Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

critical ischaemia

1st line – hospital admission + immediate smoking cessation

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ACUTE
|
critical ischaemia
1st line – 

hospital admission + immediate smoking cessation

Patients often present with critical ischaemia and need admission to hospital at the time of diagnosis. Critical ischaemia is defined as gangrene or rest pain lasting >2 weeks and requiring regular opioid analgesia. Its definition may also include ankle pressure of <50 mmHg. Initial admission to hospital involves confirming diagnosis, excluding differential diagnosis, and arterial imaging.

Smoking cessation reduces the incidence of amputation.[2][5] It improves patency and limb salvage rates in those who do undergo surgical revascularisation.[31][32] From a group of 43 patients who stopped smoking, 94% avoided an amputation.[33] Patients who continue to smoke have a 19% major amputation rate; this is 2.73 times greater than for people who have ceased smoking, according to one study.[32][34] Smoking increases flare-ups and reduces ulcer healing. A return to smoking following cessation may lead to a flare-up of the disease. Smoking only 1 or 2 cigarettes a day, using smokeless tobacco (chewing tobacco), or using nicotine replacement therapy may all keep the disease active.[19][20]

For more information see the BMJ Best Practice topic 'Smoking Cessation'.

Plus – vasoactive medication

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ACUTE
|
critical ischaemia
Plus – 

vasoactive medication

Treatment recommended for ALL patients in selected patient group

Vasoactive dilation (e.g., with nifedipine) is done during initial admission to hospital, along with debridement of any gangrenous tissue. Further treatments are given depending on severity of ischaemia and degree of pain. Pentoxifylline and cilostazol have had good effects, although there is little supportive data. They are not routinely used. Pentoxifylline has been shown to improve pain and healing in ischaemic ulcers.[37] Treatment with pentoxifylline can be tried after other medical therapies have failed. Cilostazol could be tried in conjunction with or following failure of other medical therapies (e.g., nifedipine).[38] It is contra-indicated in the following: patients with unstable angina, recent myocardial infarction, or coronary intervention (within 6 months); patients receiving 2 or more other antiplatelet agents or anticoagulants; and patients with history of severe tachyarrhythmia.

Intravenous iloprost may improve ulcer healing rates, but is not available in many countries.

Primary options

nifedipine: 5 mg orally (immediate-release) three times daily initially, increase according to response, maximum 120 mg/day; 30 mg orally (extended-release) once daily initially, increase according to response, maximum 90 mg/day

Secondary options

pentoxifylline: consult specialist for guidance on dose

OR

cilostazol: consult specialist for guidance on dose

Consider – surgical debridement

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ACUTE
|
critical ischaemia
Consider – 

surgical debridement

Additional treatment recommended for SOME patients in selected patient group

Vasoactive dilation is done during initial admission to hospital, along with debridement of any gangrenous tissue.

Consider – intravenous antibiotic therapy

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ACUTE
|
critical ischaemia
Consider – 

intravenous antibiotic therapy

Additional treatment recommended for SOME patients in selected patient group

Antibiotics are indicated only in the presence of infection or wet gangrene. Aerobic and anaerobic cover is needed.

Regimens include a penicillin plus metronidazole, or ciprofloxacin (if Pseudomonas is present), or a third-generation cephalosporin plus metronidazole. However, local protocols should be followed.

Primary options

metronidazole: 500 mg intravenously every 6-8 hours

and

benzylpenicillin sodium: 900 mg intravenously every 6 hours

OR

ciprofloxacin: 400 mg intravenously every 12 hours

OR

cefuroxime: 750 mg intravenously every 8 hours

and

metronidazole: 500 mg intravenously every 6-8 hours

Consider – analgesia

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ACUTE
|
critical ischaemia
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

For acute ischaemic pain, paracetamol and an opioid (weak or strong) are recommended, depending on the severity of pain.[43] Severe pain often requires admission to hospital so that disease can be controlled or the extent of disease can be assessed.

