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This is the 11th in a series of 12 articles
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
Medicated bandage such as zinc paste bandage
numerous drugs have been introduced to aid the management
containing calamine, coal tar, or ichthammol
Bandages and hosiery
Compression bandages are used to treat lower limb ulcers
secondary to venous insufficiency (venous leg ulcers) andlymphoedema. Single layer compression bandages (elastic) are
classified into four groups according to the predeterminedlevels of compression they provide at the ankle. Inelastic
Any form of debridement (sharp, mechanical,
compression bandages (short stretch), when applied at full
autolytic (honey), enzymatic, or biosurgery (maggots))
extension, improve the calf muscle pump action and exerthigher pressures when the patient is upright (and walking) and
Psoralen and ultraviolet light therapy, pentoxifylline
lower pressures at rest. They are useful in patients who areadequately mobile. An elasticated tubular bandage (one to three
Non-surgical and drug treatments to consider in the treatment of chronic
layers) may be useful to treat and prevent venous leg ulcers.
Single layer compression bandages
Class (level of
Top left: Single layer elastic
compression bandage. Top right:
Inelastic (short stretch) compression
bandage. Left: Three layer
elasticated tubular bandage
Multilayer compression bandaging, such as the four layer
method, is well established in the management of venous legulcers. It consists of four layers—padding, a crepe bandage, and
Caution in use of compression bandages
classes 3a and 3b (UK classification) compression
x Appropriate clinical evaluation is essential before using any form of
bandages—applied from the base of the toes to knee. Ideally, it
should be left in place for four to seven days. Although effective,
x Injudicious use may lead to serious complications, including limb
the bulkiness of these layers may lead to non-compliance in
some patients. Its use is limited in heavily exuding ulcers as
x Distal circulation of the limb should be carefully assessed and
repeated dressing changes may be needed.
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
Left: Components of four layer bandage system. Right: Four layer bandage
veins. The use of compression hosiery below the knee is
system to treat venous ulcer (note class II compression stocking on right leg
associated with increased patient adherence
for prevention of ulceration)
VOLUME 332 15 APRIL 2006
Medicated bandages such as zinc paste bandages can be
useful in treating some leg ulcers. They can be left undisturbedfor up to a week. A zinc paste bandage containing calamine,coal tar, or ichthammol can be used if there is associated venouseczema. Medicated bandages provide no compression.
Intermittent pneumatic compression
Intermittent pneumatic compression is effective in treatinglongstanding venous leg ulcers associated with severe oedemathat 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 isgenerally used two hours a day for up to six weeks. It improvesvenous and lymphatic flow and is useful in patients withcomorbidities that limit mobility. It should be used as an adjunctto, rather than a substitute for, conventional compressiontherapy. 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,
The vacuum assisted closure device uses controlled
subatmospheric pressure to remove excess wound fluid fromthe extravascular space, leading to improved local oxygenationand peripheral blood flow. This promotes angiogenesis and
Diabetic foot ulcer suitable
formation of granulation tissue, which are particularly useful in
for vacuum assisted closure
deep cavitating wounds to expedite “filling” of the wound space.
therapy (far left) and
Vacuum assisted closure is contraindicated in patients with
vacuum assisted closure in
thin, easily bruised or abraded skin and in those with neoplasms
as part of the wound floor. Cost and patient adherence may beissues of concern in some cases.
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
Left: Grade 4 sacral pressure ulcer suitable for vacuum assisted closure
and pneumothorax have been reported with hyperbaric
therapy. Right: Vacuum assisted closure in situ
A systematic review of the Cochrane database, however, has
found insufficient evidence for its effectiveness in healingchronic wounds, although it might have a role in reducing the
Further rigorous randomised controlled trials are
risk of major amputation in patients with diabetic foot ulcers
necessary to ascertain the type of ulcers that may
benefit from treatment with hyperbaric oxygen
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. Somepatients complain of increased pain in the wound, andpsychological discomfort and aesthetics may be issues for someindividuals.
