eMedicine Specialties > Vascular Surgery > Medical Topics

Infrainguinal Occlusive Disease

Richard M Stillman, MD, FACS, Honorary Medical Staff, Northwest Medical Center; Former Chief of Staff and Medical Director, Wound Healing Center, Department of Surgery, Northwest Medical Center

Updated: Jun 24, 2008

Introduction

This article is a review of chronic infrainguinal atherosclerotic arterial occlusive disease caused by atherosclerosis involving the femoral, popliteal, and/or infrapopliteal arteries. Because chronic atherosclerotic disease may result in acute circulatory compromise, acute arterial occlusion is also covered. Less common etiologies of lower extremity arterial insufficiency, such as atheroembolism, Buerger disease, popliteal artery entrapment syndrome, and cystic adventitial disease, are briefly discussed.

Decision-making in the management of vascular disease changes frequently as new information becomes available and as new technologies emerge.¹ Furthermore, therapeutic recommendations for a given population may not be applicable to individual patients with even slightly differing risk factors, co-morbidities, or vascular anatomy.²

Problem

Although most patients with infrainguinal disease are treated nonoperatively, over 100,000 vascular reconstructive procedures are performed yearly in the United States alone. Unfortunately, intervention fails in up to 50% of cases within 5 years.³

Of the symptomatic patients under medical care, within 5 years, approximately 25% develop progressive symptoms, 5-10% require surgical intervention, and 1-2% undergo major amputation.⁴ The vast majority of patients with intermittent claudication remain stable or improve with noninvasive management. According to Baumgartner, Schainfeld, and Graziani, 25% of patients with claudication will eventually require revascularization and only 5% will develop critical limb ischemia.⁵ Within the first year after the initial diagnosis, 6-9% of patients require intervention.⁵ Subsequently 2-3% of patients per year require intervention.⁵

Because lower extremity atherosclerosis is a marker for systemic atherosclerotic disease, these patients have significant systemic morbidities. Thirty percent of patients with peripheral artery disease die within 5 years and 40% die within 10 years.^4,6 Feringa et al observed a cohort of 2,642 patients having ankle-brachial indices less than or equal to 0.9.⁶ They discovered that the major factors associated with mortality in this group of patients included renal dysfunction, heart failure, ST-segment changes, age greater than 65 years, hypercholesterolemia, ankle-brachial index lower than 0.60, Q-waves, diabetes, cerebrovascular disease, and pulmonary disease. They also found that the use of statins, aspirin, and beta-blockers correlated with reduced 10-year mortality.

Frequency

Chronic atherosclerotic lower extremity disease is present in 20% of the population older than 55 years.⁷ Most affected persons are asymptomatic. In fact, estimates indicate that only approximately 20% of people with atherosclerotic lower extremity disease present to a physician because of symptoms. Another 20% are symptomatic but do not seek medical attention.

Etiology

Commonly accepted risk factors for both the occurrence and progression of atherosclerotic vascular disease include abnormal glucose tolerance, cigarette smoking, advanced age, hyperlipidemia, and hypertension.⁸

Certain biochemical factors have also been shown to be independent risk factors for atherosclerotic peripheral vascular disease. Such factors include increased plasma fibrinogen levels,⁹ hyperhomocysteinemia,^10,11 and high-sensitivity C-reactive protein.¹² These factors may also increase the risk of bypass graft stenosis and reocclusion.

When more than one risk factor is present, the cumulative risk is often greater than individual risk factors combined. This is especially true of cigarette smoking, which, when accompanied by another risk factor (such as hypertension or hyperlipidemia) increases the disease risk to more than twice the sum of the individual risks.

Pathophysiology

Atherosclerotic occlusive disease

With atherosclerotic occlusion of a major lower extremity artery, the limb is perfused via collateral pathways. Although this alternate pathway may be adequate at rest, it becomes inadequate as the oxygen demands of the leg musculature increase with activity. This results in calf muscle pain or fatigue, a symptom known as intermittent claudication. As the degree of atherosclerotic occlusion worsens, blood flow, even at rest, may become impaired. This may cause ischemic pain at rest, ischemic ulceration, and gangrene.

Acute arterial occlusion

Acute occlusion of peripheral arteries commonly involves the infrainguinal segment. Underlying atherosclerotic disease may result in intraluminal strictures that impair blood flow and cause acute thrombosis. Emboli typically lodge at bifurcations and, hence, tend to occlude the distal common femoral artery (the most common site, comprising 34% of all arterial emboli) or distal popliteal artery (14%). Popliteal artery aneurysms may thrombose as a result of turbulent blood flow. The clinical indications of acute occlusion of lower extremity arteries are the following classic 6 "P"s:

Paresthesias
Pain
Poikilothermia (coolness)
Pallor
Pulselessness
Paralysis

The anatomic level at which pulse loss occurs helps identify the location of the occlusion.

Presentation

Most people harboring atherosclerotic disease of the lower extremities are asymptomatic; others develop ischemic symptoms. Some patients attribute ambulatory difficulties to "old age," unaware of the existence of a potentially correctible problem.

Symptomatic patients may present with intermittent claudication, ischemic pain at rest, nonhealing ulceration of the foot (see Image 1), or frank ischemia of the foot.

Cramping or fatigue of major muscle groups in one or both lower extremities that is reproducible upon walking a specific distance suggests intermittent claudication. This symptom increases during ambulation until walking is no longer possible, and it is relieved by several minutes of rest. The onset of claudication may occur sooner with more rapid walking or when walking uphill or up stairs. The claudication of infrainguinal occlusive disease typically involves the calf muscles, while symptoms that occur in the buttocks or thighs suggest aortoiliac occlusive disease.¹³

Physical

Physical examination discloses absent or diminished peripheral pulses below a certain level. Although diminished common femoral artery pulsation is characteristic of aortoiliac disease, infrainguinal disease alone is characterized by normal femoral pulses at the level of the inguinal ligament and diminished or absent pulses distally.