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

-- AND --

codeine phosphate: 30-60 mg orally every 4 hours when required, maximum 240 mg/day

or

morphine sulfate: 10-30 mg orally (immediate-release) every 4 hours when required, titrate dose according to response; 2.5 to 10 mg subcutaneously/intramuscularly/intravenously every 2-6 hours when required, titrate dose according to response

Consider – spinal cord stimulation

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ACUTE
|
critical ischaemia
Consider – 

spinal cord stimulation

Additional treatment recommended for SOME patients in selected patient group

Spinal cord stimulation may be beneficial in alleviating ischaemic pain. It is performed by an implantable stimulator.[44][45][46]

Consider – intravenous guanethidine

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ACUTE
|
critical ischaemia
Consider – 

intravenous guanethidine

Additional treatment recommended for SOME patients in selected patient group

Guanethidine reduces catecholamine release by acting on the Na+-ATPase-dependent pump. Reduction of rest pain and ulceration healing have been reported with guanethidine injections into the affected limb, sometimes with the additional use of a Bier block (intravenous regional sympathetic blockade).[47][48] Injections can be easily repeated if beneficial effects are seen.

Data on the effectiveness of guanethidine are limited, and it is not available in many countries.

Consider – surgical revascularisation/amputation

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ACUTE
|
critical ischaemia
Consider – 

surgical revascularisation/amputation

Additional treatment recommended for SOME patients in selected patient group

Due to the lack of patent distal vessels, bypass is often not an option. Angiography may reveal potential distal anastomotic sites, allowing bypass to help ulcer healing. However, primary graft patency rates are 41% at 1 year, 32% at 5 years, and 30% at 10 years; secondary patency rates are 54% at 1 year, 47% at 5 years, and 39% at 10 years.[32]

Surgical revascularisation is indicated mainly in patients with critical ischaemia. Patients with non-critical ischaemia are indicated for surgical revascularisation only if there is severe claudication and a good vessel to anastomose onto distally.

If part of a limb is clearly non-viable from the outset or attempts at revascularisation should fail, amputation is required. Careful consideration of the most appropriate type and level of amputation should be made in consultation with the patient, bearing in mind factors such as likelihood of successful healing, patient motivation and social circumstances, and the patient's potential functional outcomes with an appropriate prosthesis, if required.

ONGOING

non-critical ischaemia

1st line – urgent smoking cessation

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ONGOING
|
non-critical ischaemia
1st line – 

urgent smoking cessation

Patients with non-critical ischaemia present with either claudication or new onset of rest pain.

Smoking cessation reduces the incidence of amputation.[2][5] It improves patency and limb salvage rates in those who do undergo surgical revascularisation.[31][32] From a group of 43 patients who stopped smoking, 94% avoided an amputation.[33]

Patients who continue to smoke have a 19% major amputation rate; this is 2.73 times greater than for people who have ceased smoking, according to one study.[32][34]

Smoking increases flare-ups and reduces ulcer healing. A return to smoking following cessation may lead to a flare-up of the disease.

Smoking only 1 or 2 cigarettes a day, using smokeless tobacco (chewing tobacco), or using nicotine replacement therapy may all keep the disease active.[19][20]

Consider – vasoactive medication

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ONGOING
|
non-critical ischaemia
Consider – 

vasoactive medication

Additional treatment recommended for SOME patients in selected patient group

Nifedipine, a calcium-channel blocker, may cause peripheral vasodilation and improve distal blood flow.[5]

It has been shown to be of benefit in patients with lower limb trophic changes and symptoms, and is often given in combination with other therapies, such as cessation of smoking, antibiotics, and iloprost.[35][36]

Pentoxifylline and cilostazol are vaso-active drugs that have had good effects, although there are few supportive data. They are not routinely used. Pentoxifylline has been shown to improve pain and healing in ischaemic ulcers.[37] Treatment with pentoxifylline can be tried after other medical therapies have failed. Cilostazol could be tried in conjunction with or following failure of other medical therapies (e.g., nifedipine).[38] It is contraindicated in the following: patients with unstable angina, recent myocardial infarction, or coronary intervention (within 6 months); patients receiving 2 or more other antiplatelet agents or anticoagulants; and patients with history of severe tachyarrhythmia.

