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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 Treatment
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 Non-surgical treatments
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)
BMJ 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
Medicated bandage
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.
Intermittent pneumatic
compression device

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 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 situ (left).
as part of the wound floor. Cost and patient adherence may beissues 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
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 (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. Somepatients complain of increased pain in the wound, andpsychological discomfort and aesthetics may be issues for someindividuals.
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
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
BMJ VOLUME 332 15 APRIL 2006
Non-surgical approaches that have been advocated for treating chronic wounds
Mechanism of action/principle
Wound type
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 Pentoxifylline, 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 pentoxifylline treatment
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.
Iloprost, 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.
Antimicrobials 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 (MRSA).
Glyceryl trinitrate, 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.
Calcium antagonists 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.
BMJ VOLUME 332 15 APRIL 2006
Systemic corticosteroids 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 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 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.
remodelling phase by reducing fibroblastsactivity and inhibiting collagen synthesis Retinoids (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 Analgesics 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 Natural products
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 extracted
world to treat ulcers with varying degrees of success; controlledstudies are lacking.
Further reading
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 2001;(2):CD000265.
(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 2003;37:539-44.
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 2003;17:645-9.
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 (, 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.
BMJ VOLUME 332 15 APRIL 2006



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