Specifically, loss of the femoral pulse just below the inguinal ligament occurs with a proximal superficial femoral artery occlusion. Loss of the popliteal artery pulse suggests superficial femoral artery occlusion, typically in the adductor canal. Loss of pedal pulses is characteristic of disease involving the distal popliteal artery or its trifurcation.

Importantly however, be aware that absence of the dorsalis pedis pulse may be a normal anatomic variant, noted in approximately 10% of the population. On the other hand, the posterior tibial pulse is present in 99.8% of persons aged 0-19 years. Hence, absence of both pedal pulses is a more specific indicator of peripheral arterial disease.

Other findings suggestive of atherosclerotic disease include a bruit heard overlying the iliac or femoral arteries, skin atrophy, loss of pedal hair growth, cyanosis of the toes, ulceration or ischemic necrosis, and, after 1-2 minutes of elevation above heart level, pallor of the involved foot followed by dependent rubor (see Image 2).

Differential diagnoses

Pseudoclaudication

Although ischemic findings in the face of absent pulses clearly pinpoint arterial insufficiency as the culprit, intermittent claudication, even when associated with absent pulses, is not always due to arterial insufficiency.

If symptoms are not always reproducible (ie, the patient sometimes has "good days" when ambulation is not limited by claudication) or if the symptoms are associated with low back pain or radiculopathy, the clinician should consider the possibility of pseudoclaudication, which occurs as a result of spinal stenosis or cauda equina syndrome.

In that case, the pulse deficit may be an incidental finding of asymptomatic atherosclerosis. Noninvasive vascular laboratory testing (see Lab Studies), lumbosacral imaging, and neurologic evaluation all may contribute to distinguishing between these possibilities.

Two rather unusual conditions, venous claudication due to extensive iliofemoral venous thrombosis and chronic compartment syndrome due to calf muscle hypertrophy in athletes, result in a bursting type of pain in the calf with ambulation, which subsides slowly with elevation. In each case, the etiology is impaired venous outflow.

Atheroembolism

Patchy areas of ischemia involving the feet, especially in the presence of palpable pedal pulses, suggest the possibility of atheroembolism of plaque fragments from ulcerated, although nonocclusive, proximal atherosclerotic plaques or from thrombus lining the wall of an infrarenal aortic aneurysm (see Abdominal Aortic Aneurysm).¹⁴

Buerger disease

Severe ischemia of the toes with absent pedal pulses but normal proximal pulses in a man aged 35-50 years who smokes cigarettes may be the result of Buerger disease (thromboangiitis obliterans).¹⁵ Ischemia of the fingers may also be present. The digits are cool, moist, mottled, and sometimes have tender shallow ulcers. Migratory superficial phlebitis may occur.

Collagen-vascular disease must be excluded.¹⁶ See the eMedicine article Buerger Disease (Thromboangiitis Obliterans). Angiography reveals pathognomonic findings of "corkscrew" arteries. Treatment is discontinuation of smoking and good local wound care. Vascular surgery is rarely possible because of the poor quality of the distal arteries.

Complex regional pain syndromes (eg, posttraumatic pain syndromes, causalgia, mimocausalgia, Sudeck atrophy, reflex sympathetic dystrophy)

Complex regional pain syndromes (CRPSs) have been classified by the World Health Organization as CRPS II (ie, causalgia), which is associated with a demonstrable nerve injury, and as CRPS I (ie, mimocausalgia, reflex sympathetic dystrophy, Sudeck atrophy), which includes the remainder. Causalgia (ie, causos, heat; algos, pain) was first described in patients with arterial and nerve injuries sustained during the American Civil War. Both variants remain poorly understood and often misdiagnosed.

Although the exact pathophysiology is elusive, the sympathetic nervous system clearly plays a focal role. Therefore, surgical sympathectomy—perfected decades ago by vascular surgeons to manage nonreconstructible arterial disease (a common situation at the time)—was once the mainstay for treatment of the CRPSs.

Although surgical sympathectomy is now mostly notable only for historic purposes, sympathetic blockade is quite effective and is commonly performed for the CRPSs. Hence, currently the treatment of CRPSs is performed mainly by pain management specialists. Nonetheless, because the vascular surgeon has always been primarily responsible for the diagnosis of extremity symptoms, it is not uncommon for patients with CRPS to report to a vascular surgeon because of extremity pain.

Such pain may occur after extremity trauma but may seem disproportionate to the degree of injury.¹⁷ Pain may also manifest after delayed revascularization of an acutely ischemic extremity. The diagnosis is often one of exclusion and thus requires a high index of clinical suspicion. The diagnosis should be considered more strongly if severe superficial burning pain and agonizing hypersensitivity are present and are associated with vasomotor abnormalities such as edema, erythema, and hyperhidrosis. Radiographic studies may demonstrate relative and patchy osteopenia in the involved extremity.

In addition to symptomatic relief, management of the CRPSs requires sympathetic blockade. This is best performed during the early, acute stage when the clinical course may be reversible. As the disease progresses, the erythema gives way to cyanotic mottling, the acute edema transforms to brawny edema, and the pain becomes unrelenting and disabling. These findings occur at approximately the third month and represent the second, or dystrophic, stage. At this point, both plain radiographs and bone scans tend to demonstrate indicative findings.

Over time, disuse leads to atrophy, soft tissue fibrosis, and joint contractures. Radiographs confirm ankylosis and severe osteoporosis. This signals the third, or atrophic, stage. Note that atrophy can also occur because of intentional disuse for anticipated secondary gain. Such patients reportedly do not respond to treatment until litigation has concluded.

Typically, the clinician does not even consider the diagnosis of a CRPS until the second stage. At that point, a dramatic clinical response to sympathetic blockade may confirm the diagnosis. Unfortunately, too much damage may have already occurred for sympathetic ablation to be effective and to break the vicious cycle of pain, sympathetic overactivity, and pain; the progression of the CRPS may be inexorable and irreversible.

One other caveat is that in the face of coexisting arterial disease, the vascular surgeon who may attribute the symptoms to ischemia and thereby may consider bypass should be aware that a surgical incision tends to exacerbate the pain in an extremity afflicted with a CRPS.