Intravenous iloprost may improve ulcer healing rates, but is not available in many countries.

Primary options

nifedipine: 5 mg orally (immediate-release) three times daily initially, increase according to response, maximum 120 mg/day; 30 mg orally (extended-release) once daily initially, increase according to response, maximum 90 mg/day

Secondary options

pentoxifylline: consult specialist for guidance on dose

OR

cilostazol: consult specialist for guidance on dose

Consider – oral antibiotic therapy

Back
ONGOING
|
non-critical ischaemia
Consider – 

oral antibiotic therapy

Additional treatment recommended for SOME patients in selected patient group

Antibiotics are indicated only in the presence of infection or wet gangrene. Aerobic and anaerobic cover is needed.

Amoxicillin/clavulanate may be adequate, or a penicillin plus metronidazole, or ciprofloxacin (if Pseudomonas is present), or a third-generation cephalosporin plus metronidazole. However, local protocols should be followed.

Primary options

metronidazole: 500 mg orally three times daily

and

phenoxymethylpenicillin: 500 mg orally four times a day

OR

amoxicillin/clavulanate: 500 mg orally three times daily

More

OR

ciprofloxacin: 500 mg orally twice daily

OR

cefuroxime: 250-500 mg orally twice daily

and

metronidazole: 500 mg orally three times daily

Consider – analgesia

Back
ONGOING
|
non-critical ischaemia
Consider – 

analgesia

Additional treatment recommended for SOME patients in selected patient group

For acute ischaemic pain, paracetamol and an opioid (weak or strong) are recommended, depending on the severity of pain.[43]

Non-steroidal anti-inflammatory drugs (NSAIDs) can be used to treat superficial venous thrombophlebitis.

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

-- AND --

codeine phosphate: 30-60 mg orally every 4 hours when required, maximum 240 mg/day

or

morphine sulfate: 10-30 mg orally (immediate-release) every 4 hours when required, titrate dose according to response; 2.5 to 10 mg subcutaneously/intramuscularly/intravenously every 2-6 hours when required, titrate dose according to response

Secondary options

ibuprofen: 300-400 mg orally every 6-8 hours when required, maximum 2400 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) two or three times daily

Consider – spinal cord stimulation

Back
ONGOING
|
non-critical ischaemia
Consider – 

spinal cord stimulation

Additional treatment recommended for SOME patients in selected patient group

Spinal cord stimulation may be beneficial in alleviating ischaemic pain. It has been shown to be of benefit in patients with lower limb symptoms ranging from claudication and pain to ulceration and trophic changes. Often used after medical therapy has failed. Spinal cord stimulation is performed by an implantable stimulator.[44][45][46]

Consider – sympathectomy

Back
ONGOING
|
non-critical ischaemia
Consider – 

sympathectomy

Additional treatment recommended for SOME patients in selected patient group

Sympathectomy can be chemical or surgical, lumbar, or thorascopic. Both positive and negative results have been reported with lumbar sympathectomy.[49][40]

Sympathectomy may be sufficient to enable necrotic lesions to heal.[50] It is thought to reduce pain by reducing peripheral resistance and promoting collateral development.[51]

Thorascopic sympathectomy can be used for upper limb symptoms, and lumbar sympathectomy for lower limb symptoms. Due to the invasiveness of the procedure, sympathectomy is often a treatment tried when medical therapy has failed and there is no revascularisation option. Often used in the more severe cases where there is tissue loss. However, its use has been reported in patients presenting with claudication.[52]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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