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 ischemia

1st line – hospital admission + immediate smoking cessation

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ACUTE
|
critical ischemia
1st line – 

hospital admission + immediate smoking cessation

Patients often present with critical ischemia and need admission to the hospital at the time of diagnosis. Critical ischemia 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 the 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 revascularization.[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]

See Smoking cessation.

Plus – vasoactive medication

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ACUTE
|
critical ischemia
Plus – 

vasoactive medication

Treatment recommended for ALL patients in selected patient group

Vasoactive dilation (e.g., with nifedipine) is done during initial admission to the hospital, along with any debridement of gangrenous tissue. Further treatments are given depending on severity of ischemia 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 ischemic 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 iIoprost may improve ulcer healing rates, but is not available in the US.

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 ischemia
Consider – 

surgical debridement

Treatment recommended for SOME patients in selected patient group

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

Consider – intravenous antibiotic therapy

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ACUTE
|
critical ischemia
Consider – 

intravenous antibiotic therapy

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 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

penicillin G sodium: 1.5 million units intravenously every 6 hours

OR

ciprofloxacin: 400 mg intravenously every 12 hours

OR

cefuroxime sodium: 750 mg intravenously every 8 hours

and

metronidazole: 500 mg intravenously every 6-8 hours

Consider – analgesia

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ACUTE
|
critical ischemia
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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

Primary options

acetaminophen: 325-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

-- AND --

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 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 ischemia
Consider – 

spinal cord stimulation

Treatment recommended for SOME patients in selected patient group

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

Consider – surgical revascularization/amputation

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ACUTE
|
critical ischemia
Consider – 

surgical revascularization/amputation

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 revascularization indicated mainly in patients with critical ischemia. Patients with noncritical ischemia are indicated for surgical revascularization only if there is severe claudication and a good distal vessel to anastomose onto distally.

If part of a limb is clearly nonviable 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

noncritical ischemia

1st line – urgent smoking cessation

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ONGOING
|
noncritical ischemia
1st line – 

urgent smoking cessation

Patients with noncritical ischemia 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 revascularization.[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

Back
ONGOING
|
noncritical ischemia
Consider – 

vasoactive medication

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 vasoactive 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 ischemic 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 the US.

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

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ONGOING
|
noncritical ischemia
Consider – 

oral antibiotic therapy

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 present), or a third-generation cephalosporin plus metronidazole. However, local protocols should be followed.

Primary options

metronidazole: 500 mg orally three times daily

and

penicillin V potassium: 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 axetil: 250-500 mg orally twice daily

and

metronidazole: 500 mg orally three times daily

Consider – analgesia

Back
ONGOING
|
noncritical ischemia
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

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

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

Primary options

acetaminophen: 325-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

-- AND --

codeine sulfate: 15-60 mg orally every 4-6 hours when required, maximum 360 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: 400-800 mg orally every 4-6 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
|
noncritical ischemia
Consider – 

spinal cord stimulation

Treatment recommended for SOME patients in selected patient group

Spinal cord stimulation may be beneficial in alleviating ischemic 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

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ONGOING
|
noncritical ischemia
Consider – 

sympathectomy

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.[47][40]

Sympathectomy may be sufficient to enable necrotic lesions to heal.[48] It is thought to reduce pain by reducing peripheral resistance and promoting collateral development.[49]

Thorascopic sympathectomy can be used for upper limb symptoms, and lumbar sympathectomy for lower limb symptoms. Due to the invasiveness of procedure, sympathectomy is often a treatment tried when medical therapy has failed and there is no revascularization option. Often used in the more severe cases where there is tissue loss. However, its use has been reported in patients presenting with claudication.[50]

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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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