For more information, also see the eMedicine article Complex Regional Pain Syndrome.

Popliteal artery entrapment syndrome

Intermittent claudication occurring in younger persons (from the teens to approximately age 45 y), particularly males, raises the possibility of popliteal artery entrapment syndrome.¹⁸

In this unusual condition, the artery follows an aberrant course around the gastrocnemius muscle, usually medial to the medial head instead of between the 2 heads of this muscle. Ambulation causes the muscle to compress the artery and results in transient loss of distal blood flow. Over time, the artery may thrombose or become aneurysmal.

Prior to complete thrombosis, this condition can sometimes be confirmed clinically by noting loss of the pedal pulse upon active plantar flexion or passive dorsiflexion of the foot. CT scanning or MRI can reveal the muscular abnormality, and angiography with stress views can confirm the diagnosis.

Treatment entails sectioning the aberrant muscle fibers. Bypass grafting is needed if the occlusion is chronic in nature. Assessing the contralateral side is important because one third of cases are bilateral.

Cystic adventitial disease of the popliteal artery

Intermittent claudication of abrupt onset occurring in a relatively young male also may be the result of cystic adventitial disease of the popliteal artery.¹⁹

This rare congenital anomaly is the result of ganglionlike cysts, perhaps from an adjacent synovium, compressing the artery. This compression may eventually lead to thrombosis of the artery.

Prior to occlusion, pedal pulses may be found to disappear with flexion of the knee joint. Ultrasonography, CT scanning, or MRI may demonstrate the cyst, while angiography may demonstrate a characteristic hourglass deformity, which has been termed the scimitar sign.

Cystic adventitial disease of the popliteal artery is treated surgically by removing the cyst. Vascular bypass is required if occlusion has occurred.²⁰

Indications

Indications for lower extremity revascularization include gangrene, pain at rest, nonhealing arterial ulcer, and disabling claudication.

Relevant Anatomy

The inguinal (Poupart) ligament is a tough, fibrous band stretching from the anterior superior iliac spine to the pubic tubercle. The common femoral artery is a continuation of the external iliac artery, beginning just under the middle of the inguinal ligament. It is palpable as the femoral pulse and is well suited to both percutaneous and surgical access because of its relatively superficial position. Approximately 1-2 inches distal to the inguinal ligament, the common femoral artery divides into the deep femoral (profunda femoris) artery, usually arising in the posterolateral position, and the superficial femoral artery.

The deep femoral artery gives rise to several very proximal branches that tend to maintain patency even in persons with extensive atherosclerotic disease, thus providing the major source of collateral circulation around an occluded superficial femoral artery.

The term superficial femoral artery is somewhat of a misnomer in that it is superficial for only a few inches until it courses under the sartorius muscle and into the aponeurotic covering of the adductor (Hunter) canal.

When it emerges anterior to the adductor magnus, the superficial femoral artery becomes the popliteal artery. Because the popliteal artery is bounded posteriorly by the popliteal vein, nerve, and fascia and the semimembranosus, gastrocnemius, plantaris, and soleus muscles, it is the most difficult of the lower extremity pulses to accurately assess.

The popliteal artery passes posterior to the knee joint and into the upper leg where, just distal to the popliteus muscle, it divides into the anterior tibial artery and the tibioperoneal trunk. The anterior tibial artery passes laterally through the interosseous membrane and lies on the interosseous membrane throughout much of the leg. As it reaches the lower leg, it lies on the tibia and then becomes superficial at the ankle joint, at which point it is called the dorsalis pedis artery and, hence, is palpable as the dorsalis pedis pulse.

The tibioperoneal trunk divides within approximately 1 inch of its origin into the peroneal artery and the posterior tibial artery. The peroneal artery lies on the medial surface of the fibula and ends in terminal branches near the os calcis. The peroneal artery, which is too deep to be palpable as a pulse, often remains patent despite atherosclerotic occlusion of the anterior and posterior tibial arteries and, thus, may be a usable site for the distal anastomosis of bypass grafts in patients with advanced infrapopliteal occlusive disease. The posterior tibial artery runs along the medial side of the leg and posterior to the medial malleolus, where it is superficial and palpable as the posterior tibial pulse.

The greater (long) saphenous vein originates on the medial side of the dorsum of the foot and runs anterior to the medial malleolus. It then runs posteromedially to the tibia, posteriorly to the medial condyle of the femur, and along the medial thigh, coursing anteriorly until it enters the femoral vein through the foramen ovale, just below the inguinal ligament. The length and relatively superficial course of the greater saphenous vein make it ideally suited for use in infrainguinal bypass surgery.

Contraindications

In nonambulatory patients with ischemic pain at rest, gangrene, or extensive nonhealing wounds, primary lower extremity amputation may be a better choice than vascular bypass surgery.

