepatitis, HIV, and syphilis.
However, products obtained from human sources cannot be
terminally sterilised owing to the presence of viable human
cells, and existing tests cannot provide absolute assurance that
such products will not transmit unknown diseases.
Similarly, tissue (for example, serum, collagen, cells)
obtained from animal sources also carries the theoretical risk of
transmitting infection, particularly prion diseases such as
Creutzfeldt-Jakob disease.
Other concerns
Most biological based products contain bovine, porcine, or
human constituents and thus have religious and ethical
implications.
Tissue engineered skin substitutes and growth factors
produced by recombinant DNA technology are expensive,
which may limit their widespread use.
Stuart Enoch is research fellow of the Royal College of Surgeons of
England and is based at the Wound Healing Research Unit, Cardiff
University.
The ABC of wound healing is edited by Joseph E Grey
(joseph.grey@cardiffandvale.wales.nhs.uk), consultant physician,
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professor
of rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
Competing interests: For series editors’ competing interests, see the first
article in this series.
Products targeting different phases of wound healing
process
Phase Product Growth factors
Inflammatory
phase
Promogran G-CSF, TGF- 1
and 2
Proliferative
phase
Dermagraft, TransCyte,
Alloderm, Apligraf, OrCel
PDGF, FGF,
VEGF
Epithelialisation Epicel, Laserskin, CellSpray,
BioSeed-S, LyphoDerm, Trancell
EGF, KGF,
GM-CSF
Remodelling
and scarring
Silicone based products, such as
silicone gel sheet (Cica-care)
TGF- 3
For abbreviations, see footnote to previous table.
Cutaneous wound healing is a multistep process
requiring the interaction and coordination of many
different cell types and molecules—including growth
factors and proteases. Given the multiple molecular
mechanisms involved, no single mediator, growth factor,
or gene is likely to be successful in accelerating healing.
Similarly, there is heterogeneity within wound types;
identification of the cellular and molecular dysfunction
in individual wounds and targeting or supplementing
them is one of the goals for the future
Current areas of research include regulation of target
genes of cells involved in wound healing; new methods
of delivery of specific cell products to the wound
(including nanotechnology); use of adult pluripotent
stem cells, which are capable of differentiating into
essential cells involved in wound healing (such as
fibroblasts, endothelial cells, keratinocytes). To date,
there is only experimental (though promising) evidence
for gene and stem cell therapy in the treatment of
chronic wounds
Basics of advanced wound care
x Tissue engineered skin substitutes and other biological wound
manipulations are seldom effective in sloughy and exudative
wounds with unhealthy wound beds
x Good wound care (wound debridement and exudate management),
adequate rest, compression, pressure relief, and skin care must be
provided as clinically indicated
x The new approaches and biological based treatments should
complement, not replace, the tenets of good, basic wound care
Key references and further reading
x Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med
1999;341:738-46.
x Harding KG, Morris HL, Patel GK. Healing chronic wounds. BMJ
2002;324:160-3.
x Enoch S, Shaaban H, Dunn KW. Informed consent should be
obtained from patients to use products (skin substitutes) and
dressings containing biological material. J Med Ethics
2005;31(1):2-6.
x Jones J, Nelson E. Skin grafting for venous leg ulcers. Cochrane
Database Syst Rev 2005;(1):CD001737.
x US National Human Genome Research Institute. www.genome.gov
The wound healing chart is adapted from Clark RA. In: Goldsmith LA, ed.
Physiology, biochemistry and molecular biology of the skin. 2nd ed. Vol 1. New
York: Oxford University Press, 1991:577.
BMJ 2006;332:962–5
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