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
Left: Pressure ulcer before debridement with larval (maggot) therapy. Right:
However, few randomised controlled trials have studied the
The same ulcer 12 days after debridement with larval therapy (with maggots
VOLUME 332 15 APRIL 2006
Non-surgical approaches that have been advocated for treating chronic wounds
Mechanism of action/principle
Evidence; current status
Radiant heat dressing Improves tissue oxygenation and increases
Mechanical effect causing micromassage of tissue;
anti-inflammatory effect (due to reduction in
collagen metabolism; promotes neovascularisation;
Form of mechanical debridement; removes loosely
attached devitalised tissue and other cellular debris
Stimulates body’s endogenous bioelectric system by
delivering therapeutic levels of electric current into
Promotes cytokine synthesis in the topically applied Ischaemic ulcers, pressure ulcers, Limited evidence; not in
, a methylxanthine that improves perfusion of
peripheral vascular beds, is useful in patients with ulcerssecondary to peripheral vascular disease. It improves capillarymicrocirculation by decreasing blood viscosity and reducingplatelet aggregation. It may also inhibit tumour necrosis
Arterial ulcer suitable for
factor- , an inflammatory cytokine involved in non-healing
wounds. Although mainly indicated for ulcers secondary toperipheral vascular disease, pentoxifylline is useful in patientswith venous leg ulcer who cannot tolerate compression or inwhom compression is ineffective. It may also be beneficial inrare but complex ulcers such as sickle cell ulcers, livedoidvasculitis, and necrobiosis lipoidica.
, a prostacyclin analogue, is an established treatment
for intermittent claudication, severe limb ischaemia, andprevention of imminent gangrene, and to reduce the pain andclinical symptoms associated with Raynaud’s disease.
Intravenous iloprost is useful in promoting healing of arterialulcers and vasculitic ulcers secondary to connective tissue
Left: Ulcers secondary to Raynaud’s disease suitable for iloprost therapy.
Right: Ulcer secondary to rheumatoid arthritis suitable for iloprost therapy
diseases such as rheumatoid arthritis and scleroderma.
including iodine based preparations and silver
releasing agents are used to treat infected wounds (there may bea dose dependent effect). Antimicrobial agents target bacteria atseveral level (cell membrane, cytoplasmic organelle, and nucleicacid), thus minimising bacterial resistance. They can be usedeither on their own or in conjunction with systemic antibiotics.
The many silver releasing agents, in dressing form, aim todeliver sustained doses of silver to the wound. In addition to themicrobicidal effect of silver on common wound contaminants,silver may also be effective against methicillin resistantStaphylococcus aureus
, a nitric oxide donor, is effective in the
management of chronic anal fissures when applied topically as
Infected wound suitable for topical antimicrobial therapy
0.2% ointment. Nitric oxide causes vasodilatation, anduncontrolled studies have suggested a potential role for glyceryltrinitrate in treating chronic wounds of ischaemic aetiology,including vasculitic ulcers. Headache, sometimes troublesome, isthe most commonly encountered side effect with glyceryltrinitrate: lower concentrations may avoid this side effect.
such as diltiazem and nifedipine are
useful in treating vasculitic ulcers secondary to Raynaud’sdisease and connective tissue diseases. In Raynaud’s disease,
Vasculitic ulcer suitable
they restore blood flow to the digits and thus are useful in
for treatment with glyceryl
treating ulcers and the prevention of necrosis in the extremities.
VOLUME 332 15 APRIL 2006
are useful in treating ulcers secondary
Effect of some commonly used drugs on wound healing
to connective tissue diseases, including rheumatoid arthritis,scleroderma, and other vasculitic disorders. They promote
Class and name
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
cyclo-oxygenase production; reducestensile strength of wound
, 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
, 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.
remodelling phase by reducing fibroblastsactivity and inhibiting collagen synthesis
(derived from vitamin A) have an impact on
wound healing through their effects on angiogenesis, collagen
platelet aggregation; inhibits inflammation
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
Affects haemostatic phase by its effect on
been shown to accelerate re-epithelialisation of dermabraded
and chemically peeled wounds in humans, and partial and full
are needed for many ulcers. They may range from
Affects haemostatic phase by its effect on
simple analgesics to opiates in individuals whose the pain is
fibrin formation; can cause tissue necrosisand gangrene by release of atheromatous
severe. Pain from ulcers associated with neuropathy may benefit
plaque emboli in form of microcholesterol
from treatment with certain tricyclic antidepressants (such as
amitriptyline) or antiepileptic drugs (such as gabapentin).