Workup

Laboratory Studies

Several screening laboratory studies are useful to evaluate the possibility of associated systemic risk factors and contributing problems.
- Perform a complete blood cell count to screen for hematologic diseases such as thrombocytopenia, thrombocytosis, polycythemia, and leukemia.
- Obtain a fasting blood glucose level to screen for diabetes.
- Creatinine and blood urea nitrogen determinations help screen for renal insufficiency.
- A fasting and lipid profile helps screen for hyperlipidemia.
- Perform a urinalysis to screen for glycosuria or proteinuria.
- Perform a coagulation workup to assess the prothrombin and activated partial thromboplastin times. In some cases (eg, patients with a personal or family history of thrombotic problems, particularly a history of failed vascular interventions), the workup should include a fibrinogen level, a euglobulin lysis time, a protein C assay, a protein S assay, antiphospholipid antibody titers, and an anticardiolipin antibody assay.
- Consider obtaining a serum homocysteine level to screen for hyperhomocysteinemia in patients with an atypical history, early onset, or a family history. This problem, which is associated with both arterial and venous disease, can be treated by dietary supplementation with folate and vitamin B-12. However, note that no conclusive data indicate that such treatment lowers long-term vascular risks.
- Consider determining the erythrocyte sedimentation rate. Although elevation of the erythrocyte sedimentation rate is a nonspecific finding, the test screens patients with vascular disease for 2 potential risk factors that are somewhat difficult to measure directly, hyperfibrinogenemia and hyperviscosity syndromes.
A noninvasive vascular laboratory evaluation of peripheral arterial occlusive disease includes the following:
- Pulse-volume recording (PVR), or plethysmography, uses pneumatic cuffs encircling the thighs, calves, ankles, feet, and sometimes toes to sense segmental volume changes with each pulse beat. The resulting tracings provide useful information about the hemodynamic effects of the arterial disease at each level. In patients with severe disease, tracings at the transmetatarsal level may become nearly flat. In patients with mild disease, particularly involving the aortoiliac segment, PVR tracings may appear normal at rest and may become abnormal only after the patient walks until symptoms occur. PVR is noninvasive and rapid; therefore, it may be repeated frequently to help assess the overall hemodynamic response to medical or surgical treatment.
- A handheld Doppler scanner may be used to assess arterial signals, to localize arteries to facilitate palpation of pulses, or to determine loss of the Doppler signal as a proximal blood pressure cuff is inflated. The latter pressure divided by the upper extremity systolic pressure is called the ankle-brachial index (ABI) and can help indicate the severity of arterial compromise.²¹ A normal ABI averages 1. An ABI less than 0.9 suggests atherosclerotic disease with a sensitivity of approximately 95% and a specificity of 99%.⁵ In general, an ABI below 0.3 suggests a poor chance for healing of distal ischemic ulcerations. Unfortunately, the ABI is often falsely elevated if the underlying arteries are heavily calcified, a finding common in patients with diabetes.
- Skin perfusion pressure (SPP) is defined as the pressure at which skin perfusion returns as an inflated blood pressure cuff is slowly deflated. This point can be measured using washout of a radioisotope, the reappearance of pulsatile flux on photoplethysmography, or the motion of erythrocytes on laser Doppler. An SPP over 40 mm Hg correlates with the likelihood of the healing of ischemic wounds.²²
- Duplex scanning can provide images of arterial segments that help localize the extent of disease, and simultaneous Doppler measurement of flow velocity can help estimate the degree of stenosis. Duplex scanning is quite useful in visualizing aneurysms, particularly of the aorta or popliteal segments. Unfortunately, Doppler techniques are not accurate for assessing the hemodynamic consequences of atherosclerotic peripheral arterial disease involving the extremities.

Imaging Studies

Conventional Angiography: If surgical treatment is contemplated, angiography is needed to delineate the extent and significance of atherosclerotic disease. Major risks associated with conventional contrast-injection angiography are related to the puncture and to the use of contrast agents.
- Technique: Typically, a catheter is inserted retrograde via a femoral puncture, and contrast is power-injected into the infrarenal aorta. Films are taken as the contrast is followed down to both feet. In certain cases, as with aortic occlusion, a femoral approach to the aorta may not be possible. In this case, the radiologist may use an alternate entry such as via an axillary artery or even directly into the infrarenal aorta via a translumbar approach.
- Puncture-related complications: The arterial catheter is usually passed through a 5-F sheath that is 1.6 mm in diameter. This is a sizable hole in the femoral artery, which may be only 6-10 mm in diameter. After the catheter is removed, gentle pressure must be applied to the puncture site for approximately 30 minutes, and the radiologist must balance the need for hemostasis against the possibility of arterial occlusion. Risks include hemorrhage, pseudoaneurysm formation, and clotting or dislodgement of an intimal flap, which may acutely occlude the artery at or near the entry site. Currently, newer methods of percutaneous closure of the puncture sites have significantly reduced the site complication rates.
- Contrast-related risks: Angiographic contrast material is nephrotoxic. The risk of precipitating acute renal failure is highest in patients with underlying renal insufficiency and those patients with diabetes. Patients with both of these risk factors have a 30% rate of acute renal failure following contrast angiography. Hence, an acceptable serum creatinine level must be confirmed prior to elective angiography. Avoid contrast angiography (if possible) for patients with any significant degree of renal impairment. If contrast angiography is absolutely required despite renal impairment, use a minimal volume of contrast material. In addition, providing adequate hydration prior to, during, and after the procedure is essential. Oral administration of the antioxidant acetylcysteine (Mucomyst) the night prior to and then just before angiography may be protective of renal function for patients at risk of contrast-induced nephropathy.²³
- Metformin warning: To prevent the possibility of fatal lactic acidosis, patients with diabetes who are taking metformin (Glucophage) must not take this medication immediately following contrast angiography. Patients may resume taking the medication when normal renal function is confirmed 1-2 days after contrast exposure.
Alternatives to conventional angiography
- Magnetic resonance angiography: Magnetic resonance angiography (MRA) is an alternative both for patients for patients who are allergic to iodinated contrast material. MRA is not innocuous. Gadolinium chelates, the contrast agents used in MRA, have been linked recently to three potentially serious side-effects in patients with renal insufficiency: acute renal injury, pseudohypocalcemia, and nephrogenic systemic fibrosis.²⁴ MRA is contraindicated in patients with implanted hardware such as a hip prostheses or pacemakers. The resolution may be inadequate for the vascular surgeon in planning reconstructive procedures, particularly in the smaller infrapopliteal arteries, although MRA technology and contrast agents continue to improve.²⁵
- Multidetector computed tomographic angiography (MDCT): MDCT avoids arterial puncture. By using precisely timed intravenous contrast injection, multidetector (16 or 64 channel) CT scanners can generate angiographic images of excellent resolution and at a relatively high acquisition speed. MDCT carries the contrast-related risks described above.²⁶
- Carbon dioxide angiography: Carbon dioxide angiography is an alternative for patients with renal insufficiency; however, it is not widely available and requires some iodinated contrast material in addition to the carbon dioxide gas in order to provide useful images.
- Plain radiography: Plain radiographs are not routinely obtained in the workup of peripheral arterial occlusive disease. This is because arterial calcification seen on plain radiographs is not a specific indicator of severe atherosclerotic disease. Calcification of the arterial media is not diagnostic of atherosclerosis, and even calcification of the arterial intima, which is diagnostic of atherosclerotic disease, does not necessarily imply hemodynamically significant stenosis.

Histologic Findings

Atherosclerotic vessels demonstrate proliferation of smooth muscle cells in the intima and invasion of the damaged intima by atherosclerotic plaque consisting of necrotic cells, lipids, cholesterol crystals, and connective tissue. These lesions typically occur in an eccentric location with respect to the arterial lumen. Soft thrombus may deposit on ulcerated atherosclerotic plaques.

Treatment

Medical Therapy

Most patients with atherosclerotic lower extremity disease do not undergo surgical treatment. In fact, only 25% of patients presenting with intermittent claudication eventually require invasive treatment of limb-threatening ischemia or intractable symptoms, and only 5-10% do so within 5 years of the onset of claudication.

The cornerstones of medical management of intermittent claudication are walking and elimination or control of medical risk factors.^27,28 For further reading, see the eMedicine articles Atherosclerosis and Coronary Artery Atherosclerosis.

Walking

Encourage walking.²⁹ Regular walking of approximately 1 hour per day usually results in a significant increase in walking distance over time. This increase in walking distance has been noted to range from 80% to more than 200%. Improvement results from improved flow in collateral pathways.

Risk factor management

Discontinue cigarette smoking. A major factor contributing to progressive and intractable atherosclerotic disease is cigarette smoking. One study noted an 85% chance of improvement if smoking is stopped versus only a 20% chance of improvement if the patient continues smoking.
Control medical risk factors. Other risk factors that must be assessed and controlled are obesity, hypertension, hyperlipidemia, and diabetes.³⁰
Ensure meticulous foot care. Because an ischemic foot is at risk for developing limb-threatening ulceration from even minor trauma, good foot hygiene and appropriately fitting shoes are important. This is even more vital for patients with diabetes, who are also at risk for neuropathic foot ulcers.

Pharmacotherapy

Discuss pharmacotherapy. Currently available drugs that may benefit patients with mild or moderate claudication include pentoxifylline and cilostazol.^31,32 Controlled studies suggest that each of these drugs improves walking distance by approximately 20% more than placebo, cilostazol perhaps slightly more than pentoxifylline.
Cilostazol (Pletal), administered at 100 mg orally twice daily, has demonstrated some benefit for claudication symptoms.³³ Cilostazol is contraindicated in patients with congestive heart failure.³⁴ The product's black box warning reads as follows:

Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV congestive heart failure. Pletal is contraindicated in patients with congestive heart failure of any severity.

Pentoxifylline (Trental), 400 mg orally 3 times per day taken with meals, has been available for many years. After 2-3 months of use, 25-60% of patients demonstrate some improvement in walking distance. However, much of this improvement may be attributable to exercise and to modification of the risk factors mentioned above. The major adverse effects of this medication are gastrointestinal in nature.
Antiplatelet agents (eg, aspirin, clopidogrel), angiotensin-converting enzyme inhibitors, and statins should also be considered.

Caveats regarding pharmacotherapy are that vasodilators and chelation therapy have no demonstrated benefit in the treatment of claudication. Beta-blocking agents may worsen claudication and must be discontinued, if medically feasible.

Surgical Therapy

Surgical or endovascular intervention is indicated for intractable and disabling claudication, for ischemic pain at rest, and for ischemic necrosis (see Image 1). Surgery also may be useful for nonhealing ischemic ulceration.

Before considering surgical intervention, the clinician must address the possibility of coexisting atherosclerotic heart and cerebrovascular disease, which are extremely common in patients with atherosclerotic peripheral arterial disease. One study found that only 14% of patients with peripheral arterial disease had normal coronary arteries, while 15% had severe coronary artery disease that required surgical correction. See the eMedicine article Atherosclerosis for the cardiologic workup.

Obtain appropriate imaging studies. Before surgical intervention, the exact extent of the atherosclerotic disease is mapped using high-quality contrast angiography (see Imaging Studies).

Preoperative Details

Prior to vascular surgery, a routine laboratory workup is performed, including complete blood cell count, biochemical profile, clotting studies, urinalysis, chest radiography, and ECG. Abnormalities are addressed.

Radiographic contrast

If an endovascular procedure is to be performed, iodinated contrast material is required, and hence, one must check for renal insufficiency, a history of contrast allergy, and the use of metformin (Glucophage; see Imaging Studies).

Infection prevention

Take appropriate measures to prevent vascular graft infection:

For routine prophylaxis in bypass surgery, a broad-spectrum antibiotic, such as a broad-spectrum cephalosporin, a penicillin/β-lactamase inhibitor, or an aminoglycoside, is administered just before surgery and postoperatively for 1 to 3 doses.
If there is known colonization with or local prevalence of methicillin-resistant staphylococcus aureus (MRSA), consider vancomycin or teicoplanin.³⁵
Consider a preoperative antiseptic shower or scrub.
Patients harboring a potential infection (eg, foot ulcer, gangrene) may fare better having the infected tissue excised, even with limited amputations, prior to vascular intervention in order to avoid graft or wound infections.

Urgent intervention

If urgent intervention is required, the workup may have to be truncated. In the case of acute arterial occlusion, the workup may have to be minimal because prompt thrombectomy is often required for limb salvage. Preoperative angiography may still be warranted, especially if evidence of underlying atherosclerotic disease is present.

Intraoperative Details

Although peripheral arterial disease is a diffuse process, often the preponderance of findings can be attributed to a particular segment of the arterial tree. Angiographic findings combined with knowledge of the patient's symptoms, physical findings, and noninvasive laboratory results leads the vascular specialist to determine which artery or arteries are best treated by invasive means.³⁶ This determination is not an exact science, and it is not unusual for the vascular specialist to correct a single lesion and then discover that the recurring symptoms dictate another procedure at a later date. Nonetheless, attempting to correct all diseased segments at once usually confers too high an operative risk.