Affects proliferative phase by inhibiting
Intractable pain may necessitate intervention by specialist pain
granulation tissue formation; impairsmicrocirculation and increases graft
Honey, of the pasture and manuka varieties, has some
NSAID = non-steroidal anti-inflammatory drug.
antibacterial action, inhibits excessive inflammatory response,and promotes autolytic debridement. It is available as animpregnated dressing or as a gel. Honey is used in thetreatment of a range of chronic wounds. Clinical data to
Far left: Infected leg
support its widespread use are limited, however, with
ulcer suitable for
insufficient evidence on the type of wounds that may benefit
treatment with honey.
and the amount and duration of application required.
Left: Flowers from
Many other natural products—including yoghurt, tea tree
Manuka bush from
which honey is
oil, and potato peeling—have been used in various parts of the
world to treat ulcers with varying degrees of success; controlledstudies are lacking.
Drugs and agents that impair healing
x Cullum N, Nelson EA, Fletcher AW, Sheldon TA. Compression for
Vasoconstrictors, such as nicotine, cocaine, adrenaline
venous leg ulcers. Cochrane Database Syst Rev
(epinephrine) and ergotamine, cause tissue hypoxia by
x Berliner E, Ozbilgin B, Zarin DA. A systematic review of pneumatic
adversely affecting the microcirculation, leading to impaired
compression for treatment of chronic venous insufficiency andvenous ulcers. J Vasc Surg
wound healing. They should be avoided in patients with acute,
x Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric
surgical, or chronic wounds. Little evidence exists to suggest
oxygen therapy for chronic wounds. Cochrane Database Syst Rev
that immunosuppressants and antineoplastic drugs (such as
azathioprine, ciclosporin, cyclophosphamide, methotrexate)
x Eginton MT, Brown KR, Seabrook GR, Towne JB, Cambria RA. A
affect wound healing in humans. Patients taking
prospective randomized evaluation of negative-pressure wound
immunosuppressants, however, have a slightly increased risk of
dressings for diabetic foot wounds. Ann Vasc Surg
developing malignant ulcers. A biopsy should be taken if an
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
The photos of maggot therapy were provided by Dr S Thomas of
Zoobiotic, and the photo of the manuka bush was provided by Dr RCooper, University of Wales Institute, Cardiff.
The ABC of wound healing is edited by Joseph E Grey
Stuart Enoch is research fellow of the Royal College of Surgeons of
(firstname.lastname@example.org), consultant physician,
England and is based at the Wound Healing Research Unit, Cardiff
University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, and
honorary consultant in wound healing at the Wound Healing
Competing interests: For series editors’ competing interests, see the first
Research Unit, Cardiff University, and by Keith G Harding, director of
the Wound Healing Research Unit, Cardiff University, and professorof rehabilitation medicine (wound healing) at Cardiff and Vale NHS
Trust. The series will be published as a book in summer 2006.
VOLUME 332 15 APRIL 2006
The following items must be submitted to office in a sealed envelope: 1. Information as described in attached document. 2. Letter of Agreement (see below). A. All proposals must be submitted in TRIPLICATE. B. The Letter of Agreement must: 1. Be addressed to the Westmoreland County Commissioners. 2. Indicate specifically that the proposal is for Westmoreland Manor 3. Indicate that the c
Copyright 2008 by The Gerontological Society of AmericaRacial and Ethnic Disparities in the Treatment ofIlene H. Zuckerman, Priscilla T. Ryder, Linda Simoni-Wastila, Thomas Shaffer,Masayo Sato, Lirong Zhao, and Bruce StuartLamy Center on Drug Therapy and Aging, Department of Pharmaceutical Health Services Research,University of Maryland School of Pharmacy, Baltimore. Objectives. Numerous stu