Disease of the iliac artery

Hemodynamically significant disease involving the iliac arteries, particularly short-segment stenotic and even occlusive disease, can usually be successfully treated using percutaneous angioplasty, percutaneous insertion of an arterial stent, or both.

If endovascular reconstruction is not possible, femorofemoral crossover bypass is usually the best choice for unilateral iliac artery occlusion and aortobifemoral bypass is usually the best choice for bilateral or diffuse aortoiliac disease.

Axillofemoral bypass is an alternative in high-risk patients who cannot tolerate an intra-abdominal or retroperitoneal operation (see the eMedicine article Aortoiliac Occlusive Disease).

Disease involving the femoral artery

Hemodynamically significant disease involving the femoral artery is usually the result of relatively long-segment occlusion of the distal superficial femoral artery in the adductor canal.

Endovascular approaches to infrainguinal disease have become increasingly successful. Secondary interventions are often required, but assisted patency rates are reported as over 90% in appropriately selected patients.

Correction of this type of disease often requires bypass from a pulsatile distal common femoral artery to the pulseless popliteal artery. Such a bypass is best performed using the ipsilateral greater saphenous vein. If this vein is not suitable (or has been used previously), alternative conduits for above-knee bypasses include expanded polytetrafluoroethylene prosthetic graft (Gore-Tex, Impra), Dacron, tanned bovine umbilical vein graft, and glutaraldehyde tanned human human umbilical vein.³⁷

Because of inferior patency rates with prosthetic grafts extending below the knee, the vascular surgeon usually tries to locate a usable autologous vein from the contralateral lower extremity by combining available short segments from both sides, upper extremity veins, or even composite grafts (in which a prosthetic graft extends to the knee and a piece of autologous vein is attached distally or when a vein patch is used to attach the prosthetic graft to the distal artery).

Angioplasty with or without stenting may be appropriate for short-segment superficial femoral artery occlusive disease.

Disease involving the infrapopliteal arterial tree

Extensive disease involving the infrapopliteal segments is best managed by autologous vein grafting. Arguably, the best technique is the use of the ipsilateral saphenous vein in situ.

This is a somewhat tedious procedure in which the saphenous vein is first disconnected from the femoral vein in the groin and anastomosed to the common femoral artery. The vein is then transected distally, and a valvulotome is inserted retrograde and withdrawn in order to destroy the valves that would have prevented arterial flow from the groin to the leg in the vein. Next, an anastomosis is created between the distal end of the vein and a usable small artery, even as far distally as the dorsalis pedis at the ankle or foot. Finally, the vein branches are ligated to stop arteriovenous flow.

Patients must be selected carefully for this technique. The vein must be patent and of adequate length and caliber, and a usable, soft distal artery must be available. Preoperative vein mapping using duplex scanning is sometimes helpful.

Endovascular procedures

Percutaneous transluminal angioplasty is often appropriate for strictures or short-segment occlusions of the superficial femoral, popliteal, and, occasionally, infrapopliteal arteries.^38,4,39 Angioplasty is performed by passing a guidewire through the lumen of the strictured artery and then advancing a balloon angioplasty catheter over the guidewire. The balloon is inflated to several atmospheres of pressure under angiographic visualization. This effectively disrupts the plaque and provides a wider, patent lumen.

Although angioplasty has been used increasingly for claudication, whether the risks justify the benefits for many patients in this group is a serious question.⁴⁰

Somewhat surprisingly, even if the guidewire cannot negotiate the lumen of a stricture and instead passes through the subintimal plane, subintimal (extraluminal) angioplasty may succeed.⁴¹ This method seems to create a new channel in a virgin plane. Low echogenicity at the distal end of the plaque, as measured by duplex ultrasound–derived gray-scale median, seems to increase the chance of successful subintimal angoplasy.⁴²

Angioplasty may be combined with percutaneous stenting. Self-expanding nickel-titanium alloy (nitinol) stents have demonstrated a 2-year primary patency rate of 47% and a limb salvage rate of 66% when used to treat limb ischemia.⁴³

In addition to intra-procedure anticoagulation, patients are typically treated with an antiplatelet agent, such as clopidogrel, both before and for a month or more postprocedure.⁴³

Percutaneous endovascular removal of atherosclerotic plaque (ie, atherectomy) seemed quite promising in the early 1990s, but it was abandoned because of very poor long-term success rates. More recently, however, it has garnered some renewed interest in research settings.^44,45,46,47

Endarterectomy

Removal of atherosclerotic plaque and underlying diseased arterial intima (endarterectomy) at anastomotic sites is sometimes necessary as an adjunct to bypass surgery but is indicated only rarely as the sole management for lower extremity arterial occlusive disease.

One exception is endarterectomy of the deep femoral artery (profundoplasty), which may be useful in the rare case of severe limb-threatening stenosis of the origin of the deep femoral artery associated with a superficial femoral artery occlusion that cannot be bypassed for technical reasons.

Another indication for endarterectomy is to remove localized embolizing ulcerated plaque.

Management of acute arterial occlusion

The usual immediate management of acute arterial occlusion is immediate heparin anticoagulation and rapid surgical thromboembolectomy. If time allows, especially if atherosclerotic thrombosis is suggested, preoperative angiography is often wise. It may provide information vital to performing bypass surgery should thrombectomy disclose severe underlying atherosclerotic disease. In some cases, particularly very high-risk patients, thrombolytic therapy by selective intra-arterial infusion (if available) is a reasonable alternative to emergency surgery. For infrainguinal acute occlusions, a medial approach to the distal popliteal artery trifurcation is usually the best method to allow complete evaluation and clearance of all outflow vessels.

After relief of an acute arterial occlusion, one must be alert to the possibility of reperfusion complications such as compartment syndrome or myopathic-metabolic-nephrotic syndrome. Compartment syndrome is characterized by tense edema of the leg, which raises interstitial tissue pressures and impedes arterial inflow. Emergency 4-compartment fasciotomy can save limbs. Myopathic-metabolic-nephrotic syndrome is the result of reperfusion of essentially irreversibly ischemic muscle. It is characterized by metabolic acidosis, dark urine, and renal failure. Emergency limb amputation may be required to save the patient's life.

After emergent treatment to salvage the ischemic limb, the clinician must determine the etiology of the acute occlusion. If it was thrombotic, the underlying atherosclerotic disease may require correction. If it was embolic, the source must be sought. Ninety percent of arterial emboli originate in the heart. The remaining emboli originate in the aorta (see Differential diagnoses) or from venous thrombi that pass into the arterial circulation via a right-to-left intracardiac shunt (paradoxical embolism). Sometimes, the source can be treated, but usually, long-term anticoagulation is required.

Aneurysm resection is indicated for symptomatic, expanding, or sizable popliteal artery aneurysms. A vein graft is usually used to replace the resected or excluded popliteal artery segment. Management of aortic aneurysms is covered in the eMedicine article Thoracic Aortic Aneurysm.

Postoperative Details

Postoperative care after vascular surgery requires in-hospital observation in order to expeditiously detect and treat complications.

Occlusion

The most frequent complication of endovascular and vascular surgical procedures is occlusion. Some authorities recommend the use of antiplatelet therapy (eg, aspirin or clopidogrel) starting before angioplasty or bypass surgery and continuing indefinitely. For grafts considered to be at high risk for thrombosis, such as those with poor runoff, with a previous occlusion, with a prosthetic graft, or in a hypercoagulable state, heparin may be given perioperatively, and warfarin may be administered for long-term prophylaxis.

Acute postoperative thrombosis

Any change in circulatory status beyond the bypass graft warrants a rapid evaluation. If thrombosis has occurred, rapid return to the operating room for thrombectomy and repair is required. In such cases, a technical problem (eg, intimal flap) must be sought.

Normal postoperative recovery

Ambulation with the assistance of a physical therapist usually starts gradually on the first or second postoperative day. The timing of hospital discharge varies with the extent of the procedure and the patient's general condition. If bypass surgery has been performed in conjunction with significant distal amputations, recovery in a skilled nursing facility or rehabilitation center may be beneficial.

Management following percutaneous procedures

Following percutaneous procedures, the patient is observed from 4 hours to overnight to ensure absolute bed rest and detect possible complications of the puncture and intervention. Antiplatelet therapy is usually prescribed. For patients with renal compromise and those on metformin, check serum creatinine values 1-2 days after the procedure.

Follow-up

A routine postoperative follow-up assessment is essential for 2 reasons. First, medical management of the underlying atherosclerotic disease must continue. Second, bypass graft surveillance using noninvasive vascular laboratory testing may help detect problems that can threaten graft patency. Such problems include progressive atherosclerotic disease of inflow or outflow vessels or buildup of scar tissue (neointimal fibrous hyperplasia) at the anastomotic sites. If these problems can be detected before they lead to graft thrombosis, they may be corrected using endovascular means (ie, angioplasty, stenting). Open surgical revision for restenosis of vein grafts, however, carries a higher long-term success rate than percutaneous intervention.⁴⁸

A typical schedule for outpatient follow-up after peripheral arterial intervention is at 2 weeks, 1 month, 3 months, 6 months, and every 6 months thereafter.

Complications

Important complications of vascular surgery include early postoperative occlusion, hemorrhagic problems, graft infection, cardiac morbidity, and restenosis.

Early postoperative occlusion

Early postoperative arterial or graft occlusion usually occurs as a result of technical factors such as an intimal flap or the use of a suboptimal conduit.⁴⁹ Early reocclusion warrants a quick return to the operating room for thrombectomy and repair of any potential technical defect.

Unfortunately, the long-term prognosis after a take-back procedure for early graft occlusion is poor, with only approximately one quarter of such grafts still functional 5 years later.

Hemorrhagic problems

Hemorrhage and pseudoaneurysm formation may occur at the arterial puncture site or, less commonly, at a graft suture line. Management of the latter usually requires a return to the operating room for surgical repair; however, endovascular puncture site pseudoaneurysms can sometimes be treated using ultrasound-guided compression repair.⁵⁰ In this technique, guided by continuous duplex scanning, the pseudoaneurysm is compressed just enough to stop flow outside the lumen of the involved artery but still preserve distal arterial flow. This compression continues for approximately 45 minutes, until the pseudoaneurysm thromboses. Arteriovenous fistulas have also been treated using this technique. More recently, ultrasound guided percutaneous thrombin injection has been shown to be quite effective and more expeditious.⁵¹

Graft infection

Prosthetic graft infections are rare but serious and may require removal of the bypass graft and even amputation of the limb. They occur in approximately 1% of prosthetic graft bypasses. Currently, methicillin-resistant Staphylococcus aureus is the preponderant pathogen.

Treatment usually requires complete removal of the graft and, if possible, reconstruction using a new graft via an extra-anatomic pathway, such as an iliac-popliteal bypass from the iliac artery via the obturator foramen to the popliteal artery beyond the infected graft's distal anastomosis.

Cardiac morbidity

Plaque in the superficial femoral artery (SFA) tends to be a late development in patients with generalized atherosclerotic disease. Therefore, the presence of SFA plaque conveys a very high likelihood of coexisting cardiac or carotid atherosclerosis.⁵²

Because of this association of atherosclerotic coronary artery disease with peripheral arterial disease, postoperative myocardial events such as cardiac death, nonfatal myocardial infarction, unstable angina, ventricular tachycardia, and congestive heart failure may occur following infrainguinal bypass operations.

Although most studies suggest an overall cardiac complication rate of approximately 5%, one study found that such myocardial events occurred at an alarming rate of 24% in 87 patients undergoing infrainguinal reconstruction.

Restenosis

The most common late complication of both endovascular and vascular reconstructive procedures is restenosis resulting from a proliferation of smooth muscle cells causing an excessively thickened neointima, which can lead to late arterial or graft reocclusion. This is best prevented by routine postoperative graft surveillance and managed by endovascular repair, patch grafting, of bypass revision before occlusion occurs (see Follow-up care).

Outcome and Prognosis

Outcome and prognosis are considered separately for patients treated medically and for patients treated surgically.

Outcome of the medical management of claudication

Infrainguinal arterial disease is associated with a risk of limb-threatening ischemia. However, most patients improve with medical treatment. Approximately 10% of patients with intermittent claudication develop findings necessitating vascular reconstructive procedures.

Outcome of endovascular management

Patency rates following endovascular treatment of infrainguinal occlusive disease vary significantly among published series. Overall, primary patency is somewhat inferior to that of bypass surgery. Nonetheless, successful endovascular management improves quality of life and patient satisfaction.⁵³ Furthermore, further endovascular or surgical management can often correct a failed endovascular intervention.^54,55

Outcome of vascular surgery

Graft patency rates vary widely among series. One study in which graft patency was assessed by using MRA disclosed an 84% limb salvage rate and a 78% primary graft patency rate at 21 months of follow-up. Prosthetic grafts carry a primary 3-year patency rate of 39% and a 3-year secondary patency rate of 59%, with a 25% risk of amputation within 3 years.⁵⁶

Limb salvage rates are lower among patients with insulin-dependent diabetes.⁵⁷ Infrainguinal reconstructive surgery is associated with a mortality rate of somewhat less than 5% despite the high-risk nature of these patients.⁵⁸ The likelihood of coexisting coronary artery disease is a major risk factor.

The overall survival rate for patients with lower extremity arterial occlusive disease is approximately 50% over 10 years. For patients who require bypass surgery, the survival rate drops to approximately 50% over 5 years.

Future and Controversies

Technological enhancements and wider availability of existing technology should continue to improve the safety and efficacy of endovascular and vascular surgical techniques.^59,60

Improvements in imaging technology

Imaging technology continues to improve.⁶¹

Three-dimensional ultrasound visualization can help better detect early plaque formation to allow for even more timely correction of vein graft stenoses.

Gadolinium-enhanced 3-dimensional MRA images can provide highly detailed views of the arterial system. The applications of MRA, including MR-guided endovascular interventions,⁶² will expand with continuing improvements in hardware, software, and nonnephrotoxic contrast agents.

Improvements in endovascular techniques

Endovascular procedures continue to benefit from improved technology both in imaging modalities and instrumentation.⁶³

When performing in situ bypass, endovascular technology allows valvulotomy and coil occlusion of side branches by direct angioscopic visualization.

Endoscopic assistance

As in other surgical fields, endoscopy may have a greater role in infrainguinal vascular surgery. For example, endoscopic harvesting of the saphenous vein limits the extent of the dissection required for bypass procedures.⁶⁴

Arterialization of the distal venous bed

Recent studies suggest that in patients with limb-threatening ischemia but inoperably diseased distal arteries, arterialization of the distal venous bed may be of benefit.^54,65

Prevention of restenosis

Gene therapy holds promise for inhibiting vascular restenosis after endovascular procedures or bypass surgery. Rat and rabbit models suggest that neointimal hyperplasia after arterial injury is inhibited by overexpression of the GAX gene and that adenovirus-mediated delivery of the GAX gene diminishes proliferation of intimal cells in animal models. Gene therapy may be suitable for vein grafts prior to implantation.

Some research is underway on inhibitors of smooth muscle proliferation, such as drugs that block E2F transcription factors.^3,66 Unfortunately, a multicenter, randomized, double-blinded study of 1,404 patients revealed no benefit from the use of edifoligide, an E2F inhibitor.^67,68

Low-dose intravascular beta-irradiation may inhibit restenosis by blocking early medial and adventitial cell proliferation.⁶⁹

Multimedia

Media file 1: Pressure ulcer of the heel exacerbated by infrainguinal arterial occlusive disease.

Media file 2: Cyanosis of the first toe and dependent rubor of the foot characteristic of arterial insufficiency.

Media file 3: Contrast angiogram showing severe atherosclerotic disease in the distal superficial femoral artery.

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Keywords

infrainguinal occlusive disease, peripheral atherosclerotic disease, peripheral vascular disease, chronic arterial insufficiency, femoropopliteal occlusive disease, aortoiliac occlusive disease, stent, stenting, ischemic lower extremity disease, arteriosclerosis obliterans, complex regional pain syndromes, CRPS, posttraumatic pain syndromes, causalgia, mimocausalgia, Sudeck atrophy, reflex sympathetic dystrophy, intermittent claudication, gangrene, amputation

Contributor Information and Disclosures

Author

Richard M Stillman, MD, FACS, Honorary Medical Staff, Northwest Medical Center; Former Chief of Staff and Medical Director, Wound Healing Center, Department of Surgery, Northwest Medical Center
Richard M Stillman, MD, FACS is a member of the following medical societies: American College of Angiology, American College of Surgeons, Association for Academic Surgery, and Society of University Surgeons
Disclosure: Nothing to disclose.

Medical Editor

William H Pearce, MD, Chief, Division of Vascular Surgery, Violet and Charles Baldwin Professor of Vascular Surgery, Department of Surgery, Northwestern University School of Medicine
William H Pearce, MD is a member of the following medical societies: American College of Surgeons, American Heart Association, American Surgical Association, Association for Academic Surgery, Association of VA Surgeons, Central Surgical Association, New York Academy of Sciences, Society for Vascular Surgery, Society of Critical Care Medicine, Society of University Surgeons, and Western Surgical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Travis J Phifer, MD, Chief, Division of Vascular Surgery, Professor, Department of Surgery and Radiology, Louisiana State University Health Sciences Center in Shreveport
Travis J Phifer, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Surgeons, American Medical Association, Association for Academic Surgery, Society for Academic Emergency Medicine, Society for Vascular Surgery, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

CME Editor

Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy
Paolo Zamboni, MD is a member of the following medical societies: American Venous Forum and New York Academy of Sciences
Disclosure: Nothing to disclose.

Chief Editor

Further Reading